U if' { 1 5 ) fyxmW ^nxvmxi^ Jilratg THE GIFT OF y4.i..S,.oiA.«b..at :^^ _..... i*4^-|-C!l.3u Cornell University Library RD 57.P13 1876 Lectures on surgical pathologydelivered 3 1924 012 183 061 Cornell University Library The original of tiiis book is in tine Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924012183061 LECTUEES SUBGICAL PATHOLOGY LONDON : i'lUNTEI) KY ■^l-Ol'IMSWOOD-; AND CO., XF.iV-STItKKT SQL'AKE AND PAItLIAMKNT STREKT LECTUEES ox SURGICAL PATHOLOGY DELITBKED AT THE ROYAL COLLEGE OF SURGEONS OF ENGLAND BY SIR JAMES PAGET, BART. r.R.S., D.C.L, OxoN., LL.D. Cjlstas. SERJEANT- SITRGEGX EXTRAOKDESTARY TO HER MAJESTY THE QUEEN SURGEON TO H.Tl.H. THE PRINCE OF WALES CONSULTING SUKGEON TO ST. BARTHOLOMEW'S HOSPITAL bevij;eb axd edited by WILLIAM TURNER, M.B. Lond. PROFKSSOE OP AJJATOMY IN THE TrmVERSTTT OF EDINBURGH FOURTH EDITION LONDON LONGMANS, GEEEN, AND CO. 1876 All rights reserved /'CORNEL, LIBRA.fiY TO P. M. LATHAM, M.D. and GEORGE BURROWS, M.D, WHOSE SKILL HAS DEBN PBRMITIBB TO rEESHEVE MY LTPE, WHOSE FRIENDSHIP ADDS LARGELY 10 MY HAPPINESS, AND 10 WHOSE TEACHING I SHALL ATIHinUIE MUCH OF WHATEVER GOOD MY WORK MAT DO, I b-ibttalc t^ts il3nlume, WITH GEAIITIJDE, AFFECTION, AND RESPECT. PREFACE 10 THE FIRST EDITION. Neaklt all the Lectures in these volumes were delivered at the Royal College of Surgeons, during the six years, from 1847 to 1852, in which I held the office of Professor of Anatomy and Surgery to the College. So many listened favourably to them, that I venture to hope I am not wrong in thus enabling many more to read them. But, in offering them to this larger class, some explanation of their scope and plan seems necessary. The circumstances of my election to the professorship indi- cated the Pathological Museum of the College as the appropriate subject of the Lectures ; and the first portion of the Museum, devoted to the illustration of Greneral Pathology, seemed to offer the best plan by which knowledge acquired in a long study of the whole collection might be communicated. The modes were many in which such a subject might be treated in lectures ; but, as circumstances had decided the subject, it seemed well to let them determine, also, the method, and to adopt that which was most natural to one engaged in the simultaneous practice of surgery and teaching of physiology. Thus guided, I designed to give lectures which might illustrate the general pathology of the principal surgical diseases, in con- formity with the larger and more exact doctrines of physiology ; viii PREFACE TO and the plan seemed the more reasonable, because it was in accordance with the constant design of the great founder of the Museum. The Museum limited, while it indicated, the subjects of the Lectures. They were, therefore, not constructed to form a system of surgical pathology ; several subjects, which might fill consider- able places in such a system, were scarcely alluded to in them ; and, although I have added some Lectures, which could not be conveniently included in any of the courses, yet I have not gone beyond the range of such pathology as a Museum may illustrate. The wood-engravings are, for the most part, copied from the same specimens and drawings as were the diagrams used in the Lectures ; and I wish them to be regarded as intended for only the same piu'poge as such diagrams may serve ; — viz. that of assisting the more difficult parts of the descriptions of the objects to which they refer. I have endeavoured to make the Lectures less incomplete, and more correct, by the aid of numerous facts ascertained since they were delivered, and have added to them many things which time, or their inaptness for oral delivery, obliged me to omit. Among these are the references to specimens and illustrations ; as well as to numerous authors who could not, in speaking, be conveniently quoted, but whom I am now glad to acknowledge as instructors. And I will here offer my thanks to some, to whom my debts are more than would be expressed, even by referring to all the occasions on which their works have aided me in the composition of the Lectures. Such acknowledgments are due, especially, to Mr. Lawrence, Mr. Stanley, Professor Owen, and Dr. Carpenter, from whom, during many years of valued friend- ship, I have derived, at every interview, either knowledge, or guidance in observing and in thinking. I am deeply obliged, also, to all my colleagues on the staff of St. Bartholomew's, from whom the constant help that I receive adds daily to the debt of THE FIRST EDITION. ix gratitude incurred during my pupilage. And there are many friends, besides, to whom it is my happiness to be indebted for knowledge used in these Lectures, and whom I thank collectively, not because I owe them little, but because I cannot name them all, and cannot thank some without appearing ungrateful to the rest. I desire, in conclusion, to express my acknowledgments to the Members of the Council of the College, both for the repeated honour they conferred on me by so often electing me to the Professorship, and for the kindness with which many of them devoted their valuable time to attendance at the Lectures. The encouragement they thus aiforded me makes me hope, that the labour with which I strive to justify their choice may have some success in the promotion of scientific surgery. JAMES PAGET. May 30, 1853. PEEFACE TO THE SECOND EDITION. When the time came for preparing a Second Edition of these Lectures, I was anxious that they should be revised with all the light of the knowledge of Pathology acquired since their publi- cation. But although I had collected some materials for this purpose, yet a thorough revision of the whole subject was a task for which I felt unfit. For in the passage of nine years, I had been carried into the active practice of my profession ; and, at their end, had no sufficient time for either studying or thinking carefully about the many facts, and probabilities, and guesses at truth which had been added to Pathology. I was, therefore, glad to be able to commit the work of revision to my friend and former pupil, Mr. Turner, whom I know to be not only very conversant with the progress of medical science, but able to test others' observations by his own. It is not for me to say how well he has done the work, for I have so worked with him as to be equally with him responsible. May 1, 1863. PEE FACE TO THE THIRD EDITION. For the present Edition of my Lectures, the last Edition has been carefully revised hy both Professor Tuknee and myself : by him from the Pathological point of view, by me from the Clinical. Many parts have been re-written, and several new figures have been added. The result will be, I hope, that, whether for doc- trine or for practice, the Lectures will be deemed better than they were. Mai/ 2, 1870. NOTE TO THE FOURTH EDITION. An unexpected demand for copies of the Third Edition has led to the necessity of printing a Fourth before there could be time for a complete revision. This Edition is, therefore, only a careful reprint of the last. TITLES OF THE LECTUEES. LECTUltE PAGE I. Nutrition : its Nature, Pvirpose, and Conditions .... 1 II. The Conditions necessary to Healthy Nutrition . . . . 17 III. Tie Formative Process ; Growth 42 IV. Hypertrophy ......... 55 V. Atrophy : Degeneration . . .... 69 VI. Atrophy .... 86 VII. General Considerations on the Repair and Eeproduction of Injured and Lost Parts 115 VIII. The Materials for the Repair of Injuries 130 IX. The Processes of Repair of Wounds 143 X. The Processes of Repair of Wounds . . ... 158 XI. The Repair of Fractures . 178 XII. Healing of Injuries in various Tissues 194 XIII. Phenomena of Inflammation 218 XIV. Products of Inflammation . . . ... 237 XV. Developments of Inflammatory Products 260 XVI. Degenerations of Inflammatory Products .... 277 XVII. Changes produced by Inflammation in the Tissues of the affected part 296 XVIII. The Signs, Nature, and Causes of Inflammation . .317 XIX. Mortification .... . . . 338 XX. Specific Diseases ... 364 XXI. General Characters and Classification of Tumours . 373 XXII. Simple or Barren Cysts . . .... . 392 XXIII. Proliferous or Compound Cysts . 417 XXIV. Fatty Tiimours : Fibro-cellulitr Tumours : Myxoma : Glioma : Hydatid Mole ; ^Cylindroma . . 444 XVI TITLES OF THE LECTURES. LBCTURE PAGE XXV. Fibrous Tumovirs : Myomata : Neuromata : Painful Subcutaneous Tumours ... 471 XXVX. Cartilaginous Tumours . .... ■ 495 XXVII. Part 1. Osseous Tumours 526 Part 2. Myeloid Tumours 541 XXVIII. Part 1. Glandular Tumours, Lymphoid Tumours. . . . 555 Part 2. Erectile or Vascular Tumours, Papillary Tumours . . 673 XXIX. Recurrent Tumours 591 XXX. Scirrhous or Hard Cancer : Parti. Anatomy .... 605 Part 2. Pathology ... 630 XXXI. Medullary Cancer : Parti. Anatomy .... . 654 Part 2. Pathology 678 XXXII. Epithelial Cancer : Part 1. Anatomy ... . 696 J, „ Part 2. Pathology 728 XXXIII. Melanoid, Hsematoid, Osteoid, Villous, Colloid, and Fibrous Cancers 744 XXXIV. General Pathology of Cancer : Part 1 . Conditions preceding the Can- cerous Growth 779 XXXV. The same: Part 2. Development, Structure, and Life of the Cancerous Growth 804 INDEX 827 LIST OP ILLUSTRATIONS. 1 . Development, Growth, and Separation of an Eyelash . . , . 2. Symmetrical Disease of a Lion's Pelvis ...... 5. Hydrocephalic Skull .....,,.,, 4. Skull Thickened, especially at the Centres of Ossification d. Tibia, elongated and curved ........ 6. Fatty Degeneration of Fibres of the Heart : from Dr. Quain . 7. Senile Atrophy of the Bones of the Vault of the Cranium , ■8-9-10. Fatty Degeneration of minute Cerebral Vessels . . ^ 11. Formation of Fat-cells between the bundles of nerve-fibres in a Neiv* 12. "White matter of the Cerebrum, to show the Corpuscles of the Nexiroglia 13. Repair of Crystals .......... 14. Eepair of Hydra Tuba : From Sir J. G. Dalyell 1 5. Repair of Tubularia : from the same . . 16. Vessels and Minute Structiu^ of an Organised Blood-clot 17. Granulation-cells 18. ^Nucleated Blastema or Protoplasm 19. Outgrowth of new Bloodvessels . 20. Channelling of new Bloodvessels . , , , 21. Bloodvessels of Granulations 22. A Vascular Loop among Granulation-cells 23. Pus-opUs 24. Eepair of Fracture with Ensheathing Callus . 25_/6-7. Repairs of FracUires with Intermediate CaUus . Z-S. Eepair of divided Tendons 29-30. Eepair of Skin , , . .... 81. Vessels of a Babbit's Ear ; enlarged in Inflammation : from Hunter 82. Small Bloodvessels dilated in Inflammation .... 33-4. Vessels of the Bat's Wing ; enlarged in Inflammation . 3.5. Corpuscles of Inflammatory Blood : from Wharton Jones . 36. Corpuscular lymph with Bloodvessels from Inflamed Pericardium . 37. Proliferation of Corpuscles of connective tissue from an Inflamed Pleura 38. The same from an Inflamed Peritoneum . 39. Pigmental Degeneration in Mucus-cells . 40. BloodTessels of Adhesions ... a 13 . 59 60 . 64 97 . 101 108 . 112 112 . 118 123 . 124 134 . 141 142 . ISO 162 , 163 164 - 171 185 186-190 198 214, 215 220 . 222 228 . 235 246 . 247 248 . 269 27a xvni LIST or ILLUSTRATIONS. FIS. 41. Lymphatics of Adhesions : from Schroeder van der Kolk 42. "Withered Lymph-eorpuscles ...... 43. Fatty-degenerate Lymph-corpuscles .... 44. BloodTessels of an Abscess-wall ..... 45. Humerus swollen in Inflammation , , . . 46. Separation of the Laminse of the Wall of a Femur . 47. Abscess in a Tibia ....... 4S. Atrophy of the Head and Neck of a Femur : from Gullirer 49. Diagram of an Abscess ...... 30. Development of Cysts in the Kidney : from Eokitansky . 61. Ovary, with many Cysts ...... 52. Proliferous Ovarian Cyst . . ... 53. Minutely Proliferous Ovarian Cyst .... 54. Twisting of the Fallopian Tube and separation of Ovary 55. Mammary Cyst, with Endogenous Growth . 56. A similar Cyst, with Pedunculated Growths . 57. Similar Cysts, clustered and filled .... 58. Microscopic Structures of a Fibro-cellular Tumour 59. Microscopic Structure of a Myxoma .... 60. Section of a Fibro-cellular Tumour .... 61. Hydatid Mole 62. Cystic Disease of the Chorion ..... 63. Diagram sections of an Uterine Outgrowth and an Uterine Tumour 64. Minute Structure of an Uterine Fibro-muscular Tumour 66. Calcareous Deposit in a Fibrous Tumour : from Dusseau 66. Pedunculated sub-serous Fibro-muscular Tumour of the Uterus 67. Section of a Fibrous Tumour from the Hip They formed the siibject of the course of Lectures delivered at the College in 1848, an abstract of part of which is given by Dr. Kirkes in his Handbook of Physio- logy,'^. 63, et seq. 1st ed. and 74, 6th ed. ITS NATURE, PURPOSE, AND CONDITIONS. 13 the discovery of which the acutest chemistry seems yet far distant, and for the illustration and discussion of which we cannot adopt the facts, though we may adopt the language and the analogies, of chemistry. It is in such diseases as these that we can best discern how nice is that refinement of mutual influence, how exact and constant that adaptation between the blood and tissues, on which health depends. I know no instance so well adapted to illustrate this as the ex- amples of symmetrical diseases. The uniform character of such diseases Pig. 2. is, that a certain morbid change of structure on one side of the body is repeated in the exactly corresponding part on the other side. In the lion's pelvis, for example, which is shetched in the annexed diagram, Pig. 2, from a specimen (No. 3030) in the College Museum, multiform as the pattern is, in which the new bone, the product of some disease comparable with a human rheumatism, is deposited — a pattern more complex and irregular than the spots upon a mat — there is not one spot 14 NUTRITION : or line On one side whicli is not represented, as exactly as it would be in a mirror, on tlie other. The likeness has more than Dagnerreotype exactness, and was observable in nnmerous pairs of the bcnes similarly diseased. I need not describe many examples of such diseases. Any out- patients' room will farnish abundant instances of exact symmetry in the eruptions of eczema, lepra, and psoriasis ; in the deformities of chronic rheumatism, the paralyses from lead ; in the eruptions excited by iodide of potassium or copaiba. And any large museum will con- tain examples of equal symmetry in syphilitic ulcerations of the skull ; in rheumatic and syphilitic deposits on the tibiae and other bones ; in all the effects of chronic rheumatic arthritis, whether in the bones, the ligaments, or the cartilages ; in the fatty and earthy deposits in the coats of arteries. Now, these facts supply excellent evidence of the refinement of the affinities which are concerned in the formative process. Excluding, perhaps, the cases of congenital defects that are symmetrical, and some diseases which seem to depend on morbid influence of the nervous system, it may be stated, generally, that symmetrical diseases depend on some morbid material in the blood. Tou may find the proof of this position in papers written simultaneously by Dr. William Budd and myself; ' and in Dr. Budd's essay you may find it nearly demonstrated, by a masterly discussion of the subject, that in most of these cases, the morbid material enters into combination with the tissue which is dis- eased, or with the organised product of the morbid process. Now the evident and applicable truth in aU these cases is, that the morbid sub- stance in the blood, be it what it may, acts upon and changes only cer- tain portions of what we might suppose to be all the very same tissue. Such a substance fastens on certain islands on the surfaces of two bones, or of two parts of the skin, and leaves the rest unscathed : and these islands are the exactly corresponding pieces upon opposite sides of the body. The conclusion is unavoidable, that these are the only two pieces that are exactly alike ; that there was less aflanity between the morbid material and the osseous tissue, or the skin, or the cartCage, close by; else, it also would have been similarly diseased. Manifestly, when two substances display different relations to a third, their composition cannot be identical ; so that, though we may speak of all bone or of lall skin, as if it were all alike, yet there are differences of intimate com- ' Medico- Chiruvff. Trans, xxv. ITS NATURK, PUEPOSE, AND CONDITIONS. 15 position ; and in all t.lie body the only parts wMcli are exactly like each other, in their mntnal relation with the blood are those which are symmetrically placed upon the opposite sides. No power of artificial chemistry can, indeed, detect the difFerence ; but a morbid material can ; it tests the parts to which it has the greatest affinity, unites with these, and passes by the rest.' I might magnify the wonder of this truth by showing how ex- ceedingly small, in some of these cases, must be the quantity of the morbid material existing in the blood. But I prefer to illustrate a fact which singularly corroborates the evidence, afforded by symmetri- cal diseases, of the refinement of the operations of the affinities, if we may so call them, between the blood and the tissues. The fact is that of certain blood diseases having ' seats of election.' For example, in another lion's pelvis (No. 3024), diseased like that sketched above, not only is the morbid product just as symmetrical, but its arrangement is exactly similar : hardly a spot appears on one pelvis which is not imi- tated on the other. And these are only examples of a large class of cases of syphilis, rheumatism, and various skin diseases, of which the general character is, that the disease is much more apt to effect one certain portion of a bone, or of the skin, or of some other tissue, than to attack any other portion. We are all in the habit of using the fact as an aid in diagnosis : but we may have overlooked its bearing on the physiology of nutrition. It proves on the one hand, as the cases of symmetrical diseases do, that the composition of the several portions of what we call the same tissue is not absolutely identical : if it were these diseases should effect one part of a bone or other tissue as often as another part, or should affect all parts alike. And it proves, on the other hand, a constant similarity, even an identity of the morbid ma- terial on which each of these diseases depends, though it be produced ' Some of the differences here noticed are not permanent, but may seem to depend on the several parts of a bone, or of the skin, of a limb (for example), being in dif- ferent stages of development or degeneration. The symmetrical parts of the tissue, being extietly alike, may be simultaneously and equally affected by a disease, while other parts of the same remain unaffected, till, in the course of time, they attain, by development or degeneration, the very same condition as the parts first affected. Then, if the morbid material still exist in the blood, these parts also become diseased; and so in succession may nearly the whole of a tissue. This view agrees very well with the fact that symmetrical diseases often spread, and so prove that a part which, in one week or month, is not susceptible to the influence of a morbid material, may in the next, become as susceptible as that which was first affected. This susceptibility, however, may be due, not to normal changes, but to the influence which the diseased portion of the tissue exercises on those aroundit. 1 6 NUTRITION i in different individuals ; so that we may venture to predict, that Vfhen- ever chemistry shall discover the composition of these materials, it will be found as constant and as definite as the composition of those inor- ganic substances which the science has most successfully scrutinised. Moreover, Dr. William Budd has proved that, next to the pdJts which are symmetrically placed, none are so nearly identical in com- position as those which are homologous. For example, the backs of the hands and of the feet, or the palms and soles, are often not only symmetrically, but similarly, affected with psoriasis. So are the elbows and the knees ; and similar portions of the thighs and the arms may be found affected with ichthyosis. Sometimes also speci- mens of fatty and earthy deposits in the arteries occur, in which exact similarity is shown in the plan, though not in the degree, with which the disease affects severally the humeral and femoral, the radial and peroneal, the ulnar and posterior tibial, arteries. To conclude, these symmetrical diseases with seats of election, indicate — 1st, That in the same person the only parts of any tissue which are identical in composition are, or may be, first, those which occupy sym- metrical positions, on the opposite sides of the body ; and next, those which are in serial homology. 2cZZi/, That the portions of the bodies of different individuals which are identical, or most nearly so, in composition, are those in exactly corresponding positions. Mly, That even in different individuals the specific morbid materials, on which many of the diseases of the blood depend, are of identical composition. It would be foreign to my purpose to enter now upon all the sub- jects of interest which are illustrated by these cases. I may refer yoa again to the papers already mentioned, especially to Dr. Budd's. For the present it will be suflScient if I have pointed out (without pretend- ing to explain or describe) the perfect and most minute exactness of the adaptation which, in health, exists between the blood and all the tissues ; and that certain inconceivably slight disturbances of this ad- aptation may be sources of disease. If this be admitted, I shall not fear to be met with an objection against too great refinement in what I shall next say concerning some of the means by which that right state of the blood, which is appropriate to the healthy nutrition of all the parts, is "attained and preserved. 17 LECTURE 11. THE CONDITIONS NBOBS&AET TO HEALTHY NDTKITION. I NEED not dwell on tlie physiology of the processes of digestion, absorption, excretion, and others, which, on the large scale, serve in the development and maintenance of the blood. The admitted doctrines concerning these I must assume to be well known, while I proceed with the consideration of those minuter relations in which the blood and the several tissues exercise their mutual influence, and by which each is maintained in its right state. And, first, let me endeavour to develope a principle, the germ of which is in the writings of Treviranus. His sentence is, that " each single part of the body, iu respect of its nutrition, stands to the whole body in the relation of an excreted substance." ' In other words, every part of the body, by taking from the blood the peculiar substances which it needs for its own nutrition, does thereby act as an excretory organ, inasmuch as it removes from the blood that which, if retained in it, would be injurious to the nutrition of the rest of the body. Thus, he says, the polypiferous zoophytes all excrete large quantities of calcareous and siliceous earths. In those which have no stony skeleton these earths are absolutely and utterly excreted ; but in those in which they form the skeleton, they are, though retained within the body, yet as truly excreted from the nutritive fluid and aU the other parts, as if they had been thrown out and washed away. So the phosphates which are deposited in our bones are as effectually excreted from the blood and the other tissues, as those which are discharged with the urine. But Treviranus seems not to have apprehended the full importance of the principle which he thus clearly, though so briefly, stated ; for it admits, I think, of far extension and very interesting application. ' Die Erscheinwngen und Gesetze des organischeii Lebens, B. i. p. 401. In an article on hereditary influences in the Westminster Review, July 1856, and in his work on the Physiology of Common Life, i. p. 286, Mr. G-. H. Lewes states that C. F. Wolff, and not Treviranus, was the original expositor of this doctrine. — See Theoria Generationis, 1759. 18 CONDITIONS NECESSARY TO Its influence may be considered in a large class of oat-growing tissues. The hair, for example, in its constant growth, serves, not only local purposes, but for the advantage of the whole body, in that, as it grows, it removes from the blood the various constituents of its substance which are thus excreted from the body. And this excretory oflace appears, in some instances, to be the only purpose -which the hair serves ; as, for example, in the foetus. Thus, in the foetus of the seals, that take the water as soon as they are born, and, I beHeve, in those of many other mammals, though they are removed from all those con- ditions against which hair protects, yet a perfect coat of hair is formed within the uterus, and before, or very shortly after, birth this is shed, and is replaced by another coat of wholly different colour, the growth of which began within the uterus. Surely, in these cases, it is only as an excretion, or chiefly as such, that this first growth of hair serves to the advantage of the individual. The lanugo of the human foetus is an homologous production, and must, I think, similarly serve in the economy by removing from the blood, as so much excreted matter, the materials of which it is composed. Further, I think, we may carry this principle to the apprehension of the true import of the hair which exists in a kind of rudimental state on the general surface of our bodies, and to that of many other permanently rudimental organs, such as the mammary glands of the male, and others. For these rudimental organs certainly do not serve, in a lower degree, the same purposes as are served by the homologous parts which are completely developed in other species, or in the other sex. To say they are useless, is contrary to all we know of the absolute perfection and all-pervading purpose of Creation ; to say they exist merely for the sake of conformity with a general type of structure, seems unphilosophical, while the law of the unity of organic types is, in larger instances, not observed, except when its observance contributes to the advantage of the individual. Rather, since all these rudimental organs must, as they grow, be as excretions, we may believe that they serve a definite purpose in the economy, by removing their appropriate materials from the blood, and leaving it fitter for the nutrition of other parts, or by adjusting the balance which might else be disturbed by the formation of some other part. Thns they may minister to the self- interest of the individual, while, as if for the sake of wonder, beauty, and perfect order, they are conformed with the great law of the unity of organic types, and concur with the universal plan observed in the construction of organic beings. HEALTHY NUTRITIO^f. 19 And again — the principle that each organ, while it nourishes itself, serves the purpose of an excretion, has an application of peculiar interest in the history of development. For if it be influential whea all the organs are already formed, and are only growing or maintaining them- selves, much more will it be so when the several organs are successively forming. At this time, as each nascent organ takes from the nutritive material its appropriate constituents, it will co-operate with the gradual self-development of the blood, to induce in it that condition which is essential, or most favourable to the formation of the organs next in order to be developed. The importance of this principle will the more appear if we connect with it another, equally characteristic of the minuteness of the relation between the blood and the tissues — namely, that the existence of certain materials in the blood may determine the formation of structures of which they may be incorporated. This seems to be established as a general law in pathology, by the cases in which diseased structures evidently incorporate materials that had their origin or previous existence in the bloody Such are most of those inoculable and other blood-diseases in which morbid organisms are produced ; as vaccinia, variola, chancre, glanders, etc. The same law may be made very probable in physiology also. For example, when one kidney is destroyed the other often becomes much larger, does double work, as it is said, and the patient does not suffer from the retention of urine in the blood ; the full meaning of which (a well- known fact, and not without parallel) may be thus expressed : — The principal constituents of the urine are, we know, ready formed in the blood, and are separated through the kidneys by the development, growth, and discharge of the contents of the renal cells in which they are for a time included. Now, when one kidney is destroyed, there must for a time be an excess of the constituents of urine in the blood ; for since the separation of urine is not naere filtration, the other kidney cannot at once, and without change of size, discharge a double quantity. What, then, happens ? The kidney grows ; more renal cells develope, and discharge, and renew themselves ; in other words, the existence of the constituents of the urine in the blood that is carried to every part determines the formation of the appropriate renal organs in the one appropriate part of the body. An analogous fact is furnished by the increased formation of adipose tissue in consequence of the existence of abundant hydro-carbon principles in the blood. Another, bearing on the same point, though c 2 20 CONDITIONS NECESSARY TO not admitting of definite description, is the influence exercised by- various diets in favouring the especial growth of certain tissues as the muscles, the bones, the hair, the wool. Similar facts are yet more evident in the cultivation of vegetables, to which various materials are supphed, in the assurance that certain corresponding tissues wUl be consequently formed. And an evident illustration of the same principle is in the abundant formation of fruit on a branch in which the matured sap has been made to accumulate by ringmg. I add again, on this point, as on a former one, that the case as concerning nutrition is remarkably corroborated by the observation of similar facts iu instances of secretions. Thus, the excesses of albuminous materials taken in food, if they be not incorporated in the more highly organised tissues, are excreted, that is, they, or the materials into which they are transformed, enter into the construction of the transient tissue of the kidney or some excretory organ. The constituents of food, plainly as they influence the quantity and quality of milk, do so only by affecting, after their admission into the blood, the formation of the transient parts of the mammary gland-tissue. Medicines, such as diuretics, that are separated from the body by only certain organs, are, for a time, we must believe, incorporated in the tissues of those organs. These facts seem enough to make highly probable the principle I mentioned — namely, that the existence of certain materials in the blood may determine the formation of structures into the composition of which those materials may enter. At anyrate, they make it nearly certain for the more lowly organised tissues, and for the products of disease ; and hence, by analogy, we may assume it for the other tissues. Even for the highest, we may safely hold that a necessary condition of their formation is this previous existence of the peculiarly appropriate materials in the blood. Now, if we combine these two principles — first, that the blood is definitely altered by the abstraction of every material necessary for the nutrition of a part, and secondly, that the existence of certain materials in the blood induces the formation of corresponding tissues, we may derive from them some very probable conclusions bearing on the questions before us. First, we may conclude that the order in which the several organs of the body appear in the course of development, while it is conformable with the law of imitation of the parent, and with the law of progressive ascent towards the higher grade of being, is yet in part, and in this more directly, the result of necessary and HEALTHY NUTRITION. 21 successive consequences ; the formation of one organ, or series of organs, inducing or supplying a necessary condition for the formation of others, by the changes successively produced in the composition of the blood, or other nutritive material. In other words, we may hold, in accordance with these principles, that the development of each organ, or system, co-operating with the self-development of the blood, prepares it for the formation of some other organ or system, till, by the successive changes thus produced, and by its own development and increase, the blood is fitted for the maintenance and nutrition of the completed organism. Secondly, I think that these principles may be applied to individual instances. They may suggest that certain organs stand, in their nu- trition, in a complemental relation to each other ; so that neither of them can be duly formed or maintained in healthy structure, unless the right condition of the blood be induced and preserved by the formation of the other. It is, of course, very difficult, or even impossible, to find instances by which this theory of complemental nutrition can be proved ; while, really, we neither know exactly what materials are necessary for the formation of any organ, nor have the means of detecting the presence of more than a very few of them in the blood. It is very well in the discussion of certain parts of physiology to say, for instance, that a muscle mainly consists of a material like fibrine ; but when we are con- sidering the physiology of the formation of organs, we must remember that in every muscular fibre there are at least three different com- pounds — those of the sarcolemma, of the nucleus, and of the fibril ; that these are all equally essential to the formation of the fibre, and that we know not the composition of any one of them, nor could detect the absence of any one of them from the blood, though the result of that absence might be to render the formation of a muscular fibre im- possible. But, though it may lack direct evidence, the theory seems, in itself, probable ; and there are many facts which we can explain by it so well that they become evidence for it — which facts, moreover, are fair sub- jects for theoretical explanation, since, I believe, they are admitted to be as yet wholly unexplained. Among these is the general fact that a great change in nutrition rarely takes place in one organ at a time, but usually afiects simul- taneously two or more parts, between whose nutrition there is a mani- fest and constant connection, although there is little or no relation 22 CONDITIONS NECESSARY TO between their external functions. Such, to take an instance from a large class, is the connection between the growth of various appendages of the integuments, and the development or maintenance of the genital organs. This appears to be a general rule. The growth of the beard at the period of puberty in man, with which we are so familiar, is more instructively represented in many animals — especially in birds. In these, as you know, at the approach of every breeding time, the genital organs begin to develope themselves for the season, as in man they do for the whole time of vigorous life. And commensurately with this development the plumage (especially in the male bird) becomes brighter and more deeply coloured, both by the growth of new feathers and by the addition of colour to the old ones. The height and perfection of the plumage are coincident with the full development and activity of the reproductive organs ; but, as in man, when the development of the genital organs is prevented, that of the beard and all the other external sexual characters is, as a consequence, hindered ; so in birds, when the breeding season ends, and the sexual organs pass gradually into their periodic atrophy at once the plumage begins to assume the paler and more sober colours which characterise the barrenness of winter. So it is also, at least in certain instances, in the mammalia, of which we have interesting evidence in the history of specimens presented to the museum of the college by Sir Philip Egerton. These show that if a buck be castrated while his antlers are growing and still covered with the velt, their growth is checked, they remain as if truncated, and irregular nodules of bone project from their surfaces. Or if the castra- tion be performed when the antlers are full-grown, these, contrary to what Redi said, are shed nearly, as usual, at the end of the season, but in the next season only a kind of low conical stumps are formed in the place of antlers.' I need not multiply examples ; it is a general fact that the develop- ment and activity of the reproductive organs have, as a consequence, or as a necessary coincidence, a peculiar development and active growth or nutrition of certain other structures ; which structures, therefore form the external sexual characters, though their external functions stand in no apparent, often in no conceivable, connection with the generation of the species. The fact is not hitherto explained ; it is ex- plicable on the theory of complemental nutrition, by believing that the ' This formation of imperfect antlers may depend on the accessory organs of repro- duction being developed; for these would not necessarily fail to l,e developed because the testicles were extirpated. HEALTHY NUTRITION. 23 materials which, in the formation of these organs of external sexual character, ax-e removed from the blood, leave or maintain the blood in the state necessary for the further development, growth, and active function of the proper sexual or reproductive organs. In other words, I would say that where two or more organs are thus manifestly con- nected in nutrition, and not connected in the exercise of any external office, their connection is because each of them is partly formed of ma- terials left in the blood on the formation of the other ; and each, at the same time that it discharges its own proper and external office, main- tains the blood in the condition most favourable to the formation of the other. If this theory be admissible we may find through it the meaning of the commensurate development and nutrition of many other organs, which in their external functions appear unconnected. Such are the concurrent development and activity of the thymus gland and the air- breathing organs during the body's growth ; of the thyroid gland and the brain (instances of commensurate development cited by Mr. Simon)' of the spleen and pancreas (as pointed out by Professor Owen) ; and, I would add, of the embryo and the mammary gland ; for the same theory may hold true concerning the formation of certain organs which are, finally, connected in their external functions. In these, and other like cases, I think it will be hereafter proved that the several organs are in their nutrition complemental, that the formation of each leads to the production of some material necessary for the construction of the other ; and that, as we may be sure of Treviranus' law in general — that each organ of the body, while it nou- rishes itself, is in the character of an excretion towards all the rest — so we may believe, more particularly, that certain organs are mutually as excretions from each other.^ But, thirdly, if there be any probability in the principles I have endeavoured to illustrate, they must deserve careful consideration in the pathology of the blood. I shall have to illustrate them in this view • Essay on the Thymus Gland; and Philosophical Transactions, 1844, pait ii. ^ Many of the phenomena, for which the above theory is offered as an explanation, would be doubtless looked upon by Mr. Darwin, in conformity with his views of the origin of species, as due to hereditary transmission ; many structures being retained by hereditary transmission through many generations after they have ceased to have a direct relation to the habits of life of each species. But, as has been pointed out by Professor RoUeston in an able article in the Natural History Seview, 1861, p. 484, all of the above instances cannot be brought under that head, and the explanation given in the text seems warranted by the present state of our knowledge. 24 CONDITIONS NECESSAEY TO in fature lectures. At present I will only suggest that if each part in its normal nutrition is as an excreting organ to the rest, then the ces- sation or perversion of nutrition in one must, by no vague sympathy, hut through definite change in the condition of the hlood, affect the nutrition of the rest, and be thus the source of ' constitutional distur- bance.' If, in health, there be such a thing as complemental nutrition, it must, in disease, be the source of many sympathies in nutrition be- tween parts which are not specially connected through the nervous sys- tem. If the condition of the blood can, in favourable circumstances, determine the formation of organisms incorporating its materials, we may study the characteristic structures of specific diseases as the evi- dences of corresponding conditions of the blood, and as organs which, by removing specific materials from the blood, afi'ect its whole consti- tution, and either restore its health or produce in it secondary morbid changes. The extent of application that these principles admit of will, I trust, justify the distance to which I may seem to have diverged from my starting-point. Let me now return to it, and remind you that this long discussion grew out of the consideration of the first condition necessary for healthy nutrition — namely, the right state of the blood ; a state not to be described merely as purity, but as one of exact adaptation to the peculiar structure and composition of the individual ; an adaptation so exact that it may be disturbed by the imperfect nutrition of a single organ, and that for the maintenance of it, against all the disturbing forces of the outer life of the body, nothing can suflice except continual readjustment by the assimilative power of the blood itself The second condition of which I spoke as essential to the healthy process of nutrition is — A regular supply of appropriate Blood in or near the part to be nourished. The proofs of the necessity of this condition must be familiar to all. Instances wiU at once occur to your minds in which too little blood being sent to a part it has sufiered atrophy or degeneration ; others in ■which the supply being wholly cut off, mortification has ensued ; others in which the blood, being stagnant in a part, has not efficiently contri- buted to its nutrition. If I can give any interest to this part of the subject, it is only by adducing interesting examples of the fact. Reserving for future lectures the examples of merely diminished and of perverted nutrition, I will HEALTHY NUTRITION. 25 mention now only some of the specimens in tte Museums 1 have chiefly studied, which illustrate how the process of nutrition is wholly stopped by the absence or deficiency of fresh blood. One of Mr. Swan's donations to the College Museum (No. 1821) is the larynx of a man who, while in low health, cut his throat, and sufiered so great a loss of blood that the nutrition became impossible in one of those parts to which blood is with most difficulty sent ; before he died, his nose sloughed. The case is like one which, you may remember, is recorded by Sir Benjamin Brodie.' A medical man wished to be bled, in a fit of exceeding drunkenness ; and some one bled him — bled him to three pints. He became very ill, and next day both his feet were mortified from the extremities of the toes to the instep. A specimen (No. 141), presented by Mr. Guthrie, exhibits a mor- tified, i.e. a completely unnourished leg, from a case in which the femoral artery was obliterated near the groin, through disease of its coats. The leg was amputated by Mr. Guthrie, with justifying success ; for the stump, though cut at some distance below the obliteration of the artery, did not slough ; the collateral circulation was sufficient for its nutrition ; and the patient, an elderly lady, died only of exhaustion. For a similar and very rave example of sloughing after the obli- teration of a main artery, I may refer to the case described by Mr. Vincent, of a large slough in the very substance of one of the hemi- sjjheres of the cerebrum, in consequence of a wound of the supplying common carotid, — a wound made with a tobacco-pipe thrust into the bifurcation of the carotid, and nearly closing its channel.* A specimen in the Museum of St. Bai'tholomew's Hospital (Series i. 134), exhibits an instance of dry gangrene, occurring in very unusual circumstances. A woman, 48 years old, died, under the care of Mr. Earle, having received some injury of the femur eighteen months before death. Whether it were a fracture, or, indeed, what it was, cannot now be 'said ; but the injury was followed by enlargement of that por- tion of the wall of the femur with which the artery and vein are nearly in contact, as they pass through the sheath of the triceps adduc- tor muscle. At this part, then, the vein is compressed, and the artery, though not distinctly compressed, appears to have been hindered from enlarging. The consequence was dry gangrene of the leg, which slowlj destroyed life, and which had no other apparent cause than this. ' Lectures on Pathology and Surgery, p. 350. ^ Medico- Chirurgical Transactions, xxix. p. 38. 26 CONDITIONS NECESSARY TO And, lastly, let me refer to two specimeDS, wtioh are as interesting in the history of surgery as in pathology. One is a tibia and fibula, the lower ends of which, together with the whole foot, perished in consequence of the obstruction of the circulation by an aneurism in the ham. It is an Hunterian specimen in the College Museum (No. 710) ; and surely we may imagine that sometimes Mr. Hunter would contem- plate it with pride to think how rare such things would be in after times. In strong contrast is this other specimen : the limb of a man who once had an aneurism, like the one which in the former case was so destruc- tive, and on whom Hunter was permitted to confer fifty years of healthy life by his operation of tying the artery at a distance from the diseased part. The College Museum (3472 a.) owes this rare specimen and most interesting relic to the zeal of Mr. Wormald. The patient was the fourth on whom Mr. Hunter performed his operation. He was thirty- six years old at the time ; and though the tumour was not large, yet the whole leg was swollen, the veins were turgid, and he was exhausted, and in such bad health, that the case seemed desperate ; but he re- covered, and lived, as I have said, fifty years. The artery was tied in the sheath of the triceps muscle ; and in this operation, for the first time, Mr. Hunter did not include the vein in the Hgatui-e. He thus diminished exceedingly the danger of the defective supply of arterial blood. The preparation shows the whole length of the artery oblite- rated from the origin of the profunda to that of the anterior tibial, and the aneurismal sac, even after fifty years, not yet removed, but re- maining as a hard mass like an olive.' Now, the supply of appropriate blood, of which these specimens prove the necessity, must be in or near the part to be nourished. "We cannot exactly say how near it must be, but, probably, all that is necessary is, that the nutritive material should admit of being imbibed in sufficient quantity into the substance of the part. For imbibition must be regarded as the means by which all parts supply themselves with nutritive matter ; thus deriving it from the nearest bloodvessels and the bloodvessels themselves being only the channels by which the materials are brought near. The bloodvessels thus serve alike for the nutrition of the vascular, and, as we call them, the non- vascular parts the difference between which parts, in this regard, is really very little! For in both cases the bloodvessels lie outside the textures to which 'The case is in the Transactions of a Society for the improvement of Medical and Surgical Knowledge, i. p. 138 ; and in Hunter's Works, iii, p. 604. HEALTHY NUTRITION. 27 they convey the nutritive fluid, and though, in the vascular parts, this fluid is carried in streams into their interior, whilst in the non- vascular it flows only on or near the surface, yet, in both alike, the parts to be nourished have to imbibe the nutritive fluid, and the business of formation is outside the vessels. The distance between the blood- vessels and the textures in the two cases is thus simply a difierence of degree. Thus in a highly vascular glandular organ, e.g. a salivary gland, the bloodvessels are separated from the active secreting cells merely by the thin limiting membrane of the gland-vesicles. In a muscle, again, whilst the fibrils at the periphery of a fibre are separated from the bloodvessels only by the thickness of the sarcolemma, those in the very centre are removed to a greater distance from them. In the osseous tissue, when it exists in thin layers, as in the lachrymal and turbinated bones, the bloodvessels do not pass into the interior, but lie in the mucous membrane on the surface. On the other hand, when it exists in masses, as in the stronger bones, bloodvessels run into the Haversian canals in its substance. Thus the same tissue yields an illustration of a vascular and non-vascular texture. In both forms of the tissue the mode in which the nutriment is obtained is the same ; in both, the vessels are at some distance from the texture. In adaptation to its density, and consequent comparative impermeability, the osseous tissue possesses a peculiar system of canals and spaces, termed canali- culi and lacunee, in the latter of which, as Mr. Goodsir ' was the first to show, a soft, nucleated substance is situated. The laonnse communicate not merely with each other, but with the Haversian canals in which the bloodvessels lie. Nutritive material, derived from the blood, readily permeates this soft protoplasm, and is brought into close relation with the ultimate osseous texture. In the dentine of a tooth a corresponding system of canals, the dentine tubes, occupied as was shown by Professor Owen^ and Mr. Tomes,^ by delicate prolongations of the tooth-pulp, convey the nutritive material not only to the ivory itself, but to the enamel and tooth bone. The non -vascular epidermis, again, though no vessels pass into its substance, imbibes nutritive matter from those which lie in the sub- jacent cutis and maintains itself and grows. Cartilage, similarly, is nourished by the bloodvessels of the perichondrium and the adjacent ' Anatomical and Pathological Observations, 1845. Anatomical Memoirs, ii. p. 462 ; Edinburgh, 1868. ^ Article '^Teeth,' Oyclopsdia of Anatomy and Fhysiology, p. 929. ' Proc. Boy. Soc. London, March 13, 1856. 28 CONDITIONS NECESSARY TO bone. The cornea, crystalline lens, vitreous humour, peripheral part of the umbilical cord, are still more strongly marked examples of non- vascular parts. In most of these, as well as in fully formed tendon, a system of cells, the connective tissue corpuscles has been of late years described by Virchow and others, formed apparently of soft nucleated protoplasm, which probably, like the lacunse and canaliculi of bone, serve to imbibe and transmit through their processes nutritive material to the more intimate parts of the texture. This mode of nutrition by imbibition in all the forms of tissue is worth remembering, else we cannot understand how the non- vascular tissues, such as the cornea, the hair, the articular cartilages, and the various cuticles, should be liable to diseases proper to themselves, primarily and independently. And except by thus considering the sub- ject, we shall not be clear of the error and confusion which result from speaking of the ' action of vessels,' as if the vessels really made and un- made the parts. We have no knowledge of the vessels as anything but carriers of the materials of the nutrition to and fro. They only convey and emit the ' raw material ; ' it is made up in the parts, and in each after its proper fashion. The real process of formation of tissues is altogether extra-vascular, even, sometimes, very far extra- vascular ; and its issue depends in all cases chiefly, and in some entirely, on the affinities (if we may so call them) between the part to be nourished and the nutritive fluid. The third condition essential to the healthy nutrition of parts is a certain influence of the Nervous System. It may be held, I think, that in the higher vertebrata some nervous force is habitually exercised in the nutrition of all the parts in or near which nerves are distributed : and that it is exercised, not merely in aifecting or regulating the size of the bloodvessels of the part, but with a more direct agency as being one of the forces that concur in the formative process. Of late years a current of opinion has run against the belief of this ; ' and of those who admit some influence of the nervous system upon the nutrition of parts, many do it, as it were, grudeingly and doubtfully.^ They hold that at most the influence is exercised only in- directly, through the power which the nervous system has of affecting ' This could be justly said in 1853 and even in 1863, -when the first and second editions of these lectures were published. In 1869 the current of opinion is reversed and disturbances of nerve-force seem to many the great agents in pathology. ^ Virchow, Cellular Pathologie, lecture xiv. HEALTHY NUTRITION. 29 the size of the bloodvessels ; or that the nervous system influences only the degree without afi'ecting at all the mode of nutrition in a part. One chief argument against the belief that the nervous force has a direct and habitual influence in the nutritive process is, that in plants, in the early embryo, and in the lowest animals, in which no nervous system is developed, all their nutrition goes on well without it. But this is no proof that in animals which have a nervous system, nutrition is independent of it ; rather, even if we had no positive evidence, we might assume that in ascending development, as one system after another is added or increased, so the highest of all, the nervous system would be inserted and blended in a more and more intimate relation with all the rest. This would indeed be only according to the general law, that the inter- dependence of parts augments with their develop- ment : for high organisation consists not in mere multiplication or di- versity of independent parts, but in the intimate combination of m.any parts in mutual maintenance. Another argument implies that the nervous force can manifest itself in nothing but impressions on the mind, and in exciting muscular con- traction. So limited a view of the convertibility of nervous force is such an one as the older electricians would have held, had they main- tained that the only possible manifestations of electricity were the at- tractions and repulsions of light bodies, or that the electric force could never be transformed into magnetism, chemical action, or heat. We are too much shackled with these narrow dogmas of negation. The evidence of the correlation and mutual convertibility of the physical forces — of the transformation of energy — might lead us to anticipate a like variety of modes of manifestation for the nervous and other forces exercised in the living body.' We might anticipate, too, that, as the nervous force lias its origin in the acts of nutrition by which the nerve- substance is formed, so by reciprocal action its exercise might afiect the nutritive acts. As (for illustration's sake) the completed blood affects all the processes by which itself was formed, so, we might suppose, would the nervous force be able to affect all the acts of which itself is the highest product. But we need not be content with these probable deductions con- cerning the direct influence of the nervous force on the nutritive process. The facts bearing on the question are sufficient for the proof. And first we may consider the influence exercised by the nervous ' For references to the works on this subject, see note, p. 46. 30 CONDITIONS NECESSAEY TO system on the bloodvessels of a part. The ■well-known observations of Bernard, which have received additional elucidation from the experi- ments of "Waller, Budge, Brown- Sequard, Schiff, Wharton Jones and Lister, prove that division of the sympathetic nerve of a part is follow- ed by enlargement of the bloodvessels, a more rapid flow of blood, in- creased redness, and temperature of that part. Again, irritation of the same nerve produces contraction of the bloodvessels, pallor, and di- minished temperature of the part. But the influence of the nervous system in nutrition is not limited to that which it may thus indirectly exercise through the medium of the bloodvessels on the supply of blood. Indeed, some of Bernard's and other experiments show that parts whose bloodvessels are thus paralysed, retain with little change their normal structure ; and obser- vations have been made which afibrd evidence that the nervous system may exert a direct influence on the proper tissues of a part. Amongst the most important facts which may be adduced in support of this im- mediate action, are the very striking experiments of Professor Lister,^ on the cutaneous pigmentary system of the frog, in which the pigment is contained in radiated cells. When the nerves proceeding to a part of the body were divided, the pigment in the same region became diffused throughout the processes of the various cells, and the skin as- sumed a dark tint ; a condition which is comparable with the dilatation of the bloodvessels after division of the sympathetic nerves. But when the nerves were irritated, then concentration of the pigment took place and pallor of the skin was produced, a result which is analogous with the contraction of the muscular fibres in the walls of the vessels, after irritation of the sympathetic nerve. The value of these facts is strengthened by the consideration of the manifold and distinct influences of the nervous force upon secretion for the process of secretion is so essentially similar to that of nutrition that whatever can be proved of the method of one, might be inferred for that of the other. By the experiments of Ludwig, Bernard Bidder ^ and other physiologists, the nerves have been sLown to influence the quantity of secretion formed in glands. By irritating the nerves pass- ing to the lachrymal and salivary glands, the secretion poured out by the duct is increased, and the pressure of the blood augmented, so that it traverses the vessels with a greater flow, and provides a larger supply ' philosophical Transactions, 1858. 2 Eeichert and Du Bois Eeymoud's Archiv, pp. 1, 771, 1867- HEALTHY NUTRITION. 31 of pabulum for the chemical processes which take place in the gland. But the observatious of Pfliiger and Boll ' on the minute structure of the salivary glands, and those of Lstzerich ^ on the mode of termination of the nerves in the testicle, would seem to show that the minute nerve- fibres in these various glands pierce the membrana propria of the acini and tubes, and come into close relation with the secreting cells. It seems not unreasonable, therefore, to suppose that the nerves may act, not merely by affecting the pressure of blood through their influence on the contraction or dilatation of the bloodvessels, but immediately on the secreting cells, and when stimulated, may incite them to increased activity in a manner analogous to the action of a nerve on a muscular fibre. No tissue, indeed, seems to be wholly exempt from the influence of the nervous force on its nutrition. In the cuticle it is manifest ; and, for its influence in acting even through a considerable distance, I may mention a case, which is also in near relation to those in which the hair grows quickly grey, in mental anguish. A lady, who is subject to at- tacks of what are called nervous headaches, always finds in the morn- ing after such an one, that some patches of her hair are white as if powdered with starch. The change is effected in a night, and, in a few days after, the hairs gradually regain their dark brownish col jur. The effects which disturbance of the nervous force may produce on the nutrition of a part, may not unfrequcntly be observed in man. Dr. Charcot has recorded' some cases where irritation of certain of the nerves of the limbs was followed by eruptions on the portions of the skin sup- plied by those nerves. Inflammation of the conjunctiva may be excited by stimulus of the retina ; inflammation of the testicle from mechanical irritation of the urethra ; vascular congestion can be instantly produced around a killed or intensely irritated part, or in and around a part in which paroxysms of neuralgia are felt. In Herpes Zona, also, the range of the inflammation seems to be determined by the course and distribution of the cerebral or spinal nerves of common sensation, and in this, as well as in other forms of herpetic eruption,^ the attack is often preceded by violent neuralgia, and severe burning pain may persist in the part for some time even after the eruption has cleared away. Im- pairment of the nutrition of the skin, as a result of injury to the nerves is sometimes manifested by a peculiar glossy condition of the integu- ' Sehultze's Archiv, iv. p. 146. ^ Virchow's Archiv, March 1868. - Brown-Sequard's Journal, January 1859. * British MedicalJoumal, October 13, 1866. 32 CONDITIONS NECESSAEY TO ment. I have seen cases' where, after injury of the brachial plexus, the fingers have assumed a smooth, glossy, tapering appearance, almost void of wrinkles, and hairless, pink or ruddy, or blotched, as if with permanent chilblains, and, associated with this condition of the skin, was distressing local pain. The American army surgeons, Drs. Mit- chell, Morehouse, and Keen, in their admirable work on Gunshot and other Injuries of Nerves,'^ have confirmed my description of this ' glossy skin.' They compare the appearance which it sonaetimes presents to that of a highly polished scar, and especially point out that pain of a peculiarly burning character accompanies it. Not unfrequently they observed that the joints became swollen and painful, then stiff and hard and even partially anchylosed, a condition which I have also met with. Wasting of the muscles may also occur after division of their nerves, and in certain very painful affections of the nerves, wasting of whole limbs or parts of limbs naay probably be regarded as consequent on, or even diagnostic of, inflammation of the nerves themselves. Dr. Anstie also has recorded, ' as a result of successive attacks of neuralgia of the fifth nerve, conjunctivitis, ulcers of the cornea, periostitis of the frontal bone, stricture of the nasal duct, unilateral lachrymation and nasal flux, temporary unilateral blanching of the hair of the eyebrow and scalp, and unilateral furring of the tongue. In the Museum of St. Bartholomews (Ser. 9, No. 9) is an example of central penetrating ulcer of the cornea, in consequence of destruc- tion of the trunk of the trigeminal nerve, by the pressure of a tumour near the pons. * The whole nutrition of the corresponding side of the face was impaired ; the patient had repeated attacks of erysipelatous inflammation, bleeding from the nose, and at length destructive inflam- mation of the tunics of the eye and ulceration of the cornea. In the College Museum (No. 2177) is the hand of a man, whose case is related by Mr. Swan, the donor of the preparation. The median nerve, where it passes under the annular ligament, is enlaro-ed with adhesion to all the adjacent tissues, and induration of both it and them. A cord had been drawn very tight round this man's wrist seven years before the amputation of the arm. At this time it is probable the median and other nerves suffered injury ; for he had constant pain in the hand after the accident, impairment of the touch, contraction of the ' Medical Times and Gazette, March 26, 1864. ' Philadelphia, 1864. s Lancet, June 16, 1866. * The case is related by Mr. Stanley, Medical Gazette, i. 531. HEALTHY NUTRITION. 33 fingers, and (which bears most on the present question) constantly- repeated ulcerations at the back of the hand. Mr. Hilton has told me this case : — A man was in Guy's Hospital, who, in consequence of a fracture at the lower end of the radius, repaired by an excessive quantity of new bone, suffered compression of the median nerve. He had ulceration of the thumb, and fore and middle fingers, which resisted various treatment, and was cured only by so binding the wrist, that the parts on the palmar aspect being relaxed, the pressure on the nerve was removed. So long as this was done the alcers became and remained well; but as soon as the man was allowed to use his hand the pressure on the nerves was renewed, and the ulceration of the parts supplied by them returned. Mr. Travers' mentions a case in which a man had paraplegia after fracture of the lumbar vertebroe. He fractured at the same time his humerus and his tibia. The former, in due time, united ; the latter did not. Mr. De Morgan^ has related a similar case. A man fractured his twelfth dorsal vertebra, and crushed the cord; dislocated bis left humerus, and fractured fourteen ribs and bis left ankle. He lived eighteen days, during which the reparative process was active at the injuries above the damage of the cord, but seemed to be wholly want- ing at those below it. It would be easy to multiply facts of this kind, but I will only refer in general to the numerous recorded examples of the little power which paralysed parts have of resisting the influence of heat; of the sloughing after injury of the spinal cord ; of the slower repair and reproduction of parts whose nerves are paralysed or divided : all which facts alike contribute to prove that the integrity of the nervous centres and trunks, which are in anatomical relation with a part is essential to its due nutrition, or to its capacity of maintaining itself against the influence of external forces. But it should be remembered, as has, indeed, been explained by Brown-Sequard,' that it is disturbance, not mere defect of nerve force, which induces morbid nutrition. When there is cessation of action in a part, as after section of a nerve, slow and simple atrophy takes place. Obolensky* has found that, after section and removal of a portion of ' Further Inquiry cmcerning Cons/.itational Irritation, p. 436. ■■^ London Medical and Surgical Journal, Jan. 4, 1834. = Journal de la Fhysiologie, Jan. 1859. ' Central Blatt, No. 32, 1867. Journal of Anatomy and Physiology, Nov. 1867, p. 192. D 3-1 CONDITIONS NECESSARY TO the spermatic nerve, fatty degeneration of the cells within the seminal tubes occurs, together with, not unfrequently, conversion of the areolar into adipose tissue, and this takes place though the vessels of the gland remain uninjured. On the other hand, when the nervous system is irritated, as by pressure of a fractured spine, or other morbid cause on the cord, or compression of a nerve by a tumour, or inflammatory adhesion, then ulceration or gangrene is set up, as i?, indeed, illustrated by some of the cases just referred to. It may, perhaps, be said that when parts are deprived of nerve- force, their nutrition may be maintained, when all the other con- ditions, which act in the normal process, are undisturbed, but fails rapidly and extremely when these other conditions are defective, as in fevers, or in such a case as the following: — A man with nearly complete paraplegia, and distorted feet, the consequences of injuries of the spine, in whom some tendons were subcutaneously divided and appeared to be healing ; but a bandage being applied rather tightly, sloughing ensued at the instep, on which the chief pressure fell, and extended widely and deeply to the ankle-joints. Both the dorsal arteries were laid bare when the sloughs separated, and both the ankle- joints, and the case presented a most striking example of the defective self-maintenance of paralysed parts. But granulations formed after the separation of the sloughs, and the healing process went on slowly, but uninterruptedly, till all was covered in by a well-formed soar. Cases might also be cited to show the influence of the mind acting through the nervous system, and by nervous force on the formative processes in the whole body. There is scarcely an organ the nutrition of which may not thus be fifilcted by the mind. It is hardly necessary to adduce examples of a fact so often illustrated, yet I may mention this one : — Sir W. Lawrence removed, several years ago, a fatty tu- mour from a woman's shoulder ; and when all was healed she took it into her head that it was a cancer and would return. Accordingly, when by accident I saw her some months afterwards she was in a work- house, and had a large and firm painful tumour in her breast, which, I believe, would have been cut out, but that its nature was obscure, and her general health was not good. Again, some months afterwards, she became my patient at the Einsbury Dispensary : her health was much improved, but the hard lump in her breast ekisted still as large as an egg, and just like a portion of indurated mammary gland. Having heard all the account of it, and how her mind constantly dwelt in fear HEALTHY NUTEITION. 35 ■of cancer, I matin bold to assure her, by all that was certain, that the cancer, as she supposed it, wonld go away ; and it did become very much smaller, without any help from medicine. As it had come under the influence of fear, so it very nearly disappeared under that of con- fidence. But I lost sight of her before the removal of the tamour was complete. If, now, we may hold this influence of the nervous system to be proved, we may consider the question— through what class of nerves is the nutritive process influenced ? Indirectly, it is certain that the motor or centrifugal nerves may influence it, for when these are paralysed the muscles they supply will be inactive, and atrophy will ensue, first in these muscles, then in the bones (if a limb be the seat of the paralysis), for the bones in their nutrition obsoi'vo the example of their muscles ; and, finally, the want of energy in the circulation, which is in some measure dependent on. muscular action, will bring about the atrophy of the other tissues of the part. Hence, after a time, the evidences of paralysis of the facial nerve may be observed in nearly all the tissues of the face. The vaso-motor nerves, also, which regulate the size of the blood- vessels of a part, and act mediately, therefore, on its nutrition, pass to their place of distribution partly in sympathetic and partly in cerebro- spinal branches. For the vaso-motor nerves there seems to be, as Lud- wig and Thiry have shown, a central organ in the medulla oblongata,* which gives tone to these nerves, so that when the spinal cord in the neck is divided, as has not unfrequently been done in experimental inquiries into this subject, their tone is destroyed. TliG salivary-glands also, which have been carefully studied in con- nection with the influence exercised by the nerves on their secretion, receive branches, not only fiom the sympathetic, but from the trige- minal and portio dura. From experiments which have recently been made by Heidenhain,^ it wonld seem that not only an increased flow of secretion from the sub-maxillary gland, but also an elevation of tera- ' See also Salkowski, Henle und Pfevfers Zeitschrift, xxix. 167, and Dr. 'W. Eutherford s memoir ' On the Influence of the Vagus on the Vascular System,' in the Journal of Anatomy and Fkysiologi/, May 1869, p. 402, in which he argues that the contractile elements of the heart and bloodvessels are presided over by both a motor and an inhibitory system of nerves, the former of which excites contraction of the vessels, whilst the latter tlirows the motor nerves and contractile elements into a state of rest. '' Abstract by Mr. Power in Brit, and For. Med. Chir. liei'iew, July 1868, p. 260. D 2 36 CONDITIONS NECESSAEY TO peratuve, takes place both when the chorda tympani of the portio dura and the sympathetic nerves are irritated. Of late years, attempts have been made to show that some of the fibres of the nerves, which pass to a part or organ, regulate the nutri- tive process, act in short, as trophic nerves, not by influencing the size of the bloodvessels, but by direct action on the parenchyma or proper textures of the part. It is well known that when the trigeminal nerve is divided the eye-ball inflames, so that within a few days its textures may be greatly injured, or even destroyed, by the inflammation. Snellen • attempted to explain this by saying that the globe having lost its sensation, the inflammation was due to the action of irritating substances coming in contact with the eye, and that if means were taken to protect the cor- nea and conjunctiva the eyeball would remain intact. The experiments of Snellen have been repeated by SchifF,^ but not with the same results, for he found that in every case, after section of the trigeminal nerve, hyperasmia of the iris and conjunctiva occurred, though the opacity of the cornea was variable both in amount and position. Again, Meissner's^ observations show that if all the fibres of the trigeminus be divided except the innermost, no inflammation sets in, although no means be taken to protect the globe, and the loss of sensation is complete. If, on the other band, the innermost fibres only be divided, then the eye- ball inflames, though its sensation is not destroyed ; and the inference is drawn from these experiments that the trigeminus contains not only sensory fibres, but trophic nerves, which specially regulate the nutrition of the globe of the eye. The last condition which I mentioned as essential to healthy nutri- tion is a healthy state of the part to be nourished. This is, indeed, involved in the very idea of the assimilation which is accomplished in the formative process, wherein the materials are supposed to be made like to the structures among which they are deposited ; for unless the type be good the antitype cannot be. In a part which was originally well formed, and with which the three conditions of nutrition already illustrated have been always pre- sent, this fourth condition will probably be rarely wanting, for the part wiU not of itself deflect from the normal state unless in a premature degeneration, or in some disease to which it has an inherited or other • ' Be invloed der Zenuwen op de OntsteHng, Utrecht, ISr)?. 2 Nerven Phydologie, p. 387, 1859. ' HenU uni Pfeufers Zeitschrift, x-\ix. part i. p. 96. HEALTHY NUTRITION. 37 tendency. But when any part, or any constituent of the blood, has been injured or diseased, its unhealthy state will iaterfere with its nutrition long after the immediate effects of the injury or disease have passed away. Just as in healthy parts the formative process exactly assimilates the new materials to the old, so does it in diseased parts ; the new-formed blood and tissues take the likeness of the old ones in all their peculiarities, whether normal or abnormal ; and hence the healthy state of the part to be nourished may be said to be essential to the healthy process of nutrition. The exactness of assimilation accomplished by the formative pro- cess in healthy parts has been already in some measure illustrated, as preserving through life certain characteristic differences, even in the several parts of one organ ; preserving, also, all those peculiarities of structure and of action, which form the proper features, and indicate the temperament, of the individual. In these, and in a thousand similar instances, the precision of as- similation in the formative process is perfect and absolute, except in so far as it admits of a gradual alteration of the parts, in conformity with the law of chang'5 in advancing years. Nor is there less of exactness in the assimilation of which a part that has been diseased is the seat. For, after any injury or disease by which the structure of a part is impaired, we find the altered structure — whether an induration, a cicatrix, or any other — as it were, perpetu- ated by assimilation. It is not that an unhealthy process continues, the result is due to the process of exact assimilation operating in a part of which the structure has been changed — the same process which once preserved the healthy state maintains now the diseased one. Thus a scar or a diseased spot may grow and assimilate as its healthy neigh- bours do. The scar of the child, when once completely formed, com- monly grows as the body does, at the same rate, and according to the same general rule ; so that a scar which the child might have said was as long as his own fore-finger, will stiU be as long as his fore-finger when he grows to be a man. Tet though this increase and persistence of the morbid structure be the general and larger rule, another within it is to be remembered — namely, that in these structures there is usually (especially in youth) a tendency towards the healthy state. Hence, cicatrices, after long endurance, and even much increase, may, as it is said, wear out ; and thickenings and indurations of parts may give way, and all become again pliant and elastic. 38 CONDITIONS NECESSARY TO The maintenance of morbid structures is so familiar a fact tliat not only its wonder, but its significance, seem to be too mucb overlooked. "Wliat we see in scars and thickenings of parts appears to be only an example of a very large class of cases ; for this exactness by which the formative process in a part maintains the change once produced by disease, oflTers a reasonable explanation of the fact that certain diseases usually occur only once in the same body. The poison of small-pox, or of scarlet-fever, being, for example, once inserted, soon, by multi- plicatioh or otherwise, affects the whole of the blood— alters its whole composition — the disease, in a definite form and order, pursues its course — and, finally, the blood recovers to all appearance its former state. Yet it is not as it was, for now the same material, the same variolous poison, will not produce the same effect upon it ; and the alteration thus made in the blood or the tissues is made once for all ; for, com- monly, through all after-life the formative process assimilates, and never deviates from, the altered type, but reproduces materials exactly like those altered by the disease ; the new ones, therefore, like the old, are incapable of alteration by the same poison, and the individual is safe from the danger of infection. So it must be, I think, with all diseases which, as a general rule, attack the body only once. The most remarkable instance, perhaps, is that of the vaccine virus. Inserted once in almost infinitely small quantity, yet by mnltiplying itself or otherwise affecting all the blood, it may alter it once for all. For unsearchable as the changes it effects may be, inconceivably minute as the difference must be between the blood before and the blood after vaccination, yet in some instances that difference is perpetuated — in nearly all it is long retained, by assimila- tion the altered model is precisely imitated, and all the blood thereafter formed is insusceptible of the action of the vaccine matter. In another set of diseases we see an opposite, yet not a contra- dictory, result. In these, a part once diseased is, more than it was before, liable to be affected by the same disease, and the liability to re- currence of the disease becomes greater every time, although in the intervals between the successive attacks the part may have appeared quite healthy. Such is the case with gout, with common inflammation of a part, as the eye, and many others, in which people become, as they say, every year more and more subject to the disease. I do not pretend to determine the essential difference between the two classes of diseases in these respects, in which they are antipodal ; but in referenr* to the physiology of the formative process, they both HEALTHY NUTRITION. 39 proT^e the sime thing — viz. that an alteration once produced in a tissne, whether by external influence or by morbid material in the blood, is likely to be perpetuated by the exactness of assimilation observed in the formative process — i.e. by the consfcaut reproduction of parts in every respect precisely like their immediate predecessors. But it will be said, the rule fails in every case (and they are not rare) in which a disease that usually occurs but once in the same body, occurs twice or more ; and in every case of the second class in which liability to disease is overcome. Nay, but these are examples of the operation of that inner, yet not less certain, law — that after a part has been changed by disease, it tends naturally to regain a perfect state. Most often the complete return is not effected ; but sometimes it is, and the part at length becomes what it would have been if disease had never changed it. I would here refer again to what was said in the first lecture con- cerning the blood's own assimilative power. After the vaccine and other infectious or inocnlable diseases, it is most probably, not the tissues alone, but the blood as much as, or much more than they, in which the altered state is maintained ; and in many cases it would seem that whatever materials are added to the blood, the stamp once impressed by one of these specific diseases is retained ; the blood, by its own forma- tive power, exactly assimilating to itself, its altered self, the materials derived from the food. And this, surely, must be the explanation of many of the most in- veterate diseases : that they persist because of the assimilative forma- tion of the blood. Syphilis, lepra, eczema, gout, and many more, seem thus to be perpetuated : in some form or other, and in varying quantity, whether it manifests itself externally or not, the material they depend on is still in the blood ; because the blood constantly makes it afresh out of the materials that are added to it, let those materials be almost what they may. The tissues once affected may (and often do) in these cases recover ; they may have gained their right or perfect composition ; but the blood, by assimilation, still retains its taint, though it may have in it not one of the particles on which the taint first passed : and hence, after many years of seeming health, the disease may break out again from the blood, and affect a part which was never before diseased. And this appears to be the natural course of these diseases, unless the morbid material be (as we may suppose) decomposed by some specific ; or be excreted in the gradual tendency of the blood (like the tissues) to regain a normal state ; or finally, be, if I may so speak, stai-ved by 40 CONDITIONS NECESSARY TO tte abstraction from the food of all sucli things as it can possibly be made from. In some of these cases it may be doubted whether the long-main- tained change here spoken of is in the blood, or in the tissues, or in both. It may be said that the whole tissues of the body are changed in a fever or in any inoculable diseases ; and that these being once changed, and thenceforward maintained in their changed state by exact assimilation, cannot again be affected by the same morbid material, even though it should be again presented to them in the blood. It may be so ; and we must not, in the study of what we call blood-diseases, lose sight of the changes of the tissues, of the influence which, being changed, they afterwards exercise upon the blood. Yet it is hard to believe that the immunity from a second influence of the vaccine virus is due to a change produced by a first on the whole of the skin. And the vaccine is only an example of the whole class of diseases with which the body can be only once infected. In all these things, as in the phenomena of symmetrical disease, we have proofs of the surpassing precision of the formative process, a precision so exact that, as we may say, a mark o;ice made upon a par- ticle of blood or tissue, is not for years effaced from its successors. And this seems to be a truth of widest application ; and I can hardly doubt that herein is the solution of what has been made a hindrance to the reception of the whole truth concerning the connection of an im- material Mind with the brain. When the brain is said to be essential, as the organ or instrument of the Mind in its relations with the exter- nal world, not only to the perception of sensations, but to the subse- quent intellectual acts, 9,nd especially, to the memory of things which have been the objects of sense — it is asked, how can the brain be the organ of memory when you suppose its substance to be ever changing ? or, how is it that your assumed nutritive change of all the particles of the brain is not as destructive of all memory and knowledge of sensuous things as the sudden destruction by some great injury is ? The answer is, — because of the exactness of assimilation accomplished in the for- mative process ; the effect once produced by an impression upon the brain, whether in perception or in intellectual act, is fixed and there retained ; because the part, be it what it may, which has been thereby changed, is exactly represented in the part which, in the course of nu- trition, succeeds to it. Thus, in the recollection of sensuous things, the Mind refers to a brain, in which are retained the effects, or rather, the likenesses of changes that past impressions and intellectual acts had HEALTHY NUTRITION. 41 made. As, in some way passing far our knowledge, the Mind perceiv- ed, and took cognisance of tte change, made by the first impression of an object, acting through the sense organs on the brain ; so afterwards, it perceives and recognises the likeness of that change in the parts in- serted in the process of nutrition. Yet here also the tendency to revert to the former condition, or to change with advancing years, may interfere. The impress may be gradually lost or superseded, and the Mind, in its own immortal nature unchanged, and immutable by anything of earth, no longer finds in the brain the traces of the past. 42 • LECTURE III. THE FOKMATIVE PHOCESS : GKOWTn. Having now considered tte sources of the impairment to wliicli the completely formed blood and tissues are prone, and the chief conditions necessary for the perfection of the formatiFS process, by which, not- withstanding this impairment, they are maintained almost nnchanged, I propose to speak of the process itself. You may remember that I referred the impairment or wear and tear of the body to two principal sources — namely, the deterioration which every part suffers in the exercise of its function, and in the pro- duction of heat ; and the natural degeneration or death to which every part is subject after a certain period of existence, independently of the death or degeneration of the whole body, and in some measure inde- pendently of the exercise of function. The first question, therefore, in the consideration of the nntritive process may be — What becomes of the old particle, the one for the re- placement of which the process of formation is required ? In answer, we mnst, probably, di-aw a distinction, thongh we can hardly define it, between the parts which die and those which only degenerate when they have finished their conrse. Those which die are cast out entire — those which degenerate are disintegrated or dissolved, and absorbed. We seem to have a good example of this difference in the fangs of the two sets of teeth. Those of the deciduous ones degenerate, are trans- formed, so as to become solnble, and are absorbed ; those of what are called permanent — more properly, those of teeth which are not to be succeeded by others — die, and are cast out entire. And we may pro- bably hold it as generally true, that, as Mr. Hunter was aware, living parts alone are absorbed in the 1 issues ; dead parts, it is most probable, however small, are usually separated and cast out ; and, as the phen- omena of necrosis prove, this must be accomplished, not by the absorp- toin of the dead parts themselves or their borders, but by the absorp- THE FORMATIVE PROCESS. 43 tiou or retirement of the adjacent borders or surfaces of the living parts. Though, as Mr. Savory's experiments show,' dead bone may be absorb- ed if it bo subjected to continued pressure.^ External, merely integumental, parts appear thus to die and to be cast out entire from the body, but we have no certain knowledge of the changes they may undergo before they die. And with regard to the changes which take place in the degeneration that precedes absorption of the whole particles, we have again but little knowledge. Chemistry has, indeed, revealed much concerning the final disposal of the old materials : finding their elements in the excretions, and proving that the process is one of descent towards simplicity of organic chemical composition — one of approximation towards inorganic character — and, perhaps always, one accomplished by the agency of oxygen. It has also, we may safely believe, found in the muscles some of the substances into which the natural constituents of the tissues are transformed before they assume the composition in which they are finally excreted. Kreatine and kreatinine are, most probably, examples of such transi- tional compounds, intermediate between some of the proper constituents of muscle, and urea or uric acid. And I think that the frequency with v/hich fatty matter is found in degenerate parts is an indication that it is an usual product of similar transformation preparatory to absorption, and to the more complete combination with oxygen in the formation of carbonic acid and water for excretion. However, while we have so little knowledge of these intermediate or transitional substances, we can only hold it as generally probable that the components of the degenerate and worn-out tissues pass through a series of chemical transformations, which begin in their natural degeneration before absorption, and are continued during and after absorption till they are completed by the oxidation in the blood, which brings the materials to the state appro- priate for excretion. With regard to the formative portion of the process — that by which the old particle, however disposed of, is to be replaced — it is in many cases, though not in all, a process of development— a renewal for each particle of the process which was in nearly sinmltaneous operation for the whole mass in the original development of the tissue. ' Medwo-Chirurgical Transactions, p. 103, xlvii. 2 See Mr. Lister's observations in Lancet, March 23, 1867 ; also his experiments {Lancet, April 3, 1869) which prove that silk and catgut ligatures, saturated with carbolic acid, tied round an artery, the wound being dressed on the antiseptic system, may be absorbed by the action of the surrounding li^dng tissue. 44 THE FORMATIVE PEOCESS. There can be little doubt that such is the case in the hair, the teeth, the epidermis, and all the tissues which, from being situated on a free surface, we can watch ; in all these the process of repair or replacement is effected through the development of new parts. With' regard to the more internal parts, as the muscles and nervous textures, their position prevents us from obtaining so satisfactory a view of the nature of the formative process which goes on in them. Most probably there is not such a bodily replacement as in the structures more superficially placed, but the nutritive changes partake more of the molecular character, one particle being replaced by another, whilst, as it were, the original skeleton or frame-work of the texture is preserved. In all the parts, I think, which are the seats of active nutrition, nuclei, or cytoblasts, exist. These nuclei (such as are seen so abundantly in strong, active muscles) are not the loitering, impotent remnants of the embryonic tissue, but apparatus concerned in new formation. Their abundance is, I think, directly proportionate to the activity of growth. They are always abundant in the foetal tissues, and those of the yonng animal ; so they are in many quickly- growing tissues, and in the muscles, brain, and secreting tissues of the adult. And I think that their disappearance from a part in which they usually exist is an accompaniment and sure sign of degeneration. A very interesting subject of enquiry is involved in the consider- ation of the way in which parts repeat themselves in their nutrition, so that the structure which succeeds is constructed after the plan of that which preceded it. Take the case of the blood. The new red blood- corpuscles, that are being constantly formed for the renovation of the blood, are not developed from germs given oS from the old red globules ; neither are they formed by any assimilative force exercised by the old ones. The development of each is an independent repetition of the process by which those which precede it were formed. And so with the successive developments of ova and epithelial cells, and many others ; each is developed independently of the rest, and each repeats the changes through which its predecessors passed. Let it, then, be observed that each new elementary structure is made, in successive stages, like what the old one was, not like what it is ; as we see in the young hair following the course of the old one, or as the child is made like, not what his father is now, but what he was at his age. The new particle is, therefore, not made after a present model. If, now, we turn from the consideration of the method of the THE FOEMATIVE PROCESS. 45 formative process in tlie maintenance of the tissues, and from tliat of the conditions under wliicli it is exercised, to inquire into the nature of the forces which actuate it; if we try to answer why any structure just new-formed has assumed nearly the same form as the old structure had which it replaces, wo may find suggestions for an answer in the facts last mentioned. Among these facts we find (1), that a structure already formed exercises a certain assimilative influence on organic materials brought into contact with or near proximity to it ; and (2), that in many cases, and yet more clearly in instances of repair and re- production of injured and lost parts, the replacing structures are formed entirely anew, and independently of this influence. In these cases no model structure is present, to which the new-forming one may be assimilated; the new structure seems as if its own inherent properties had determined the form that it should take. Resting on the first class of facts, it seems to some a sufficient ex- planation of the process of maintenance to say, that each structure in the body has the power of taking from the blood, by a kind of electric affinity, certain appropriate materials, and of so influencing them that they assimilate themselves to it ; i.e. that they adopt or receive its form and properties, and incorporate themselves with it. Now, without doubt, the existence of such a selective power is justly assumed, and we may, by reference to it, express correctly a part of the processes by which the maintenance of the body is accomplished. Still it is, I think, clear that it is not sufficient for the maintenance of the body in its perfection. For, in the explanation of all the facts of the second class cited above, a theory of maintenance of the tissues by assimilation is inapplicable — not merely iusuflicient, but inapplicable ; for a postulate of this theory is the existence of a present model or germ for the construction of the forming part ; and in all these cases no such germ or model can be found. Therefore, finding, in these cases, that the formative process is accomplished in the maintenance of certain parts, without assimilation, we may assume, I think, that even when this condition is present, it is only as an auxiliary of some more constant and sufficient force. Of this force, whether we designate it the formative or vital force, by which the energy contained in food is directed in transforming the matter of food, in shaping and arranging it into organic structure ; of this force, and of those that co-operate with it, we can, I think, only apprehend that they are, in the completed organism, the same with those which actuated the formation of the original tissues in the 46 THE FORMATIVE PROCESS. development of tlie germ, and of the embryo. As we have seen that the new formation of elempntal strncturea in the maintenance of tissues is a repetition of the process observed in their first development, so we may assume that the forces operative are the same in both processes.' Thus, then, for explanation of the maintenance of tissues by the constant formation of nearly similar elemental structures, we are referred back to the history of their first formation ; and we might be content to rest in the belief that the mystery of the development of a germ is wholly inscrutable. We can discern in its method only this ; that the materials of which the impregnated germ first consists, and all that it appropriates, are developed according to the same method as was observed in its progenitors, so that at every stage it is like what they were at the same stage. It is in comforrnity with the same law of formation according to the example of progenitors, that when the general development of the body is completed, each of its parts is still maintained or gradually changed. In each period of life, the offspring resembles the parents at the corresponding periods of their life ; and, especially, in those degenerative changes which ensue in old age, we can discern no other method or law than still the same ; that the par- ental form, and properties, and life, are imitated or reproduced in the offspring. Now, can we trace anything further back than this fact ? Probably not: but we may express it in other terms, which may be more con- veniently used in our further inquiries, by saying that each germ de- rives from its parents such material properties that, being placed in the conditions necessary for the operation of the vilal forces, it will imitate in all the phases of the life of each of its parts, the changes through which the corresponding parts passed in the parents. It is convenient, and probably right, while we assume the operation of a vital force in the formative process, still to refer the method of its peculiar manifes- tations to the material properties of the substances in which it acts. ' The doctrine of correlation and conservation offeree, more correctly termed con- servation and transformation of energy, may be studied in its relations to physiology in the fJlowing ivorks :— Grove, The Correlation of the Physical Forces, 1842 and 1862; J. R. Mayer, Die Organische Bewegwng in ihrem Zusammenhdnge mit dem Stoffw'chse/, 1816, reprinted in Vie Mivhanik cler Wdrmr, Stuttgart, 1867 ; Carpenter, On the Mutual Itdations of the Vital and Physical Forces {Phil. Trans. 1850), and Qnartnly Journal of Science, 1864; Helmholtz, Die Erhaliung Der Kraft 1847 and Medical Times and Gazette, 1864 ; Sir W. Thomson, Proc. Roy. Soc. EdinLiu-gh, 1852 • Tyndiill, Heat Comidered as u Mode of Motion-, 1863 ; P. G. Tait, Article 'Force ' in' Gh^m] „-vs Encyc!op,r,lia, 1862, and Thermodynamic:, Edinburgh, 1868; H. Bence Jones, Croonian Lectures on Matter and Force, London, 1868. THE FORMATIVE PROCESS. 47 In the case before us we may accordiiigly assume tliat peculiar and typical properties are transmitted from its parents to tlie matei-ials of each impregnated germ ; that these determine the construction of cor- responding peculiar and typical forms ; that they are also communicated to whatever materials capable of organisation are brought within the sphere of the developing germ, so that these also determine the same, or some definitely related, method of construction ; and that thencefor- ward, throughout life, by similar communication or induction of specific properties in the forming blood or other nutritive fluid, the same method of formation is maintained in all the tissues. Unless we thus assume a dependence of form upon composition, of oro-anic structure upon organic constitution, I think we cannot under- stand, or even clearly speak of, many of the deflections from the nor- mal formative process which are due to injury or disease ; deflections which as we have seen, are maintained in the blood and lissmp, and the tendency to which is, in hereditary diseases, trausmitted from jarcnt to offspring with the other properties of the germ. The sum, then, of the hypothesis concerning the.formative processes in the maintenance of the tissues is as follows : — It is assumed first, that a certain vital or formative force is in constant operation ; secondly, that the forms and dimensions assumed under its direction depend primarily, and in greatest measure, on the specific composition, poten- tial energy,' and other properties of the organisable materials taken from the blood and continually renewed in it from the food ; and thirdly that these properties, transmitted in the first instance from the parent to the o-erm, are thenceforward communicated to the nutritive materials, subject, however, to certain progressive changes corresponding to the development and degenerations of the several tissues. It is assumed, farther, that the taking of materials from the blood, by each part for its own maintenance, depends, as to quality, on certain definite relations, or ' organic affinities ' between the blood and the part; and as to quantity, on the waste of the part. I fear I may have seemed to have engaged in a very useless discus- sion, and to have been talking of words more than of things ; but the charge will not be made by one who knows the utility of being clear in the expressions used for the ground-work of teaching ; or who will consider the importance in pathology of the principle that specific 1 Potential eneigy, in this sense, is the work wliich can be derived from the food in virtue of its quantity and chemical composition. 48 THE FORMATIVE PEOCESS. organic structares correspond with, and are determined by, specific organic compositions. I propose now to consider, bat as yet only generally, the second method of the formative process, Growth, in health and in disease. It consists in the increase of a part, or of the whole body, by addi- tion of new material like that already existing. Tlie essential charac- ters of each organ or tissne are maintained, but its quantity is increased and thus it is enabled to discharge more of its usual function. For a general expression of the course of events, we may say that the development and the growth of the body go on together till all the natural structures are attained ; and that then, development ceases, and growth goes on alone, till the full stature, and the full proportion of each part to the rest, are gained. But this is only generally true ; for we cannot say that all development ceases at a determinate period, since some organs may go on to be developed when many others are complete. Neither can we assign the period of terminated growth ; since, not only is the period, even stated generally, very various in different persons, but some parts, unless placed in unfavourable, con- ditions of disease, continue growing to the latest period of life. M. Bizot and Dr. Clendinning have proved, of the heart and arteries, that their average size regularly increases, though with a decreasing ratio of increase, from childhood to old age, provided only the old age be a lusty one.' And this is a real growth ; for the heart not only enlarges with advancing years, but its weight augments, and the thickness of its walls increases ; so that we may believe it acquires power in the same proportion as it acquires bulk — the more readily, since the in- creased power is necessary for the increasing difficulties put in the way of the circulation by the increasing rigidity of the parts. It may be that the same is true of some other parts. This certainly is true — ^that any part, after it has attained its ordinary dimensions, according to the time of life, may grow larger if it be more exercised : in other words, every part has, throughout life, the power of growing, according to its particular needs, in coirespondence with the decree in which its function is discharged. Now, when such growth as this is the result of the natural, though almost excessive exercise of a part (as of the limbs, for example, during hard work), we regard it only as an indication of health, and its result > Croonian Lectures bj Dr. ClendinDing, Medical Gazette, for 1837-8 xxu tj 450. ■ ^ HYPERTEOPHY. 49 is admitted to be a desirable accession of strength. But, when such growth in one part is the consequence of disease in another, it is com- monly described as a disease ; it bears the alarming name of Hyper, trophy; and it comes to be a subject of consideration in Morbid Anatomy. But in both these cases the process of growth is the same, and is according to the same rules ; and the tendency of the process of genuine hypertrophy in disease, like that of healthy growth in active exercise, is always conservative. I say genuine hypertrophy, meaning, under that term, to include only the cases in which the enlargement of a part is affected with development or increase of its natural tissue, with proportional retention of its natural form, and with increase of power. To include all enlargements under the name of hypertrophy is too apt to lead to misunderstanding. The rule then concerning hypertrophy is, that, so long as all con- ditions remain the same, each part of the body, after the attainment of the average size, merely retains its .state, or at most grows at a certain determinate slow rate ; but when the conditions alter, so that a part is more than usually exercised in its office, then it manifests a power of renewing or accelerating its growth. It is as if each healthy part had a reserve- power of growth and development, which it puts forth in the time of emergency. And the converse is equally true : when a part is less than usually exercised, it suffers atrophy ; so that the rule may be that each part nourishes itself according to the amount of function which it dis- charges. We may constantly see this rule in many more examples than I need refer to. The simplest case that can be cited is that of the epi- dermis. In its original formation, even before it has come into relation with the external world, it is formed on the several parts of the body — take for example the palm and the back of the hand — ill different quantity and kind, adapted to the several degrees in which the cutis it is to protect will be exposed to pressure, friction, and the influence of other external forces. And, not only are its original quantity and con- struction on these parts different, but its rate of growth is so also ; for, though the back of the hand loses comparatively little by friction or otherwise, yet its epidermis does not grow thick ; and though the palm loses moreyet its epidermis does not grow thin. So then, both in original construction and in rate of formation, the epidermis is thus adapted to the amount of function it has to discharge ; that is, to the B 50 HYPERTROPHY. amount of protection it has to afFord. But suppose now, that by some new handicraft, tlie amonnt of exercise of the epidermis is increased ; its rate of waste is increased in tlie same proportion, yet it does not grow thin ; nay, it grows thicker, till it is completely adapted to pro- tect the cutis from the greater sources of injury to which it is now exposed ; it puts forth, as it were, a reserve-power, which is enough not only to repair all amount of waste within certain limits, but farther than this, to increase the quantity of the tissue to the amount required for the discharge of its increased functions. What we can see in this case of the cuticle, we may be sure of for other tissues : for example, in a muscle ; as in a heart, when, by disease of the valves, an obstacle is put in the way of the circulating blood, and the heart, or one of its cavities, acts with additional force to drive it on. But, as we know, the more of action in a muscle, the more the consumption of the tissue, so we might now expect a diminution of the heart. On the contrary, it enlarges ; itishypertrophied ; the formative process not only meets the im.mediate exigencies of the increased con- sumption of muscular tissue, but produces enough to act with the ad- ditional power required by the increased difBculty of the circulation. Such are the effects of growth in examples of hypertrophy. But, to meet the increasing difiiculties of these and the like cases, a part may do more than grow : it may develope itself; it may acquire new structures, or it may improve those of which it is already composed, so as to become fit for higher functions and the exercise of greater power. For example, in the most ordinary hypertrophy of the heart, the mus- cular tissue is developed to more robustness : its fibres become not only larger, or more numerous, but firmer, more highly coloured, and stronger. In the pregnant utei-us, such fibres are formed as are not seen in the unimpregnated state ; they are, indeed, not a new kind of fibre, but they are so different in size and shape, and so much more powerful than those which existed before, that we may justly speak of them as developed. And this change by development, which in preg- nancy is natural, is often imitated in disease, when, by the growth of fibrous tumours in it, the uterus attains the size, the structure, and even the full capacity of action, of the pregnant organ. In several of such cases the uterus has at length imitated the course of labour, and de- livered itself of the tumour by its contractile power. A similar change, by development and growth of muscular fibres, may occur in the gall-bladder, the ureter, and, probably, in any other part that has the smooth muscular fibro-cells. HYPERTROPHY. 51 We have an example of deTelopment of a secreting strncttire in the bursa, which, as Hunter displayed it, is produced under a corn. The corn itself is the resiUt of a kind of hypertrophy, tending to shield the cutis from unnatural pressure ; but, itself becoming a source of greater trouble than that against which it was directed, it gives rise to the de- velopment of a bursa beneath it, which may, for a time, more effectually protect the joint beneath, by diffusing the pressure over a wider extent of surface. All these are examples that this hypertrophy, as we call it, though it happens in circumstances of disease, is yet in general, so far as itself is concerned, a process of full and vigorous health, serving to remedy, or keep back, the ill effects that would ensue from disease in some other part. It is, in a less degree than the repair of a fracture or other mechanical injury, an instance of the truth that we are provided for accidents and emergencies ; framed not merely to live in peace and sameness, but to bear disturbances ; to meet, and balance, and resist them, and, sometimes at least, to counteract them. The amplified healthiness of the formative process exercised in hy- pertrophy is testified by its requiring a full measure of all the conditions of ordinary nutrition. It needs healthy and appropriate blood : and one of the most interesting studies is to watch the hindering influence of disease on the occurrence and progi'ess of hypertrophy, especially that of the heart. In some of these cases, to which I shall liave again to refer, death seems clearly to be the consequence of impairment of the blood, which can no longer maintain in the heart the exceeding growth required for its increased functions. We find, moreover, very constantly, that, as if to ensure sufficient blood to the grown or growing part, the main arteries and veins belong- ing to it are enlarged. This is usually well shown in the enlarged coronary arteries of the hypertrophied heart ; an instance analogous to the enlargement of the arteries of the pregnant uterus, the growing antlers of the deer, and many others. According to all analogy, we must consider this increase of the bloodvessels to be secondary. As in the embryo, parts form without vessels, till for their further nutri- tion as their structure becomes more complex, the passage of blood into their interior becomes necessary, so, we may be sure, it is here. It may seem, indeed, strange, that a part should have the power of de- termining in some measure the rate at which blood shall flow into it and through it ; but so it is, and nearly aU examples of hypertrophy are examples of the fact ; though, as I shall presently have to mention , E 2 52 HYPERTROPHY. there are instances in wMcli hypertrophy is the consequence, not the cause, or precedent, of increased supply of blood. With the increased supply of blood proportioned to the increased nutrition of the growing part, the nerves may also increase ; as m the pregnant uterus and the hypertrophied heart. So, at least, I believe ; but probably I need not apologise for evading the discussion of this matter. The conditions which give rise to hypertrophy are chiefly or only three, namely — 1. The increased exercise of a part in its healthy functions. 2. An increased accumulation in the blood of the particular ma- terials which a part appropriates to its nutrition or in secretion. 3. An increased afflux of healthy blood. Of hypertrophy as the consequence of the increased exercise of a part, I have already spoken generally ; and we need no better examples of it than the muscles of a strong man's arm fitted for the very exercise in which they acquired bulk and power, or the great robust heart of a man who has suffered from some disease producing an obstacle to the movement of the blood. Both alike are the results of vigorous healthy growth, brought about by exercise of the part in its proper function. In a former lecture I spoke of the increased growth of the kidney, and of the adipose and other tissues, when the chief constituents of their structures exist in excess in the blood. To these I may refer again as examples of the second kind of hypertrophy. And I just now mentioned, that although in most cases an increased circulation of blood is the consequence of hypertrophy, yet there are cases in which the course of events is inverted. The increased flow of healthy blood through a part, if it be not interfered with by local disease, will give rise to hypertrophy of the part, or, at least, of some of its tissues. This fact is shown very well in a specimen (No. 6) in the Museum which Mr. Hunter described as ' a sore which had continued inflamed a longtime, where the increased action had made the hair grow.' The integuments, for about an inch round the ulcer, where probably there was simply increased supply of blood, are covered with thick-set, long and rather coarse, dark haii-s ; while on the more distant parts of the integuments, the hair is paler, more slender, and more widely scat- tered. Similar examples of overgrowth of the hair through increased sup- ply of blood, assisted probably by more than usual external warmth and moisture, are frequently seen near the ends of stumps which have HYPERTKOPHY. 53 remained long inflamed, and abont old diseased joints ; not, indeed, at tte very seat of inflammation, but at some little distance from it, where tlie parts share the increased snpply of blood, but not the disease of inflammation. Such cases are often observed on limbs in which frac- tures, have occurred. I remember one very striking case in the thigh of a child about five years old. The femur had been fractured near the middle ; the case did not proceed favourably ; and union was not accomplished without much distortion. When I saw the child, I was at once struck with a dark appearance on the thigh ; it was all covered with dark hair, like that of a strong coarse-skinned man ; yet, on the rest of the body, the hair had all the fineness and softness which are proper to it in early life. Similar facts are presented by some cases of transplantation. When the spur of a cock, for example, is transplanted from the leg to the comb, which abounds in blood, its growth is marvellously augmented, and it increases to a long, strange-looking mass of horny matter, such as is shown in two preparations in the Museum of the College. In one (54) the spur has grown in a spiral fashion, till it is six inches long ; in the other (52) it is like a horn curved forwards and down- wards, and its end needed to be often cut, to enable the bird to bring its beak to the ground in feeding, and to prevent injurious pressure on the side of the neck. It is worth observing that these excessive growths have taken place on the combs without any corresponding diminution in the growth of the spurs in their proper places. The legs of these cooks are amply sparred, though the spur reproduced is not so long as that which had not been interfered with. In one instance, moreover (No. 53), there is an excessive production of the horny scales upon the legs, while the horny spur was also excessively growing on the comb. Even' accumulations of blood or lymph moving very slowly through parts may produce hypertrophy, as in the case of muscles of limbs whose veins are obstructed, and in those of enlargement of the kidneys and liver in heart disease, and of the skin, papillae, and epithelium, in long-continued obstruction of lymphatics. I will only suggest as a probability that some of the cases of congenital or spontaneous hyper- trophy of a hand, or a foot, or of one or more fingers, may have their origin in some excessive formation of the vessels, permitting the blood to flow more abundantly through the part. An enlargement of the radial artery has been observed by Dr. John Reid ' in a case of such 1 Lonci. and Edin. Monthly .Journal of Medical Science, 18i3, and in a collection by Jlr. Curling in the Med.-Chir. Trans, xxviii. 54 HYPERTROPHY. hypertrophy of tlie thumb and fore-finger ; bat there is no evidence to determine whether in this case the enlargement of the artery was pre- vious or subsequent to the excessive growth of the part. Whatever be the case in these instances of enlargement, the fact, which the others show, that, well-organised tissue, like hair and horn, is produced in consequence of simply increased supply of blood, stands ' in interesting contrast with the phenomena of inflammation, where no tissue, or only the most lowly organised, is ever formed No fact can better show how far the mere enlargement of the bloodvessels is from constituting the essential part of inflammation. Through cases of hypertrophy such as these, the transition is made to those which, though they appear to consist in simple increase of the natural texture of parts, we yet must regard as morbid, inasmuch as they are frequently productive of inconvenience to the individual, and we do not know that they are adapted to any exigency, of the economy. Such are the simple enlargements of the thyroid, thymus, and prostate glands, of the spleen, and tonsils ; such, too, are some examples of mucous polypi, and of cutaneous outgrowths and warty growths of the skin. These all present an increase of natural textures ; and they may be instances of purposive growth, adapted and conservative ; ' but tUl it is more manifest that they are so, we must be content, I think, to regard them as occupying a kind of middle ground between the gen- Tiine hypertrophies of which I have been speaking, and the thoroughly morbid outgrowths of which a pai't of the class of tumours is com- posed. On another side, there are cases intermediate between hypertrophies and the results of inflammation, and no line of distinction can be drawn among them, if we rely on their anatomical characters alone ; for, in the lowest degrees of inflammation, the material produced may be or- ganised into a very near likeness to the natural tissues, and may thus seem to increase their quantity. If these inflammatory hypertrophies, or hypertrophies from irritation, as they have been called, can be dis- tinguished from true ones, it is only by their being unattended with increase of functional power or fitness for the part's relations. ' It is at least very remarkable tjiat almost all these simple hypertrophies occiir in organs of whose offices in the economy we are in a great measure ignorant. HYPEBTEOPHY. 55 LECTURE IV. IITPEKTEOPIIT. Let me now further illustrate the general physiology of Hypertrophy, by adducing some of the specimens in the Museum which exhibit it in the principal tissues. The first specimen in the Pathological division of the Museum is an urinary bladder hypertrophied in consequence of stricture of the urethra. It affords an admirable instance of genuine immixed hyper- trophy ; for every part of the bladder is enlarged ; it is not contracted as if it had been morbidly irritable ; and its mucous membrane, with- out induration or any similar morbid change, is increased, apparently by simple growth, to a thickness proportionate to that of the muscular coat. I adduce this especially as an example of hypertrophy of muscular tissue, concerning which, instead of adding to what was said in the last lecture, I will quote Mr. Hunter's account. Referring, perhaps, to this very specimen, be says, in a passage which I have inserted in the Catalogue ; ' ' The bladder, in such cases [of obstruction to the passage of urine], having more to do than common, is almost in a con- stant state of irritation and action ; by which, according to a property in all muscles, it becomes stronger and stronger in its muscular coat ; and I suspect that this disposition to become stronger from repeated action is greater in the involuntary muscles than the voluntary ; and the reason why it should be so is, I think, very evident ; for, in the involuntary muscles, the power should be in all cases capable of over- coming the resistance, as the power is always performing some natural and necessary action ; for whenever a disease produces an uncommon resistance in the involuntary parts, if the power is not proportionally increased, the disease becomes very formidable ; whereas in the volun- tary muscles there is not that necessity, because the will can stop when- ' Vol. i. p. 3 ; and Hunter's Works, ii. 299. 56 HYPERTROPHY OF MUSCLE. ever the nmscles cannot follow; and if the will is so diseased as not to stop, the power in volantary muscles should not increase in propor- tion.' Nothing, surely, could more appositely or more exactly express the truth concerning hypertrophy of muscle ; and it may be observed, from what he says in a note, that Mr. Hunter appears to have been the first who rightly apprehended the nature of this growth of the bladder. He says, ' This appearance was long supposed to have arisen from a disease of this visons ; but, upon examination, I found that the mns- cular parts were sound and distinct, that they were only increased in bulk in proportion to the power they had to exert, and that it was not a consequence of inflammation, for in that case parts are blended into one indistinct mass.' What this specimen shows in the urinary bladder is an example of the change which ensues in all involuntary muscles nnder the same circumstances. They all grow and acquire sti'ength adapted as much as possible to the new and extraordinary emergencies of their case. Thus, the oesophagus, the stomach, the intestinal canal, as often as any portion is the seat of stricture, display hyjDertrophy of the muscular coat above the stricture. The enormous enlargements of the intestinal canal, which gradually ensue above nearly impassable strictures of the rectum, arc not mere dilatations, but growths of the intestinal walls ; the muscular coat augmenting in power, to overcome, if it may, the increased hindrance to the propulsion of the contents, and even the glands and other textures of the mucous membrane simultaneously in- creasing. In a great majority of cases the hypertrophy of muscles, whether voluntary or involuntaiy, is the consequence of an increased obstacle to their ordinary action. Against this obstacle they exert extraordi- nary force, and this induces, indirectly, extraordinary formation of their tissue. Frequent action of muscles, unless it be also forcible, does not produce hypertrophy. As Professor Humphry' says, 'the heart, though it may act with unusual frequency for years, yet does not in these cases grow larger ; and the muscles of the hands are not generaUy so large in mechanics who use great celerity of action as in those who work with gTeat force.' But action of muscles, if it be at once frequent and forcible, may produce hypertrophy, even though the action be un- healthy. This appears to be the case with the bladders of some child- > Lectures on Surgery, in Prov. Med. and Surg. Journal; Reprint, p. 108. HYPJiRTROPHY OF MUSCLE. 57 ren, who suffer from frequent and very painful micturition, and nearly all the signs of calculus, but in whom no calculus exists. The bladder in such children is found, after death, exceedingly hypertrophied, and there may be no other disease whatever of the urinary organs. Dr. Golding Bird has shown that phymosis, by obstructing the free exit of urine, may give rise to these signs and to extreme hypertrophy of the bladder ; but in some cases it appears certain that hypertrophy may occur without either phymosis, calculus, stricture, or any similar ob- struction. It was so in a case illustrated in the Museum of St. Bartho- lomew's (xxvii. 14), in a child four years old, who had suffered intensely with signs of stone in the bladder, but in whom no stone existed ; no disease of the urinary organs could be found, except this hypertrophy of the muscular coat of the bladder. An exactly similar case was under Mr. Stanley's care, in which, after exceeding irritability of the bladder, the enlargement of its muscular coat appeared the only change. In such cases, the too frequent and strong action of the bladder, though irritable and unhealthy, seems alone to give rise to hyper- trophy of the fibres. It is, however, possible that the change may be due to temporary closure of the urethra by muscular action. If, for example, the compressors of the urethra, instead of relaxing when the muscular coat of the bladder and the abdominal muscles are contract- ing, are in the habit of contracting with them, the obstacle they would produce in the urethra will soon engender hy^aertrophy of the bladder. Certainly such cases of disagreement in the action of the bladder and urethra occur in adults, and they may be called cases of stammering bladders, for their phenomena, both muscular and nervous, are exactly parallel with those of ordinary stammering in speech.' Hunter, whose ingenuity was always tempting-on his intellect and industry, asked himself whether the hypertrophy of the heart were accomplished by the addition of new fibres, or by the enlargement of those that already exist, for it will be well to bear in mind that hyper- trophy may manifest itself, not only in the heart, but in other textures, in one or other of these two modes, either by a simple increase of the existing elements, or by their numerical increase, or hyperplasia. This question could hardly be determined without more microscopic aid than Hunter had at his command. And even since his time, with the command of much finer means of investigation, there were difficulties in the way of answering it : for whilst on the one hand, Harting^ and ' Srit. Med. Jour. Oct. 24, 18,68. "- Eechcrohs Micvomitriq^ues, 1845, p, 62. 58 HyPEKTEOPHY OF BONES. Hepp ' asserted that in the growth of striped muscles there was no numerical increase ; on the other, and probably with greater accuracy, Budge,^ G. Schmidt,^ and Weissmann* have positively stated that new muscular fibres do arise when increase in the bulk of a muscle takes place. In truth, most cases of hypertrophy are also cases of hyper- plasia, both the number and size of the elemental structures being in- creased.' Hypertrophy of bone presents itself in many interesting cases. It is usually a secondary process, ensuing in consequence of change in a part with which some bone is intimately connected. Just as in their natural development and growth, the bones of the skull are formed in adaptation to the brain, and those of the limbs are framed to a fitness for the action of the muscles ; so, in disease they submit in their nutri- tion to adapt themselves to the more active parts. Thus, the skull enlarges when its contents do ; and the bones of the limbs strengthen themselves as the muscles inserted on them become stronger and more active ; and they do this in adaptation to the force of the muscles, and not merely because of the movements they are subject to : for no ex- tent or force of passive movement would prevent the bones of a limb whose muscles are paralysed from suffering atrophy. In the skull, if in any organ, we might speak of two forms of hypertrophy, eccentric and concentric. When the cranial contents are enlarged, the skull is hypertrophied with corresponding augmentation of its area ; and when the cranial contents are diminished, the skuU (at least in many cases) is also hypertrophied, but with concentric growth and diminution of its capacity. Cases also sometimes occur in which there is great hypertrophy of the diploe, with elevation of the outer table, without the cranial cavity undergoing any diminution in capacity. The first, or eccentric form, is usually the consequence of hydro- cephalus ; wherein, as the fluid collects and distends the dura mater, so the skull grows ; stiU, as it were, striving to attain its purpose, and form a complete envelope for the expanding brain. The process of enlargement in these cases is often one of simple growth, and that, indeed, to a less extent than it may seem at first ' Canstatt, 1853, p. 43. a VirchoVs Archiv, 1859, xriii. 2 Detitschc Klinik, April 17th, 1858. * Zeitsch.f. Bat. Med., x. p. 263. 5 0. Weber in Billroth and von Pitha's Handbuch dtr Chirurgw, i. 274. HYPERTROPHY OF BONES. 59 sight : for it is very rarely that the due thickness of the skull is attained while its bones are engaged in the extension of their super- ficial area. Hence, the weight of an hydrocephalic skull is not much, if at all, greater than that of a healthy one ; a large parietal bone,' measuring nine inches diagonally, weighs only four ounces, while the weight of an ordinary parietal bone is about three ounces. It is interesting to observe, in some of these cases, the symmetrical placing of the Wormian bones, by which the extent of the skull is in a measure made-up. They show how the formative process, though thus thrown into straits and difficulties, yet conforms, both in growth and development, with the law of symmetry. It would be yet more interesting if we could certainly trace here something of conformity with the law of unity of organic type, in the mode of insoition of these Wormian intercalary bones, when compared with those of other animals. It cannot be certainly done : and yet, in some of these specimens, there appears (as if in accordance with that law) a tendency to the formation of the Wormian bones at the posterior part of the sagittal suture more than in any other part, as if in imita- tion of the interparietal bones of Rodents, or of those occasionally seen in non-hydrocephalic human crania. And in the very rare specimen ^ sketched in the diagram (Fig. 3), in the midst of great confusion of Fig. 3. the other bones, we find a remarkable bony arch, extending from be- tween the two frontals to the occipital bone ; occupying, therefore, the place of a large interparietal bone ; and reminding us of some of the monkeys, e.g. Cebus and Jacchns. We have a somewhat corroborative specimen in the immense hydrocephalic skull of the skeleton from ' No. 2 in the College Museum. 2 No. 3487 in the same Museum. 60 HYPERTROPHY OF BONES. Mr. Listen's Museum (N"o. 3489), in which the interparietal Wormian bones are larger than any others. The hypertrophy of the stnll, which may be called concentric, is that which attends atrophy with shrinking of the brain, or, perhaps any disease of the brain in which there is diminution of its bulk. In such a case it usually happens, as was first shown by Dr. Sims,' that the skull becomes very thick. All the specimens which I have examined show, however, that in these cases the thickening of the skull is not in itself a morbid pro- cess ; it manifests definite purpose ; is usually eficcted by healthy growth ; and observes the rules followed in the natural formation of the skull. Thus, as in its first formation, the skull adapts itself to the form and size of the brain, or, rather, of its membranes ; only now it does so without representing on its exterior the change which has taken place within. The thickening of the skull is eifected by the gradual remodelling of the inner table and diploij of the bones of the vault, so that, although the exterior of the skull may retain its natural form and size, the inner table grows more and more inwards, as if sinking to- wards the retiring and shrinking brain — not thickening, but simply removing from the outer table, and leaving a wider space filled with healthy diploe. Again, it is a fact of singular interest, that this thickening, this hypertrophy of the skull, most commonly, if not always, takes place, Eig. 4. especially, and to a greater extent than elsewhere, in the parts of the bones m and about which ossification commenced in the foetal state ; as if one might say, some of the potency that of old brought the foetal membrane of these parts first into the development of bone, were always afterwards concentrated in them ; or as if a reserve-power of growth had its seat in the same centres where was formerly the ' Medico -Chirurgieal Transactions, xix. p. 315. HYPERTROPHY OP BONES. 61 originative power of development. The fact' is shown in many of the specimens, especially in one that is represented here (Fig. 4) ; and we may find some fnrther, though less snre, evidence of the peculiar for- mative energy of these old centres, in the fact that those diseases of bone which are accompanied with excessive formation, such as morbid thickenings of the skull and tumours, are, in a large majority of cases, seated in or near the centres of ossification ; you rarely find them ex- cept at the articular ends, or round the middle of the shaft. The same does not hold of necrosis, rickets, ulceration, or other diseases indica- tive of depression of the formative power of the bone. Rather as some specimens (Nos. 390-1-2) of ricketty disease of the skull and femora show, the centres of ossification are remarkably exempt from the change of structure which has extensively affected the later formed parts. This peculiarity of the centres of ossification is the more remarkable when we remember that, in many cases, the thickening of the skull takes place in persons far past the middle period of life ; it may happen even in very old age, and may give one more evidence of that precision of assimilation which maintains, throughout life, characteristic dis- tinctions among portions of what we call the same tissue. Let me, however, remark that it is not peculiar to old persons ; I believe that at whatever age, after the complete closure of the cranial sutures, shrinking of the brain may happen, this hypertrophy of the skull may be its consequence. One specimen, for instance (No. 379), is part of the skull of a suicide, only thirty years old ; another (No. 380), from an idiotic woman, has not the characters of an old skull. I once examined a remarkable case, showing the same conditions, in a person less than thirty years old, in whom the thickening of the skull must have begun in early life. She was a lady of remarkable personal attractions, but of slenderly developed intellect, whose head did not externally appear below the average female size. Yet her cranial cavity was singularly contracted ; the skull had adapted itself to an imperfectly grown brain, by the hypertrophy of its diploe, which was nearly half-an-inch thick at and near the centres of ossification of the frontal and parietal bones. But this cranial hypertrophy does not necessarily aff"ect the whole of the bones forming the walls of the brain cavity. It may be limited in extent, as in those cases in which a partial atrophy of the contents of the cavity occurs, as when one hemi- sphere only of the cerebrum, or cerebellum, is diminished in size.' • An interesting case of this kind has been recorded by Professor S. Van der Kolk, whose essay is translated, by Dr. Moore, in vol. si. of New. Syd. Soc. PMications, 62 HYPERTROPHY OF BONES. Sucb hypertrophy, however, is not always the mode by which the skull is adapted to the diminished size of the brain. In congenital and very early atrophy of the brain, the skull is proportionally small, and may exactly represent the size and shape of the cerebrum. It does so in the cases of small-skulled idiots, and in a remarkable skull in the Museum of St. Bartholomew's Hospital. The man from whom this skuU was taken received a compound fracture of the left frontal bone when he was only fourteen years old. Portions of bone were removed; hernia cerebri ensued, and several pieces of brain were sliced off. But he recovered and lived thirty-three years. The left hemisphere of the cerebrum was altogether small. Where the brain had been sliced off its surface had sunk in very deep, and had left a cavity filled with a vascular spongy substance, containing ill-formed nerve-fibres. You will observe here, that in the modelling of the skull, the left side has become in every part less capacious than the right, adapting itself to the diminished brain without any hypertrophy of the bones The cases are very rare in which hypertrophy of any other bones than those of the skull occurs in connection with what is recognised as disease. For, as I have said, the bulk of most of the other bones is principally determined by the activity of the muscles fixed on them ; and a morbidly excessive action of muscles, sufficiently continued to produce hypertrophy of bones, is seldom, if ever met with. But there is a condition of bones so similar to hypertrophy in many respects, and so little different from it in any, that I may well speak of it hero ; yet not without acknowledging that nearly all I know about it is derived from Mr. Stanley. When any of the long bones of a person who has not yet attained full stature is the scat of disease, attended with unnatural flow of blood in or near it, it may become longer than the other or more healthy bone. For example, a lad, suppose, has necrosis of the femur, it may be of a small portion of it, and he may recover completely from his dis- ease ; but for all his life afterwards (as I had constant opportunity once of observing in a near relative) he may be lame, and the character of his lameness will show that the limb which was diseased is now too long ; so that he is obliged, in walking, to lift the lame leg, almost like a hemiplegic man, lest his toe should trip upon the ground. 1861. Tarin, Ostcographie., Paris, 1763, figures, pi. 3, p. 26, a frontal bone, which in some places was one inch in thickness. Sandifort, &(-mi!ffft'o«fs Acadeviicte, 119,5, Tab. 3, figures excellent examples of hypertropied crania. In the Anatomical Musenra of the University of Edinburgh are several illustrative spcoimens, in one of which the none is iJ^inch in thickness. HYPERTROPHY OF BONES. 63 Sucli cases are not xincommon ; I once saw -with Mr. Stanley, a member of our profession, in wliom this elongation of one femur liad taken place to such an extent that he was obliged to wear a very high shoe on the other, that is, the healthy limb. And this, which he had adapted for himself, affords the only remedy for the inequality of limbs. Nor is the remedy unimportant ; for to say nothing of the unsightly lameness which it produces, the morbid elongation of the limb is apt to be soon complicated by one of two serious consequences. Either the patient, in his endeavours to support himself steadily and upright, will acquire first the habit, and then the malformation, of talipes of the healthy limb ; or else, through the habit of always resting on the short healthy, and stronger limb, he will have lateral curvature of the spine. Cases of both these kinds occurred in Mr. Stanley's practice ; being brought to him for the remedy, not of the elongated femur, but of the consequent deformity of the foot or tlie spine. A considerable elongation of the lower extremity almost always depends on the femur being thus affected ; another, and very charac- teristic result, ensues from the same kind of hypertrophy when it occurs in the tibia. The femur can grow longer without materially alberino- its shape or direction, but the tibia is tied by ligaments at its two ends to the fibula ; so that when it lengthens, unless the fibula should lengthen to the same extent, it, the tibia, must curve : in no other way, except by the lengthening of the ligaments, which, I believe, never happens to any considerable extent, is elongation of the tibia pos- sible. Tibiffl thus curved are far from rare ; specimens are t.o be found in nearly every museum ; yet I know of none in which the pathology of the disease is clearly shown, except one in the Museum of St. Bartho- lomew's (Subser. A, 46), which is here sketched (Fig. 6). In this, the fibula, and the healthy tibia of the opposite limb, are preserved with the elongated tibia. The anterior wall of this tibia, measuring it over its curve, is more than two inches longer than that of the healthy one ; the posterior wall is not quite so long. In all such specimens you may observe a characteristic form of the curve, and its distinction from the curvature of rickets. The distinc- tion is established by these particulars ; the ricketty tibia is always short : the other is never short, and may be longer than is natural : in the ricketty one the articular ends always enlarge very suddenly, for the shortening is due to the imperfect formation of the ends of the shaft ; in the elongated tibia, there is usually even less contrast of size 64 HYPERTROPHY OF BONES. between the shaft and epiphyses than is natural, because the elongation of the shaft is commonly attended with some increase of its circumfer- ence ; but, especially, the ricketty tibia is compressed, usually curved inwards, its shaft is flattened laterally, and its margins are narrow and spinous ; while in the elongated tibia, the curve is usually directed for- wards, its margins are broad and ronnd, its sur- faces are convex, and the compression or flattening, if there be any, is from before backwards. The elongation of the bones in these cases may occur in different instances, in two ways. In some cases it seems due to that change in bone which is analogous to chronic inflammation of soft parts, and which consists in the formation of the products of inflammation in the interstices of the osseous tissue, their accumulation therein, and the re- modelling of the bone around them as they accu- mulate. Such a change appears to have occurred in the specimen from which the sketch was taken, and would necessarily give rise, in a grooving bone, as it does in soft parts, to enlargement in every direction, to elongation as well as increase of circumference. But in other cases the elongation is probably due to the more genuine hypertrophy which follows the increased flow of blood. When, for example, a small portion of bone, as in circumscribed necrosis, is actively diseased, all the adjacent part is more vascular ; hence may arise a genuine hypertrophy, such as I have shown in hair under similar circumstances. Or when an ulcer of the integuments has long existed in a young person, the subjacent bone may share in the increased afflux of blood, and may enlarge and elongate. Even, it appears, when one bone is diseased, another in the same limb may thus be increased in length. A remarkable instance of this kind has been observed by Mr. Holden in a young man who, in childhood, had necrosis of the left tibia, one of the consequences of which was defective growth of the left leg, with shortening to the extent of more than an inch. Yet the whole limb is not shorter than the other ; for without any apparent morbid change Fig. 5. HYPERTROPHY OP JBONES. 65 of texture, the femur of the same side has grown so as to compensate for the shortening of the tibia. An interesting example of similar increased growth of one bone, in compensation for the weakness of another, is found sometimes in cases of ill-repaired fractures or diseases of the tibia. The fibula, at the part corresponding with the weak portion of the tibia, is in such cases strengthened sufBoiently for the support of the limb. So in a specimen in the Museum of St. Bartholomew's (Ser. 3 ; 86), taken from a dog ten weeks after a piece of the radius was cut out with its periosteum, while the gap in the radius is filled with only soft tissue, the exactly corresponding portion of the ulna is increased by the formation of new bone beneath its periosteum. I must not forget to say, that the interest of these cases of inequality of the limbs, by lengthening of one of the bones is increased by comparison with a much more numerous class of cases in which a great or greater inequality of length depends on one limb being anormally short. In these the short limb has been the seat of atrophy, through paralysis of the muscles dependent on some of the very numerous conditions in which they may be rendered inactive, chiefly through infantile or so-called essential paralysis. The complication of the cases, the talipes, and the curvatures of the spine, depending as they do, on the inequality of the length of the limbs, from whatever cause arising, will be alike in both ; and much care may be needed in diag- nosis, to tell which of the limbs, the long one or the short one, is in error. The best characters probably are, that when a limb is, through disease or atrophy, too short, it will be found, in comparison with the other, defective in circumference as well as in length ; its muscles, ipartaking of the atrophy, will be weak and flabby, and all its tissues will bear signs of imperfect nutrition. If none of these characters be found in the short limb, the long one may be suspected ; and this suspicion will be confirmed, if there be found in it the signs of increased nutrition, such as enlargement, growth of hair, and the rest ; or if in the history of the case, there be evidence of a disease attended with an excess in the supply of blood. Continuing to select from the Museum only such examples of Hypertrophy as may illustrate its general pathology, I pass over many, and take next, those which display the formation of corns ; a subject which, while Hunter deemed it worth consideration, we shall not be degraded by discussing. He made many preparations of corns, 66 HYPEETEOPHY CAUSED BY PEESSUEE. to sLow not only the thickening of the cuticle, but the formation of the little sac of fluid, or bursa, between the thickened cuticle and the subjacent joint. His design appears to have been, mainly, to illustrate the different results of pressure; to show how that which is from without produces thickening ; that from within, thinning and absorp- tion of parts. He says, having regard to these specimens, ' The cuticle admits of being thickened from pressure in all parts of the body : hence we find that on the soles of the feet of those who walk much, the cuticle becomes very thick ; also on the hands of labouring men. We find this wherever there is pressure, as on the elbow, upper part of the little toe, ball of the great toe, &c. The immediate and first cause of this thickening would appear to be the stimulus of necessity given to the cutis by this pressure, the effect of which is an increase of the cuticle to defend the cutis underneath. Not only the cuticle thickens but the parts underneath ; and a sacculus is often formed at the root of the great toe, between the cutis and ligaments of the joint, arising from the same cause, to guard the ligaments below.' ' In another place he says, ' When from without, pressure rather stimulates than irritates ; it shall give signs of strength, and produce an increase of thickening : but, when from within, the same quantity of pressure will produce waste ' [as illustrated in Nos. 120 and 121 in the Pathological Museum] ; ' for the first effect of the pressure from without is the disposition to thicken, which is rather an operation of strength ; but if it exceeds the stimulus of thickening, then the pressure becomes an irritator, and the power appears to give way to it, and absorption of the parts pressed takes place ; so that nature very readily takes on those steps which are to get rid of an ex- traneous body, but appears not only not ready to let extraneous bodies enter the body, but endeavours to exclude them by increasing the thickness of the parts.' ^ It is evident from these passages that Mr. Hunter was aware that pressure from without might produce atrophy ; though he may appear to favour the belief, which, I think, is commonly adopted as on his authority, that the direction of the pressure is that which deter- mines its result. B.eally, the result seems to depend on whether the pressure be occasional or constant. Constant extra-pressure on a part always appears to produce atrophy and absorption ; occasional pressure may, and usually does, produce hypertrophy and thickening. All the ' Hunter's Wur/cs, i. p. 560. z Jiid. iii. p. 466. HYPERTROPHY CAUSIil) BY PRESSURE. 67 thickenings of the cuticle are the consequences of occasional pressure ; as the pressure of shoes in occasional walking, of tools occasionally used with the hand, and the like : for it seems a necessary condition for hypertrophy, in most parts, that they should enjoy intervals of rest in which their nutrition may go on actively. But constant pressure, whether from within or from without, always appears to give rise to unrepaired absorption : and most museums contain interesting exam- ples of its effects. Some vertebrre in the College Museum (121 A.) illustrate very well the results of pressure by aneurisms and tumours. So far as the vertebrae are concerned, the pressure of the aneurism was from with- out inwards ; yet they are atrophied ; not ulcerated, but hollowed out, and re-modelled in adaptation to the shape of the aneurismal sac : their cancellous tissue is not exposed, but, as in the natural state, is covered with a complete thin external layer of compact tissue. The pressure of a loose mass of bone in the knee-joint (No. 965 in the same Museum) was from without inwards : but its result was atrophy, as shown in the formation of a deep pit at the lower end of the femur, in which it lay safely and almost tightly lodged. Again, the effect of constant pressure is shown in the cases in which one of the lower incisor teeth of a rodent animal has continued its growth after the loss of the corresponding upper incisor, and, being no longer worn down by attrition in growing, attains an unnatural length. In such a case the extremity of the tooth, turning round so as to form nearly a complete circle, has come into contact with the side of the lower jaw, and (like, as they tell, the Fakir's finger-nails growing through the thickness of his clenched hand) it has perforated the whole thickness of the jaw ; the absorption consequent on its pres- sure making way for its onward course.' A yet stranger example was taken from the body of a woman in the dissecting-room of St. Bartholomew's Hospital, and the specimen (Ser. 1 ; 232) tells all the history that can, or perhaps need be given. She had an aperture in the hard palate, and for remedy of its annoy- ance used to wear a bung, or cork, in it. But the constant pressure of so rough an obturator produced absorption of the edges of the openmg, making it constantly larger, and requiring that the cork should be often wound round with tape to fit the widening gap. And thus the remedy went on increasing the disease, till, of all the palatine por- ' Owen's Odontography, Plate 104, Fig. 7. Mr. Tomes figures in his work on the teeth, a like example of unrestricted growth in the tooth of the hippopotamus. F 2 68 HYPEETBOPHY EFPECTS OF PEESSUEE. tions of the upper maxillary and palate bones, nothing but their margin or outer shell remains : the rest is all absorbed. The antrnm is on each side obliterated by the apposition of its walls, its inner wall having probably been pushed outwards, as the plug was enlarged so as to fit the enlarging aperture in the palate. Nearly the whole of the vomer also has been destroyed, and the superior ethmoidal cells are laid open. Lastly, as an instance in which, in the same part, permanent pres- sure produced atrophy, and occasional pressure hypertrophy, I may show a Chinese woman's foot. The bandaging, and constant compres- sion in early life, produced this diminished growth ; but afterwards, when, with all the miserable doublings and crowding of the toes, the foot was used in walking, the parts of pressui-e became the seats of corns. We may sometimes observe the same contrast after amputations. A hole may be absorbed in an upper flap where it lies on the end of the bone, and is subject to the constant pressure of its own weight ; but, in older stumps, the greater occasional pressure on the artificial limb leads to thickening and hardening of the parts. These examples, then, may sufiice to show, as I have said, that constant pressure on a part produces absorption ; occasional pressure (especially if combined with friction) produces thickening or hyper- trophy : and that these result whatever be the direction of the pressure. And yet, let me add that Mr. Hunter was not far wrong — he never was : for nearly all pressures from without are occasional and inter- mittent, and nearly all pressui-es from within, arising, as they do, from the growth of tumours, the enlargement of abscesses and the like, are constant. ATROPHY: DEGENERATION. 69 LECTURE. V. ATEOPHY: DEGENEEATION. I PROPOSE now to consider tho subject of Atrophy ; the very contrary of the Hypertrophy which I endeavoured to elucidate in the last two lectures. By atrophy is commonly implied, not the cessation or total priva- tion of the formative process in a part, but its deficiency ; and as I limited hypertrophy to the cases in which an increased power is ac- quired for a part by the growth, or by the development, of healthy tissue, so shall atrophy be here taken to mean only that process by which a part either simply wastes and is reduced in size, with little or no change of texture, or else gradually and regularly degenerates. By the terms of this limitation it is implied, that, as there are two modes of hypertrophy, the one with growth, the other with develop- ment ; so there are two modes of atrophy, the one with simple decrease, the other with degeneration of tissue; And as in hypertrophy, so con- versely, in atrophy ; the decrease may be in either the number or the size of the tissue elements, or in both number and size at once. Whether with decrease or with degeneration there is a loss of functional power in the part ; but in one, this loss is due to the deficient quantity, in the other to the deteriorated quality, of the tissue. And as in hy- pertrophy the development and the growth of the affected part usually concur, so in atrophy a part which becomes smaller usually also de- generates, and one which degenerates usually becomes smaller. Still, one or other of these, either the decrease or the degeneration, com- monly prevails ; and we shall see reasons why the distinction is very necessary to be made. Let me first state, and even at some length, what is to be under- stood by degeneration, and how its effects may be distinguished from those of disease. I implied in a former lecture, that the maintenance of a part in its 70 ATROPHY: DEGENERATION. nnfcrition must not be understood as being the maintenance of an un- changed state ; rather each part may be said to present a series of mm- ute progressive changes, slo"wly effected and consistent with that exer- cise of its functions which is most appropriate to the successive periods of its existence. Now, after a certain length of life, these changes accumulate into a very noticeable deterioration of all, or nearly 'all, parts of the body, and they suffer a manifest loss of functional power. Thus changed, we say they are degenerate ; these accumulated changes are the signs of decay, the infirmities of age, the senile atrophy. They are the indications of defective formative power, and often speak more plainly of old age than do the years a man may have counted; they testify that the power which prevailed over the waste of the body in childhood and youth, and maintained the balance in vigorous manhood, has now failed : as the tide after a flood and a period of rest, turns and ebbs down. All the expressions usually employed about these changes imply that they are not regarded as the results of disease : nor should they be : they are, or may be, completely normal. For to degenerate and die is as normal as to be developed and live ; the expansion of growth and the full strength of manhood are not more natural than the decay and feebleness of a timely old age ; not more natural, because not more in accordance with constant laws, as observed in ordinary conditions. As the development of the whole being, and of every element of its tissues, is according to certain laws, so is the whole process regulated by which all that has life will, as of its own workings, cease to live. And as in healthy development and growth all parts concur in equiva- lent changes, so in the natural decline of life do all parts change in equivalent degenerations, till all together cease to be capable of living. For it is natural to become feeble and infirm, to wither and shrivel, to have dry, dusky, wrinkled skins, and greasy brittle bones, to have weak fatty hearts, blackened inelastic lungs and dusky thin stomachs, and to have every function of life discharged feebly, and, as it were, wearily ; and then, with powers gradually decreasing, to come to a time when all the functions of bodily life ceasing to be discharged, death, without pain or distress, ensues. But such a death as this is very rare, no dis- ease is rarer. I have seen only two or three such cases ; for it is very common for people to reach nearly the goal of natural life, and then by some accident, or through disease or advancing degeneration of a single organ, to fail to reach it. The definition of life that Bichat gave, is, in this view, as untrue as it is illogical. Life is so far from ATEOPHY: DEGENERATION. 71 being ' the sum of the functions that resist death,' that it is a constant part of the history of life that its exercise loads naturally to decay, and through decay to death. Of the manner in which this decay or degeneration of organisms ensues we know but little. Till within the last few years the subject of degenerations was scarcely pursued : and even of late, the inquiries, which ought to range over the whole field of living nature, have been almost exclusively limited to the human body. Tet it coxild not be without interest to watch the changes of the body as life naturally ebbs ; changes by which all is undone that the formative process in development achieved ; by which all that was gathered from the inorganic world, impressed with life, and fashioned to organic form, is restored to the masses of dead matter ; to trace how life gives back to death the elements on which it had subsisted ; the progress of that decay through which, as by a common path, the brutes pass to their annihilation, and man to immortality. Without a know- ledge of these things our science of life is very partial, very incomplete. And the study of them would not lack that peculiar interest which appertains to inquiries into final causes. For all the changes of ruitural decay or degeneration in living beings indicate this design ; that being gradual approximations to the inorganic state of matter, they lead to conditions in which the chemical elements of the body, instead of being on a sudden and with violence dispersed, may be collected into those lower combinations in which they may best rejoin the inorganic world ; they are such, that each creature may be said to die through that series of changes which may best fit it, after death, to discharge its share in the economy of the world, either by supplying nutriment to other organisms, or by taking its right part in the adjustment of the balance held between the organic and the inorganic masses. Nor would the student of the design of these degenerations do well to omit aU thought of their adaptation, in our own case, to the highest purposes of our existence. When, in the progress of the ' calm decay' of age, the outward senses, and all the faculties to which they minister, grow dim and faint, it may be on purpose that the Spirit may be in- vigorate and undisturbed in the contemplation of the brightening future — that, with daily renewed strength, it may free itself from the encumbrance of all sensuous things, or may retain only those fragments of thought or intellectual knowledge which, though gathered upon earth, yet bear the marks of truth, and being Truth, may mingle with 72 ATEOPHY: DEGENERATION. tHe Truth from Heaven, and form part of those things in which Spirits of infinite purity and knowledge may be exercised. Moreover (and this is in the closest relation to my present subject), the changes of natural degeneration in advanced life have a direct im- portance in all pathology, because they may guide us to the interpreta- tion of many similar anomalies which, while they occur in earlier life, we are apt to call diseases, but which are only premature degenera- tions, and are to be considered, therefore, as methods of atrophy — as defects, rather than as perversions, of the nutritive process — or as dis- eases, only in consideration of the time of their occurrence.' The changes that mark the progress of natural decay or degenera- tion in old age, and that may, therefore, be regarded as the typical in- stances of simply defective nutrition, seem to be these : — 1. Wasting or withering ; the latter term may imply the usually coincident wast- ing and drying which constitute the emaciation of a tissue. 2. Fatty degeneration, including many of what have been called granular de- generations. 3. Earthy degeneration, or calcification. 4. Pigmental degeneration. 5. Thickening of primary membranes. Of each of these let me cite one or two examples. Of withering, or wasting and drying, which is perhaps the com- monest form of atrophy, we have abundant instances in the emaciation of old age, in which, while some parts are removed by complete absorp- tion, others are only decreased in size, and lose the succulency of ear- lier life. Bnt this withering atrophy must not be confounded with the mere drying and collapse of tissues, which ensue in cases in which fluids are discharged in excessive quantity, as in cholera, diabetes, and hsemon-hage. A good illustration of the natural withering of the ele- mentary stmctures of a part is afforded in the hardening and drying (corniftcation) of the epithelial cells. This is especially exhibited by the tesselatcd epithelium and cuticle, the cells of which, in their pro- gress from the deeper, to the superficial layers, not only become har- der and dryer previous to their final separation, but assume a flattened withered aspect. The fatty degeneration in senility is best shown, as a general occur- ' Ono can here have in view only the cases in which the degeneKition afiFects the whole, ov some considerable part, of an organ ; for it is very probable that some of the degenerations which we see en masse in the organs of the old, or in tho seats of prema- ture defect of nutrition, are the same us occur naturally in the elementary structures or molecules of organs when the term of their natural life is ended, previous to their being absorbed and replaced, as it were, by one particle at a time, in the regular pro- cess of nutrition. ^ ATEOPHY : DEGENERATION. 73 rence, in the increasing obesity which some present at the onset of old age, and in the general fact that there is more fatty matter in all the tissues, and most evidently in the bones, than there is in eai-lier life ; while, as local senile fatty degenerations, we find the arcus senilis, or fatty degeneration of the cornea, and the accumulating fatty or athero- matous degenerations of arteries. The calcareous degeneration is, in old age, displayed in the gradual increasing proportion of earthy matter iu the bones — in the extension of ossification to cartilages, which, in all the period of vigour had re- tained their embryonic state— and in the increasing tendency to earthy deposits in the arteries, lymphatic glands, and other parts. It may manifest itself in one or other of two way — either as a creti- fication, that is a mere deposition of lime salts, or as a true ossification, that is, accompanied by the formation of lacuna and canaliouli, can- cellated, and compact tissue, and even, in some cases, periosteum. In most instances these two foi'ms are so well marked, and the differences between them, both to the naked eye and the microscope, are so obvious, that there can be no difficulty in distinguishiBg one from the other. The simple calcareous deposit possesses no definite structure, and is generally so fragile as readily to crumble down beneath the fingers, whilst the true ossific formation presents all the well-known characters of bone. But it is not unusual to meet with instances of calcareous degeneration in which it is not so easy to pronounce with certainty if the formation be true bone or not. In these cases the sub- stance may be hard and compact, but the existence of a lacunary struc- ture is not very decided. Small dark-looking spaces, appearing like very imperfectly formed lacunas, may occasionally be seen, irregular in size, shape, and arrangement, and destitute of canaliculi. These re- mind one somewhat of the imperfect structures met with in the cement and granular layer of the crusta petrosa of the fang of a tooth. Pro- bably the best test of the lacunary nature of these irregular spaces would be the detection in them of nuclei, such as are found in the lacunas of true bone. The tendons not unfrequently exhibit true bony growths in their in- terior, which may either spring from the surface of attachment, and ex- tend for a greater or less distance into their interior, or may exist as dis- tinct isolated masses in their substance. In the muscles also, very exten- sive bony growths occasionally take place. Mr. Hawkins ' has recorded a ' Med. Gu:. xxxiv. 1841, p. 273. 74 ATEOPHY : DEGENERATION. very curious case, in which there was a most extensive formation of bone in the voluntary muscles, and there is in the Museum of the College a preparation in which nearly all the muscles of the back have undergone ossification. Whether in cases such as these the bone is formed in the muscular fibre itself, or originates in the connective tissue between the fibres, and by its growth produces, through pres- sure, atrophy and destruclion of the proper muscular substance, has been made a matter of question, bat there are very strong grounds for believing the latter to be the case, as the formation of bone in connec- tive tissue is a well-recognised fact in development. Otto Weber ' has, however, described specimens in which the muscular fibres themselves were converted into rigid cylinders from calcification of their substance and the same writer has observed calcareous formations within epithe- lium cells. The pigmental degeneration has its best instances in the gradually accumulating black pigment, spotting and streaking the lungs ; in the slate or ash colour, which is commonly seen in the thin mucous mem- branes of the sf omach and intestines of old persons ; in pigmental dis- colorations of the skin, which are manifested in their highest form, though not necessarily occurring in old persons, in apparent connection with disease of the supra-renal capsules, as first pointed out by Dr. Addison ; in the black spotting of the arteries of some animals, in which pigment seems to hold the place of the fatty degeneration so usual in our own arteries,^ and, under some as yet imperfectly understood con- ditions, in the accumulation of pigment in considerable quantities, not merely in the walls of the bloodvessels, but even in the tubes them- selves.^ Of the thtd'eniiig of primarg vietnhranes we have indications in the usual thickening of the tubules of the testes, and, I think, of some other glands, as their function diminishes in old age ; in the opaque white thickening of the primary or inner membrane of nearly all bloodvessels ; ' Pitha and Billroth's Bandhuch der Chirurgie, i. p. 316. ^ In Virchow's Arckiu 1860, xvi. p. 5Gi, an abstract is given of an inaugural dis- sertation by Von Stein, iu which it is stated that in sixty-two cases of diseases of the brain which he examined, pigment was deposited mostly in the middle and outer coats of the ressels in no less than fifty-three cases. = A lengthened account of this form of pigment deposit in the capillaries, especially of the liver, spleen, br.iin, and other viscera, has been given by Frerichs in his Clinical Treatise on Diseases of the Liver. In the Medico- Chirvrgical Scview 1861, xxrii., Dr. Laycock has publithed an article on morljid, cutaneous, pigmentary changes, in which the question of pigment-deposits is discussed very fully. ATROPHY: DEGENERATION. 75 in tke tliickening of the wall of cartilage cells in senile and some other ossifications ; and, probably, in the toaghening of the brain and spinal marrow in advancing years. To this, also, we have a strong analogy in the thickening of the cell-walls of the heart-wood of plants. These changes, singly or in various combinations, constitute the most evident degenerations of old age in man. Their combinations give rise to numerous varieties in their appearance ; such as, e.g. the increase of both fatty and earthy matter in old bones ; the dry, withered, and darkly-tinged condition of the epidermis ; the coincident fatty and calcareous deposits in the arteries ; the thickened walls and fatty contents of the seminal tubes. But at present, I need not dwell on these, nor on the conditions which determine the occurrence of one rather than another mode of degeneration, for these I cannot tell. Now, if we observe the conditions in which these senile, and there- fore typical, examples of degeneration are imitated in earher life, they are such as indicate that the changes are still to be ascribed to a defect, not to a perversion, of the conditions of nutrition, or of the vital forces. Thus these changes are all especially apt to occur in a part of which the functions are abrogated ; the uterus, after parturition, shrinks to its usual size, with wasting and fatty degeneration of its structures, previously enlarged by a normal and purposive hypertrophy ; a motion- less limb wastes or becomes fatty as surely as an old one does. Similar changes are found ensuing when one or more of the conditions of nu- trition are removed, not changed. For example, a fatty degeneration of part of a heart may ensue when, through disease of a coronary artery, its supply of blood is diminished. They often occur in parts that fail to attain the development for which they seemed to be intended. Thus fatty degeneration usually ensues in the cells of unfruitful Graafian vesicles.' In short, all the history of degenerations, when we can trace it, is that of atrophies. We may therefore safely hold, that as the changes to which the several tissues are naturally prone in old age are certainly the results of defect, not of perversion, of the nutritive process, so are the correspond- ing changes when they happen in earlier life, although, through their appearing prematurely, they may bear the features of disease. The distinction between degeneration and disease is essential, though often it may be obscure. Degeneration as to its process is natural, ' Eeinhardt, in Traube's Beitrdge, B. i. p. 146. 76 ATEOPHY: DEGENEEATION. thougli it may be premature ; disease is always unnatural ; the one has its origin within, the other without the body : the one is constant, the other as various as the external conditions in which it may arise : to the one we are prone, to the other only liable. The general diagnostic characters of degenerations are chiefly these : — 1. They are such changes as may be obsei-ved naturally occurring in one or more parts of the body at the approach of the natural ter- mination of life, or if not then beginning, yet then regularly in- creasing. 2. They are changes in which the new material is of lower chemical composition, ie., is less remote from inorganic matter than that of which it takes the place. Thus fat is lower than any nitrogenous or- ganic compound, and gelatine lower than albumen, and earthy matter lower than all these. 3. In structure, the degenerate part is less developed than that of which it takes the place : it is either more like inorganic matter, or less advanced beyond the form of the mere granule or the simplest cell. Thus the approach to crystalline form in the earthy matter of bones, and the crystals in certain old vegetable cells, are characteristic of degeneration ; and so are the granules of pigment and of many granular degenerations, and the globules of oil that may replace mus- cular fibres or the contents of gland- cells, and the crystals of choles- tearine that are often mingled with the fatty and earthy deposits. 4. In function the part has less power in its degenerate than in its natural state. 5. In its nutrition it is the seat of less frequent and less active change, and without capacity of growth or of development. Such are the characters by which in general we might separate the processes and results of degeneration from those of disease and of natural nutrition. But we must remember always that the process of degeneration may concur with either of those from which, in its typical examples, it may be so clearly separated. It may mingle with develop- ment ; or, at least, by a process of degeneration, a part may become adapted to a more developed condition of the system to which it be- longs. So it is in the process of ossification. It is usual to speak of cartilage as being developed into bone, and to regard bone as the more developed and more highly organised of the two tissues. But I think it is only in a very limited sense that this mode of expression is just. ATEOPHY : DEGENERATION. 77 Professor Owen, in some admirable remarks ' on the cartilaginous state of the endo-skeleton of Chondropterygian fishes, has said — ' I know not why a flexible vascular animal substance should be supposed to be raised in the histological scale because it has become impregnated, and, as it were, petrified by the abundant intussusception of earthy salts in its areolar tissue. It is perfectly intelligible that this acceler- ated progress to the inorganic state may be requisite for some special ofi&ce of such calcified parts in the individual economy ; but not, there- fore, that it is an absolute elevation of such parts in the series of ani- mal tissues.' Let me add, that all that one sees of the life of cartilage, in the narrower survey of the higher mammalia, is conformable with this view, and would lead us to speak of its change into bone as a de- generation, rather than a development. The change is effected not only in the vigour of life, but as constantly, in certain parts, in its decay ; and, whenever it is effected, the part that has become bone almost ceases to grow, except by superaddition ; the interstitial changes of normal nutrition are reduced to their lowest stage. Cartilage, too, is less frequently and less perfectly repaired after injury than bone is ; and its repair is commonly effected by the production of bone ; yet it would be contrary to all analogy for a lower tissue to be repaired by the formation of a higher one. It may be added that the granular, and in some instances even crystalline, form, in which the earthy matter of bone is deposited, is inconsistent with the supposition that its animal matter has acquired a higher development than it had before in the state of cartilage. So far, therefore, as its position in the series of animal tissues is concerned, bone should be placed below cartilage, as a tissue which has degenerated into a state of less active life, and has ac- qnired characters that approximate it to the more lowly organised and to the inorganic substances. An osseous skeleton is, indeed, proper to the most highly developed state of the individual, and in this relative view bone appears superior to cartilage ; but, with as much right, in the same view, the atrophied thymus gland, and the renal capsules al- most arrested in their- growth, might claim to be regarded as develop- ments from their fcetal state ; for these, also, are normal parts of the more perfect organism : they are like the degenerate members of an ennobled society, except in that, in their humiliation, they augment the common weal. The points of contact, and even of complete fusion, are yet more 1 Lectures on Comparative Anatomy, edition 1846, ii. p. 146. 78 ATROPHY: DEGENERATION. nnmeroTis between degeneration and disease. In many diseases, in- cluding the whole class of inflammations, a degeneration of the alFected tissue is a constituent part of the morbid process ; and in many cases we must still doubt whether the changes of texture that we observe are the resxdts of degeneration or of disease. Among these are the instances of the simple softening of certain organs, such as the brain and spinal cord, and the liquefactions of inflammatory products in the suppurative process. If we limit the term degeneration to the changes that imitate the typical examples of old age, these changes cannot be included under it ; but they may be if we consider the conditions in which they occur, and the mere decrease of power which some of them manifest. The softening of the brain and spinal cord, for example, oc- curs in. some cases through mere defect of blood ; in some through mere abrogation of function ; it is often concurrent with distinct signs of atrophy ; and, as I shall describe in the next lecture, it is attended with changes that closely imitate those of fatty degenei-ation. On the whole, therefore, while admitting the difficulty that must often occur in endeavouring to separate such changes as these from the efieets of disease, or of local death, yet I think we should do well to classify them under such a title as that of ' liquefactive degeneration.' The sum of this discussion respecting degenerations is as follows : — We observe certain changes naturally ensuing in the tissues during advanced age, and we ascribe these to defect, not to disorder, of the formative process : we notice the same or similar changes in earlier life, and we refer them to a similar defect, and class them as methods of atrophy : we seem justified in thus regarding them, by the general fact that they often have the same origin, and are concurrent with the atrophy which is attended with merely defective quantity of tissue ; and, lastly, we regard certain changes of texture, such as some forms of softening of organs, as degenerations or atrophies, because, though they are not natural in old age, they occur in nearly the same conditions, and manifest some of the same characters, as the atrophies which imi- tate those of senility.' ' Several other changes of structure, wliich are commonly called degenerations appear so plainly to be duo to perver.'^ions, not to more deficiencies, of nutrition that they do not fall in the same category as the degenerations described in 'the 'text Such are the waxy, lardaceons, or Mmyloid degeneraion, the caseous and colloid changes of structure. In the amyloid degeneration, a pale, trans'ucent. s.'igo-like nitrogenous substance, apparently allied to albumen, is formed in the naturaUissues' more especially in the coat, of the arteries and the secreting cells of some glands' The caseous seems to be a fatly change of very loivly organised morbid structures ,ind the ATROPHY : DEGENERATION. 79 Among tlie degenerations tliat I have enumerated, that whicla may- best be used for general illustration of the whole process, is the fatty. This deserves a full description, first, because of its own great impor- tance in pathology, for there is scarcely a natural structure or a pro- duct of disease in which it may not occur ; and, secondly, for its illus- tration of the general doctrine of defective nutrition, and for guidance in the study of the degenerations that are at present less understood. For we may be nearly sure that general truths, deducted fi-om exam- ples of fatty degeneration, will hold equally of the other forms, and especially of the calcareous and pigmental, between which and the fatty degenerations there are so many obvious features of close resemblance, that I shall content myself with merely referring to the examples of them that will bo described in future lectures.' The anatomical characters of many examples of fatty degeneration will be described in the next and in subsequent lectures. Their prin- cipal general feature is, that in the place of the proper substance of an elemental structure, e.g. in the place of the contents or the nucleus of a cell, or in the very substance of a simple membrane, or a fibre, minute particles or granules are seen, which are recognised as consisting of oily or fatty matter, by their peculiar refraction of light, their solubility in ether, their aptness to coalesce into larger oil-drops, and, when they are very abundant, by the greasiness of the whole tissue, its burning with a bright flame, and its yielding to analysis an unusual quantity of fatty matter. In examining organs in the state of fatty degeneration, we may commonly see the progress of the change in the gradual in- crease of the fatty particles. Some cells, for example, may appear quite healthy ; some may deviate from health only in containing two or three shining, black-bordered, oil-particles ; in others, these are in- creased, and a large part of the cell-cavity is filled with minute oil- particles, or with one or more larger oil-drops ; and in others, the con- tents of the cell have given place to a single cluster of oil-drops. In this last case the degeneration is nearly complete : the transformed cell is called a ' gi'anule-cell,' or when, as often happens, the cell-wall has wasted and disappeared, it is a ' granule-mass : ' and the last stage of colloid is also a morbid change of structure. They are all associated, not with mere deficiency of the nutritive act, but with distinct morbid processes ; they are diseases, therefore, and not degenerations. For they hare no representatives in the normal textures, they are not imitated in instances of simple defect in the conditions of nutri- tion, and they are not more frequent in old age than in early life. ' The index will afford at once a sufficient guide to these examples. 80 ATROPHY: DEGENERATION. degeneration is tliat such masses may break up, their constituent molecules may dispart, and the tissue wHch was an aggregate of nu- cleated cells may become little more thau amass of molecules or drops of oily matter. It is probably due in part to such disintegration of degenerate ceUs, that, ia most organs thus degenerate, abundant fatty matter is found free, that is, lying in drops not enclosed among the proper constituents of the tissue. But this free fat is also derived, iu part, from the de- generation of iater-cellnlar substance, which is usually concnrrent with that ensuing iu the cells ; and ia some cases (as Virchow has observed in the liver) it so follows the arrangement of miunte bloodvessels that it may be considered as the residue of a direct deposit from them. In most instances the fatty degeneration affects, first and chiefly, as I have described it, the contents of cells or tubules, or the proper substance of membrane or other tissue. And when it thus happens the nuclei aknost always waste, and either shrivel or disappear after gradually fading in their outlines. This may be commonly seen in the fatty degeneration of the renal and hepatic cells, and of the mus- cnlar fibres ; ' and it is a fact of some significance, when we remember the constancy and abnndance of nuclei iu actively gi'owiag parts. But, in certain cases, as in fatty degeneration of cartilages, the change appears to begin in the nuclei, which are gradually transformed into granule masses, while the ceU-wall may remain unchanged, or may become thickly walled or laminated, or may coalesce with the surround- ing tissue. Such a transformation of a nucleus, while it retains its place and general form, might at once suggest that the fatty matter which col- lects in these degenerations is not introduced from without into the cells or other elements of the tissues ; that it is not placed in them, as it may be in the parts around them, as a morbid deposit, but rather is one of the products and residues of some chemical transformation which they undergo when the proper nutritive changes are suspended. We might derive the same suggestion from the similarly degenerate mus- cular fibres, in which we may often find the fat particles arranged in the same manner as the proper constituents of the fibrils, and looking as if there were a gradual transformation of the ' sarcous elements ' into the little oily particles, which, by clustering, and then by fusion, at length compose the larger oil-drops. ' See also tlie observations ef Bottcber in Vircbow's Arcldv, xiii. p. 227, 1858, and of C. 0. Wtlicr, Die Entwiuklung des Eiters, in tbe same Arc/iie, xv. Fatty degeneration. 81 We gain other and better evidence of tlie fatty matter being de- rived from chemical changes in the tissue that is degenerate, from many other sources. Such changes are exemplified in the production of fatty matters during the spontaneous decompositions of nitrogenous substances. Many instances ' of this are known, but none are so ap- propriate as the formation of adipocere in muscular tissue. Here, as Dr. Quain discovered, the places of the muscular fibres, bloodvessels, and nerves, are occupied by fatty matter which could not have existed in them during life, which is far too abundant to have been derived from changes in the fatty matter that they naturally contain, and which, in confused crystals, retains their natural shape, size, and arrangement ; and Dr. Quain has completed the evidence of the chemical nature of these degenerative changes by an artificial imitation of them. He has shown that the textures of hearts (and the same is true of other parts), when placed in very dilute nitric acid, or in diluted spirit, pass into a condition exactly resembling that of the fatty degeneration which I have been describing.^ N"o fact could be more apposite to prove that this form of degeneration is an atrophy ; for we may be very sure that when imitable chemistry prevails in a part, the forces of life, even those of morbid life, are defective or suspended in it. The whole history of fatty degenerations concurs to prove that they are the result of defect, not of disease, of the nutritive process } and that they may be therefore classed with the atrophy which we recognise in merely diminished quantity of formation. Let me point out the chief features of this history : for even some repetition of the earlier part of the lecture will be justified by the utility of assigning ' Many are collected by Virchow in his Archiv, B. i. p. 167, and others by Dr. Quain, Mcd.-Chir. Trans, xxxiii. p. 140, et seq. The facts concerning the formation of sugar from nitrogenous compounds in the liver are of the same kind. '' Dr. Quain has candidly referred to many previous observers by whom similar changes were recognised ; but the honour of the full proof, and of the right use of it, belongs to himself alone. Respecting the method of the chemical transforma- tions by which the change is accomplished consult Virchow's essay (ArcJiiv, B. i. p. 162), The recent observations of Dr. Ormerod, St. Hartholomenf s Bospitcd Beforts, iv. 30, throw, however, great doubts on the statement made in the text. They seem to prove that the fatty matter is infiltrated into the textures, and tbat this infiltration only takes place in structures previously disorganised, and is a consequence, not a cause, of the disorganisation. ' In no sense of the word, nor at any step of the pro- cess, is adipocerous transformation a conversion into fat.' But the text is loft un- changed, for it expresses the view originally entertained, and which many indeed may still hold, and, whichever view be accepted, the general principle of the fatty degene-. ration being a defect in nutrition may be still maintained. G 82 FATTY DEGENERATION. their right place in. pathology to changes of which (as is the case with all these degenerations) we are every year gathering new and very importani; illnstrations. I have said that the types or standards of degenerations are the changes naturally ensuing in old age. Now, accunnilations of fat, which in many parts assume the forms of the fatty degeneration of tissues, are striking characteristics of old age, and especially of the commencement of senile infirmities. The results of senile atrophy are not, indeed, the same in all persons : rather, you find among old people, and you might almost thus arrange them into two classes, the lean and the fat ; and these, as you may see them in any asylum for the aced, impersonate the two kiuds of atrophy I have spoken of as the witherino- and the fatty degeneration. Some people as they grow old seem only to wither and dry. up ; sharp-featured, shrivelled, spinous old folk, yet withal wiry and tough, clinging to life, and letting death have them, as it were, by small in- stalments slowly paid. Such are the ' lean and slippered pantaloons ; ' and their ' shrunk shanks ' declare the pervading atrophy. Others, women more often than men, as old and as iU-nourished as these yet make a far difierent appearance. With these the first sign of old age is that they grow fat ; and this abides with them till, it may be, in a last illness sharper than old age, they are robbed even of their fat. These, too, when old age sets in, become pursy, short-winded, pot-bellied, pale, and flabby ; their skin hangs, not in wrinkles, but in rolls ; and their voice, instead of rising ' towards childish treble ' becomes grufi" and husky.* These classes of old people, I repeat, may represent the two chief forms of atrophy ; of that with decrease, and that with fatty or other degeneration of tissues. In those of the first class you find all the tissues healthy, hardly altered from the time of vigour, I examined the muscles of such an one ; a Woman, seventy-six years old, very lean, emaciated, and shrivelled. The fibres were rather soft, yet nearly as ruddy and as strongly marked as those of a vigorous man ; her skin, too, was rough and dry ; her bones, slender indeed yet hard'and clean'; her defect was a simple defect of quantity and of moisture. > Mr. Barlow, in some admirably written 'General Observations on Fatty De- generation {Medical T^v^esand Gazette, May 15, 1852), has pointed out that the chmactenc disease described by Sir H. Halford, and the 'Decline of the Vital Pomrs m Old Age described by Dr. Marshall Hall, are probably, in great measure, dependent on such tatty degeneration as these persons extremely exemplify. FATTY DEGENEBATIOK. 83 But in those that grow fat as they grow old, you find, in all the tissues alite, bulk with imperfect texture ; there is fat laid between and even within, the muscular fibres ; fat about and in the fibres of the heart, in the kidneys, and all the vessels ; their bones are so greasy that no art can clean them ; and they are apt to die through fatty de- generation of some important part, such as the heart, the minute cere- bral bloodvessels, or the emphysematous lungs. The defect of all these tissues is the defect of quality. Now, I do not pretend to account for this great difference in the concomitants of the other infirmities of old age in different people. The explanation probably lies far among the mysteries of the chemical physiology of nutrition, of the formation of fat, and of respiratory ex- cretion ; and we may hope to find it when we know why, out of the same diet, and under all the same external conditions, one class of men, even in health and vigour, store up abundant fat, and another class excrete the elements of fat. In relation, however, to the present sub- ject, the maiu point is, that the similarity of the conditions in which they occur implies similarity in the essential nature of the two changes, and that the defective quantity and the defective quality of the tissues are both atrophies. The same conclusion may be drawn from the frequent coincidence of the two methods of degeneration in the same part. In the limbs the most common form of atrophy from disease is manifested in dimi- nution of size, together with increase in the fatty matter combined with the muscles and bones. Such is the condition usually displayed by the bones and muscles of paralysed limbs — in the majority of atrophied stumps after amputation — and in many other similar cases. In like manner, the fatty degeneration of a part is commonly seen as the consequence of the very causes which, in other instances, give rise to simple wasting or emaciation of the same part. Thus, when the function of a part is abrogated, from whatever cause, the part may in one person shrink, in another degenerate into fat. The emaciation of a paralysed limb is a familiar object ; but in some cases the muscles of paralysed limbs are hardly reduced in size, but are all transformed into fat. In the College Museum there is a pancreas, with a cancerous tumour pressing on its duct, and all behind the part obliterated is de- generated into fat ; and in the Museum of St. Bartholomew's (Ser. 20, No. 2) there is also a pancreas, the duct of which was obliterated ; but in this the part behind the obstruction is simply shrivelled, dry, hard, Q- 2 84 FATTY DEGENEEATION. and scarcely lobulated. So, too. among tte bones atrophied in different bed-ridden persons, some are exceedingly Hgbt, small, and dry ; others are not small, but very greasy, fall of fatty matter. Either of these results also, or the two mingled in varions proportions, may resnlt from defective snpply of blood, as in the cases of atrophy of parts of bones, after fractnres, as described by Mr. Curling, to which I shall Lave again to refer. So that from these, and from many other cases hereafter to be mentioned, we may say generally that nearly all the ordinary causes of atrophy may produce, in any part, in one case, re- duction of size, in another, fatty degeneration, in another, a concurrence of the two. Much yet remains to be said of this important change, but it will be more appropriate to the next and other lectnres, in which I shall describe the fatty degenerations of several parts, and of the products of inflammation and other diseases, as well as that remarkable foiin of degeneration which ensues, with the rapidity of an acute disease, in the proper textures of some inflamed parts. It seems only necessary, in conclusion, to state that there appears no necessary or even frequent connection between the fatty degeneration of any organ in particular, and that general tendency to the formation of fat which constitutes obesity. No doubt, a person, especially an elderly one, who has a natural tendency, even when in health, to become corpulent, will, cceteris paribus, be more likely to have fatty degeneration than to have a wasting atrophy in any organ which may fall into the conditions in which these changes originate. And, as a general rule, spirit- drinkino-, and the excessive use of hydro-carbonaceous articles of food, while favouring a general formation of fat, are apt to give rise to special fatty degeneration in the liver or some other organ. Tet, on the other hand, one commonly finds the proper elements of the tissues — the heart, the liver, and the rest — quite healthy in men who are very corpulent. The muscular fibres of the heart, or of the voluntary muscles, may be im- bedded in adipose tissue, and yet may be themselves free from the least degeneration. So, also, the hepatic cells may be nearly free from fat within, though there be much oil around them. Fat accumulated in tissue round the elements of a part is a very difierent, probably an essentially difi'erent, thing from fat within them; the one is compatible with perfect strength, the other is always a sign of loss of power. In the muscles of some fish, such as the eel, it is hard to get a clear sight of the fibres, the oily matter uround them is so abundant ; but the fibres are peculiarly strong, and in their own texture make a striking FATTY DEGENERATION. 85 contrast witli the fibres of a degenerate muscle, in wMch. tlie fat is in great part witliin. The same essential distinction between general and local fat forma- tion, thougb they may often coincide, is shown in the fact that the local formation very often happens in those whose general condition is that of emaciation, as in the phthisical and ohlorotic. On the whole, therefore, we must conclude that soraething much more than a general tendency to form fat, or a general excess of fat in the blood, is necessary to produce a local fatty degeneration. The general conditions are favourable, but not essential, to this form of atrophy. 86 ATROPHY. LECTIJEE VI. ATEOPHr. The last lecture was chiefly occupied with a general account of those changes of texture which are to be regarded as atrophies ; and now, having pointed out what affections may be classed under this term, the whole subject may be more largely illustrated by particular examples. First, as to the conditions in which atrophy, whether with de- crease or with degeneration, may ensue. Many of them may be most easily explained as the very contraries of the conditions in. which hy- pertrophy originates. Thus, as we have seen that when a part is, within certain limits, over-exercised, it is over-nourished ; so, if a part be used less than is proper, it suffers atrophy. For instance, in the Museum of St. Bartholemew's (Ser. 12, 112) is the heart of a woman, set. 46, who died extremely emaciated, with fibroid thickenings of the pylorus. It is extremely small, and weighed only three ounces one drachm ; whereas, according to the estimates of Dr. Clendinning, in a healthy man of the same age the heart weighs upwards of nine ounces. But, small as it is, this heart was adapted to the work it had to do ; and in this adaptation we have the purpose of its atrophy. For because of her disease the woman had less blood, and needed less force of the heart to propel it ; so that, in direct opposition to what I described as the course of events in hypertrophy, here, as the quantity of blood diminished, and the waste of the heart by exercise in propelling it dimi- nished, so the repair of the waste diminished somewhat more than the waste itself did ; and the heart, though less wasted, became smaller, tUl it was only large enough for the propulsion of the scanty supply of blood. The same may be said of a heart of which there is a drawing in the same museum. It was taken from a woman twenty- two years old, who died with diabetes. It weighed only five ounces, yet, doubtless, it was enough for her impoverished supply of blood. It would be superfluous to describe many instances of atrophy ATROPHY. 87 tlirougli defective exercise, or abrogated function of parts. The wasted and degenerate limbs of the bed-ridden, the shrunken brains of the aged and the imbecile, the withered ovaries and uteri of many barren women, are good examples of defective nutrition adapted to defective exercise of function ; and so are the atrophied distal parts of nerves whose trunks have been divided, and the atrophied columns of the spinal cord that correspond with inactive portions of the brain. The rapid degeneration and removal of the tissue of the uterus after partu- rition, and the rapid disappearances of temporary organs of various kinds, are as striking examples of atrophy following the abrogation or completion of ofB.ce. To some of these examples I shall again refer. It is in similar contrast with the history of increased growths, that, as an excess of the constituents of which a tissue may form itself pro- duces hypertrophy of that tissue, so may defect of those constituents produce atrophy. Thus, the quantity of adipose tissue diminishes even below what is natural to the several parts, as often as the fat-making constituents are deficient in the food, and therefore in the blood. So, the formation of bones is defective during de6ciency of the supply of bone-earths ; the mammary glands waste when the materials for the formation of milk are imperfectly supplied ; and the whole body wastes in general defect or poverty of blood. Again, as I showed instances in which the increased flov?" of healthy blood through a part produced hypertrophy, so are there more nume- rous examples of merely defective nutrition in consequence of a dimi- nished supply of blood. Some of the most striking of these were first described by Mr. Curling,' in cases of fractured femora and other bones, showing atrophy of that portion which, by the fracture, was cut ofi" from the supply of blood thrc^ugh the great nutritive or medullary artery. The consequence of the withdrawal of so much of the blood from the upper or lower fragment, according to the position of the fracture, is not death ; for the anastomosis between the vessels of the wall and those of the medullary tissue of the bone is enough to support life, though not enough to support vigorous nutrition ; but the frequent consequence of the fracture is an atrophy of the part thus deprived of a portion of its ready supply of blood. Similar instances are seen in the decrease or degeneration of portions of hearts when single branches of a coronary artery are obstructed ; ^ in the wasting of a portion of kidney when a branch of a renal artery ' Medico-Chirurg. Trans, xx. ^ Quain, Medico-Chir. TVans. xxxiii. p. 148 ; Virchow, Archiv, iv. p. 387. 88 ATEOPHY. is closed ; ' and in local softening of tte brain, mth obliteration of single cerebral arteries.'' In all these instances we see that conditions contrary to those giving rise to hypertrophy prodnce atrophy. But there are many other conditions from which atrophy in a part may ensne ; defects in qnan- tity or in the constitution of the blood ; defective or disturbed nervous influence, as through excessive mental exertion; the disturbances of disease or injury, as in inflammation, specific morbid infiltrations, etc. In short, whatever interferes with or interrupts any of those conditions which I enumerated as essential to healthy nutrition, may give rise to atrophy, either general or local. The clinical history of the fatty de- generation of the heart, so largely illustrated by Dr. Ormerod^ and Dr. Quain,* may best prove how multiform are the events from which the atrophy of a single organ may arise. But besides all the instances in which atrophy of a part may arise as a secondary process, there are others in which we are so unable to trace its precedents, that we are tempted to speak of it as primary, or spontaneous, in the same sense as we might so call the natural wasting of the Wolffian bodies, the thymus, and other temporary organs. It is as if an atrophy of old age, instead of affecting all parts simultaneously, took place prematurely in one. The instances of grey-hairedness and baldness are so familiar that one is apt to miss their meaning as examples of a premature senile dege- neration and death. Tet it is highly probable that what occurs in the hair occurs also, though it may be less frequently, in more important parts ; and that as many look prematurely old with white hair, so some have a more gravely premature old age in the heart, or lungs, or nervous centres. Whatever the true explanation may be, most of the parts of the body appear to be subject to this seemingly spontaneous atrophy ; and it generally manifests itself in some form of degeneration. Its most frequent seats are the heart and arteries, the bones, muscles, liver, and kidneys ; but it occurs also in the pancreas and the salivary glands, in the testicle, and even in the blood. It is yet more frequent in morbid products, such as are formed during inflammation, and in tumours of every kind. ' Simon, Lectures on Pathology, p. 94. 2 Kirkes, Med.-Chir. Trans, xxxv. ' Medical Gazette, 1849. British Medical Journal, ii. 154, 1864, and i. 475, I860 ; and his recent admirable essay in the St. Bartholomew's Hospital Reports, iv. 30, 1868. < Medico-Chirurgical Transactions, xxxiii. 1850. ATEOPHY. 89 The contrast betweea hypertrophy and atrophy is, thus, nearly as great in the number as in the kind of the conditions in which they may severally arise. And, once more, "we may contrast them in regard to the mode in which the vessels and nerves adapt themselves. As a part becomes atrophied, its bloodvessels and its nerves are consequently and proportionally changed. In atrophy of the eye, the optic nerve and artery diminish ; and, in a case of fatty degeneration of the adductor muscles of the thigh, in consequence of disease of the hip-joint, I found corresponding atrophy of their nerves. The atrophy of the nerves must have been, in this case, secondary : the course of events being, inaction of the muscles in consequence of the disease of the joint; then, atrophy of them in consequence of their inaction ; and, finally, atrophy of the nerves following that of the muscles. From these general considerations I proceed to speak particularly of Atrophy as it manifests itself in some of the principal organs and tissues of the body, and first of the Atrophy of Muscles. The affection has been well studied in all the three forms of mus- cular tissue — namely, in the voluntary muscles, in the heart, and in the organic or smooth-fibred muscles ; and I will describe it in each of these in order. The voluntary muscles exhibit, in different conditions, both the chief forms of atrophy ; that, namely, with decrease or wasting, and that with fatty degeneration. In a wasted muscle, such as one sees, for example, in the limbs of those who are only emaciated, the fibres may appear almost perfectly healthy : they are rather paler, indeed, and softer, and more disposed to be tortuous than in the natural state, for muscles are commonly withered when they are thus reduced in size ; yet their transverse striffi, and all their other characteristic features, are well marked. In the state of fatty degeneration the whole of a voluntary muscle may appear pale, bleached, or of some yellowish or tawny hue, soft, and easily torn. But a more frequent appearance is that in which fasciculi in the healthy state, and others in various degrees of degeneration, lie in parallel bands, and give the whole muscle a streaky appearance, with various hues intermediate between the ruddiness of healthy flesh, and the dull, pale, tavmy-yellow, or yellowish- white, of the complete dege- neration. In such a case, healthy primitive fibres may lie among those that are degenerated as dark hairs are mingled with white in grey- |iaired men. Of the latter, some, in place of the transverse strice, 90 ATROPHY OF VOT.TJNTARY MUSCLES. present dark, very minute dots arranged in transverse lines ; m others, the whole fibre has a dim, pale, granular aspect, with no definite arrange- ment of the granules : in others, little oil-globules adhere to the interior of the sarcolemma; and in others such globules are collected more abundantly, and to the proportionally greater exclusion of the proper constituents of the fibres ; but the characters of fatty degeneration are rarely if ever so well marked in the fibres of voluntary muscles as in those of the heart. In the examination of different examples of fatty degeneration of the voluntary muscles you may find much diversity in the tissue between the fibres and fasciculi. In some instances the interspaces between the fasciculi are filled with connective tissue, both more abundant and tougher than that in healthy muscle, so that it may be hard to dissect the fibres for the microscope. With this there may be no unusual quan- tity of fat ; but, in other cases, the quantity of fat between the fibres is very great, and the fibres themselves may seem empty or wasted, as if overwhelmed by the fat accumulating around them. In such a case, when the accumulating fat has coalesced with that which before sur- rounded the whole muscle, it may be difficult to find where the muscle was ; for the whole of what belonged to it, after its degeneration, may be gone, and in its place there may remain only an obscure trace, if any, of fibrous arrangement, dependent on the position of the principal par- titions of the new fatty tissue. I cannot speak positively in explanation of this diversity in the state of parts between the fibres. But, I think, the increase and toughness of the connective tissue (when it is not the product of organised inflam- matory deposit) exist only in atrophied muscles which have had to resist stretching, after the manner of ligaments ; as, for example, when their antagonists are not as powerless as themselves. And the increase of fat seems to be found only when a muscle has been very long atro- phied, and has remained completely at rest ; then, the fibres themselves, after degenerating, may be removed, and give place to a formation of common adipose tissue, which collects in every part that they are leav- ing, just as it does about shrinking kidneys, some cancers of the breast, old diseased joints, and other parts similarly circumstanced. In either case we must distinguish between these formations of fat outside, and those within, the fibres ; the former are in no necessary connection with the proper atrophy of the fibres, but generally appear subsequent to it ; and when they attain their highest degree, they are not to be regarded as degenerations of the muscular tissue, for they are ATKOPHY OF VOLUNTARY MUSCLES. 91 not, in any sense, formed out of it, thotigli they occupy the place from wliicli it was removed. This external, or interstitial, formation of fat, possesses the structure of adipose tissue, for the fat is contained in cells which present the well-known characters of fat-cells, These cells are developed in the connective tissue, which lies between the fibres. The condition in which atrophy of the voluntary muscles most commonly ensues is inaction. Whenever muscles lie long inactive, they either waste or degenerate ; and this, whether the .inactivity de- pend on paralysis through affection of the nervous centres or fibres, or fixity of the parts they should move, or on any other cause. The degenerative process may be so rapid, that, in a fortnight, muscles paralysed in hemiplegia may present a manifest change of colour ; but it is commonly a much slower process. The course of events in these cases appears to be, that the want of exercise of a muscle, whether paralysed or fixed at its ends, makes its due nutrition impossible : and the atrophy thus brought about is the cause of loss of irritability of the muscle, i.e. of loss of its capacity for contracting. For the experiments of Dr. John Reid ' show that loss of contractile power in a paralysed muscle is due, directly, to its imperfect nutrition, and only indirectly to the loss of connection with the nervous centres. When he divided the nerves of a frog's hind legs, and left one limb inactive, but gave the muscles of the other frequent exercise, by galvanising the lower end of its divided nerve, he found (to state the case very briefly) that at the end of two months the exercised mus- cles retained their weight and texture, and their capacity of contraction : while the inactive ones (though their irritability, it might be said, had not been exhausted by exercise) had lost half their bulk, were degene- rate in texture, and had also lost some of their power of contracting. In other cases, too, he found the loss of proper texture always ensuing in the inactive state before the power of contraction was lost. It is doubtless the same in man. A muscle which, by no fault of its own, but through circumstances external to itself, has been pre- vented from acting, soon becomes incapable of acting even when the ex- ternal obstacles to action are removed. Hence we may deduce a rule which ought to be acted on in practice. When a person has had hemi- plegia, one commonly sees that long after the brain has, to all appear- ance, recovered its power, or even through all the rest of life, the para- lysed limbs remain incapable of action, and as motionless as at the first ' Edin. Monthly Journ. of Med. Science, May 1841. See also M. Brown-Sequard , in the Gaz. Medicak, No. 9, 1850. 92 ATEOPHY OF VOLUNTARY MUSCLES. attack. Now, it is not likely that this abiding paralysis is the conse- quence of any continuing disease of the brain : rather, we must ascribe it to the imperfect condition into which the muscles and nerve-fibres have fallen during their inaction. So long as the state of the brain makes voluntary action impossible, the cord, nerves, and muscles, are suffer- ing atrophy ; then, when the brain recovers, they are not in a state to obey its impulses, because they are degenerate ; and thus, their inaction continuing, they degenerate more and more, and all remedy becomes impossible. If this be true. Dr. Reid's experiments suggest the remedy. "When muscles are paralysed through affection of the nervous system, we ought to give them artificial exercise : they should be often put in action by electricity or such other agents as may not injure the damaged nerve organs ; their action, though thus artificial, will ensure their nu- trition ; and then, when the nervous system recovers, they may be in a condition ready to act with it. You will find this suggestion ingeniously supported by my friend Mr. W. F. Barlow, in a paper published by him in the Lancet. In one case, in which I could act upon it, the result was encouraging. A little girl, about eight years old, had angular curvature and complete loss of voluntary movement in the lower extremities. This had existed some weeks, but as I found she had reflex movements, the legs twitch- ing in a very disorderly way as often as the soles were touched, I advised that the limbs should be put in active exercise for about an hour two or three times a day, by tickling the feet, or in some similar way. The result was, that when, several weeks afterwards, the spinal cord recovered, and she could again direct the effort of the will to the lower limbs, the recovery of strength was speedy and complete ; more so, I think, than if, in the paralysed condition, the muscles and nerves had been left to the progress of the atrophy. A similar para- lysis, about two years later, occurred again, and was similarly recovered from. The hindered action of muscles, though the most frequent, is not the only condition from which their atrophy may ensue. They waste, together with all the rest of the body, in most emaciating diseases — as, for example, in phthisis ; and they may degenerate into fat, in concert with other tissues, in a generally defective nutrition. But, besides the general atrophies of muscles, a similar affection occurs sometimes as an apparent primary or spontaneous affection of one or more muscles. We find sometimes one of the muscles of an ex- tremity, or of the back, thoroughly atrophied, whUe the others are ATROPHY OF VOLUNTARY MUSCLES. 93 healthy ; and no account can be given of its failure; or we may even have in the same muscle limited patches of degenerated structure sepa- rated by intervening healthy tissue. Thus, it is not very unfrequent to find a portion of the lower and posterior part of the recti abdominis muscles in a state of fatty degeneration, and the same may be occasion- ally seen in portions of the deep muscles of the back. In the cases which Dr. Meryon' has described as granular and fatty degeneration, the change in the structure of the fibre generally began in the muscles of the lower limbs, and gradually extended to aU the voluntary muscles. Eokitansky ^ briefly refers to a spontaneous fatty degeneration of the muscles of the calf attended with extreme pain : Mr. Mayo ^ has recorded two cases of apparently spontaneous atrophy of the muscles of the shoulder, in which, in a few weeks after severe pain, but no other sign of acute inflammation, all the muscles about the shoulder became simply, but exceedingly, atrophied. Rapid wasting of muscles is usual in certain cases of sciatica — chiefly, I think, in such as depend on sciatic neuritis, and the cessation of the pain is commonly followed by renewed growth of the muscles, as rapid as was their wasting. Dr. Bauer ■* has pointed out that the wasting of the limb, in very painful dis- ease of the hip-joint, is much greater and more rapid than in mere in- action, and, referring it to a reflected nervous influence, has related an illustrative case in which pain in, and contraction and wasting of, the muscles of the calf followed a stab in the back near the spine. We may name these spontaneous atrophies, and may believe that the defective nutrition of the muscles is in some cases the first event in the abnormal chain ; but in other cases,' the atrophy of muscles is due to changes in the central organs of the nervous system. Sometimes muscular atrophy may occur as a part of an inflamma- tory process ; for, as I shall have to describe in future lectures, there is no tissue in which it is more evident than in the muscles, that a de- generation of the proper elements of an inflamed part is associated with the more obvious effects of inflammation.'^ ' Med.-Chir. Trans, xxxv. xlix. ; and Practical and Pathological Researches on Paralysis, London, 1864. ^ Pathol. Anat. B. 2, S. 348. ' Outlines of Human Pathology, 1836, p. 117. * On Hip Disease, New York, 1859. ' Lockhart Clarke, Beale's Archives, October 1861 ; Mid.-Chir. Bcv., July 1862 ; Med.-Chir. Trans., 1867, 1868; H. C. Bastian, Med.-Chir. Trans., 1867. Dr. Gull, Guy's Hospital Reports, viii. 1862 ; ' Address in Medicine,' Lancet, August 8, 1868. " Virchovr has recorded in his Archiv, xiii. p. 266( 1858, two cases of pericarditis, in which there was fatty degeneration of the muscular fibres of the heart. The 94 ATROPflY OF THE HEART. Atropky of tlie miascBlar substance of the heart may, like that of ■which I have jnst been speaking, appear in either wasting or degenera- tion, or in a combination of the two. Of the former I mentioned ex- amples in the beginning of the lectnre, in the heart of a woman, forty- five years old, which weighed only three ounces one drachm ; and that of a diabetic woman, twenty-two years old, which weighed only five ounces. Both these had deviated from the general rule of enlargement of the heart with advancing years, in adaptation to the diminished quantity of blood, and the general diminution of the body. In these cases there is a uniform decrease of the heart ; its cavities become small, and its walls proportionally thin ; and the fat on its ex- terior dimiuishes, or is changed into a sncculent, oedematous tissue. In other instances the cavities are dilated, without proportionate thicken- ing, or, it may be, even with thinning of their walls. This, probably, occurs chiefly in cases of such increased obstacle to the circulation as might, in other persons, or in other conditions, engender hypertrophy of the heart. Or, the dilatation may be the consequence of wasting in a heart that was once large and strong. But an atrophy of the heart much more important than any of these is that which consists in fatty degeneration. Extreme instances of fatty degeneration of the heart have been long known. The whole, or the greater part of the heart, in such cases, may seem reduced to fat ; the degenerate tissue having coalesced with that which lies on its surface, and the degeneration being accompanied by thinning and softening of the walls. In like manner the cases have been well known and described for which Dr. Quain proposes the name of ' fatty growth,' to distinguish them from the ' fatty degenerations' of the heart. In these, the adipose tissue accumulates in unusual quantity on those parts of the exterior of the heart in which it naturally exists, and is found, though often ema- ciated and very soft, even in the thinnest people — viz. along its trans- verse furrow, the furrows in which the coronaiy vessels run, and others. From these positions, the fat, dipping more and more deeply, may nearly displace the fibres, and may lead to a secondary degeneration of them ; but commonly the heart's fibres are themselves healthy, even when they lie completely imbedded in the overgrown fat. degeneration Tvas much more strongly marked in those fibres ivhich -ncre nearest the onter surface, and gradually diminished in the deeper parts. From this cirenmstanee he is of opinion that in these cases the fatty metamorphosis was a consequence of the pericarditis. ATEOPHY OF THE HEART. 95 But these conditions and their combinations are too well known to need that I should describe them, or refer particularly to any specimens of them, except to a sheep's heart which is in the College Museum (No. 1529), and which shows, in an extreme degree, a method of the growth of fat which is rarely imitated in even a trivial measure in the human subject. It exhibits a great accumulation of fat on its surface, and its walls are thin ; but the greater parts of the cavities of the ventricles and of the left auricle are occupied by large lobulated growths of suet-like fat. The weight of the fat here added to the heart is 26 ounces, and it is said that there was also a large accumulation of fat about the kidneys. But no other history of the case is extant than that the sheep was inactive, and had dyspnoea on exertion. These cases of extreme fatty growth, or of extreme degeneration, of the heart are much rarer than those of which I have now to speak. The most common form of fatty degeneration is that in which you find, on opening the heart, that its tissue is in some degree paler and softer than in the natural state, and lacks that robust firmness which belongs to the vigorous heart. But what is most characteristic is, that you may see, especiallyjust under the endocardium, spots, small blotches or lines, like undulating or zigzag transverse bands of pale, tawny, bnfi', or ochre-yellow hue, thick-set, so as to give at a distant view a mottled appearance. These manifestly depend, not on any deposit among the fasciculi, but on some change of their tissue. For at their borders you find these spots gradually shaded off, and merging into the healthy colour of the heart ; and, when you examine portions of such spots with the microscope, you never fail to find the fatty degeneration of the fibre. The yellow spotting, or transverse marking of the heart, may exist in the walls of all its cavities at once, or may be found in a much greater degree in one than in the others. It may exist in all parts of the thickness of the walls, or may be ohiefiy evident beneath the endocar- dium and pericardium. It is far less common in the auricles than in the ventricles ; and when it exists simultaneously in all parts, it is less advanced in the auricles. It is more common in the left ventricle than in the right ; and in the left ventricle it is commonly most advanced on the smooth upper part of the septum, and in the two large prominent fleshy columns. Indeed, it may exist in these columns alone, and when in such a case the rest of the heart remains strong, may account for the occasional occurrence of rupture of the columns. These yellow spottings of the heart, produced by degeneration of 96 ATROPHY OF THE HEAET. scattered portions of its fibres, are, as I have said, the most evident, as -well as the most frequent, indications of its degenerative atrophy. But a similar affection may exist in a worse form, though it be less manifest : worse, because the degeneration is more extensive and more uniform ; and less manifest, because it is less distinctly visible to the naked eye, and must be recognised by the touch rather than by the unaided sight. The whole heart feels soft, doughy, inelastic, unresist- ing ; it may be moulded and doubled-up like a heart beginning to de- compose long after death ; it seems never to have been in the state of rigor mortis. These conditions are more manifest when a section is made through the wall of the left ventricle. Then, if the wall be only partly cut through, the rest of it maybe very easily torn, as if with separation of fibres that only stick together ; and the cut surface of the wall looks, as it were, lobulated and granular, almost like a piece of soft conglo- merate gland, an appearance which is yet more striking when observed with a simple lens of about half-an-inch focus. In colour, the heart has not on its surface, much less on its section, the fall ruddy brown of healthy heart, a colour approaching that of the strong voluntary muscle, but is, for the most part, of a duller, dirtier, lighter brown, in some parts gradually blending with irregular marks or blotches of a paler fawn or dead-leaf colour. These appearances of the degenerate heart may be variously mingled ; and they may be variously associated with overgrowths of the external fat, or with previous hypertrophy or other changes of structure in the heart. But, however much the appearances of the afiection may be obscured, the general characters of softness, paleness, mottled colour, and friability, will be snfiicient, if not always to prove, yet always to excite suspicion that the fatty degeneration of the heart exists ; and if only suspicion is excited the microscopic examination may be always decisive. The chief microscopic appearances are delineated in the adjoining sketch. When a portion of the heart's walls, especially if they are very soft, is dissected in the ordinary way, with needles, for the microscope, the fibres are broken into short pieces, some twice, some five or six times as long as they are broad. The broken ends of these short pieces are usually squared, but some are round, or irregular, or cloven, and broken ofi' lower down. The pieces are almost always completely separated, having no appearance of even cohering at then- sides, and they lie scattered disorderly. In whichever form the degeneration is examined, you may find that ATEOPHY OF THE HEAET. 97 in some pieces the transverse strias are still well seen and undisturbed, appearing quite as in health. In more they are interrupted or obscured by dark dots, or by glistening particles with shady black margins, like minute oil-particles scattered without order in the fibres. Where such particles are few they appear to lie especially, or only, in contact with the interior of the sarcolemma ; but where more numerous they appear to occupy every part of the fibre, leaving the transverse strice discern- ible only at its margins, or even completely ohscuring or replacing them, and making the fibre look like a gland-tube filled with dark gra- nules and larger glisteiaing dark-edged fat particles. Where these particles are very numerous in a fibre they appear also generally larger and m.ore generally glistening and black edged; like larger oil-par- ticles. There may be no oil-drops floating about, no fat-cells, scarcely even any of the minute particles, which are seen in the fibres, may be out- side them ; the field of the microscope may be perfectly clean. In these minor respects, however, many differences exist, though I think it may be stated that the degeneration is very rarely, if ever, accom- panied by any morbid product deposited between the fibres ; whatever fatty matter may appear between them is only such as has escaped from them. As a general rule the jialBst jjarts of the heart are most advanced in the disease, but even, in microscopic portions some pieces of fibres appear hardly chahgedj while those all I'ound them a,re completely granular. Eig. 6. A. MuscvJar fibres of tlie healthy human heart. S. Fatty degeneration of the fibres of the human heart; b, early stage ; b', more adyanced. C. The same, yet more adTanced, dll inagnified 400 times. From Dr. Quain's plates; Med.-Ohir. Trans, xxxiii. pi. 3. H 98 ATEOPHY OF THE HEART. I alluded in tte last lecture to the defective condition of the nuclei of degenerate elemental structures. This is peculiarly weU shown in the degenerate fibres of the heart. When those of a healthy heart are placed in diluted acetic acid they display a longitudinal series of nuclei at nearly equal distances apart, and usually lying in the middle of the presenting surface of the fibre. Nuclei of this form are, so far as I know, pecuhar to the heart-fibres. They are large, reddish-yellow like blood-globules, especially when the heart is very robust ; they are elong- ated oval, or nearly quadrilateral, and at each of their ends one al- most always sees tapering groups of small, isolated, yellowish granules like particles separated from them, and gradually withering. But in the degenerate fibre, when the change is least advanced, the outline of the nucleus looks dim, and it loses its colour ; when the change has made further progress the nucleus cannot be seen at all, though its former place may be indicated by some of the narrow group of granules ; and in a yet later stage, when the sarcolemma appears nearly full of fatty particles, all trace is lost alike of the nucleus and of the granules. I have spoken of fatty degeneration of the heart at this great length both because there is no better example for illustration of the general pathology of such affections, and because it is extremely important that this condition of the heart should be recognised after death, even when no suspicion could be entertained of it during life. For it often intro- duces unexpected dangers into the ordinary practice of surgery ; it is, I believe, not rarely the cause of sudden death after operations ; it is one of the conditions in which chloroform should be administered with more than ordinary caution. They who labour under it may be fit for all the ordinary events of calm and quiet life, but they are unable to resist the storm of a sickness, an accident, or an operation. And let it not be said that one learns little in learning too late the existence of an incurable disease, for very often the death that has come from such a disease has been ascribed to a wrong cause, and has spoiled confidence in good men and their good measures. Nor does the caution seem un- necessary that, serious as the effects of the disease are, the change of structure may escape any but a very careful and practised examiner. For often the change is hardly manifest to the eye, though, while it affects the whole heart, it may have destroyed life. Atrophy of the organic or smooth-fibred muscles doubtless occurs, as a simple decrease of them, in the thinning of the coats of the intes- tines, stomach, and other hollow organs, which is sometimes associate.d with general emaciation, or with diminished function ; but the change ATROPHY OF THE BONES. 99 has not been carefully studied. Of the fatty degeneration of this mus- cular tissue, examples are described in the muscular coats of the ar- teries/ which partake in. the corresponding change, or atheromatous affection of their thickened internal coats ; in the coats of the urinary bladder ; ^ and in the uterus.^ In the latter organ the change has pe- culiar interest ; taking place, as it does, quickly after the fulfilment of office in parturition ; affecting all the muscular fibro-cells which, during gestation, had been developed to their perfection ; and preceding their absorption and replacement by new-formed fibro-cells, like those which existed in the young and unimpregnated uterus. The series of changes thus traced by Kilian tells a complete history of nutrition, in the suc- cession of- development and growth to perfection, of discharge of func- tion, consequent degeneration, absorption, and replacement by new structures that, in their progress, pass through the same phases as their predecessors. The production of fat in the uterine tissue confirms also the probability which I have already mentioned (p. 43), that fat is one of the usual results of the chemical change which takes place in mus- cular action, and is in this relation a substance, like the kreatine, which is also found in the uterine tissue after birth,* intermediate and transi- tional between the proper constituents of the tissues and the oxidised materials of excretions. It may be added, that the whole substance of the uterus and its membranes partakes of the degenerative change, and that the removal of the old tissues and the formation of new ones is so total, that, as it has been justly said, a person has a new uterus after each delivery. But the peculiarity of the case is only in that the change is accomplished quickly, manifestly, and simultaneously in a large mass of tissue : in the same sense, though at unknown times, men have often new hearts, new glands, and new brains. In the Bones we may probably consider that a calcareous degenera- tion occurs as a method of atrophy^ in addition to those just described in the muscles ; for to such a degeneration we may ascribe the increased proportion of bone-earths in the skeletons of aged persons. The aug- mentation of earthy constituents is not attended with increased strength ' Eokitansiy, Fathol. Anat. ii. p. 543 ; Kolliker, ZeUschr.fiir wissensch. Zoologie, i. p. 81. - Mr. Hancock, as quoted by Mr. Barlow, Med. Times and Gazette, May 15, 1852. ' Kolliker, 1. c. p. 73. Kilian, in Henle and Pfeufer's Zeilmln: fur rat. Mcdichi, viii. and ix, ' Siegmund, in the Wiu:hurg Vcrhandhcngen, B. iii. H. 1, H 2 100 ATEOPHY OF THE BONES. of the bones : rather, they become, in old persons, thin-walled, and more easily broken ; the change being commonly associated with both wasting and fatty degeneration, and the whole tissue being rarefied. It is through this general want of compactness in their construction that old bones are weak ; for, as Dr. Stark's analyses show very well, the strength of bones depends more on their compactness than on the proportion of their constituents. I am not aware that any analyses of diseased or other bones have shown a calcareous degeneration of them, except in old age ; but its frequent occurrence is highly probable. The other modes of atrophy may be more fully illustrated in the two forms already often referred to. The simple wasting of a bone is a common change. -Examples have been already adduced in connection with the subject of unequal length of the limbs (p. 64), and with that of the effects of pressure (p. 66), as well as in relation to the general history of atrophies. Among many specimens in the College Museum, the most striking is the skele- ton of an hydrocephalic patient from the collection of Mr. Liston (No. 3489). It is the more remarkable, because, while all the bones of the trunk and limbs are reduced by atrophy to exceeding thinness and lightness, the bones of the cranium are as exceedingly enlarged in ad- aptation to the enormous volume of their contents. In the skulls of old persons, more especially in the alveolar bodies of the jaws, absorption of the osseous tissue extensively occurs. But senile atrophy of the skull is not necessarily limited to the jaws and other bones of the face. The bones of the cranial vault occasionally waste, and undergo a marked diminution in weight. The thinning is especially seen at the centres of ossification of the parietal bones, each of which, instead of an eminence, presents a depression, such as the thumb would make if pressed into soft clay, and a deep groove not un- frequently forms along the hlie of the sagittal suture (Fig. ?). Some- times a formation of new bone may take place in other parts of the skull on the free surface of the inner table.' ' These changes have been carefully described by Virchow ( Wilrzh. Verhandl. B. iv. p. 354 ; Gcsam. Abhandl. p. 1000). Several specimens of this form ot skull are in the Anatomical :Museum of the University of Edinbiirgh. Fig. 7, an aged female skull (No. 60), IS an example. The freight of this skull is only Hi oz. avoir., ^vhUst that of a female, set. 27, -n-ith which it was compared, was 17 oz. In a memoir on 'Plastic ,DeforiQities of the Skull' Dr. J. Barnard Davis has described (^Mhn. de la Soc. d Anthropologic, 1862) some crania in which, apparently from softening and atrophy, the condyloid portion of the occipital bone had been pushed upwards towards the cranial cavity. Prof. Eetziiis has also figured a skull (JlUseum Anat. Holmiense ATROPHY OF THE BONES. 101 An interesting specimen is a skull (No. 8) fitted up by Hunter to show the movements of the edentulous lower jaw, as he has described them in his Natural History of the Teeth. It shows the atrophy not only of the alve- olar margins, but of every part of the jaws, and even of their palatine parts, and those of the palate bones, which are quite thin and transparent. A rare specimen of atrophy of the lower jaw is shown in a case of complete osseous auchylosis of both temporo- maxillary articulations, from Mr. Howship's museum (No. 966). Atrophy of a long bone in its extreme state is illustrated Fig. 7. by an example of anchylosis of the knee (No. 384), from the case de- scribed by Mr. Thurnam.' Considerable apei-tnres are formed in the wa^ed walls of the femur and tibia, which are covered in by the perios- teum alone, the whole thickness of these portions of the walls having been removed in the progress of the atrophy. In the museum of St. Bar- tholomew's (3 C 116) is a specimen in which simple atrophy of the femora led to such fracture as, being effected by a slight force, is called spontaneous. The atrophy of these bones occurred ooincidently with extreme emaciation of all the other parts, as well as of the skeleton; an emaciation which was to be ascribed, I believe, more to starvation than to anything else. The shafts of the femora are exceedingly small, and their walls are so thin that, although their texture appears healthy, they could not resist the force of the musoles acting on the articular ends. They broke, and the result shows a remarkable example of the capacity for repair of injuries even while the process of ordinary nutrition seems almost suspended, for the fractures were firmly reunited. In senile atrophy of the long bones the wasting takes place from within ont- 1855) -which had undergone considerable distortion, with great alterations in the size and shape of the cranial foramina, occasioned by a fatty degeneration of the osseous texture. ' Medioal Gazette, xxiii. p. 119, 102 ATEOPHY OF THE BONES. wards, the medullary canal being increased at the expense of tlie compact tissue, so that the external form of the bone is not altered. On the other hand, when atrophy of a bone in an amputation stump occurs, the diminution in size takes place by absorption of its exterior, and the bone assumes an attenuated, tapering form at its free end. I might greatly multiply examples of such simple wasting atrophy of bones, but let these suffice, that I may speak now of fatty degenera- tion of the bones. I have already said that it is common in many atrophied bones to find an excess of fatty matter ; I referred to old bones laden with fat as examples of a form of senile atrophy ; and sometimes, in oases of diseased joints, the form of atrophy assumed by the disused bones is that not merely of exceeding thinness of the walls and wasting of the cancelli, but of an accumulation of soft fat, fiUing every interstice, and main- taining the size of the bone. But it is now to be added that the bones, like other organs, are liable to a fatty degeneration, which, because of the obscurity of its origin, we must be content to call spontaneous; and this fatty degeneration of the bones is the disease which most English writers have described as Mollities Ossium. The Museum of the College has a remarkably rich collection of specimens of this disease : a collection embracing specimens from nearly all the cases with whose histories we are most familiar. Well-marked examples of the fatty degeneration are shown in No. 400. These are two femora fractured by a slight force, and, in their dried state, light, very greasy, mahogany-brown, and so soft that you may crush many parts of them with the fingers. Their excess of fat is evident ; but no more of their history is known than that they came from an elderly, if not an old, man — an Archbishop of Canter- bury. In No. 398 is a section of a humerus, afiected, as many other bones of the same person were, with extreme fatty degeneration ; and the catalogue contains, with its description, a reprint of an essay by Mr. Hunter, which escaped even the careful research of the editor of his works, Mr. Palmer. His essay is entitled ' Observations on the Case of Mollities Ossium, described,' etc., by Mr. Goodwin, in the London Medical Journal} It was communicated in a letter to Dr. Simmons, the editor of that journal, and I will quote one passage to show both what was the original appearance of the bones, and how completely Mr. > Vol. vi. 1785. ATROPHY OF THE BONES. 103 Hunter's description confirms tlie opinion that tliis mollities ossium was really a fatty degeneration of the bones. He says, speaking of this humerus, ' The component parts of the bone were totally altered, the structure being very difierent from other bones, and wholly composed of a new substance, resembling a species of fatty tumour, and giving the appearance of a spongy bone deprived of its earth, and soaked in soft fat.' Nothing can better express the character of the change, or its similarity to the fatty degenerations of other organs, in which we find the proper substance of the part gradually changed for fat, and the whole tissue spoiled, while the size and outer form of the part remain unaltered. The same characters are shown in the often-quoted case by Mr. Howship, of which specimens are preserved in Nos. 401-2-3. The last of these specimens shows what remained of the upper part of a femur after boiling ; scarce anything besides a great quantity of white crystalline fatty matter. It is the same with a femur (No. 403 B) presented to the Museum by Mr. Tamplin, in the examination of which I first obtained, with the microscope, the conviction of the nature of the change which constitutes what we call mollities ossium. This has the same characters as the specimens already shown, and the medulla of the bone had the bright yellow, pink, and deep crimson hues, which are so striking in many instances of the disease. But the constituents of this apparently peculiar material were, free oil in great quantity ; crystals of marga- rine, free, or enclosed in fat-cells ; a few fat-cells fall of oil as in health, but many more, empty, collapsed, and rolled up in strange and decep- tive forms. The pink and crimson colours were owing to the bright tints of a part of the oil-globules, and of the nuclei and granules in the collapsed fat-cells ; and there was no appearance whatever of an excess of blood in the bone, or any of its contents. From this examination, therefore, as well as from all the other facts, I concur entirely in Mr. Curling's opinion respecting this disease.' A specimen (No. 403 A) from the case on which he chiefly founded his opinion, and which he has very accurately described, closely resem- bles those I have referred to. He proposes the name ' Eccentric Atrophy of Bone ' to express one of the principal characters of the disease ; and I would have adopted it, as preferable to ' Osteoporosis,' ' Mcd.-Chir. Trans, xx. 104 ATROPHY OF THE BONES. under which. I think Rokitansky would include these cases, but that it seems desirable to class this affection with others to which it bears the closest analogy, by giving it the same generic name in the designation, fatty degeneration of bones. The cases above referred to include the principal examples of the disease observed and recorded ia England under the name of mollities ossium ;' and to these, I think, might be added the case described by Mr. Solly,^ for the appearances presented by the femur (No. 403 C) are strikingly similar to those in the specimens already referred to, and the material filling its medullary cavity contained abundant fatty matter. Ton might ask, then, what is the real moUities ossium ? or is there such a disease different from what these specimens show ? I could not from my own observations answer such a question ; for I have never seen a specimen which appeared to fulfil in any degree the general notion of mollities ossium, as a disease consisting in the removal of the earthy matter of bone, and the reduction of any part of the skeleton to its cartilaginous base. Bokitansky, however, and other contiaental pathologists, have described by the name of Osteomalacia, Malakosteon, Knochenerweichung, and Rachitismus adultorum, a pathological con- dition of the boiri.es which they conceive to be related to the disease termed mollities ossium in this country, but which differs in many of its characters from the extreme fatty degeneration just described. At the commencement of an attack of osteomalacia, the medulla, as Litz- mann ^ has shown, is very rich in blood, which is partly contained in the vessels, and partly extravasated, so that it possesses a wine-red or almost black colour. The fat,cells also have to a large extent disap- peared, but the proper n^yeloid cells are present in considerable ' Since these lectures were delivered, however, several additional cases have been recoKled. Dr. T. K. Chambers relates (Mcd.-Chir. Trans, xxxvii.) the case of a woman, set. 26, in whom the bones and mnscles had undergone fatty degeneration ; Dr. Ormerod that of an adult male {British Med. Jour. Sept. 1859) in whom the skeleton generally was affected ; Dr. W. C. M'Intosh, two cases in women past the middle period of life {Edin. Med. Jour., August 1862); Dr. Barnes {Med.-CJiir. Trans. xlv.) that of a woman aet. 40 ; Dr. Lory Marsh {Lancet, Nov. 14, 186.3) the case of a woman set. 36 ; Mr. Arthur Durham {Guy's Hospital Rep. x. 1864) that of a woman the account I have given above exactly fits, and the consequences of which, in puhnohary apoplexy, correspond with the cerebral apoplexies due to rupture of the small bloodvessels of the brain. In the capillaries of the Uaucous membrane of the small intestine, also. Professor Turner has seen^ in one case, extensive fatty degeneration, similar in its charactei? to that which I have figured in the cerebral Many facts of exceeding interest are known concerning the degene- rations of Nervous tissues, but, as yet-, they are rather fragments than a continuous history. First, it! relation to the causes of degeneration, two are chiefiy knofrn ; niamely, defect of bloodj and arrested function. Cases of soft- ening of the brain have been long recognised as the consequences of ' Ueber den Laennccschen Lnngen-wfarJetus. Erlangen, 1850. 110 ATEOPHY OF NEEVOtTS TISSUES. ligature, or obstructive disease, of tke carotid or other large arteries ; but they have received a new interest from the discovery by Virchow, and independently by Dr. Kirkes, of their frequency in consequence of the obstruction of healthy cerebral arteries by masses of fibrine carried into them, after being dislodged from the valves of the left side of the heart or from some part of the arterial system. In these cases, the extent of softening nearly corresponds with the range in which the bi'anches of the obstructed artery are distributed : for, beyond the circle of Willis, the anastomosis among the cerebral arteries, like that among the cardiac, is not sufficient to carry a full supply of blood into a part from which the main stream is hindered, though generally enough to prevent the complete death or sloughing of the part. Of the atrophy following diminished or abrogated function of nervous parts I have already mentioned examples in the shrinking of the brain in old people, in the v^asting of the nerves of paralysed or fixed muscles, and in that of the optic nerve and tract in cases of blind- ness. To these may be added the cases observed by T)r. Waller ; ' who has discovered that when a nerve is divided, its distal part, i.e. the portion between the place of division and the place of distribution, the portion in which the nerve-office can be no longer exercised always suffers atrophy, wasting and dt generating. The same atrophy ensues in the vrhole length of any spinal nerve whose root is divided ; and in any system of nerves through which, after injury of the spinal cord, reflex actions cannot be excited. The change, in divided nerves, begins at the distal extremities of the nerve-fibres, and gradually extends upwards in the branches and trunk of the nerve ; but is repaired if the divided portions of the nerve be allowed to reunite. I need not say how great interest these facts have in relation to the anatomy and physiology of the nervous system . but it is equalled by those related by Dr. Turck,^ which may be used for ascertaining the functions of the several columns of the spinal cord, and their relations to the difiFerent parts of the brain, in the same manner as, by those of Dr. Waller, knowledge may be gained of the course and distribution, and of the centripetal or centrifngal office, of the several nerves. The main fact discovered by Dr. Turck is, that after diseases of parts of the brain or spinal cord there gradually ensues a softening, as by atrophy, of those tracts or oolamns of the cerebro-spinal axis, through which, in health, ' PJii/ps. Trans. 1850, Part 2 ; and in the London Journal of Mcdichic, July 1862. 2 Ueber secmiddre Erkranhing eimdiier Huckeivmarkitrwige. Wit-ii, 18.51. ATROPHY OF NERVOUS TISSUES. Ill impressions were habitually conveyed from tte diseased part. The same general truth is illustrated by both these series of observations ; namely, that nerve-fibres, through which, from whatever cause, nerve- force can be no longer exercised, are gradually atrophied. The atrophy took place very quickly in the frogs that were the subjects of Dr. Waller's esperiments ; commencing in young frogs, during the summer, in from three to five days, and being completed in from twenty to thirty days. But, in the human subject, the process, reckoned by the obser- vations of Turck, and those in which I have examined nerves atrophied in paralysed muscles, is much slower. Changes in the spinal cord are not, he says, discernible in less than half-a-year after the apoplexy or other affection of the brain of which they are the consequence. The changes in the nerve-fibres thus atrophied are minutely de- scribed by Dr. Waller. At first, transverse lines appear in the intratu- bular substance, indicating its loss of continuity j then it appears as if divided into round or oblong coagulated masses, as if its two component materials were mingled ; then these are converted into black granules, resisting the action of ether, acids, and alkalies ; and finally, these granules are slowly and imperfectly eliminated.' Some interesting observations have just been recorded by Dr. Dickinson,^ which show that, after amputation of a limb, important structural changes take place in the nerves of the stump, and in the part of the cord from which they spring. He found though the nerves retained their bulk and external appearance, yet that the nerve-fibres themselves had almost entirely disappeared. The nerve-roots, more especially the posterior, had wasted, and the posterior column on the amputated side had atrophied, and its connective tissue had underp-one considerable condensation. But in the degenerations of nerves, as has already been described in that of muscles, the pathological changes are not necessarily con- fined to the substance of the fibres. For in some cases (Fig. 11) fat- cells form in considerable numbers in the connective tissue between the funiculi, and the nerve, losing its brilliant white colour, becomes softer and more easily torn. ' G-. "Walter has recently (Virchow's Arckivs, 1861, xx. p. 426) re-examined the changes which take place in nerve-fibres after division. He distinguishes the follow- ing stages— ls<. Coagulation of the medullary substance in the nerve-fibre. 2r7. liesorption of the pre-e?isting contents of the medullary sheath. Sd. Fatty degenera- tion of the nuclei of the nerve-sheath, ith. Resorption of the axial cylindei-, ultuv Cracking and breaking up into granules. ' Journal of Analomy and Physiology, Nov. 1868. 112 ATROPHY OF NERVOUS TISSUES. In the atropLiee of tte brain and spinal cord, whether from ob- structed circulation or from hindered function, the chief changes that are observed are, the lique- faction or softening of the whole substance, the breaking-up of the nerve-fibres, and the pro- duction of abundant granule- Cells, or masses, and free-float- ing granules. TJntil very re- cently there was a difficulty in accounting for the origin of these granule-cells on the sup- position that they were cells un- dergoing fatty degeneration, as it was thought that no cell-struc- tures existed in the white part of the brain and spinal cord. But the discovery by Virohow in the great nervous centres of the delicate intermediate form of connective substance, termed by him Neuroglia, in which numerous small delicate corpuscles are im- bedded (Fig. 12), and the ob- servations by liockhart Clarfce and others on the existence of a fine hetwork of con- nective tissue (in which mul- titudes of fine cells and nuclei are interspersed) between the fibres of the columns of the ■^'S- 12. cord, supply ts with a source from which these fat-containing granule-ceUs may be derived. Fig. 11. a, Nerve-fibres, forming a funiculus; i, sheath of oonnectire tissiie ; 0, fat-cells formed within this sheath. Magnified view of part of the left ulnar nerVe of a male siibject dissected in 1864 in the Practical Anatomy Rooms of the University of Edinburgh. Extensive fatty degeneration of the heart, liver, muscles of .the lower limbs, and of some of those in the left upper limb was seen. The fatty change in the muscles was both between and within the fibres. The connective tissue sheaths of the nerves passing to the degenerated muscles were laden with fat-cells, and the axial cylinders of the corresponding nerve-fibres were shrivelled, and could not be satis- factorily tinted with carmine. Fig. 12. Magnified view of the white centre of a convolution of the cerebrum, showing capillaries, nerve-fibres, and the corpuscles of the Neuroglia. From a pre- p.aration by Mr. A. B, Stirling, assistant in the Anatomical Museum, University of Edinburgh. AECUS SENILIS. U3 The last example of atrophy of which I -will speak is that which is manifested in the Arcus senilis, — the dim greyish-white arches or ellipse seen near the borders of the cornea in so many old persons. Its nature was discovered and is fully described by Mr. Canton.' It is a true fatty degeneration, and consists in the accumulation of minute oil-drops ; in the first instance, in the corpuscles of the cornea, and subsequently in and between the lamellae of which it is composed. By his and others'' investigations, it has also acquired a larger interest, in being found the frequent concomitant and sign of more widely extended degenerations that are not within sight during life. Thus, it is com- monly associated with fatty or calcareous degeneration of the ophthal- mic artery ; with fatty degeneration of the muscles of the eyeball ; and especially in old persons, with fatty degeneration of the heart and many other organs. In short, the arcus senilis seems to be, on the whole, the best indication that has been yet found of proneness to an extensive or general fatty degeneration of the tissues. It is not, indeed, an infal- lible sign thereof; for there are cases in which it exists with clear evidences of vigour in the nutrition of the rest of the body ; and there are others in which its early occurrence is due to defective nutrition oon- seqvient on purely local causes, such as inflammatory affections of the choroid, or other parts of the eye ; but, allowing for these exceptions, it appears to be the surest, as well as the most visible, sign and measure of those primary degenerations which it has been the chief object of the last two lectures to describe.-' • ' ObseiTations on the Arcus Senilis,' in the Lancet, 1850 and 1851 ; and On the Arcus Senilis, London, 1863. ' Especially Drs. Qxiain, Williams, and Virchow {Archit, B. iv. 288). ' The degenerations of organs not described in the lectures, and the authorities not already quoted, may be studied by the aid of the following references : — Arterie», Testicles, Lungs, and Liver: Gulliyer, in Med.-Chir. Trans, xxvi. p. 86. Liver : Bowman, in Lancet, 1841-2, i. p. 560. Kidney: io\vasou,\n Med.-Chir. Trans, xxix. p. i.; with Appendix, in xxx. p. 182. Simon, in Med.-Chir. Trans, xxx. p. 141 ; Virchow, in his Archiv, B. iv. p. 261, et seq. ; and Gairdner, Pathology of the Kidney, Edin. 1848 ; Arnold Beer, Die Biti- desubstanz der rMnschliclien Mere, Berlin, 1859. Colourless Blood-cells, various Epithelial cells. Cartilage-corpuscles, Nerve-cells ; Virchow, in his Archiv, i. p. 144, et seq. Lungs : Eainey, in Med.-Chir. Trans, xxxi. p. 297. Placenta: Barnes, in Med.-Chir. Trans, xxxiv. and xxxVi., and Druift, Med.-Chir. Trans, xxxvi. Pl.icenta, Deciduft, and OtJier tissues of the Uterus, as well as the Miisonlar; Kilinn, as quoted at p. 131. Cartilage: Kedfern, Anormal Nutrition in the Articular Cttrtitages, 1850; and Virchow, in his Archiv, B. iv. p. 289. C. 0. "Weber, Virchow's Archiv, V>. xiii. 1858. I 114 AROCrS SENILIS. Numerous calcareous degenerations : Dusseau, Het Beeaweefad en Verbceningen, Amsterdam, 1850. The Transactions of the Pathological Society of London abound in records of cases of fatty and calcareous degenerations of, and in the different textures. Pigmental Degenerations : Virchow, in his Archiv, B. i. Prostatic Concretions : Hassall, Microscopic Anatomy. Wedl, Pathological Histology. Paulizky, Virchow's Jrchiv, xri. Waxy or Amyloid Degeneration : W, K. Sanders, Edinhirgh Med. Journal, Jan. 1853, Peb., April, Nov., 1854. J. H. Bennett and W. T. Gairdner, Edin. Med. Journal, Feb. 1854. Yircho-w, Archiv, vi. et seq.. Cellular Path., Lect. xiii. H. Meckel, Annal. des Charite Kravk. Jahrgang iv. C. Schmidt, Ann. des Chemie, B. ex. Drs. Bristowe and Ord, Ti-ans. Path. Soc. Lond. x. G. Busk, Quart. Jour. Mic. Sci. January 1854. T. A. Carter, Edin. Med. Jour. 1855 and 1858. Fr. Harris On the Kaiure of the Substance found in the Amyloid Degtrwration, 1860. Billroth, BeitrSge zur Path. Hist. Lockhart Clarke in Beale's ^rcAjVei, 1861. Pagenstecher, TJeber die Amyloide Degeneration, Wiirzburg, 1858. Porster, Atlas der Path. Anat. 1859. Eouget, in Brown Sequard's Jcmr. de la Phys. Jan. 1859. T. G. Stewart, ' On the Waxy or Amyloid Degeneration of the Kidney,' £1?. Med. Jour. 1861; 3.nA. Bright' s Diseases, Edinburgh, 1868. Dr. Pavy, Guif s Hospital Beports, 1864. Caseous and Colloid Metamorphoses: Otto Weber in Billroth and von Pitha's Handbuch. The chief general histories of degenerations are by Eokitansky, Pathol. Anat. ; C. J. B. Williams, Principles of Medicine ; and Virchow, in the places cited above, and in his Archiv, B. iv. p. 394. W. H. Walshe, ' Adventitious Products,' Cyclopmdia of Anatomy and Physiology, iv. The degenerations of products of disease will be described in future lectures. 115 LECTURE VII. GENEEAL CONSIDERATIONS ON THE EEPAIE AND EEPEODUCTION OF INJURED AND LOST PAETS. Amokg tBe general considerations that may be suggested by tlie preced- ing lectures, none, perhaps, is more "worthy of earnest thought than that of the capacity of adaptation to the variety of their circumstances, which is displayed by the several parts of the body. Each part may be said to be conformed, in its first construction, to a certain standard of measure, weight, and power, by which standard it is adjusted to the other parts of the whole organism. The first perfection of the economy is in the justness with which its several parts are thus balanced in their powers ; and the mutual adaptation thus established is continued, in or- dinary life, by the nutrition of each part being regulated according to a law of direct proportion to the quantity of work that each discharges. But when the external conditions of hfe vary, and require, for the main- tenance of health, varying amounts of function to be discharged by one or more parts ; and, still more, when disease disturbs the functional re- lations of any part to the rest ; then each part displays a capacity of adap- tation to the new conditions in which it is placed : each can assume a less or greater size and weight ; each can acquire a less or more powerful tis- sue ; each can thus rise above, or descend below, its standard of power. This capacity of adaptation is shown in a yet more remarkable manner in the recovery of parts from the effects of injuries and diseases. It is surely only because it is so familiar, that we think lightly, if at all, of the fact, that living bodies are capable of repairing the efiects of injury, and that in this capacity they prove themselves adapted for events of which it is not certain whether they will ever occur to them. The exact fitness in every part of a living body for its present office, not as an independent agent, but as one whose work must be done in due proportion with many others concurring in opera- tion with it, is a very marvellous thing ; but it seems much more so I 2 116 GENERAL CONSIDERATIONS ON THE REPAIR AND that in the embryo each of these parts was made fit for offices and rela- tions that were then future ; and yet more marvellous than all it seems that each of them should still have capacity for action in events that are not only future but uncertain ; that are indeed possible, yet are in only so low a degree probable, that if ever they happen they will be called accidents. Let us have always in mind this adaptation of the living body to future probabilities, while we consider the phj'^siology of repair. If it be fairly weighed, every part of the process of repair will be an argu- ment of Divine design ; and such an argument as cannot be impugned by the suspicion that the events among which each living thing is cast have determined its adaptation to them ; for all the adaptations here noted prove capacities for things future and only not improbable. And let us also keep in view how the reparative processes may illus- trate the laws of ordinary nutrition ; and especially observe that they furnish evidence of the nature of the formative process exercised in the complete organism. I mentioned in a former lecture (p. 45) that, in naany instances of repair and reproduction, the formation of the new replacing structures cannot be ascribed to an assimilative force, or to the development of tissue-germs derived from the injured or lost parts. The completeness of repair after injury, and the extent to which it is sometimes accomplished, become thus most striking evidences of the principle that the formative process is, in the completed organism, the same and continuous with that which actuated the formation of the original tissues in the development of the germ and embryo. There is in every considerable process of repair a re-making of a part ; and the new materials assume the specific form and composition of the part that they replace, through the operatign of no other, or otherwise directed, force, than that through which that part was first made. For, in all grave injuries and diseases, the parts that might serve as models for the repairing materials to be assimilated to, or as tissue-germs to develop new structures, are lost or spoiled ; yet the eflfects of such injury and disease are recovered from, and the right specific form and composition are regained. In all such cases, the reproduced parts are formed, not according to any present model, but according to the appropriate spe- cific form ; and often with a more strikingly evident design towards that form as an end or purpose than we can discern in the natural construc- tion of the body. Moreover, it will be obscived, in the instances of repair of injury even more plainly than in the maintenance of the body in thejpuccessive EEPEODUCTION OF INJURED AND LOST PARTS. 117' ordinary stages of its life, that the law of formation is at each period of life the same : — that every part is formed after the same method as was observed in the corresponding part of the parent at the same pe- riod of life. Thus, when, in an adult animal, a part is reproduced after injury or removal, it is made in conformity, not with that condition which was proper to it when it was first formed, or in its infantile life, but with that which is proper according to the time of life in which it is reproduced ; proper, because like that which the similar part had, at the same time of life, in members of former generations. In the repro- duction of the foot or the tail of the lizard, they grow, as it were, at once into the full dimensions proper to the part, according to the age of the individual. Spallanzani expressly mentions this : — that when a leg is cut from a full-grown salamander, the new leg and foot are developed, as far as form and structure are concerned, just as those of the larva were ; but as to size, they from the beginning grow and are developed to the proper dimensions of the adult. The power, therefore, by which tliis reproduction is accomplished, would seem to be, not the mere revi- val of one which, after perfecting the body, had lapsed into a dormant state, but the self-same power which, before the removal of the limb, was occupied in its maintenance by the continual mutation of its particles, and is now engaged, with moi-e energy, in the reconstruction of the whole. The ability to repair the damages sustained by injury, and to repro- duce lost parts, appears to belong, in some measure, to all bodies that have definite form and construction. It is not an exclusive property of living beings ; for even crystals will repair themselves when, after pieces have been broken from them, they are placed in the same condi- tions in which they were first formed. The diagram (Fig. 13) represents a series of casts made from a crystal with which I imitated the experiments of Jordan.' A large piece was broken off an octohedral crystal of alum (a). Before the fracture it was perfect in its form, except at one small pit on its surface, where it had what (writing of animal physiology) might be called a congenital defect. Thus broken (b) it was placed again in the solution in which it had been formed, and after a few days its injury was so far repaired as it appears in the figure (c). The whole crystal had in- creased, but the increase on its broken snrface was proportionally so ' Miiller's Archiv, 1842, p. 46. 118 GENERAL CONSIDERATIONS ON THE REPAIR AND much greater than on any other, that the perfect ootohedral form was nearly regained. The little congenital defect, also, was completely healed. In a few days more, the whole crystal would have been as if it had suf- fered no injury. Fig. 13. I know not what amount of mutual illustration, if any, the repair of crystals and of living bodies may afford ; but, in any case we may trace here something like an universal property of bodies that are naturally and orderly constructed : all, in favourable circumstances, can repair at least some of the damages to which they are liable from the violence of external forces. But, to speak only of the repair and reproduction that occur in the several orders of the animal kingdom ; among these they exist in sin- gularly different degrees, and in such as can be only partially included in rules or general expressions. The general statement sometimes made, that the reparative power in each species bears an inverse ratio to its position in the scale of animal life, is certainly not proved ; and many instances^ are contrary to it — such as the great reparative power possessed by the Triton and other lizards, and the apparently complete absence of it in the perfect insects. Rather, the general rule which we may expect to find true, and for which there is already much evidence, may be that the repara^tive power bears an inverse proportion to the amount of power coi^umed in the development and growth of the in- dividual, and in its maintenance in the perfect state. Our ideas of the consumption of power in the organisation of matter, are, perhaps unavoidably, very vague ; yet are there facts enough to prove that the power which can be exercised in a germ is limited, so that the capacity of assuming the specific organic form cannot be communicated to an indefinite quantity of matter ; and there are also enough to justify the expression, that the power, thuB limited, is in some measure consumed — 1st, in the development of every new gtruc- tupe, and, 2dly, in a less measure, in the growth and maintenance of those already formed. KEPRODUCTION OF INJUEED AND LOST PARTS. 119 Thus, first, it appears constantly true that the reparative power is greater in all parts of the young than in those of the older individuals of all species. Even when we compare individuals that have all attained their highest development and growth, this rule seems to be true. We know it from general observations of the results of similar injuries and diseases in persons of different ages : numerous as the exceptions may be, the general rule seems true. And it is yet more evidently proved in the case of some lower animals. Spallanzani mentions it in regard to the reproduction of the tail of the tadpole. The quickness with which the work of reproduction is both begun and perfected was always, in his experiments, in an inverse ratio to the age. He says the sam.e for the reproduption of the legs of salamanders ; and it is only in the young among frogs and toads that any reproduction of the limbs will take place. So, too, in experiments on the repair of frac- tures, the union of tgndons and the like, in the mammalia, one may see abundant evidence that the vigouy and celerity of the process are in an inverse proportion tq the anin^al's age. There is, indeed, some reason to believe that, in the very early period of embryonic life, a true repro- duction of parts of limbs may take place even in the human species. Not to speak of the possibility th£|,t supernumerary members may be formed in consequence of accidental figsion of the budding limbs of the embryo, thepe ap§ oases in vyhich fingers are found on the stumps of arms in such circumstances as justify the belief that, after a limb had been accidentally amputated in the uterus, these had been produced on its remaining portion.' All these facts agree well with the belief that the formative power is gradually diminished in the acts of organising matter for the main- tenance of the body ; ^nd the difference between the completeoess of repair in children and that in adulta appears so much greater than the difference in adults of digbrent ages, that it is probable the formative power ia more diniini^hed by growth than by mere maintenance. But, secondly, it seems that the capacity for the repair or repro- duction of injured parts is mnch more diminished by development, than by growth ar maintenance of the body j i.e. nauch more by those trans- ' Sir J. Y, Simpson, in the London and Edinburgh MontUy Journal, Jan. 1848. White, Begeneration of Animal and Vegetable Substances, 1789. Dr. Struthers, Edinburglfi New PltUosopliical Journal, July 1&63, Mi\ Annandale On Malformations ^c, of Fingers and Toes, p, 20, I860. An excellent summary of this subject is given by Mr. Darwin in the Variation of Animals and Plants under Domestication, chap. xii. 1868. 120 GENERAL CONSIDERATIONS ON THE REPAIR AND formations of parts by which they become fitted for higher offices, than by the multiplication or maintenance of those that are already perfect in their kind and function. In other words, to improve a part requires more, and more perfect, formative power, than to increase it does. This, as a general principle, is exemplified in many instances. In the greater part of congenital malformations we find arrest of develop- ment, but no hindrance of growth ; as a heart, in which a septum fails to be developed, yet grows to its full bulk. If tadpoles be excluded from due light and heat, their development will be much retarded, but their growth will be less checked : in other words, the conditions of nutrition which are enough for growth are not sufficient for develop- ment. When a part is, without disease, unduly supplied with blood, it may grow beyond its normal size, but it is never developed beyond its normal structure : that which is sufficient for increase of growth is not enough for an advance in development. Again, in the miscalled cultivation and improvement of flowers, growth is increased, but de- velopment is hindered ; and an excess of coloured leaves is formed, in- stead of the due number of male and female organs. In an old ulcer or a sinus, cells may be continually reproduced, maintaining or even in- creasing the granulations, yet they will not develop themselves into connective tissue and cuticle for the healing of the part. And so, lastly, even when repair and reproduction have gone far towards their ultimate achievement, that which takes a longer time, and oftener fails, is the improvement, the perfecting of the new material, by its final development. This is observed in all cases of reproduced limbs, and even in ordinary scars. These facts, and many others like them, seem to justify the ex- pression that, not only more favourable conditions, but also a larger amount of organising force, are expended in development than in growth or maintenance ; and that the reparative power bears an inverse ratio to the amount of force already expended in these processes. If it be so, we might expect that in each species, in its perfect state, the repara- tive power might be measured by the degree of likeness between the embryonic and the perfect form, structure, and composition. There are many apparent exceptions to such a rule, especially in the Asteridae, which, though constructed through manifold metamor- phoses, have great capacity of restoring detached rays ; • yet it is con- ' A good account, by Dr. H. S. Wilaon, of the mode of reproduction of lost rays in the Asteridae may be found in the Trans. Linncean Soc. 1860. REPEODUCTION 03? INJUEED AND LOST PARTS. 121 sistent with such a rule that the highest amount of reparative power exists in those lowest polypes in which the materials of the germ-mass are least transformed, but are multiplied, and, as it were, grouped into the shape of their bodies. In the Hydra viridis, and Hydra fusca, it seems literally true that any minute portion derived from the germ- mass may, after being separated from the perfect body, reproduce the perfect form. This is the general truth of the numerous experiments performed on HydriB by Trembly; Boesel, and others. They have been so often quoted, that I need not do more than mention the greatest instances of reproductive power that they showed. Trembly cut a Hydra into four pieces : each became a perfect Hydra ; and, while they were growing, he cut each of these four into two or three. These fractions of the quarters being on their way to become perfect, he again divided these, and thus he went on, till from the one Hydra he obtained fifty. All these became perfect ; he ijept many of them for more than two years, and they multiplied by their natural gemmation just as much as others that had never been divided. Again, he cut similar polypes longitudinally, and in an hour or less each half had rolled itself, and seamed up its cut edges, so as to be a perfect Hydra. He split them into four ; he quartered them ; he cut them into as many pieces as he could : and nearly every piece became a perfect Hydra. He slit one into seven pieces, leaving them all con- nected by the tail, and the Hydra became seven-headed, and he saw all the heads eating at the same time. He cut off the seven heads, and, Hydra-like, they sprang forth again. And even the fabulist dared not invent such a prodigy as the naturalist now saw. The heads of the LerriEean Hydra perished after excision : the heads of this Hydra grew for the^lselves bodies, and multiplied with as much vigour as their parent-trunk. Now these instances may suffice to show not only the great capacity of reproduction in the lowest polypes, but, also, that in them the pro- cess of reproduction after injury confounds itself with that of their natural generation by gemmation, or, as it prohably more rarely hap- pens, by spontaneous fission. We cannot discern a distinction between them ; and there are facts which seem to prove the identity of the power which operates in both. Thus, in both alike, the formative power is limited according to the specific characters of the Hydra : immense as the power-of increase is which may be brought into action by the mutila- tions of the Hydra, yet that power cannot be made to produce a Hydra of much more than ordinary size, or to raise one above its ordinary 122 GENERAL CONSIDERATIONS ON THE REPAIR AND specific cliaracters. And, again, the identity of the power is shown in this, that the natural act of gemmation retards that of reproduction after injury. Trembly particularly observes, that when a Hydra, from which the head and tentacula had been cut off, gemmated, the re- productioi}. of thp tentaculq, -vfas retar4e4 soon after the gemmule appeared, Many other species manifest this coincidence of the power of pro- pagating by gemmation, or fission, and of reproducing large portions of the body, and even of reconstructing, from fragments, the whole body. Among them, as chipf e:^mp}es, are thp Actinias, which after bisection form two individuals ; and the Holothurise, which, as Sir J. G. Dalyell ' has observed, when hurt or handled, will eject all their viscera, leaving their body a mere empty sac, and yet in three or four months will have all their viscera regenerated. And to thesp may be added, from among the Annelida, the young Ifereids, and those species of Nais, on which Bonnet, SpaUan^ani, and others, made their esperiments ; experiments of which the climax seemed to be achieved when a JTais was cut by M. Lyonnet into thirty or forty separate pieces, and there were produced from those fragments as many perfect individuals. Among the instances of greatest capacity of repair, some obperved by Sip J. G, Dalyell seem to illustrate, in a remarkable jnanner, the general laws of the reparative processes in even the higher animgils. In Actinia laper^ta, Dalyell observed that numerous ragged processes were put forth f^om the whole circumfepenpe of j;he disc, which were gradu- ally torn off, and became afterwards developed into minute Actinise. Observations of a similar nature have been made by Tjr. gtrethill Wright' with regard to Actinia dianthus. Thp latter author, gifter noting the process of natural fissure in Ap^iini^ dianthus, prodniced similq,r phenomena, by ^rjji^ciaj figsi:jre. Froffl. the fopt of a specip?.en. of this Actinia, which showed no tendency to natural genpfat}.pn, ]\e detached a very minute portion, which by careful examination he satis- fied himself contained no ovum or structure different from the ordinary tissue of the wall of the body. This minute portion in three weeks became a perfect Actinia. From this product of artificial fissure, again, he divided other portions, which also in time developed into perfect animals ; all that appeared to be necessary to this process of multipli- ■ Bare and Bemarkable Animals of Scotland, i. pi. 14 ; ii. p. 230, pi. 47, « Proc. Roy. Phys. Soc. Ed., i. 161. EEPEODUCTION OF INJURED AND LOST PARTS. 123 cation being the existence in the severed part of the three elemental tissues of the body — the dermal, muscular, and mucous. In the Hydra tuba, the species in which Dalyell traced that mar- vellous development into MedusEe, he found that, when cut in halves, each half may regain the perfect forni ; but thia perfect form is regained only very slowly, and, as it were, by a gradual improven^ent of parts that are at first ill formed. The sketch (Fig. 14), copied ixom hig Kg. H- plate, shows the succession of forms marking these stages of improve- ment in the distal part of. a Hydra tuba (4), which had been detached by cutting through the animal with a pair of scissors. Through these forms, commencing at B, into which the distal or free half of A was first changed, the perfect state of a Hydra was at length reached, as at c. The obliteration of the old tentacles, together with the changes which take place in the new, before they assume their fnUy developed form, may possibly be explained (as he suggest?) by the mutilation having disturbed the progress of the Hydra in its de, velopment of young Medusse ; for the experiment -jvas made in March, nearly at the tinje when the series of changes should have commepced, But, if I may venture not to accept the suggestion of so admirable an observer, I should suspect rather that this is an instance of gradual recovery of perfection, such as we see more generally in the repair of injuries and diseases in the higher animals, He has noticed something of the same \iud, g.nd n).ore definite, iij. the Tubularia indivisa (PI. iv.) ; one of his e;?perimpnts on which is illustrated by Fig. 15. A fine specimen was cut ne^r its root, and .after the natural faU of its head, the summit of its stem w^s clovei?.. 4-iJ imperfect head was first produced, at right angles to the stem, frop!. one portion of the cleft (a) ; after its fall, another and more nearly per,, feet one was regenerated, and, as it grew, improved yet more (b). A 124 GENERAL CONSIDERATIONS ON THE REPAIR AND tliird appeared, and then a fourtli, whicli was yet more nearly perfect, thongh the stem was thick and the tentacula imperfect. The cleft was almost healed ; and now a fifth head was formed, qnite perfect (c) ; and after it, as perfectly, a sixth and a seventh head. All these were pro- duced in fifteen months. The lower half of this specimen had been cnt ofi" four months after the separation of the stem. Its npper end bore — first, an abortive head ; then, secondly, one which advanced fnrther in development ; a third, more perfect ; and then, in succession, other four, which were all well formed. The upper portion of this lower half of the stem now showing signs of decay, a portion was cut from its lowest part, and further manifested the reproductive power of the stem ; for three heads were produced from the upper end of the piece cut off, and four from the lower end of the upper piece which had seemed to be decaying. In 550 days this speci- men had grown twenty-two heads. Now, I cannot but think that we have, in these instances of gradual recovery from the effects of injury, a type of that gradual return to the perfect form and composition which is noticed in the higher animals. Our theory of the process of nutrition leads us to believe that, in the constant mutation of particles in nutrition, those elements or those molecules of the blood, or of any structure, that have been altered by disease, in due time degenerate or die, and are cast off or absorbed ; and that those which next succeed to them partake, through the assimi- lative force, of the same morbid character ; but that, after every re- newal, the new particles approach a step nearer to the perfect state. Thus, as it were, each generation of new particles is more nearly per- fect, tUl all the effects of the injury or the disease are quite obliterated. Surely, in the gradual recovery of perfection by these polypes, we have an apt illustration of the theory ; one which almost proves its justice. The power of reconstructing a whole and perfect body by the devel- REPRODUCTION 0¥ INJURED AND LOST PARTS. 121 opraent of a fragment is probably limited to the species that can propa- gate by spontaneous fission or gemmation, or that increase their size, as some of the Annelida do, by the successive addition of rings that are developed after the manner of gemmules from those that precede them. Where this power is not possessed, there, whatever be the position of the species in the animal scale, the l*epa,rative power appears to be limited to the reproduction of lost members, such as legs, claws, a part of the body, the head, an eye, the tail, and the like. Within this limit, the rule seems again to hold good, that the amount of reparative power is in an inverse ratio to that of the development, or change of structure and mode of life, through which the animal has passed in its attain- ment of perfection, or on its way thitherward. Here, however, even more than in the former cases, we need, not perhaps more experiments, but experiments on a larger number of species. It appears generally true, that the species whose development to the perfect state is comparatively simple and direct have great repa- rative powers ; while many, at least of those in which the development is with such great changes of shape, structure, and mode of life, as may be called metamorphosis, retain in their perfect state scarcely any power for the repair of losses. Yet we want more instances of this ; and especially, it were to be wished that we had the results of experi- ments upon the lowest animals that pass through such metamorphoses ; e.g. on the Hydra tuba, not only in its Hydra state, but in all the changes that succeed, till it attains its complete Medusal form. In the absence of such evidence as experiments of tliis kind might furnish, the best examples of the rule are furnished by the experiments of Mr. Newport. They show that among the insects the reparative power, in the complete state, is limited to the orders in which that state is attained by a comparatively simple and direct course of devel- opment ; as the Myriapoda and Phasmidse, and some of the Orthoptera. These can reproduce their antennse, and their legs, after removal or mutilation ; but their power of reproduction diminishes as their devel- opment increases. Even in the Myriapoda, whose highest development scarcely carries their external form beyond that of the larvas of the more perfect insects, such reparative power apparently ceases, when, after the last casting of their integuments, their development is completed. In the higher hexapod insects, such reproduction has been seen in only the larval state ; none of them, in its perfect state, can reproduce an antenna, or any other member. The Myriapoda then, are, in their 126 GENEEAL CONSIDERATIONS ON THE REPAIR AND reparative power, equal to the larvae of the higher insects, and nearly all the power for formation which these manifest appears to be exhausted in the two later metamorphoses. The case is the stronger, as illustrating the expenditure of power in metamorphoses, when the higher insects are compared with the Arachnida ; for in these, which attain their perfect state through more direct development, the reparative power remains equal to the reproduction of limbs and antennee. A yet stronger contrast is presented between the higher insects and the several species of sala- mander, in which so profuse a reproduction of the hmbs has been observed ; for though they be much higher in the scale of animal life, yet the amount of change in external form and habits of life, through which they pass, in their development from the embryo to the perfect state, appears less than that accompUshed in the metamorphoses of insects. Many instances, besides those which I have cited, appear to support this rule, that the reparative power, in eacli perfect species, whether it be higher or lower in the scale, is in an inverse proportion to the amount of change through which it has passed in its development from the embryonic to the perfect state.' And the deduction we may make from them is, that the powers for development from the embryo are identical with those exercised for the restoration from injuries : in other words, that the powers are the same by which perfection is first achieved, and by which, when lost, it is recovered. This is, again, generally confirmed in the instances of the Verte- brata ; but of the repair in these, or at least in the highest of them, I shall have to speak so exclusively in the future lectures, that I will now only say that, in man and other mammalia, a true reproduction after loss or injury seems almost entirely Hmited to three classes of parts : — ' Observatione on the mode of reproduction of lost parts in the Crustacea, by H. D. S. Goodsir, may be found in the Anat. and Path. Observations, Edinburgh, 1845 • and in Dr. W. C. M'Intosh's Observations on the Carcinus Manas, 1861. The latter naturalist has also observed the process of reproduction of lost parts in Borlasia oetoculata, one of the Nemerteans {Proc. Linn. Soc. 1868). Bonnet related in his (Euvrcs d'Histoire Naturelle et de P/iiiosophie, 1781, various experiments on the reproduction of parts in adult Newts ; and Dr. Giinther has pointed out (Owen's Anat. of Vertebrates, i. 567, 1866) that the power of reproducing lost parts in the tail-less" Batrachia is limited to their larval condition. In his Address in Physiology, Lancet August 8, 1868, Professor KoUeston argues that the power of reproducing a lost limb or of recovering from injury, has no relation to the metamorphoses which the animal imdergoes, or is capable of undergoing, but is in inverse proportion to the activity of the ref.piratory process. EEPEODUCTION OF INJUKED AND LOST PAETS. 127 1. To those whicli are formed entirely by untritive repetition, such as the blood and the epithelia. 2. To those which are of lowest-organisation, and (which seems of more importance) of lowest chemical character ; as the gelatinous and the connective tissues, and the bones. 3. To those which are inserted in other tissues, not as essential to their structure, but as accessories, as connecting or incorporating them with the other structures of vegetative or animal life ; such as nerve- fibres and bloodvessels. With these exceptions, injuries or losses in the human body are capable of no more than repair, in. its most limited sense ; i.e. in the place of what is lost, some lowly organised tissue is formed, which fills up the breach, and sufBces for the maintenance of a less perfect life. I may seem in this, as in some earlier lectures, to have been discuss- ing doctrines that can hardly be applicable to our daily practice, and with illustrations drawn from objects in which surgeons may have but little interest. Let me, then, if only in apology, refer to some of the considerations which are suggested by studies such as these. Let me, first, express my belief that, if we are ever to escape from the obscurities and uncertainties of our art, it must be through the study of those highest laws of our science, which are expressed in the simplest terms in the lives of the lowest orders of creation. It was in the search after the mysteries — that is, after the unknown highest laws — of generation, that the first glance was gained of the largest truth in physiology ; the truth of the development of ova through subdivision and multiplication of the embryo- cells. So may the study of the repair of injuries sus- tained by the lowest polypes lead us to the clearer knowledge of that law, in reliance upon which alone we dare to practise our profession ; the law, that lost perfection may be recovered by the operation of the powers by which it was once achieved. Already, in the facts that I have quoted from Sir J. Graham Dalyell, we seem to have the foresha- dowing of those through which the discovery maj' be made. Then, let us not overlook those admirable provisions, which we may find in the lives of all that breathe, against injuries that, but for these provisions, would too often bring them to their end before their appointed time, or leave them mutilated to finish a painful and imper- fect life. We are not likely to undervalue, or to lose sight of, the design of all such provisions for our own welfare. But we may better 128 GENERAL CONSIDERATIONS ON THE REPAIR AND appreciate these, if we regard ttem as only of tlie same kind as those more abnndantly snpplied to creatures whom we are apt to think insig- nificant : indeed, so abundantly, that, as if with a consciousness of the facility of repair, self-mutilation is conunonly resorted to for the preservation of life. When the Ophiuradse, or any of the brittle star- fishes, break themselves to fragments, and disappoint the grasp of the ausious naturalist, they probably only repeat what they are instinctively taught to do, that they may elude the jaws of their more ravenous enemies. But death would be much better than such mutilation, if their rays could not Ijje reproduced almost as easily as they can be rejected. The experimentalist, too, who cuts off one or the other end of any of the Annelida, perhaps only puts them to a necessity to which they are liable from the attacks of their carnivorous neighbours. Almost defenceless, and so easily mutilated, their condition, were it not for their faculty of reproduction, might be more deplorable than that of any other creature ; and even their existence as species might have been endangered long ago. It would almost seem as if the species that have least means of escape or defence from mutilation were those on which the most ample power of repair has been bestowed ; an admirable instance, if it be only generally true, of the beneficence that has provided for the welfare of even the least (as we call them) of the living world, with as much care as if they were the sole objects of the Divine regard. Lastly, if I may venture on so high a theme, let me suggest that the instances of recovery from disease and injury seem to be only ex- amples of a law yet larger than that within the terms of which they may be comprised ; a law wider than the grasp of science ; the law that expresses our Creator's will for the recovery of all lost perfection. To this train of thought we are guided by the remembrance that the heal- ing of the body was ever chosen as the fittest emblem of His work, whose true mission was to raise man's fallen spirit and repair the inju- ries it had sustained ; and that once, the healing power was exerted in a manner purposely so confined, as to advance, like that which we can trace, by progressive stages to the complete cure. Tor there was one, upon whom when the light of Heaven first fell, so imperfect was his vision that he saw confusedly, ' men, as trees walking ; ' and then, by a second touch of the Divine hand, was ' restored and saw every man clearly.' Thus guided by the brighter light of revelation, it may be our privilege, while we study the science of our healing art, to gain, by the illustrations of analogy, a clearer insight into tlie Oneness of the plan by which things spiritual and corporeal are directed. Even EEPEODUCTION OF INJURED AND LOST PARTS. 129 now, we may trace some analogy between the acts of the body and those of man's intellectual and moral nature, as in the development of the germ, so in the history of the human spirit, we may discern a striving after perfection ; after a perfection, not viewed in any present model (for the human model was marred almost as soon as it was formed), but manifested to the enlightened Reason in the ' Express Image ' of the ' Father of Spirits.' And so, whenever, through human frailty, amid the violences of the world, and the remaining ' infection of our nature,' the Spirit loses aught of the perfection to which it was once admitted, still its implanted Power is ever ufgent to repair the loss. The same power, derived and still renewed from the same Parent, working by the same appointed means, and to the same end, restores the fallen spirit to nearly the same perfection that it had before. Then, not unscarred, yet living — ' fractus sed invictus ' — the Spirit still feels its capacity for a higher life, and presses to its immortal destiny. In that destiny the analogy ends. We may watch the body developing into all its marvellous perfection and exact fitness for the purpose of its existence in the world ; but, this purpose accomplished, it passes its meridian, and then we trace it through the gradual decays of life and death. But for the human Spirit that has passed the ordeal of this world, there is no such end. Emerging from its imprisonment in the body, it soars to the element of its higher life : there, in perpetual youth, its powers expand, as the vision of the Infinite unfolds before it ; there, in the very presence of its Model, its Parent, and the Spring of all its Power, it is ' like Him, for it sees Him as He is.' 130 EEPARATIVE MATERIALS LECTURE VIII. THE MATEEIALS FOE THE HEPAIE OF INJDEIES. In the present lecture I propose to give a general account of the mate- rials employed for the repair of some of the injuries inflicted on the human body. I hope I do not err in thinkiag that the most advantageous mode of treating this subject will be to confine myself to that class of injuries which may be called visible breaches of continuity ; such as wounds and fractures. For, in regard to the recovery from diseases, our know- ledge of the effects of any disease seems, as yet, too imperfect for ns to trace the stages by which the morbid state reverts to that which is healthy. "We may be sure it is in conformity with the same general laws as those of recovery from injury, and almost sure that it is by the gradual improvement of the particles that in succession replace those altered by disease. But the whole details of the process have yet to be discovered. Even within the narrower field of the repair of breaches of contin- uity, I must yet assign to myself a closer limit. A future lecture wiU be devoted to the healing of fractures ; in this, therefore, I shaU speak almost exclusively of the healing of divided soft parts ; and I shall take, as the chief and typical examples, the repairs of wounds made in opera- tions. References to the healing of other injuries may, however, be made by the way, and for collateral illustration.' Modern surgery has shown how right Mr. Hunter was, when, in the very beginning of his discussion concerning the healing of injuries, he points out as a fundamental principle the difference between those two forms of injuries of which one is subcutaneous, the other open to the ' The pathology and repair of wounds otlier than those here considered, and the managernent of wciinds of all kinds, are treated of by the author in the article ' Wounds ' in Holmes's System of Surgery, vol. i. EEPARATIVE MATERIALS. 131 air. He says : ' The injuries done to sound parts I stall divide into two sorts, according to the effects of the accident. The first kind con- sists of those in which the injured parts do not communicate externally, as concussions of the whole body, or of particular parts, strains, bruises, and simple fractures-, which form a large division. The second consists of those which have an external communication, comprehending wounds of all kinds and compound fractures.' ' And then, he says, ' The in- juries of the first division, in which the parts do not communicate ex- ternally, seldom inflame ; while those of the second commonly both inflame and suppurate.' In these sentences Mr. Hunter has embodied the principle on v^hich is founded the whole practice of subcutaneous surgery ; a principle of which, indeed, it seems hardly possible to exaggerate the importance. For, of the two injuries inflicted in a wound — the mechanical disturbance of the parts, and the exposure to the air of those that were covered — the exposure, if continued, is the worse. Both are apt to excite inflam- naation : but the exposure excites it more certaLuly, and in the worse form — i.e. in the form which most delays the process of repair, and which is most apt to endanger life. Abundant instances of this are shown in the difference between a simple and a compound fracture, though the former may have been produced by the greater violence ; or, between a simple fracture, even with much violence, extending into a joint, and an open wound, never so gently made into one. Or, for parallel instances, one may cite the rarity of suppurations after even extensive ecchymoses, and their general occurrence when wounds are left open. I had frequent occasion to observe these differences, in a series of experiments made for the illustration of the healing of divided muscles and tendons. Some of these were divided through open wounds, and some by subcutaneous section ; and the recital of a single experiment may afford a fair example of the difference of results that often ensued. In the same rabbit, the tibialis anticus and extensor longus digitorum were divided on the right side with a section through the skin ; on the left, with a subcutaneous section, through a small opening. Twelve days ?ifterwards the rabbit was killed. The wound on the left side was well repaired, and with comparatively little trace of inflammation : the gap on the right was closed in with a scab, and an imperfect scar, but under these was a large collection of pus, and no trace of a reparative ' Works, iii. p. 210. 1 32 EEPAEATIVE MATERIALS : process. The contrast is the stronger, because in all these cases there is, unavoidably, more mechanical violence inflicted in the gradual subcutaneous division than in the simple open wound. And, it must be added, that a speedy closure of the external wound made in an open section may bring the case into more favourable conditions than those of a subcutaneous wound made with more \-iolence. This, also, I saw in some of the experiments : a clumsy subcutaneous division of one Achilles-tendon excited great inflammation about it ; while the open section of the other tendon in the same rabbit was quickly and well re- paired, if the external wound had been speedily united, and had suffici- ently soon converted the open into a subcutaneous injury. Still, what Mr. Hunter said is true, especially in wounds in our own bodies : subcutaneous wounds seldom inflame ; open wounds generally both inflame and suppurate. It will be a principal object of this lec- ture to show something like an anatomical reason for this difierence, in the fact that the materials produced for the repair of open wounds do not develope themselves quite in the same manner as those for the repair of closed or subcutaneous ones. The physiological and nearer reason is to be discovered in the influence of the atmosphere abnormally ad- mitted to the tissues, and producing in them such effects as are more nearly traced in the phenomena of inflammation. For, as has been ar- gued by Mr. Lister,' the organic germs which Pasteur and others have shown to exist floating in the air, excite, when in contact with the surface of a wound, decomposition of the blood, and occasion suppura- tion. Before speaking of the materials for repair, I must briefly state that the healing of open Wounds may be accomplished by five different m^odes : namelyj 1. By immediate union ; 2. By primary adhesion ; 8. By granulation ; 4. By secondary adhesion, or the union of granulations; 5. By healing under a scab.^ The repair of subcutaneous wounds may be effected by immediate union, but is generally accomphshed by con- nection, or the formation of bonds of union between the divided and retracted parts. Very rarely it is effected by means of granulations without suppuration. Of these modes, which I hope to describe hereafter in detail, it is the peculiarity of the first, or process of immediate union, that it is ac- ' Lancet, March 16, 1867. ^ These five modes of healing are otherwise called — 1. By the first intention (Hunter) ; 2. By the adhesive inflammation (Hunter) ; 3. By the second intention ; i. By the third intention; 5. Subcrustaceous dcatrisation. MODES OF UNION. 133 complislied by the mere re-union or re-joining of the divided parts, without the prodnction or interposition of any new material. In all the others, new material is produced and organised. This process of im- mediate union corresponds with what Mr. Hunter called ' union by the first intention.' It is not the same as that which, in modern surgery, is called union by the first intention ; for that is the same as Mr. Hun- ter named ' union by adhesion' or ' by the adhesive inflammation,' which, as he describes it, is effeced by the organisation of lymph interposed be- tween two closely approximated wounded surfaces. Mr. Hunter main- tained that union by the first intention is effected by means of the fibrine of the blood extravasated between the surfaces of the injured part, which fibrine, there coagulating, adheres to both the surfaces, becomes organ- ised, and forms a vascular bond of union between them.' Doubtless, Mr. Hunter was, in this, in error ; but, as the blood extravasated in wounds is not without influence on their repair, I will endeavour to state the several modes in which it may, when thus extravasated, be finally disposed of. There are ample evidences for believing that masses of effused, or stagnant and coagulated, blood maybe organised : i.e., may assume the characters of a tissue, and may coalesce with the adjacent parts and be- come vascular. These evidences include cases of blood efi'used in serous sacs, especially in the arachnoid as Mr. Prescott Hewett^ has fully de- scribed ; of clots in veins organising into fibrous cords, or, after less organisation, degenerating into phlebolithes ; clots organising into tumours in the heart and arteries, and the clots so organised above liga- tures on arteries as to form part of the fibrous cord by which the obliterated artery is replaced. These last oases afibrd most conclusive evidence, because they have been very carefully investigated in a series of experiments and microscopic observations by Dr. Zwicky^and Prof. 0. Weber.'' In 1848 I had the opportunity of examining a specimen which, more fully than any other I had seen, confirmed Zwicky's account of the mode in which blood-clots become organised. It supplied, too, some facts which appear important to the present subject. It was obtained from an insane person, by my friend Mr, Holmes Coote. A thin layer of pale blood-coloured and ruddy membrane lined the whole ' Works, iii. 253. 2 Med.-Chir. Trans, xxviii. Holmes's System of Surgery, ii. p. 109. ' Die Metamorphose des Throm/ms, Zurich, 1845. ■* Billroth und von Pitba's Handtmch der Chiruryie, i. p. 141, 1865. 134 EEPAEATIVE MATERIALS; internal snrface of tlie cerebral dura mater, and adhered closely to it. Its colour, the existence of patolies of blood-clot imbedded in it, and all its other characters, satisfactorily proved that it had been a thin clot of blood, — an example of such as are eflFused in apoplexy of the cerebral membranes. Numerous small vessels could be seen passing from the dura mater into this clot-membrane ; and with the microscope, while they were still fuU of blood, I made the sketch engraved (Kg 16, a). The arrangement of the bloodvessels bears a close resemblance, but, perhaps, more ia its irregularity than in any positive characters or plan, to that which exists in false membrane formed in inflammation of a serous membrane ; but the vessels were, I think, generally larger. Fig. 16. Such were the bloodvessels of this organised clot. Its minute struc- ture, as represented above (b), showed characters which are of peculiar interest, because of their resemblance to those observed in the material that is commonly formed in the repair of subcutaneous injuries. In the substance of what else appeared like a filamentous clot of fibrine, sprinkled over with minute molecules, the addition of acetic acid brought into view corpuscles, very elongated, attenuated, and, in some instance.", like short strips of flat fibre. Of course, such corpuscles are not to be found in any ordinary clot of fibrine ; they exactly resemble such as may be found in certain examples of rudimental connective tissue, and, among these, in the material for the repair of subcutaneous injuries. In short, the minute structure of this clofc now organised was an ex- ample of what I shall have often to refer to under the name of ' nucle- BLOOD. 135 ated blastema' or 'protoplasm.' With regard to the mode of origin of these corpuscles, it would seem, as Otto Weber has suggested,' that in the coagulation of the blood, white corpuscles are entangled in the clot. These gradually elongate, and form such corpuscles as are repre- sented in the figure, and in time, perhaps, may become the corpuscles of the connective tissue which ultimately occupies the place of the coagulnm,^ With such evidence as this of the organisation of a thin layer of blood-clot, I was surprised to find that extravasated blood can, com- monly, have no share at all in the reparative process. One of the best proofs of this is, that scarcely the smallest portion of blood is eflFused in the cases in which the largest quantity of repar- ative material is produced in the shortest time, and in which the heal- ing process is most perfectly accomphshed. In twenty cases in which I divided the Achilles-tendon in rabbits, I only once found, in the sub- sequent examinations, a clot of extravasated blood in the track of the wound. In this case, I believe, the posterior tibial artery was wounded ; for in all others, and in similar divisions of muscles, unless a large ar- terial trunk were cut, the only effusion of blood was in little blotches, not in separate clots, but infased or infiltrated in the areolar tissue near the wound. In some cases there was blood-stained infiltration of the inflammatory products, but in none were there such clots as could be organised iuto bonds of union. In short, parts thus divided scarcely bleed : what blood does flow escapes easily through the outer wound, as the surrounding tissues collapse into the space left by the retracting parts ; or, what remains is infiltrated into the tissues, and forms no separate clot. It is the same with fractures. In a large proportion of these, one finds no clots lying between the fragments where they are to be united, and only very small spottings of blood, like ecchymoses, in or beneath the periosteum. The abundant extravasations that commonly exist in the subcutaneous tissue are generally confined to it ; they are not con- tinued down to the periosteum or bone. In all these cases, then, we have sufiicient proof that extravasated ' Op. cit. p. 147. ^ The deseription here given has been fully confirmed hy the examination of a similar membranous clot, the vessels of which were beautifully injected by Mr. Gray {Pathol. Trans.) ; and more recently by that of one injected by Mr. Ooote. Dr. W. T. Gairdner, in Edin. Med. Jour. Oct. 1861, also describes a specimen of false membrane from the arachnoid cavity, iu which bloodvessels containing blood-corpuscles were seen ; and Di. J. Ogle, in Beale's Archives, vol. i. and part 6, records similar 136 EEPAEATIVB MATERIALS: blood is not necessary for union by the first intention, or for any other mode of repair, in the simple fact that where the repair is best, and the material for it most ample, no blood is so extrayasated as to form a clot that could be organised. But, though this may be the usual case, the question stUl remains— When blood is effused and coagulated between wounded surfaces, how are the clots disposed of ? For often, though not generally, such clots are found in wounds, or between the ends of a broken bone, or a divided tendon when an artery by its side is cut ; and in most operation- wounds, one sees blood left on them, or flowing on their surfaces, after they are done up. How, then, is this blood disposed of? If effused in large quantity, so as to form, a voluminous clot, and especially if so effused in a wound which is not perfectly excluded from the air, or if effused in even a subcutaneous injury in a person whoso health is not good, the blood is most likely to excite inflammation ; and the swelling of the wounded parts, or their commencing suppuration, will push it out of the wound. Thus we often see blood ejected. But, in more favourable circumstances, the blood may be absorbed; and this may happen whether it have formed separate clots, or, more readily, when it is infiltrated in the tissues. What I have seen, how- ever, in the experiments to which I have already referred, leads me to dissent from the account commonly given of the absorption of blood thus effused. The expressions generally used imply that the first thing towards the repair of such a wound is the absorption of the ex- travasated blood ; and that then, in its place, the reparative material is produced. But this can hardly be the case ; for the absorption of blood is a very slow process, and commonly requires as much time as would suffice for the complete healing of a wound, or even of a fracture. Not to mention the very slow absorption of the extravasations of blood in apoplexy or in serous sacs, I have found the blood effused in the subcutaneous tissue and the muscles, after a simple fracture, scarcely changed at the end of five weeks ; that ia a tied artery was as little changed after seven weeks ; and even in common leech-bites we may sometimes find the blood- corpuscles, in little ecchymoses, unchanged a month after their extravasation ; yet in much less time than this it is commonly implied that all the blood extravasated in an injury is cleared quite away, that lymph may occupy its place. My impression is, that this opinion is founded on imperfect observations. Blood is supposed to be effused in all subcutaneous injuries ; and where it is not found, it is supposed to have been absorbed ; the truth rather being, BLOOD, 1 37 that, where no blood appears, none ever was, and that a blood-stained fluid, consisting apparently of serum, with suspended blood- cells and dissolved colouring matter, has been mistaken for blood itself.' The true method of the absorption of blood left in a wound seems to be that it is enclosed within the reparative material, and absorbed by the vessels of that material as its organisation proceeds. The best instance that I have seen in support of this statement was in the case of a rabbit's Achilles- tendon, divided subontaneonsly six days before death. The reparative process had proceeded favourably, and as strong a band of union as is usual at that period was formed of the new reparative material deposited between the retracted ends. On slitting open this band, I found within it a clot of blood, such as must have come from a large vessel : and this clot was completely enclosed within the new material ; not closely adherent to it, or changed as if towards organisa- tion; but rather decolorised, mottled, and so altered as clots are in apoplexy before absorption. I believe that this case only showed in a very marked manner what usually happens with blood thus effused and not ejected . for it is quite common, after the division of tendons, to find new reparative material, if not containing distinct clots, yet blotched with the blood that was infiltrated in the tissue in which the reparative material is deposited : and even when the repair of a fracture was nearly perfect, I have still found traces of red blood-corpuscles enclosed in the reparative material, and degenerating, as if in preparation for absorption. Ejection and absorption are, doubtless, the usual means by which blood effused in injuries is disposed of; yet I feel nearly sure it may in some instances become organised, and form part of the reparative material. The cases of manifest organisation of blood already referred to leave no doubt of the possibility of this happening : its occurrence can no longer be set aside as a thing quite improbable. The only question is, whether blood effused in injuries has been seen organised. Now, I think no one familiar with Hunter's works will lightly esteem any statement of his as to a matter of observation. He may have been sometimes deceived in thinking that he saw blood becoming organised in subcutaneous injuries (for subcutaneous granulations are sometimes very like partially decolorised clots) ; yet I believe he was often right, for sometimes one finds clots of blood about the fractured ends of bones which have every appearance of being in process of organisation. They ' On this subject the article ' Contusions,' by the author, in Holmes's System of Surgery, vol. i., may be consulted. 138 REPAEATIVE MATERIALS: do not look mottled, or rusty, or brownish, as extravasated blood does when it is degenerating, preparatory to its absorption ; but tbey are uniformly decolorised to a pinkish-yellow hue. They have more appearance of filamentous structure than recent clots have ; and they are not grumous or friable, like old and degenerating ones, but have a peculiar toughness, compactness, and elasticity, like firm gelatine. When clots are found ia this condition I believe it is a sign that they were organising, for this is the condition into which, commonly, the clot in a tied artery passes in its way to be fully organised; and (which is very characteristic) you may find clots in the track of wounded parts thus changing, as if towards organisation, while those about them, and out of the way of the reparative process, are degenerating. On the whole, then, I believe we may thus generally conclude con- cerning the part that blood, when it is extravasated, takes ia the repair of injuries : — 1. It is neither necessary nor advantageous to any mode of heaUng. 2. A large clot, at all exposed to the air, irritat-es and is ejected. 3. In more favourable conditions the efiused blood becomes enclosed in the accumulating reparative material ; and while this is organising the blood is absorbed ; and Lastly, it is probable that the blood may be organised and form part of the reparative material ; but even in this case it probably retards the healing of the injury. I proceed now to the consideration of the new material which is produced for the repair of injuries that are not healed by the imme- diate union. From the surfaces of the wound or injured part a fluid oozes out, which coagulates, and has long been known as lymph or coagulable lymph, a term which i^also applied to the material formed in acute inflammations, with which indeed it was supposed to be identical. Until very recently it was considered that this coagulable lymph developed itself into the tissue by -which the repair was effected, and its natural tendency seemed to be to form the fibrous or the common fibro-cellular or connective tissue — the lowest form of vascular tissue — the structure which, in nearly all cases in man, constitutes the bond by which disunited parts are agaiu joined. But of late years the views of pathologists on this matter have un- dergone considerable modification, and the opinion has been gaining ground that the part played by the lymph in the repair of injuries is merely passive, that an organisation of the coagulated fibrine of the COAGULABLE LYMPH. 139 lymph, does not occur, and that the new-formed connective tissue is produced from and by the agency of the tissues of the part in which the wound or injury has occurred. The method of development, indeed, is probably not unlike that which has been observed in the formation of the same tissue during embryonic life. It may be well, therefore, that we should next inquire into the normal development of the fibrous or connective tissue in the embryo. This undoubtedly constitutes one of the most difficult questions in his- tology, and the opinions of anatomists have passed through various phases since Schwann published his description of the process. If the great omentum of a very young embryo be examined,' it may be seen to consist of oval, nucleated cells, which lie close together, and the boundaries of which are only feebly indicated. The nucleus, also, is not separated by a sharp contour from the surrounding protoplasm. At a somewhat later stage the cells elongate and attenuate themselves iuto spindles, and the tail-like processes branch, cross each other, and apparently become connected together. These spindle-cells are separa- ted from each other by a pellucid material, in which at first nothing is seen but a few short, curved, and irregularly arranged lines. In the course of time the characteristic wavy fibrillee of the white fibrous connective tissue form in this clear material between the cells, which gradually increase in quantity until they become the preponderating anatomical constituent of the texture. The fibrillie, therefore, are formed by a differentiation of the blastema or protoplasm, which lies between the spindle-shaped cells, and not, as was at one time supposed, by a fibrillation of the attenuated extremities of the cells themselves. In the tendon of a young embryo also, roundish cells lying close together are at first seen. These gradually become elongated in the direction of the long axis of the tendon, and, as this takes place, the peripheral part of the protoplasm, or germinal matter as Dr. Beale would term it, of each fusiform cell, gradually differentiates into fibrillss, without apparently the formation of any smooth, pellucid, inter- mediate substance such as has been seen in the embryonic great omentum. As the fibrillation of the protoplasm advances, the fusiform cells or corpuscles of the tendon become obscured, so that in this, and in the other denser varieties of fibrous tissue, they can only be recog- nised after the addition of acetic acid, which, by rendering the bundles ' The description by Dr. RoUett, in Strieker's Handbuch der Lehre von den Geweben, part i. p. 62, Leipzig, 1868, has been mainly followed in this account of the develop- ment of the embryonic connective tissue. 140 EEPAEATIVE MATERIALS : of filaments transparent, permits the corpuscular. elements to be seen. These corpuscles have long been known as the ' nuclei ' of the fibrous tissue, but of late years, more especially in connection with the obser- vations of Bonders and Virohow, they have been termed the connective tissue corpuscles. As the filamentous bundles of the conuective tissue are formed by a conversion of the protoplasm, it follows that the propor- tion which the latter bears to the former necessarily diminishes as the tissue reaches its adult condition, so that ultimately the corpuscles con- sist of the nuclei, with but a small quantity of investing protoplasm, and the bundles of wavy filaments constitute the great bulk, and the most easily recognised constituent of the tissue. With regard to the formation of the yellow fibrous or elastic tissue, though its development has not been traced so precisely as has been done with the white fibre, there seems reason to believe that it is also produced by a conversion of the protoplasm ; the chemical and struc- tural change which takes place in that substance being, however, of a character difiereut from that which occurs when the white fibre is in process of formation. In the process of repair the development of the connective tissue takes place in the granulations, and the same texture is formed in in- flammatory adhesions and indurations. The cells first formed in granulations are spherical, palely or darkly nebulous, from about l-1800th to l-2500th of an inch in diameter. They contain a few shining, dark-bordered granules, and lie imbedded in a variable quantity of clear pellucid substance, or protoplasm, by which they are held together, and which it is hard to see unless acetic acid be added. When water is added it penetrates the cells, and, as they swell up, their walls appear more distinct, and their contents are diffused. Some cells thus become much larger and clearer, and show in their interior numerous vibrating molecules : others display fewer molecules, but a distinct round, dark-bordered nucleus, which appears attached to the inside of the ceU-wall. Such a nucleus is rarely seen in granulation-cells, uuless they are distended with water : acetic acid, acting more quickly than water brings the nucleus more evidently and constantly into view, and often makes it appear divided into two or three portions. In the development of the fibro-cellular or connective tissue in granulations, the first apparent change is in the nucleus. It becomes more distinct ; then oval (even before the cell does), and at the same GHANULATIOK CELLS. 141 time clearer, brighter, like a vesicle teasely filled With pellucid sub- stance. One or two nucleoli now appear distinctly in it, and soon it attenuates itself ; but this it does later, or in a less deo;ree, than the Kg. 17. cell ; for a common appearance is that of elongated cells bellied out at the middle by the nucleus. While these changes are ensuing in the nucleus, each cell also is developing its structure ; first becoming minutely, yet more distinctly, granular, and dotted; then having its cell- wall thinned, or even losing it. It elongates at one or both ends, and thus are produced a variety of lanceolate, caudate, or spindle-shaped cells, which gradually elongate and attenuate themselves, and along with this the formation of the characteristic wavy bundles of connective tissue by a fibrillation of the protoplasm takes place. In some granulations, but, I think, only in such as are formed on bones, one may often find large compound cells, or masses, or laminae, of blastema, of oval fornij and as much as I-2S0th of an inch in diameter, containing eight, ten, or more nuclei. They are like certain natural constituents of the medulla of bone (as described by Kolliker ' and Robin ^), and like the bodies which are found constituting the chief part of fibro-plastic tumours. Sometimes, also, even in the deeper parts of gfanulations, cells are found expanded, flattened, scale-like, and nucleated, as if approximating to the formation of epidermal cells. The process of repair which takes place after subcutaneous wounds differs somewhat from that which has just been described in connection Eg. 17. — Development of granulation-cells; the elongated cells in the group belffw are eketched as less magnified than those aboTe. ' Mikrosk. Anatomie, Figs^-01.3 and 121. ' Bull, de la SocieU de Biologie, 1849, p. 150. 142 EEPAEATIVE MATERIALS. with the organisation of a granulating surface. For the material which lies between the divided surfaces does not consist of cells capable of being readily isolated and separated from each other, as is the case with granulation-cells. It i-ather exists in the form of a mass of nucleated blastema or protoplasm (Kg. 18), in which the cells are not, as it were, individualised. In this blastema fibrillation begins to take place, until ultimately the characteristic wavy bundles are produced. At the same time the nuclei become elongated, and, with attenuated, and perhaps branching, processes of the protoplasm immediately around them, form the corpuscles of the connective tissue. Just as the granulation- cells are derived by descent from the tissues, which form the surface of an open FiQ. 18. wound, so is this nucleated blastema in all probability chiefly produced by proliferation from the corpuscles of the surrounding texture ; though it may be that in the healing of subcutaneous wounds, as in the organisation of a blood-coagulum, the -n-hite corpuscles of the blood, which may have become extravasated at the time when the wound was inflicted, become fusiform and are converted into the corpuscles of the new formed connective tissue. HEALING BY IMMEDIATE UNION. 143 LECTURE IX. THE PKOCESSES OF EEPAIR OF WOTJNDS. I PEOCEED uow to the description of the several modes of healing of woiinda, and shall at present speak of only such wounds as are exter- nally open. Among the modes which I enumerated, the first was that which, as I stated in the preceding lecture, is effected by immediate union. It corresponds with what Mr. Hunter called union by the first intention; but, since that term has been applied more recently to another mode of healing, I have adopted the term ' immediate union ' from Dr. Macartney^ who, so far as I know, was the first to observe clearly that the healing of wounds may be eJEfected ' without any inter- vening substance, such as blood or lymph.' ' He says — ' The circum- stances under which immediate union is effected, are the cases of incised wounds that admit of being, with safety and propriety, closely and im- mediately bound up. The blood, if any be shed on the surface of the wound, is thus pressed out, and the divided bloodvessels and nerves are brought into perfect contact, and union may take place in a few hours ; and as no intermediate substance exists in a wound so healed, no mark or cicatrix is left behind. ' We have familiar examples of this mode of healing in slight outs received on the fingers, which, after being bound up, if no inflammation be induced, perfectly heal without the individual having any unpleasant sensation in the part after the m.oment of the infliction of the wound. A case has been lately communicated to me, of a considerable cut of the hand having been cured by this mode of direct union, without any sensation of pain, in the short space of four or five hours.' It is singular that Dr. Macartney should speak of the process of immediate union occurring in so few and very trivial instances as these ; for it seems certain that many even very large wounds are usually, in favourable circumstances, thus healed. The characteristics of this ' Treatise on Injlammation, p. 49. 144 HEALING BY IMMEDIATE UNION. mode are, that the divided parts, being placed in exact contact, simply conjoia or re-unite ; no blood or new material is placed between them for a connecting bond, and no sign or product of inflammation is pre- sent. All these characters meet in such cases as the favourable union of flaps of skin, which have been reflected from the subjacent parts, and are then replaced or transferred to some other adjacent wounded surface. The instances in which I have best observed it have been after wounds reflecting portions of the scalp, and after operations for the removal of the mammary gland. In these operations, as you know, the usual proceeding is to remove some of the skin, including the nip- ple, and to uncover the rest of the surface of the gland by reflecting from it an upper and lower flap of skin. Then the gland being removed, these flaps, which are often of considerable extent, are laid down upon the parts on which the base of the gland rested, chiefly upon the fascia over the great pectoral muscle. One of the fii-st specimens I examined well illustrated the healing that may now ensue. It was taken from a woman thirty-three years old, whose breast and several axillary glands were removed for cancer. Her general health seemed good, and all went on well after the opera- tion. The flaps, which were of course very large, had been carefully laid down, strapped vsith isinglass plaster, and well tended. They ap- peared to unite in the ordinary way, and there remained only a narrow space between their retracted edges, in which space granulations arose from the pectoral muscle. Three weeks after the operation these were making good progress towards cicatrisation ; but erysipelas and phle- bitis ensued, and the patient died in four or five days. I cut off the edges of the wound with the subjacent parts, expect- ing to find the evidences of union by organised lymph, or, possibly, blood. But neither existed ; and the state of parts cannot be better described than by saying that scarcely the least indication remained of either the place where the flap of skin was laid on the fascia, or the means by which they were united. It was not possible to distinguish the relation which these parts held to each other from that which naturally exists between subcutaneous fat and the fascia beneath it. There was no unnatural adhesion ; but, as the specimen, which is in the Museum of St. Bartholomew's, will still show, the subcutaneous fat which did lie over the mammary gland was now connected with the fascia over the pectoral muscle, just as (for example) the corresponding fat below the clavicle is naturally connected to the portion of the same HEALING BY IMMEDIATE UNION. 145 fascia that lies there. The parts were altered in their relations, but not in their structure. I could find small points of induration where, I suspect, ligatures had been tied, or where, possibly, some slight in- flammation had been otherwise excited ; and one small abscess existed under the lower flap. But with most careful microscopic examination, I could discover no corpuscles of inflammatory lymph, and only small quantities of what looked like the debris of such oil-particles or cor- puscles of blood as might have been between the cut surfaces when the flaps were laid down. In short, we cannot otherwise more minutely describe this healing than by the term ' immediate union : ' it is im- mediate at once in respect of the absence of any intermediate substance placed between the wounded surfaces, and in respect of the speed with which it is accomplished. Opportunities of making post mortem examinations of wounds thus healed being rare, I made three experiments on rabbits (with my friend Mr. Savory), and found the description I have just given quite con- firmed. A portion of skin, which my extended fingers would just cover, was raised from the back of a rabbit, replaced, and fastened down with a few sutures. Three days afterwards the rabbit was killed. The edges of the wound were slightly retracted, and the space between them was covered with scab for about half-an-inch under the edge of the replaced flap of skin, the tissue was inflamed and infiltrated with exudation-matter ; but beyond this no trace of the injury or of its heal- ing could be seen. The parts appeared as they had appeared before the operation. Even the microscope could detect only a slight infil- tration of inflammatory matter, which one might certainly ascribe to the wound being open at its edges, and to some hairs having by acci- dent been enclosed under the flap when it was replaced. Of course, it is only from such examinations as these after death, that we can speak certainly of the absence of inflammation and of all intermediate uniting substances ; yet confirmatory evidence may be obtained from the examination of any such wound during life, — I mean in any such case as that of a flap of skin raised up, then laid down on the subjacent wounded surface, and there uniting favourably ; or in any case of that kind of plastic operation in which a flap is raised, and then made to slide to some further position. In such cases, with favourable progress, no sign of inflammation is observed ; though, if the skin were in even a small degree inflamed, it could scarcely fail to be manifested by the ordinary appearances of redness and heat. If the flap be pressed, no fluid oozes beneath its edges (I speak, of course, of L 146 HEALING BY IMMEDIATE UNION. only saoli cases as are makiag favourable progress) ; and after one or two days, according to tlie extent of the wound, the flap will move on the subjacent parts, not with the looseness of a part separate from them, nor with the stiffness of one adherent through inflammation, but with the easy and pliant sliding which is peculiar to the natural connection of the skin with the subjacent fascia. Such is the nature of ' immediate union,' the best imaginable pro- cess of healing. Two conditions appear essential to it : flrst, exactness of the coaptation of the wounded surfaces ; and secondly, the absence of all inflammatory process. To obtain the former, the simple replacement of the raised pieces of skin may sometimes be suflicient. But there is a class of cases to which this mode of healing is peculiarly applicable, and in which more than this may be required ; I refer to the removal of large subcutaneous tumours — fatty tumours and the like — where, after the operation, large cavities are left, and commonly left to granulate. In these cases I believe that modern surgery does not often enough employ the older method of carefully and softly padding the parts, and of so bandaging them that the exposed surfaces may be held in contact and at rest for the one, two, or three days necessary for immediate union. Many surgeons, I know, commonly employ these means, but by many they are avoided — through fear of exciting inflammation by over-heating the parts, or hindering the discharge of secreted fluids. Doubtless, no single rule of management would be safe ; yet the antiseptic mode of treatment leads us to hope that) even when blood and inflammatory, or efiused and decomposing fluids, have collected in the wound and soaked into and infected thfe adjacent tissues, there may be a fair prospect of success in healing without the intervention of the suppurative process.' And, if these things be looked to, I think the fear of exciting inflam- mation by these attempts to promote union need not be entertained. One may generally observe that, foi^ at least two or three days after such an injury as an amputation, the raising of a flap of skin in a re- moval of the breast; or the like, scarcely any reparative process appears in the parts that are kept from contact ; no granulations are formed, no pus secreted, only a littlfe serous-looking fluid oozes from them. Now, during this calm, which would certainly not he disturbed by the parts being softly padded aid kept in perfect rest, the immediate union may be accomplished. If, through any uiitoward circumstance, it be not in ' The infection may be preyented by the thorough ■washing of the wounded parts with solution of chloride of zinc, carbolic acid, or strong spirit. HEALING- BY IMMEDIATE UNION. 147 this period completed, its occurrence is, I believe, impossible, and then the means more appropriate for other methods of healing may be em- ployed. The attainment of the other necessary condition, the absence of in- flammation, is quite consistent with these means for insuring perfect and continued contact of the wounded surfaces. How the condition is to be fulfilled I need not say : the means are some of those that are commonly laid down for preventing inflammation from being, as it is said, more than is necessary for the union by the first intention ; and the best of them are temperance, rest, and uniform temperature. The necessity of observing them will appear the greater, if it is remembered that what is wanted for immediate union is, not a certain undefined slight degree of inflammation, but the complete absence of inflamma- tion ; for the probability of the occurrence of immediate union may be reckoned as being in an inverse ratio to the probability of inflammation occurring in the time necessary for its accomplishment. The second mode of repair that I enumerated is that by primary adhesion. This is the process which Mr. Hunter named union by adhesion, or union by the adhesive inflammation. My reasons for preferring the term ' primary adhesion ' will presently appear. He says, ' Where the former bond of union [i.e. the union by blood or by the first intention] is lost in a part, to produce a new one a second operation takes place — namely, inflammation.' ' Observe how carefully Mr. Hunter distin- guishes the case in which inflammation ensues from that in which none is necessary : and presently after — ' If the divided parts are allowed to remain till the mouths of the divided vessels are entirely shut, inflam- mation will inevitably follow, and will furnish the same materials for union which are contained in extravasated blood, by throwing out the coagulated lymph ; so that union may still take place, though some time later after the division of the parts. This inflammation I have called the adhesive.' On this sentence Mr. Palmer, expressing the opinion entertained by all the pathologists of some five-and-twenty years ago, says, — ' It is now generally considered that union by the first intention and adhesive inflammation are essentially the same pro- cesses, modified by the degree of inflammation. Union by the first in- tention is uniformly attended with some degree of pain and swelling, > JTorfo, iii. p. 253. L 2 148 HEALma BY PEBIAEY ADHESION. together witli increased heat and vascularity, which, taken conjointly, constitute the definition of inflammation.' And again : ' According to the modern views, the modes of union above detailed [_i.e. the modes of union included by Mr. Hunter under the union by the first intention] are always accompanied by adhesive inflammation The parts are united, not by the extravasated blood becoming vascular, but by the eff'usion and organisation of coagulable lymph.' After what I have said respecting the process of immediate union, it may appear that Mr. Hunter was more nearly right than his succes- sors. It would be an iustructive piece of the history of surgery, to show exactly how his truth, being mixed with error, came therefore to be thrown away, and to make room for an error which had less truth mixed with it. The stages of transition in opinions seem, to have been, that, first, sufiicient reason was found for disbelieving Hunter's statement, that blood forms the bond of union by the first intention ; then, as it was assumed that there must always be some intermediate bond, and this, it seemed, could be none but coagulable lymph. Now, coagulable lymph being known only as the product of inflammation, it followed that inflammation must be necessary for the healing of every wound ; and then there ceased to be any dis- tinction between the union by the first intention and the union by adhesion ; both alike seemed to be the result of lymph, the product of inflammation, beiug exuded between the wounded surfaces, and nnited to them both. Typical examples of union by primary adhesion may be watched in the cut edges of skin that are brought near together. When the cut surfaces are not in exact contact, the wound is exposed, and lymph is formed, and fills up the space ; or, when they are in contact, the sutures, or other means employed to keep them so, excite inflammation and some lymph is produced between them. The lymph is simply laid on the cut surfaces ; and scarcely any is infiltrated in the tissues. It connects the two edges or surfaces, and, finally, bloodvessels and a thin layer of connective tissue form between them, on the surface of which latter, if it be exposed, a very delicate layer of cuticle is developed. The smooth shining siu'face of this cuticle gives the peculiar character of the scar, and one that scarcely changes, except in the alteration of apparent colour when the new material becomes less vascular. Healing by primary adhesion may be very quickly accomplished. A boy died eighty hours after receiving a lacerated wound of the abdo- men ; and, for forty-eight lionrs of these eighty, he was so manifestly HEALING BY PRIMARY ADHESION. 149 dying, that I think no reparative process could have been going on. A portion of the edges of the wound was united with lymph, which con- tained looped bloodvessels full of blood and well-marked cells, like those of granulations. But it may be accomplished more quickly than in this case. In a rabbit that I operated on as for harelip, I found, after forty-eight hours, the edges of the wounds partially, but firmly, united by lymph, in which many elongated cells sach as I have already described were found. Or, even more quickly than in this instance : — if a small abscess beopened, and theedges of the openingare not gapingor inverted, they may be found united, except at the middle, within twenty-four hours. 1 have seen them so united, with a distinct layer of soft, pinkish, new substance, in a wound made seventeen hours previously. There are no cases in which the process of primary adhi.'sion can be better observed than after operations for harelip. The inner portions of the wounds made in them may be healed by the immediate union, when the surfaces have been in exact coaptation; but the edges of the skin and mucous membrane seem always united by the adhesive in- flammation, for a scar is always visible — a scar formed of connective tissue and epithelium, and one which, as well as any, shows how little of assimilative force can be exercised by adjacent tissues ; for,' narrow as it may be, it does not become quite like the adjacent skin, nor, like it, bear perfect epidermis and hair. The history of union by primary adhesion cannot be conveniently completed till an account has been given of the healing by granula- tion and by secondary adhesion. Of these I will next speak ; now I will only say of this union by primary adhesion, that it is less desirable than the immediate union, because — 1st, it is probably not generally so speedy ; %idly, it is not so close, and a scar is always formed by the organisation of the new matter ; and Srdly, the forma- tion of lymph-cells is a process so indefinitely separated from that of the formation of pus-cells, that union by primary adhesion is much more likely to pass into suppuration than any process is in which no lymph is formed. In describing the modes of healing by granulation and by secondary adhesion, I shall venture again to take my account from certain typical examples : such as cases in which, after amputation of a limb, the sur- faces of the wound are not united by either of the means already des- cribed, but, as the expression in, are left to ' granulate : ' or such cases as the removal of a breast and subsequent suppuration of the flaps and 150 HEALING BY PRIMARY ADHESION. the exposed fascia ; or such as wounds into inflamed parts, when the edges gape wide asunder, and the spaces left between them are filled up with granulations. These may serve as examples of a process which, although in all cases it may preserve certain general features of simil- arity, is yet in detail almost infinitely diversified, and often so inex- plicably, that any more than a general account of it might fiU volumes. Granulations will generally arise on all wounded surfaces that are left open to the air and are not allowed to dry. They will do so whether this exposure be continued from the first infliction of the wound, or commence after the edges, which have been brought together, have been again forced asunder by the swelling of the deeper-seated parts, or by hemorrhage, or secretion of fluid, between them. Exposure of a wound to the air is not prevented by any ordinary dressings : the air that is enclosed beneath them, or that can penetrate them, appears to be quite enough to determine all the difference of the events that fol- low open and subcutaneous injuries, iinless the organic naatter in it be destroyed or rendered innocuous by carbolic acid or some similar anti- septic substance.' The simplest case for illustration is that of an open gaping incised wound, which, from the time of its infliction, is only covered, as in ordinary practice, with water-dressing, or some soft and moist sub- stance. Blood gradually ceasing to flow from the surface of such a wound, one may see still some blood-tinged serous-looking fluid oozing from it. Slowly, as this becomes paler, some of it collects, like a whitish film or glazing, on the surface : and this, if it be examined with the microscope, will be found to contain an abundance of corpus- cles, having the appearance of white corpuscles of the blood, imbedded in a fibrinous film. The collection of these corpuscles on the surface of the wound, especially on wounded muscles and fascise, appears to de- pend only on the peculiar adhesiveness which they exhibit as soon as they are removed from the canal of the healthy bloodvessel, and brought in contact with extraneous substances. One sees them adhering much more firmly than ever the red corpuscles do to the glass on which they are examined ; and so on cut surfaces, while the other constituents of the blood flow away, the white corpuscles, and probably also some of the fibrine, quickly coagulating, adhere. The share which the white corpuscles thus collected may take in the healing of a wound, is a subject at present attracting some attention. " See the ntimerous papers by Professor Lister in the Lancet and other journals for 1868-69. HEALING BY GBANULATION. 151 Apparently, they do not hinder it ; for it is by many believed to be favourable to union by primary adhesion to leave cut surfaces exposed till they appear glazed over with the whitish film, and then to put them into contact. It is probable that these corpuscles become organised into the corpuscles of connective tissue when the surfaces that they cover are brought together. If a wound be left open, the glazing remains on such parts as it may have formed on, especially on the exposed muscles. No evident change ensues in it, except that it appears to increase slowly, and makes the surface of the wound look as if covered with a thin greyish or yellow- ish-white layer of huffy coat. This increase of glazing is the prelude of the formation of granulations ; but while it is going on, and often for some days latei-, there is in and about the wound an appearance of com- plete inaction ; a calm in which scarcely anything appears except a slight oozing of serous fluid from the wound. Such a calm continues from one day to eight, ten, or more, according to the nature and extent of the wounded part, and the general condition of the body. In a cut or sawn hard bone, about ten days will generally elapse before any change is manifest ; in cancellous bone the change ensues a few days more speedily • on the under surface of a large flap of skin, with sub- cutaneous fat, three days may thus pass without change ; on the cut or ex- coriated surface of the more vascular part of the skin, two days or three. These periods of repose, after severe injury, are of equal interest in physiology and in surgery ; but in the former it is chiefly the interest of mystery. Observations on injuries of the frog's web ' make it pro- bable that the blood is stagnant in the vessels for some little distance from the wound during several days after the injury : but why it is so, and what are the changes ensuing in and about it preparatory to its again moving on, we cannot quite tell. The interest to the surgeon watching this period of repose is more practical. The calm may be the brooding-time for either good or evil ; whilst it lasts the mode of union of the wound will, in many cases, be determined : the healing may be perfected, or a sIotv uncertain process of repair may be but just begun ; and the mutual influence, which the injury and the patient's constitu- tion are to exercise on one another appears to be manifested very often at or near the gnd of this period. Moreover, in open wounds, the time at which, on e^ch tissue, granulations are produced, is determined ' See especially those detaile.d ty Mr. Travers in his Essai/ on Inflammation and the Healing Process ; and those by Mr. Wharton Jones, On the State of the Blood and Bloodvessels in Inflammation. 152 HEALING- BY GRANULATION. by this calm ; for they begin to be distinctly formed at its end. Thus, on a stump, after a circular amputation, one may find the margin of the skin and the surface of the muscles well covered with granulartions, while the surface of the fat reflected with the skin is barren of them, and the sawn walls of the bone are dry a.nd bare. But from the sawn end of the medullary tube there may already protrude a florid mush- room-shaped mass of granulations, overhanging the adjacent walls ; as if parts in which nutrition is habitually carried on under restraint, within hard and rigid boundary- walls, were peculiarly apt to produce abundant organisable material as soon as they are released.' Generally, also, the granulations springing from these diflFerent tissues observe the same order in their rate of development as in their first appearance. Those that first take the lead keep it, or, for a time, increase it. But suppose the period of calm after the violence of the injary to be well over-past — How does the right process of repair set in ? Apparently, first of all, by the supply of blood to the injured part being increased. The experiments on the webs of frogs, to which I have already referred, have shown that, immediately after the infliction of an injury, the blood in the adjacent parts remains for some days quite stagnant ; and we may believe the same occurs, but for a shorter time, in our own case. During this stagnation, materials may ooze from the vessels, enough to form the glazing of the wounded surfaces of certain parts ; but before granulations can be formed, the flow of blood must again begin, and its supply must be increased by enlargement, and perhaps by multiplication, of the vessels in the injured part. We cannot often see this increase so well in soft parts as in bone exposed after injury. If, in this condition, compact bone be closely watched, there may be seen, two or three days before the springing up of granulations, rosy points or minute blotches, which gradually deepen in their hue, and become larger. From these, presently, granulations will arise. The same process may be well seen when a portion of the skull has been exposed, as by suppuration under the pericranium. In such a case, which I watched carefully, nearly one-third of the upper part of the skull was bared, and it became dry and yellowish, and looked quite life- less ; but after some days a few rosy points appeared on its surface, and ' One may sometimes observe a similar fact in the growth of granulations out of the very centre of the cut end of a divided tendon, while its margins are unchanged. The abundant growth of substance like brain, covered with granulations, in cases of hernia cerebri, is of the same kind. HEALIJTG BT GEANULATION. 153 tliese multiplied and enlarged, and from each of thom granulations grew up, till tte w'lole surface of tlie skull was covered. I watched them nearly every day, and it seemed evident, at least to the naked eye, that, in all cases, an increased supply of blood preceded the production of the new material from which granulations were to be formed. Doubtless, just the same happens in soft parts as in bone ; so that it may be stated, generally, that the first visible change that ensues after the period of calm, — the period of incubation, as it is called, — is an increased supply of blood to the parts in which repair is to ensue. This, probably, corresponds exactly with the increased afflux of blood which ensues in inflammation ; and Mr. Travers's and other observa- tions on the healing of the frog's web make it nearly sure that this increased afflux is attended with slower movement of the blood, or at first even with stagnation of the blood in the minute vessels nearest to the cut edges or surface. Of the force by which this increased afflux of blood is determined, I believe that as yet no sufficient explanation can be rendered ; but the fact serves to show that the ordinary process of granulation is, in its commencement, morbid. It is beneficial, indeed, in its end or purpose, but is morbid in its method, being comparable with the process of in- flammation more than with any of those that are natural to the body. The granulating process displays, I think, two points of resemblance to inflammation, and of dissimilarity from natural processes : namely — 1st, that the increased quantity of blood, in the part producing granu- lations, moves more slowly than in health ; while, when the supply is naturally increased, its movement is not retarded ; and 2ndlij, that the increased supply of blood precedes the increased production of material. For, in the discharge of natural functions, the increased supply of blood to a part appears always to be a secondary event, the consequence of some increase in the formation of the part. As, in the embryo, many parts form themselves before blood appears, and the growth of these and other parts always a little precedes the proportionate supply of blood to them ; so always, subsequently, the increase or diminution of growth, or any other organic act, appears to precede, by some small interval, the proportioned change in the supply of blood. But with unnatural and morbid processes it appears to be usually different : in these, with inflammation for their type and chief example, the increased afflux of blood precedes the increased production of matei'ial to be organized, and the decrease of blood precedes the decrease of organic processes. 154 HEALING BY GRANULATION. That which nezfc follows, after the increased afilux of blood, is the production of thematerial that is to be organised into granulations. This IS added to, or perhaps displaces, the glazing that already exists upon some surfaces ; and where none such exists, as on fat or bone, the new material forms on the bare surface of the wound. No account of the appearance presented by the reparative material, so far as it is visible to the naked eye, can be better than Mr. Hunter's (iii. 491). 'I have often been able,' he says, 'to trace the growth and vascularity of this new substance. I have seen upon a sore a white substance, exactly similar, in every visible respect, to coagulating lymph. I have not attempted to wipe it off, and the next day of dressing I have found this very substance vascular ; for by wiping or touching it with a probe it has bled freely. I have observed the same appearance on the surface of a bone that was laid bare. I once scraped off some of the external surface of a bone of the foot, to see if the surface would grannlate. I remarked the following day that the surface of the bone was covered with a whitish substance, having a tinge of blue ; when I passed my probe into it I did not feel the bone bare, but only its resistance. I conceived this substance to be coagulating lymph thrown out from inflammation, and that it would be forced off when suppuration came on ; but on the succeeding .day I found it vascular, and appearing like healthy granulations.' To this description little can be added more than the microscope has shovm. In the minute structure of granulations, or at least of such growths of new substance as present all the characters that we imply by that term — the bright ruddy texture, soft and elastic, the uniformly granulated free surface, the succulency ^.nd abundant supply of blood — in these we may discern two varieties. In subcutaneous injuries or diseases granulations sometimes form, which develop thepiaelves into connective tissue through nucleated blastema or protoplasm. So I found in a case of simple fracture in which the ends of the bone remained long disunited ; they were enclosed in a cavity formed by con- densation of the surrounding tissues, but containing no pus, and were covered with a distinct layer of florid granulations. It was just such a case as that which Mr. Hunter had in view, and preserved,' as an instance of the formation of granulations without suppuration, in the repair of subcutaneous fractures and other injuries. But in by far the greater proportion of cases, granulations are only ' College Museum, No. 16. HKAIiING BY GRANULATION. 155 formed in exposed injuries ; and in these they consist of cells that, together with their intermediate protoplasm, may develop themselves into connective tissue : and of such as these I will now exclusively speak. Cells upon cells, such as I have already described (p. 141), are heaped up together in a layer, from half-a-line to two lines, or rarely more in thickness, without apparent order, and connected by very little intermediate substance. (Figs. I 7 and 22.) Singly they are colour- less, but in clusters they are ruddy — even independent of the blood- vessels. In granulations that are making healthy progress — in such as, after three or four days' growth, are florid, moist, level, scarcely raised above the surrounding tissues, uniformly granular, or like a surface of minute papillae — one can conveniently trace the cells in various stages, according to the position they occupy. The deeper seated ones are always most advanced, and often much elongated and fdsiform : while the superficial ones are still in a rudimental state, or, near the edges of the granulating surface, are acquiring the character of epithelial cells. The connective tissue thus constructed by the development of the granulation-cells, finally assumes all the characters of the natural ex- amples of that tissue. Thus it is found in the thin layer of substance of which scars, that are formed in the place of granulating wounds, are composed. After some time, elastic tissue is mingled with the white fibrous ; but this, as I have already said, appears to be effected by a later process. I found, in one case, no elastic tissue in scars that had existed, the one twelve months, the other eighteen months ; but in scars several years old, I have always found it, The cuticle that forms on granulations is usually developed from the borders towards the central or middle part of the wound. Cover- ing the ruddy granulation-layer with an opaque white film, it gives a subdued purplish tint, and just within it there is a narrow border of vascularity, greater than that of the rest of the granulations, indicating, I suppose, the greater supply of blood necessary to the development of the indifferent cells into cuticle. Like the connective tissue that it covers, the new cuticle presents the interesting fact of adaptation to the purposes of the part on which it is placed. Thus, in granulating wounds or ulcers on the sole of the foot, one may often see that, from the first, the new cuticle is more opaque and thicker than it is on other parts on which the natural cuticle, in adaptation to the protection required from it, is naturally thinner ; and let it be observed that this 156 HEALING BY GRANULATION, peculiar formation of the new cuticle is in adaptation to conditions not yet entered upon. It justly excited the admiration of Albinus ' when he saw in the foetus, even long before birth, the cuticle of the heel and palm thicker than those of other parts ; ada.pted and designed to that greater friction and pressure, to which, in future time, they would be exposed. It is the same when, in adult life, the new cuticle is to be formed on the same parts. While it is forming, all pressure and all friction are kept away, yet it is constructed in adaptation to its future exposure to them. Surely such a provision is, beyond all refutation, an evidence of design ; and surely in this fact we may discern another instance of the identity in nature and in method of the powers that are put in operation in the acts of first construction and of repair. But before I end this lecture, let me add, that although one may so clearly trace, in the development of the granulation-cells, and in the end which they achieve by the formation of connective tissue and cuticle, an imitation of the natural processes and purpose of the cor- responding developments in the embryo, yet is there a remarkable con- trast between them, in regard to the degrees in which they are severally liable to defect or error. We can scarcely find examples of the arrests or errors of development of mere structure in the embryo ; but such events are quite common in the formation of granulations, as well as of all other new products. All the varieties in the aspect of granulating wounds and sores, which the practised eye can recognise as signs of deflection from the right way to heabng, are so many instances of different diseases of the granulation-substance ; diseases not yet enough investigated, though of much interest in the study of both the healing process and the organisation of new products in inflammation, and often indicative of constitutional rather than of local disease. Comparatively few observations enable one to trace morbid con- ditions of these new structures, closely answering to those long known in the older and more perfect tissues. Thus, one may find simply arrested development of granulations ; as in the indolent healing of wounds and ulcers, whether from locally or generally defective con- ditions. Herein even j'ears may pass, and the cells will not develop beyond one or other of their lower forms. There is probably a con- tinual mutation of particles among such cells, as in common nutrition, or they may increase, as in growth ; but no development ensues, and the wound or the ulcer remains unhealed, ' Annotationea Academioce, HEALIIMG BY GRANULATION. 157 In other cases, tlie cells not only do not develop, but degenerate, becoming more granular, losing tbe well-marked characters of their nucleus, and acquiring all the structures of the pus-cell ; thus are they found in the walls of fistulse and sinuses. Or, worse than this, the granulation-ceUs may lose all structure, and degenerate into a mere layer of debris and molecular substance. Thus they may be found on the surface of a wound for a day or so before death in exhaustion, or in erysipelas, or fever ; and in this state they are commonly ejected when a granulating wound ulcerates or sloughs. With more active disease, granulations become turgid with blood or cedematous : such are the spongy masses that protrude beyond the openings leading to diseased bone. Or they inflame, and abundant large inflammatory granule-cells are found among their proper struc- tures. Or they suppurate internally, and purulent infiltration pervades their whole mass. All these are among the many hindrances to healing : these are the dangers to which the heahng by granulations is obnoxious ; it is the proneness to these things that makes it even slower and more insecure than, in its proper course, it might be. And these are all instances of a class of changes which it is most important to study for exact- ness in morbid anatomy — I mean, the diseases of the products of disease. 158 LECTURE X. THE PEOCESSES OF REPAIR OF WOUNDS. With the structural development of the granulation- eel Is into con- nective tissue and cuticle, as described in tlie last lecture, there coin- cides a chemical change which seems to be the contrary of development ; for the granulation-substance, being converted from albuminous into homy and gelatinous principles, becomes, in chemical composition, less remote than it was from the constitution of inorganic matter. The granulation-cells and young connective tissue present the characters of pyine, a somewhat indefinite principle, yet an albuminous one ; finally, in its perfect development, the new-formed connective tissue is gelatin- ous, and the epithelium appears to be like other specimens of horny matter. These changes are in conformity with what appears to be a general rule ; namely, that structures which are engaged in energetic develop- ment, self-multiplying, the seat of active vital changes, are generally of the highest organic chemical composition ; while the structures that are already perfect, and engaged in the discharge of functions such as are attended with infrequent changes of their particles, are as generally of lower composition. The tauch higher chemical development (if I may so call it) of the blood, than of the greater part of the tissues that are formed from it, is a general instance of this : in it albumen and fibrine-forming constituents predominate, and there is no gelatine ; in the tissues gelatine is abundant, and fatty naatter ; and both these, through their affinities to the saccharine and oily principles, approach the characters of the lower vegetable and inorganic compounds. The granulation-substance is a good instance in point : while lowly developed, but in an active vegetative life it is albuminous ; when per- fect in its development, its perfected structures are gelatinous or horny. In this state its particles have probably a longer existence : they ex- change a brief life of eminence for longevity in a lower station. FORMATION OF NEW BLOODVESSELS. 159 I have spoken hitherto of the development of only those structures ■which form the proper material of granulations; and of the scars that remain after the healing of wounds. But, commensurately vyith these, bloodvessels and perhaps also nerves are formed. Of these, therefore, I will now speak. In the last lecture I referred to thS fchanges that ensue in the cir- culation of a wounded part. At first, it appears that the blood stagnates in the vessels immediately adjacent to the wound. This is evident in the wounds made in frogs' webs, and ia most probable in the case of wounds in our own tissues ; for else we could hardly understand the total absence of bleeding from a surface on whicb, as in every large wound, myriads of small vessels must be cut, and lie exposed. But after a time, of various duration in the difierent tissues, the movement of the blood is renewed, though not to its former velocity ; the vessels of the wounded parts enlarge, and they all appear more vascular. Then the material of granulations accumulates, and very soon blood and bloodvessels appear iu this material. By what process are these new vessels formed ? Mr. Hunter's opinion was (and it is still held by many) that both the blood and its vessels form in the granulation-substance, as they do in the germinal area of the chick ; and that, subsequently, they enter into communica- tions with the vessels and blood of the part from which the granulations spring. This is certainly not proved ; although the development of the new vessels is according to a method that is equally natural. In embryos, we may discern three several modes according to which bloodvessels are formed — a good example of the manifold ways by which, in development, the same end may be reached. In the first and earliest method solid cylinders of round cells, lying compactly together, are formed in the area vasculosa, in which cylinders changes then take place. The cells in the central part of the cylinders loosen and become converted into blood-corpuscles, or, as Billroth appears to think,' their membranes disappear, and their contents only constitute the blood-corpuscles. The membranes of the cells on the outer parts of the cylinder coalesce and form the membranous wall of the vessel, which may afterwards be developed into the more compli- cated structures of the heart, or larger bloodvessels. To increase the extent and number of vessels that must be added in adaptation to the enlargement and increasing complexity of the embryo, two methods are ' Vntersuckungen iiber die EniwicMung der Slutgcfdsse ; Berlin, 1856. 160 FORMATION OF NEW BLOODVESSELS. observed. In one, primao^y cells, in the interspaces of vessels already existing, enlarge and elongate, and send out branches in two or more directions, so as to assume a stellate form. These branches are hollow : and while some of them are directed into anastomosis with each other, others extend towards, and open with dilatations into, the vessels already formed and carrying blood. Then, these fine branches of each cell becoming larger, while the main cavity of the cell from which they issued attenuates itself, they are altogether transformed into a net-work of tubes of nearly uniform calibre, through which the blood, entering by the openings of communication with the older vessels, makes it way. Thus the wide network formed in the primordial circulation is sub- divided into smaller meshes, and each part receives a more abundant sup- ply of blood. Billroth has described a kind of vascular formation, which may be considered as a modification of the above method. He has seen long spindle-like cells lie with their long axes parallel to each other and close together, but not in contact, so that a fine canal existed between them, which constituted the canal of the newly-formed vessel, the wall being formed by the spindle-like cells themselves. From these cells new blood-corpuscles proceeded into the vessel, as in the first method of vascular formation. This process he has noticed not only in em- bryonic tissues, but also in granulations. The other of these secondary modes of formation of new blood- vessels, is, I believe, the most frequent mode in which bloodvessels are formed in granulations, /^g3v _-_-^<^**c^\ or in superficial forma- 'ssi — . '^Si.^A'^a^ sions, and the like. The diagram is made from what may be seen in '^' ■ the growing parts of the tadpole's tail, and it accords with what Spallanzani observed of the extension of vessels into the substance of the tail when being reproduced after excision. Mr. Travers ' and Mr. Quekett watched the same pro- cess in the new material formed for the filling up of holes made in the frog's web ; and the same is indicated in the specimens illustrating the ' On Inflammation and the Healing Frocess. See, also on a similar formation, Virchow in the Wurzhirg Verhandlungen, B. i. p. 301. PORMATION OF NEW BLOODVESSELS. 161 repair of similar wounds, -which are in the College, from the Museum of the late Dr. Todd of Brighton. There is, I think, sufficient reason to suppose that it is the principal method for the supply of bloodvessels to any granulations, or similar new productions. For, though the pro- cess in granulations or in lymph cannot he exactly watched during life, yet every appearance after death is consistent with the belief that it is the same as has been traced in the cases I have cited, and T have never seen any indications of either of the other methods of development having occurred. The method may be termed that by out- growth from the vessels already formed. Suppose a line or arch of capillary vessel passing below the edge or surface of a part to which new material has been superadded (Kg. 19). The vessel will first present a dilatation at one point, and coincidently, or shortly after, at another, as if its wall yielded a little near the edge or surface. The slight pouches thus formed gradually extend, as blind canals, or diverticula, from the original vessel, still directing their course towards the edge or surface of the new material, and crowded with blood-corpuscles, which are pushed into them from the main stream. Still extending, they converge ; they meet ; the partition wall that is at first formed by the meeting of their closed ends clears away, and a perfect arched tube is formed, through which the blood, diverging from the main or former stream, and then rejoining it, may be continuously propelled. Or a delicate thread-like process shoots out from a vessel, which becomes connected either with corresponding shoots from other vessels, or with processes from other cells. These fine processes widen out, become tubular, and their cavi- ties form canals continuous with that of their parent vessel.' In this way, then, are the simplest bloodvessels of granulations and the like out-growths formed. The plan on which they are arranged is made more complex by the similar out-growths of branches from ad- jacent arches, and their mutual anastomoses ; but, to all appearance, the whole process is one of out-growth and development from vessels already formed. And I beg of you to consider the wonder of such a process ; how, in a day, a hundred or more of such loops of fine mem- branous tube, less than y-jiVji- of an inch in diameter, can be upraised ; not by any mere force of pressure, though with all the regularity of the simplest mechanism, but each by a living growth and development as orderly and exact as that which we might trace in the part most essential ' Billroth, op. cit. M 162 FOBM-iTION OF NEW BLOODVESSELS. to tlie continuance of life. Observe, that no force so simple as even that of mere extension or assimilation can determine such a result as this : fcir, to achieve the construction of such an arch, it must spring with due adjustment from two determined points, and then its flanks must be commensurately raised, and these, as with mutual attraction, must ap- proach and meet exactly in the crown. Netting could accomplish such a result but forces determining the concurrent development of the two out-growing vessels. The wonder of the process is, perhaps, in some degree enhanced by the events that will follow what may seem to be an accident. When the new vessel has begun to project, it sometimes bursts, and the diagram Q '^f^'V^ stows what then will hap- pen. I have to thank Mr. Quekett for the sketch, which he made while as- sisting Mr. Travers in the examinations already cited. The blood-corpuscles that ^ig- 20. issue from the ruptured pouch or diverticulum collect in an uncertain mass within the tissue, like a mere ecchymosis ; but, before long, they manifest a definite direction, and the cluster bends towards the line in which the new vessel might have formed, and thus opens into the other portion of the arch, or into some adjacent vessel. For this mode of formation from vessels, the name of channeling seems more appropriate than that of out-growth ; for it appears certain that the blood-corpuscles here make their way in the parenchyma of the tissue, unconfined by membranous walls. That they do so in a definite and purposive manner, though their fii'st issue from the vessel has appeared so accidental, may be due to the fact that in the more regular development by out-growth, the cells of the parenchyma concur with the extension of the new vessels, by clearing away from them as they approach ; so that, even before the out-growth, the way for it or for its contents (should they happen to escape) is in some measure determined.' ' Billroth has described and figured (p. 15 PI. i. Eig. 21) an appearance very similar to that recorded in the text. He at first thought that it was simply an ex- travasation, but further consideration has led him, in accordance with certain views which ho entertains respecting the mode of formation of blood-corpuscles, to think that here, perhaps, a new free formation of coloured blood-coi'puscles, out of the colourless shining homogeneous cells of the part takes place. At the same time he confesses the difficulty of understanding how they got into the circulation. FORMATION OF NEAV BLOODVESSELS. 163 The general plan of arrangement of the bloodvessels in grannktions, represented in the adjoining sketch, agrees with this account of their development by out-growth. Some of Sir A. Cooper's preparations in the Museum of the College' show how the new vessels ex- tend from the parts on which the granulations lie, in lines directed vertically towards their surface, not often divid- ing,, but communicating on their way by frequent trans- verse or irregular branches. Of these branches, some pro- bably represent the loops or arches successively formed in the deepening layer of granu- lation-cells, while others must be formed by ofishoots from Fig. 21. the sides and other parts of the several arches. Near the surface of the granulations, at a very little distance below the outermost layer of the cells, the vessels communicate much more frequently, and form their loops or terminal arches — arches of junction between the out- going and the returning streams of blood. On the same plan are formed the vessels of the walls of abscesses lined with granulations ; but here (at least in the specimens I have been able to examine) the vertical vessels are not so long, and the whole number of vessels is generally greater. I believe the vessels of granulating ulcers are always similarly arranged ; so they are repre- sented by Mr. Listen^ in a common ulcer ; so also. Sir A. Cooper* described them in granulations from an ulcerated scirrhous cancer ; and I have found the same general plan in the warty ulceration of soot- cancer on the scrotum. The new vessels formed in granulations possess a very simple struc- ture. Their walls consist of a thin membrane in which nuclei are im- bedded. Some of these nuclei are arranged longitudinally, others transversely, to the axis of the vessels, and it is often noticeable that ' Nos. 19, 20, 356. ' Medico-Chirurgical Transactions, xxiii. p. 85. ^ Catalogue of the Pathological Museum of the College, i. p. 111. M 2 164 FOEilATIOiN" OF NEW BLOODVESSELS. the development of the tissues of the bloodvessels makes more progress than that of the granulation-cells which they subserve. Respecting the purpose of the supply of blood thus sent to granula- tions, one traces, in the development of vessels, a series of facts exactly answering to those in ordinary embryonic development. Organisation makes some progress before ever blood comes to the very substance of the growing part ; for the form of cells may be assumed before the granulations become vascu- lar. But, for their continuous active growth and development, fresh material from blood, and that brought close to them, is essential. For this, the blood- vessels are formed ; and their size and num.ber appear always proportionate to the volume and rapidity of life of the granula- tions. No instance would show the relation of blood to an ac- tively growing or developing part better than it is shown in one of the vascular loops of a granulation, embedded, as the sketch shows it, among the crowd of living cells, and maintaining their contin- ual mutations. Nor is it in any case plainer than in that of granula- tions, that the supply of blood in a part is proportionate to the activity of its changes and not to its mere structural development. The vascular loops lie embedded among the simplest primary cells, or, when granulations degenerate, among structures of yet lower organisation ; and as the structures are developed, and connective tissue formed, so the bloodvessels become less numerous, till the whole of the new mate- rial assumes the paleness and low vascularity of a common scar.' But, though the quantity of bloodvessels is determined by the state of the substance they supply, the development of their tissues has no such relation. It is often complete while the granulation-cells are rudimen- ' Billroth {Beitrdge zur Path. Hist.) describes the group of cells situated around a capillary loop on a granulating surface, as formed by the proliferation, by division of the nuclei, of the adjacent connective-tissue corpuscles. C. 0. "Wehev {Enimc7dunff dvs Eitirs), referring to Eig. 22 in this lecture, states that the delicate colls -whicli surround the vascular loops of a granulating surfsiee are of a spindle-Uke shape, and are em- bedded in a thick layer of growing connective-tissue nuclei. Fig. 22. rOEMATION OF NEW BLOODVESSELS. 165 tal, and remains long unchanged when they are degenerate. The fact may be regarded as evidence of the formation of the new bloodvessels by out-growth from the older ones; for it is not probable that well- developed bloodvessels and ill-developed granulation-cells should be formed out of the same materials at the same time. Of the development of Nerves in granulations I know nothing ; I have never been able to see any in either granulations or cicatrices. The exquisite pain sometimes produced by touching granulations would indicate the presence of nerves ; but it would be more satisfactory to see them ; for the force of contact, or the change that it produces, may be propagated through the layer of granulations, and stimulate the nerves beneath them, as contact with the exterior of a tooth excites the nerve-filaments in its pulp. The sensibility that granulations seem to have may, therefore, be really that of the tissues from v/hich they spring. Lymphatics do not exist in granulations. Professor Schroeder van der Kolk has demonstrated them in false membranes by mercurial in- jections ; ' but in a letter he tells me that they cannot, either by these or by any other means, be traced in either scars or granulations ; and, he adds, ' they cannot be demonstrated in the skin, even in the healthy state, except in the scrotum.' The subject of suppuration should perhaps be considered now ; but I had rather defer it till I have spoken briefly of the two remaining modes of healing open wounds ; those, namely, by secondary adhesion, and by scabbing. The healing by secondary adhesion, or union of granulations, has been long and often observed ; yet it has been only casually described, and having never been distinguished by a specific name, has not received that attention to which its importance in practice seems to entitle it. It occurs wherever surfaces of granulations, formed in the manner just described, well developed, but not yet covered with cuticle, are brought into contact, and so retained at rest. As often as this happens, the cells of which the surfaces are composed adhere together ; vessels passing through them form mutual communications; and the surfaces, before separate, are connected ; out of the two ' Lespinasse, Ve Vasis Novis Pseudo-mcmhranarum, Figs. iii. v. 166 HEALING BY SECONDARY ADHESION. layers of granulations one is formed, whicli pursues the normal deve- lopment into connective tissue. In all its principal characters, therefore, the process of secondary- adhesion is like that adhesion for which, to mark at once their likeness and their diflFerences, I have suggested the term of primary. In the primary adhesion, the granulation cells, placed between the wounded and bare surfaces, are probably formed equally and coincidently from both ; and, being developed in the same manner as the granulations of which I have spoken, probably receive vessels from both surfaces, and so become the medium through which the vessels communicate and combine the severed parts. In the process of secondary adhesion, the superficial cells on the surfaces of two layers of granulations are placed together, and receiving vessels from both combine them into one. Mr. Hunter observed this process, and says of it — ' Granulations have the disposition to unite with one another when sound or healthy ; the great intention of which is to produce the union of parts, somewhat similar to that by the first intention, although possibly not by the same means.' And ' I have seen two granulations on the head — viz. one from the dura mater, after trepanning, and the other from the scalp — unite over the bare bone which was between them, so strongly in twenty-four hours, that they required some force to separate them, and when separated they bled.' ' In illustration of this process he put up a preparation ' which, in his MS. Catalogue, he describes as 'granulations under the skin in an abscess in the leg, which were opposed by others on the muscles, and which were to unite. Those under the skin only are saved and folded towards each other, to show the opposition of two granulating surfaces.' There are several circumstances in which the healing by secondary adhesion should be attempted. For example, in a case of ordinary amputation of the thigh, no immediate union and no primary adhesion took place after the operation, and the whole interior of the stump was granulating. Had it been, as the expression is, ' left to granulate,' or ' to fill up with granulations,' the healing process would have occupied at least a month or five weeks more, and would have greatly exhausted the patient, already weakened by disease. But Mr. Stanley ordered the stump to be so bandaged that the opposite surfaces of granulations ' Works, iii. p. 493. 2 Pathological Museum of the College, No. 27. HEALING BY SECONDARY ADHESION. 167 might be brought into close contact : they united, and in a week the healing of the stump was nearly perfected. In all such cases, and 1 need not say that they are very frequent, the healing by secondary adhesion may be attempted without danger, and often with manifest advantage. Again : Mr. Hunter operated for hare-lip, and no primary adhesion of the out surfaces ensued. He let them both granulate : then brought the granulations together, as in the common operation, and they united and healed soundly. Or, again : Mr. Skey, some time ago, operated for fissure of the soft palate. The edges of the wound sloughed and retracted, and the case seemed nearly hopeless ; but he kept in the sutures, and granulations sprang up from the edges of the cleft, after the separation of the sloughs ; they met in the mid-space of the cleft, and coalesced, and formed a perfect scar. Doubtless, cases like these are of no rare occurrence ; but I am induced to mention them as illustrations of a process of which the im- portance and utility are not generally considered, and which is rarely applied in practice. In applying it certain conditions are essential to success ; especially that — 1st, the granulations should be healthy, not inflamed, or profusely suppurating or degenerated, as those in sinuses commonly are ; 2ndly, the contact between them should be gentle but maintained; and perhaps, Srdly, they should be as much as possible of equal development and age. The healing of wounds by scabling may be regarded, as Mr. Hunter ' says, as the natural one, for it requires no art. It is the method by which one sees nearly all open wounds healed in animals ; for in them, even in the warm-blooded, it is difficult to excite free suppuration from the surfaces of wounds ; they quickly become coated with a scab, formed of the fluids that ooze from them and entangle dust and other foreign bodies ; and under such a scab the scar is securely formed. In general, the scabbing process is effected by some substance which is effused on the surface of the wound, dries there and forms a hard and nearly impermeable layer. The edges of this substance adhere over those of the wound, so as to form for it a sort of air-tight covering, under which it heals without suppuration, and with the for- ' Works, iii. 262. 168 HEALING UNDER A SCAB. mation of a scar, whicli is more nearly like the natural parts than are soars formed in wonnds that remain exposed to the air, and which does not, like them, contract, so as to produce deformity of the parts about it. The scab may be formed of either dried blood, dried lymph and serum, or dried purulent fluid. Instances of the healing of wounds under dried blood are not rare. It is especially apt to occur in the oases of wounds in which a large flat surface is exposed, as after the re- moval of the breast with much integument. The most remarkable case of this kind is recorded by Mr. Wardrop.' The largest wounded sur- face he ever saw, remaining after the removal of a diseased breast, almost entirely healed under a crust of blood, which remained on for m.ore than thirty days.^ But the most common examples of healing under blood-scabs are in small wounds, such as are made in bleeding, or more rarely in some compound fractures. The excellent, though nearly obsolete, practice of laying on such wounds a pad of lint soaked in the blood, was a good imitation of the most natural process of their re- pair. If a blood-scab be not formed over a wound, or if such an one have been detached after being formed, then at once a scab may be derived from the serum and lymph that ooze from the surface of the wound. Thus it is commonly with wounds in animaJs that are left to themselves, and in many small wide-open wounds in our own case. Thus, also, I imagine the best healing of superficial burns and scalds is efiected, when the exposed surface is covered with cotton wool or other substance, which, as the oozing fluids become entangled with it, may help them to form a scab. At a yet later period, the pus produced from exposed granulating wonnds may concrete on them, and they will heal under it excluded from the air. Such a process may also ensue in the heahng of ulcers, and has been successfully imitated in Mr. Stafibrd's plan of filling deep ulcers with wax.^ In any case, the healing process is probably just the same as that under scabs of blood or sernm ; but I believe it has not yet been exactly determined what are the changes that ensue in the surface beneath the scab. So far as one can discern with the naked ' In his 'Lectures on Surgery,' in the Lancet for 1832-3, ii. ' Mr. Henry Lee tells me that a similar case has occurred in his practice. An excellent instance of healing under blood-scabs is also related by Dr. Macartney (Treatise on Inflammation, p. 208). ' On the Treatment of the Beep and Excavated Ulcer. 1829. HEALING UNDER A SCAB. 169 eye, the wounded surface forms only a thin layer of outiole on itself ; no granulations, no new connective tissue, appear to be formed : the raw surface merely skins over, and it seems to do so uniformly and not by the progressive formation of cuticle from the circumference towai-ds the centre, as is usual in open wounds. The healing of a wound by scabbing has always been thought a de- sirable process ; and when one sees how quickly, by means of this pro- cess, wounds in animals are bealed, and with how little general disturb- ance, one may well wish that it could be systematically adopted. But to this there seems some hindrance. Many surgeons have felt, as Mr. Plunter did, that the scabbing process should be permitted much oftener than it is, in the cases of both wounds and ulcers ; but none have been able to lay down sufficient rules for the choice of the cases in which to permit it. Probably, the reason of this is that, at the best, in the huma,n subject, the healing by scabbing is an uncertain process. When the scab is once formed, and the wound covered in, it is necessary that no morbid exudation should take place. Whenever, therefore, inflam- mation ensues in a wound or sore covered with a scab, the inflammatory material, collecting under the scab, produces pain, compresses the wounded surface, or forces off the scab, with discomfort to the patient and retardation of the healing. I suspect that the many instances of disappointment from this cause have led to the general neglect of the process of scabbing in the treatment of wounds. The observance of perfect rest, and of the other means for warding off inflammation, will, however, make it a valuable auxiliary in the treatment of wounds, especially of large superficial ones : in the treatment of small wounds, collodion appears sufiioient to accomplish all that scabbing would do ; and in deep wounds, fluid is too apt to collect under the scab.' Such are the several methods of healing observed after wounds of soft parts ; and in connection with them, two subjects remain to be con- sidered — namely, the process of suppuration, and that of the perfecting of scars. Eeserving until a future Lecture (XVI.) the consideration of the ' One of the tiesfc applications of Professor Lister's antiseptic method of treating wounds may be regarded as a means of imitating the healing under a scab, and averting the causes which, in man, too generally spoil the natural process. The covering of a wound, as in a compound fracture, with materials soaked in solution of carbolic acid, excludes all the external air, or at least those organic materials in it that would be injurious. Thr.s the wound is rendered practically air-tight, and may heal without suppuration, simply scarring over. 170 SUPPURATION. textural changes which result in the production of pus, I shall at present show its relations to the healing process, and the points of re- semblance and difference between it and the materials of which granu- lations are formed. Let me remind you that the formation of granulations is not necess- arily attended with the production of pus. I have already referred to this fact in speaking of the formation of subcutaneous granulations, such as are sometimes seen on the end of bones that do not unite, in the ordin- ary way, after simple fractures. Mr. Hunter also expressly describes these cases ; and the same kind of granulations without suppuration may be sometimes seen springing from the ulcerated articular smfaces of bones, in cases of diseased joint without any external opening. However, when granulations are formed on an open wound, there is always suppuration — i.e. an opaque, creamy, yellowish-white or greenish-white fluid, pus, or matter, is produced on the surface of the granulatjons. If the surface be allowed to dry, the pus may form a scab : if it be kept moist, fresh quantities of pus are produced, till the surface of the granulations is covered with the new cuticle. Granula- tions that are skinned over no longer suppurate. The essential constituents of pus are cells, and the liquid (liquor puris) in which they are suspended. In pus produced during healthy granulation, no other material than these may be found. But often minute clear particles, not more than ^^^jm of au inch in diameter, are mingled with the pus-cells. And, when the process deviates from health, we find not only variations in the pus-cells, but multiform mix- tures of withered cells, molecular and fatty matter, free or escaped and shrivelled nuclei, blood-corpuscles, fragments of granular substance like shreds of fibrine, and other materials. All these indicate defects or diseases of pus, corresponding with those of the granulations to which I have already referred. Pus-cells, in their ordinary state, are represented in the following sketch. As shown at A, they are spherical or spheroidal, or even discoid bodies ; the differences in shape depending apparently on the density of the fluid suspending them. In the same proportion as it becomes less dense, they tend to assume the more perfectly spherical shape. They have a uniform nebulous or grumous aspect ; distinct granules, more or less numerous, are commonly seen in them : and they appear more darkly nebulous and more granular in the same proportion as the fluid becomes more dense. Their usual diameter is from ^^ru ^° aroVir ^^ ^^ inch. SUPPURATION. 171 Sometimes a distinct, ciroiilar, dark-edged nuclens may be seen iiv the paler corpuscles ; and, more rarely, two or even three particles Mite a divided nucleus. When, as in the corpuscles B, water is added to pus, it usually penetrates the cells, expanding them, raising up a distinct fine cell-wall, and separating or diffusing their contents. Sometimes the contents are uniformly dispersed through the distended cell, which thus becomes more lightly nebulous, or appears filled with a nearly clear protoplasm in which the minute particles vibrate with molecular movement, while in or near the centre a dark-edged well-defined nucleus may appear. Sometimes, while the cell-wall is upraised, the whole contents of the cell subside into a single ill-defined darkly nebulous mass, which remains attached to part of the cell-wall, looking like a nucleus, but differing from a true nucleus in the characters just assigned, as well as in the absence of the two or three shining particles like nucleoli. Lastly, a few pus- corpuscles appear unchanged by the action of water ; they seem to be merely masses of soft colourless protoplasm, having the shape and appearance, but not the structure, of cells. When dilute acetic acid is added to pus (as in Fig. 23, C), it pro- duces the same effects as water, but more quickly and with a more con- stant appearance of two, three, or four small bodies like nuclei. These bodies are remarkable, though far from characteristic, features of pus- cells. They are darkly edged, usually flattened, clear, hour-glass shaped, or grouped, as if formed by the division of a single nucleus ; and com- monly each of them appears darkly shaded at its centre. When the acetic acid has been too little diluted, these bodies alone may be at first seen ; for the cell-wall and the rest of its contents may be rendered so transparent as to be scarcely visible. If the pus-cells be carefully examined in their living state, neither nucleus nor cell-wall can be recognised, but the cells may be seen to possess the power of spontaneous movement, and pass through various changes of form. They may send forth processes, either blunt, or thread-like, which they can again withdraw and re-assumo the spher- 172 SUPPURATION. oidal form, and in this manner they may change their place.' Bat this power of spontaneous movement is not confined to pus-cells : it has been seen also in the white blood-corpuscles, lymph-corpnscles, and in- deed in rudimentary cell-forms generally, and as the series of phenom- ena exhibited correspond very closely with those seen in Amcsba and other E/hizopods, they have been termed ' amoeboid movements.' Such are the pus-cells found in healthy suppurating wounds. The liquor puris contains albumen, a compound called pyine, regarded by Mulder as identical with tritoxide of protein, occasionally chondrin, glutin, and leucine, abundant fatty matter, and inorganic substances similar to those dissolved in the liquor sanguinis. Pus not distinguishable from that of granulating wounds is formed in many other condition s ; as in inflamed serous and mucous cavities, and in abscesses. In these relations it will be considered in the lectures on Inflammation. But the histories of all cases of the formation of pus concur, with that of suppurating wounds, to the conclusion that pus may be regarded as a rudimental substance ill developed or degenerate ; as a substance essentially similar to the materials of granulations, or to the cells of inflammatory lymph ; but which fails of being developed like them, or, after having been developed like them to a certain stage, degenerates. To illustrate this relation between the pus and the granulations of healing wounds, I may state that the last figure was copied from sketches that I made, at the same time, of some granulation-cells from the walls of a sinus, and some pus-cells from a healthily granulating wound. I choose those sources purposely, that I might be able to com- pare ill-developed granulation-cells with well-constructed pus-ceUs ; and a comparison of them showed that, whether as seen without addition, or as changed by the action of water and acetic acid, they were not to be distinguished from one another. Had I not seen the vessels in the tissue that the granulation-cells formed, I might, in the first examina- tion, have almost thought I was deceived in thinking they were not pus-cells. The six varieties of the appearances of the cells, which are represented, might have been taken from either source ; so might some other varieties : but these may suiEce to show the apparent identity of structure between well-formed pus-cells and ill-developed or degenerate granulation- cells, such as are found in the walls of sinuses and the like ' An account of these phenomena, -vrith figures, may be seen in C. 0. Weber's article, p. 458, already quoted ; also in Dr. Beale's Urinary Deposits, p. 304, pi. xxiii. London, 1869. SUPPUEATION. 173 lialf-morbid struotnres. I do not mean to say, generally, tliafc granala- tion-cells and pns-cells cannot be distingaislied ; for between well-formed granulation-cells, sucli as are found in liealing wounds, and any par- ticles that are usually found in pus, certain distinctions are almost al- ways manifest. The pus-cells are darker, more and more darkly, granular, more various in size, and more various, not in shape, but in apparent structure, more often containing numerous particles, like fatty molecules, more rarely showing a nucleus when neither water nor acetic acid is added, and much more commonly showing a tripartite or ill-formed nucleus under the action of the acid, None, however, of these characters is indicative of essential difference ; and between even the widest extremes there are all possible gradations, till distinction is impossible ; so that when you place, as I have often done, ill-developed or degenerate granulation- cells on one side of the microscope-field, and pus-cells on the other, there is not a form of corpuscle on the one which is not repeated on the other. Degeneracies and diseases of pus-cells and of granulation-cells — in other words, such morbid changes in these morbid products as I referred to at the end of Lecture IX. — result in the production of forms that cannot be distinguished, and that may be taken as evidences of a common origin. From this, one cannot but conclude that the cells of pus from wounds are ill developed or degenerate granulation-cells. Some of them may be degenerate — i.e. they may have been, as granulation-cells, attached for a time to the surface of the granulation-layer, and having lived their time, may, in ordinary course, have been detached and shed, as epithelial cells are from healthy surfaces. They may be thus detached after more or less degeneration, and hence may result some of the modi- fications that they present. But some pus-cells, I imagine (at least in the healing of wounds), may be ill-developed; that is, imperfectly formed of the granulation material, which, being exposed to the air, or being too remote from the supply of blood, cannot attain its due develop- ment, and, in an imperfectly developed state, is soon cast off. The many characters of imperfection or of degeneracy that pus-cells show, accord with this view : such as the general imperfection of their nuclei : the frequent abundance of fatty-looking granules in them ; the large quantity of fatty matter that analysis detects in pus ; and the limitation of the cells to certain forms, beyond which they are never found developed, though none of these forms is more highly organised than that of the youngest or most rudimental granulation-cell. A further eonfii-mation of the opinion that pus-cells sje ill-developed 174 SUPPUEATION. or degenerate grannlation- cells is furnished in tlie cases, to which I shall hereafter I'efer, in which pus-cells are produced after, or to gether with, inflammatory lymph-cells ; as in abscesses, inflamed membranes, and the like. Now such lymph-cells are not distinguishable in apparent structure from granulation-cells, and like these they may show every gradation of form to that of the pus-cell. But it is not only in the cells that we may trace this appearance of the degeneracy or incomplete development of pus. It is equally shown in the fluid part, or liquor pitris, which, unlike the intercellular substance of granulations and inflammatory lymph, is incapable of organisation even when, by evaporation or partial absorption, it assumes the solid form. The liquor puris answers, in its relations to the cells, to the solid and organisable intercellular sabsta,nce of granulations ; and as un- due liquidity is among the most decided marks of ill-formed pus, so the abundance of the blastema, in proportion to the cells, is one of the best signs that granulations are capable of quick development. These considerations may suggest, in some cases, the imperfection of the liquor puris ; and an observation, which any one may easily make, seems to indicate that it may, in other cases, be the product of the degeneration and liquefaction of the solid blastema, as the pus-cells are, in the same cases, of the granulation-cells or inflammatory lymph- cells imbedded in it. If the formation of abscesses be watched, one may see on one day, a large solid and inflamed swelling, firm and almost un- yielding, giving no indication of containing any collection of fluid ; but next day one may detect in the same swelling the signs of suppuration ; the border may feel as firm as before, but all the centre and the surface may be occupied with an ounce or more of pus. And observe, this change from the solid to the liquid state may hare ensued without any increase of swelling. Such an increase must have occurred had the pus been secreted in a fluid state into the centre of the soHd mass ; and the changes cannot, I think, be explained except on the admission that the inflammatory product, which was infiltrated through the tissue in a solid form, has been hquefied : its cells degenerating into pus-cells, its blastema into liquor puris.' ' Such a liquefaction is not that assumed in tlie older doctrines, which held that pus was partly formed of the dissolved materials of the original tissues. The original tissues doubtless remain, unless partially absorbed ; yet there appears to he thus much of liquefaction in the formation of an abscess, that part of the inflammatory product, first formed as a soft solid, degenerates and becomes fluid. SUPPURATION. 175 Let "US now consider tlie case of a wound completely healed, and the scar that occupies its place. It is hard to describe in general terms the characters of scars, vary- ing as they do in accordance with the peculiar positions, and forms, and modes of healing of wounds. But two things may be constantly observed in them : namely, their contraction, and the gradual perfect- ing of their tissues. A process of contraction is always associated with the development of granulations. Mr. Hunter has minutely described it, and preserved several specimens to illustrate it : among which are two stumps,' in which its occurrence is proved by the small size of the scars in com- parison with that of the granulating surf aces which existed before them. This healing of stumps, especially after circular amputations, will al- ways show the contraction of the granulations, even before the cicatrix is formed ; for one sees the healthy skin dra-mi in and puckered over the end of the stump before any cuticle is formed on the granulations, except perhaps on the very margin. And many injuries, but especially burns, show the contraction of the scar continuing long after the ap- parent healing is completed. To what may we ascribe this contraction of both the granulations and the scars ? It has been regarded as the result of some vital power of contraction ; and possibly it may be so in some raeasure. Tet, on the whole, it seems rather to be the necessary mechanical effect of the changes of form and construction that the parts undergo. The same change ensues in the organisation of inflammatory products — as, e.g., in false membranes, indui'ations, thickenings of parts, and the like. Now, in all these cases, the form of the cell, while elongating into a fusiform bodj'-, is so changed that it will occupy less space. The whole mass of the developing cells become more closely packed, and the tissue that they form becomes much drier ; with this also, there is much diminution of vascularity. Thus, there results a oon.siderabIe decrease of bulk in the new tissue as it develops itself; and this decrease, be- ginning with the development of the granulation- cells, continues in the scar, and, I think, sufficiently accounts for the contraction of both, without referring to any vital power. The force with which the contraction is accomplished is often enor- mous. One sees its result in the horrible deformities that follow the healing of severe burns. Deep scarred and seamed depressions, even of ' Kris. 28 and 29 in the Museum of the College. 176 SCABS. the bones, may be produced by the contraction of granulations and scars over them. The whole process shows the error of snch expressions as 'filling tip with granulations,' commonly applied to deep healing wounds, as ii granulations, increased in thickness till they attained the level of the upper margins of deep hollows. The truth is, that, even in the deepest open wounds, the granulation-layer is, as usual, from one to three lines thick ; and that, when such a wound grows shallower in healing, it is not by the rising of the granulations, but by the lowering of its margins. The granulations and the scars of deep open wounds remain alike thin and depressed. The improvement and perfecting of the tissue of the scar is, again, a very slow process. It is often thought remarkable that nerves and some of the higher tissues should require so long time for their repair ; but scarcely less is necessary for the perfecting of a common scar. The principal changes by which it is accomplished include the removal of all the rudimental textures, the formation of elastic tissue, the improvement of the fibrous or fibro-cellular tissue, and of the new cuticle, till they are almost exactly like those of natural formation ; and the gradual loosening of the scar, so that it may move easily on the adjacent parts. The scar also becomes paler and more shining than the surrounding unaffected skin, for the numerous vessels, which the granulating surface possessed, gradually disappear, and are, for the most part, converted into fibrous cords. All these changes are very slowly accomplished. One sees their effects, it may be, only after the many years in which, as it is said, the scars of childhood gradually wear out; i.e., in which the new-formed tissues gradually .acquire the exact similitude of the old ones. Thus, the remains of the rudimental connective tissue, imperfectly developed, may be found in apparently healthy scars of ten months' duration. After second operations, in which the scar of some foriner wound was removed, I have still found imperfectly-developed granulation-cells in the tissue of a scar. Elastic tissue also, I think, is not commonly formed in the first construction of a scar, but appears in it sometimes as much as twelve months after its first formation, and then gives it the common structure of the mixed white fibrous and yellow elastic tissues which exist in the cutis. But an occurrence which may appear more singular than this slow perfecting of tissues, is, in all good scars, as they are called, that gradual loosening of the tissue which at first unites the scar to all SCARS. 177 the adjacent parts. Thus, in sttch a wound as is made for tying a deep artery, or in lithotomy, at first the new tissue, the tissue of the scar, extends down to the bottom of the wound, equally dense in all parts, and fastening the skin to the parts at the very deepest portion of the wound. But after a time this clears up. The tissue of the scar in the skin becomes more compact and more elastic ; but that beneath it becomes looser and more like natural connective tissue, and the morbid adhesions of one part to another are freed. So, after injuries or diseases, followed by sears about joints, the stiflFness depending on the adhesion of the scar to the deeper tissues gradually decreases ; and so, iu like manner, the scars of burns often become gradually and of themselves more pliant, and the parts which they held become more freely movable, though sometimes scarcely seeming to change for a year after the first healing of the injury. Now, in all this gradual return of tissues to the healthy state, we may trace, I think, a visible illustration of the recovery from the minute changes of disease. In all there is a gradual approach of the new particles that are successively produced to a nearer conformity with the specific character of the parts they should replace, till repair becomes almost reproduction. And how, let me ask, can all this be reconciled with any theory of assimilation ? How can assimilation alter the characters of a scar ? how make one part of it assume one character, and another part a character quite different, till at length, that which looked homogeneous, as a mass of new-formed tissue, acquires in separate parts the characters of the several tissues in whose place it lies, and whose ofi&ce it is destined, though still defec- tively, to discharge ? 178 EKPAIE OF FRACTURES. LECTURE XI. THE BBPAIR OF FRACTUKES. The necessity, wMcb. I have felt in the preceding lectures, of describ- ing the healing process as it is observed in a few typical examples, is increased when I come to the consideration of the repair of fractures. A Tolume would not suffice for all that could be said of it ; for there are no examples of the reparative process which present so many features of interest as this does, whether we consider its practical importance, or the wide field which it offers alike for the science and for the art of sur- gery, or the abundant illustrations of the general principles of recovery from injury which are present in every stage of the process, or the perfect evidences of design which it displays — of design that seems nnlimited in the variety and point with which it is adapted to all the possible diversities of accident. To consider the repair of fractures completely, in any of these views, would be far beyond my purpose, and farther beyond my ability. I shall therefore limit myself almost entirely to an account of the repair of the simple fractnres of long bones. What is true of this will he so nearly true of the repairs of other fractures, that a few words may sufiB.ce in reference to the chief modifications of the process in them. Moreover, I shall in general describe only what occurs in the adult human subject. The injury inflicted in the fracture of a long bone is rarely limited to the bone. The two or more fragments, driven in opposite direc- tions, penetrate the adjacent tissues, wounding and bruising them, and giving rise to bleeding of various amount. Provided all these injuries are subcutaneous, and the air has no access to the damaged parts, their repair is perfectly, though slowly, effected. It is not unfrequent, in recent fractures, to find portions of muscle or other soft parts com- pletely crushed by the bones, or even, in minute fragments, enclosed in the reparative material or the inflammatory products ; and yet, when similar fractures are examined a year or more after their occurrence. REPAIR OF FRACTURES. 179 the tissues round the bone appear quite normal in their structure, however disturbed they may be in their relations. The periosteum is rarely much damaged in fractures of long bones. It is seldom stripped off the broken ends. Commonly, it is cleanly rent across at the same level as the bone is broken at, and maintains its close union, having only its fibres somewhat frayed or pulled from their natural direction. Sometimes, indeed, it remains entire, even in extensive fractures ; and in this case, thickening, it contributes to the security of the repair of the injury. The extravasation of blood and of blood-stained fluid about frac- tures is not only uncertain in amount, but unequal in the several tissues. Its abundance in the subcutaneous tissue is often so remarkable as to be among the useful signs for diagnosis in cases of doubtful fracture near joints ; but in the deeper soft tissues less is shed ; and, commonly, in the periosteum, near the broken ends of the bone, only a few spots of blood and a little serous fluid are seen. I have already spoken (p. 137) of the manner in which the extravasated blood is disposed of ; and since it rarely appears to take part in the reparative process, I shall make no further mention of it. Some days elapse, after a fracture, before any clear marks of a reparative process can be found. An early consequence of the injury appears to be the production of a small quantity of inflammatory lymph ; so that the fibro-cellular tissue and the periosteum in and near the seat of injury appear raore succulent than is natural, being in- filtrated with a serous looking fluid, in which are cells like those of granulations or lymph. In bad cases this may increase, atad add to the swelling that is often seen to augment in the second or some later day ; but, in better instances of repair, and wheti the parts, eVen though much injured, are kept at rest, I think the production of inflammatory lymph usually ceases after the second or third day, and that then some days pass before the proper reparative material is produced. The state of the injured parts during this period of calm, or of incubation, is probably like that observed in wounds of soft parts (p. 153). Its duration is uncertain, but I think, in the adult, is rarely less than one week or more than two. In this long period of inaction we find the first contrast between the repairs of fractures in man, and in the animals that have been used for experimental inquiry into the process, as dogs, rabbits, pigeons, and others. In any of these, an abundant reparative material will be .480 EEPAIE OF FRACTURES. produced, and organised into cartilage or bone, in a time little longer than elapses before the first commencement of the process in a man.' "We cannot, therefore, from the rapidity of repair in the lower animals, form any just calculation of its rate of progress in ourselves. The proper reparative process, commencing after this period of rest, may usually be divided into two chief parts ; namely, the process of uniting the fragments, and that of shaping or modelHng them and their combining substance. The uniting and the modelling parts of the pro- cess are so different in nature and in time, that they may well be considered separately. They are comparable with the forming and the subsequent perfecting of the scars of wounded soft parts ; and in the union of fractures, even more evidently than in any other instance of repair, we may note how safety is first provided for, then symmetry ; how the welfare of the individual is first secured, and then the confor- mity of the repaired part to the typical or specific form ; for the model- ling scarcely begins before the uniting is completed. The union of fractures is commonly effected by the organisation of new material connecting the fragments. Sometimes, indeed, immediate union occurs. When portions of bone arc placed and held in exact apposition, they may be united without any new material being formed for their connection ; a continuity of tissues being restored, as in the cases of healing by immediate union of soft parts. But this is rare, and has not yet been suflBciently studied. The material produced for the more, usual method of repair of simple fractures — the Callus, as it is called when it has become firm or hard — is, I think, in the first instance, not visibly different from the material formed for the repair of other subcutaneous injuries. Its pe- culiarity is shown in the direction and end of its development ; and, in this respect, the repair of fractures supplies an extreme case of the variety of ways through which the same end of development may be attained. Both the medullary tissue and the periosteum of the fractured bone take a part in its formation, but more especially the latter, the deeper layers of which, lying next the bone, seem to be more particu- larly concerned in the production of new osseous tissue.^ ' See Nos. 418, 419, 420, in the Museum of the College; and Series iii., Nos. 69, 70, 71, etc., in that of St. Bartholomew's. ' The share which the perioatenm takes in the production of new bone was indicated by Du Hamel, and experimentally proved many years ago by JVIr. Syme. Of late years, Flourens, Oilier, Demarquay, and others, have corroborated these experiments by many remarkable instances. In cases of necrosis, more especially in children, the whole lengtli of the shaft of a long bone, between its terminal epiphyses, may be re- EEPAIE OF FRACTLTRES. 181 In its first production the reparative material is a dimly-sliaded or granular substance, or perhaps, at a later period, it is ruddy, elastic, moderately firm, and succulent, like firm granulation-substance. Of the manner in which it is placed, in the space and in the tissues around or between the fragments to be connected, I will speak presently. At first it has none of the firmness belonging to the ' callus ; ' this, however, it soon attains, as it makes progress towards being transformed into bone. Its ossification, as I have said, may be accomplished through several transitional forms of tissue, which might be distinguished as so many varieties of callus, if the term be worth retaining. It may become, before ossifying, either fibrous or cartilaginous, or may assume a structure intermediate between these ; and, in either of these cases, ossification may ensue when the previous tissue is yet in a rudimental .state, or may be delayed till the complete fibrous or cartilaginous struc- ture is first achieved. I cannot tell the conditions which will determine, in each case, the route of development towards bone that the reparative material will take ; nor in what measure the differences that may be observed are to be ascribed to the seat or nature of the injury, or to the condition of the patient. All these things have yet to be determined ; and I believe that years of patient and well directed investigation will be requisite for them. I can do little more than point out the modes in which the ossification may be accomplished. And, first, it may be accomplished through perfect fibrous tissue. Thus I found it in a case of fracture of the lower part of the femur after six weeks, and in a fracture of the radius after about nine weeks; thus, too, I think, whatever new bone is formed after fractures of the skull is developed ; and thus one may find, in the neighbourhood of fractures and other injuries of bone, ossifications of interosseous fibrous membranes, and of the tissue of the periosteum, or just external to it.i But, secondly, the new bone may be formed by ossification of the fibrous tissue in a rudimental state, as when granulations or inflamma- tory products ossify. The process may be often seen in the union of stored if the periosteum be preserred. But in tlieso and other cases of extensive reparation of bone, it is probable that not merely the periosteum, but the connectivo tissue generally around the seat of repair, may assist in the reproduction of the uow osseous tissue. ' The thin plate of bone -which closes in the exposed medullary canal of the end of a fractured long bone, where one fragment overlaps another, will usually, I think, present a good example of ossification of fibrous tissue. 182 REPAIR OF FRACTURES. compound fractures, or of simple ones whea much inflammation has been excited. But, best of all, though here only for illustration of ■what may occur in fractures, ossification in granulations may be ob- served, when bone is formed in the mushroom-shaped mass of granula- tions that is protruded through the medullary canal of a bone sawn across in an amputation.' In all these cases there appears to be a direct transformation into bone, without the intervention of either cartilage or perfect fibrous tissue. The ossification of nucleated blastema or protoplasm, such as I have described as a rudimental form of fibrous tissue, may also be seen in simple fractures ; and my impression is, that it is an ordinary mode of ossification in simple fractures of adult long bones that unite well and quickly. In such a case, in a fracture of the tibia of five weeks' date, I found, in long-continued examinations, that the bone is formed with- out any intermediate state of cartilage ; a finely and very closely granu- lar osseous deposit taking place in the blastema, and gradually accumu- lating so as to form the delicate yet dense lamellEe of fine cancellous tissue. The nuclei of the blastema appeared to be enclosed in the new- forming bone, and I thought I could trace that they became the bone- corpuscles ; but I could not be sure of this. Tet the belief is justified by the opinion now generally entertained that, in the normal develop- ment of bone out of fibrous membrane, the cells of the connective tissue become the corpuscles of the bone. Thus, the new material produced for the repair of fractures may be ossified through an intermediate fibrous stage. In other instances it may pass through a cartilaginous stage. In animals, perfect cartilage, with its characteristic homogeneous intercellular substance, its cells, and all the characters of pure foetal cartilage, may be produced. Through the ossification of such cartilage, Miescher^ and Voetsch,^ and others, describe the repair of fractures as accomplished in dogs, pigeons, and other animals ; and A. Wagner"* has noticed, in his experiments on the resection of bones in rabbits and pigeons, a process of repair of a closely corresponding nature. I have not yet found the very same pro- cess in the human subject ; but I should think it would occur in favourable instances of simple fractui-e in children. In youths and ' College Museum, Nos. 552, 553. ^ De Inflammatioiie Ossium, 1836. ' Die Heilung der KnocJienbruche, 1847. * Essay translated for the New Syd. See., 1859. The statements in the text are also coniirmeJ generally by Wedl in his Pathological Histology. EEPAIE OF FEACTURES. 183 adults, I liave found only varieties of fibrous cartilage; and these have presented mimerous gradations from the fibrous towards the perfect cartilaginous structure. In diiFerent specimens, or sometimes even in different parts of the same, the reparative material has displayed, in one, fibrous tissue, vt^ith a few imbedded corpuscles, like the- large nearly round nuclei of cartilage-cells ; in another, a less appearance of fibrous structure, with more abundant nucleated cells, having all the characters of true cartilage- cells ; and in a third, a yet more nearly perfect car- tilage.' Through any of these structures the reparative new bone may be formed. It may be formed, first, where the reparative material is in contact with the old bone, and thence extending, it may seem as if it grew from the old bone ; or it may be formed in the new material, in detached centres of ossification, from which it may extend through the intervening tissues, and connect itself with the old bone. (See Figs. 24 and 26.) The new bone, through whatever mode it is formed, appears to ac- quire quickly its proper microscopic characters. Its corpuscles or lacunse, being first of simple round or oval shape, and then becoming jagged at their edges, subsequently acquire their canals, which appear to be gradually hollowed out in the preformed bone, as minute channels communicating with one or more of the lacunte. The laminated canals for bloodvessels are later formed. At first, all the new bone forms a minutely cancellous structure, which is light, spongy, soft, and succu- lent, with a reddish juice rather than marrow, and is altogether like foetal bones in their first construction. But this gradually assimilates itself to the structure of the bones that it repairs ; its outer portions assuming a compact laminated structure, and its inner or central por- tions acquiring wider cancellous spaces and a more perfect medulla. It acquires, also, a defined periosteum, at first firm, thin, and distinctly lamellar, and gradually assuming toughness and compactness. But, in reg9,rd to many of these later changes in the bonds of union of fractures, ' I do not describe the minute methods of ossification occurring in the callus, or reparative material ; for my opportunities of studying it in man have been too few for me to conclude from ; and, although I have seen nothing opposed to the belief that the normal methods of ossification are imitated, yet the process seems capable of so many modifications that I think it would not be safe to adapt, unconditionally, to the case of the reparative material in man, such conclusions as are drawn from the normal ossification of his skeleton, or from the ossification of the reparative material in lower animals. 184 EEPAIE OF FRACTUEES. there are so many varieties in adaptation to the pecnliarities of the cases, that no general acconnt of them can be rendered. A subject of chief interest in the repair of fractures is the position of the reparative materia}; and in relation to this we find a greater difference than any yet mentioned between the processes traced res- pectively in man and in the animals submitted to experiments. There are two principal methods according to which the reparative naaterial, or callus, may be placed. In one, the broken ends or smaller fragments of the bone are com.pletely enclosed in the new material ; they are ensheathed and held together by it, as two portions of a rod might be by a ferrule or ring equally fastened around them both. In such a case, illustrated by Fig. 24, the new material, surrounding the fracture, has been usually called ' provisional callus,' or ' external caUns ;' but the term ' ensheathing callus ' will, I think, be more explanatory. In the other method (as in Figs. 25 and 26), the new material is placed only between those parts of the broken bone whose surfaces are op- posed ; between these it is inlaid, filling the space that else would exist between them, or the angle at which one fragment overhangs another, and uniting them by being fixed to both. Reparative material thus placed may be called ' intermediate callus.' In either method (as in Figs. 24 and 25), there is usually some reparative material deposited in and near the broken medullary tissue ; and this may be still named 'interior callus.' The method of repair with an ensheathing or provisional callus is rarely observed in man, but appears to be frequent in fractures of long bones in animals.' From these it has been admirably described by Dupuytren and others. The chief features of the process are as follows (omitting dates, which, have not been ascertained in man, and cannot well be calculated for him.) : — In the simplest case, when the fragments (as represented in this dog's tibia : Fig. 24) lie nearly in apposition, and nearly correspond, ' Eren in animals it is not constant. To obtain irliat would be called good specimens of provisional callus, the injuries must be inflicted upon youug animals, and among these I cannot but suspect that particular instances have been selected for description ; those in which less callus was formed having been put aside as imperfect instances of repair, though, in truth, they may have displayed the more natural process. Such good specimens are, in the Museum of the College, Nob. 418 to 426 ; and in that of St. Bartholomew's, Ser. iii. 69, 70, 71, 96, 81, 82, 92, 106. Fig. 24 is drawn from No. 60. It is very desirable to obtain examinations of fractured long bones recently united in young children ; for it is probable that in these the process would be very like that described from the experiments on animals. No opportunity for such an examination has yet occurred to me. EEPAIR OF FEACTUEES. 185 the reparative material acc-amulatee at once around and within them, and in any interspaces that may be left between them. That around them — that is, the ensheathing callus — forms most quickly and in greater abundance, and lies chiefly or solely between the wall of the bone and the periosteum, which is thus lifted up from the wall, the bloodvessels that passed from it into the bone now passing to their destinations through the callus. The distance from the broken ends to which the callus extends up each fragment is uncertain : in the long bones of dogs, and the ribs of men, - it is usually about half-an-inch. The thickness of the callus is greatest at a little dis- tance from the plane of the fracture : exactly in that plane it is usually less thick than either above or below ; so that, even when it is ossified, it is often marked with a slight annular constriction. The interior callus fills up the spaces in the cancellous tissue, extending in the medullary canal of each fragm.ent to a distance somewhat short of that to which the ensheathing cal lus reaches. At the end of each fragment there is usually an abrupt contrast between the firm repa- rative material that forms this interior callus and a softer substance, like that of granulations, which remains between the fragments even till the callus without and within is quite ossified. As the section drawn in Fig. 24 shows (Ser. iii. 69), the reparative material is abundant and well developed both round and within the fragments ; but be- tween them, i.e. in the plane of the fracture, it is sparingly formed and soft, so that the fragments, if the ensheathing callus were removed, would be no longer held together : they are, in fact, combined long before they are united. The ossification of the ensheathing callus is accomplished chiefly or solely by outgrowth of bone from the fragments on which it is placed. Here, also, the same method of progress is observed, in that the for- mation of new bone extends gradually towards that part of the callus which exactly corresponds with the plane of the fracture. This part of the callus is last ossified ; but, at length, its ossification being com- plete, the fragments are combined by and within a sheath or ferrule of rig. 24. 186 REPAIK OF FEACTUEES. new bone. The interior callus, ossifying at about the same time, con- solidates the cancellous tissue of the fragments, and, at a later period, unites them. The walls remain still longer disunited. The ossified callus is, indeed, sufficient to render the bone fit for its office, but it re- tains the nearly cancellous tissue of new bone, and it is still only pro- visional ; for when the walls o£ the fragments are themselves united and their continuity is restored, all, or a part, of the external callus is removed, and the cancellous tissue loses its solidity by the removal of the internal callus. Such is the process of repair with an ensheathing callus. It is, as I have said, usual in animals ; but in man I have never seen its occur- rence as a natural process in any bones but the ribs. In these it may be traced as perfectly as I have described it from the instances of repaired fractures of long bones in the rabbit and dog. Sometimes, indeed, a similar process occurs in otlier human bones. I have seen it in the clavicle and humerus ; ' but in both these capes the more proper mode of repair had been dis- turbed by constant movement of the parts, and in the humerus the process had manifest signs of exaggeration and disease. The normal mode of repair in the fractures of human bones is that which is accomplished by ' intermedi- ate callus.' The principal features of difi"erence between it and that just described are— (1), that the repar- ative material or callus is placed chiefly, or only, between the fragments, not around them ; (2), that when ossified it is not a provisional, but a permanent, bond of union for them ; (3), that the part of it which is external to the wall of the bone is not exclusively, or even as if with ' Museum of St. Bartholomew's, Ser. iii. 92, 65, and 66. The clavicle was broken twelve weeks before death ; but the fracture was not detected, and the fragments were allowed to move unrestrained. The humerus was taken from a man who died some weeks after the fracture, and whose arm had, for several days after the injury, been the seat of severe spasms. See Mr. Stanley's Illustrations of Diseases of Bones, pi. xxiii. fig. 3. REPAIR OF FRACTURES. 187 preference, placed between the bone and tlie periosteum, but ratber in the tissue of the periosteum ; or indifferently, either in it, beneath it, or external to it. When the fragments are placed in close apposition and correspond- ence, they may, I believe, be joined by immediate union ; but if this do not happen, a thin layer of reparative material is deposited between them ; it does not, in any direction, exceed the extent of the fracture ; neither does it, in more than a trivial degree, occupy the medullary canal ; but, being inlaid be- tween the fragments, and there ossifying, it restores their continuity. The pro- cess may be compared with that of union by primary ad- hesion. When, as more commonly happens, the fragments, though closely apposed, do not exactly correspond, but at certain parts project more or less one beyond the other, the reparative material is, as in the former case, inlaid be- tween them, and to a slight extent in the medullary canal ; / ' but it is also, in larger quan- jf ' tity, placed in the angles at If which the fragments over, hang one another. Its posi- tion is, in these cases, well shown in the specimens drawn in Pigs. 25 and 26. In the fractured radius ' (Fig. 26) the carpal portion, laterally displaced, pro- jects beyond the radial margin of the upper and impacted portion ; and the angle between them is exactly filled, without being surpassed, by a wedge-shaped mass of reparative material. So, but less perfectly, is the angle on the ulnar side. In the fractured femur ^ (Kg. 26), with great displacement of the fragments, the same rule is observed ; the in- ' Museum of St. Bartholomew's, Ser. iii. No. 04. 2 The same Museum, Ser. Hi. Ko. 103. Fig. 26. 188 REPAIR OF FRACTURES. terspace between the fragments, and parts of the angles at -which the one projects beyond the other, are filled with partially ossified repara- tive material. In neither case is there an ensheathing callus, in neither is any reparative material placed on that aspect of the one fragment which is turned from the other. Lcistly, when the fragments neither correspond nor are apposed, ■when one completely projects beyond or overlaps another, and when, it may be, a wide interval exists, still the reparative material is only placed between them. It just fills the interval ; it does not even cover the ends of the fragments, or fill any part of the medullary canal ; much less does it enclose both the ends of the mutually averted surfaces, as the provisional callus would in a similar fracture in a dog or a rabbit ; it passes, bridge-like, from one fragment to the other, and thus when ossified combines them. Thus it appears in the fractured femur, part of which is represented in fig. 27.' The three instances which I have cited, of different relative posi- tions of the fragments, may suffice as examples of classes in which nearly all simple fractures of long bones might be described. But, whether the displacement were like either of these, or of any other kind, I have seen no examples (other than the exceptions already men- tioned) in which the reparative materia,l has been placed according to a different method.^ It is always an intermediate bond of union ; it is inlaid between the fragments ; and when formed in largest quantity, is only enough to smooth the chief iiTegularities, and to fill up the interspaces and angles between them. And, regarding the par- ticular position which it may in each case occupy, I do not know that it can be more exactly described than by saying that it is deposited ' Museum of St. Bartholomew's Hospital, Ser. iii. No. 98. ' I exhibitedat thislectureallthe spocimensof fractures examined -within six months of the injury that are contained in the Museums of the College and St. Bartholomew's ; and they all, with the exceptions already mentioned, exemplified this account of the repair b-v intermediate callus, and of the absence of provisional or ensheathing callus. They included a radius, four weeks after the fracture ; another, four or five weeks ; a tibia, five weeks ; a femur, six weeks ; another of the same date ; a third about eight or nine weeks ; a radius, of somewhat later date ; a tibia, eight weeks ; a fibula, eleven weeks ; a tibia, twelve weeks ; a tibia, sixteen weeks after the injury ; and many others of various but unknown dates, all in process of apparently natural repair. Since the lecture was given, the description has been con- firmed by many examinations by myself and others. My conclusions respecting the absence of ensheathing callus in the ordinary repair of fractures, are fully confirmedby the observations of Dr. F. Hamilton, which were conducted at the same timp as mine, and led him, independently, to the same conclusion. See his Essay in the Bttffaln Medical Journal tov Fehma-Ty 1853; and PracHcal Treatise on Fractures and Dislocations, Philadelphia, 1863. REPAIR OF FRACTURES. 189 whore it is most wanted for the strengthening of the bono ; so that, wherever would be the weat part, if unhealed, there is the new material placed in quantity as well as in position just adapted to the exigencies of the case, and restoring, as much as may be, the original condition and capacities of the bone. If, now, it be inquired why this difference should exist in the cor- responding processes in man and other animals, I believe it must be ascribed principally to two causes — ^namely, the quietude in which fractures in our bones are maintained, and the natur&lly greater tendency to the production of new bone which animals always mani- fest. Even independently of surgery, in the case of fractures of the lower extremity, the human mode of progression almost compels a patient to take rest : and in fractures of the upper extremity, the cir- cumstances of human life and society permit him to do so far more than animals can. The whole process of repair is, therefore, more quietly conducted ; and, as we may say, there is comparatively little need of the strength which the formation of provisional callus would give a broken limb. The exceptions to the rule, of difference in the repair of human bones and those of animals, confirm it as thus explained ; for they are found in the ribs, which are certainly never kept at rest during all the time necessary for repair after fracture, and in bones of which, from various causes, the repose of the fragments has been disturbed, or which have the seats of disease, with inflammatory formation, during or subsequent to the reparative process. The comparative restlessness of animals is, however, I think, not alone sufiicient to account for all the difference in the processes. The remainder may be ascribed to their greater tendencjy, in all circum- stances, to the formation of new bone. Not in fractures alone, but in necrosis this is shown. It is very rarely that such quantities of new bone are formed even in children, as are commonly produced after necrosis of the shafts of bones in dogs or other animals ; nor is there in the human subject any such filling up of the cavities from which superficial sequestra have been separated, as the experiments of Mr. Hunter showed, after such exfoliations from the metatarsal bones of ' Museum of tlie College, Nos. 6-11 to 653. The denial of the formation of an enslieathing callus in the repair of fractures is sometimes met by the statement that such a callus can be often felt during life. The deception is produccil either by thickening and induration of the Soft parts around the 190 REPAIE OF FRACTUEES. It remains, now, that I should describe the latter part of the repair of fractures — that which consists in the shaping or modelling of the fragments and of their bond of union. Omitting the removal of the provisional callus, where such an one has been formed, this modelling is best observed when there has been much displacement of the fragments. In these cases, the chief things to be accomplished are — 1st, the removal of sharp projecting points and edges from the fragments ; 2ndly, the closing or covering of the exposed ends of the medullary tissue ; 3rdly, the forming a compact external wall, and cancellous interior, for the reparative new bone ; and lastly, the making these continu- ous with the walls and cancellous tissue of the fragments. The first of these is effected by the absorption of the offending points and angles ; and an observation sent to me by Mr. Delagarde tells much of the process : ' A patient in the Exeter Hospital had a bad comminuted fracture of the leg, and a long spike of the tibia, including part of its spine, could not be reduced to its exact level, but continued sensibly elevated, though in its due direction. At the end of five weeks (union having taken place) the end of the spike began to soften ; at six, it was quite soft and flexible, like a thin cartilage ; at the conclusion of the seventh week it was blunt and shrunken. Six months later, the cartilaginous tip had disappeared, and the spike was rounded off.' I have since, in similar cases, seen the same process repeated. They seem to show that the absorption of the bone is accom- plished, as Mr. Hunter described it in cases of necrosis, by removing first the earthy matter, and then the softened remains of animal substance. fracture ; or by the two overlapping ends of the fragment heing grasped at once ; or, much more rarely, by new bone aocumulated about the fragments in consequence of inflammation. EEPAIR OF PKACTURES. 191 Tlie closing or oovering-in of the parts of tlie broken medullary tube, wbicb are exposed in fractures with much displacement, is slowly accomplished by the formation of a thin layer of compact bone, like that which covers the cancellous tissue at the articular ends of bones. It is well shown in the original of Fig. 27.' In a fracture of the femur, after six weeks, I have seen the exposed medullary tube covered in with a thin fibrous membrane, tense like a drum-head, new formed, and continuous with the periosteum. The permanent closure appears to be effected by the ossification of such a membrane; and the new bone becomes smoothly continnous with the rounded and thinned broken margins of the walls of the old bone. So are the ends of stumps covered in ; and neither in these nor in fractures have I seen new bone extending into the medullary canal, as if formed by the ossi- fication of an internal callns. The same sketch shows the nearly-completed formation of distinct walls and medullary tissue in the bridge of new bone connecting the two fragments of the femur. At an earlier period we may be sure that all this new bone was soft and cancellous ; it has now acquired the textures proper to the bone which it repairs, and, as if to complete its conformity with the structures among which it was thus, by acci- dent, introduced, the process was begun by which the new and the old compact and medullary tissues would become respectively continuous. Already those parts of the walls of the shaft that intervene like par- titions, separating the new from the old medullary tissues, are thin, uneven on their surfaces, and in their interior half-cancellous. At some later time, as other specimens show, they would have been reduced to mere cancellous tissue, and the repair of the fracture would have been completed, crookedly indeed, but with unbroken continuity of tissue. To adapt the foregoing account to the case of compound fractures, it is, I believe, only necessary (so far at least as the normal process of repair is concerned) to say that the reparative material is more mingled with products of inflammation ; that that part of it which is formed within reach of the air, or in a suppurating cavity is developed into bone through the medium of granulations, like those formed in open wounds of soft parts ; and that the whole process of repair is, generally slower, less secure, and more disturbed by morbid growths of bone, and other effects of what has been named ' ossific inflammation.' ' from tlio Museum of St. Jjartliolomow's, Sor. iii. No. 98. 192 EEPAIR OF FEACTURES. Tlie data, at present collected, concerning tlie times in wHcli the several parts of tLe reparative process are usually completed after frac- tures of adult human bones, are not sufficient for more than a general and approximate estimate. They may be thus generally reckoned. To the second or third day after the injury, inflammation in and about the parts ; thence to the eighth or tenth, seeming inaction, with subsidence of inflammation ; thence to about the twentieth, production of the re- parative material, and its gradual development to its fibrous or cartilaginous condition ; thenceforward its gradual ossification, a part of the process which is, however, most variable in both its time of commencement and its rate of progress, and which is, probably, rarely completed before the ninth or tenth week, although the limb may have long previously recovered its fitness for support or other use. From this time the rate of change is so uncertain, that it is impossible to assign the average time within which the perfection of the repair is, if ever, accomplisbed. The consequences of failure in the process of repair may be illus- trated by what I have described as its normal course. In a large part of the oases of ununited fracture the fragments are connected by fibrous or fibro-cartilaginouB tissue, inlaid between them. Such is the defec- tive union of most cases of fracture of the neck of the femur within the capsule, and of the olecranon and the patella when their fragments are not held close ; and such a defect may occur in any long bone. It is an example of arrested development of the reparative material; and may be, in this respect, compared with the condition of granulations whose cells persist in their rudimental form. Every other part of the process may be complete ; but this part fails, and the fragments are combined by a yielding, pliant, and almost useless bond. In other cases, the failure seems to occur earlier. No reparative material is formed, and the fragments remain quite disunited. This may be the result of accidental hindrances of the normal reparative process ; but it sometimes appears like a simple defect of formative power : a defect which, I believe, cannot be explained, and which seems the more remarkable when we observe the many changes which may at a later time be effected, as if to diminish the evil of the want of union. Thus, commonly, the ends of bones thus disunited become covered with a thin layer of fibrous tissue, polished as if with a covering of epithelium, and as smooth as an articular surface : similar smooth linings form in the cavities that enclose them, the tissues immediately EEPAIE OF FEACTtJKES. I93 around tBem become condensed and fibrous ; and thus, at length the ends of the fragments are brought to the imitation of a joint, in which they may move without mutual injury. Or else, in the place of such a false joint, the end of each fragment has a kind of bursal sac formed on it, protecting the adjacent parts from injury in its movements. But, much as may be thus accomplished, new bone is not spontaneously produced. As the result of disease it may be formed ; and in this case it is often formed uselessly and without evident design, in heaps or nodules about the ends of the fragments ; yet it is of such disease that surgery may often make bappy use when it can excite inflammation of the fragments, and so hold them close that the new bone may grow between or around them, and fasten itself to both." ' It -wiW diminish the defects of the foregoing description of the repair of frac- tures, which I have drawn almost entirely from my own observations, if I sub- join a list of the works especially or chiefly devoted to this subject, in which the reader may find the best help to a larger knowledge of the subject — Dupuytren ; Expos^ de la doctrine de M. Dupnytren sur le Cal, par Sanson. Ill Journ. Univ. des Sciences Merlicales, t. xx. Breschet: Recherches .... sur la Formation du Cal; Thise. Paris, 1819. Howship : ' On the Union of Fractured Bones.' Med.-Chir. Trans, vol. ix. Miescher : Be Ivflammatione Ossium eorumque Anatome. Berlin, 1836. Flourens : Sur le Siveloppement des Os et des Dents. Paris, 1842 ; and Theorie Experimentale dela ForTnation des Os. Paris, 1847. Lebert: 'Sur la Formation du Cal.' In his Physiologie Pathologigue, t ii. Paris, 1845. Voetsch: Vie Heilung der Knoch^^ibruche. Heidelberg, 1847. Stanley : Illustrations of the Effects of Disease and Injury of the Bones, p. 27, 1849. Malgaigne : Traite des Fractures et des Luxations, t. i. Paris, 1 847- Dusseau : Ondersoek van het Beenweefsel en van Verbeeningen in zachte Deelen, Amsterdam, 1850. Dusseau : ' De Oallasvorming en de genezing van Beenbreuking,' in the Neder- landsch WeeJMad, 1851. From an extract in the Nederlandsch Lancet, Mai 1852, I judge that his account confirms, in all essential particulars, what I have written. Schweigger — Seidel, Disquisitioncs de Callo. Halle, 1858. Oilier: 'On the Artificial Production of Bone.' Brown-Sequard's Journ. de Fhys. Jan. 1859. E. Gurlt: Handbuch der Lehre v. d. Knochenbruchen. Frankfort, 1860. R. Volkpiann : ' Verletzungen der Knochen,' cap. xxxix. In Billroth und v. Pitha's Handbuch der Chirurgie, ii. B. Ab. ii. 1865. 194 HEALINa QY CARTILAGE. LECTURE XII. HEALING OF INJURIES IN TAEIOUS TISSUES. This last lecture on the process of repair I propose to devote to the consideration of the modes of healing of several different tissues ; modes vfhich, although they be all consistent with what has been said of the general rules and methods of the healing process, yet present each some peculiarity that seems worthy of observation. And first (though it matters little which I begin with), of the Healwg of wounds and other injuries of Cartilage. There are, I believe, no instances in which a lost portion of cartilage has been restored, or a wounded portion repaired, with new and well- formed permanent cartilage, in the human subject. When a fracture extends into a joint, one may observe that the articular cartilage re- mains for a long time unchanged, or else has its broken edges a little softened and rounded off. In one case I saw no other change than this in six weeks : but at a later period the gap is filled with a tough fibrous tissue ; or rather, the gap becomes somewhat wider and shallow- er, and the space thus formed is so filled up. The excellent researches of Dr. Redfern ' have ascertained the method of this process in incised wounds of the articular cartilages of dogs. As showing the slowness of the repair, he found in one instance, in which he made three incisions into the cartilage of a patella, and two into that of the trochlear surface of the femur, that no union had taken place in twenty-nine weeks. No unusual cause for the want of union had been apparent, yet a reparative process had but just commenced. In another case, twenty-four weeks and four days after similar incisions, he found them completely and firmly united by fibrous tissue formed out of tho substance of the adjacent healthy cartilage. The cut snr- ' Anormal Nutrition in Articular Cartilages: Edinburgh, 1850. And 'On tlio Healing of Woniids in Ai'ticular CartilageB,' in the Monthly Journal of Medical Science, Sept. 1851. HEALING OF CARTILAGE. 195 faces of the cartilage were very uneven, and were hollowed into small pits, produced by the half-destroyed cartilage-cells, the former contents of which were now lying on the surface. No evident change had taken place in the texture of the cartilage at a little distance from the cut surfaces, except that here and there the intercellular substance presented a fibrous appearance. The substance uniting the cut surfaces consisted of a hyaline, granular, and indistinctly striated mass, in which were numbers of rounded, oblong, elongating, or irregularly-shaped corpus- cles. A nucleated fibrous membrane, formed by the conversion of the superficial layers of the cartilage bordering the wounds, was continuous with their uniting medium. ' The essential parts of the process [of union of such incised wounds] appear to be,' Dr. Redfern concludes, ' the softening of the intercellular substance of the cartilage, the release of the nuclei of its cells, the formation of white fibrous tissue from the softened intercellular substance, and of nuclear fibres by the elongation of the free nuclei.' Such a process has peculiar interest as occurring in a tissue which has no bloodvessels, and in which there can be no question but that the reparative material is furnished by transformation of its own sub- stance. In the same view the results of inflammation of articular car- tilage will have to be particularly noticed. In membraniform cartilages that have perichondrium, the healing process is, probably, in some measure modified ; a reparative material being furnished, at least in part, from the perichondria! vessels. The cai'tilaginous tissue was less changed than in Dr. Redfern's cases, in an example of wounded thyroid cartilage that I examined. A man, long before death, cut his throat, and the wound passed about half-an inch into the angle of his thyroid cartilage. In the very narrow gap thus made, a gap not more than halE-a-line in width, there was only a layer of tough fibrous tissue ; and with the microscope I could detect no appearance of a renewed growth of cartilage. The edges of the cartilao-e, to which the fibrous tissue was attached, were as abrupt, as clean, and as straight as those would be of a section of cartilage just made with a very sharp instrument. The cut cartilage was unchanged, though the union between it and the new-formed fibrous tissue was as close and as firm as that of the several parts of a continuous tissue. The perichondrium on both sides was equally firmly attached to the fibrous bond.' ' A ease h;is been recorded Ly Mr. Edwards [Edin. Monthly Joiirn. Marcli 1861), in -ffhich tliere was such complete re-union (apparently cartilaginous), o 2 196 HEALING OF TENDONS. In some instances (but I suppose in none but those of cartilages which have a natural tendency to be ossified in advancing years) the fractures of cartilage may be united by bone. This commonly happens in the fractures of the costal cartilages ; and it has been noticed in fractures of the thyroid cartilage, and in a case of cut throat exam- ined by Professor Turner five years after the infliction of the wound, the incision both in the thyroid and cricoid cartilages was united by bone. The union of a fracture of the cartilaginous portion of a rib is usually effected, as that of one in the osseous portion is, by an enclosing ring of bone, like a provisional external callus ; and the ossification extends to the parts of the cartilage immediately adjacent to the fracture.' Healing of Tendons. — I have already often referred to the pheno- mena that follow the division of tendons by subcutaneous and by open wounds ; but the practical interest of the subject will justify my giving a connected account of the process, as I observed it in a series of numerous experiments performed, with the help of Mr. Savory, on rabbits from three to six months old. Such experiments are, I know, open in some measure to the same objection as I showed in the last lecture to those on fractures in the lower animals ; but the few instances in which examinations have been made of human tendons, divided by subcutaneous section, have shown that the processes in man and in animals are not materially different. The chief differences are, we may believe, that, as in the repair of bones, the production of reparative material is more abundant, and its organisation more speedy in animals than in man. I have already, in the eighth lecture, stated generally the differences in the several consequences of open and subcutaneous wounds. In the case of divided Achilles- tendons, the disadvantages of open wounds — i.e. of wounds extending through the integuments over and on each side of the tendon, as well as through it, were as follows r — 1. There were always more inflammation in the neighbourhood of the wound, and more copious infiltration of the parts, than in a subcutaneous division of the tendon in the same rabbit ; 2. Suppuration frequently occurred, either between the retracted ends of the divided tendon, or beneath its of the tracheal rings of an infant, who died about twelve months after the opera- tion of tracheotomy had been performed, that no scar was visible. No micro- scopic examination of the new material was, however, made. ' Museum of the College, No. 377; and of St. Bartholomew's, Ser. iii. Nos. 48 73. Numerous examples of the partial repair of larger injuries of articular and other cartilages will be found in llildubrandt's AmiJomw, B. i. p. 80G. HEALING OP TENDONS. 197 distal end; 3. tl:e skin was more apt to become adherent to the tendon, and so to limit and hinder its sliding movements, when the healing was completed ; 4. The retracted ends of the tendon were more often dis- placed, so that their axes did not exactly correspond with each other, or with that of the reparative bond of union. Sucli mishaps were often observed in the open wounds, but were rare after the subcutaneous operations. In the cases of open wounds they were avoided as often as the wound through the integuments healed quickly ; and whenever this happened the case proceeded like one in which the subcutaneous division had been made. It was evident that the exposure of the wounded parts to the air did little harm, if it was continued for only a few hours ; a fact that may be usefully remem- bered when operations must be performed on tendons which it is not convenient to divide unseen. These same cases of speedy healing of the opening in the integu- ments served to show that it is unimportant for the healing of divided Achilles-tendons, whether the connective-tissue sheath or covering of the tendon be divided completely or only partially. In all the cases of open division in these experiments, it was completely cut through ; yet, when the external wound healed quickly, the union of the divided ten- don was as speedy and as complete as in any case of subcutaneous divi- sion in which it might be supposed that the .sheath of the t(mdon was only partially injured. I will describe now the course of events after subcutaneous division of the Achilles- tendon ; stating only what was generally observed, and illustrating it, as far as may be, with the annexed diagram (Fig. 28), in which, as in longitudinal sections, A may represent the natural condition of the tendon and its muscles, and the succeeding iigures the effects of its division and the successive stages of its repair.' At the instant of the division the ends of the tendon separate to the distance of nearly an inch, the upper portion of the tendon being drawn up the leg by the action of the gastrocnemius and soleus muscles (b) . The retraction is comparatively much greater than is usual in opei'ations on the human Achilles-tendon ; for when these are done, the muscles are seldom capable of strong or extensive contraction. It is in all cases ' The account here gireu agrees in all essential respects with that by Lebert, m his Abhandhmgen . . . d^r prakl. Chirurffie, -p. 403. Neither do the accounts materially differ, except in being less minute, which are given by Von Amnion {Se Physiologia Temotomid!) : Duval (Bull, de I' Acad. Boyale de Mklecinc, 1837); and Duparc (Kederlandseh Lancet, 1837). 198 HEALING OF TENDONS. to be remembered that the separation is effected entirely by the with- drawal of the upper portion of the tendon : the lower, being not con- nected with mnscle, remains with its end opposite the wound. To this we may ascribe the general fact that the reparative process is more active and the inflammatory process less so, at the upper than at the lower portion of the tendon : for the latter lies in the very centre of the chief inflammatory action ; while the former is removed far from it, ABC D E Fig. 28. being drawn away at once from the seat of the injury and from even the slightest exposure to the air. T have already said that very little blood is effused in the subcutan- eous operations. Commonly, only a few blotches of extravasation appear in and near the space from which the upper part of the tendon is retracted (b). The first apparent consequence of the division of the tendon is the production of a substance in which the well-known forms of lymph-cells and white blood-corpuscles may be seen. These, speedily becoming more distinctly nucleated and elongated, undergo the changes which I mentioned in describing the development of cells in granula- tions. The lymph makes the tissues at and near the wound succulent and yellow, like parts infiltrated in anasarca. The bloodvessels near the divided tendon enlarge as in an inflamed part, and appear filled with blood (b, c). The new material produced, together with the enlarge- ment of the vessels, swells the parts, so that the skin is scarcely at all HEALING OF TENDONS. 199 depressed between the separated ends of the tendon. But in well-made subcutaneous sections this inflammatory product is of small amount, and takes, I believe, little or no share in the healing of the injury ; and its cells are not developed beyond the state in which, they appear spindle-shaped. I have never seen indications of their forming fila- ments of connective tissue. In rabbits, forty-eight hours usually elapse before there are distinct signs of the production of the proper reparative material. This is formed in the fibro-cellular tissue that lies between and close round the separated ends of the tendon, as well as in the interspaces of the ten- dinous fasciculi of those ends. It thus swells up the space between the separated ends, and makes the ends themselves larger, and somewhat ruddy, soft, and succulent. Some portioii, at least, of it being formed where the inflammatory effusion was, one flnds their constituents mingled ; but I believe that, while the proper reparative material develops itself, the product of the inflammation is either arrested in its development, or even degenerates ; its cells shrivelling and gradually wasting. I need not now describe the mode of development of the reparative material provided for divided tendons ; for I have taken it as a typical example of the development of nucleated blastema into fibrous tissue (p. 143). To the naked eye it appears after three days as a soft, moist, and greyish substance, with a slight ruddy tinge, accidentally more or less blotched with blood, extending from one end of the tendon to the other, having no well-marked boundary, and merging gradtially into the surrounding'"parts (c). In its gradual progress, the reparative material becomes commensurately firmer, tougher, and greyer, the ruddiness successively disappearing from the circumference to the axis : it becomes, also, more defined from the surrounding parts, and, after four or five days, forms a distinct cord-like vascular bond of connection between the ends of the tendon, extending through all the space from which they have been retracted, and for a short distance ensheathing them both (d, e). As the bond of connection thus acquires toughness and definition, so the tissue around it loses its infiltrated and vascular appearance : the bloodvessels regain their normal size, the inflammatory eff'usion clears up, and the integuments become looser, and slide more easily. In every experiment, one flnds cause for admiration at the manner in which a single well-designed and cord-like bond of union is thus gradually formed, where at first there had been a uniform and seem- 200 HEALING OF TENDONS. ingly purposeless infiltration of the whole space left by the retraction of the tendon. With the iacrease of toughness the new substance acquires a more decidedly filamentous appearance and structure. After the fourth day the microscope detects nuclei in the reparative material ; and after the seventh or eighth day there appear well-marked filaments, like those of the less perfect forms of fibrous tissue. GraduaUy perfecting itself , but with a rate of progress which becomes gradually less," the new tissue may become at last, iu all appearance, identical with that of the original tendon. So it has happened in the valuable specimens presented to the Museum of the College by Mr. Tamplin.^ They are the Achilles-tendon and the tendons of the anterior and posterior tibial muscles of a child nine months old, in whom, when it was five months old, all these tendons were divided for the cure of congenital varus. The child had perfect use of its feet after the operation, and when it died, no trace of the divi- sion of any of the tendons could be discerned even with microscopic aid. In the instances of divided hunaan tendons, less retraction, I have already said, takes place than in those of lower animals. The connect- ing bond is therefore comparatively shorter ; and it is yet more shortened when, like a scar, it contracts as it becomes firmer. It is impossible, therefore to say what length of new material was, in this case, formed into exact imitation of the old tendon. But, however little it may have been, such perfect repair as these specimens show is exceedingly rare. More commonly the differences between the original tendon and the new substance remain well marked. The latter does not acquire the uniform arrangement of fibres, or the peculiar glistening thence accruing to the normal tendons ; it is harder and less pliant, though not tougher ; its fibres, appear irregularly interwoven and en- tangled, dull- white, like those of a common scar. And these diflirences, though as time passes they become gradually less, are always seen when a longitudinal section is made from behind, through both the ends of the tendon and the new substance that ensheaths and connects them. In such a section (as in Fig. 28, e) one sees each of the retracted ends of the divided tendon preserving nearly all its peculiar whiteness, only ' One may remark this as a general fact, that when once the reparative process has commenced much more appears to be done in it in the first few days than in any ecjnal subsequent period of time. It may be another instance justifying the general expression, that production is easier than development or improvement, and that the earlier or lower developments require less organising force than the higher or later. 2 Nos. 358, 359, 360. HEALING OF MUSCLES. 201 somewhat rounded or mis-shapen, swollen, and imbedded in the end oF the new substance, which is always greyer, or less glistening, and looks less compact and regular. In the retracted ends of the tendon one may discern the new substance mingled with the old and interposed between its fasciculi, with which one may believe it is connected by the finest dove-tailing.' The strength, both of the new substance itself, and of its connection by intermingling with the original substance, is worthy of remark. To test it, I removed from a rabbit an Achilles -tendon, which had been divided six days previously, and of which the retracted ends were con- nected by a bond of the size and texture usual at that period of the re- parative process. I suspended from the half-section of this bond gradually increased weights. At length it bore a weight of ten pounds, but presently it gave way with it : yet we may suppose the whole thick- ness of the bond would have borne twenty pounds. In another experi- ment I tried the strength of a bond of connection which had been ten days forming in a small young rabbit : this, after bearing suspended ■weights of twenty, thirty, forty, and fifty pounds, was torn with fifty- six pounds. But surely the strength it showed was very wonderful when we remember that it was not more than two lines in its chief dia- meter ; and that it was wholly formed and organised in ten days, in the leg of a rabbit scarcely more than a pound in weight. With its tena- city it had acquired much of the inextensibility of the natural tendon. It was indeed stretched by the heavy jveights suspended from it, yet so slightly that I think no exertion of which the rabbit was capable would have sufficed to extend it in any appreciable degree.^ The Healing of Striped Muscles, subcutaneously divided, presents many things exactly similar to those just described as observed in the healing of tendons similarly divided. In experiments which I made on the triceps extensor brachii, and the tibialis anticus of rabbits, there was always observed a peculiar inversion, subsidence, or taahing-in of the muscular fibres at the divided part ; so that nearly all the fasciculi ' The appearances are shown in specimens in the College Museum, Nos. 3'18 to 354 ; and in those from the experiments on rabbits in the Museum of St Bar- tholomew's, Ser. v. ; 36 to 44. '' Eeference may here be made to the observations of Mr. W. Adams On the Reparative Process in Human Tendons after Division, London, 1 860, as confirming generally what is described in the text. In this work a,n abstr,act of the various opinions entertained by surgeons on the process of reparation of these structures has been incorporated in the form of an appendix. 202 HEALING OF MUSCLES. directed their cut ends towards the subjacent bone or fascia. Thus it sometimes appeared to happen that though the retracted portions of the muscle were imperfectly united, yet the action of the mnscle was not lost ; for one or both its ends, acquiring new attachment to the subja- cent parts, could still act, though with diminished range, upon the joint over which its fibres passed. In general it appeared that the reparative material was less quickly produced than after division of the tendons ; but this might be because of the greater violence inflicted in the operation, more than because of the structure of the divided parts ; and at length, but always, I think, more slowly than with them, the ends of the retracted portions became enclosed in a tough fibrous bond of union. After the formation of this bond the healing of divided muscles is improved, both by the clearing up of the surroundiug tissues infiltrated with inflammatoiy products, and by the contraction of the new bond, which thus draws together the re- t racted portions of the muscle, so that they may nearly coalesce. Thus in a man who had cut his throat long before his death, and had divided the left stemo-hyoid, omo-hyoid, and stemo-thyroid muscles, I found that the ends of these muscles, though they must at first have retracted considerably, had all been drawn to attachments on the cricoid cartilage, over which their several portions nearly united. Although, as a rule, fibrous tissue forms the medium of connection between the two ends of a divided muscle, yet some recent observations show that a new formation of striped muscular fibre may occur, both when a muscle is wounded and when it is the seat of suppuration. 'For elongated, spindle-like cells form at the seat of injury, the protoplasm of which undergoes transverse striation, in the gajne manner as is seen in the development of muscular fibres in the embryo. By some these new fibres are supposed to bo derived either from the nuclei of the original fibres of the muscle or from its interstitial connective tissue, whilst by others the white blood-corpuscles are considered to take a part in their production.^ The observations of Zenker ^ also, on the pathological changes which take place in the voluntary muscles during abdominal typhoid fever, ' Consult on this subject C. 0. 'Weber, in Billroth vrnd tou Pitha's JIandbuch B. i. p. 270; and Virchow's Archiv, 1867, p. 215; Maslowsky, Wiener Med. Wochenschrift, 1868, 12; Aufrecht, Virchow's JrcWu, xliv. p. 196. 2 Ueber die Veranderungen der Willkiirliehen Muskeln in Typhus Abdomiualis, Leipzig, 1864. Also Waldeyor, Virchow's Archiv, xxxiv ; C. E. Hoffman, idem, xl. HEALING- OF ARTERIES AND VEINS. 203 have directed attention to the regenerative process which subsequently occurs in them. He has pointed out that a new formation of trans- versely striped fibres occurs, and that for the reparation of this tissue a multiplication of the nucleated corpuscles of the intermediate connec- tive tissue takes place, some of which elongate, and become ribbon- shaped and transversely striped. The Healing of Injured Arteries and Veins is conamonly a more com- plicated process than those already described, on account of the changes that ensue in the blood that is stagnant within, or shed around, the in- jured vessel.' Small Tvounds of either arteries or veins may heal by unmediate nnion, or primary adhesion, as those of any other tissue may, and the blood shed into the adjacent tissues may be absorbed as from common ecchymosis. An artery divided in only part of its circumference, al- though it may be for a time contracted, yet does not remaia so ; neither is it commonly, ia such a case, obstructed by clot within its canal. Hence, after such wounds, the pulse in the distal or lower part of the artery is often unaffected. After the first outburst of blood, some that remains extra vasated among the tissues usually clots and covers the wound in the artery ; but the closure is often ineffectual, or only for a time, and fresh bleedings ensue, either increasing the accumulation of extravasated blood or pushing out the clots already formed. In this way, with repeated haemorrhages at uncertain intervals, the wound in an artery is often kept open, and at the end of two or three weeks may show no trace of healing, but rather appear widened and with softened everted edges. In such a case it is possible that a wound in an artery may still heal by granulations, either rising from its edges or coalescing over it from adjacent parts ; but the event is too unlikely to justify the waiting for its occurrence, if there be opportunity for surgical in- terference ; and even if healing should go so far as to close the opening in the artery, yet it is likely to be insecure, for both the elastic tissue and smooth-fibred muscle, on which its strength largely depends, are very slowly formed in scars. Hence a form of traumatic aneurism seems not very rare, in which the sac is chiefly formed of scar-tissue, which closed the wound in the artery and then yielded to the pressure of the blood. ' Nearly all that follows relates to the healing of wounds of arteries. Tlia process in veins appears to be essentially the same, but more quickly accomplished. See Stilling: Die naturlichen Processe hei der Heiiung durclischlungener Blutgefasse . Eisenach, 1834, pp. 147 and 289. 204 HEALIXG OF ARTEEIES AND VSISS. In the case of an artery divided quite across, three chief things are to be considered— namely, the natural immediate arrest of the bleeding, the closing of the two orifices, and the disposal of the blood that may become stagnant at and near the ends of the divided vessels. The bleeding is arrested, mainly, by the contraction of the mns- cnlar coat of the artery. Stimulated by the injury and by exposure to the air, and relieved from much of the pressure of the blogd, whose onward course is less resisted, the muscular tissue of the divided artery contracts and closes ; or, at least, diminishes the canal. In some instances the contraction is narrowly funnel-shaped or like the neck of a Florence oil-flask, and the end of the artery may be open ; while, at aHttle distance within, its canal is closed or much narrower, and this contracted part is filled with a clot. In some, the exterior layers of the muscular fibres seem to contract rather more than the interior, and the end of the artery appears prominent or pouting. Many, perhaps trivial, differences of this kind may be noticed in diffe- rent arteries cut across in amputations. Moreover, the processes for the Stoppage of bleeding are not equally effective in the upper and lower ends of a divided artery, for whilst the upper end may be permanently closed and remain so, the lower end, perhaps because of the division of its nerves, may re-open, and bleeding be renewed from it, some time after the wound has been inflicted. The retraction of the divided art eiy within its sheath, or among the adjacent tissues, assists to stay the bleeding, by giving opportunity for the blood to become diffused, as it flows through the tissues that collapse over the end of the artery before it closes. But the degree to which this retraction can take place is very uncertain. It depends chiefly on the laxity or the closeness of the attachment of the artery to the surrounding tissues, and on the extent to which they with it are divided, and with it are capable of retraction. In amputations, one sees many differences in these respects. Arteries divided close to ligamentous parts and the origins of muscles appear much retracted, because the tissues about them are scarcely at all drawa back ; so it is in amputations just below the knee : but those that are divided where there is much areolar tissue, or where muscles are far from their origins, as in the middle or lower part of the forearm, appear less re- tracted, because the surrounding parts are retracted as much or more than they. In like manner, arteries, from which branches are given off just above the place of division, retract less than others, the branches holding them in place. HEALING OF ARTIiRlES AND VEINS. 205 Equally various is the degree in which the bleeding from a wounded artery is arrested by the blood collecting around it, and in front of its orifice. It depends mainly on the degree of retraction of the artery, and on the facility with which the blood can escape throiigh the external wound. It is assisted, in case of large haemorrhage, by the weakening of the action of the heart, and, perhaps, by the readier coagulation of the blood which ensues in syncope. The efficacy of these means for the arrest of bleeding from all but the principal arterial trunks is evident enough immediately after the amputation of a limb. However many arteries may need ligature, they are probably not a tenth of those that were just now traversed by quick streams of blood. The rest are already closed by their own muscular action, needing no assistance from a diminished action of the heart, or the eiFusion of blood around them. One of the m.ost simple instances, probably, under which the closure of an artery may be studied, is seen in those cases in which temporary metallic compression by means of needles is employed, as in one or other of the various modes of acupressure suggested by Sir J. Y. Simp- son.' If carefully performed, it is stated that no rupture of the internal or middle coats of the artery occurs, but the blood coagulates within the vessel, and forms, as a rule, a conical plug immediately above the line of pressure, whilst the apposed walls of the artery become adherent by means of lymph. Organisation and contraction of the clot then take plaoe,^ and although the changes which occur in it have not yet been fully worked out by the aid of the microscope, it is probable that they are similar to those which have been seen in the clot which forms in an artery after the application of a ligature. When torsion is the method employed to close the end of the artery, the inner coats of the divided end of the vessel are separated from the outer coat, and are turned upwards within the artery in a funnel-like manner, so as to form a valvular arrangement, which as Professor Humphry has shown,^ offers to the blood-current a resistance pro- portioned to the depth of the funnel and the tightness with which the fibres of the outer coat are twisted together. When a divided artery is tied with an ordinary ligature, the injury ' See more especially his treatise on Acupressure, Edinburgh, 1864. 2 See two cases, pp. 112, 169, in Professor Pirrie and Dr. Keith's work on Acupressure, London, 1867; and the experiments of Mr. Lawson Tait in Mcdica. Times and Gazttte, July 15 and 22, 1865. 3 Journal of AiuUomy and PhysioJocpj, Ko\i.inber, 1808, p. 13, p). i. 206 HEALING or AUTERIES AND VEINS. to be repaired is not merely that of the wound, but that of the liga- ture ; an injury in which a bmised wound dividing the middle and internal coats of the artery, a bruise with continued compression of its external coat, and the continued presence of a foreign body, are super- added to the injuries which preceded the application of the ligature. For simplicity's sake, let us consider the repair of such an injury in only that part of an artery which is above the ligature — i.e. nearer to the heart. The changes in the part beyond the ligature are, according to Stilling, the same, but more quickly accomplished. Now, in this repair three parts are chiefly concerned — namely, (1), the injured walls of the vessel at and immediately adjoining the ligature ; (2), the part of the vessel between the ligature and the first branch above it, through which the blood can flow ofi'; and (3), the blood which, with in the same part of the vessel — i.e. between the liga- ture and the first branch nearer to the heart, lies nearly stagnant. The healing of the artery may indeed be accomplished without the help of this blood, but certain changes in it commonly concur with the rest of the process. (1.) The injured walls of the vessel, and the tissue immediately around them, inflame, and production of lymph takes place in them, especially at and just above the divided parts of the coats constricted and held in contact by the ligature. Thus, as by primary adhesion, or by an adhesive inflammation, the wound made by the ligature in the middle and internal coats is united ; and, through the same process, this union is strengthened by the adhesion of these coats to the outer coat, and of the outer coat to the sheath, or other immediately adjacent tissues. There is a general adhesion of these parts to one another ; they appear thickened, infiltrated, and morbidly adherent : beneficial as the result is, it is the result of disease. Through the same disease, the portion of the outer coat of the artery included within the ligature sloughs, and is brought away,' or it ulcerates and permits the remova of the ligature, and a more natural process of organisation of the inflammatory products, among which it lay, and which its presence had tended to increase.^ ■ See a specimen from a tied .subclavian artery in tlie Museum of St. r,artliolomew'!5 Ser. xiii. ; 155. ' ^ If the antiseptic ligature be employed it merely inflicts a wound or injury upon the vessel, without mtroducing any permanent cause of irritation. The injured part therefore becomes repaired after the manner of a subcutaneous wonnd, without pas.sing through the process of grannhition and suppur,^tion, which is indnccdbv the employ- ment of the ordmary septic ligature. (Lister in Lancet, April 1869.) HEALING OF ARTERIES AND VEINS. 207 (2.) When any part of an artery, tlarougli any cause, ceases to be traversed by blood, its walls tend to contract and close its canal. The application of a ligature brings into this condition all that part of the tied artery which lies between it and some branch or branches higher up, through which the stream of blood may be carried oif. The walls of this part therefore slowly contract, gradually reducing the size of its canal, and, in some instances, probably, closing it. There is not in this, as in the last-described part of the process, any disease : the con- traction is only the same as that of the ductus arteriosus, the umbili- cal arteries, and other vessels, from which, in normal life, the streams of blood are diverted ; and the closure may, as in them, according to Rokitansky,' be assisted by deposit from the blood thickening with an opaque white-layer the internal coat. The time occupied by this con- traction, and its extent in length along the artery, are too various to be stated generally. When it is permanent, the coats of the artery, at its completion, waste, lose their peculiar structures, and are slowly transformed into a fibrous tissue, such as that which composes the solid cord of the ductus arteriosus. Respecting these two consequences of the application of ligatures, little difference of opinion can exist ; and it may be repeated, that either of these may suffice for the safe closure of the artery. Thus, on the one hand, we sometimes see an artery pei-vious to the very end of a stump, but there safely closed at the seat of ligature ; and,on the- other, the naturally torn umbilical arteries of animals, and, I suspect, the arteries which in common wounds are divided and spontaneously cease to bleed, are closed and obliterated without inflam m ation. (3.) Much more commonly, the blood contained in and near the end of the tied artery becoming stagnant, concurs with both the pro- cesses just described, to the closure of the canal. Concerning this third constituent of the process, more questions have been raised, and admirable observations have been made by Stilling,^ Zwicky,' and Otto Weber,* in a large series of experiments on the arteries of animals : those of Stilling refer chiefly to the changes visible to the naked eye, those of Zwicky and Weber to the more minute. When an artery is tied, the blood, as already said, becomes nearly ' Pathologische Anaiomie, B. ii. p. 023. 2 DU natiirl. Frocesse bei dcr Heilung durchscMimgcncr Blutgefasse. Eisenach, 1834. ' Die Meiatmrphose des Thrombus. Zurich, 1845. * Billroth und von Pithii's Huiidbuch dcr CIdruryie, B. i. Ab. i. S. 142. 208 HEALINa OF AETERIES AND VEINS. stagnant in the canal, from the ligature upwards to the first principal branch. In an uncertain time, varying from one to eighteen hours, a part of this blood coagulates ; and the clot commonly assumes a more or less conical form. The base of this ' conical clot,' 'internal obturator,' 'plug,' or 'thrombus,' rests in and fills the end of the artery, at the wound made by the ligature ; its apex usually lies nearly opposite the first branch above, in the axis of the artery : it is surrounded by fluid, but still nearly stagnant, blood, which, except at its base, intervenes between it and the internal surface of the artery. At its base, and higher up if it fills the artery, the clot is dark and soft, like a common blood-clot : its upper part and apex, are denser, harder, and whitish, like coagulated fibrine ; and layers of white substance, mark- ing it with pale spots, are often gradually superadded to its middle and apex, and increase its adhesion to the walls of the vessel. The red corpuscles also in it shrivel up and disappear. Changes soon begin to occur in the colourless blood-corpuscles within the clot. They elongate into spindles, or form stellate corpus- cles, such as are seen in young connective tissue, and anastomose with each other, forming a net-work which traverses the clot in all directions. The clot now becomes porous, spongy, and cavernous as if it were being gradually channelled from its surface towards its central parts. In this state, injection impelled into the artery will enter and distribute itself in the clot, making it appear vascular, or like a cavern- ous tissue, which led Hunter ' into the belief that he had found the beginning formation of new bloodvessels in the clot. StUling and Weber are of opinion, based on numerous observations, that the clot thus becomes vascular independently of the vessels of the surrounding parts, but that in the course of time its vessels join the vasa vasorum of the arterial wall, so that a circulation is established through the thrombus. Wiile thus changing, also, it becomes gradually more decolorised, passing through ruddy, rosy, and yellowish tints, till it is nearly colourless. As it loses colour it gains firmness, and its base and the greater part of its length become more firmly adherent to the inner surface of the artery, directly or through the medium of the lymph formed on it. In this increasing firmness, the clot, moreover, is acquiring a more definitely fibrous texture, and, as the same changL is gradually ensuing in the inflammatory products deposited near the ligature, the clot and they unite more firmly than before. The walls ' JVorks, in. p. \19; and Miisoum of College, No. 11. HEALING OF DIVIDED NEEVES. 209 of the artery, also, gradnally closing in on tlie clot, unite with it ; and, finally, as they also lose their peculiar texture, and become fibrous, the clot and they together form the solid fibrous cord by which the tied portion of the artery is replaced ; a cord which commonly extends, as did the clot, from the seat of the ligature to the first principal branch above it.' The minuter changes in the clot, associated with those visible to the naked eye, are, chiefiy, that it acquires a fibrous or fibro-cellular tex- ture, and its vascularity diminishes as it acquires firmness. The de- velopment, or at least the later part of it, is accomplished much more slowly than in the reparative material of tendons in rabbits ; needing more than ten weeks in the clots formed in dogs, and more than two years in those in men. In applying the description drawn from experi- ments on animals to the cases of human arteries, the same allowance must be made as in the repairs of fractures and of divided tendons. The process is less speedy, less simple, less straightforward (if I may so speak), more prone to deviate and to fail, through excess of that disease, by a measured amount of which the security of the artery is achieved. The Healing of Divided Nerves may be accomplished in two methods, which may be named, respectively, primary and secondary union, and may probably be compared with the processes of primary adhesion (p. 148), and of connection by intermediate new- formed bonds (p. 199.) I know no instances in which nerves healed in the first method have been examined, but the nature of the process may be explained by the history of a case in which it occurred : — A boy, eleven years old, was admitted into St. Bartholomew's Hospital, under Mr. Stanley, with a wound across the wrist. This wound, which had been just previously made with a circular saw, extended from one margin to the other of the fore-arm, about an inch above the wrist-joint. It went through all the flexor tendons of the fingers and thumb, dividing the radial artery and nerve, the median nerve and artery, and extending for a short distance into the radius ' Professor Waldeyer (Virchow's ArcMv, xl. 379) and Professor Thiersch (Billroth imd TOn Pitha's tlanShuch, B. i. Ab. ii.) are of opinion that the epithelium lining the inner coat of the arteries and veins plays the chief part in the organisation of the clot. Dr. Bubnofif (Virchow's ArcUv, October 1868), whilst admitting that the white hlood- corpuscles participate in the organisation of the clot, yet considers that the larger portion of the cells found in it are derived from the vascular coats and the surrounding tissue. P 210 HEALITSfG OF DIVIDED NKRVES. itself. The ulnar nerve and artery were not injured ; the condition of the interosseous artery was uncertain, but the interosseous ligament was exposed at the bottom of the wound. Half-an-inoh of the upper portion of the divided median nerve lay exposed in the wound, and was distinctly observed and touched by Mr. Stanley, myself, and others. All sensation in the parts supplied from the radial and median nerves below the wound was completely lost directly, and for some days after the iujury. The radial artery was tied, and the edges of the wounded integu- ments put together. No particular pains were taken to hold the ends of the divided median nerve in contact, but the arm was kept at rest with the wrist bent. After ten days or a fortnight the boy began to observe signs of returning sensation in the parts supplied by the median nerve, and these increasing, I found, a month after the wound, that the nerve had nearly recovered its conducting power. When he was blindfolded, he could distinctly discern the contact of the point of a pencil with his second finger, and the radial side of his third finger ; he was less sure when his thumb or his fore-finger was touched, for though generally right, he sometimes thought one of these was touched when the contact was with the other; and there were a few and distant small portions of the skin supplied by the median nerve from which he still derived no sensation at all. Now all this proves that the ends of the divided median nerve had coalesced by immediate union, or by primary adhesion, with an exceed- ingly small amount of new substance formed between them. In the ordinary secondary healing of divided human nerves, twelve months generally elapse before, if ever, any restoration of the function is ob- served ; in this case, the nerve could conduct in a fortnight, and perhaps much less, after the wound. The imperfection of its recovery is just what one might expect in such a mode of union. One mio-ht anticipate that some of the fibres in one of its portions would fail to be united to any in the other portion : and the parts supplied by these filaments would necessarily remain insensible. So, again, one mio-ht expect that some of the fibres in one portion would unite with some in the other, with which tliey were not before continuous, and which supplied parts alien from those to which themselves were destined : in all such dislocations of filaments there would be confused or transferred sensations. But among all the fibres, some would again combine in the HEALING OF DIVIDED NERVES. 211 same continuity in which they had naturally existed : and in these oases the function would be at once fully restored.' While this case was under observation, Mr. Gatty sent me, with the permission of Mr. Heygate, in whose practice the case occurred, the following particulars of a similar instance of repair : — A lad near Market Harborough, thirteen years old, had his hand nearly cut off at the wrist-joint by the knife of a chafT-cutting machine. The knife passed through the joint, separating a small portion of the ends of the radius and of the ulna, and leaving the hand attached to the forearm by only a portion of integument about an inch wide, connected with which were the ulnar vessels and nerve, and the flexor carpi ulnaris muscle — all uninjured. The radial artery and some small branches being tied, the hand and arm were brought into apposition, and, after removing a small portion of extensor tendon that protruded, were re- tained firmly with adhesive plaister and a splint of pasteboard. The wound went on very well, and was left undisturbed for a week. The warmth of the hand returned ; in ten or twelve days after the injuiy there was slight sensation in the fingers, but in the thumb none was discernible till more than a fortnight had elapsed. Finally, the sensation of the hand and fingers, and most of their movements, were perfectly restored. In this case, again, it seems impossible to explain the speedy resto- ration of the conducting power of the nerve, except on the supposition that its divided fibres had immediately reunited. We have no evidence that new nerve-fibres could in so short a time be formed : all the cases ' I saw this boy again nearly a year after the injury. He had almost perfect sensation in all the distribution of the median nerve, except in the last phalanges of the thumb and fore-finger. These had not decreased or changed in texture ; but they were very liable to become cold, and he came to the hospital because large blisters had formed on them. He had been warming his hands at an open fire, and the heat, which was not uncomfortable to the rest of the hands, had blistered these parts, as boiling water would have blistered healthy ones. He had almost completely recovered the movement of his fingers. Schiff in his Fhydologie (p. 123), remarking on this and the case immediately following, states that the rapid union and recovery cf sensation observed in them correspond with what he has frecjuently found in the warm-blooded animals on which he has experimented. He ascribes the quick recovery to the wound being made with a sharp cutting insti-ument, and states that such wounds, when unaccompanied by loss of substance, heal within a few days. Moreover, he considers that, next to the connective tissue, nerves, when cleanly divided, heal more readily than any other texture, surpassing in this respect even the bones. On the other hand, if the nerve be greatly injured previous to, or during, the section, as by pinching it with the forceps, etc., then the process of restoration takes a much longer time. p 2 212 HEALING OF DIVIDED NERVES. of less favourable healing show that they require a year or more for their formation. I need hardly add the practical rule we may draw from these cases. It is, briefly, that we may, with good hope of great advantage, always endeavour to bring into contact, and immediately nnite, the ends of di- vided nerves ; and that we need not, in all such cases anticipate a long- continued suspension of the sensation and other functions of the part the nerves supplied. The secondary healing of divided nerves presents many features similar to that of divided tendons. A bond of new substance is formed, which connects the ends of the retracted portions of the nerve, and in which, though at first it is like common reparative material, new nerve- fibres form, and connect themselves with the fibres in the portions above and below. I need not dwell on the formation or development of this connecting bond : the subject is amply treated in several works on phy- siology ; ' and it is thoroughly illustrated, so far as the appearances to the naked eye are concerned, by the valuable series of preparations given to the Museum of the College by Mr. Swan.^ "When a nerve is cut across in an amputation, its divided end swells up, granulations form in and about it, out of which connective tissue and sometimes nerve- fibres may arise. The production of the connective tissue is usually so great as to form a bulbous knot at the end of the nerve, which consti- tutes one of the forms of neuroma.' The observations of Dr. Waller,^ have added some remarkable facts to those previously known of the mode in which nerve-fibres regenerate. By watching the process which follows the division of the glosso-pha- ryngeal nerve in frogs, he found that, after a nerve is divided, the old fibres in the distal portion never recover their functions. They degen- erate, and new fibres gradually form in the whole length of the nerve from the place of division to the peripheral distribution. These new fibres connect themselves with those in the connecting bond of repair, and through these with the old fibres in the proximal portion of the ' See especially Muller'a Physiology, by Baly, i. p. 457 ; Valenciu's Physiologic, \. p. 702 j Hildebrandfs Anatomic, i. p. 291 ; Sehiff's Pliysiologie,\. 1850. '^ Xos. 2169 to 2175. All these specimens, and the appearances of the formation of new nerve-fibres which they display, are described and illustrated by Mr. Swan, in his Treatise on the Diseases and. Injuries of Kcrvcs. ^ In Nos. 21 65 to 2168 in the College Museum, Mr. Hunter has shown theformation of the bulb at the ends of divided nerves as in a stump after amputation, and tlio exten.sinn of nerve-fil n-cs into it. ■' London Journal of ifnliciiic, ,Tuly IRo'!. HEALINa OF XERVOUS CENTRES. 213 nerve. To liow great an extent this degenerative atrophy affects the various constituents of each fibre it is difiicult to determine ; for whilst some experiments would seem to show that the atrophy only affected the white substance of Schwann, in other cases both that and the. axial cylinder had disappeared, and required to be reproduced.' The repair of Nervous Centres has been comparatively little studied. Flourens has indeed shown ^ that deep wounds both of the brain and spinal cord unite, and that a restoration of function occurs. The ex- periments of M. Brown-Sequard ^ have proved that, after complete division of the mid-dorsal part of the spinal cord of pigeons, and after division of more than half of that of guinea-pigs, the sensibility and movements of the hinder part of the body may be almost completely restored in about twelve months ; and that the substance by which the injury of the cord is healed contains, with connective tissue, abundant well-formed nerve-fibres connected with those of the cord above and below, and sparing nerve-cells. Schroder's experiments of dividing and removing small portions of tlie cervical ganglia, and the ganglion of the vagus, of rabbits, found union by fibrous bonds, but no regeneration of ganglion-cells after eleven weeks.'' Valentin's ° and Walter's ^ similar experiments had scarcely a more positive result, though in one case the latter saw, after excision of the lower ganglion of the vagus, many normal ganglion-cells in the upper part of what seemed to be a new-formed ganglion. But as the extent of this ganglion is not very precisely defined, it is doubtful if it had been entirely removed in the course of the experiment. After wounds and losses of substance of the brain, a large quan- tity of new material may be formed to fill up the gap ; ' but observa- tions are wanting to show how much this may contain of proper cere- bral substance. I have found nerve-fibres in it after thirty-three years (see p. 62) ; bat in the same specimen there was no appearance of grey matter.* ' See Bruch, Schiff, and Lent, in KoUiker's Manual of Mic. Anat. 1860 ; Hjelt in Virehow's ArcUv, xix. ; Remak in vol. xxiii. ; and Hertz in vol. xlvi. 2 Becherches Exper. sur Us Si/sf. Nerv. » Comptes Bendus de la Soc. de Biologie, t. i. p. 17 ; t. ii. p. 3 ; t. iii. p. 77. ■■ Experimentu circa Begeneratiouem in Gangliis nerveis, Giittingen, 1850. * Physiologic, i. 703. ' Be Begeneratione Gangliomm, Bonn, 1853. ' See especially Arnemann : Versuchi iiber das Gehirn und Bilokenmarlc, Gottingen, 1787. « Cases are recorded by Virchow {Gesam. Abhand. p. 098), Tiingel (Virchows Ar- ch'V, B. xvi. p. 166), E. K. Hoffmann (Henle and Pfeufer's Zeitschrift, 1868, p. 104), 214 HEALING OF SKIN. Healing of Skin.— The last tissue to the healing of which I shall par- ticularly refer, is the skin. I need not iadeed describe the whole process, Isecause nearly all that was said of the healing processes generally was chiefly illustrated by instances of wounds involving the skin. Yet. it may be useful to indicate the skin as, on the whole, the part which, being most exposed to injury, is capable of the best repair ; that which heals most commonly by the immediate union, most quickly by primary adhesion ; that which produces the most rapidly and securely organ- ising granulations. The healing of skin is farther favoured by its extensibility and loose connection with adjacent parts ; so that, when large surfaces are to be healed, the contracting granalations can draw over their borders the loose skin around. Moreover, the new-formed skin imitates the old skia very well if we consider the complexity of its structure. I am not aware that the smooth muscular fibres, or any of the glandular structures of the skin, or hair-follicles, are formed in its scars ; but its white fibrous and elastic tissues, its connective-tissue corpuscles,' its papillae and epidermis, are all well formed in them. The new cuticle grows chiefly from the margin of the wound cen- tripetally over the surface ; but it may arise, though it very rarely does so, in the midst of a raw surface ; on granulations, independently of any pre-existing cutioular structures from which it might be derived.^ The new epidermal cells, as C. 0. Weber's observa- V I tions ^ would sho w, are formed by a conver- Fig. 29. sion of the connective-tissue corpuscles of the superficial layer of granulation-cells, which lose their spindle-like and assume a polygonal shape. It is commonly said that the smoothness of a scar is due to the absence of papillae, but I believe it depends only on the tightness of the new-formed skin and its want of such wrinkled and furrowed lines as naturally exist. If a thin section be made of the border of a healing wound, so as to include the new formed layer of in which nodules of grey cerebral Bubstance are stated to hai-e been found in parts of the brain, in which no such masses should have been present. Butthereis no ei-idence that theise formations were occasioned by any preyious injury to the parts. 1 Billroth, Beitrdge zur Path. Hist. 1858, Berlin. ' The most recent experiments and observations on the formation of new cuticle on the surface of a wound are related by Julius Arnold (Virchow's Archh; xlvi. 209, 1869), who figures islets of epithelium arising in the midst of the granula- tions. ^ " Entwicklung des Eiters," etc. Virchow's .4re/«'i), B. xv. HEALING OF SKIN. 215 epidermis, the granulations now skinned, over will be found as iu the annexed diagram (Fig. 29), presenting the papillary form. They con- sist still of nucleated cells, but the shape of papilte is acquiied, or rather is retained ; for the likeness of a granulating surface to a finely papillary one is evident, and may be regarded as an example of the general tendency of new-formed structures, even in disease, to assume a plan of construction similar to that of the adjacent parts. The like- ness extends to the arrangement of the blood-vessels ; and the papillary structure is not lost in the later development of the scar. If the epidermis of a scar be separated, its under surface will present a series of depres- sions corresponding -with the elevations of the papilltB on which it was adapted. The adjoining sketch represents the under surface of epidermis so reflected from a scar on the arm of a negro : and may illustrate not only the plan of the papillae, of which it was like a mould, but, by its colour, the complete reproduction of a rete nigrum.' In concluding the lectures on Repair, and before beginning those on Inflammation, let me briefly state the relations of the one process to the other. It is not because we have any well-defined Kg. 30. idea of inflammation, that it is desirable to refer to it, as if it were a standard with vfhich we might compare other organic processes ; but such a reference seems necessary, because some idea of inflammation mingles itself with nearly everything that is considered in surgical pathology. Nowhere is this more manifest than in what has been written in surgical works upon the methods of repair; concerning which a general impression seems still to be, that a process of inflam- ' For the further study of the healing process, especially in the tissues and organs not mentioned in this lecture, I must refer the reader either to special treatises on the pathology of those parts, or to the chief works on General Anatomy, especially in relation to all but microscopic observations ; to that of Hildebrandt, edited by E. H. Weber ; and to the chapters on Eeproduction in Miiller's Phj/siology, by Baly, i, p. 440, and in Valentin's Physiologie, i. 700. The poiver of repair in the cornea is illustrated especially by Dr. Bigger, in the Dublin Journal of Med. Science, 1837 ; and by Bonders, in the Onderzoekingen . . . der Utrechtfche Hoogeschool, D. i. p. 31 — The repair of fractured teeth by bone is described by Mr. Tomes in his hental Surgery. The Museum of the College has the best specimens, illustrating repair, that I am acquainted with. 216 RELATIONS OF EEPAIE ANl) INFLAMMATION. matioti forms part of the organic acts by wliich even the smallest instance of repair is accomplished. Now the processes we have traced appear to warrant these general conclusions : — 1. In the healing of a wound by immediate union, inflammation forms no necessary part of the process ; rather, its presence always hinders and may completely prevent it. The healing by immediate union should be a simple re-joining of the several parts without the production of any new material ; and in the same proportion as, in any case, inflammatory matter is effused, either in or between the wounded parts, in that proportion does the healing deviate from the true and best process of immediate union. 2. For subcutaneous wounds and injuries, as in divided tendons, simple fractures, and the like, nearly the same may be said. Inflam- mation is excited by the local injury, but its products form no necessary part of the material of repair ; rather, the more abundant they are, the more acute the inflammation is, and the longer it continues, the less speedy and the less perfect is the process of repair. For here the necessary or best reparative material is a substance which is produced without the signs of co-existent inflammation, and of which the development is diff'erent from that of the inflammatory products that are mingled with it. And this, which is most evident in the case of the healing of subcutaneous injuries by bonds of connection, is pro- bably equally true in the case of subcutaneous granulations. 3. In the healing of a wound by primary adhesion, or by open granulations, we usually have evidence of a process of inflammation, in the first instance, in the presence of its ordinary signs, in a degree generally proportioned to the severity and extent of the injury. 4. Still, in these cases, the signs of an inflammatory process are often absent ; and even when they exist, the process appears necessary for no more than the production of the organisable matter, and, in the case of granulations, for the production of only the first portions of it. The right formation of the cells, and, yet more evidently, their higher organisation into connective and other tissues, ensue only while the signs of inflammation are absent. They are manifestly hindered or prevented when signs of inflammation are present, or when its exis- tence may be suspected in consequence of the presence of some irrita- tion, as a foreign body, dead bone, or the like. The continuance of suppuration, also, during the process of healing, is no proof of the con. tinuance of inflammation, if the account that I have given of pus be true. EELATIONS OF REPAIR AND INFLAMMATION. 217 In these two modes of healing, therefore, we may conclude that inflammation is sometimes absent, and is, in any case, only partially, and at one period, requisite; and that, in regard to its requisite degree, the least amount with which a production of lymph is possible is that which is most favourable to repair. 5. For the process of healing by scabbing, the absence of inflam- mation appears to be essential ; indeed, the liability of our own tissues to the inflammatory process appears to be that which prevents their injuries from being healed as easily and surely, by the scabbing process, as nearly all open wounds in animals are. Lastly, in certain cases, the artificial production of an inflammatory process is necessary for repairs for which the natural processes are insufiicient or insecure. Among these, are the cases of fractures remaining disunited, and of arteries and veins needing ligatures. Such may be regarded as the relations of the reparative process to that of inflammation, as it is commonly understood ; but, I repeat, such a comparison can be made only for the sake of deference to the general state of opinion in matters of surgical pathology. In truth, we know less of inflammation than of the reparative process. "218 PHENOMENA OF INFLAMMATION. LECTURE XIII. PHENOMENA OF INFLAMMATION. It is no more than the trnth which Mr. Travers has well expressed in his work on the Physiolugy of Inflammation and the Mealing Process — ' that a knowledge of the phenomena of inflammation, the laws by which it is governed in its course, and the relations which its several processes bear to each other, is the keystone to medical and surgical science.' It is important, therefore, that we should study this morbid pro- cess with care, and inquire with some minuteness even into its at- tendant phenomena, not only on account of the frequency of its oc- currence, and the variations it may exhibit under different circum- stances, but from its co-existence in many instances with other morbid processes. Three things may be regarded as concurring to produce inflamma- tion of a part : 1st, Defective maintenance of the natural structure of the part ; 2nd, Increased afflux of nutritive materials to it ; 3rd, In- creased production of lowly organised, or of organisable, materials in or about it. These three conditions must not be taken as famishing a strict de- finition of inflammation, for a definition should be a brief description, telling in terms of undoubted meaning the truth, the whole truth, and nothing but the truth, about that to which it relates, and about nothing else. I could easily show that in this sense I have not given a defini- tion of inflammation ; but I could show the same of all other definitions attempted in pathology. Definitions, indeed, are not for the present state of medical science. They can only incompletely circumscribe their subject, and must have shadowy outlines. Still, the three things I have named as concurring in inflammation, are those which we must chiefly keep in view in all our studies of the process ; and we may re- fuse to call anything inflammation in which we have not reason to think that they all concur. PHENOMENA OF INFLAMMATION. 219 The increased afflux of nutritive material being during life the most obvious of these constituents of the inflammatory process, and that on which the chief signs of inflammation depend, may best be considered first. But, in giving it precedence in the description, I do not imply that it is the most important part of the process, or that it most often takes the initiative. The enlargement of the bloodvessels is, I suppose, a constant event in the inflammation of a part ; for, although in certain parts, a.s the cornea, the vitreous humour, and the articular cartilages, some of the signs or effects of inflamjnation may be found where there are naturally no bloodvessels ; yet I doubt whether these ever occur without enlarge- ment of the vessels of the adjacent parts, and especially of those vessels from which the diseased structure derives its natural supply of nutritive material, and which may therefore be regarded as its bloodvessels, not less than those of the part in which they lie. Thus, in inflammation of the cornea, the vessels of the sclerotica and conjunctiva are enlarged, and in ulceration of articular cartilages, those of the surrounding synovial membrane or subjacent bone ; and during the progress of the inflammation, as organisation of the new material produced takes place, not only in these parts, but even in the epithelial coverings of the skin, mucous and serous membranes, new bloodvessels may form continuous with those of the surrounding vascular area.^ The enlargement usually afiects alike the arteries, the capillaries, and the veins of the inflamed part ; and usually extends to some dis- tance beyond the chief seat or focus of the inflammation. To it we may ascribe the most constant visible sign of inflammation, the redness, as well as much of the swelling. Its amount is various ; it may be hardly perceptible, or it may increase the vessels to two or three times their natural diameter. Extreme enlargement is admirably shown in Hunter's specimen^ of the two ears of a rabbit, of which one was in- flamed by thawing it after it had been frozen. ' The rabbit was killed when the ear was in the height of inflammation, and, the head being injected, the two ears were removed and dried.' A comparison of the ears, or of the drawings from them (Fig. 31), shows all the arteries of the inflamed ear three or four times larger than those of the healthy one, and many arteries that in the healthy state are not visible, are, ' 0. Weber in Von Pitha und Billroth's HanSbitoh, i. p. 367. ^ Museum of the CjUege, No. 71. See also Hunter's Works, in. 323, and pi. XX. 220 STATE OF THE BLOODVESSELS. in the inflamed state, bronght clearly into view by being filled with blood. . , I have repeatedly seen similar enlargements of both arteries, and veins, and capillaries, in the stimulated wings and ears of bats, ihe like phenomena occur in the webs of frogs, and other cold-blooded animals ; but in these, I think, the amount of enlargement is generally less.' The redness of an inflamed part always appears more than is pro- portionate to the enlargement of its bloodvessels ; chiefly because the red corpuscles are much more closely crowded than they naturally are in the bloodvessels. The vessels of an inflamed part are not only di- lated, but appear crammed with the red corpuscles, which often lie or move as if no fluid intervened be- tween them : their quantity is in- creased in far greater proportion than that of the liquid part of the blood. This peculiarity is even more manifest in the frog than in the bat ; for in the former, the crowding of corpuscles may occur in vessels that appear to have undergone no change of size on the application of the stimulus. Another, but a minor, cause of the increased redness of the inflamed part, is sometimes to be observed in the oozing of the colouring matter of the degenerating blood-corpuscles, both into all the interspaces be- tween them, and through the walls of the small vessels into the adjacent tissue. During life this may be noticed, especially when the blood is stagnant in the vessels, and it may give them a hazy, ruddy outline ; but it is generally much more considerable after death, when we may ascribe to it no small portion of the redness that an inflamed part may still present. ' Emmert, who is among the few that have measured it, says it is equal to one-half or one-third of the normal diameter of the vessels. Lebert says one-sixth to one-third (Ga-elfc Mhlkale, Mai 15, 18.52). Eig. 31. STATE OF THE BLOODVESSELS. 221 In parts that are naturally vascular, no new bloodvessels are formed in the early stage of inflammation. Many more may come into view than were at first seen in the part ; bat these are only such as were invisible till tho flood of blood-corpusoles fiUed and distended them. So it was in the rabbit's ears ; in the healthy ear no trace can be seen, with the naked eye, of any vessels corresponding with one of the largest, or with many of those of inferior size, in the inflamed ear. So it is, too, in microscopic examinations. Within half-an-hour after stimulating a bat's wiag, many vessels may come into view wbich could not be seen before with the same Ions, and with which none can be seen corresponding in the other wing, though doubtless such vessels exist there of smaller size. Similarly it seems probable that it is only when the inflammation has subsided, and its product begins to be more highly organised, that new vessels are formed in it, as if for the maintenance of its increase or development. So long as the inflammation lasts, the intensest red- ness in parts naturally colourless, though vascular, — even such redness as we see in acute inflammations of the conjunctiva, or yet more remark- ably in those of periosteum,' or in congestion of the stomacb, — is due to the enlargement of the natural bloodvessels, to their admitting crowded red corpuscles, and in a much less degree, and perhaps in only certain cases, to the diffusion of the oolourhig matter of the blood. With the enlargement of the bloodvessels a change of shape is com- monly associated. Being usually elongated as well as dilated, they are thrown into curves and made more or less wavy or tortuous. Thus we may see the larger vessels in an inflamed conjunctiva, and, more plainly, the subperitoneal arteries in cases of peritonitis ; so, too, they are re- presented in the inflamed rabbit's ear. A more remarkable change of shape of the small vessels of inflamed parts is that in which they become aneurismal or varicose. Amongst the first observations of this state were those by Kolliker and Hasse, in an account of a case of inflammatory red softening of the brain, in which many of what, at first sight, appeared to be points of extravasat- ed blood, proved to be dilatations of capillary vessels filled with blood. After this they found the same changes, but in much less degree, in some cases of inflammation artificially excited in the brains of rabbits > As illustrated in Mr. Stanley's plates; plate rii. fig. 1, which reprfc.sents a specimen in tho Museum of St. Bartholomew's, Series i. No. 105. The whole inner surface of the iiiflameil pnrinsLnnn ufa til.ia is bright scarlft. 222 PHENOMENA OF INFLAMMATION ; and pigeons.* Many, as well as myself, have since made similar ob- servations, most of which, however, seem to show that the peculiar di- latation has its seat in the small arteries and veins, as well as in the capillaries of the inflamed part. Among the various forms of partial dilatation, some are like gradual fusiform dilatations of the whole circumference of the vessel; some like shorter and nearly spherical dilatations of it ; some like round, or oval, or elongated pouches, dilated from one side of the wall : in short, all the varieties of form which we have long recognised in the aneurisms and aneurismal dilatations of the great arteries may be found in miniature in the small vessels of such inflamed parts. Some of these Fig. 32. forms ai-e represented in Pig. 32, from the small vessels of an inflamed pericardium. Frequently, however, as this state of the small vessels has been ob- served in inflamed parts (and I believe some measure of it may be found iu the inflammations of most membranes) ; "= yet I think we may not as- sume it to have a necessary or important connection with the other phe- nomena of inflammation. It is often observed, as Virchow ^ especially has shown, in other, besides inflammatory, diseases ; and, in all alike may be referred to a gradual deterioration of the structure of the • ZdUchr. fur missemch. Zoologie, B. i. p. 262. Mr. Kiernau had observed the same changes some years previously. See Dr. Williams' Frinomles of Medicine 2d edit. p. 287. ^ Lebert says it is ,. constant occurrence in experimental inflammations of the subcutaneous tissue of frogs. (Gazette Medicate, Mai 22, 1852.) ' In his Archiv, B. iii. p. 132. STATE OF THE CIRCULATION. 223 vessels, weakenitig them, and rendering them unable to resist uniformly the increased pressure of the blood. That such a deterioration of the bloodvessels should take place in an inflamed part is only what one might expect : it is but a part of the degeneracy of the natural structures, which is a constant constituent of inflammation. Such is the ordinary state of the bloodvessels of an inflamed part : all dilated and elongated, tensely filled with blood, of which the red corpuscles are in excess, often wavy and tortuous, and sometimes variously aneurismal. But the supply of blood to an inflamed part is affected by its mode of movement, as well as by the size of the bloodvessels : this, therefore, I must now describe. Nearly all the observations hitherto recorded, on the morbid changes in the movement of the blood, have been made with the webs of frogs ; and it has been objected that it is not safe to apply conclusions drawn from them to the case of warm-blooded animals. I have therefore employed the wings of bats, in which (when one has acquired some art in quieting them with chloroform or gentle management) nearly all the phenomena of the circulation, as affected by the application of stimuli, may be watched as deliberately as in the frog, and in some respects even more clearly. I think we may believe that what may be seen in the wings of bats occurs, in the like circnmstances, in all warm-blooded animals. It is true that, like the other hybernants, the bats, while they are in their winter-sleep, resemble the cold-blooded animals, in that their tempera- ture is conformed to that of the external air, and scarcely exceeds it. It is true, also, that when they are ill-nourished, their temperature, even in their active state, is comparatively low, ranging from 65° to 80° F., ia an atmosphere of 60° ; and that generally they are liable to much greater diversities of temperatufe than our own bodies are.' And the ' For instance, I found the temperature of a strong and aetire Noctule Bat ( Vespertilio Koctida) thus various in two days : — April 29th, at noon, after he had been nearly two hours under the influence of chloroform, and on awaking had been struggling very actively, his temperature was 99° F. At 9 P.M., having meantime been quiet, hanging by his hind feet, and looking sickly, his temperature was only 70° "When disturbed he became very fierce and active', shrieking and biting the bars of his cage ; and at 9h. 40m. his temperature was 92°- Soon after this he became quiet again, and at lOh. 30m. his temperature was 80°. The temperature of the atmosphere during these examinations had gradually increased from 61° to 67°.— April 30th, at 8 a.m., he was feeble, but not torpid : the temperature of the room during the night had been between 40° and 45°, and was now 224 PHENOMENA OP INFLAMMATION: remarkable condition, discovered by Mr. Wharton Jones,' that those veins in the wing that have valves, contract with regular rhythm for the acceleration of the venous stream, may affect in some measure the morbid as well as the normal movement of the blood. Still, since in the development of their nervous system, and the commensurate deve- lopment of their heart and respiratory organs, and in the close recipro- cal relations in which these act, the bats resemble the other warm- blooded vertebrata, we may, I think, fairly assume a close resemblance also in their processes and conditions of nutrition. The simplest effects upon the bloodvessels are produced by a slight mechanical stimulus. If, as one is watching the movement of blood in a companion artery and vein, the point of a fine needle be drawn across them three or four times, without apparently injuring them, or the mem- brane over them, they will both presently gradually contract and close. Then, after holding themselves in the contracted state for a few minutes, they will begin again to open, and, gradually dilating, will acquire a larger size than they had before the stimulus was applied. Simple as this observation is, it involves some cardinal facts in pa- thology. It illustrates, first, the contractile power of both arteries and veins ; it shows that this is possessed by the smallest, just as it is by the larger, vessels of both kinds ; and by the manner of their con- traction, which follows at some interval after the application of the stimulus, and is slowly accomplished, it shows that their power of con- traction is due to the presence of smooth or organic muscular fibres in their walls. But, again, the experiment shows the vessels re-opening and becoming wider than they were before ; either yielding more to the pressure of the blood which previously they resisted with more strength, or else dilating, as of their own force, with that which Mr. Hunter called active dilatation, and compared with the act of dilatation of the OS uteri. In whichever way the dilatation is effected, whether it be active or passive, the vessels will not at once contract again under the same 67° ; the temperature of the bat was onlj- 59°. At 11 a.m., after struggling violently for half-an-houT, it rose to 69°. After being long under chloroform, and nearly dying, he remained all the afternoon only one or two degrees warmer than the atmosphere! But at night, at 12h. 15m., he recovered and beciimo active ; and, while the atmosphere was at 65° he was at 85°. At 12h. 40m., after being made very fierce, he -was at 88" - and at Ih. 30m. remained at 85°. Nest morning he was again scarcely warmer tlian the atmosphere. The temperature was always taken with a small thermometer applied to the surface of the abdomen. ' Thil. Trail f. 185^, Pait I. STATE OF THE CIRCULATION. 225 Btimulus as before affected tl:em. The needle may now be drawn across them mncb oftener and more forcibly, but no contraction ensues, or only a trivial one, which is quickly succeeded by dilatation. Yet with a stronger stimulus, such as that of great heat, they will again contract and close. And such a contraction excited by a cautery may last more than a day, before the vessels again open and permit the flow of the blood through them. Moreover, we may observe in this experiment the adapted move- ment of the blood. As the vessels are contracting the blood flows in them more slowly, or begins to oscillate ; nay, sometimes, I think even before the vessels begin visibly to contract, one may observe that the blood moves more slowly in them, as if this were an earlier effect of the stimulus : nor have I ever seen (what has been commonly described) an acceleration of the flow of blood in the contracting vessels. Such an acceleration, however, is manifest as the vessels reopen ; and as they dilate, so, apparently in the same proportion, does the flow of blood through them become more free, till, at length, it is manifest that they are traversed by both fuller and more rapid streams than passed through them before the stimulus was applied. How long this state may last depends on many circumstances hard to estimate : but at length it ceases, and the vessels, and the circulation through them, resume their average or normal state. Such are the effects of the mechanical stimulus of bloodvessels. The effects of other stimuli applied to the wings of bats correspond in kind, but differ in degree and extent. If a drop of acetic acid, of tincture of capsicum, of turpentine, or of ethereal solution of canthar- ides, be placed on a portion of the wing, or washed over it, one sees a quickly-ensuing dilatation of the bloodvessels, and a rapid flow of blood through them. I am not sure that the dilatation is preceded by con- traction. Certainly the contraction is very slight, if it occur at all ; but the dilatation is usually much more extensive. When the stimulus has been applied to only one small spot upon the wing, the whole of the bloodvessels in the corresponding metacarpal space, and even those of the adjacent spaces, may enlarge. One might imagine that the dilata- tion of vessels was due to an increased action of the heart, if it were not that (as I think) it is always greater at the very point to which the stimulus was applied than in any other part of the same wing, and is never at all imitated in the corresponding parts of the opposite wing. The state which is thus induced by stimuli is what is commonly understood by the expressions ' active congestion,' or ' determination of 226 PHENOMENA OF INFLAMMATION: blood,' in a part. It consists, briefly, in general enlargement of the bloodvessels of tbe part, induced, as Mr. Lister's observations sliow,i by a relaxation of the muscular fibres of the arterial coats, with an increased velocity of the blood in them. It is, probably, jast such a state as this that is felt by suckling women in what they term the ' flow of milk.' It seems to be an increased flow of blood in the mammary gland just before a quicker secretion of the milk. Less normally, it is such a state as this that we observe in the skin after the application of mustard, or sharp friction, or a heat from 20° to 60° above its own, or in the most striking instance, when a drop of strongest nitric acid is placed on the skin, and, in a few seconds, all the surrounding area seems to flash, and feels burning hot. Such, too, we may suppose to be the state of the vessels of the conjunctiva, when stimulated by dust that is soon dislodged ; and such the condition of many internal organs, when we might doubt whether they are inflamed, or are only very actively discharging their natural functions. Herein, indeed, in what I have described, is one of the pieces of neutral ground between health and disease : a step in one direction may effect the retarn to health ; in another the transit to what all might admit to be the disease of inflammation. Now this transit appears to be made when the circulation, which was rapid, begins to grow slower, without any diminution, but it may be with an increase, of the size of the vessels. This change one may see in the bat's wing. After the application of such stimuli as I have already mentioned, the movement of the blood may become gradually slower, till, in some vessels, it is completely stagnant. The stagnation commences, according to Mr. "Wharton Jones, in the capil- laries ; and first in those which are least in the direct course from the artery to the vein (in the stimulated frog's web) : thence it extends to the veins and to the arteries. A. corresponding state of retardation of blood, leading to partial stagnation of it, may be well seen after such an injury as that of a fine red-hot needle driven into or through the membrane of the wing. The first effect of such an injury (in addition to the charring and searing of the membrane, the obliteration of its bloodvessels, and the puckering of the portion of it adjacent to the burn) is to produce con- traction of the immediately adjacent arteries and veins. They may remain closed, or, as I have already described, after being long closed, ' FhU. Trans. 1858, p. 658. STATE OF THE CmCULATION. 227 may again open, and become wider than they were before. This dila- tation follows more certainly, and perhaps without any previous con- traction, in the arteries and veins at a little distance from the bum. In these there speedily ensues such a state of ' determination of blood ' as I have already described : in arteries and veins alike the stream is full and rapid ; and the greater accumulation, as well as the closer crowding, of the red corpuscles, makes the vessels appear very deep-coloured. The contrast of two diagrams, showing the natural and stimulated conditions in a single segment of the vascular plan of the wing, illustrates this difference sufficiently well ' (Kgs. 33 and 34). The vessels of the one are nearly twice as large as those of the other, darker, and more turgid with blood ; and, in the one are numerous capillaries which are not visible in the other. But diagrams cannot show the changes in the mode of movement. Close by the bum, the blood which has been flowing rapidly begins to move more slowly, or with an uncertain stream ; stopping, or sometimes ebbing, and then again flowing on, but on the whole, becoming gradually slower. Thus it may, at length, become completely stagnant ; and then, in the vessels in which it is at rest, it seems to diffuse and change its colour, so that its crowded corpuscles give the vessels a brilliant carmine appearance, by which, just as well as by the stillness of the blood, they may always be distinguished. As one surveys an area surrounding this part, one sees streams the more rapid the more "distant they are from the focus of the inflammation. Aud often, when there is stagnation in a considerable artery, one may see the blood above or behind it, pulsating with every action of the heart, driven up to the seat of stagnation, and thence carried ofi" by the collateral branches ; while in the corresponding vein, it may oscillate less regularly, delaying till an accumulated force pro- pels it forward, and, as it v/ere, flushes the channel.^ In the area still more distant, one sees the full and rapid and more numerous streams of ' determination ' or 'active conjestion,' which extend over a space alto- gether uncertain. Such is the general condition of the circulation in and around a part that is inflamed. In a few words, there is, in the focus of severe inflam- mation, more or less of stasis — i.e. stagnation of blood ; in and close around it, there is congestion— i.e. fulness and slow movement of blood : ' The plan of vessels drawn is copied from a portion of Mr. Wharton Jones's plate. Phi'. Trans. 1852, parti, plate v. 2 "What I thus described was, no douLt, the result of the rhythmical contraction of the reins, which Mr. Wharton Jones has since discovered. a 2 228 PHEN01IEN"A OF INFLAMMATION ; move distantly aroand there is determination — i.e. fulness and rapid movement of blood. The varieties in lesser points that may be pre- Fig. 33. sented cannot be described. These must be seen ; and, indeed, the whole sight should be viewed by every one who would have in his mind's eye Fig. 3i. a distinct image of what, in practice, he must often too obscni-cly template. STATE OF THE CIRCULATION. 229 The phenomena that I have described as seen in the bat's wing correspond very closely with those observed in the frog's web. Only I think the stagnation of blood is neither so constant nor so extensive in the bat : it is seen in portions of single vessels, rather than in dis- tricts of vessels ; often in corresponding portions of arteries and veins, as they lie side by side. The stagnation usually extends into such branches as may be given from the vessels that are its principal seats ; and three or four such seats of stagnation may appear placed irregu- larly about the burn, or other focus of the inflammation ; but I have never seen a general stagnation of blood in all the vessels of even a se- verely stimulated part. My impression is, that, in strong and active warm-blooded animals, stagnation of blood would be found in only the most severely inflamed parts : in others, I think, retardation alone would exist. To sum up now what concerns the supply of blood in an inflamed part. — We seem to have sufficient evidence that, in general, in the focus of the inflammation, blood is present in very large quantity, distending all the vessels, gorging them especially with red corpuscles, but often moving through them slowly, or even being in some of them quite stag- nant ; that all around this focus, the vessels are as full, or nearly as full, as they are in it, but the blood moves in them with a quicker stream, or may pulsate in the arteries, and oscillate in the veins ; that, yet further from the focus, the blood moves rapidly through full but less turgid vessels. And this rapidity and fulness are not to be ascribed, 1 think, merely to the blood, which should have gone through the inflamed part, being driven through collateral channels, but are in such a state as is commonly understood as an ' active congestion,' or ' determination of blood ' in the part. I have already said that we may believe that what is seen in the bat represents fairly the state of inflamed parts in all warm-blooded animals. I am quite conscious that the most one can see with the microscope, in these experimental inflammations, is but a faint picture of such iaflam- mations as we have to consider in practice ; that it is very trivial in both its appearance and its results. Still, it is a picture of a disease of the same kind ; and a miniature, even faintly drawn, may be a true likeness. Besides, all that can be observed of the complete process of inflammation in man is consistent with what we can see in these lower and lesser creatures. Tbe bright redness of an inflamed part testifies to the fulness of its bloodvessels and the crowding of the corpuscles ; the occasional duskiness or lividity of the focus is characteristic of stag- 230 PHENOMENA OF INFLAMMATION : nation ; the tlirobbing in the part, and about it, and the full hard pulse in the ministrant arteries, are sure signs of obstruction to the passage of blood ; the gush of blood on cutting into the tissues near an in- flamed part, or in bleeding from one of their veins, tells of the deter- mination of blood in these, and of the tension in which all the containing bloodvessels are held. It is particularly to be observed that the stagnant or retarded blood is not apt to coagulate. I have found it fluid after at least three days' complete stagaation, and so, I believe, it would remain till it is cleared away, unless the part sloughs. In the latter case it would coagulate, as it does in carbuncles and the like, which hardly bleed when we cut them through ; but, so long as the blood is fluid, though staguant, it may be driven from the vessels with full force, so soon as an easy exit is made for it by cutting into the inflamed part, or opening one of its large veins. I need only here refer to Sir W. Lawrence's well- known and instructive experiment. In a patient with an inflamed hand he made similar openings into veins in both arms. From the vein on the diseased side three times more blood flowed than from the veiu in the healthy arm in the same time. This increased flow repre- sented at once the greater determination of blood about the focus of the inflammation, and the greater tension in which the walls of the blood- vessels, and, indeed, all the tissues of the inflamed and swollen part, were held. Now, to what can we ascribe these changes in the movement of the blood ? It has been commonly said that, as the vessels contract, therefore the movement of blood becomes more rapid in them, as when a river entering a narrow course moves through it with a faster stream ; and that then, as the vessels widen, so the stream becomes, in the same proportion, slower. But this is far from true. The Stream becomes slower as the artery or vein becomes narrower by contraction ; and then, as the tube again dilates, the stream grows faster; and then, without any appreciable change of size, it may become slower again, till complete stagnation ensues in at least some part of the blood- vessel.i I think I can be quite sure that the velocity of the stream, in any vessel of an inflamed part, is not wholly determined either by the ' As Mr Wliarton Jones has shown, the retarded stream exists only when the Tessel is generally contracted, and the accelerated stream when it is generally dilated ; when a siiigle vessel presents successive enlargements and diminutions of calibre, the rate of the stream in it diminishes in the former and increases in the latter. STATE OF THE CIRCULATION. 231 diminution or enlargement of the channel, or by the stagnation or con- gestion of blood in the vessels beyond. That much of the change in rate of movement depends on these conditions cannot be doubted ; and it may seem unnecessary to question their suf&cienoy for the explana- tion of that change, after Mr. Wharton Jones's observations. Bat I think other forces must still be considered, whose disturbance may contribute to the result. Whether we name it vital affinity, or by any other term, or (which may, as yet, be better) leave it unnamed, I can- not but believe there is some mutual relation between the blood and its vessels, and the tissues or other substances around them, which, being natural, permits the most easy transit of the blood, but, being disturbed, increases the hindrances to its passage. Such hindrances appear to be produced by the addition of salts of baiyta, or of potash, to the blood ; and by an excess of carbonic acid in the blood that should traverse the minute pulmonary vessels. The presence of an excess of urea in the blood probably produces the like effect : and some of the facts connected with other than traumatic inflammations ajspear quite inexplicable without such an hypothesis as this. This hypothe- sis is supported by the very striking experiments made by Mr. Lister,' as to the influence exercised by irritants on the pigment-cells in the frog's web, and on the movements of the cilia, which indicate that an impairment in the functional activity of the tissues is the essential occurrence which leads to inflammatory stasis. These observations are in harmony with those made by the same author on the blood- corpuscles, which appear to acquire adhesiveness, and accumulate in the capillaries of an irritated part, in consequence of the aifected tissues ceasing to maintain their normal relations to the blood. Thus not only in the bloodvessels and the rate at which the blood moves through them, but in the blood itself, important changes occur in inflammation, which no longer adapt it for the normal nutrition of the parts through which it flows. That this adaptation of the blood to the maintenance of the tissues is disturbed, in many cases of inflam- mation, is proved by the instances to which I shall have to refer, and which plainly have their origin in morbid conditions of the blood. But I fear that the nature of this disturbance cannot yet be chemically expressed, and that the facts which chemistry has discerned, in the condition of the blood in inflammations, cannot be safely applied in explanation of the local process. For, first, we observe the phenomena ' Phil. Trans. 1858. 232 PHENOMENA. OF INFLAMMATION : of inflammation wliere we cannot suppose the whole blood disordered ; as after the application of a minute local stimulus, such as a foreign body on the conjunctiva : secondly, the chemical changes observed in the blood during inflammations are not peculiar to that state, but are found more or less marked in pregnancy, and in other conditions in which no inflammatory process exists : and, thirdly, among the changes observed in inflammatory blood, the principal one — namely, the supposed increase of the fibriue-forming substances, as in the pro- duction of the ' buffy coat ' — is ambiguous ; it may be at once an increase of those substances and of the white corpuscles, which con- stituents of the blood cannot be well separated by any process yet invented ; and in all the estimates of fibrine, whether in health or in disease, the weight of the white corpuscles is included. Now in some inflammations these corpuscles are increased ; and in such cases we have no means of clearly ascertaining how much of an apparent increase of fibrine is really such, and how much is due to the corpuscles en- tangled in the fibrine. Till this can be settled, I think we may not deduce any of the local phenomena of inflammation from the increase of fibrine in the blood ; neither, more assuredly, can we trace, as some do, the fever and other general signs of inflammation to the abstrac- tion of fibrine and albumen by the exudation from the blood. The other principal changes of the blood in inflammation — the diminution of its red corpuscles and increase of water — are even less adapted to explain any of the phenomena of the Ijcal process. What- ever may be their strength or value as facts, they are as yet isolated facts, such as we cannot weave into the pathology of the disease. I fear, too, that the structural condition of the blood will not, more than the chemical, help us to explain all the phenomena of inflamma- tion. Some of oUr nlost worthily distinguished pathologists have ascribed much to the existence of large numbers of the white blood- corpuscles, and their accumulation and even passage through the walls of the vessels of the inflamed parts. ^ Indeed, they have taken this for ' Nearly thirty years ago Dr. W. Addison stated, as the result of his experimeatal researches into the Phenomena and Products of Inflammation (first series in Trans. Prov. Med. Associatiom ioi 1842; second series, Loudon, 1843; third series, London, 1845, and in several subsequent writings), that when the frog's web is irritated, the white blood-corpuscles not only accumulate in the vessels, and adhere to their walls, but become incorporated with the latter, and even pass through into the sur.ounding tissue, where they constitute corpuscles of the inflammatory lymph, pus, or mucus corpuscles. He also pointed out (second series, p. 50) that the red corpuscles adhere, in an inflamed part, to the walls of the capillaries and minute vuiiis and arteries, and STATE OF THE BLOOD. 233 ths foundation of nearly thoir whole doctrine of inflammation, ascribing to it the stagnation of the blood, the changes it is presumed to undergo, and the origin even of the pas and inflammatory lymph- corpuscles, which are found in the tissues of the inflamed parts. Their observations have been chiefly made on frogs, and the extent to which they may admit of application to our own case, or perhaps to that of enter into the composition of the tissue. In 1846, Dr. Augustus "Waller {Phil. Magazine, Oct. Nov.) described the mode of passage of the white corpuscles through the walls of the capillaries, and applied this observation to the formation of pus and mucus corpuscles. Although the accumulation of white blood-corpuscles in, their adhesiveness to the walls of the vessels of an irritated part, and the close structural resemblance between them and the corpuscles of pus and inflammatory lymph, have been recognised by pathologists, yet the migration of the white blood-cells through the walls of the vessels, and their actual convertibility into mucus corpuscles, or inflammatory lymph-cells, or pus after they had passed into the tissues, have by no means generallj' been admitted. Two years ago Dr. Cohnheim of Berlin (Virchow's Archiv, xl. 1) reopened this question in a memoir on Inflammation and Suppuration. He entered into the subject with great minuteness, and from numerous experiments and observations came to the conclusion that not only the white, but the red corpuscles of the blood, pass through the walls both of the capillaries and veins of an irritated and inflamed part, and, when in the tissues, they may migrate to some distance from the vessel out of which they have wandered ; their movements being of the same ' amceboid ' character as has already (p. 172) been referred to as exhibited by the living pus cells. Like Addison, he considers that they become pus-corpuscles, and constitute an important source from which those cells are derived. It must, without doubt, be admitted that the progress of anatomical and physio- logical research, more especially during the past seven years, has rendered the possibility of a 'wandering' of the blood corpuscles through the walls of the vessels much less difficult to conceive than when Addison's observations were first published for at that time, and for many years afterwards, nothing was known of the power of spontaneous movement possessed by the corpuscles ; and the yielding ductile character of the walls of the living capillaries, formed apparently of a soft nucleated protoplasm, was not recognised. Just as the spermatozoa may, in the higher mammals, bore through the capsule of the ovum, where no micropyle is present, so may it be possible for the blood corpuscles to j)ierce the walls of the capillaries even without the aid of visible pores, or stomata. Cjhnheim's observations have led other pathologists to repeat his, and devise new, experiments, and a whole series of memoirs has recently appeared, some of which are confirmatory of, others antagonistic to, these doctrines. It may sufiice in this place to give the references to the publications where the literature of this subject may ba studied: — Von Eecklinghausen, Virchow's Archiv, 1863. Med. Centralblatt, No, 31, 1867. Strieker, Wiener Sitzuligs berichte, li. and xii. C. J. Eberth in part 2 of Strieker's Handbuch der Grewebelehre. H. 0. Bastian : Trans. Path. Soc. London, April, May, 1868. Lionel Beale : Med. Times and Gazette, May, 1868. J. Kremiansky: Wiener Med. Woch.'Sos.l-6,'\.%&&. F.A.Hoffmann: Virohow's Archiv, -siu. ZOi. K. Balogh: Idem.ylv. 19. J. Cohnheim: Ide7n, xlv. 333. W. Donitz: Seichcrt- u. JDii Bois Reymond's Archiv, 1868, 394. W. Koster: Nederl. Archie/, iii. iv.; Jnl. of Anat. and Phys. iii. 246. W. Leissler : Inaugural Dissert. Giessen. J. G. Richardson : Qiiart. Jour. Micros-. So. July, 1869. 234 PHENOMENA OF INFLAMMATION: any -warm-blooded animal, will require to be tested by further examina- tion before all the conclasions which have been drawn from them can be admitted. In many frogs, especially in those that are young, or sickly, or ill-fed, the white corpuscles are abundant in the blood. They are rudimental blood-cells, snch as may have been formed in the lymph or chyle : and in these cases they are probably either increasing quickly in adapta- tion to quick growth, or else relatively increasing, because, through disease or defective nutriment, although their production is not hindered, their development into the perfect red blood-cells cannot take place. But I doubt if this happens in older or more healthy frogs, or in any ordinary inflammation in the warm-blooded animals. I have drawn blood fronn the vessels in the inflamed bat's wing, in which it was quite stagnant, and have found not more than one white corpuscle to 5,000 red ones. I have often examined the human blood in the vessels of inflamed parts after death, and have found no more white corpuscles in them than in those of other parts. In blood drawn from inflamed parts during life, I have in various instances found only the same proportion of white corpuscles as in blood from the healthy parts of the same person. I therefore cannot but accord with the opinion, often expressed by Mr. Wharton Jones and Dr. Hughes Bennett, that an especial abundance of white corpuscles, in the vessels of an inflamed part, is neither a constant nor even a frequent occurrence ; and I believe that, when such corpuscles are numerous in an inflamed part, it is only when they are abundant in the whole mass of the blood.' Now, as already stated, they are thus abundant in some cases of inflammation ; especially, I think, in those occurring in people that are in weak health, and in the tuberculous ; but, even in these cases, I have never seen an instance in which they were present in sufficient quantity to add materially to the obstruction of the blood in the inflamed part, nor one in which their number could be suspected to alter peculiarly the consti- tution of the blood therein. It has long been known that when healthy blood is received on a glass plate, and immediately examined with the microscope, the cor- puscles may be seen, in about half-a-minute, to run together into piles, or rouleaux, which arrange themselves in a small meshed network, as in the adjoining figure (a), (Fig. 35). Mr. Wharton Jones was the first • Dr. Hughes Bennett's rpsearches on Leueocythsmia liave shown that even the extremest abundance of white corpiiscles in the blood has no tendency either tj produce or to aggrarate inflammations. STATE OF THE BLOOD. 235 to point out that if a drop of blood of a patient suffering from acute rheumatism, or inflammation, be similarly examined, the piles of corpuscles are formed more rapidly and run more closely into masses, which have large spaces between them (b). By this arrangement, the thin clot outspread on the glass has the peculiar mottled pink and white appearance, which Mr. Hunter observed as one of the characters of inflammatory blood. The same condition is observed in the blood of pregnant women, and appears natural in that of horses ; and in all these cases it may be regarded as the chief cause of the formation of the ' bufiy coat,' inasmuch as the clustered blood-cells, sinking rapidly, generally subside to some distance below the surface of the liquid part of the blood, before the ooagalation of the fibrine is begun. This B Fig. 33. aggregation of the corpuscles does not appear to be due, as was at one time supposed, to an increased viscidity of the liquor sanguinis owing to an excess of fibrine, for Lister's observations have shown that they aggregate quite as closely after the removal of the fibrine, as they did before. That a similar adhesion of the blood-cells, both white and red, to each other, and to the inner wall of the vessel, occurs in the vessels of an inflamed part, has been very powerfully advocated by some path- ologists. This view has been more especially held by those who have studied the process by watching the effects of iiTitants on the frog's web, and to this adhesiveness of the corpuscles they ascribe the produc- tion of the stasis of the blood in the part. Such experiments as Mr. Lister has performed show, without doubt, that when the web is irri- tated or inflamed, both kinds of corpuscles acquire such a degree of 236 PHENOMENA OF INFLAMMATION. adbesiveness as makes them stick to each other and to the walls of the vessels. But I have seen nothing of the kind in either the inflamed bat's wing or the vessels of inflamed organs examined after death. When the blood is not stagnant, the corpuscles are indeed closely crowded, but they are not clustered, nor do they appear adherent : neither does such clustering appear even in stagnant blood; the change here appears to be a difiusion of the colouring matter, so that the out- lines of individual blood-cells cannot be seen, and all the contents of the vessel present a uniform bright carmine tint. But whatever naay be the cause of the stagnation, there is evidence that the stasis and con- gestion are independent of the general circulation ; for if irritants are applied to the web of a frog's foot which has been amputated, an accumulation of corpuscles in the vessels of the part takes place,' in the same manner as when the limb is connected with the trunk. Far- ther, it must not be lost sight of, that, whatever be the visible condition of the blood -corpuscles in an inflamed part, they are constantly degene- rating, like the vessels and the surrounding textures. The blood which cannot maintain these textures is as Httle able to maintain itself, and hence in great measure ensue those general effects and con- stitutional disturbances which are met with in the train of an inflam- mation of purely local origin. ' H. Weber, Miiller's ArcMv, 1853 ; Schuler, Wurzhurg Verhandl. B. iv. H. iii. Gunning, pamphlet, Utrecht, 1857 ; Lister, FhiL Trans. 1858. PRODUCTS OF INFLAMMATION. .2b7 LECTURE XIV. PRODUCTS OF INFLAMMATION. The state described in tlie last lecture may, without farther change, cease and pass by, and leave the part, to all appearance, jnst as it was before. And there are two chief modes in which this may happen ; namely, by resolution or the simple cessation of the inflammation, and by metastasis, in which, while the inflammation, disappears from one part, it appears in another. So far as the inflamed part itself is con- cerned, I believe the changes are in both these cases the same, and con- sist in a more or less speedy return to the normal method of circulation, and the normal condition of the blood and of the nerves ; the tissue itself presenting no apparent change of structure. I do not know that any description of the process of recovery from the inflammatory state would tell more than is implied by calling it a gradual return to the natural state, a gradual retracing of the steps by which the natural actions had been departed from. As it has been watched in the frog's web, and in the bat's wing, the vessels, that were filled with quick-flowing blood, become narrower, the streams in them also becoming slower, and less gorged with red blood-corpuscles, till the natural state is restored. The pulsating or slower streams are equalised with those about them, and, gradually making their way into the stagnant columns, drive them on or disperse them. In the frog, clusters of blood- corpuscles have been seen to become detached, by a stream breaking off portions of the stagnant blood, and then to float into the cui-rent, where, gradually, they disperse. So, too, in the tad- pole, after injury, I have seen fragments of fibrine, washed from the blood in the vessels of the injured part, floating in some distant vessels. Virchow's and Kirkes's observations leave no doubt that similar changes may occur in the warm-blooded animals, and may be the source of great evil by carrying the materials of diseased or degenerate blood from a diseased organ to one that was previously healthy (p. 110). 238 PRODUCTS or INFLAMMATION: It may be difficult to explain this recovery in the cas3 of complicated inflammations. When a slight mechanical stimulus has been applied, and the vessels, after contracting, have dilated, we may see some signs of "weakened muscular power, in the fact that the same stimulus will not make them contract again ; and then their gradual recovery may be the consequence of their regaining their weakened and exhausted power, just as a wearied muscle does when left at rest. This must al- ways be one element in the recovery of the natural state, by a part that has been inflamed ; indeed, it is probably that part of recovery which is most slowly achieved. Still, it is perhaps only one element in the process of recovery. In an inflammation in which all the conditions of nutrition are at fault, each must recover its normal state ; but of the manner in which they severally do so we have no knowledge. The order in which they are restored is scarcely less uncertain : probably it is not constant, but may depend, in great measure, on the order in which they were involved in error. But we have no clear facts in this matter ; only we may observe, that in many cases, if we correct the error of one of the conditions of nutrition, the rest will be more apt to correct themselves. Thus, of the remedies for inflammation, few can act upon more than one of the conditions on which it depends ; yet they may be remedies for the whole disease ; for, as it were, by abstracting one of its elements, they destroy the consistence and mutual tenure of the rest. The cessation of the disease may be regarded as the most perfect cure of which inflammation admits. It is in many cases an unalloyed advantage ; but in some, though the local change may be the same, it is not so ; for materials accumulated ia the stagnant blood of the in- flamed part, or absorbed from its morbidly altered tissues, may, when the inflammation subsides, pass into the general current of the blood, and infect its whole mass, or disturb the nutrition of an organ more ' important than that which they have left. Such are the events of the metastasis of gout, and the premature subsidence of cutaneous erup- tions. At the commencement of the last lecture I pointed out that one of the three factors which concurred in inducing the process of inflamma- tion was an increased production of lowly organised, or of organisable materials in or about the part. To the consideration of the varieties and mode of production of those materials I shall now proceed. In natural nutrition the material which enters into the tissues of a EFFUSION OF SERUM. -239 part for their nutrition is unseen ; we cannot trace its passage throuo-h the vessels ; it does not accumulate within or about them ; and it as- sumes its due organic form by becoming incorporated with the textures as soon as it is outside the vessels. Even in secretion, the sister process, though we recognise by the flow of the secretion from a gland, that it has acquired material from the blood, yet the passage of this material through the vessels into the gland-cells cannot be seen. In repair the material may be visible, though difficult to collect in the raw state — i.e. before it assumes organic forms, and is assimilated to the structure it has to replace. But in inflammation an abundant material often exudes from the blood, or is produced in the tissues of the part. It collects in the sub- stance of organs and tissues, and makes them succulent ; it mingles with their own degenerating materials ; it infiltrates layers of mem- branes, and makes them thick and spongy ; it oozes out on free sur- faces, and may be obtained nearly pure ; it collects in the interior of epithelium and other cells, swells them out and makes tham opaque, and when it is produced in glands it is mixed with their proper secre- tions, and may even block up and obstruct their ducts. The material thus exuded, or produced, in inflammation, which represents a morbid state of the productive process, varies according to many varying conditions. It may be like the serum of the blood, or the liquor san- givinis, or even may be blood itself, or it may be mucus ; or, so soon as we can discern, it may be solid or organised, and may contain cell structures which are not unlike the white corpuscles of the blood or lymphatic fluid. These substances may be mingled with each other in many varying proportions, which are apparently determined either by the structure of the tissue of the inflamed part, the violence of the in- flammation, or the state of the blood. The serum and the liquor sanguinis are mei'e exudations from the blood, characterised by containing an excess of chloride of sodium ' and of phosphates, which have passed in the liquid state through the walls of the vessels into the tissues of the inflamed part. But the cell structures in the solid product are apparently produced in the inflamed part itself. Under some conditions they may develope and organise into likeness with the tissues amidst which they are placed. Under other conditions they may degenerate, and the degeneration may ' Dr. Lionel Beale, Medioo-Chir. Trans, xxxv. 240 PEODUCTS OF INFLAMMATION : at the same time involve the proper textures of the inflamed part, and excite a series of destructive changes which may lead to the softening, absorption, ulceration, and death, not only of the products of ihe in- flammation, bat of the proper elements of the part itself. A natural division, therefore, of the inflammatory changes of the nutritive pro- cess may be into those that are productive and those that are des- tructive. I shall proceed now to the consideration of the materials which are exuded or produced in the inflammatory process. 1. The effusion of serum, except as the result of the lowest degrees of inflammation, or as a diluent of other products, is probably a rare event. That which is usually regarded as a serous effusion in inflam- mation, is, in many cases, a fluid that contains fibrine or rather a fibri- nogenic substance, which coagulates on exposure to the air and re- sembles the liquor sanguinis rather than mere serum. It is this kind of effusion on which Vogcl ' has fully written, under the designation of ' Hydrops fibrinosus.' A good example of it maybe seen in the fluid contained in blisters, raised by the action of cantharides or heat applied to healthy persons. Another example is in the fluid that rapidly fills an injured and immediately inflamed joint or hernial sac. And another form of liquid effusion differs from serum, in that it contains cells : such is the fluid that fills the early vesicles of herpes, eczema, and some other cntaneous diseases. The fluid that contains fibrine or fibrinogen, and is most generally described as a serous effusion, may have the ordinary aspect of serum ; more rarely it is colonrless or opalescent, like the liquid part of the blood which one sees collecting for the formation of a buffy coat. The fibrinogen that it contains may remain in solution, or without coagula- tion, for an indefinite time within the body, but will coagulate readily when withdrawn. For example, the so-called serous effusion which is abundant in the integuments near the seat of an acute inflammation in deeper parts, and which flows out like a thin yellowish serum, after death, will soon form a soft jelly-like clot, that is made succulent with the serum soaked in it. The fibrine appears tough, opaque-white, and stringy, when the fluid is expressed from it, and shows all the recog- nised characters of the fibrioe of the blood. Thus, to mention but one case which was remarkable for the delay of the coagulation. — A man ' Paihohgische Anatomie, p. 23. EFFUSION OF BLOOD. 241 received a compound fracture of the leg, and it was followed by pUeg- monous inflammation and abscesses up tie limb. As soon as the inflam- mation had subsided enough, the limb was amputated ; and, three days afterwards, in examining it, a quantity of serous-looking fluid oozed from the cut through the integument. I collected some of this, and, after four hours, it formed a perfect fibrinous clot ; yet the fibrinogen in this case had remained among the tissues without coagulating for three days after the death of the limb, and for many more days during the life of the patient. Such, too, are the efiusions like serum in blisters raised on the skin by heat or cantharides ; such the serous efiusions of peritonitis, as in hernia, and of many cases of pleurisy and pericarditis. All these fluids, though they may retain their fluidity for weeks or months within the body, during life, may yet coagulate when they are removed from the body. With these, too, may be reckoned, but as the most nearly serous of the class, the fluid of common hydrocele ; for I have seen a small coagulum form in such fluid spontaneously ; and the presence of fibri- nogen may always be proved by the formation of a clot, when a small piece of blood-clot, of some organised tissue or other fibrino -plastic substance, is introduced into the fluid.' One can rarely tell why the production of the fibrine in these cases should be delayed : there are here, the same diflfioulties as are in all the esceptions from the general mles of the coagulation of the blood. But, it may be observed, the delay of the coagulation is a propitious event in all these cases ; for, so long as the effusion is liquid, absorption may ensue on the subsidence of the inflammation ; but absorption is more unlikely and tardy when the fibrine has coagulated. Thus, large quan- tities of fluid, which, we may be sure, contained fibrinogen, may disap- pear by absorption from the seats of acute rheumatism or gout, or from the pleura or peritoneum, or from the subcutaneous tissues, and leave onlyinconsiderable adhesion, or thickening of the affected part. But, on the other hand, when, in the same class of cases, the fibrine coagulates, its absorption necessarily requires a much longer period. Thus it is in the cases of what has been called solid cedema, where, in the neighbour- hood of acute inflammation, an efiusion long abides with all the charac- ters of ordinary serous oedema ; but, at length, the tissues are found indurated and adhering) the oedema having consisted in the effusion of serum with fibrine which has coagulated. Thus too, it is that the dam- ' Dr. A. BnchanaD, Frccudings of Glasgow Philosophical Society/, 1845. 242 PRODUCTS OF INFLAMMATION: age done by rhetimatism in a part is, on the whole, in direct proportion to the length of time it has subsisted there, and the opportunity given by time for the coagulation of the fibrine. From what I have said, it will appear that nearly all of what are called serous effusions in inflammation are effusions of fluid containing a fibrinogenic material. But it may be said that we often find, after death, effusions which contain nothing but the constituents of serum though produced in an inflammatory process. If, however, we examine these cases more closely, they will appear consistent with the others : some of the fluids will coagulate if kept for several hours, or if mixed with other serous fluids, or if fibrino-plastic substances be placed in them ; in others we find flakes of molecular matter, indicating that fibrine had been already coagulated, or that corpuscles had existed in it, but that subsequently they were disintegrated, or even partially dis- solved ; and in some we may believe that similar materials were decomposed in the last periods of life, or after death. On the whole, it seems sure that an efi'usion of serum alone is a rare effect of inflammation, and that generally it is characteristic of only the lowest degrees of the disease. Among the instances of it are, probably, the cases of the chronic forms of hydrops articuli, some forms of hydrocephalus, and some cases of inflammatory oedema of the mucous membrane, as in the cedema of the glottis, and chemosis of the conjunctiva. In the nearly constant fact of the presence of fibrinogenic materials and of corpuscles in the products of inflammation, we have one evidence of the likeness between inflammation and the normal process of nutri- tion, and of its difference from the merely mechanical obstructions or stagnations of the blood. In these, the material effused from the blood is usually the merely serous part : the fluids of anasarca and ascites will not coagulate ; they present neither fibrine nor corpuscles, except in the cases of extremest obstruction, when, as in cases of ascites from advanced disease of the heart, oiie may find flakes of fibrine floating in the abdomen, or masses of it soaked and swollen up with serum. Any cause indeed which increases the pressure of the blood in a given local- ity, and at the same time diminishes the resistance ofi'ered by the walls of the vessels, tends to facilitate the passage, not merely of the fibrino- genic substance, but of an increased quantity of albumen out of the blood. As both these conditions exist in the inflammatory process, the effusion of these materials is readily accounted for. EFFUSION OF BLOOD. 243 II. Effusion of Blood. — Among the effasions of blood that occur in connection -with the inflammatory process, many, as Eokitansky has explained, are examples of hcemorrhage from rupture of the vessels of the inflammatory products recently become vascular. The new vessels, or their rudiments, are peculiarly delicate ; and being apt to rend, like the vessels of new granulations, with a very slight force, especially when they are made turgid or dilated by an attack of inflam- mation of the newly-formed material in which they lie, they will commonly be sources of considerable bleeding. So, for example, it probably sometimes happens when, as the expression is, a hydrocele is converted into a hsematocele ; some inflammatory products becoming vascular, and being submitted to even slight violence, their vessels break and blood is poured into the sac. So, too, probably, it is with many or all the cases of what are called heemorrhagic pericarditis. But of these, which may be called secondary Jicemorrhages, I will speak hereafter. Primary efiusions of blood, i.e. efiusions of blood poured from the ruptured vessels of the inflamed part, and mingled with the inflamma. tory products, appear to be rare in some forms or localities of inflam- mation, but are almost constant in others. Thus, e.g. in pneumonia, extravasated blood-corpuscles give the sputa their characteristic rusty tinge. In the inflammatory red softening of the brain, blood is also commonly efiused ; and the condition of the vessels which I described in the last lecture (p. 221) as well as the increase in the blood-pressure, may readily account for their rupture. There are also other cases of these effusions of blood in inflammation ; but I beheve these imply no more than accidents of the disease. We must not confound with hasmorrhages the cases in which the inflammatory products are mei-ely blood-stained, i.e. have acquired a more or less deep tinge of blood, through the oozing of some dissolved colouring matter of the blood. The natural colour of inflammatory products is greyish or yellowish-whitcj and, even when they have become vascular, their opacity in the recent state prevents their having any uniform tint of redness visible to the naked eye. When they pre- sent the tinge of redness, it is either because of heemorrhage into them, or because they have imbibed the dissolved colouring-matter of the blood : and when this imhibition happens during life, or soon after death, it is important, as implying a cachectic, ill-maintained condition of the blood in which condition the colouring matter of the corpuscles becomes unnaturally soluble. Thus, blood-stained efi'usions are among the evil E 2 244 PEODUCTS OF INFLAMMATION : signs of the products of inflammation during typhus, and other low eruptive fevers, in syphilis, and in scurvy. III. Productmi of ' Inflammatorij LympJi.' — Serous effusions, then, appear to be rare as the results of inflammation ; and effusions of blood are but accidents in its course. The characteristic primary product of the inflammatory process is the soft, solid material, which the elder writers named ' lymph,' ' coagulating ' or ' coagulable lymph ;' and which more lately has been called ' exudation,' or ' inflammatory exudation.' It is to be regretted that all these terms fail in affording, with sufficient exactness, a distinctive appellation to this substance. The term ' exudation ' is objectionable, because it has been employed as well for the act of separation from the blood, as for the material sepa- rated, and it has been applied alike to the liquid material effused from the blood — e.g. the serum and the liquor sanguinis — and to the cor- puscles produced in the inflamed part as a result of the inflammatory process itself. The term ' lymph ' is also objectionable, since the same word is employed to designate the fluid (and corpuscles suspended in it) which flows along the lymphatic vessels. But as, in speaking of this product of inflammation, some term must be used, and as it is diflEL- cult to dispense with one which has long been employed, it may be convenient, seeing that it is the older term, to retain, till some better new one be proposed, that of ' inflammatory lymph ' to express those forms of inflammatory products which are or may become organized. The form assumed by the ' inflammatory lymph ' product, when in the solid state, is not always the same. There are, father, two chief forms, which, though they are often seen mixed in the same material, are yet so distinct as to warrant the speaking of two varieties, by the names otfibrinoils and cor]}uscular.^ To the fibrinous variety belong, as typical examples, all the instances in which a liquid effusion coagulates into the solid form, and yields, when the fluid is pressed from the solid part, either an opaque- whitish, elastic substance, having the general properties of the fibrine of the ' Corresponding vaiielies are distinguished ol' impiie'd Ly Vogel, p. 30, Dr. Andrew Clark {Medical Gazette, vol. xliii. p. 286), and others. It should be understood, however, that the term ' fibrinous ' is used withoutintending more than that an apparent lilieness to the fibrine, obtainable from blood, is observed in the material of those varieties of inflammatory products which are distinguishable by firmness, or toughness, or by readiness to form adhesions. INFLAMMATORY LYMPH. 245 clot of blood, or tlie softer, and, as it is supposed, the less perfect or less developed, fibrins of tke chyle or the absorbed lymph. Such examples of fibrinous inflammatory product, free or nearly free from corpuscles, are found, in the cases already referred to, among what have been supposed to be efi'usions of mere serum. Such are many instances of efi'usions produced by blisters and other local irrita- tions of the skin in healthy men : such, too, are most of the effusions in acute inflammations of serous membranes, especially in those of traumatic origin, and iu those that occur in vigorous men. If, in any of these cases, the ' inflammatory lymph ' be examined after coagula- tion, it may be hard to distinguish it from the fibrine of the clot of blood. The layers of fibrinous substance thus formed may be known to the naked eye, when, on the surface of membranes, by their pecuHar elasticity and toughness, their compact and often laminated structure, their greyish or yellowish- white and semi-transparent aspect, and their close adhesion to the membrane, even before they have become vascular. In the corpuscular variety colourless corpuscles are found, which, in many of their characters, closely approximate to the white corpuscles of the blood, or lymphatic fluid, or those of granulations.' Sometimes they float free in a liquid effusion, as in the early-formed Contents of the vesicles of herpes, eczema, pemphigus, and vaccinia; in the fluid of blisters raised in cachectic patients ; in some instances of pneumonia ; and in the fluid contained in the sac of an inflamed serous membrane. But at other times they are closely aggregated together, and form a soft solid mass, such as may be readily recognized on the free surface, or in the substance of an inflamed serous membrane, or in a solid organ as an inflamed muscle. The first discernible organic form in the fluid of herpes, for example, is that of a mass of soft, colourless, or greyish-white protoplasm, about ss^-B^^ of an inch in diameter, round or oval, pellucid, but appearing, as if through irregularities of its surface, dimly nebulous or wrinkled. It does not look granular, nor is it formed by an aggrega- tion of granules ; nor, in its earliest state, can any cell- wall be clearly ' This structural resemblance shows that a single primordial form may exist in the rudiments of many structures, which in later periods of their existence are widely different. It is a repetition of a fact in the first development of beings. In the early embryo, the most diverse forms are developed from a nearly uniform mass of primordial embryo or germ cells. And so it is in later life ; many of both the normal and the morbid structures start from one primordial form, and thence proceeding, diverge more and more %videly in attaining their several perfect shapes. 246 PEODUCTS OF INFLAMMATION demonstrated, or any nucleus, on adding water. But, in a few hours, as the development of the cell-germ proceeds, a pellucid membrane appears to form as a cell- wall over its whole surface ; and now, when water is added, it penetrates this membrane, raising up part of it like a clear vesicle, while upon the other part the mass retreats, or subsides, and appears more nebulous and grumous than before. In yet another state, which appears to be a later stage of development, the action of water not Fig. 36. Fig. 36. Vertical section through a portion of an inflamed pericardium. It Represents the thick layer of corpuscular lymph at the free surface of the serous membrane. Owing to the compact manner in which the cells are packed, it is difficult without dissection to recognise the forms of the individual corpuscles, hut at the marginal part of the figure several cells, isolated from the general mass, have been drawn, c. Pale round corpuscles consisting of a weU-marked nucleus invested by soft faintly granular protoplasm, d. Corpuscles undergoing nuclear subdivision, e. Cor- puscles which are becoming elongated into fibro- cells, b. The sub-epithelial connective tissue, in which small groups of inflammatory lymph-corpuscles may be seen. The lymph had become vascular, and vessels filled with a carmine injection passed into it from the sub- epithelial connective tissue. It is probable that these vessels were dilated somewhat from the force used in the injection. The preparation from which the section was taken is No. 2052 a, Anatomical Museum, University of Edinburgh. INFLAMMATOEY LYMPH. 247 only raises up a cell-wall, but breaks up and disperses tlie outer part of the contents of the cell, and exposes in the interior a nucleus which is commonly round, clearly defined, pellucid, and attached to the cell- wall. These cell-forms, and those met with in other vesicular erup- tions, are, it is probable, developed from the nuclei or immature cells of the deeper layers of the epidermis, which become detached and float freely in the fluid, owing to the separation and elevation of the super- ficial cuticular layers during the formation of the vesicle ; though, if it be admitted that the white corpuscles of the blood can migrate through the walls of the vessels, then it is possible they may, in part at least, be derived directly from the cell elements of the blood itself. If we now turn our attention to the material produced in the early stages of inflammation of a serous membrane, we shall find the free surface no longer smooth and glistening, but covered by soft ' lymph,' which is no mere exudation yielding solidified fibrine, but is loaded with rudimentary colourless corpuscles (Fig. 36, a), not unlike those just described in the fluid of herpes. The changes in the serous membrane itself, which result in the production of these corpuscles, have been Kg. 37. enquired into by various observers. The epithehal cells on the free surface become swollen, opaque, loosened, and then fall off into the serous cavity, and these changes are accompanied by a rapid multipli- cation of their contained nuclei, which are set free by a breaking down of the cells themselves. In the corpuscles of the sub-epithelial con- nective tissue productive changes also occur (Figs. 37, 38), and small groups of rudimentary corpuscles, formed by germinating changes in Fig. 37. Section through the sub-epithelial tissue of an infjaraed pleura, showing the proliferating changes in the corpuscles of the connective tissue. 248 PRODUCTS OF INFLAMMATION: their nucleated protoplasm, appear. As the inflammation advances, these rudimentary ceUs multiply with great rapidity, so that adjacent groups run together and form masses of immature corpuscles, which are so numerous in the focus of the inflammation that the part seems to be altogether composed of these new productions, and all trace of its natural structure is lost. Not unfrequently the more superficial layers of this corpuscular lymph become detached and fall into the liquid exudations, which is poured with more or less abundance into the Fig. 38. serous cavity, where they may be mingled with the fibrinous coagula which usually form in that fluid. When a solid organ inflames, a parallel series of productive changes here also occurs. In a muscle, for example, it would seem that the in- flammatory lymph-corpuscles may arise not only from proliferation of the nucleated corpuscles of the connective tissue, which exists between the fasciculi and fibres, but from germinative changes in the nucleated corpnscles within and proper to the fibre itself.' Fig. 38 represents corresponding changes in the corpuscles of the sub-epithelial tissue of an inflamed peritoneum. At the right hand of the figure a mass of inflammatory lymph-cells, apparently produced by nuclear multiplication in one or more adjacent connective-tissue corpuscles, is represented. ' It is difficult at this time to write or speak dogmatically on the mode of origin of the corpuscles of inflaminatory lymph. For though pathologists generally have renounced the opinion at one time entertained that lymph- or pus-corpuscles arise by molecular aggregation in a coagulated exudation, yet Cohnheim's recent observations (note, p. 233) throw douht on the general fitness of the theory that, in all cases, they are produced by germinative changes in the normal corpuscles of the solid textures : whilst, on the other hand, there are strong reasons against regarding the ' migratory ' theory as universally applicable. The evidence, on which the statement is made in the text, of the origin of the corpuscles of the inflammatory lymph from proliferation of the nucleated corpuscles of the tissue of the inflamed part — the local-production theory, as we may term it — INPLAMMATOEY LYMPH. 249 From the various developments whicli the inflammatory lymph- corpusoles may undergo, when they are produced in these and other organs, are derived all those cells which are described as plastic cells, flbro-cells, caudate or fibro-plastic cells, and which may, if the de- velopment advances, proceed to the formation of connective tissue. On the other hand, from the various degenerations of these corpuscles descend those forms known as pus-corpuscles, granule-cells, granule- masses, inflammatory globules, and much of the molecular and debris- like matter that makes inflammatory effusions turbid. The examples of inflammatory lymph which I have quoted are such as may be considered typical of the two varieties : the first, in which spontaneously coagulating, it presents fibrine, either alone or mingled with very few corpuscles ; and the second, in which corpuscles are found alone, or with only a few flakes of fibrine. But, in a large num- lias been worked out by so many observers, and with so much fulneSs of detail, that it probably expresses a large part, if not the whole, of the truth as to their mode of origin. Commencing with the observations of John Goodsir, on tlie morbid changes which take place in Peyer's glands, and on the process of ulceration in articular cartilage (see the reprints in his Collected Anatomical Memoirs, Edinburgh, 1868), the subject has been still further illustrated by those of Dr. Eedfern on the morbid changes in articular cartilage, and by the elaborate investigations of Virchow, more especially as regards the part which the connective tissue takes in the production of these cor- puscles (see his published lectures on Cellular Pathology, and several papers by himself in the earlier volumes of his Archiv). Numerous papers also may be found in the same Arckiv by Buhl, Bottcher, Foreter, C. 0. Weber, Eindfleiseh, Burckhardt, Sczelkow, Neumann, Hjelt, and Cohnheim, in which original observations are made. The writings of Strube and His on inflammation of the cornea, the paper by C. 0. Weber in vol. xv. of Virchow's Archiv, and his article in the first volume of Billroth imd von Pitha's Handhuch, and the observations recorded by Forster in his Atlas, all form important contributions to the development of this doctrine. Original observations have also been recorded by Dr. Haldane in the Edinburgh Medical Journal, Nov. 1862, and by Prof. Turner in the same journal, April 1863 and April 1864. The morbid changes which take place in the inflammation of cartilage offer an especial difficulty to the general reception of the 'migratory' theory. There can be no doubt that when cartilage is irritated a rapid production of new cells takes place. And, as it is impossible to see how these can have wandered from the adjacent bloodvessels into the midst of the compact substance of this solid tissue, they can only have originated within the cartilage itself, from changes in the elements of its own texture. But in those tissues where bloodvessels and texture are in more intimate relation than in cartilage, it is possible that a wandering of the white blood corpuscles, and their conversion into the corpuscles of lymph or pus may to some extent take place ; in which case the blood-cells must be looked upon as a further source from which the new corpuscles formed in the course of an inflammation may arise. Both on the theory of local production, and on that of emigration, the general statement holds good that the new corpuscles which form in the course of an inflammation take their rise in pre-existing cell-elements. 250 PRODUCTS OF INFLAMMATION : ber of examples of inflammatory lymph, tlie fibrine and tlie corpuscles occur together, mixed in various proportions, the one or the other pre- ponderating. Such instances of mixed lymph are found in the fluid of blisters in all persons not in fall health ; in all bnt the freshest inflam- mations of serous membranes ; in most of the inflammatory deposits in cellular tissue, and in most of the viscera ; and in the false membranes of croup and other similar inflammations of mucous membranes. ' I will now proceed to inquire into the conditions that determine the production of one or the other variety of lymph. The conditions which are chiefly powerful in determining the character and tendency of in- flammatory lymph, are three — namely, 1. The state of the blood ; 2. The seat of the inflammation ; 3. The degree of the inflammation. First, in regard to the influence of the state of the blood in de- termining the characters of an inflammatory product, Rokitansky has happily expressed it by saying that ' the product of the inflammation exists, at least in part, in its germ preformed in the whole blood.' I will not refer here to the cases of inoculable diseases, in which some of the morbid material that was in the blood may be incorporated with the product of a local inflammation, though in these the correspondence of the blood and the inflammatory product is manifest enough ; but I will refer to cases that may show a more general correspondence be- tween the two, a correspondence such that, according to the state of the blood, so is the lymph more fibrinous or corpuscular in its cha- racters. Some of the best evidence for this is supplied by Rokitansky, in the first volume of his Pathological Anatomy : a work that I cannot again mention without a tribate of respect and admiration for its author, since in it, more than in any other of his writings, he has proved him- ' The fibrinous and the corpuscular varieties of lymph nearly correspond with those which Dr. Williams, in his Principles of Medicine and others, have named plastic and aplastic ; hut they do not completely do so. In different instances of both varieties, very diverse degrees of plastic property may be found ; and the occurrence of develop- ment or degeneration depends on many things besides the primary characters of lymph. They more nearly correspond with what Rokitansky (Pathologiscke Anatomie, i. 96) has distinguished as fibrinous and croupous ; the varieties which he names croupous ij., j3, and y, representing the several grades of lymph in which the corpuscles gradually predominate more and more over the fibrine, and assume more of the characters of the pus-cell. I would have used his terms, but that, in this country, we have been in the habit of considering croupous exudations to be peculiarly fibrinous. INFLAMMATORY LYMPH. 251 self amongst the first of all patliologists, in knowledge at once profound, minnte, and acciirate, in power of comprehending the vastest catalogue of single facts, and in clear discernment of their relations to one ano- ther, and to the great principles on which he founds his systems. In this work, he has shown clearly, that the characters of inflammatory deposits, in different diatheses, correspond very generally and closely with those of the coagnla found in the heart and pulmonary vessels ; and that, in general, the characters of inflammatory lymph, formed during life, are imitated by those of clots found in the body after death, when the fibriae of the blood may coagulate very slowly, and in contact with organic substances. Other evidence may be obtained by examining the products of similar inflammations excited in several persons, in whom the state of the blood may be considered dissimilar. And here, the evidence may be more poiated than in the former case ; for, if it should appear that the same tissue, inflamed by the same stimulus, will, in different per- sons, yield difierent forms of lymph, we shall have come near to cer- tainty that the character of the blood is that which chiefly determines the character of an inflammation. To test this matter, I examined carefully the materials contained in blisters, raised by cantharides-plaisters applied to the skin in thirty patients in St. Bartholomew's Hospital.' Doubtless, among the results thus obtaiued, there might be some diversities depending on the time and severity of the stimulus applied ; still, it seemed a fair test of the question in view, and the general result proved it to be so. For, al- though the difierences in the general aspects of these materials were slight, yet there were great diEEerences in the microscopic characters ; and these differences so far corresponded with the nature of the disease, or of the patient's general health, that, at last, I could usually guess accurately, from an examination of the fluid in the blister, what was the general character of the disease with which the patient suffered. In cases of purely local disease, in patients otherwise sound, the lymph thus obtaiued formed an almost unmixed coagulum, in which, when the fluid was pressed out, the flbrine was firm, elastic, and apparently fila- mentous. In cases at the opposite end of the scale, such as those of advanced phthisis, a minimum of fibrine was concealed by the crowds of corouscles imbedded iu it. Between these were numerous inter- mediate conditions which it is not necessary now to particularise. It ■ Observations of a similar nature have recently been recorded by C. 0. Weber in Billroth und von Pitha's Handbuch, i. 203. 252 PEODTTCTS OF INFLAMMATION: may suffice to say that, after some practice, one might form a fair opinion of the degree in which a patient was cachectic, and of the de- gree in which an inflammation in him would tend to the adhesive or the suppurative character from the contents of these blisters. The highest health is marked by an exudation containing the most perfect and unmixed fibrine ; the lowest, by the production of the most abun- dant corpuscles, and their nearest approach, even in their early state, to the characters of pus-cells. The degrees of deviation from general health are marked, either by increasing abundance of the corpuscles, their gradual predominance over the fibrine, and their gradual approach to the characters of pus-cells ; or, else, by the gradual deterioration of fibrine, in which, from being tough, elastic, clear, uniform, and of fila- mentous appearance, it becomes less and less "filamentous, softer, more paste-like, turbid, nebulous, dotted, and mingled with minute oil- molecules. I would not make too much of these observations. They are not enough to prove more than the rough truth, that the products of similar inflammations, excited in the same tissue, and by the same stimulus, may be in different persons very difiFerent, varying especially in accord- ance with the several conditions of the blood. Yet I cannot doubt that a still closer correspondence between the blood, and the products of in- flammation derived from it, would be found in a series of more complete observations ; in such, for instance, that the characters of the blood drawn during life, or, much better, of the clots taken from the heart after death, might, in a large number of patients, be compared with those of inflammatory exudations produced, as in the cases I have re- ferred to, by the same stimulus applied to the same tissues. In the few cases in which I have been able to make such examinations, this view has been established ; and it is confirmed by the parallelism be- tween the varieties of lymph that may be found in blisters, and the varieties of the fibrinous coagula in the heart described by Rokitansky.' The varieties of solidified fibrine, which he classes as fibrines 1, 2, 3, 4, are very nearly parallel with what I have enumerated as the stages from the best fibrinous to the corpuscular lymph ; and, as I have already implied, he regards these clots found in the heart and vessels as representing the different ' fibrinous erases ' or diatheses of the blood. I mentioned, as the second condition determining the character of ' Patholoyisclu Anatomie, B. i. p. 142, INFLAMMATOKY LYMPH. 253 inflammatory lymph, the seat or tissue which the inflammation occupies. I need hardly remind you that, since the time of Bichat, there has been a general impression that each tissue has its proper mode and product of inflammation. The doctrines of Bichat on this point were, indeed, only the same as John Hunter held more conditionally, and, therefore, more truly ; but they gained undisputed sway, among the principles of that pathology which rested on general anatomy as its foundation. The facts on which it has been held that, in general, each part or tissue is prone to the production of one certain form of inflammatory material, are such as these : that, e.g., ia the apparently spontaneous inflammation of the skin, lymph with corpuscles alone is produced, as in herpes, eczema, erysipelas ; that in serous membranes, the lymph is commonly fibrinous, and has a great tendency to be organised, and form adhesions ; that in mucous membranes there is as great a tendency to suppuration ; that in the lungs, both fibrine and corpuscles are abund- ant in the lymph, and the corpuscles have a remarkable tendency to de- generate into either pu.s-cells or granule-cells ; that in the brain and spinal cord the tendency is to the production of a preponderance of corpuscles, that quickly degenerate into granule- cells, while in the are- olar tissue, both fibrine and corpuscles appear, on the whole, equally apt to degenerate into pus, or to be developed into filamentous tissue. Now these are, doubtless, facts ; but the rules that it is sought to establish from them are not without numerous exceptions. The in- stances I have lately quoted show that, in one tissue at least, the skin, the product of inflammation will vary according to the condition of the blood, although the inflammation be always similarly excited by the same stimulus. So, too (as Mr. Hunter remarks ' ), if it were the tissue alone that determines the character of an inflammation, we ought to have many forms of inflammation in the same stump after amputation ; whereas all is consistent, or the differences among the tissues are only differences of degree ; they all adhere, or all granulate and suppurate, or all alike inflame and slough. It is therefore not unconditionally true that each tissue has its proper mode and product of inflammation. It has been too much overlooked that a morbid condition of the blood, or of the nervous force, may de- termine, at oncCj the seat of a local inflammation, and the form or kind 1 Wcflcs, ill. p. 313. 254 PROD t GTS OF INFLAMMATION: of iDflammatory product. Thus, e.g., the variolous condition of the blood may be said to determine, at once, an inflammation of the skin, and the suppurative form of inflamnaation ; for, in variola, whatever and wherever inflammations arise, they have a suppurative tendency. So, in rheumatism, whether it be seated in muscles, ligaments, or syn- ovial membranes, in serous membranes, or in fibrous tissues, there appears the same tendency to serous and fibrinous eflEusions, which are slow to coagulate, and even less prone to suppuration. The same might be said of the local inflammations that are characteristic of ty- phus and of gout, and, I believe, of all those diseases in which a morbid condition of the blood manifests itself in some special local error of nu- trition. And all these cases are illustrative of the general truth, that each morbid condition of the blood is prone both to produce an inflam- mation in a certain part, and to give to that inflammation a certain form or character. Cases, however, remain, that prove some influence of the tissue in determining the product of its inflammation ; in determining, I mean, the primary form, as well as the later development, of the product : and the true influence of the tissue in this respect is best shown in some of the cases in which the inflammation, excited, apparently, by the same means, has happened coincidently in two or more very different parts in the same person. Thus we may flnd, e.g., that, in pleuro-pneumonia, the lymph on the pleura is commonly more fibrinous than that within the substance of the lung ; and adhesions may be forming in the one, while the other is suppurating, though this may, in part at least, be due to the circumstance that in the latter case the air is brought in contact with the lymph, whilst in the former it is not. In cases of coincident pneumonia and pericarditis, the lymph in the lung may appear nearly all corpuscular, and all the corpuscles may show a tendency to degene- rate into granule-cells, while the lymph on the pericardium may have a preponderance of fibrine, and what corpuscles it has may tend to dege- nerate into pus-cells. So, too, one may find, in the substance of an inflamed synovial membrane, abundant lymph- cells, while those met with on its surface may appear purulent. I have said that the fluid of the sac in cases of strangulated hernia coagulates on withdrawal from the body : it may be regarded as a mix- ture of serum and fibrinous lymph from the inflamed serous membrane. But, in a case in which I was able to examine a pellucid fluid contained in large quantity in the cavity of the strangulated intestine, and which appeared to be the nearly pure product of inflammation of the mucous INFLAMMATORY LYMPH. 255 membrane, there was no fibrine; the fluid was albuminous and contained abundant lymph-cells. Other instances of this might be mentioned. Those, however, may- seem enough to establish the influence of the second condition that I mentioned ; namely, the seat of an inflammation, as determining the character of its products. The third condition on which the character of the lymph chiefly depends is, the degree of the inflammation producing it. The influence of a tissue, in determining the character of the lymph formed in its inflammations, may be in some measure explained, by believing that the primary product of inflanimation is often a mixture of lymph, and of the secretion, or other product of the in- flamed part, more or less altered by the circumstances of the inflam- mation. When it is seen that in inflammations of bone the lymph usually ossifies; in those of ligament, is converted into a tough ligamentous tissue ; and that, in general, lymph is organised into a tissue more or less corresponding with that from whose vessels it was derived ; it is usually concluded that this happens under what is called the assimila- tive influence of the tissues adjacent to the organised lymph. But we may better explain the facts, by believing that the material formed in the inflamm.ation of each part partakes, from the first, in the proper- ties of the natural products of that part; in properties which, we know, often determine the mode of formation independently of any assimila- tive force (p. 44). We have some evidence of this in the products of inflammation of secreting organs, the only structures the natural products of which we can well examine in their primary condition. In a moderate amount of inflammation of a secreting gland, the discharge is usually a mixture of the proper secretion in a more or less morbid state, and of the in- flammatory product. Thus we find morbid urine mixed with fibrine, or albumen, or pus. In cases of inflamed mucous membranes, the product is often a substance with characters intermediate between those of the proper mucous secretion and those of corpuscular lymph or pus. Or, &o-a,m. in serous membranes, we may perceive a relation between their natural secretion and the usual products of their inflammation. Now, these considerations are equally illustrative of the influence of the third among the conditions enumerated as determining the charac- ter and tendency of inflammatory products — namely, the degree or 256 PRODUCTS OF INFLAMMATION : severity of the disease. For, as a general rule, tlie less the degree of inflammation is, the more is the iaflammatory product like that naturally formed in or by the part, till we descend to the border at "which inflammation merges iato an exaggerated normal process of se- cretion : as in hydrops articuli, hydrocele, coryza, etc. These, it may be said, are only instances of secretions. But the instances of the so-called inflammatory hypertrophies may be regarded as parallel with those just referred to ; and the analogies between secretion and nutrition are so numerous, the parallel between them is so close, that what can be shown of one may be very confidently assumed of the other. We may therefore believe, that, in the inflam- mation of any part, the product will, from the flrst, have a measure of the particular properties of the material employed in the normal nutri- tion of the part : that, as in the inflammation of a secreting organ, some of the secretion may be mingled with the product of the inflammation, so in that of any other part, some of the natural plasma, i.e. some of the natural material, that would be effused for the healthy nutrition of the part, may be mingled with the lymph ; or else, that, as the inflam- matory product in parenchymatous inflammation is morbidly changed plasma, so it will be, in difierent cases, less or more modified in its tendencies to organisation. The measure of likeness to the natural structure acquired by the inflammatory product in its development, will thus bear an inverse proportion to the severity of the inflammation ; be- cause, the more the conditions of nutrition deviate from what is normal, the more will the material efinsed from the vessels deviate from the normal type. In severest cases of inflammation we may believe that unmixed, or wholly morbid, lymph is produced, the conditions of the due nutrition of the part being whoUy changed ; but when the inflam- mation is not altogether dominant, its product wUl be not wholly contrary to the natural one, and will, from the first, tend to manifest in its development some characters correspondent with those of the natural formations in the part. Thence, onwards, this correspondence will increase as the new tissue is itself nourished : as scars improve, so do false membranes and the like become more and more similar to natural tissues. To sum up, then, what may be concluded respecting the conditions that, in the first instance, may determine the adhesive or suppurative characters of an inflammatory product : they arc, 1^;^, The state of the blood— its diathesis or crasis — the power of which is evident in that the same material may be produced in many inflamed parts in the same INFLAMMATORY LYMPH. 257 person ; in that this material may exhibit peculiar characters corres- pondent with those of the blood itself ; and in that, in different per- sons, an injSammation excited in the same tissue, and by the same stimulus, will produce different forms of lymph, corresponding with differences of the blood. 2nd. The seat of the inflammation, and the tissue or organ affected ; of which the influence is shown by cases in which, with the same condition of blood, different forms of lymph are produced in different parts or organs. Srd. The severity, and acute or chronic character, of the inflammatory process, according to which the product deviates more or less from the character of the natural secre- tion or plasm, or blastematous effusion in the part. The primitive character or tendency of any case of inflammation might be represented as the resultant of three forces issuing from these conditions. IV. ProducUon of Mucus. — Peculiar difBculties, owing to imperfect investigations of what normal mucus really is, beset this portion of our subject. Normal naucus, so far as it has been examined, is a peculiar viscid, ropy, pellucid substance, which, of its own composition, has no cor- puscles or organised particles. Such mucus is to be found in the nasal cavities of sheep and most large mammalia, and in the gall-bladder when its duct has been totally obstructed. In these parts, mucus may be found without corpuscles : and probably there are other examples of such pure and unmixed mucus. With all these, however, accidental mixtures commonly occur of epithelial particles from the mucous membrane, and of corpuscles from the imbedded mucous follicles. And these particles vary according to the seat of the membrane, the fluid with which the mucus may be mixed, as gastric acid, intestinal alkali, etc., the time the mucus may lie before discharge, and other such conditions. The first effect of a stimulation, as in the case of a common cold, is to increase the secretion of the proper mucus, making it also more liquid ; to increase the quantity of the mucus-corpuscles cast off with the liquid ; and to induce the premature desquamation of the epithelium, so that particles of it imperfectly formed may be found in the mucus. But the changes which inflammation induces in a mucous mem- brane, as it becomes more and more established, are not confined to the surface. The membrane swells, and this is due not only to afflux of blood, and infiltration into its substance, but to the increased pro- duction of corpuscles, which may arise, from nuclear multiplication, 258 MUCUS. both wifctiu tke epithelium-cells, oa the surface of the membrane,' or within its follicles, and in the corpuscles of the sub-epithelial connec- tive tissue, for a greater or less depth according to the degree of the inflammation ; though some would say that they are corpuscles which have wandered from the blood. These corpuscles, though commonly called muous-corpasoles, yet differ only from the corpuscles formed in inflammation of a serous membrane (p. 247), because of the more\'iscid fluid in which, when set free, they lie. All are, alike, inflammatory lymph-corpuscles ; but in the one case they lie in a serous, in the other in a mucous, fluid, in which they appear clearer, more glistening, more perfectly pellucid, less plump, and are less acted on by water. In all these cases, then, not merely is there a transudation or ejection of flnid from the surface into the canal which the mucous membrane lines, but an interstitial production or infiltration of new-formed corpuscles within the tissue of the membrane itself. In certain inflammations of mucous membranes, fibrinous exudations are also found ; as in Hunter's experiment^ of injecting strong irritants into the vaginae of asses ; in bronchial polypus,^ in diphtheria, and in croup.'* And I have seen them in the renal pelvis, ureters, and bladder, in a case of calculus. From these products of inflammation of a mucous membrane may be derived, by various degenerations of the fibrine, the flaky and molecular materials which commonly make morbid mucus look turbid and opaque ; and by corresponding degenerations of the corpuscles the more frequent pus-cells, which make the transition to the complete pus formed on mucous membranes in active inflammation. Such degenerations are more frequent in the products of inflamed mucous surfaces than are any forms of development. Some indications indeed of development may be found in the cor- puscles, especially when the inflammation is very slight, as in the end of a bronchitis. In this case, many corpuscles may be found enlarged, having distinct cell-walls and clear well-defined nuclei with nucleoli. But among these there are usually many that present a peculiar pig- mental degeneration. In the grey, smoke-coloured mucus, commonly expectorated at the close of bronchitis, the peculiar colour, though commonly ascribed to the mixture of inhaled carbon, is due to the ' See Eemak and Eberth in Virchow's Archiv, xx. 198 ; xxi. 106. 2 Works, iii. p. 341. Museum of the College, Nos. 83, 84. ' Henle, Zeiischrifi, ii. 178. ' 0. 0. Weber, in Billroth und von Pitha's Handbuck, i. 376, Fig. 54. PRODUCTS OF INFLAMMATION. 295 abundance of cells containing more or less nnmerons black pigment- granules. Particles of carbon or soot may by chance be present, but they only trivially contribute to the colour : it depends on the number of these pigment-cells, to which it is easy to trace the transitions from the lymph or mucus-corpuscles. The chief stages are seen in that the cells enlarge to a diameter of about f^'^h of an inch, become clearer, and acquire one or two clear oval nuclei ; but, at the same time minute black granules (Fig. 39), almost like those of melanotic cells, accumu- Fig. 39. late in them ; and these increasing in number and clustering, may at length fill the whole cell, while the nucleus disappears. Subsequently, the cell- wall may burst or dissolve, and the black granules be set free. It can hardly be supposed that the black granules are in any way derived from inhaled carbon, although it seems that this kind of mucus is most abundant in those who are exposed to atmospheres laden with coal-smoke ; for the colour is completely destroyed by immersing the mucus in nitric acid or solution of chlorine. The occurrence of such pigment-cells being, I believe, peculiar to the mucus of the air-passages, may be connected with the general tendency of inflammatory products to imitate the properties of the natural products of the inflamed part; for they closely resemble the black pigment-cells from which the lungs and bronchial glands derive their black spots and streaks and other marks. And it may be added, that their peculiar abundance in the slightest forms of bronchitis compared with their absence in acute cases, affords an example that the likeness of the morbid to the natural products is inversely proportionate to the severity of the inflamma- tion. s 2 260 DEVELOPMENTS OF INFLAMMATOEY PRODUCTS ; LECTURE XV. DEYELOPMENTS OF INFLAMMATOKT PRODUCTS. In tlie last lecture I considered part of tlie contrast between the pro- cesses of nutrition in the normal and in the inflammatory state, en- deavouring to illustrate the nature of the materials exuded from the blood or produced in the inflamed parts. The contrast in this particu- lar cannot, indeed, be accurately drawn : for we have, as yet, no certain knowledge of either the properties or the quantity of the material sepa- rated from the blood, for the ordinary nutrition of each part ; we have no normal standard wherewith to compare, in this respect, the processes of disease. It is evident that the exudation or production in an in- flamed part is superabundant ; but its error in quality can be proved ouly by its diversity in various cases, and by the differences which it commonly presents in the rate and method of its development or de- generation. It is of these processes in the inflammatory products, and of the contrast between them and the normal maintenance of a part, that I propose next to speak. The biography of these products comprises much of the most im- portant part of the pathology of inflammation ; and if it were required to point out what, since Hunter's time, has contributed most to the progress of general pathology, one could scarcely hesitate to name the full appreciation of the fact, that they and other primary products of disease have an independent life, and are of their own nature capable of appropriate development, degeneration, and disease. We may regard this as one of the best achievements of the observations which Schleiden and Schwann began to generalise ; for, till it was clearly apprehended, the idea of a part being organisable meant scarcely more than that it admitted of being organised by the forces of the parts around it ; that it could be built up by the arteries, and modelled by the absorbents, as a material plastic, yet passive, in the hands of workmen. Hence was derived the erroneous direction of inquiries, which sought for blood- HOW THE TERM IS USED. 261 vessels as the essential characters of organic life in a part ; and for their varieties of size, and number, and arrangement, as the measures of the ability and method of development. Now, more truly, we may study the inflammatory lymph, as having a life only so dependent on the blood and vessels as are all the tissues of the body — dependent on them as conditions of life, but not as sole arbiters of the method or direction of the vital transformations. And I venture to think that the chief aim of our observations, in this part of the pathology of inflammation, should be to learn, now, the exact relation in which the several products of inflammation stand to certain primary forms, as developments or degenerations from them. The catalogue of various corpuscles is already swollen to an extent that is confusing to those who are familiar with them, and repulsive to those who would begin to study them. It would be an easy task to increase it, and it might have a seeming of accuracy to do so : but what we want is such a history of the inflammatory lymph, that we may arrange the components of this catalogue as indicating so many progressive stages of development, degeneration, or disease, in the primary products of inflammation. An attempt to construct such a history is the more ad- visable, for the sake of the illustration which it may afford to the his- tory of normal structures. There are, as I have already said, no nor- mal instances in which we can see the materials that are effused for the nutrition of parts ; but we may assume something concerning them and their progressive changes from the analogy of the materials that are more abundantly produced in inflammations. I propose, then, to devote the present lecture to some general, and only a very general, account of the developments of inflammatory lymph. But let me first state the sense in which the term development is here to be employed. I have said (pp. 3, 76) that, in the generally accepted meaning of development) we have adopted an arbitrary standard of comparison, in the assumption that the nearest approach to organic perfection is in the human body, at the age of manhood. The assumption may be right on the whole ; and a less arbitrary definition of development would, probably, be less useful ; yet it may be observed, that in what we take for the period and standard of perfection, many parts that were once highly organised and active have passed away, as the thymus gland ; and some are, in certain respects, rather degenerated than developed, a^ the supra-renal capsules and the bones. Development, in its highest 262 DEVELOPMENTS OF INFLAMMATORY PEODUCTS : sense, should imply not merely that a part becomes more fit for mem- bersMp under the most perfect economy, but, also, that such fitness is acquired with greater complexity of chemical composition, or with greater evidence of formative or other organic power, or with greater difference from the stracture or composition of lower beings. With none of these characters of development does such a process as that of ossification agree; and, therefore, as I have said before, when we call it the development of bone from cartilage, it should be with the under- standing that the term is applicable only because bone is the proper material of the skeleton of the adult human body. This distinction is important in the pathology of inflammation. In all true or complete development we may believe there is a larger ex- penditure of vital force than in any other organic act ; for all such de- velopment, too, the external conditions need to be the most complete, and the least interfered with ; such development is the highest achieve- ment of the formative force, the highest instance of what might be un- derstood as ' increased action ' in a part. To speak, therefore, of the development of inflammatory products, when already the normal development of the body is completed, may seem to imply the exercise of unusual vital force ; the renewal, as it were, of the pristine embryonic vigour ; and the existence of conditions more favourable for nutrition than even those of health are. Bat we may be led to judge difierently, if it should appear that most or ah of the so- called developments of inflammatory products are instances in which the tissues, though they are formed into the likeness of such as exist in the perfect human frame, yet acquire characters of lower organisation than those they had in their earliest state. It vrill appear that they are such ; and that, however much the inflammatory products may be- come, by their changes, better suited for the general purposes of the economy, they are, in relation to their own condition, rather degenerated than developed. The changes that they undergo are, therefore, not always declaratory of a large expenditure of vital force ; they are not such as the term ' sthenic ' or ' increased action,' applied to the inflam- matory process, would suggest ; not such as to imply that it is an exag- geration of any normal method of nutrition. With this understanding, however, the changes I shall presently describe may be called developments of inflammatory lymph ; they are developments in the scuse of being approximations to the likeness of the natural tissues of the adult human body. For the development of lymph, nearly all those conditions are re- NECESSARY CONDITIONS. 263 quisite whicli are necessary for the normal development of the proper constituents of the body. It needs, in general, the dne supply of healthy and appropriate blood, the normal influence of the nervous force, and, for the highest and latest forms of development, the normal conditions of the proper elements of the afiFeoted part. Now, the existence of these conditions for the development of lymph implies a cessation of the inflammatory process, and a recovery from whatever originated or maintained the inflammation. So long as in- flammation lasts, no high development of the new material already formed will take place ; rather, fresh lymph will be continually pro- duced, hindering the due process of development, and hindering it the more, because, as the general health suffers through the continuance of the disease, so the lymph freshly formed will be less and less prone to organisation. We may see an illustration of the ill effects of abiding inflammation, in the healing of wounds by granulation. An inflamma- tion, ensuing or continuing in the wound, hinders all development ol granulation-cells, even though it may be too slight to hinder their for- mation, and may be favourable to the production of the ichor and jdus- cells. We may truly say, that the conditions most favourable to the abundant production of lymph are among the most unfavourable to its development, i.e. to its complete and higher organisation. Even when the inflammation has ceased, and fresh lymph is not formed, still, development is often prevented or retarded for want of some necessary condition. The bloodvessels, long dilated, may remain in a state of congestion, distended as if paralysed, and filled with slowly moving blood. In such a state of ' passive congestion,' so apt to follow more acute attacks, and probably one of the most frequent causes of chronic and relapsing inflammations, development will not happen in even well-disposed lymph. We have parallel facts in the tardy develop- ment of granulations on the legs, in the healing of ulcers ; and how much this depends on the defective movement of the blood is well illus- trated by a specimen ' appropriate to an observation of Mr. Hunter's. It shows three ulcers of the integuments of a leg ; they were all granu- lating, and all healing ; but their progress in healing was inversely proportionate to the hindrances of the blood. The lowest of the three, that most distaat from the heart, and of which the vessels were subject to the pressure of the highest column of blood, was least advanced in healing ; while the uppermost of the three was most advanced, and was neai-ly cicatrised. ' Museum ()f the College, No. 26. 26i DBVELOPxXENTS OF INFLAMMATOEY PEODUCTS : But let us suppose all the conditions for development provided ; ■what -will now determine the direction or result of the process ? Into vfhat tissues will the lymph be formed ? Two chief things will deter- mine this : first, the general natural tendency of organisable lymph, produced in iuflammation, is to form filamentous, i.e. fibro-cellular, or fibrous, connective tissue ; and, secondly, all lymph has some tendency to assume, sooner or later, the characters of the tissues in or near which it is seated, or in place of which it is formed. The natural tendency of lymph to the construction of the fibro- cellular form of connective tissue, such as composes false membranes or adhesions, and many permanent thickenings and indurations of parts, is shown by the production of this tissue under all varieties of circumstances, and in nearly all parts, — even in parts which naturally contain little or none. Thus, it is found in the brain, and in glands, as in the testicle : within joints, even where adhesions only pass from one articular cartilage to another ; in the adhesions and thickenings of the most diverse serous membranes ; in the thickenings of the most diverse mucous ones. And with all these, we have the corresponding facts in the healing of wounds. All granulations, springing from what surface they may, tend, at least in the first instance, to the formation of filamentous tissue, such as we see uniting all parts in a stump ; and a large proportion of subcutaneous injuries are repaired by similar tissues, whatever parts may have been divided. And, sometimes, we may find incomplete instances of this development where the lymph is not even in continuity with any tissue, but floats free ; as in ascites, or in effusions into joints. But, besides this general tendency, we may recognise in inflam- matory lymph a disposition to assume characters belonging to the part in which it was produced ; so that, for instance, that about fibrous and ligamentous parts, will be developed into peculiarly tough fibrous tissue ; that about bone will become osseous ; that in the neio-hbour- hood of epithelium will form for itself an epithelial covering ; and so on. I referred to this fact in the last lecture, and suggested that this tendency of the developed lymph, to conform to the characters of the parts around it, is probably due to the oiiginal and inherent quality of the lymph ; that the material formed in the inflammation of each part partakes, from the first, in the properties of the natural products of that part, and partakes of them in an inverse proportion to the severity of the inflammation ; because, the more the normal conditions of nutri- tion are deviated from, the more will the material produced be unlike CONNECTIVE TISSUE. 265 the normal product. Besides, when the conditions are restored to the normal type, the organized product of inflammation will constantly- approximate more and more to the characters of the parts among which it is placed, or with which it has acquired membership. As scars improve, i.e. gain gradually more of the characters of skin, so do false membranes, and the like structures, formed by the organisation of inflammatory lymph, acquire by their own nutrition and development, more nearly the characters of the parts with which they are connected. Thus, false membranes in the serous cavities acquire a covering of epithelium exactly like that which covers the original serous membrane, and their structure is that of connective tissue ; adhesions of the iris may become black, apparently from the production of pigment cells like those of the uvea ; thus, too, in adhesions of the pleura, even when they are long and membranous, pigment may be formed, as in the pulmonary pleura itself ; and thns many other inflammatory products are gradually perfected, till we may com.e to doubt whether they be of normal or of morbid origin, so complete is the return from the aberrant action. I will endeavour, now, to describe more particularly the transitions to the several tissues that may be formed fi'om inflammatory lymph. If it seems strange that the products of disease should thus so closely imitate health, let it be repeated that this process of development of the lymph is not disease. The lymph is, indeed, produced in inflam- mation, but it is developed in health, when all the natural conditions of nutrition are restored. Gonnective Tissue. — The instances are very numerous in which the inflammatory lymph, following its natural tendency, becomes connec- tive tissue. The general forms which, in these instances, it assumes are (1) adhesions, when the new-formed tissue is between free surfaces, and unites them ; (2) thickenings, where the formation is in the sub- stance of membranes ; C3) indurations, with, or without, contractions, where it is in the substance of organs ; (4) opacities of certain parts that were transparent. The best examples of the formation of connective tissue from inflammatory lymph are in the adhesions, or false membranes, found after inflammation of serous or synovial membranes. In the former, especially, the lymph is apt, in such favourable conditions as I have specified, to be thus developed. In an acute peritonitis, or pleuritis, for instance, it is usually, in the first instance, formed in layers of 266 DEVELOPMENTS OF INPLAMMATOKY PKODUCTS : nncertain thickness on and in the substance of the membrane. The condition of these layers is variable. The lymph is sometimes grey- ish, half-translucent, compact, and laminated, with a, large intermix- ture of fibrinous material ; in other cases, it is yellowish, opaque, soft, succulent, or almost creamy, having a great preponderance of cor- puscles : and between these forms are many connecting varieties of appearance. In the first instance, the connection of the lymph with the surface of the serous membrane is, usually, such that it may be readily stripped off. Its free surface presents great varieties ; it may be flocculent, or villous, reticular, perforated, or nearly smooth. Commonly, at first, the surfaces of the two layers (the visceral and parietal layers as they may be called, after the portions of the serous membrane on which they are severally placed) are separated by a variable quantity of serous fluid. But they may be, in parts, continuous, or connected by bands or columns ; and, usually, when the inflammation ceases, and such a state of circulation is restored as is favourable to the organisation of the lymph, the same state is equally adapted to the absorption of the superabxmdant fluid. In this case, the opposed surfaces of the two layers of lymph are gradually brought into contact with one another, and with portions of lymph which had floated in the fluid : and now, as their organization proceeds, they are all united ; they become continu- ous, and form ' adhesions ' between the opposite surfaces of the serous membrane, whether these be the surfaces of adjacent organs, as the abdominal viscera, or of any organ and of the cavity enclosing it, as in the case of the testicle and tunica vaginalis. The method, and the chief part of the plan, of the organisation of lymph in these cases, are, I believe, similar to those described in the healing of wounds by primary or by secondary adhesion ; and the general results are the same. Various as are the forms and other con- ditions of adhesions and false membranes (depending as they do on the relative positions and mobilities of the parts tliat they connect), yet their structure, when complete, i.i, I believe, uniform. They consist of well-organised connective tissue, with which (perhaps only at a late period) the elastic form of this tissue may be mingled : they possess abundant bloodvessels, the chief of which are parallel to the direction of their filaments ; and their free surfaces are covered with an epithe- lium like that of the membranes which they connect. Connective tissue is formed in adhesions of synovial membranes as well as of serous membranes ; and probably in the same manner. In CONNECTIVE TISSUE. 267 both eases, moreover, inflammatory lymph is produced, in and just beneath the membrane, as well as on its surface ; and this infiltrated or interstitial lymph, becoming organised, produces thickening and opacity of the membrane. — The coincident organisatiou of the inflam- matory lymph, in both positions, is well shown in the frequent instances of white spots in the cardiac pericardium, with adhesions between the pericardial surfaces. Such white spots, when completely formed, con- sist of new connective tissue, exactly like that of the adhesions. It is by similar interstitial prodaction of inflammatory lymph, and by its development into this kind of tissue, that the frequent adhesions take place between parts which, though connected, should slide freely upon one another : such as adjacent tendons, etc. From this is derived a large share of the stiShess that remains about injured joints; the parts that should slide pliantly over them are fixed by the new-formed inter- stitial connective tissue. So, too, are formed the various morbid thickenings of parts ; as of pieces of integument, capsules of joints, etc. But in many of these cases, the lymph retains very long its rudi- mental structures, and is, perhaps, on this account, peculiarly apt to degenerate and permit absorption or the ulcerative process. I know no better example, for microscopic examination of interstitially deposi- ted infiammatory lymph, than an indurated chancre : but I have never found one in which the lymph-cells had reached a further development than the elongated caudate form. When the lymph is interstitial in any of the more compact forms of connective tissue — as in ligaments, capsules of joints, and the like — it is developed into the denser kinds of connective tissue. The best examples of it are in the laminated and nodular thickenings of the capsule of the spleen, or the thickening and induration of the periosteum, or the capsule of the hip-joint in chronic rheumatic arthritis. In all these cases, the new material is derived from repeated, but not acute, inflammations ; therefore, probably, though excessive, it is not widely difierent from the normal material for nutrition ; and, the conditions for nutrition being little disturbed, it is developed into the exact likeness of the original texture with which it is intermingled and confused. As the connective tissue formed from inflammatory lymph becomes more perfectly organised, it is prone to contract : imitating the con- traction already described in granulations and scars (p. 174). Hence, in part, the contraction of the wall of the chest after pleurisy, and the various displacements and deformities of organs that have become adherent to adjacent parts : hence, in part also, the contractions of 268 DEVELOPMENTS OF INFLAMMATORY PEODUCTS : inflamed organs, as of the liver in cirrliosis : hence, too, an addition to the rigidity of joints when the parts around them have been inflamed ; and hence, with yet greater mischief, the oontraotions of the thickened valves and tendinous cords of the heart. The elastic form of connective tissue is sometimes abundantly pro- duced in the adhesions developed from inflammatory lymph. I have not seen it except in such as are completely organised ; and I think it is, in this case, as in the formation of scars, a late production (see p. 176). I believe, also, with Virchow,' that its formation depends, in some measure, on the membrane that ia inflamed ; pleural adhesions being most favourable to it. In these it is often abundant ; its princi- pal, but always slender, filaments lying in the same general direction as those of the white fibrous tissue. Adipose Tissue m.ay be formed, if not directly from inflammatory lymph, yet in the connective tissue of completely organised adhesions. I think it is not often so formed : but, some years ago, Dr. Kirkes found a lung of which all the anterior part was covered with well-organised false membrane ; and in part of this was a quantity of perfect adipose tissue, more than four ounces in weight. Epithelium I have already mentioned as covering the surfaces of well-formed adhesions. It is not rare to find, in inflammation of serous membranes, recent lymph-cells presenting many characters indicative of development towards epithelium; flattened and enlarged, and having circular or oval clear nuclei : and it may be developed in the form of epidermis on the surface of granulating sores. Bone is often formed from inflammatory lymph. It may appear as a late transformation of lymph that has been organised into pei'fect fibrous tissue ; as in the osseous plates that are sometimes found in the false membranes of the pleura, or in the pericardium. In most of these however, there is not true bone, but an amorphous deposit of earthy matter, which is imbedded in the fibrous tissue, or which (as Eokitan- sky holds) is the residue of the degenerated and partially absorbed tissue. The proper condition for the transformation of inflammatory lymph ' Verhandl. cfer. Phys.-Med. Gesdlschaft in Wureburg, i860, p. U2. Ho describes here a peculiar thorny or dentate structure often presented by the elastic filaments in old adhesions. BONE. 2G9 into bone is that m whioli it is produced in tlie course of any inflamma- tion seated in the bone itself, or else in or near tlie periosteum. Such inflammations have been called ' ossific ; ' and the Museum of the Col- lege, like every other, abounds with specimens of their various results. There is a great lack of minute observations respecting both the characters of the products formed in inflammations of bone or periosteum , and the methods of its ossiflcation. Such as have been made, indicate, as might be expected, a close resemblance to the processes described in the repair of fractures ' (p. 181, et seq.). The lymph produced in mo- derate inflammation, and therefore likely to ossify, is at first, according to Rokitansky, a dark red material, like gelatine, which, being gradually decolourised, becomes white ; and at the same time acquiring firmness, becomes like soft flexible cartilage, and then like ruddy succulent bone. But though it be like cartilage, I suspect that cartilage is very rarely, if ever, formed in inflammation of bone ; for it seems to be formed in the repair of fractures only when the conditions are more favourable than they are likely to be in any inflammations. Probably the lymph is more or less developed towards the flbrous tissue when it ossifies ; and as in the repair of fractures, so here, we may believe that ossification may be postponed till the fibrous tissue is quite formed, or that it may ensue in the rudimental state of the tissue whether in a nu- cleated blastema, or in cells like those of granulations. It would be hardly possible to explain, without illustrative speci- mens, all the various appearances of bone new formed in or after inflammations. It may be produced in the very substance of compact bone, after the softening and expansion of the original tissue which occur in the earlier parts of the inflammatory process, and to which I shall have again to refer. Or, it may be produced in the medullary or cancellous tissue ; and here, commonly, it appears as a gradual thicken- ing of the minute cancellous lamellse and fibres of bone, which, as they increase, gradually exclude the proper structures of the diploij or me- dulla, and flnally coalesce into hard solid bone. But by far the most common seat of the formation of new bone, and that in which it is almost always found when it exists in either of the former situations, is on the surface, between bone and periosteum, or even in the periosteum itself. Here it forms the various growths to which the general term Osteophyte has been given. In a series of specimens of common inflammation of bone or periosteum, it is not > Kostlin, Miillor's ^reAsB, 1845, p. 69; Eoldtansky, ii. p. 172; Virchow, in his Archil), i. p. 135. 270 DEVELOPMENTS OF INFLAMMATOEY PEODUCTS : difficult to trace tlie changes of construction of the new bone, by which, like that formed in a process of repair, it gradually approximates to conformity with the bone on which it grows.' At first it is, when dried, light and friable, with a close filamentous, velvety texture, and a smooth surface, gradually rising from that of the surrounding healthy bone. As it increases in thickness it becomes longitudinally grooved, as if lodging bloodvessels passing, through it, from the periosteum to the old bone. Then, as fresh formations of new bone take place, they assume the form of nodules and thick plates, laid over the longitudinal grooves, and leaving large apertures for the pas- sage of bloodvessels. Such plates, like nearly all bone new formed in disease, present, at first, a porous surface and a finely cancellous lung- like texture. But, gradually, in whatever form, the new bone tends to become harder and heavier ; the apertures that made its surface porous gradually diminish till they are obliterated, and thus the new bone, while still cancellous within, acquires a compact external layer, and be- comes more firmly united to the bone beneath it. The process of indu- ration continuing, the new bone acquires throughout a hard compact texture : its outer surface, no longer porous, becomes nearly as smooth as that of the old bone ; its colour also changes to that of the old bone ; and, finally, the two unite so closely that the bouniary line between them can hardly be discerned. Such is the gradual assimilation of the inflammatory product to the characters of the normal structure from whose disease it is issued : a process peculiarly worth studying in the bones, because in them, more than in any other tissue, the changes can be leisurely examined. Those which I have described occur in common inflammation : such, e.g., as follow injuries, or exist in the neighbourhood of necrosis, or ulceration, or foreign bodies. They are generally observed, also, in specific inflam- mations of bone : but, among these it is worth observing how charac- teristic of different diseases are certain formations of the new bone. The pustules of variola, or the vesicles of herpes, are scarcely more characteristic of those diseases, than are the hard nodules of oancelloas bone, clustered about the articular borders of bones that have been the ' Any large miiseum -will supply Buch specimens. Those in the College of Surgeons are minutely described in the catalogue, ii. p. 83, et seq., and v. p. 43, et seq. ; those at St. BartholomeVs may be studied through the Indices pp. 1 and 57. Even different parts of a single specimen will show much of what is described. BLOODVESSELS. 27] seat of chronic I'heumatism ; or the porous, friable, dirty, and ulcerating thin layers formed on the shafts in syphilis.' Cartilage, I have said, is probably not formed in inflammatory lymph m the process of its ossification. Neither does it appear to be formed in the more acute inflammations of articular cartilage ; but we must not exclude it from the possible developments of inflammatory products, while we remember the observations of Mr. W. Adams ^ respecting the enlargements of the ends of bones in chronic rheumatic arthritis. In these, which are marked by such formations of new bone and such thickenings of fibrous tissue as we constantly ascribe to inflammations, there is manifest increase of the articular cartilage, and a subsequent ossification both of that which is new formed, and, more slowly, of that which normally covered the head of the bone. The early conditions of the increase of the cartilage are not traced : but that it depends on in- flammation, rather than on true hypertrophy, is probable, both from, the concurrent signs and results of inflammation, and from the new car- tilage falling short of the perfect characters of the old ; for it has a fibrillated intercellular substance, and scattered nuclei, and is prone to ossiflcation. Non-striped Muscular Fibre. — Under some conditions non-striped muscular fibre is developed in inflammatory lymph. Julius Arnold has recently described ' a case of encysted empyema in the right side of the thorax, in which smooth muscular fibres were developed in the layer of lymph lining the free surface of the pleural sac, in such num- bers, as to give the lymph a fleshy appearance and trabecular character, not unlike that of the muscular wall of the bladder. The muscular fibro-cells were derived from the rounded cells of the inflammatory lymph by gradual elongation ; and transitional forms, from the simple lymph- corpuscle to the spindle-shaped contractile fibro- cell, were traced in the different layers of the false membrane. It remains that I should describe the adjunct structures of organised inflammatory lymph. But this may be briefly done, because the account ' As in Nos. 572, 628, and others, in the College Museum. 2 Trans, of Pathol. Soo. of London, iii. 1851. ' Virchow's Archil), 1867, xxxix. 270. — Arnold also refers to two observations recorded by Leo Wolf in 1832, in which muscular fibres were stated to occur in an inflamed pleura, and in a pericardium. The specimens which are preserved in the museum of the University of Heidelberg have been re-examined by Arnold, and smooth muscular fibres found in considerable numbers. 272 DEVELOPIiENTS OF INFLAMMATOEY PfiODUCTS : of the formation of new bloodvessels in granulations and otter repara- tive materials might, I believe, be transferred thither (from p. 162). The question is, indeed, often raised, as in the corresponding instance of granulations becoming vascular, whether the bloodvessels are formed entirely of the material of the lymph, and, as it were, by its own power of development, or whether they are outgrowths from adjacent natural or original vessels, which, as the expression is, shoot out into the lymph. I think it nearly certain, for the following reasons, that tlie lymph forms neither vessels nor blood, but receives those that are projected into it from the parts on or in which it is placed. 1. The direct observations supposed to prove that blood is formed in inflammatory lymph are very liable to fallacy, through the facility with which blood may be accidentally mixed with the lymph, in conse- quence of haemorrhage during life or after death, or in the preparation of the specimens. Where these sources of fallacy have been avoided, I have never seen anything suggestive of a transformation of lymph into blood. 2. The development of blood from tissue-cells is limited, naturally, to the earliest period of embryo-life, as if it needed the greatest amount of force for development ; afterwards, blood is not formed except through a long process of elaboration, and with the aid of many organs. Its formation, therefore, in the mal-conditions of inflammation is very improbable.' 3. In no specimen of inflammatory lymph have I seen appearances of transitions from inflammatory lymph-cells to blood-cells, such as we may see in the lymph of the lymphatics, both before and after it is poured into the bloodvessels. 4. Neither in any lymph have I seen appearances of such stellate cells as the interstitial bloodvessels of the early embryo are formed from ; nothing comparable with them has ever come into view. 5. In the formation of vessels for granulations and the walls of chronic abscesses, all is favourable to the belief that they grow up from the bloodvessels of the adjacent parts ; and there are no structures ' It should be stated, liowever, that Billroth, in his researches into the mode of formation of bloodvessels in granulations, has described and figured appearance ■which have led him to suppose that here, as in the origin of the first blood-corpuscles in the embryo, the contents of some of the gramdation -cells may form new blocd- corpusclcs, whilst the cell-membranes may assist in the formation of the walls of the new bloodvessels. LYMPHATIC VESSELS. 273 to -which the lymph bears so close analogy as it does to these, or to which it is so likely to be conformed in the production of its vessels.' On the whole, therefore, although direct observations are wanting, I think we may conclude that the greater part of, if not all, the vessels of inflammatory lymph are formed by outgrowth from adjacent vessels, as in the process of repair, and that through these vessels, not by its own development, it derives its supply of blood. In the first instance, the bloodvessels of lymph appear to be usually very numerous and thin-walled : therefore easily bursting, or dilated by congestions during life, or in the attempt to inject them after death. The College-collection contains an extremely beautiful specimen of soft recent lymph from the pericardium of a Cheetah, the vessels of which, injected by Mr. Quekett, appear as numerous and close-set as those of some of the more vascular mucous membranes. They present occa- sional slight and gradual dilata- tions, especially when they branch or anastomose. But after an uncertain time, as the lymph becomes more highly organised, so its vessels waste and diminish in number ; and while it acquires the proper structure of the connective tissue, so it descends to the low degree of vascularity of that tissue. The vessels of false mem- branes, as represented here (Fig. 40), from an instance in which they were naturally injected with blood, are usually rather wide apart, long, slender, and cylindriform. In all these particulars they differ from those of more recently vascularised lymph ; and their changes are, in these respects, parallel with those of the vessels of granulations during the gradual formation and perfecting of scars. Fig. 40. Perhaps the most perfect instance of the conformity with the natu- ral tissues of the body to which the developed lymph can attain, is manifested in its acquiring a supply of lymphatic vessels. We owe the ' See Eig. 36, wheje the continuity of the new-formed vessels of the inflammatory lymph with those of the subjacent connective tissue is represented. T 274 DEVELOPMENTS OE INFLAMMATORY PEODUCTS : knowledge of t"he lympliatics of false membranes to the masterly skill of Professor Schroeder van der Kolk, whose preparations of them are described and represented by his pupil, Dr. de Lespinasse.' In Fig. 41, copied from one of his plates, beautiful networks of lymphatics, with their characteristic bead- ed forms and abundant anas- tomoses, are shown traversing adhesions extending between two lobes of a lung ; while yet closer networks are seated in the thickened and opaque- white substance of the pleura or of false membrane covering it, beneath the adhesions. It seems to be in only the most perfect state, and when bloodvessels have long existed, that lymphatics are formed in false membranes. In recent lymph Schroeder v. d. Kolk has never succeeded in injecting any ; and we can only suppose that they are, like the bloodvessels, produced by out- growth from the lymphatics of the membrane with which they are con- nected. Virchow^ has twice seen nerve-fibres in adhesions. In one case, two fine nerve-fibres passed through an adhesion of the pleurae ; in the other, a single fibre extended into, but not through, an adhesion be- tween the liver and diaphragm. The time in which these complete developments of inflammatory lymph may be accomplished must vary so much, according to the cir- cumstances of the inflammation, that perhaps no reasonable estimate of it can be made. The experiments of Villerme and Dnpuytren ^ upon ' Spec. Anat. Path, de Vasis novis Pseudo-membranarum, 8to, Daventrise, 1842, Figs, iii. ir. In another instance he injected lymphatics in an adhesion between the liver, and diaphragm. Van der Kolk's injections, together with many other valuable pathological specimens, which he collected, are now in the Pathological Museum of the University of Oxford. A similar injection of these in adhesions between an ovarian tumour and the small intestines is described by Lebert : Traite des Maladies Cancereuses, p. 40. ' Wiirzhurg Verhandlungen, i. 144. ' Quoted hy Dr. Hodgkin, in his Lectures on the Morbid Anatomy of the Serous Memlrraiies, p. 42. TIME OF FORMATION. 275 dogs assign twenty- one days as the earliest time in which new vessels are formed, but I am disposed to agree with Dr. Hodgkin, that a shorter time is sufficient. On the other hand, I am sure that the supposition of their being formed in one or two days is incorrect. The principal case in support of this opinion is that recorded by Sir Everard Home ; but the specimens preserved in the College Museum ' show that he was deceived as to the true nature of the case. He says^ that he operated for strangulated hernia in a man, and found in the sac a portion of ileum, which was healthy, except in that its vessels were turgid with blood. The patient died twenty-nine hours after the operation ; and on examination ' several small portions of exuded coagulable lymph' were found adhering to the intestine that had been protruded. When the vessels of the intestine were injected, the injection passed into vessels in all these portions of supposed lymph, each, ' having a considerable artery .... and a returning vein.' Sir Everard Home, therefore, concludes ' that the whole operation of throwing out coagulable lymph, and supplying it with bloodvessels after it had become solid, was effected in less than twenty-four hours.' Now one of these specimens was figured by Mr. Hunter,' ' to show a small portion of coagulating lymph .... which is supplied with vessels ; ' but neither here, nor in his manuscript catalogue, does he allude to a probability of the vessels having been formed in twenty- four hours, although, had he believed it, he would scarcely have failed to record it.* An examination of the specimens shows that the small shred-like portions of membrane, attached by little pedicles to the in- testine, have not the appearance of recently coagulated lymph, but are fully organised, with traces of filaments and fat-cells. They are also very regularly disposed, at distances of from half-an-inch to an inch from each other, and are nearly all placed in two rows on each side of the intestine, about half-an-inch from the attachment of the mesentery, like very minute appendices epiploic®, such as are occasionally met with on the coats of the small intestine. Whether they be such appendices or not, it is in the highest degree improbable that they were formed after the operation ; especially since they are too minute and delicate ' Kos. 81 and 82 in the Pathological Museum. 2 In his Dissertatwn on Pus, p. 41. The whole ease is given in the College Catalogue, i. p. 37- » Works ; pi. xxi. fig. 2. ■> In the treatise on the Hood {Works, iii. p. 350) he speaks of nine days as a short time for the complete organisation of adhesions. T 2 276 DEVELOPMENTS OF INFLAMMATOEY PEODUCTS: to have prevented the intestine from exhibiting, when exposed in the sac, the natural polished appearance of its surface. I am not aware of any other case adapted to prove the earliest period at which bloodvessels may be formed in lymph. Serous surfaces may, indeed, become adherent in twenty-four hours, bnt this does not imply vascularity of the lymph between them ; it is simply adhesion by the coaptation of the intermediate lymph. DEGENEBATION OF INFLAMMATOKY PRODUCTS. 277 LECTURE XVI. DEGENEEATIONS OF INrLAMMAIOET PRODUCTS. Having given, in the last lecture, a general history of the chief develop- ments of the lymph produced in the inflammatory process, I propose now to tell a corresponding history of its degenerations ; and herein to describe what appear to be the transitions, from the ordinary forms of lymph in its primary state, its fibrine and its corpuscles, to those many lower forms enumerated as molecular and granular matter, pus- cells, granule-cells, inflammatory globules, and the rest. I said that, for the development of lymph produced in inflammation, it is requisite that the inflammation shall have ceased, and the condi- tions of healthy nutrition be restored. In the failure of this event, if the inflammation continue, or the due conditions of nutrition be in any way suspended, then, instead of development, degeneration will occur, with more or less rapidity, according to the original character of the lymph. And this may happen in any of the stages of formation which I described in the last lecture : it may happen alike to the fibrinous substance, or to the earliest lymph-cell, or to either, in any part of its progress to complete development. The following appear to be the chief degenerations of the fibrinous part of lymph, or of the materials derived from its earliest stages of development, whether in the purely fibrinous, or in any of the mixed, forms of lymph : — 1. It may wither ; wasting, becoming firmer and drier, passing into a state which Rokitansky has designated hm-nij. One sees the best examples of this change in the vegetations on the valves of the heart, or in the large arteries, when they become yellow, stiff, elastic, and nearly transparent, and in this state it may have all the simplicity of structure of ordinary fibrine, being only drier and more compact. A nearly similar character is acquired when lymph is formed over a lung which is extremely compressed in empyema, or in hydrothorax. The tough dry lymph that here forms the greyish layer over all the lung is not always developed, though it may adhere firmly : it may be withered, 278 DEGENERATIONS OF INFLAMMATORY PRODaCTS: wasted, and dried (as the lung itself may be), apparently in conse- quence of the compression. 2. The fibrinous substance of lymph is subject to a degeneration which we may compare in many respects with fatty degeneration, or, more closely, with the changes by which lymph-corpuscles are transformed into those of pus, with which changes, indeed, this is commonly associ- ated in the mixed forms of lymjah. In the solid parts of effusions that are found in the lower forms of inflammation, or in very unhealthy persons, this substance is usaally not clear and uniform and iilamentous but opaque or turbid, nebulous or dotted, presenting just such an appearance as marks the earliest stages of fatty degenerations in the muscular fibrils. In such lymph, also, one sees, not unfrequently, minute, shining, black-edged particles, which we may know to be drops of oil ; while some general alteration in its composition is shown by its not being made transparent with acetic acid. In all such cases as these it is very soft, and easily broken : it is devoid of all that toughness and elasticity which is the peculiar characteristic of well-formed fibrine; and by breaking it up, one may see the meaning of what one so often finds in the lowest forms of inflammatory exudation, such as occur in erysi- pelas and typhus — namely, films and fragments of molecular and dotted substance, floating in fluid that is made turbid by them, and by abundant minute molecules and granules and particles of oily matter. These represent the disintegration of fibrine that has degenerated after clotting, or has thus soHdified in an imperfect coagulation. Of such changes, also, an excellent instance is presented in the softening and disintegra- tion of clots within the heart, which Mr. Gulliver ' first described. These indeed, or any of the instances of the apparent suppuration within clots in the bloodvessels, might be studied for the illustration of the corresponding changes in inflammatory lymph ; especially in rela- tion to the ; likeness which, in both cases, the degenerate fibrinous substance bears to the molecular matter in the thinner and more turbid kinds of pus.^ We have examples of numerous varieties of this degenerate and disintegrated substance in inflammation. It is a principal constituent of most of what has been called ' aplastic lymph,' in inflammation o£ the serous membranes. Similarly it occurs, mingled with mucus, in ' Medico- Chirurgical Transactions, -K-^n. p. 136. ' We ought, doubtless, with Mr. Gulliver, to regard the corpuscles found in these cases of softened clots within the heart as blood-corpuscles retained in the clot, modified by stagnation and concoction. OF THE FIBRINOUS PRODUCTS. 279 the severer inflammations of the mucous membranes. And to the same source we may trace much of that molecular and granular matter which is usually mingled with all the less perfect forms of pus : e.g. with that formed in the suppuration of chronic inflammatory indura- tions ; with the variously changed corpuscles of ' scrofulous matter ' ; or with the granule-cells, and other corpuscles of pneumonia and the like inflammations. The general characters of the materials here described, and the coincident changes ensuing in the corpuscles that may be mingled with the fibrinous substance, mate it probable that the changes are of the nature of fatty degeneration occurring in the lymph. But when, as I have said elsewhere (p. 174), we see how a large mass of inflamed hard substance will become fluid, as it suppurates, and this with scarcely any, if any, increase of bulk, we may believe that another change ensuing in the fibrine is that which I called liquefactive degeneration (p. 78). In such a swelling, we may be nearly sure there is coagulated fibrine, both from the general circumstances of the in- flammation, and because neither corpuscles alone, nor fibrine in the liquid state, would give such hardness. The suppuration, therefore, if without increase of bulk, can hardly be explained, except on condition of the fibrinous substance, which had solidified, undergoing disintegra- tion and liquefaction. Just as Mr. Baker has shown ' that blood-clots after long remaining in the tissues may liquefy. A point of some practical importance is connected with these forms of degeneration of lymph, whether affecting the fibrinous substance or the coi-puscles. When the former has withered and become dry, it is probably put out of the capacity of being further developed, and is ren- dered passive for further harm or good, except by its mechanical effects. But the fatty and liquefactive degenerations may be yet more beneficial in that they bring the lymph into a state favourable to its absorption, and therefore favourable to that which is termed the ' resolution ' of an inflammation in which lymph has been already formed. I suppose it may be considered as a general truth, that the elements of a tissue cannot be absorbed so long as they retain their healthy state. There is no power of any absorbent vessels that can disintegrate or decompose a healthy portion of the body : for absorption, there must, in general, be not only an absorbing power, but also a previous or concurrent change, as it were a consent, in the part to be absorbed ; so that it may be 1 St. Bartholomew's Reports, 1865. 280 DEGENERATIONS OF INFLAMMA.TOBY PRODUCTS : reduced (ov, rather, may reduce itself) into miautest particles, or may- be dissolved. And this change is probably one of degeneration, not death, in the part ; for dead matter is usually rather discharged from the body than absorbed. Now such degeneration of the fibrine-products of inflammation as I have described, brings them into a state most favourable for absorption ; indeed, one may see in lymph thus changed many things which, in re- gard to the fitness for absorption, make it parallel with chyle.' Of such absorption of the fibrinous substance, we may find many instances. In rheumatic iritis we may believe the lymph to be fibrinous ; but we see its complete absorption taking place ; and the observations of Dr. Kirkes on the rarity of adhesions of the pericardium, in comparison with the frequency of pericarditis,^ may be in the same manner ex- plained. In rheumatic pericarditis we may be sure this substance is produced ; and the observed friction-sound has, in some cases, proved its coagulation ; yet in these cases, when death occurred months after- wards, scarce a trace of fibrine was found in the pericardinm ; it had been absorbed, and the degeneration I have been describing was pro- bably the preparation for its absorption. 3. I am not aware of any direct proof of the calcareous degenera- tion ensuing in the fibrinous product of an inflammation ; but we have the strongest evidence from analogy for believing that this change may be a frequent one, Tor there are numerous instances of calcifications of fibrine within the vessels : as, e.g., in the ordinaiy formation of phle- bolithes from clots of blood, in the branching and irregiilar pieces of bone-like substance found in obliterated veins, and in the lumps and grains of substance like mortar imbedded in fibrinous deposits on the heart's valves. We can, therefore, hardly doubt that, even before de- velopment, it may take part in formations of earthy matter in inflamma- tory products ; but the calcareous degeneration seems much more fre- quent in purulent fluids, and in the later developments of inflammatory lymph. 4. Lastly, we have examples of the pigmental degenerations of fibrinous lymph in the various shades of grey and black which often pervade the lymph formed in peritonitis, and which are produced, not by staining or discoloration of the blood by intestinal gases, but, accord- ing to Rokitansky, by the incorporation of free pigment- granules. ' See also the ingenious contrast of the progress of chyle and the regress of pus drawn by Gerber, in his Allgem. Anatomic, p. 49. ^ Medical Gazette, April 5, 1850, p. 581, OF THK COEPUSCLES. •281 Siicli appear to be the degenerations of the fibrinous part of inflammatory lymph : such, at least, are the changes in ib which we may refer to defects in its power or conditions of nutrition, because they correspond with changes that may be traced in the gradual degenera- tions of old age. I need hardly say, that it is chiefly by such corres- pondence that we can interpret them ; for when we find them, it is often, beyond our power to tell, by direct observ^atiou, whether, or in what way, the conditions of nutrition were defective. The corpuscular products of inflammation, in any of their stages of development, may retrograde, and present degenerations corresponding , and usually concurrent, with those which I have just described. 1. Their withering is well seen in some forms of what is called scrofulous matter, such as occur in chronic and nearly stationary scrofulous enlargements of lymphatic glands. In the dull ochre-yellow and half-dry material imbedded in such glands, may be found abundant cells, such as are sketched in Fig. 42. They are collapsed, shrivelled, wrinkled, glistening, and altogether irregular in size and form. One might suppose them to be the remnants of pus dried up, or the corpus- cles of chronic tuberculous matter, if it were not that among them are some with nuclei shrivelled like themselves, and some elongated and attenuated, which are evidently such as withered after they had been developed into the form of fibro-cells ; into which form it is certain that neither pus-corpuscles nor those of tubercle are ever changed. Fig. 42. These are the best examples of withered infiammatory lymph-cor- puscles ; but they may be also found in the pus of chronic abscesses. especially, of course, in that of such abscesses as ensue by suppuration of inflammatory lymph-formations like those just referred to. It may be hard, sometimes, to say whether corpuscles in these cases may not be pus-corpuscles shrivelled up ; but on the whole, I am inclined to believe that the shrivelled corpuscles of the pus of chronic abscesses are usually derived from the lymph, in which, having withered, they had become incapable of further change. 282 DEGENERATIONS OF INFLAMiM"ATOEY PEODUCTS ; 2. The fatty degeneration of lymph-cells is shown in their transi- tion into granule- cells — the inflammatory globules of Grluge. We owe the first demonstration of this to the excellent observations of Rein- hardt,^ who has also shown how, by similar degenerations, corres- ponding forms of granule-cells may be derived from the primary cells of almost all other, both normal and abnormal, structures.^ This method of degeneration appears peculiarly apt to occur in the inflammation of certain organs ; as, especially, the lungs, brain, and spinal cord ; but it may be found occasionally prevalent in the inflam- matory lyiQph of nearly all other parts, and in the granulations forming tbe walls of abscesses or of fistulce. It may occur alike in the early forms of lymph-cells, and after they have already elongated and attenuated themselves, as if for the formation of filaments, and after they have degenerated into pus-cells. The changes of transition (as shown in Fig. 43) are, briefly, these : — The lymph-cells, which may Fig. 43. have at first quite normal characters, such as I have described (p. 245) present a gradual increase of shining, black-edged particles, like minute oil drops, which accumulate in the cell-cavity, and increase in number, and sometimes in size also, till they neai-ly fill it. The fatty nature of these particles is proved by their solubility in ether ; and their accunaulation is attended with a gradual enlargement of the cell, which also usually assumes a more oval form. Moreover, while the fatty matter accumulates, the rest of the contents of the cell become very clear, so that all the interspaces between the particles are quite transparent ; and, coincidently with all these changes, the nucleus gradually &des and disappears, and the cell- wall becomes less and less distinct. I need hardly say, that, in these particulars, the changes of the inflammatory lymph-cells (which may also ocrnr when they have been ' Traube's Beitrdge, B. ii. 217. Observations similar to part of those of Eeinhardt were made independently b Dr. Andrew Clark {Medical Gazette, vols. xlii. xKii.). See also Dr. Gairdner's description of the formation of granule-cells from epithelium-cells in pneumonia (Coniributwms to the Pailwlogy of the Kidney, p. 20); and the list of references, pp. 114, 115. FORMATION OF PUS. 283 already developed into the form of fibro-cells) correspond exactly with those of the fatty degenerations observed in the cells of the liver or kidney, or in the fibres of the heart. There can be hardly a doubt of the nature of this process ; and it presents an important parallel with the similar changes described in the fibrinous substance. For, we may observe, first, that where this degeneration is apt to occur in inflam- matory lymph, it is least likely to be developed. A proper induration and toughening of the lungs and brain, such as might happen through development of the products of inflammation is extremely rare ; it is rarely seen, except in the scars by which the damages of disease are healed. And, besides, this degeneration is a step towards the absorp- tion of the lymph ; for commonly we may trace yet later stages of degeneration in these granule-cells. They lose their cell-walls, and become mere masses of granules or fatty particles, held together for a time by some pellucid substance, but at last breaking up, and scatter- ing their components in little clusters, or in separate granules. Thus, if at no earlier period of their existence, or after no fewer changes, the inflammatory lymph-corpuscles may pass into a condition as favourable for absorption as is that of the fibrinous substance when similarly degenerated and broken up : and such as this, we may believe, is a part of the process by which is accomplished that ' clearing up ' of parts indurated and confused in inflammation, and, especially, that of the solidified lung, which is watched with so much interest in pneu- monia. 3. Calcareous degenerations of the lymph-cells appear in cases, such as Henle' refers to, in which granule-cells are composed not wholly of fatty matter, but in part also as granules of earthy matter. In this combination they correspond with a common rule; for the fatty and earthy degenerations are usually coincident : they are combined in the advanced stages of the degenerations of arteries, and may be said to have their normal coincidence in ossification. 4. Of the pigmental degeneration of lymph-cells there are, I suppose, examples in the black matter effused in peritonitis : but the best examples are in the cells in bronchial mucus, to which I have already referred (Fig. 39). The most frequent degeneration of inflammatory lymph is into pus. It may ensue in nearly all the cases in which lymph is placed in condi- tions unfavourable to its development ; as in the persistence of inflam- ' In his Zeiischrift, B. ii. 284 DEGENERATIONS OF INFLAMJIATOEY PRODUCTS: mation, or in exposure to air, or in general defects of vital force. Ifc affects alike the fibrinous and the corpuscular parts of lymph. For although we do not call any liquid ' pus,' unless it have the character- istic pus- corpuscles, yet the materials of degenerate fibrine are commonly mixed with these ; and indeed many of the varieties of the pus formed in inflammations owe their peculiarities to the coincident degenerations of the fibrine. The changes which seem to prove the transformation of inflamma- tory lymph into pus correspond very nearly with those already cited (p. 173) concerning the similar relations of granulations to pus in the process of repair. But a few may be mentioned here : — 1. The fluid of such vesicles as those of herpes, is, in the first instance, a pure inflammato^ lymph, containing corpuscles which might be taken as types of the lymph-corpuscles,' and which may be as easily distinguished from any cells of pus, as the cells of well-formed granula- tions may be. If we watch these vesicles, we see their contents not increased, — ^rather, by evaporation, they are diminished; but the Ij'mph is converted into pus and the lymph-cells become pus-cells. And the change may ensue very quickly : I think I have known it accomplished in twelve hours at the most. 2. In like manner, as I said before (p. 174), when we watch the pro- gress of an abscess, we may find one day a circumscribed, hard, and quite solid mass, in which a premature incision will find no pus ; but in a few days later the solid mass is fluid, and this with little or no increase of bulk. Now the solidity and hardness are due to inflam- matory lymph, the corpuscles of which are apparently produced by the multiplication or proliferation of the normal nucleated corpuscles of the tissues of the inflamed part. The latter fluid is pus, and the change is the conversion of lymph into pus : the lymph-cells becoming pus-cells, which are separated from each other by a fluid, albuminous, inter- cellular substance. 3. As in common suppuration of a granulating wound, the granu- lation cells appear to be convertible into pus- cells, the superficial cells being detached in pus, while the deeper ones take a part in the deve- lopment of connective tissue ; and as in worse-formed granulations, the ' The mode of production of the corpuscles in the fluid of herpes is described on p. 246, and on the following page an account is given of the mode of origin of inflammatory lymph-corpuscles in other localitif s. The formation of pus-corpuscles in the vesicles of small-pox is described by Dr. W, E. Sanders in Ediii. Med. Journal, May, 1862. CIECUMSCKIBED SUPPURATION. 285 cells may be often by no cliaraoters, except by their forming a solid tissue, distinguisbable from pus-cells ; so, in an inflamed serous mem.- brane, pus-oells may float in tlie fluid, such, as cannot be distinguished from cells in the vascularised lymph that lines the cavity. In the fluid exudation, and in the solid product, the same forms may be found ; though, by comparison, we may be able to trace that in the former none of the cells were being developed, and many were proceeding beyond the degeneration to which any had attained in the latter. 4. One may see the same conversion of inflammatory lymph into pus thus illustrated. An amputation through the thigh was performed when all the parts divided were infiltrated with lymph, formed in con- nection with acute traumatic inflammation of the knee-joint. Next day pus flowed freely from the wound. Now, in amputation through healthy tissues, free suppuration does not appear till after three or four days :^ the pus here seen must have been formed by the conversion of the inflammatory lymph previously infiltrated in the divided tissues. Similar facts may be less strikingly observed in any wound, ^ From these and the like facts we have an almost exact parallel, in their relations to pus, between the material for repair by granulations and that produced in the inflammatory process ; and between, if they may be so called, the reparative and the inflammatory suppurations. And in some of the facts we may trace a transition from the one pro- cess to the other. In the formation of an acute abscess, for example, inflammatory lymph is transformed into pus ; then the pus, say, is discharged ; the signs of inflammation cease ; the process of repair is established, and reparative granulations line the abscess-cavity in the place of, or formed by, the peripheral layer of the lymph. Now, pus continues to be formed : but this pus is derived, not from inflam- matory lymph, but from granulation-substance. So, also, when an in- flamed part is cut, the first pus is from lymph : the latter pus, when repair is in progress, is from granulation-substance. In both cases, alike, the pus manifests itself as a rudimental substance iH-developed ' This is a very general rule; but I have seen suppuration after a primary amputation occur, in a boy, in thirty-six hours. 2 E Kiis's in his essay, De la Vasculariti et de l'Inflammatvm,l&i6, calls the pus-corpuscle ' U cadavre ' of the inflammatory lymph-corpuscle. This essay, although quoted by Lebert and Virchow, has scarcely received due attention in this country. Many of the opinions expressed in it are in advance of those which generally prevailed at the time it was written. Its author had a clear conception of the need of studying the phenomena of inflammation in their simplest form— not in the vascular tissues-, but in cartilage, epithelium, and the cornea. 286 DEGENERATIONS OF INFLAMMATOTY PEODUCTS : or degenerated (see p. 173); and tbe transition from the one condition to the other is an evidence of the impossibility of exactly defining between the inflammatory and reparative processes, unless -we can see their design and end. Much, therefore, of what was said respecting suppuration in connec- tion with repair, might be repeated here. But, avoiding this, let me only point out the principal methods in which inflammatory suppura- tion ensues, and the relation of the pus in each to the previous or coin- cident inflammatory product. In this last respect, the suppuration of disease difiers in an important manner from that of the reparative pro- cess, in that the degeneration may take place in any of the different varieties of lymph, and that, according to the primary character of the lymph, there may be traced (though as yet too obscurely) different ap- pearances of the pus.^ The methods of such suppuration may be named the circumscribed, the diffuse, and the superficial. The first may be exemplified by the formation of an abscess or a pustule ; the second by phlegmonous ery- sipelas, or purulent infiltration of any organ ; the third by purulent ophthalmia, or gonorrhoea : and in these and the like instances we may often, at the close of the disease, watch the transition from the suppura- tion that depends on the infiammatory process, to that which is coinci- dent with repair. In circumscribed suppuration, which has its most usual seat in the areolar tissue, we can generally observe the previous signs of inflam- mation, and of lymph-formation, in a certain area of the tissue. The lymph is interstitial, or infiltrated ; and, probably, in most acute abs- cesses, is a mixed product, containing some liquid exudation, a fibri- nous substance, and corpuscles. The proper elements of the tissue are separated or expanded by the exudation, or by the lymph produced among them ; and the inflamed part derives from it much of its swelling, and much of its hardness while the fibrinous part of the lymph is solid. Generally, such a swelling is at first, comparatively, ill-defined, and the natural textures not softened by their infiammatory degeneration ; and if it be near the skin, the visible inflammatory redness very gradually fades out at its borders, where, in the deeper tissue, we may believe, the lymph is gradually less abundant. But, in time, the swelling usually becomes more defined ; the inflammation, as it were, concentrates it- self, and appears more completely circumscribed. Now, the lymph, in ' See especially Eokitansky: Pathol. Anat. B. i. p. 210. ABSCESS. 287 such a case, may be absorbed, or may be developed so as to form, a long- continuing thickening and induration of the part as in an abortive boil ; but, in the case I am supposing, it is transformed into pus ; its corpuscles changing their characters in the miarmer already described, and a portion, perhaps, of its previously solidified part becoming liquid. The change almost always begins at or near the centre of the lymph, where, we may believe, the conditions of nutrition are most impaired. It may extend from a single point, or from many which subsequently coalesce. In either case the central collection of matter remains sur- rounded by a border or wall of indurated tissue, in which the infiltrated lymph is not transformed into pus, but rather tends to be more highly organised. This border or peripheral layer of lymph now forms the wall, as it is called, of the abscess, and the finger may detect, as the best sign of abscess, a soft or fluctuating swelling with a firm or hard border. The expressions commonly used are, that the suppurative in- flam.mation has taken place in the centre of the swelling, and that its effects are bounded by the adhesive inflammation : it might be said, with the same meaning, but perhaps more clearly, that, of a certain quantity of lymph produced in the original area of the inflammation, the central portions have degenerated into pus, and the peripheral have been maintained or more highly developed into tissue : and probably, we may add in explanation, the difference has depended on the degrees in which the conditions of nutrition have been interfered with in the places in which the two portions have been seated. In the central parts of an inflammatory swelling, the circulation, if not wholly arrested, must be less free than in the peripheral ; the blood, moving very slowly or stagnant, must lose more of its fitness for nutrition ; the tissues themselves are more remote from the means of maintenance by imbibi- tion : in these parts, therefore, degeneration, if not death, ensues, both in the lymph, and in the tissues in which it is infiltrated ; while, in the peripheral parts, maintenance, or even development is in progress.' I^ow, in the ordinary course of such an abscess, the purulent mat- ' Expressions are sometimes used which imply that the wall of the abscess is formed by an adhesive inflammation following, and purposely consequent on, the suppurative. This certainly happens, if ever, very rarely: it only seems to take place when suppuration is accompanied by extending inflammation. In such a case, that which is to-day the indurated abscess wall, may, to-morrow, have become pus ; and new inflammatory products, formed around it during its degeneration, will form then the boundary of the enlarged abscess. It may be, indeed, that the lymph situated at the centre of the inflammatory process is, naturally, less organisable than that .it the periphery; but this is not proved. 288 DIFFUSE SUPPURATION. ter is discharged. (I shall speak in the next lecture of the manner in which this takes place, as well as of the changes that ensne in the tis- sues among whose proper elements the inflammatory lymph is infil- trated.) On the interior of its wall, especially if its course have been very acute, we may find a thin, opaque, yellowish-white layer, easily to be detached, flaky, or grumous. It is usually formed of lymph-cells, or pus-cells imbedded in flakes of soft fibrinous substance. It has been made to seem more important than it is, by being called by some a ' py- ogenic membrane,' and by its being supposed that it is the work of the cells to secrete the pus. But the existence of such a layer is far from constant in abscesses ; it is often a sign of the imperfect organisation of the abscess-wall; its materials are probably oftener detached and mingled with the pus than they are vascularised ; and no such layer is found when free suppuration continues in an open abscess. A more normal course is observed when the progress of suppuration has been slower. In this case, the wall of the abscess becomes more highly organised after the discharge of the contents ; the circulation being restored in the infiltrated tissues of which the wall is formed, the lymph is devel- oped, or at least, if I may so speak, more highly vivified, and its cells, or new ones formed next to the abscess-cavity, are constructed into granulations, and are supplied with bloodvessels, hke those on the sur- face of a healing suppurating wound. Such vessels are represented in the sketch (Fig. 44). Fig. 44. With, or soon after, the evacuation of the purulent matter, the dis- ease on which the abscess depended may cease : and, if this be so, the later progress of a case is a process of healing which may, in every es- sential character, be likened to the healing of a wound by granulation. There is the same gradual development of the lymph-cells, or, as they might now be called, the granulation-ceUs of the walls of the abscess, first of the deeper, and then of the more superficial cells. The same SUPERFICIAL SUPPUKATION. 289 contraction, also, attends tliis process, and serves to diminish the area of the cavity, and to bring its walls more nearly into correspondence and proximity with the external opening, till, coming into contact, the opposite surfaces of granulations may unite, as in healing by secondary adhesion ; or till, as the edges of the opening are retracted and depressed, and the floor of the abscess is raised, they are brought nearly to a level, and heal as a single granulating surface. Such an abscess as I have described is often called acute or phleg- monous, in contradistiaction from those collections of pus which, being formed without the observed signs of inflammation, and generally slowly, are named cold or chronic abscesses. Observations are wanting, I believe, which might show how far the chronic abscesses, in their early condition, difier from such as I have described ; and, especially, whether there be first a circumscribed infiltration of lymph, of which part degenerates and the rest is developed. It is probable the pheno- mena are essentially the same ; for instances of all possible gradations between the two forms may be observed ; and, in the complete state of the chronic abscess, the structures are not widely different from those of the acute. The abscess- wall is usually firmer, more defined, so that it can often be dissected entire from the adjacent parts, and has its tissue more developed, and more like those of a membranous cyst : the lining is generally less vascular, smoother, and.less distinctly granulated, the contents are usually thin and serous, and indicate not only that the material of which they are composed was peculiarly unapt to be or- ganised, but that, even after its transformation into pus, further de- generations ensued in it. The diffuse suppuration, as I have said, may be exemplified by phlegmonous erysipelas, or any acute wide-spread infiammation of con- nective tissue. Here, with well-marked phenomena of inflammation, lymph is produced through a wide extent of the subcutaneous areolar tissue, and, from first to last, its boundaries are ill defined : the suppu- ration is, indeed, most certain and complete at the centre, or where the inflammation began ; but it may be nearly co-extensive with the diffu- sion of the lymph, and most rarely presents a well-defined boundary- wall, as in abscess. The lymph, in its primary character, is mixed ; its fibrinous constituent is evident in the coagulation that ensues when it is let out (see p. 240), and, usually, in the abundant, molecular mat- ter in the pus. The lymph is even more distinctly interstitial than in an abscess ; the tissue is thoroughly infiltrated with it, and is, com- u 290 DEaENERATION OF IKFLAMMATOEY PRODUCTS: paratively, little expanded : and when suppuration has ensued, and we cut into the inflamed parts, the pus often flows out slowly, even remains entangled in the tissue. The same condition is often yet more plain in the purulent infiltrations of such organs as the lungs ; their tissues are completely soaked with pu-s. The infiltrated tissues themselves are softened, not only by the mixture of the unorganised inflammatory matter, but through their own degeneration ; and, very generally, large portions of them perish, and are found as sloughs infiltrated with pus. In regard to their structural changes, there may appear little differ- ence between this condition and that of acute abscess, except in the contrast of the one being less, the other more circumscribed. But in regard to the inflammatory materials, they are, probably, in the phleg- monous erysipelas, much less naturally apt for organisation than in the abscess. The central suppuration of an abscess, while the lymph around is organising, implies that the degeneration depends much on the local defect of the conditions of nutrition : the diffuse suppuration seems due, in a larger measure, to original defect of the lymph ; and these differences correspond with those of the constitutional states at- tending the two diseases. After the discharge of the pus, the healing of the diffuse suppura- tion is, in all essential respects, similar to that of the abscess ; but the methods of discharge are much more diverse. Sometimes, after exten- sive sloughing of the skin, wide-spread suppurating cavities are exposed, which then granulate and heal like wide-open wounds ; sometimes, numerous isolated suppurations ensue, whence the pus is discharged as from so many small ill-defined abscesses, in each of which the ordinary healing occurs, while the intermediate parts are indurated by the im- perfect organisation of the lymph ; sometimes, from a comparatively small opening, large sloughs are discharged, and then the boundaries of the subcutaneous cavities which they leave granulate, and healing takes place as by secondary adhesion. The superficial inflammatory suppuration is such as we observe in gonorrhoea, and in purulent ophthalmia, and generally in the inflam- mations of mucous membranes. Here, the lymph is least apt for or- ganisation, partly because of the situation in which it is produced, and partly through its own natural condition ; for though it is formed, in these cases, both within the tissue of the inflamed membrane, as well as on its surface, yet the amount of thickening, or other structural DEGENERATION OF PUS CELLS. 291 change that takes place is slight, if we compare it with the changes that, in the same duration and severity of inflammation, would ensae m connective tissue, or in serous membranes. I have already spoken of the changes of mucus in the inflammatory process, and of the mixture of lymph that then occurs. The lymph is mostly of the corpuscular kind. It is, indeed, chiefly, in some of these cases of inflamed mucous membranes, that one may doubt whether it is reasonable to speak of the formation of lymph-cells as preceding that of pus ; for, especially in the more acute inflammations, the pus-cells seem to be directly derived from the mucus-corpuscles. And this character of the cells is often retained, even after the product of the inflamed membrane has regained, to the naked eye, a more mucous ap- pearance ; for here (unless ulceration of the membrane have ensued), the process of recovery from inflammatory suppuration is not through such healing by granulation, as in the former cases, but by a gradual return to the secretion of a more normal material ; and in this recovery, the proportion of corpuscles which possess the characters of pus-cella diminishes by degrees, until at last they are not sufSoient to give a purulent character to the liquid. The superflcial suppuration from inflamed mucous membranes is closely related to that from an ulcerated surface. An inflamed mucous membrane may yield purulent matter, even though it remain covered with an epithelium ; this happens in gonorrhoea, and in purulent oph- thalmia ; the vascular tissues in these affections have epitiielium on them, though it is thin and immature, and is reduced to a condition analogous to that of the thin and moist glistening epidermis on the inflamed ' weeping ' leg. The transition from this state to the suppura- tion from an ulcerated surface takes place when the epithelium is whoUy removed from a mucous membrane. This constitutes its abrasion or excoriation ; in the next stage the surface of the membrane itself is cast oiF, and this is its ulceration or erosion. Such are the several chief methods of inflammatory suppuration, and the relations of the pus to other products of the disease. In all the cases a point of contrast between pus and any form of inflam- matory lymph is to be found in its complete incapacity for organisa- tion. When once formed, the pus-cells, if they are retained within the body, have no course but to degenerate further ; it is characteristic of u 2 292 DEGENERATIONS AND DISEASES their being already degenerate, that they can neither increase nor de- velop themselTes. Various corpuscles found in pus, besides those I have already mentioned, may find their interpretation in these degenerations ; for the pus-cells are prone to all the degenerations that I described as occurring in the lymph-cells. They may wither, as in the scabbing of pustular eruptions, or in long-retained and half-dried strumous abscesses. Or, they may be broken up, whether before or after passing into the fatty degeneration, which is one of their most com in on changes, and in which they are transformed into granule-cells. It is this breaking np into minute particles, which, probably, precedes the final absorption of pus. Or, lastly, both the cells and the fluid part of the pus may alike yield fatty and calcareous matter, and this may either remain diffused in fluid, or may dry into a firm putty- or mortar-Kke substance. It is to such degenerations as these, in various degrees and com- binations, and variously modified by circumstances, that we must ascribe the diverse appearances of the contents of chronic abscesses, and of the substances that remain when abscesses close without complete final discharge of their contents. In such abscesses we may find mix- tures of pus-cells, granule-cells, and molecular matter, diffused in more or less liquid ; or pus-cells, half-dried, shrivelled, and showing traces of their divided nuclei ; or, all the cells may be broken up and their debris may be found mingled with minute oily particles, which appear in such cases to be always increasing ; or with these may be abundant crystals of cholestearine ; or, such crystals may predominate over all other solid contents. In yet other chronic abscesses (though, still, without our being able to tell why the pus should degenerate in these rather than in the foregoing methods) we find molecules of carbonate and phosphate of lime, mixed with fat-molecules and crystals, which are diffused in an opaque white fluid, and look like a deposit from lime- water, or like white oil-paint ; and as these contents dry in the healing of the abscess, so are formed the putty- and mortar-Uke deposits, and the hard concretions such as are found in the substance of lymphatic glands, in the kidney, or other organs that have been the seats of chronic abscesses. Time and patience would fail in an attempt to describe all the varie- ties of material that may thus issue from the transformation of pus. What I have enumerated are the principal or typical forms with which I believe, nearly all others may be classed ; though not without con- OF OEGANISED LYMPH. 293 sideration of the various substances that may be accidentally mixed with the pus : as blood, debris of tissues, etc. In conclusion of this part of the subject — of this biography of in- flammatory lymph — a few words must be added respecting the degene- rations and diseases which may occur after it is completely organised. The degenerations to which I have now so often referred, may be observed in fully-formed adhesions, or in the corresponding organised tissues in the substance of organs. Of the wasting of adhesions we often see instances in the pericardium, where films of false membrane are attached to one layer of the mem- brane, while the opposed portion of the other layer is only thickened and opaque. A more remarkable instance is presented in a case by Bichat, in which a man made twelve or fifteen attempts at suicide, at distant periods, by stabbing his abdomen. In the situations of the more recent wounds, the intestines adhered to the walls of the abdomen ; in those of the older wounds, the older adhesions were reduced to narrow bands, or were divided and hung in shreds. To similar wasting atrophy we may refer the extreme thinning and perforation of false membranes, by which, as Virchow ' has well described, they become fenestrated like wasted omentum. Of fatty degeneration I have seen no good examples in adhesions or similar inflammatory products, but of calcareous degenerations, or of such as present a combination of fatty and earthy matter, museums present abundant specimens. Among these are most of the plates of bone-like substances imbedded in adhesions of the pleura, in thickened and opaque portions of the cardiac pericardium, in the tunica vaginalis in old hydroceles, in the thickened and nodulated capsule of the spleen, in the similarly altered mitral and aortic valves. So, too, many of the so-called ossifications of muscles and ligaments are examples of calca- reous degeneration of fibrous tissue, formed in consequence of inflam- mation of these parts, and imbedded in masses of fibrous-looking bands, within their substance. In some of these cases, indeed, there may be an approximation to the characters of true bone (p. 73) ; but in others the earthy matter is deposited in an amorphous form, and seems to take the place of the former substance, as if, according to Rokitansky, it were a residue of the transformation of the more organised tissue, whose soluble parts have been, after decomposition, absorbed.^ ' Wikzhurg. Verhandlungm, B. i. p. 241. " Numerous specimens of the calcareous degeneration of adhesions are in the College Museum ; e.g. Nob. 103, 1493, U94, 1516, etc. 294 DEOENEKATIONS OF LYMPH. Pigmental degeneration of adhesions may be seen sometimes m those of the pleura, in which black spots appear like the pigment- marks of the lungs and bronchial glands.' Adhesions of the iris, also, may become quite black, by the formation of pigment like that of the uvea. Lastly, it must be counted among the signs of its attainment of complete membership in the economy, that the organised product of inflammation is liable to the same diseases as the parts among -which it is placed; that it reacts, like them, under irritation; is, like them, aifected by morbid materials conveyed to it in the blood ; and, like them, may be the seat of growth of new and morbid organisms. No more complete proof of correspondence with the rest of the body could be afforded than this fact presents ; for it shows that a morbid mate- rial in the blood, minute as is the test which it applies, finds in the pro- duct of inflammation the same qualities as in the older tissue to which it has peculiar affinity. The subject, however, of the diseases to which these substances, themselves the products of disease, are liable, has been little studied. I can only ennmerate the chief of them. Lymph, while it is being highly organised, is often the seat of hsem- orrhage ; its delicate new -formed vessels bursting, under some external violence, or some increased interior pressure, and shedding blood. Such are most of the instances of hismorrhagic pericarditis, and other hsemor- rhages into inflamed serous sacs. Even more frequently, the lymph, when organised, becomes itself the seat of fresh inflammation. Thus, in the serous membranes, we may find adhesions, in the substance or interstices of which recent lymph or pus is formed ; ' or, in other cases, adhesions, or the thicken- ings and opacities of parts, become highly vascular and swollen. It is, indeed, very probable that, in many of the instances of the recurring in- flammations that we watch in joints, orbofles, or other parts, the seat of the disease is, after the first attack, as much in the organised product of the former disease as in the original tissue. I suppose, also, that to such inflammations of organised inflamma- tory products, we may ascribe many of the occasional aggravations of ' As in No. 96 iu the College Museum. ^ As in No. 1512 in the College Museum. The specimen has some historic interest. It is one of those by which, in 1808, attention was first drawn, by Sir Darid Dundas, to the connection between acute rheumatism and disease of the heart. EESIDUAL ABSCESSES. 295 clironic iDflammations in organs ; the renewed pains and swellings of stiff joints, of syphUitic nodes, and tlie like ; wMch. are so apt to occur on exposure to cold, or in any otherwise trivial disturbances of the economy. In such cases we may believe that the former seat of disease becomes more inflamed, and that with it are involved the organised products of its previous inflammations. And in such cases there are, perhaps, none of the effects of inflammation which may not ensue in the newly-organised parts : evidently, they may be softened, or thickened and indurated, and made more firmly adherent : or they may be in- volved in ulceration, or may slough with the older tissues among which they are placed. Sometimes one sees cases in which abscesses form in or about the residues of former inflammations, and for such cases I have proposed the name 'residual abscesses.' ' They are mostly formed where pus, produced long previously, has been wholly or in part retained and become dry, or in some form ' obsolete.' But some, it is probable, are formed in the thickenings, adhesions, or other lowly organised products of inflammation long past. Suppuration among the products of a former inflammation is characterised by the discharge of thick, caseous, and calcareous matter, the residues of the earlier inflammatory forma- tions. When they form in the seats of past necrosis, pain and oonstitu.. tional disturbance, such as are attendant on acute abscesses, may be experienced, but more frequently they form slowly without pain, or fever, or any other distress. In these cases it may be difiScult to diagnose them from bursse, or fatty or fibro-cellular tumours. The his- tory, however, of a swelling, not unlike an abscess, appearing in a part that has long previously been the seat of inflammation, especially if it appears or greatly increases soon after anything has impaired the gene- ral health, may help to distinguish them. Lastly, the products of inflammation may be the seats of the morbid deposits of specific diseases. In their rndimental state they may incorporate the specific virus of inoculable diseases ; such as primary syphilis, variola, and the rest, and, when fully organised, they may be the seat of cancer and tubercle. ' See an essay on this subject by the author, with illustrative cases, in St. Bartholomew's Hospital Ecports, v. p. 73, 1869. 296 DESTEUCTIVE EFFBCTS OF INFI>AMJIATION, LECTURE XVII. CHANSES PEODUCED BY INFLAMMATION IN THE TISSUES OF THE AFFECTED PAKT. The account of the results of inflammation in the tissues of the part in which it has its seat, will include the chief among those destructive processes (p. 240) which form a part of the inflammatory changes of the nutritive process. The effects of inflammation are always injurious, if not destructive, to the proper tissues of the part in which it is seated. All the changes I shall have to describe are characteristic of defect of the normal nutrition in the parts : they are examples either of local death, or of some of the varieties of degeneration, modified and pecu- liarly accelerated by the circumstances in which they occur. The de- generations are observed most evidently in the processes of softening and absorption of inflamed parts. These I shall, first, endeavour to illustrate ; and then, after some account of the minute changes that are associated with them, I will describe the process of ulceration ; re- serving for another lecture the account of the death of parts that may occur in inflanxmation. Softening of inflamed parts. — One of the most common destructive changes induced by inflammation in an organ is a more or less speedy softening of its substance ; and this is due not only to infiltration of the part with fluid, but to a proper loss of consistency, a change ap- proaching to liquefaction, or to disintegration, of which, indeed, it is often the first stage. Of such softening, some of the best examples are in the true inflammatory softening of the brain and spinal cord, in which the softened part is usually found to consist of broken-up nerve substance, together with more or less abundant granular products of in- flammation. Such softening also may be found in the lungs : the pe- culiar brittleness and rottenness of texture, which exist with the other characters of hepatisation, are evidently due to changes in the proper tissue, inore than to incorporation of the products of inflammation. SOFTENlffG OF BONE. 297 In staphyloma of the cornea, similar softening ensues in connection with the opacity and other changes of appearance. But, perhaps, the most striking instance of softening in inflammation is to be found in bones. One may generally notice that an acutely inflamed bone is soft, so that a knife will easily penetrate it. Thus it may be found in the phalanges of the fingers, and in the bones of the carpus and tarsus, when they partake in deep-seated inflammation, and thus, sometimes, in the neighbourhood of diseased joints. The change depends partly on an absorption of the earthy matter of the bone, this constituent being removed more quickly, and in greater proportion, than the animal matter ; but the entire material of the bone is softened. In inflamma- tion and caries of bone, in addition to the softening caused by the re- moval of the earthy matter, there j is also a considerable widening of the Haversian canals, lacunae, and canaliculi, so that many of them disappear, owing to numerous spaces and canals being thrown to- gether.' The enlarged Haversian canals present the appearance of medullary spaces, and are fiUed with a soft rapidly growing tissue, not unUke that of granulations.^ The softening of bones may per- mit peculiar subsequent changes, especially their swelling and ex- pansion. Thus, in a remarkable case communicated by Mr. Arnott to Mr. Stanley, after excision of the bones of an elbow-joiut, inflammation ensued in the shaft of the Kg. 45. A, The inflamed humerus. The swelling of its lower part is shown by contrast with that of the corresponding part of the healthy humerus b. The separation of laminae is shown in c : all the figures are reduced one-half. Prom Mr. Stanley's Illustrations, PL i. Pigs. 4, 5, 6. ' See for a more detailed description of the process, Goodsir, Anat. and Path. Ohs. 1846; Monthly Medical Journal, Peb. 1850; and Anatomical Memoirs, Edinburgh, 1868 • "V. Bibra, in Liebig and Wohler's Annalen, toI. Ivii. ; and, in conjunction with Geist in Die Kranlcheiten der Arbeiter in den Phosphor^undhohfahriken; Virchow, Cellular Pathologic, lecture xviii. ; Barwell, Diseases of Joints. 2 E. Volkmann in Billroth und von Pitha's Handhuch, B. ii. Ab. ii. 255. 298 IMFLAMMATOEY CHANGES IN TISSUES: humerus, and after four months the patient died. The end of the humerus was red, and swollen, with expansion or separation of the layers of its walls (Fig. 4S). And the case showed well the coinci- dence of absorption and of enlargement by expansion ; for though the inflamed humerus was thus enlarged, and contained more blood than the healthy one, ' yet it was found not to weigh so much by half.' Similar expansions of bone, with all the characters of inflam- mation, and such as could not have happened without previous softening of the tissues, form part of the many swollen and enlarged bones which are common in all museums.' Doubtless, in many of these cases, the disease has been of very slow progress, and the separa- tion of the several layers of the compact bone, which the specimens display, must be ascribed to their gradually altered form, as they have grown about the enlarging bloodvessels and interlaminar inflammatory materials. But in other cases the expansion has in all proba- bility been more rapid, the softened bone yield- ing and extending, as the naturally softer tissues do, in an inflammatory swelling. The characters of a bone thus expanded are easily discerned. Its substance may be irregularly cancellous or porous ; but the most striking change is a more or less exten- sive and wide separation of the concentric laminse of the walls of the bone, so that, as in the section of this femur (Fig. 46), the longi- tudinal section of the enlarged wall appears composed of two or more layers of compact tissue, with a widely cancellous tissue be- tween them : and these layers may sometimes be traced into continuity with those forming the healthy portion of the wall. Usually, the separated layers are carried outwards, and the bone appears outwardly enlarged ; but sometimes the inner layers of the Fig. 46. Erom a specimen in the Museum at St. Bartholomew's, Series i. No. 94. Fig. 46. ' In the College Museum, Nos. 593, to 600, and 3085 to 3094 ; and in the Museum of St. Bartholomew's, Series i. Nos. 66, 94, 138, 196, 197, 198, etc. ABSORPTION OF BONE. 299 ■wall are pressed inwards and encroaoli upon the medullary tissue. In the first periods of the disease, the cancellons tissue between the sepa- rated layers of the wall has wide spaces, which are usually filled with a blood coloured medulla : but this tissue, like the often coincident external formations of new bone, appears to have a tendency to become solid and hard ; and its fibrils and lamin® may thicken till they coalesce into a compact ivory-like substance, harder than the healthy bone. Again, for examples of softening in inflammation, I may adduce the softening of ligaments, such as permits that great yielding of them which we almost always see in cases of severely inflamed joints. This is not from mere defective nutrition ; for it does not happen in the same form, or time, or measure, in cases of paralysis or paraplegia engen- dering extreme emaciation. Neither is it from the soaking of the liga- ments with the fluid products of the inflammation ; for it does not happen in the abundant efiusions of the slighter inflammations of the joints ; and when ligaments are long macerated in water they yet re- tain nearly all their inextensibility. It appears to be a peculiar softening, or diminished cohesion of the proper tissue of the ligaments ; the result of a degeneration combined with infiltration of infiamraatory products. We may see such changes in the ligaments of all joints ; in the hip, in the oases of spontaneous dislocation occasionally seen, independent of suppuration or ulceration of the parts belonging to the joint ; in the wrist, when the ulna after disease becomes so prominent ; in the spine, especially in the ligaments of the atlas and axis. But we see the eflects of this softening best in diseased knee-joints and elbow-joints ; and in all these cases we may often observe an interesting later change when the inflammation passes by. The hgaments, softened during the in- flammation, yield to the weight of the distal and unsupported part of the limb, or possibly, sometimes, to a muscular force, and the joint is distorted. Then, if the inflammation subsides, and the normal method of nutrition in the joint is restored, the elongated ligaments recover their toughness, or are even indurated by the organisation or contrac- tion of the inflammatory products within them. But they do not recover their due position ; and thus the joint is stiflened in the distor- tion to which its ligaments had yielded in the former period of inflammation. In the crowds of stiff', distorted, and yet not immovably fixed, joints, that one sees as the consequences of inflammation, these changes must generally have bappened to the ligaments : first soften- 300 INFLAMMATORY CHANGES IN TISSUES: ing and yielding ; then recovery, with induration, and perhaps some contraction, dne to their atrophy and the organisation of the inflamma- tory material. The cases are aggravated by similar changes in the adjacent parts ; for the stiflness of such joints is not due to the liga- ments alone ; all the subcutaneous tissues are apt to be adherent and indurated. Absorption of inflamed parts. — The absorption of the affected tissues is another example of the destructive changes ensuing in the inflam- matory process. Lite the degenerations which, probably, always precede it, it is, in many inflammatory conditions, a peculiarly rapid event ; and it may affect, at once, the proper elements of a part, its bloodvessels, and the inflammatory products that may have been previously formed among them. I shall refer here only to that which has been called interstitial absorption ; to the removal of parts from within the very substance of the tissues, as distinguished from the removal by the ejection of parti- cles from the surface, of which T shall afterwards speak as occurring in ulceration. Interstitial absorption of inflamed parts is seen very well in inflamed bones. The head of a bone may be scarcely enlarged, while its interior is hollowed out by an abscess ; what remains of the bone may be indurated, as by slight and tardy inflammation, but so much of the bone as was, where now the abscess is, must have been inflamed and absorbed. The changes are well shown in the instance of abscess in the lower end of the tibia which is here drawn (Fig. 47).' Here, too, the evidence of absorption is completed by the similar excavations formed in bones within which cysts and tumours grow ; for in these cases no other removal than by absorption seems possible. To similar absorption of inflamed tissue we may refer the wasting that we noticed in the heads of bones that have been •^'S- ^'^- the seat of chronic rheumatism. The besi MTiseum of St. Bartholomew's, Series i. No. 82. ABSOEPTION OF SOFT PARTS. 301 examples of this are in tlie liead and neck of tlie femur ; and the retention of the compact layer of bone, oovering-in the wasted cancellous tissue of the shortened neck and flattened head, is characteristic of intersti- al absorption, as distinguished from ulceration, by which the cancellous tissue is commonly exposed. In these cases of chronic inflammation of the bones, we may notice, also, an appearance of degeneration that precedes a peculiar mode of absorption or of ulceration. While the articular cartilages are passing through the stages of fibrous degenera- tion, and are being gradually removed, the subjacent bone is assuming the peculiar hardness which has been term.ed ' eburnation,' or ' por- cellaneous ' change. Now this change is effected by the formation of very imperfect bone ; of bone that has no well-formed corpuscles ; and it resembles the result of mere calcareous degeneration rather than a genuine ossifying induration. And its character as a degeneration is further declared in this — that it is prone to destructive perforating ulceration, which often gives a peculiar worm-eaten appearance to the bones thus diseased.' With these changes in rheu- matic bones we may also cite, as instances of absorption during slow infl^ammation, the changes which Mr. Gulliver^ first described as apt to ensue after injuries about the trochanter of the femur (Fig. 48). In such cases, without any appear- ance of ulcerative destruction, the head and neck of the femur may 1 Hein (Virchow's Archiv, B. xiii. p. 18, 1858) states that the worm-eaten apertures are occupied in the recent state with villous-like processes of the degenerate fibro- eartilage. A change, which appears to correspond with the eburnation of bone, is described by Mr. Tomes as occurring in a part of a tooth which lies beneath a carious cavity. In both cases the induration might suggest that it is calculated to retard the progress of the disease, but we have no evidence that it does this in an effective manner ; and in the case of the bones there is every appearance that the destruction is most rapid where there is most ind\iration. 2 Edinburgh Med. and Surg. Journal, 46. His illustration of a well-marked case is here copied. The change is illustrated in No. 3312 in the College Museum. wit. 'ffeyfc •■ a 1' 48. 302 INFLAMMATORY CHANGES IN TISSUES: waste by absorption, the neck becoming sbortened and tbe bead assuming a peculiar conical form. We might regard these effects as simple atrophy, if it were not that they are like the effects of the more manifest inflammation in the rheumatic cases, and that the existence of inflammation during life is often declared by the abiding pain and other symptoms following the injury. Again, other examples of the absorption of inflamed parts, or of parts that have been inflamed, are presented in the wasting of glands after inflammation ; as in cirrhosis of the liver, in some forms of gran- ular degenerations of the kidney, in tbe indurated and contracted lung after pneumonia. No doubt, in these cases, the reduction of the organ depends, in a measure, on the contraction of the diffused inflammatory product, as it organises ; but in many cases the quantity of new tissue is extremely small (it is so in the shrivelled granular kidney and in the wasted bone) ; and, in all the cases, we may well doubt whether the contrac- tion of organising infla.mmatory products would produce such exten- sive and uniform absorption of the proper substance of an organ, if there were not a previous condition favouring the absorption. The explanation of these cases is, that as, in the early periods of the inflam- mation, the softening and the degeneration of the inflamed tissues coin- cide with the formation of these products ; so, as the inflammation sub- sides, and subsequently, the absorption of the degenerated tissues coin- cides with their full organisation and contraction. And it is most probable that these events are independent though concurrent ; and that each occurs as of itself, not as the cause or consequence of the others. To all those cases must be added the fact of the absorption of the bloodvessels, and other accessory apparatus, of the inflamed tissues. Tbe absorption of the vessels themselves must coincide with that of the tissues. What a problem is here ! These, that had once been the aids to maintaining life, that had been adjusted to its energy and fashion, now, as it fails, are removed in adaptation to its failure. How can this be ? We can only guess that its method is just the reverse of the method of formation ; that, as in growth the bloodvessels and lym- phatics follow in the course of evolution of the growing parts, opening and extending into each new part as it forms, so, in decrease, they fol- low, and closing in harmoniously with the general involution, mingle their degenerate materials with those of the tissue, and are absorbed by the nearest remaining streams of blood. OPENING OF ABSCESSES. 303 Once more ; not only the original elements of the tissue may be ab- sorbed, but, even more rapidly, the new-formed products of iniiamma- tion. We have the best examples of this, as well as, indeed, of many of the facts which I have been mentioning, in the spontaneous opening of a common abscess ; which, though it be so common a thing, I will venture to describe here. Let us suppose the case of an abscess formed in the subcataneous tissue ; of such an one as I described some pages back, and may illus- trate by this sketch of an imaginary section through its cavity and the superjacent skin (Fig. 49). It has had its origin in small collections Fig. 49. of pus, produced originally in distinct areas, wbich collections subse- quently run together so as to form a hard, circumscribed, and more or less globular, inflamed mass. The pus is collected in the central parts of the abscess : while the peripheral part acquires more abundant bloodvessels, assumes the character of a granulation-layer on its surface, and forms the proper wall of the abscess. The pus of such an abscess as this will contain, probably, besides its proper constituents, some of the disentegrated tissue of the part in which it has its seat. In the pus of abscesses, we often find abundant molecular, fatty, and granular matter, a part of which may be the debris of the broken-down pus-cells, which not uufrequently undergo fatty degeneration, but a part is apparently derived from degenerating changes in the tissue itself For though some of the circumscribed portion of tissue, in which such an abscess has its seat, may be absorbed the rest is probably disintegrated andr-mingled more or less with the pus. 304 INFLAMMATORY CHANGES IN TISSUES. The abscess ttus formed has a natural tendency to open, unless aU the inflammation in which it had its origin subsides. Inflammation appears to be not only conducive, but essential, to the spontaneous opening of abscesses ; for, where it is absent, the matter of chronic abscesses will remain, like the contents of any cyst, quiet for weeks, or months, or years ; and when in chronic abscesses, or in cysts, inflam- mation ensues through the whole thickness of their coverings, it is usually certain that their opening is near at hand. This difference between acute and chronic abscesses makes it very doubtful whether the inflammation of the coverings of an abscess can be ascribed to any local influence of the pus. But to whatever it may be ascribed, we may refer to this inflammation, and to the degenerative changes that accompany it, the comparatively quick absorption of the integuments and of the infiltrated inflammatory products, over the collection of pus : and thus the fact, however we may account for it, that the integuments are more prone to inflammation and more actively engaged in it, than the other tissues about an abscess are, may be used to explain the pro- gress of matter towards the surface. Possibly (though this, I think, is much less probable) the tissues and the inflammatory products between an abscess and the surface may, after the degeneration which accompanies the inflammation, be disintegrated, and may mingle their molecules with the purulent contents of the abscess. But, in favour of the belief that they are absorbed, we have the evidence of analogy ; for just the same thinning and removal of integTiments takes place when they inflame over a chronic abscess with a thick impenetrable cyst, or over an encysted or even a solid tumour. In these cases, absorp- tion alone is possible ; and the cases are so similar to the ordinary progress of abscesses, that I think we may assign all the changes of the integuments over these to the same interstitial absorption much hastened in inflammation. During, or preparatory to their absorption, the integuments over an abscess become softer and more yielding. The change, of which the detection is often an indication of suppuration long before fluctua- tion can be felt, is due to such softening as I have described in de- generating inflamed parts. It takes place especially in the portion of the integuments over the middle, or over the most dependent part, of the abscess ; and this most softened portion, yielding most to the pressure of the pus, becomes prominent beyond the parts around it and 'points. Mr. Hunter refers to this as ' the relaxing or elongating process.' He says : ' Besides these two modes of removing whole DEGENERATION OF INl'LAMED TlSSUliS. 305 parts, acting singly or together [that is, besides the interstitial and the progressive absorption], there is an operation totally distinct from either, and this is a relaxing and elongating process carried on between the abscess and the skin, and at those parts only where the matter begins to point. It is possible that this relaxing, elongating, or weakening process, may arise in some degree from the absorption of the interior parts ; but there is certainly something more, for the skin that covers an abscess is always looser than a part that gives way from mere mechanical distension, excepting the increase of the abscess is very rapid. ' That parts relax or elongate without mechanical force, but from particular stimuli, is evident in the female parts of generation, before the birth of the fcetus ; they become relaxed prior to any pressure, the old women in the country can tell when a hen is going to lay from the parts becoming loose about the anus.'' While these changes of degeneration, leading to softening and absorption, are ensuing in the cutis, and the inflammatory products over such an abscess as I have described, we commonly notice that the cuticle separates, leaving the very point, or most prominent part of the abscess bare (Fig. 49). The cuticle is sometimes raised as. in a blister; but much more often it cracks and separates, and then, with its broken edges raised, peels off like dead cuticle : and we may believe that it is dead, partaking in the failure of nutrition in which all the parts over the abscess are involved, and being removed as a dead, not as a merely degenerated, part. At length, after extreme thinning of the integuments, they perish in the centre of the most prominent part. — Sometimes the perished part becomes dry and parchment-like, with a kind of dry gangrene ; but much more commonly a very small ordinary slough is formed, and the detachment of this gives issue to the purulent matter. The dis- charge is usually followed by a more or less complete cessation of the inflammation in the integuments, and then the wall of the abscess, having the character of a cavity lined with healt,hy granulation, heals. Degeneration of inflamed tissues.— Ihe softening and absorption of inflamed tissues of which I have been speaking are the chief conse- ' On the Blood, etc. WorJcs, iii. p. 477. The last fact is, probably, not appropriately cited. The change in the state of parts before the birth is most likely due to relaxation of the abundant muscular fibres that they all contain. 306 INPLAMMATORY CHANGES IN TISSUES : quences, or attendants, of minuter molecular changes to whicli I must now refer. These changes are derived from one or both of two sources ; namely, the natural but hurried degenerations of the inflamed tissues, and their penetration by the inflammatory product. The rapid softening of an inflamed tissue is, probably, in most cases, dependent on both these conditions ; and yet in some cases, and in some measure in all, it may be ascribed to a simple degeneration, such as might be classed with those named liquefactive. Thus, in the case of the integuments OTcr an abscess, we find it associated with infiltra- tion of degenerating inflammatory products, and probably in some measure due to their presence : but in the brain and spinal cord, the softenings of inflammation are, in structure and probably also in nature, very like those of mere atrophy. Less rapid softening is often connected with a well-marked fatty degeneration of the inflamed tissues. This is especially the case in the muscles, bones, cartilages, cornea, and certain glands, as the liver and kidney. I found such a degeneration well marked in the fibres of the heart of a man, who thrust a needle through his left ventricle four days before his death. There were evident signs of pericarditis ; and of inflamma- tion of the portion of the heart close by the wound ; and both in this portion, and, in a less degree, in all other parts of the heaxt, I found such a fatty degeneration of the muscular fibres as I could not have distinguished from that which occurs in the corresponding atrophous degeneration. The same changes may be oftener observed at later periods after inflammation of the substance of the heart ; and in some of these cases the interstitially-formed products are organised into flbrous tissue, while the muscular fibres themselves are degenerate. The extended observations of Virchow, on the inflammations of muscles,' show that such fatty degeneration of the fibres usually occurs in nearly all but the most acute cases ; in these, softening and disinte- gration of the muscular fibrils rapidly ensue, and fatty particles appear subsequently, if at all, in the inflammatory products and disintegrated tissue that are mingled with the sarcolemma. He shows, also, very clearly, how the changes in the muscular fibres may be associated with the effects of lymph produced interstitially among them, as well as with- in them, and passing through its ordinary progress of development or degeneration ; and that they may be followed by the complete wasting ' In his essay on Parenchymatous Inflammation, Archiv, B. iv. h. i. p 266. OPACITY OF THE CORNEA. 207 or absorption, of the degenerate tissue, in the place of which the new fibrous tissue formed by the developed lymph may remain like a scar or a tendinous spot. In inflamed bone, also, Virchow has traced fatty degeneration as a part of the process of softening which precedes its expansion or absorp- tion. The change is observed not constantly, yet very often, as a fatty degeneration of the bone-coi-puscles, in the interior of which small fatty molecules appear. After, or sometimes without, such previous changes in the corpuscles, he has also traced their enlargement, and the gradual softening, disintegration, and final liquefaction and separation of the proper bone-substance, immediately surrounding and including each corpuscle. The changes he has thus traced accord completely with those described by Groodsir' and Refern^ in the cartilage ; and, as he well observes, they have peculiar interest in relation to the occur- rence of degeneration, as a part of the infiammatory process, inasmuch as they are the results of the same process as that by which, normally, the medullary spaces and areolse of growing bone are formed, by which, as the bone grows, the compact cortical tissue is gradually changed into areolar or spongy tissue, and by which the peculiar ' mollities ossium,' or ' osteomalacia,' is produced. Changes like these in infiamed bone have been found in ulcerating and articular cartilage ; and they are here the more important, as showing the process essentially similar to the degeneration of infiam- mation, although occurring in a tissue that has, normally, no blood- vessels, and into which we have no evidence of the penetration of an exudation. They have been chiefiy observed by Goodsir and Redfern ; and have been confirmed by many.' They consist essentially in the enlargenient of the cartilage- cells, with increase of the nuclei, or of peculiar corpuscles contained in them, or with fatty degeneration of their contents, and fading or similar degeneration of their nuclei. The ' Anatomical and Fathological Observations, 1845; sai. Anatomical Memoirs,'E.iia., 1858 2 Aiwrmal Nutrition in Articular Cartilages; Edinburgh, 1850. Aud'On the Healing of Wounds in Articular Cartilages,' in the MouthUj Journal of Medical Science, Sept 1851. ' C. 0. Weber, in Virchow's Archio, B. xiii, 1858, and Barwell's Treatise on Diseases of Joints, 1861. Weber describes new vessels as extending, not only over the surface of the ulcerating cartilage, but afterwards penetrating its substance. Kiiss in his essay(i)eZ« Vascularite et de V Inflammation, 1846) stated that he had recognised in articular cartilages under the influence of irritants certain fibrous tran.^formations, and believed that he had seen, in one case, changes taking place within the cartilage- cells. X 2 308 INFLAMMATORY CHANGES IN TISSUES: hyaliue intercellular substance at fhe same time splits up, and softens into a gelatinous and finely molecular and dotted substance, or else is gradually transformed, in the less acute oases, into a more or less fibrous tissue. The enlarged cartilage-cells on the surface are released, and may discharge their contents on the surface of the ulcer ; and the intercellular substance is gradually disintegrated and similarly dis- charged, or, whatever part of it remains, is transformed into fibrous tissue, and becomes the scar by which the ulceration is, in a measure healed. Lastly, in the cornea, observations on the efiects of inflammation, purposely excited in it by various stimuli,' have shown that the changes in it are not due to any free exudation of lymph, but to altera- tion in its proper constituent textures. They consist, chiefly, in swell- ing and enlargement of its corpuscles, the appearance of minute fatty molecules in them, an increase and enlargement of their nuclei, and the production of numerous colourless corpuscles, like the white cor- puscles of the blood, or the lymphatic fluid." The intercellular substance becomes, at the same time, turbid, more opaque, denser, more fibrous, and sonaetiraes finely granulated ; and in some cases fatty molecules appear in it. The changes thus produced in the cornea are not essentially difierent from those that follow its idiopathic inflam- mations ; and, as Virchow concludes, they are extremely like those of the arcus senilis. Now, from all these cases, with which others of similar impori mighit be combined, we may conclude that the degeneration of the proper tissues of inflamed parts, which we recognise in the mass as a ' They are published briefly in Virchow's essay already cited ; and in detail in a dissertation — Der normale Ban, der Cornea und die pathologischen Abweichungen in dermelben, Wiirzhnrg, 1851 — by Fr. Strube, by whom the observations were made under the superintendence of Virchow. Additional and more extended observations have been made by His in the Wiirzburg Verhandl., iv. in Virchow's Archiv, vi., and in 'Beitrage zur norm, and path. Hietologie der Cornea,' Basel, 1866, by Eindfleisch in the Archiv, xvii. 1859, and Poster in Atlas der pathologischen Anatomic, 1859, taf. xxxiii. 2 According to the 'migratory' theory, some of these corpuscles would have wandered into the cornea from the bloodvessels of the adjacent parts. Oohnheim in his latest memoir (Virchow's Archiv, xlv. 1869), thinks that all the corpuscles which appear in the first stage of the inflammation have migrated from the blood, but leaves in doubt the origin of those which are seen in the later stages. He also admits that all the corpuscles (such as the ' granule-cells,' or the epithelial-cells mingled with the purulent secretion from an inflamed mucous membrane) met with in the course of an inflammation, or in an abscess, do not exist in the circulating blood, and cannot there- fore proceed out of it. ULCERATION. 309 softening of tlieir substance, or an aptness to be absorbed, is, very often, essentially like the fatty degeneration wMch we have studied as a form of atrophy of the same parts ; that the changes of structure are, in both, essentially the same ; differing in rate of progress, but not in method or result. And the cases of the bones, cartilages, and cornea, are the more to be considered, because the changes described in them can- not be referred, in any considerable measure, if at all, to a process of exudation into the elements of their tissues. The fatty degeneration and that of softening, as by progressive liquefaction, are doubtless the m.ost general forms in which the defec- tive nutrition in an inflamed part is manifested. But something allied to the calcareous degeneration occurs in the ossifications of the laryngeal cartilages when they are involved in inflammation, and of such other cartilages as are prone to an imperfect ossification in old age. These are frequent events ; and as Virchow observes, the ossification occurs constantly and often exclusively in the very part of the cartilages which corresponds with the seat of the inflammation. To the same class of cases we maj' refer the ossifications of parts of the articular cartilages in chronic rheumatic arthritis and the formation of the imperfect dentine or osteo- dentine which ensues in inflammatory affections of the tooth-pulp, or in the pulp of the elephant's tusk around bullets lodged in it. In all these cases it may be observed, the inflammatory process is attended with such changes as occur almost normally at some later period of life, or in old age ; such changes, then occurring, are reckoned among the natural degenerations, the signs of simply defective forma- tive power : the difference, therefore, between the natural degeneration and that of the inflammatory process seems to be one of time more than of kind ; the inflammatory is premature and comparatively rapid, and ensues with the characters of disturbed, rather than of merely defective, nutrition. Such are some of the evidences of degeneration ensuing in the proper tissues of inflamed parts. The oases I have selected are of the simplest kind ; whose results ate least confused by the changes that may ensue in inflammatory products infiltrated in the degenerating tissue. When this happens, it is perhaps impossible, at present, to separate the degeneration of the elements of the tissue from those which are occurring in the products themselves. The latter are espe- cially described by Virchow in the muscular fibres, and in the renal cells in what he calls the parenchematous form of granular degenera- 310 INFLAiniATORY CHANGES IN TISSUES: tion of the kidney. la the latter he says' that while, as in the croup - oas form, fibrinous cylinders of free inflammatory exudation may be found in the straight, and a part of the convoluted tubes, other changes are ensuing in the epithelial cells ; and by these chiefly, and sometimes alone, the characteristic altered structure of the kidney is induced. They occur especially in those parts of the tubes which run transversely or obliquely. In the first stage of the disease these cells enlarge, and their molecular nitrogenous contents increase, by the penetration of the inflammatory product into them. In the second stage, the in- crease is such that the cells break up, and the urine-tubes appear filled with a molecular albiiminous substance ; or else the fatty transforma- tion ensues in them, and they are filled with finely granular fatty matter, and appear as granule-cells or granule-masses. In the third stage the fat granules dispart, and an emulsive fluid is formed which may be absorbed or discharged with the urine. Virchow describes similar changes in the hepatic cells : but it may safiice only to refer to these. What has been already described will be enough, I hope, to justify the expressions formerly used : namely, that the changes (short of death) which ensue in the proper elements of an inflamed part are twofold : first, those of a degeneration, such as might ensue in simply defective or suspended nutrition ; and secondly, those which depend on the infiltration or commingling of the inflammatory product. Either of these may, perhaps, occur alone, but the first can be rarely, if ever, absent. When they are concurrent, their several effects cannot be clearly separated ; and when they both take place rapidly, the degeneration is apt to lose all likeness to such as naturally occur, and to appear as only contributing to the rapid disintegration and liquefaction of both the tissue and the infiammatory product. This appears to be the case in many instances of ulceration; a process which I have deferred to the very end of the history of inflammation, because all the other parts of the disease appear to be engaged in it. TJlceration. — I need hardly say that, ever since Hunter's time, con- fusion has existed in the use of the terms employed for various kinds or methods of absorption and ulceration. Of all that Hunter wrote, nothing I think is so intricate, so difficult to understand, as his chapter on ulcerative inflammations ; and much of the obscurity in which he left the subject remains. Some of this depends on the same terms ' In his essay alreaily cited. Many of his facts were published hy one of liis pupils, Dr. Niemann, in his dissertation, De iiijlammaiione renum parencliymatosa, Bero), 1848. ULCERATION. 31] having been nsed in different senses, and may be avoided if it is agreed to speak of the removal of those particles of inflamed parts, which are not on an open or exposed surface, as the ' interstitial absorption ' of inflamed parts. Then, the term 'ulceration' may be employed to express the re- moval of the superficial or exposed particles of inflamed parts : or rather when the epithelium or epidermis of an inflamed part is alone removed, it may be called ' abrasion ' or ' excoriation'; and when any of the vascu- lar or proper tissue is removed from the surface, it may be called ' ulceration.' If in such ulceration the superficial particles may be supposed to be absorbed, the process of removing them may be termed ' ulcerative absorption ; ' but if, as is more probable, their removal is effected entirely by ejecting them from the surface of the inflamed part, then the term ' ulceration ' may sufiiciently express this ejection, and will stand in stronger contrast to the ' interstitial absorption ' of the particles that are not so ejected, but are taken into the blood. I have lately referred to the uncertainty whether, as the cavity of an abscess enlarges or opens, the tissues and infiltrated inflammatory products that are removed from the inner surface of its boundary walls are absorbed, or are disintegrated and mingled with its fluid con- tents ; in other words, whether they are absorbed or rejected. The same uncertainty exists, in some measure, in the case of ulceration, concerning which, indeed, all that was said, respecting the necessity of inflammation to the opening of abscesses, might be here repeated, inas- much as inflammation seems essential, not only to the formation, but to the extension or enlargement of an ulcer. The ulcerative process cannot take place in healthy tissue ; previous degeneration of the tissue, and that such as occurs in the inflammatory process, is a condi- tion essential to it. But, when this condition is provided, is the enlargement of an ulcer effected by absorption of its boundaries, or by the gradual detachment and casting off of particles from their free surface ? Both methods of enlargement may, perhaps, in some cases, ensue ; but the probabilities are in favour of the enlargement being as a general rule, effected by the ejection of particles. Thus: — 1. Parts to be removed from a surface are generally cast off rather than absorbed, as cuticles of all kinds are, and the materials of secretions ; so that, by analogy, we might assume that the particles of the surface of a spreading ulcer would also be cast off. 2. The materials of the ulcerating tissue may be sometimes found in the discharge from the nlctr. In most cases, ind(ied, this is impos- 312 INFLAMMATOEY CHANGES IN TISSUES: sible ; but perhaps it is so only because, when the tissues, and the inflamnjatorj products in them, are degenerate and broken up, or decomposed and dissolved, we have no tests by which to recognise them. In the ulceration of cartilage in. which iuflammatory exudation ha;S no share, the process of ejection of the disintegrated tissue is clearly traced ; and we might deem this almost a proof of the same pro- cess being observed in other tissues, if it were not that in the cartilage a necessary condition of absorption, the presence of a circulation, is wanting. The same process of ejection, however, is traceable in ulcerating bone, where absorption might occur. It is shown by the observations which I have quoted from Virchow ; and Mr. Bransby Cooper has observed that, while in pus from soft parts only traces of phosphate of lime are found, the pus from around diseased bone con- tains in solution nearly 2^ per cent.' A similar but less complete observation has been made by Mr. Thomas Taylor,^ and by v. Bibra ;^ and we may believe that at least some of the phosphate of lime in these cases was derived from the diseased bone.^ 3. It strengthens this belief to observe that, ia many cases, small fragments of bone and other tissues are detached, and cast out with the fluid from the ulcerating part. These, indeed, when they are not fragments of tissue detached by ulceration extending around them, are good examples of the transition that may be traced from ulceration to sloughing or gangrene of parts, between which, if ulceration be always accomplished by ejection, the only essential difference will be one of degree ; the ulceration being a death and casting-off of invisible par- ticles of a tissue, while gangrene implies the death and casting-off of visible portions. ' Mrdieal Gajelfr, Jlay, 1845. ' Stanley : Treatise on Diseases of the Bones, p. 89. ' Chemische Untersnchungen ■verschiedeiier Eitcrurten, p. 85. ' The belief may seem the more reasonable, because of the similar fact of the quick absorption of bone-earths in inflamed but not ulcerating bones. Still, it must be admitted, more evidence is needed that the quantity of bone-earths discharged ^vith the pus is proportionate or equal to the quantity lost by the ulcerating bone. For if what has been said of the conformity of the properties of inflammatory and reparative products with those of the tissues from which they are produced, be true, then will also pus from diseased bone possess more bone-earths than pus from any other tissue, even though the bone be not ulcerating. Granulations upon bone doubtless contain more bone-tarths than those on soft parts, and they may ossify: now the relation of pus to granulations is commonly that of degenerating cells to the like cells developing; therefore we might expect that pus from bono, like granulations from bone, will contain a large proportion of bone-earths, independent of what may be derivi-d from the ulceration of the bone. ULCERATION. ■ 313 4. And it may be proved of many tliat we call ulcers, that they begin as slouglis, wMcb are cast oif, and leave the ulcerated surface beneath. "We may often see this, on a large scale, in the instances of what are called sloughing ulcers ; but Dr. Baly has proved it for a much wider range of cases, in his observations on dysentery, in which he has traced how even the smallest and the most superficial ulcers of the intestine are preceded by the death and detachment of portions of the mucous membrane, with its epithelial investment.' From these considerations we may hold it as probable that ulcera- tion is, usually, the result of the detachment of dead portions or molecules of an inflamed tissue, and that the substance removed in the process is not absorbed, but ejected. There are, indeed, some cases which may make us unwilling to admit, at present, that all ulceration is by ejection ; such as those of bone ulcerating under cartilage, or in the rapid extension of inflammation within it, or such as the spreading ulceration of the vertebrse, or of the heads of bones, that is not attended with external discharge of fluid. These may, for the present, interfere with the universality of the rule, but not with its generahty. But, if we may believe that the removal of a tissue by ulceration is generally effected by ejection of its substance, the question may be asked. In what form is it ejected ? Dr. Baly's observations enable us to say that, in the first instance, a visible slough is detached, a portion of the tissue dying and being disconnected from the adjacent living tissue. But, after this is done, when an ulcer enlarges, or extends and spreads, is the material of the tissue still removed in visible slough or fragments ? Certainly it is so sometimes ; for we may find little fragments of bone in the discharge from ulcerating bone, especially in strumous ulceration. But in other cases we have no evidence of this kind ; we cannot detect even microscopic fragments of tissues in the discharges, and we must suppose that they are removed in a state of solution or of molecular division, as it were pulverised in the dis- charge from the diseased part.^ To speak of the solution of tissues in the discharges of ulcers may ' Giilstoniau Lectores : Medical Gazette, 1847. 2 The late Professor O-oodsir considered {A7iat. and Path. Observations, 18 i5, p. 15 ■ Anatomical Memoirs, 1868) that the disappearance of the textures of an idcorated surface was due to the rapid formation of a layer of cells on the surface and at the margin of the ulcer, which caused the destruction of the normal textures, either by previous solution and subsequent absorption of the latter, or by the vigorous growth of the cells monopolising the proper resources of the part, so tl^at it gradually dissolved and disappeared. 314 INFLAMMATORY CHANGES IN TISSUES: seem like the revival of an old error long since disproved. But though the expression may be revived, it is with a new meaning. The proof has, truly, been long completed, that healthy tissues, even though they be dead, cannot be dissolved in pus, or any such discharge ; but the tissues that bound or form the walls of a spreading ulcer are not healthy ; they are inflamed, and, as I have been just saying, their ele- ments, and the products of inflammation in and among them, are degenerate, so that they may be now minutely divided, or even soluble in fluids that could not dissolve them while they were sound. Insolu- bility is as great an obstacle to absorption as to ejection in discharges ; no tissue can be absorbed without being first so far changed as to be soluble or very minutely divided in fluids with which it was before in contact and unharmed. Therefore, whether we hold the ordinary spreading of an ulcer to be by absorption of its boundaries, or ascribe it to their ejection, we must, in either case, admit that they are first made soluble. And if this be admitted, then it is most consistent with analogy, and most probable, that the extension of an ulcer, inde- pendently of sloughing, is accoiapUshed by the gradual degeneration of the tissues that form its walls, and by their being either disintegrated and cast off in minute molecular particles, or else dissolved and ejected in solution in the discharges from the ulcer. The solution here spoken of is such as may be efiected by the fluid discharge from any spreading ulcers ; but we may doubt whether all discharges from ulcers possess a corroding property, such as Rokitan- sky seems to ascribe to them, and such as he considers to be the chief cause of the extension of all ulcers. We may doubt, I say, whether all ulceration can be described as a corrosion or erosion of the tissues by ichor ; but, on the other side, we cannot well doubt that the properties of the discharge from an ulcer, or a sloughing sore, may have a great influence in accelerating the degeneration and decomposition, and thereby the solution, of the tissues that form its walls or boundaries. Many ichorous discharges from ulcers inflame and excoriate the parts over which they flow, and thus inflaming them, they promote their degeneration, and lead them more readily to enter into the ulcerative process. Many such discharges, also, are in an active state of de- composition ; and their contact with the inflamed tissues cannot but have some tendency to excite decomposition in them; a tendency which the tissues will be less able to resist, in the same proportion as they are already feebly maintaining themselves, or as they have been moved by HEALING OF ULCERS. 315 inflammation from their normal conditions and their normal tenacity of composition. Oq the whole, then, we may conclude, respecting the process of nlceration, that its beginning is usually the detachment of a slough, or portion of dead tissue, by the removal of the layer of living tissue that bounded it ; that the spreading of an ulcer, independent of such visible sloughing, is effected by the inflamed tissues that bound it becoming degenerate, and being detached in minute particles, or molecular matter, or being decomposed and dissolved in the fluid discharge or ichor ; and that this spreading may be accelerated by the influence of the discharge itself, which may inflame the healthy tissues that it rests on, and may exercise a decomposing ' catalytic ' action on those that are inflamed already. I need hardly say that we have no knowledge by which to explain the peculiar and characteristic forms of certain ulcers. We seem wholly without a guide to such knowledge ; but the existence of such specific forms is conclusive against the supposition that the extension of an ulcer is entirely due to corrosion by an exuded fluid. Such a fluid would act uniform.ly, unless the various efi'ects of disease on the tissues bounding the ulcer should make them variously amenable to its influence. We have as little knowledge of the nature and real differences of the various fluids discharged from ulcerating surfaces, — the various kinds of ichor* that they yield. They consist, generally, of fluid exuded from the surface, and holding in suspension or solution the disintegrated materials of the ulcerating tissue, and of the inflammatory products infiltrated in them. It may contain, indeed, the constituents of lymph or pus ; but they appear immature or degenerate, consisting of abun- dant molecular matter, with flakes of soft, dotted fibrine, and ill- formed lymph- or pus-cells, floating in an excess of liquid. Such a substance is probably, always incapable of organisation, both because of its own defect and because of the inflamed state of the parts it is in contact with. The differences that may from the first, exist in the several ex- ' I think it woulJ be useful to employ the term ichor exclusively for those dis- charges mixed with exudation that take place from ulcerating, i.e. from progressively ulcerating or sloughing surfaces. For, although it may be often impossible to distinguish, by any manifest properties, such ichor from some of the thinner kinds of BUS yet if the account of suppuration and of ulceration be true, a constant difference between' pus and ichor will be, that the latter contains disintegrated or dissolved materials of the ulcerating tissue, the former does not. 316 INFLAMMATOEY CHANGES IN TISSUES. amples of ictor are moreover quickly increased by the various chemical transformations that they undergo. Rokitansky alone has endeavoured to enumerate the varieties of property that may hence issue, and the influences they may exercise in the maintenance of the disease.' As from other inflammatory processes, so from ulceration, we may trace the transitions to the healing process. In the case of the ulcera- ted cartilage, Dr. Redfern's researches show that the healing is accomplished, mainly, by the complete transformation of the remaining cartilage-substance into fibrous tissue. Here is no proper process of exudation, for here are no interstitial bloodvessels ; the materials of the tissue itself, by transformation, form the scar. But in the vascular tissues, the reparative material is produced at and near the boundaries of the ulcer. As the inflammation subsides (for here, as in other cases, the inflammation must cease before its products can be developed), its products pass through changes like those described in the abscess-wall, and the tissues in which they are infiltrated may, perhaps, recover from their degeneration. A part assumes the characters of granulations, which, as we watch the pro- gress of an improving ulcer, assume daily more of the characters of those on healing open wounds. We cannot, indeed, mark the very act, or tell the hour, at which the inflammatory process was changed for the reparative ; at which the degeneration ceased, and development began ; there are no hard boundary lines here, or in any passage from disease to health ; but the change is gradually accomplished, and is manifest both in the organising material of the granulations, and in the pus which takes the place of the ichor, and exactly resembles that of the healing granulating wound. The ulcer is no longer ulcerating, but healing ; and the histories of the healing ulcer and of the healing wound might be told in the same words. ' FathulogUche Anatomie, "B. i. p. 213. SIGNS, NATURE AND CAUSES OF INFLAMMATION. 317 LECTURE XVIII. THE SIONS, NATURE, AND CAPSES OF INFLAMMATION. The presence of inflammation is indicated by certain sigtis, dependent on the processes described in the foregoing lectnres, and commonly- more evident than the processes themselves, though, severally, less constant, more transient, less essential. These signs are redness, heat, swelling, pain, and impaired function in the inflamed part, and a general condition of fever. One or more of these may, in many cases, be absent, or not appreciable ; there is not one of them which may not be observed in morbid conditions that have nothing else in common with inflammation; and even the concurrence of many of them may be found in oases in which there is no degeneracy of old or production of new structures, as in the unwisely called hysterical affection of joints. Nevertheless, these signs of inflammation are in practice very service- able ; there is no disease other than an inflammation in which they all concur, or in which more than half of them are for many days persis- tent. It is therefore very necessary to study at least the local signs in their relations with the essential constituents of the inflammatory process. The redness of an inflamed part is due to the increased afflux of blood in the dilated bloodvessels, and to the crowding of red blood-cor- puscles in them, and, in some instances, to the diffusion of the colouring matter of the corpuscles into the adjacent textures. The redness varies in tint and in intensity in various conditions. As a general rule, the greater the natural vascularity of a part, the more intense and bright is its redness when acutely inflamed. At one extreme may bo the pale rose-redness of an inflamed tendon or bone ; at the other the bright scarlet-crimson of the inflamed conjunctiva. Generally, too, the stronger the patient, and the more recent the inflammation, the brighter is the redness ; duskiness, with either a livid or a rusty tint, being sio-nificant of inflammations of long date a.nd in feeble patients. The heat of an inflamed part may be ascribed partly, and in strnc- 3 1 8 SIGNS, NATUKE, AND CAUSES OF INFLAMMATION : tures near the surface, to the accumulation of blood in them, and to the increased speed of the blood around them, so that they are less cooled than in their healthy state. But, besides, heat is produced in the inflamed part itself, so that the blood traversing it becomes warmer than it entered. Probably this is due both to the oxydation of the degenerating structures, and to the organizing of new materials ; but in what proportion it is due to each of these, or to any other molecular changes in the part, it is not yet possible to tell. The fact, however, is certain, and so constant that, when our means of observing it are sufficiently accurate, the increased heat of the part is the local sign of inflammation most to be relied on. The inflamed part is always warmer than it is in its healthy state ; warmer also than the corresponding part on the opposite side. More- over, the temperature of the focus of an inflamed part is higher than that of the arterial blood flowing into it, or of the venous blood flowing from it ; and this venous blood is warmer than the inflowing arterial blood, and than the venous blood in the corresponding part on the opposite side of the body.' The swelling of an inflamed part must be ascribed to many things — the dilatation and falness of the bloodvessels ; the exudation of serum or of liquor sanguinis; possibly the migration of blood-corpuscles from the vessels into the adjacent textures ; the rapid production of new cell- forms ; the ' collateral oedema '• — that is, the oedema due to the over- tension of the vessels about the inflamed part ; all these contribute to the increased size of the part. Their influence is the greater because of the softening and easier yielding of the inflamed textures ; for when an inflamed part feels too hard, it is only because of the increased tight- ness, not of any increase of hardness or toughness of texture. It is due to its dependence on. the degrees of toughness of the natural structures that the extent of swelling is in different parts widely various. In a loose texture, like that of the eyelid or scrotum, it is extreme ; in a tendon or fascia it may be hardly discernible ■ in a hard bone it cannot be discerned till the inflammatory softening of the bone-texture permits the expansion of its lamellse. When serous or synovial membranes are inflamed the apparent swelling is augmented by the collection of fluid transuded into the cavities enclosed by them ; the swelling of mucous membranes appears the less because of the fluid passing away from them by the open cavities which they line. ' On all these points see Simon, in Holmes's System of Surgery, Art. " InflaromHtion ; " .i.nfl 0. Weber, in Billroth n. v. Pitha's Handhueh, i. p. 381. INCREASED ACTION. 319 Pain is too narrow a term for designating tlic morbid sensibility of an inflamed part. It may be pain in any or all of its varieties of aching, smarting, burning ; or it may bo itching, heat, or tinglinw ; and any of these may be with throbbing or tension. Such varieties of pain may be ascribed chiefly to the varieties of natural sensibility in difierent parts ; for it may be almost truly said that each part has its own mode of morbid as well as of natural sensibility. But, besides, the varieties of pain are due to disturbances of circulation and of ten- sion, and of the other conditions in the inflamed part, especially of any condition by which the inflammatory swelling is hindered, for by all these pain is' augmented ; for instance, in the inflamed matrix of a nail, or fang or pulp of a tooth. Moreover, all the natural stimulants of a part excite excessive sensation in the same part when inflamed ; the skin or deeper textures become tender — that is, over-sensitive to moderate pressure ; the eye cannot bear ordinary light ; the ear is dis- tressed by ordinary sounds ; the slightly raised temperature of the inflamed part is felt by the patient as a burning. We have no clear knowledge of the condition of nerve- structures in these morbid sensibilities. We may safely believe that the nerve-fibres in an inflamed part degenerate as all the other structures do ; and there are reasons sufiicient for believing that acute degenerations of nerve-structures are attended with niorbid emissions of nerve-force ; but it would be unsafe to form nearer hypotheses on the relation of pain to the essential constituents of inflammation. It seenas needless to try to explain how disturbance of the function of a part is a sign of inflammation. It is not possible that a texture in which all the conditions of nutrition are disordered — as they are in inflammation — should be orderly in its functions, whatever they may be ; and so it is that, for example, an inflamed gland secretes, if any- thing, an unnatural fluid, and an inflamed muscle is inactive, or tremulous and weak; and an inflamed bone of support can bear no weight ; and with an inflamed eye objects are dimly if at all seen. Such are the local signs of inflammation. An examination of its very nature may best be made in the form of a comparison of its eS'ects with those of the normal process of nutrition. And this comparison may be drawn with two principal views ; namely to determine — 1st, how the effects of inflammation difier in respect of quantity from those of the normal process ; and 2nd, how they difier from the same in respect of quality or method. 320 SIGXS, NATURE, AND CAUSES OF INFLAMMATION : The decision on the first of these points may seem to be given in the term 'increased action,' which is commonly used as synonymous with inflammation. As used by Mr. Hunter, this term was meant to imply that the small vessels of an inflamed part are more than naturally active in formation or absorption, or in both these processes. This is probably the meaning still generally attached to the term by some ; while, as employed by those who believe the vessels are only accesso- ries in the work of nutrition, the expression ' increased action ' may be used to employ m.erely increased formation or increased absorption. In either, or in any, meaning, however, the term seems to involve the idea of an LQcreased exercise of vital forces — i.e. of those forces through the operation of which the various acts of organic formation are accom- plished. But if ' LQCreased ' action is to imply this, the description of the process and effects of inflammation show that the term cannot be properly used without some limit or qualification. If we consider the quantity of organic formation achieved during the inflammatory process, in the proper substance of the inflamed part, it is evidently less than in health. All the changes described in the last lecture are examples of diminished or suspended nutrition in the tissues of the inflamed part : they are all characteristic of atrophy, degeneration, or death. The tissues become soft, or quite disorgan- ized ; they are relaxed and weakened; they degenerate, and remain lowered at once in structure, chemical composition, and functional power ; or else, after degeneration, they are absorbed, or are disinte- grated, or dissolved, and cast out ; tbey die in particles or in the mass. During all the processes of inflammation there is no such thing as an increased formation of the natural structures of the inflamed part ; they are not even maintained ; their nutrition is always impaired, or quite suspended. It is only after the inflammation has ceased that there is an increased formation in some of the simpler tissues, as the connective tissue and the bones. So far, then, as the proper substance of the inflamed part is con- cerned, there appears to be decreased action ; that is decreased forma- tion. There may be, indeed, an increased absorption ; but this is also, in one sense, characteristic of decreased exercise of vital force, since all absorption implies a previous degeneration of the part absorbed. Nor can we justly call this in any sense ' increased action,' till we can show how absorption is an action of vessels. Thus far one of the constituents of the inflammatory process, one of the characters in which it difiers in respect of quantity from normal INCEEASEC ACTION. 321 nutrition, is a defect in the nutrition of the proper substance of the inflamed part. Bnt it is characteristic of the complete pi'ocess of inflammation, that while the inflamed structure itself suffers deterioration, there is a production of lovvly organised corpuscles in the part. Here, therefore, may be an evidence of increased formation, of increased action. Doubtless in relation to the productive part of the inflammatory- process, the expression ' increased action ' may be in some sense justly used ; for the weight of an inflamed part, or of the material separated from it, may be much increased by the morbid formation of organized matter. But the quantity of organised matter formed in an inflamma- tion must not be unconditionally taken as a measure of increase in the exercise of the vital forces ; for it is to be observed that the material formed presents only the lowest grades of organisation, and that it is not capable of development, but rather tends to degeneration, so long as the inflammation lasts. It may be but a vague estimate that we can make of the .amount of force exercised in any act of formation ; yet we may be sure that a comparatively small amount is sufficient for the production of low- organic forms, such as are the early products of inflammation. The abundant production of lowly organised structures is one of the fea- tures of the life of the lowest creatures, in both the vegetable and animal kingdoms. And in our own cases, a corresponding abundaut production is often noticed in the lowest states of vital force ; witness the final inflammations, so frequent in the last stages of granular degeneration of the kidneys, of phthisis, of cancer, and other exhausting diseases. In all these, even large quantities of the lowly organised cells of inflammatory lymph may be formed, when life is at its last ebb, and with these cases those correspond which show the most rapid increase of tubercle and cancer, and of lowly organised tumours, when the health is most enfeebled, and when the blood and all the natural structures are wasting. From these considerations we may conclude that the productive part of the inflammatory process is not declaratory of the exercise of a large amount of formative or organizing force ; and this conclusion is confirmed by observing that development, which always requires the highest and most favoured exercise of the powers of organic life, does not occur while inflammation lasts. The general conclusions, therefore, may be, as well from the productive as from the destructive, eff'ects of the inflammatory process, that it is accomplished with small expenditure Y 322 SIGNS, NATURE, -AND CAUSES OF INFLAMMATION: of vital force ; and that even when large qnantities of lymph are lowly organised, such an expression as ' increased action ' cannot be rightly used, unless we can be sure that the defect of the formative power, exercised in the proper tissue of the inflamed part, is more than counterbalanced by the excess employed in the production and low organisation of lymph. It may be said that the signs of inflammation are signs of increased action. But these are fallacious, if, again, by increased action be meant any increased exercise of vital force. The redness and the swell- ing of the iaflamed part declare the presence of more blood ; but this blood moves slowly ; and it is a quick renewal of blood, rather than a large quantity at any time in a part, that is significant of active life. An abundance of blood, with slow movement of it, is not characteristic of activity in a part ; it often implies the contrary, as in the erectile tissues, and the cancellous tissues of bone. The local increase of heat may be compared with that of an actively growing part, or of one which is the seat of ' determination ' of blood, or of ' active congestion.' In these cases the heat is high, chiefly because the blood, brought quickly from the heart, is quickly renewed ; and the quickly moving blood around the inflamed part may communi- cate its heat to that which is moving more slowly. But the proper heat of inflammation (I mean that which is measurable by the thermo- meter at the inflamed part) is probably due also to the oxydation of the degenerating tissues ; a process which we might safely assume to be rapidly going on in the more destructive inflammations, and which is, indeed, nearly proved by some of the evidences of the increased excretion of oxydised substances in inflammations, especially by the increase of phosphates in the urine during inflammation of the brain.' It is far from proved, indeed, that this source of heat is sufiicient for the explanation of the increase in an inflamed part ; and it may be at once objected that we have no evidence that the hottest inflamed parts are those in which the most destructive processes are going on. Still, in relation to the question, how far the increased heat is a sign of the quantity of formative force that is being exercised, we may argue that, as the general supply of heat in our bodies is derived from oxydation or combustion of wasted tissues or of surplus food, so iu these local aug- mentations of heat, the source is, perhaps, rather from similar destruc- tion of organised substances than from increased formation of them. ' Dr. Bence Jones : On the contrast between Delirium Tremens and Inflammation of the Brain, Med.-CMr. Trans, xxx, p. 37 ; and Yirchow, in his Archiv, B. iv. H. 1. LOCAL INCREASE OF HEAT. 323 If it be so, the increased heat will give no ground for regarding tlie inflammatory process as the result of a greater exercise of formative force than is employed in" ordinary nutrition ; none for speaking of it as increased nntrition or increased action. Rather, this sign may be added to the evidences, that the inflammatory process presents, of diminished formative force, and of a premature and rapid degeneration, in the affected part. In thus endeavouring to estimate the difference between the normal and the inflammatory modes of nutrition, in regard to the quantity of formative or other vital force exercised in them respectively, I have also stated the chief differences in relation to the quality or method of nntrition. The most general peculiarity of the inflammatory method is the con- currence of the two distinct though usually coincident, events, of which I have spoken at such length ; namely, 1st, the impairment or suspen- sion of nntrition of the proper substance of the inflamed part; and 2nd the production, from the blood, of material more than sufficient in quantity for the nutrition of the part, but less than sufficient in its capacity of development. By these concurring, inflammation is plainly distinguished from the normal method of nutrition. The same combination of events estab- lishes the chief differences between the inflammatory and every other mode of nutrition in a part. Thus, from all the forms of mere atrophy or degeneration, the inflammatory process, at least in the typical examples, is distinguished by the production of the lymph, which may be organising, even while the proper tissue of the inflamed part is in process of atrophj^, degeneration, or absorption. So far as the tissues inflamed are concerned, some inflammations might be classed with atrophies or degenerations ; but the concurrent production of lymph is distinctive of them. On the other side, the inflammatory mode of nutrition is distin- guished from hypertrophy by the failure of the nutrition of the inflamed part itself. So far as mere production and formation of organic foiins are concerned, some inflammations might be paralleled with hyper- trophies ; but the organisation of the lymph commonly falls short of that proper to the part in which it is produced ; and the substance of the part, instead of being augmented, is only replaced by one of lower organisation. And, lastly, from the production of new growths, such as tumours, ^ 2 324 SIGNS, NATURE, AND CAUSES OF INFLAMMATION: tlie inflammatory process is distingaished by this, — that its organised products, though like natural tissues of the body, are usually infiltrated, fused, and interwoven into the textures of the inflamed parts ; and that, when once their development is achieved, they have no tendency to increase in a greater ratio than the rest of the body. I am well aware that these can be accepted as only the generally distinguishing characters of the complete inflammatory process. Cases might be easily adduced in which the border lines are obscured ; in- flammations confounded on one side with atrophies, on another with hypertrophies, on a third with tumours, and on others with yet other local phenomena of disease But the same difficulties are in every department of our science ; yet we must acknowledge the value of general distinctions among diseases even more alike than these are. The case that I have chosen for illustrating the general nature of the inflammatory process is one representing the disease in its simplest form and earliest stage, manifesting only the formation of lymph, and such a change as the softening or absorption of the inflamed part. This is but the beginning of the history : but, if the inflammation continues or increases in severity, all that follows is consistent with this beginning ; all displays the same double series of events, the same defective nutri- tion of the part, and the same production of low organic forms. But these additions are observed : the part is more and more deteriorated, and perishes in the mass, or in minute fragments ; the newly-organised products, not finding the necessary conditions of nutrition, partake in the degenerative process, and, instead of being developed, are degene- rated into pus, or some yet lower forms, or perish with the tissues in which they are imbedded. Eespecting now the causes of inflammation, I shall not say more of its exciting causes, than that from the external ones, which alone we can at all appreciate, we may derive a confirmation of the opinion I have expressed concerning the nature of the process. They are such as would be apt to produce depression of the vital forces in a part ; all being, I think, such as, when applied with more severity, or for a lon- ger time, lead, not to inflammation, but to the death of the part. If a certain excess of heat will inflame, a certain yet greater heat will kill : if some violence will inflame, a greater violence will kill : if a diluted chemical agent will only irritate, the same concentrated will destroy the part. The same may be said, I think, of cold, and all the other external exciting causes of inflammation. I am aware that other ex- CAUSES OF INFLAMMATION. 325 planations of their action are given ; but none seems to me so simple, or so consistent with the nature of the process that follows them, as this which assumes that they all tend (as it may be said) to depress the vital forces exercised in the affected part. They may be stimulants or excitants of the sensitive nerves of the part, but they lead to the opposite of activity in its nutritive processes. In the reaction which follows the application of some of them, they may seem to have been the excitants of nutritive action ; but if the inflammatory state ensue, the formative process, we have seen, is really diminished. The proximate causes, or immediately preceding conditions, of in- flammation, appear to be various perversions of the necessary conditions of healthy nutrition in a part (p. 11) ; that is, morbid changes in either the supply of blood, the composition of the blood, the influence of the nervous force, or the condition of the proper substance of the inflamed part. Any one or more of these four conditions of nutrition being changed in quality may initiate an inflammation. A change in quantity more usually produces either an excess or deficiency of nutrition in the part, or some process different from inflammation. Thus, a diminution or withdrawal of the blood, without alteration of its quality, is usually followed by atrophy, degeneration, or death : a mere increase of blood in a part may produce hypertrophy, or something more nearly resem- bling inflammation, yet falling short of it. Similar effects may ensue from a mere increase or decrease, or abstraction, of nervous force. Change in the quality, whether with or without one in the quantity, of the conditions of nutrition, appears essential to the production of the phenomena of inflammation. I wiU endeavour now to show that inflammation may follow such perversion or qualitative change in each of ths conditions of nutrition, even though all the rest of them remain for a time in their normal state : selecting, for this purpose, such cases of inflammation as we may trace, proceeding, in the first instance, from the uncomplicated error of a single condition of nutrition. I. Inflammation may perhaps be produced — it certainly may be commenced, and in some measure imitated — by changes in the blood- vessels ; changes attended with alteration of their size, or their per- meability, or the other qualities by which they affect the supply of blood to a part. This may be conclnded from the similarity to some of the phenomena of inflammation which may be observed in certain cases of mechanical obstruction to the venous circulation. In cases of ascites 326 SIGNS, NATURE, AKD CAUSES OF INFLAMMATION: from diseased heart or Iwer, the peritoneum often contains coagnla of fibrine floating free in the sernm, though no organ may present ap- pearances of having been inflamed. In such a case, moreover, I have found a form of nucleated blastema ' developed in these coagnla, even while floating free. In another case of mechanical dropsy, I have found the fluid of anasarca in the scrotum containing both fibrine and abun- dant lymph-corpuscles. In like manner an apparently uncomplicated obstruction at the left side of the heart may produce many of the phe- nomena of bronchitis. Such as these are the cases through vyhich mechanical congestions of blood connect themselves with inflammation. And if to these we add the constancy of increased vascularity among the phenomena of inflammation, they may be sufficient to make us believe that disturbances in the circulation of a part may produce some of the principal phenomena of inflammation, even though all the other conditions of nutrition are, in the flrst instance, unchanged. But I know no other good evidence for the belief; and I think we should not lay much stress on these cases, since they display an imitation of only some parts of the process of inflammation ; namely, the fulness of the vessels, the retarded blood, and the production of organisabls matter. The nutrition of the proper tissues of a part, with merely obstructed circulation, sufiers but a trivial loss or disturbance in comparison with that which would accompany an inflammation with an equal amount of retardation in the movement of the blood. So far as the exudation in an inflamed part depends on the altered mechanical relations of the blood and vessels, so far may similar alterations alone produce effects imitating those of inflammation ; they may also be the beginning of the more complete process ; but I believe that the merely mechanical dis- turbances of the circulation are no more adequate alone to the explana- tion of the whole process of inflammation, than the normal movements of the blood are adequate to the explanation of the ordinary process of nutrition.^ II. We may speak much less eqaivocally of the influence of the state of the blood itself in causing inflammations ; for there can be little ' In 1870 one would not venture to say that there were not ' migrated' white blood-eorpnscles taking the chief part in this development, or that the cells of some adjacent epithelial surface.may not have been detached and undergone proliferation in the coagula. - The experiments by CI. Bernard and others, alluded to on p. 30, conclusively show that great hyperaemia and increased redness and temperature may occur in a part, under certain conditions, without being accompanied by any of the other evidences of inflammation. STATE OF THE BLOOD. 327 doubt that a very great majority of the so-called spontaneous or con- stitutional, as distinguished from traumatic, inflammations, have herein their origin. We might anticipate this, from the consideration that, m normal nutrition, the principal factors are the tissues and the blood m their mutual relations ; but we have better evidence than this, in cases of local inflammations occurring in consequence of general diseases of the blood. Some instances of this are clearly proved, as, e.g. the inflammation of the kidney and bladder by cantharides, of the stomach by irritant poisons injected into the blood, and others. Not less evi- dent is the inflaence of the blood as a cause of inflammation in the cases of eruptive fevers, vrhen the presence of morbid materials in the blood is proved by the effects of their transference in inoculation. Scarcely less thoroughly demonstrated are the cases of rheumatism and gout, of lepra, psoriasis, herpes, eczema, erysipelas, and other such afiections, vyhose primary seat in the blood aU acknowledge in practice, if not in theory — whose only probable common action is on the blood. Now, in all these cases, local inflammations are the external signs of the general affection of the blood : and I apprehend, that if acy difSculty be felt in receiving these as evidences that the morbid con- dition of the blood is the cause of the local inflammation, it will be through doubt whether a general disease of the blood — a disease affect- ing the blood sent to every part — can produce peculiar phenomena of disease in only certain small parts or organs. But this local effect of a general disease of blood has its illustration in some of the sure prin- ciples of physiology ; especially in one which I have fully illustrated in former lectures (pp. 11 et seq., and p. 47) ; namely, that the presence of certain materials in the blood may determine the formation of ap- propriate organisms, in which they may be incorporated. It is in exact parallel with the facts in physiology which I then adduced, that in certain general diseases of the blood, organs are formed, as the products of inflamm.ation, within which the specific morbid material is incorporated. Thus, in small-pox, cow-pox, primary syphilis, and whatever other diseases may be transferred by inoculation, the morbid material from the blood is incorporated in the products of inflammation, which are enclosed within the characteristic vesicle or pustule, or infiltrated lymph, just as, in the cases already cited, the constituents of urine or of medicines are incorporated in the renal cells, which are formed within the substance of the kidney ; or just as the constituents of sap are incoi-porated in fruit. In the cases of disease produced by a demonstrable virus, we have 328 SIGXS, NATUKE, AND CAUSES OF INFLAMMATION: all tlie evidence that can be necessary to prove the principle, that a general disease of the blood may be the cause of a local inflammation in one or more circumscribed portions of a tissue. And the analogy is so close, that I think we need not hesitate to receive the same explanation of other inflammations, which I have cited as occurring during morbid conditions of the blood. For although we cannot, by inoculation, prove that a specific morbid material of such a disease as herpes or eczema, gout or rheumatism, has been incorporated in the inflammatory products, yet we find great probability hereof in the many analogies which these . diseases present to the inoculable diseases, in their whole history, and, especially, in the decrease or modification of general illness which ensues on the fall manifestation of the local inflammation. If it be asked why a morbid material is determined to one part or tissue rather than another, or why, for example, the skin is the normal seat of inflammation in small-pox, the joints in rheumatism, and so on, I believe we must say that we are, on this point, in the same ignorance as we are concerning the reason why the materials of sweat, though earned to all parts, are only discharged at tbe skin, those of urine at the kidneys, of bile at th« liver, or why the greater part of the albuminous principles are incorporated in the muscles, and of the gelatinous in the bones. We cannot tell why these things are so, but they are familiar facts, and parallel with what I here assume of the incorporation of morbid materials derived from the blood. Again, it may be said that we need some explanation of the fact that the morbid condition of the blood does not influence the whole extent of any given tissue, but only portions of it. In the secretion of urine, it may be believed that the whole kidney is affected and works alike ; but in the assumed separation of the virus of small-pox, only patches of the skin are the seats of pustules ; in vaccinia and primary syphilis, only a siugle point ; in secondary and tertiary syphilis, a certain, bat sometimes disorderly, succession of various parts ; and so on. It must be admitted that many of the facts here referred to cannot yet be explained. In some cases, however, we can assign, with much probability, the conditions that determine the locality in which a gene- ral disease of the blood will manifest itself by inflammation. In some instances, it is evident that the localisation is determined by such as we may call a weakened or depressed condition, a state of already impaired nutrition, in some one part. For instance, when a stream of cold air is impelled on some part, say the shoulder, of a person disposed to rheu- matism, it determines, as a more general exposure to cold might do in STATE OP THE BLOOD. 329 the same person, the rheumatic state of the blood with all its general symptoms ; bat it determines, besides, the part in which that rheumatic state shall manifest itself first or alone. The depressed nutrition of the chilled shoulder makes it more liable than any other part to be the seat of iuflammation excited by the diseased blood. Or, again, when a virus is inserted, as in all cases of poisoned wounds, the local inflammation produced by the disease with which the the whole blood is infected will commonly have its seat in the wounded part. The virus must have produced some change in the place in which it was inserted, as well as in the whole mass of the blood. The change is not merely that of a wound ; for a simple wound made in the same person, at the same time, will not similarly inflame ; it is a change due to the direct and local influence of the virus. And the part thus changed may long remain in a peculiar morbid state, and peculiarly prone to inflammation from diseased blood. Thus, an infant was vac- cinated in the middle of June, and the disease had its usual course ; six ordinary vesicles formed in the punctures in the left arm, and common cicatrices remained, and all appeared well. In the middle of July, inflammation of the left axillary glands ensued. When I saw the child on August 21st, the glands were very large, and partially suppurated, and there was extensive inflammation of the skin of the upper arm. On August 30th, the pus having been partially discharged by incision, the glands had subsided, but superficial inflammation of the integuments existed still, and now there was, on the middle of each vaccine cicatrix, a distiuct circular low vesicle, not unlike that of the true vaccine erup- tion, except that it was not umbilicated, and appeared to have an undivided cavity. I observed in myself a trivial yet proving instance of the same principle. In 1857 I sprained my wrist, and applied twelve leeches for the relief of pain. The bitten places inflamed and slightly ulcerated, and scars formed slowly. But I had forgotten them till in 1862, when, more than five years after the accident, I was, for the first time, travelling in the summer heat of Italy. Then the scar of every leech-bite, but of no other part of my skin, became inflamed, and in the place of each a troublesome papule formed, and did not get well till my return to England. All remained quiet till, in my next vacation, and again in the heat of Italy, the same renewed inflammation occurred in every scar. The same event ensued in the three following summers. After this the scars bore, without change, the heat and other disturb- ances of travelling : but nine years had elapsed before the local ' weak- ness ' caused by each leech-bite was completely remedied. 330 SIGNS, NAT DEE, AND CAUSES OE INELAMJLITION : Such, cases are, probably, only examples of a general rule, that a part whose natural force of nutrition is in any way depressed, is, more than a healthy part, liable to become the seat of chief manifestation of a general blood disorder. A part that has been the seat of former dis- ease or injury, and .that has never recovered its vigour of nutrition, is always so liable ; it is a vieali: part. Thus, the old gouty or rheumatic joint is apt to receive the brunt of the new attack. And the same may happen in a more general way. A man was under my care with chronic inflammation of the synovial membrane of his knee, and general swelling about it : he was attacked with measles, and the eruption over the diseased knee was a diffused bright scarlet rash. A patient under Dr. Budd's care had small-pox soon after a fall on the nates : the pustules were thinly scattered everywhere, except in the seat of former injury, and on this they were crowded as thickly as possible. Thus, too, when a part has been injured, and, it may be, is healing, a disease having begun in the blood will manifest itself in this part. Impetigo appears about blows and scratches in unhealthy children ; erysipelas about the same in men with unhealthy blood. Such are some of the cases in which we seem able to explain the apparent choice of locality for inflammation, made by a morbid mate- rial which is difitlsed through all the blood. Many remain unexplained ; if it were not so, this portion of pathology would be a singular excep- tion to the general condition of the .science. Bat these difficulties afibrd no warrant for the rejection of a theory, of which the general probability is aflGirmed by so many analogies, by the sufficiency of its terms for the expression of the facts, and, it may be added, by nearly every particular in the constitutional treatment of local inflammation. For I suppose there are few parts of the m.edicinal treatment of local inflammation for which any reason can be shown, unless it be assumed that the medicine corrects some morbid condition of the blood. Let it be added that the state of the blood may, in part, or chiefly, determine, not only the locality, but also the degree and form of the inflammation. It may, as Dr. Ormerod has well expressed it, ' imprint on the morbid product (of inflammation) certain tendencies which take effect after the morbid products have entered upon a condition of com- paratively independent existence.' ^ But on this point I need not dwell : for a large portion of Lecture XIV. is devoted to it, and it will be again considered in the Lecture on Specific Diseases. ' In his Lectures on the Pathology and Treatment of Valvular Disease of the JJeart, in the Medical Gazette, 1851. STATE OF THE BLOOD. 331 III. To lest the influence of a disturbance of the nervous force in engendering the inflammatory process, we must not, as is commonly done, take cases of the efiects of external injury. Such an injury, or the presence of a foreign body, is supposed to excite inflammation by stimulating the nerves of the part, and by changing, through their in- fluence, the state or action of the bloodvessels. This may be true ; but we should remember that when a common injury is inflicted, it acts not only on the nerves of the part, but also on its proper tissues ; and it may so afiect the state of these tissues that the changes produced in them may be the excitant of inflammation, independent of the afiection of the nerves. All such cases as these are thus ambiguous. For a better test, we must select cases in which the excitant of in- flammation acts (at least in the first instance) on the nervous system alone. The simplest paay be the most proving instances. Whoever has worked much with microscopes may have been conscious of some amount of inflammation of the conjunctiva, in consequence of over- work. Now the stimulus exciting this inflammation has been directly applied to the retina alone ; and I have often had a slightly inflamed left conjunctiva, after long working with the right eye, while the left eye has been all the time closed. I know not how such an inflamma- tion of the conjunctiva can be explained, except on the supposition that the excited state of the optic nerve is transferred or communicated by the filaments of the nerves of the conjunctiva, gene- rating in them such a state as interferes with its nutrition. It is true that in these simpler cases, the retina is not itself evidently inflamed ; but after yet severer stimulus it commonly is so, and the conjunctiva shares in the evil effects of the communicated stimulus ; effects which we cannot ascribe to any alteration in the blood, or the size of the bloodvessels. I may mention another case ; the occurrence of inflammation of the testicle in cases of severe irritation of the urethra. The most unexcep- tionable cases of the kind are those in which the irritation is produced by a calculus impacted in a healthy urethra. I have a specimen, in which extensive collections of lymph and pus are seen in the testicle of a man in whose urethra a portion of calculus was impacted after lithot- ritv. Here is such an inflammation as we cannot refer to disease of the blood, and attended by such changes as we cannot explain by any enlargement or paralysis of the bloodvessels ; nor do I know how it can be at all explained, except by the disturbance of the exercise of the nervous force in the testicle, which disturbance was excited by trans- 332 SIGNS, NATURE, AND CAUSES OF INFLAMMATION : ference from the morbidly-ajffected nerves of the primary seat of iri-ita- tion in the urethra. For similar evidence of the influence, not of suspension, but of dis- turbance of the nervous force, in producing inflammation, many of the cases might be again cited which were referred to (p. 31) as evidence of the influence of the nervous system in ordinary nutrition. Among these are the cases of Herpes Zona, in which inflammation ensues only in certain patches of skia or mucous membrane, supplied by the bi-an- ches of one nerve previously neuralgic ; those also of eczema and of ' glossy flngers,' of csdema, and of rheumatoid inflatamation of joints, following injury and abiding irritation of nerves, without any indica- tion of other disturbance, whether local or general. Now, for the explanation of such cases as these, there appear to be two chief theories : 1. It may be that the nerves distributed to the minute bloodvessels of a part may be so affected that these vessels may dilate, and their dilatation may produce the other phenomena of inflammation ; or, 2. The disturbance of the nervous force may more directly interfere with the process of nutrition, inasmuch as this force exercises always some influence in the nutrition of each part. The flrst of these theories had at one time acquired a dominant place in some systems of pathology, especially in those of Germany. The principal form of it, which was maintained most proniinently by Henle, enlisted also the approval of Rokitansky, and was largely recei- ved, professing to explain all inflammations, and passing by the name of ' neuro-pafchological,' to distinguish it from the ' humoral,' and all other theories of inflammation. This theory may be thus briefly stated. The exciting cause of inflammation, whether an external cause, such as an injury of a part, or an internal one, such as diseased blood, acts, in the first instance, on the sensitive, centripetal, or afferent nerves of the part. These it affects as a stimulant, producing in them an excited state, which state, being conveyed to some nervous centre, is thence re- flected on the centrifugal or motor nerves of the bloodvessels of the same, or some other related part. This reflection, however, is supposed to bring about a kind of antagonistic sympathy, such that, instead of exciting the motor forces of the bloodvessels to make them contract, it paralyses them, and is followed by their dilatation or relaxation. This dilatation being established, the effusion and other phenomena of in- flammation are assumed to follow as natural, and most of them as mechanical, consequences. DISTUEBANCE OF THE NERVOUS FORCE. 333 The eminence of those who have supported this hypothesis makes one hesitate in rejecting it ; and yet I cannot help believing it to be groundless. If we remember that parts may present the chief pheno- mena of inflammation, though they have no nerves, as the firmest ten- dons, and articular cartilages ; that the degrees of inflammation in parts bear no proportion to the amounts of pain in them when inflamed ; that the severest pains may endure for very long periods with only trivial, if any, phenomena of inflammation ; we may well think that there can be no suflicient ground for the invention of such an hypothe- sis as this. And, if we add that, even admitting the dilatation of bloodvessels as a possible consequence of the stimulus of sensitive nerves, yet the phenomena of even simple inflammation would be no necessary consequence thereof ; that the varieties of inflammations would be quite unintelligible as results of similar mechanical distur- bances of the circulation ; and that the dilatation of bloodvessels, in any mechanical way produced, is followed by only feeble imitations of a part of the inflammatory process ; then we may think that the hy- pothesis, if all its postulates be granted, will yet be insufficient for the explanation of the facts. I believe that, if we would have any clear thoughts respecting the influence of the nerves in initiating inflammations, we must first re- ceive the theory already referred to (p. 28), that a certain exercise of the nervous force is habitually and directly engaged in the act of nor- mal nutrition. If we admit this, there can be little dif&culty in believ- ing, whatever there may be in explaining, that the perturbations of the nervous force may engender the inflammatory mode of nutrition more directly than by first paralysing the bloodvessels of a part. We attain nearly to a proof of this in the instances of altered nutrition adduced in a former lecture (p. 31), and in those of secretions altered, not in quantity alone, but in quality, by affections of the nervous system. It is almost inconceivable that any of the essential properties of a secretion should be changed by an alteration in the quantity or movement of the blood in a gland : yet sach changes are frequently manifest in the milk, tears, urine, and sweat, under the influence of mental aff'eotions of the nervous force ; and the analogies of secretion and nutrition give these cases nearly the weight of proof in the question of the influence of the disturbed nervous force in causing inflammations. rV". The last of the necessary conditions of normal nutrition in a part is the healthy state of the part itself; and it appears highly pro- 334 SIGNS, NATURE, AND CAUSES OF INFLAMMATION : bable that a disturbance of this may initiate, and in this sense be the canse of, inflammation. This is probable for many reasons ; and, first, from analogy with normal nutrition. Generally, the principal condi- tions of nutrition are in the relative and mutual influences of the ele- ments of the tissues and the blood. More particularly, the state of the tissues determines, at least in great measure, both the quantity and the rate of movement of the blood supplied to them : the changes of the tissues, whether in growth or decrease, usually just preceding the ad- apted changes in the supply of blood (p. 61). So, we may believe, a change in a part, anyhow engendered, may, by altering its relation to the blood, alter its mode of nutrition, and some of the changes may produce the inflammatory mode of nutrition, together with the altered supply of blood, and other characteristic signs.' I am disposed to think such changes would be especially effective, as causes of inflamma- tion, when they ensue in the rudimental and still developing elements of the tissue ; for, as it seems to be chiefly these which determine the normal supply of blood in a part, so, probably, the abnormal state of them would most afiect that supply. Secondly, we may judge the same from the analogy between inflam- mation and the process of repair. Certainly it is the state of the in- jured part, i.e. of its proper tissues, not of its nerves and bloodvessels, which initiates the processes of repair. Now some of these are so like those of inflammation, that they are commonly identified, and are not capable of even a refined distinction. This is especially the case with the articular cartilages and the cornea.' And thirdly, the infli\ence of the condition of the proper tissues of a part in initiating inflammation in it, is illustrated by more direct facts ; such as, that injuries of parts that have no vessels or nerves are followed by altered modes of nutrition which are more or less exact resemblances of inflammation. Thus, e.g., it is in the lens, vitreous humour, and the like, after injury. In all of these it is difficult to imagine any other cause of inflammation than the altered relations be- ' See, as confirming this statement, the obserrations of Prof. Lister, referred to on pp. 30 and 231. ' See Dr. Redfern's Researches, I. c. ; and compare Mr. Bowman's account of the healing of wounds in the cornea, in his Lectures on the Parts concerned in Operations on the Eye, p. 29, with the observations already quoted from Virchow. The doctrine of the Cellular Pathology, as illustrated by Virchoiv, is based exclusively on the state of the tissues. The action of irritants on a part being ascribed to the eifects produced by them upon the elements of the tissues directly and not through the nerves or Woo 1 vessels. STATE OF THE PART. 335 tween the tissue and the blood or the materials deriv'ed from it. And, though with some fear of straining an analogy too far, I beliuve that we may gather illustrations of the same principle from the formation of gall-nuts and other morbid out-growths from ' irritated ' vegetable structures. Here are no flowing, changing nutritive materials, no nerves, no vessels that can be justly compared with bloodvessels ; yet local and generally long-continuing injury is followed by a defective maintenance of the injured structures, and an excessive production of less perfectly organised new ones, in as near an imitation of inflamma- tion as seems possible in materials and conditions so unlike as the vegetable and the warm-blooded animal structures. On the whole, therefore, I think we may conclude that inflammation may have its origin in disturbance of the normal condition of the pro- per tissues of a part ; in such a disturbance as may be pi'oduced by in- jury, or by the proximity of disease. To this source, indeed, I should be disposed to refer nearly all inflammations that originate in the direct application of local stimuli, whether mechanical or chemical. It is true that, in most cases, the stimulus afi'ects at once the proper ele- ments of the part, its nerves, and its bloodvessels, so that we cannot say how much of the disease is to be ascribed to the affection of each ; but the fact that a process resembling, so far as it goes, that of inflam- mation, may ensue after injury in parts that have neither vessels nor nerves, may make one believe that, in parts that have both, the in- flammation depends mainly on injury or other affection of the proper tissue. I have thus endeavoured to show that inflammation may take its rise, may have its proximate cause, in a disturbance of any one of the conditions of nutrition. In the examination of different cases, we find that, even while any three of the four chief conditions may be nor- mal, a qualitative error of the fourth may bring in the phenomena of the inflammatory process. In the necessity of choosing pointed cases, I may seem to have imphed that it is usual for inflammation not only to begin, but to be maintained, by an error in one of the conditions of nutrition : but this is improbable. It is true that inflammation may have its beginning in any one of these conditions. Indeed there is not one of them that has not been made the cause of inflammation by some one who has looked at the subject from too narrow a point of view,— as in an alteration of the blood in rheumatism, in an alteration of the nervous force in irritation of the retina, in an alteration of the proper 336 SIGNS, NATUEE, AND CAUSES OF INFLAMilATION : elements of the tissue in inflammation of the cornea ; but probably it is never fully established -without involving in error all the conditions of Uutrition: and both the manner in which they may be thus all involved and their subsequent changes, should be studied as concurrent events, rather than as a series of events, of which each stands in the relation of a consequence to one or more of those that preceded it. Nowhere more than here is the mischief evident, of trying to discern in the economy of organic beings a single chain or series of events, among which each may appear as the consequence of its immediate predecessor : most fallacious is the supposition that, starting from a turgescence and stagnation of blood in the vessels of a part, we may explain the pain, the swelling, the heat, and all the other early and consecutive pheno- mena of inflammation. The only secure mode of apprehending the truth in this, as in every other part of the economy of living beings, is by studying what we can observe as concurrent, yet often independent, phenomena, or as events that follow in a constant, but not necessarily a consequent, order. The following are references to some of the recent essays on inflammation, from "which the reader, if he have learned the main principles concerning the disease from some of the classical works upon it, — such as those of Hunter, Thomson, Alison, or G-endrin, — may gather the best facts and guidance for future inquiry : — W. Addison : Experimental Besearches on Inflammation and on Tubercle. 1842, 1843, 1843. John Goodsir: Monthly Medical Journal, 1842; Anatomical and Fathological Observations, 1845, and Anatomical Memoirs. Edinburgh, 1868. 0. J. B. Williams : Principles of Medicine, 8vo. 1843 and 1848. Travers: Fkytiology of Inflammation and the Healing Process, 8vo. 1844. Carpenter: In an article in the British and Foreign Medical Eeview, xviii. p. 91. July 1844. J. Hughes Bennett ; On Inflammation as an Anormal Process, of Nutrition. Edinburgh, 1844. — Lectures on Clinical Medicine, 3d ed. 1859. Kiiss : Be la Vasculariie et de V Inflammation. Strasbourg, 1846. Keinhardt : Ueber die Genesis der mihrosk. Elemente in den Entzilndungsproducten ; in Traube's Beitrdge, H. ii. 1846. Bruecke (as quoted by Lebert): Bemerhmgen iiber Entziindiing ; in the Sifzungsberichte d'^r Wiener Akademie. June and July 1849. Andrew Clark : In the Medical Gazette, xlii. p. 286 ; and in subsequent numbers. Gluge : Pathologische Histologic, 4to. Jena, 1850. Henle: EationeUe Pathologic, B. i. And in his Zeitschrift, especially the 2nd volume. G. M. Humphrey : Lectures on Surgery ; in the Provincial Medical and Surgical Journal, 1849, and following years. SIGNS, NATUBE, AND CAUSES OF INFLAMMATION. 337 Lebert : Physiohgie Pathologique. Eedfern : Anormal Nutrition, in Articular Cartilages. Edinburgh, 1850. And, especially, in an Appendix to a Paper in the Monthly Journal of Medical Science, Sept. 1851. Eokitansky : Pathologische Anatomic, B. i. Simon: Lectures on General Pathology. In the Lancet, 1850; and collected, 8vo. London, 1850. Article 'Inflammation' in Holmes's System of Suraery. 1860. Wharton Jones ; On the State of the Blood and the Bloodvessels in Inflammation ; in Guy's Hospital Beforts, Tii. 1861. Virchow : Essays in the Ist and 3rd, and especially in the 4th and 14th volumes of his Archiv fur 'pathologische Anatomic. And in the 1st volume of the Verhandlungen der phys.-med. Gesellschaft in Wilrzbvrg. Celhdar Pathologie, 1858. H. Weber : Experimente uber die Stase in der Froschschwimmhaut, in MuUer's Archiv, H. iv. 1852. Lister : On the Early Stages of Inflammation. — Philos. Trans, part 2, 1858. 'Billroth : Beitrdge zur Path. Histologic. 1858. Berlin. C. 0. Weber: Die Entwickelung des Eiters. VirchoVs Archiv. 1859. Die Gewelserkrankungen im Allgemeinen in Billroth u. von Pitha's Handbuch der Chirurgie. B. i. Ab. i. A Moers : Be lentis injiammatione jturidenta. Bonn. 1864. S. Samuel: Lie Blutcirculation in der acuten Entzimdmig. Virchow's Archiv, :^\. p. 213. J. Cohnheim : JJeber EntzUndvng und Eitcnmg. Virchow's Archiv, xl. 1867. And the other writers referred to on p. 233. Lionel Beale: How to work with the Microscope. 4th ed. 315. The process of inflammation, so far as it can be illustrated by specimens, may be fully studied in the Museum of the College, in the preparations Nos. 71 to 129, and in those which are referred to after the descriptions of these in the first volume of the Pathological Catalogue. Many of the facts relating to the state of the bloodvessels, also, are illustrated by the microscopic specimens in the same Museum. All the best illustrations of the process, in the Museum of St. Bartholomew's, may be studied by the references in the Catalogue, vol. i. p. xii. 338 MOKTIFICATIOJf. LECTURE XIX. MOETIFICATION. By Mortification, or Sphacelus, is meant tlie death of any portion of the body, -while the rest remains living. The term ' gangrene ' is commonly used in the same sense; ' necrosis ' for similar death of portions of bone or cartilage, or, by some recent writers, of any other tissae; 'necrffimia' for a corresponding death of the blood. The dead piece of tissue is called a ' slough,' or, if it be a bone, a ' sequestrum.' The process of progressive dying is commonly called ' sloughing,' a term which is, however, also applied to the process by which a slough is separated, with the same meaning as ' exfoliation ' is used for the process of sepa- rating a ' sequestrum ' or dead piece of bone. None of these terms however, are used unless the portions of dead tissue be visible to the naked eye. It is probable that what is ejected from the tissues in the ulcerative process is quite dead ; but so long as it is in the form of minute particles, visible only with the microscope, we speak of the disease as ulceration, not sloughing or mortification. The two processes are, however, often mingled, and can be only in general terms, and in well-marked examples, distinguished. It might, also, be difficult to define, in precise terms, this death of parts from some examples of their degeneration. We may doubt, some- times, whether the degenerative changes, imitated, as certain of them are, by chemical changes in the tissues after death, are not consequences of the total cessation of the influence of vital forces ; and it seems nearly certain that degeneration of a part may proceed to its death, and is very apt to do so when, during its progress, many of the conditions of nutrition are at once interfered with. In a general view we may distingnish the degeneration of a part from its death by this, — that the degenerate part never becomes putrid, and that no process ensues for its separation or isolation, such as we can see in the case of a dead part. However degenerate a tissue may be, it either remains in con- SUSPENDED ANIMATION. 339 tinuity with those around it, or is absorbed. Tf tho same tissue were dead, those around it would separate from it, and it would be ejected from them. Still, it may not be pretended that degeneration and death are sepa- rated by a strong border-line. Rather, many of the instances of mor- tification to which I am about to refer may be read as histories of the transitions from one of these conditions to the other. It will appear that a part may degenerate even to death while the rest of the body remiains alive ; that, as a certain diminution of the supply of arterial blood may lead to degeneration, so a greater diminution may lead to death ; that, as a certain amount of inflammation has always in it a de- fective nutrition of the inflamed part, so, in a greater amount, the death of the same part ensues ; and that the same agent may kill one portion of a tissue and inflame the portions around it. Of all such cases we might say that the local death is the extreme of degeneration. Sometimes, indeed, irrespective of evident degeneration, we see con- ditions of parts in which it is hardly possible to say whether they are living or dead, and to which the term ' suspended animation ' may be fairly applied, with the same meaning as we have when we speak of it in reference to the whole body. In a drowned man we may find no signs of life ; he is in a state of ' suspended animation ; ' if he re- covers, we say he was alive during the period of suspense ; if he does not, we do not know the exact time at which he ceased to live ; for; as between degeneracy and death, so, in larger terms, between life and death, whether of the whole body or of any of its parts, there is no strong border line. In any part, as in the whole, we may speak of suspended animation, and if the term be vague, it is not therefore unfit ; for certainly our ideas of the things are vague. I have seen the end of a finger, in a man with diseased heart, cold, livid, insensible, and shrunken, for three days. Was it alive or dead ? I have seen an old man's foot, cold, livid, purple, mottled, and numb, for a week. Was it alive or dead ? Time showed that both parts were in a state of sus- pended animation, for both regained all the signs of life. In Hke manner, and more often, we may speak of suspended animation in parts that are frozen," or crushed, or in some other way severely injured. ' The mode of producing local anesthesia introduced by Dr. Eichardson illustrates, in a familiar manner, that a part may be frozen without ts vitality being destroyed The effects produced by the congelation of animals have been particularly studied by Pouchet, Journal (fe VAnatomie, Jan. 1866, and by the late Dr. John Davy, Proc. Soy. Soc. London, 1866. ■^ 2 340 MOETLFICATION : A convenient metliod of studying the causes of mortification may be to divide those among them that are explicable into the direct and the indirect — i.e., into such as disorganise and kill the tissues at once, and directly, though sometimes slowly, and such as do so indirectly, by depriving them of some or all of the conditions of their nutrition. Such a division, however, must not lead us to forget that, in many cases, mortification is the result of many concurring causes of both kinds. I. In the first class we may reckon the m.ortifications that are the extremes of degeneration. But these can rarely be observed in un- mixed examples. The more evident instances are those which result from great heat, rapidly decomposing chemical agents, and severe me- chanical injury. The appearances of the dead tissues are, in these cases, modified by the presence of blood in those that are vascular, and by the blood being killed in and with them : but the state of the blood is no cause of their death ; the tissues and the contained blood are killed together ; and the same mode and consequences of mortifica- tion would be manifested in the non- vascular tissues. Now, as I just suggested, it may be observed of all these destruc- tive agents, that when they are appUed in smaller measure, the effect of the injury is not to kill the part at once, but to excite an inflammation in it ; and the inflammatory degeneration, thus added to the damage the part sustained from the direct efiect of the injury, may lead to an indirect or secondary mortification. To this mixed origin, probably, many of the cases of traumatic gangrene may be ascribed, which are not manifest very speedily after the injury ; in these we may say that a severe injury has so nearly disorganised a part, that the subsequent inflammation, with the concurrent defective nutrition, has completed its death. But mechanical violence, heat, or chemical action, may kill a tissue at once, without the intervention of inflammation, and al- though, in the case of the vascular tissues, it is scarcely possible to separate the influence of the injury on their proper elements, from that which is, at the same time, inflicted on their blood and vessels, yet we must consider the phenomena of mortification as having their seat, es- sentially, in the elements of the tissues. Whatever we understand as the life of a part, that life may cease ; and as the life of a part is its own property, maintained, indeed, by the blood and other conditions of nutrition, yet not derived from them, so may that life cease, or, as it is said, be destroyed, without interference of the blood or any other exterior conditions of nutrition. The immediateness of such death of a part is shown by the ra- CAUSES OF MORTIFICATION. 341 pidity with wBioh it is manifested. It is nearly instantaneous on the apphcation of extreme heat or the strongest mechanical agents ; slower after mechanical injury : but within twelve hours of the infliction of a blow the struck or crushed part may be evidently dead ; there may be little or no ecchymosis, no sign of inflammation, no pain, ex- cept that which directly followed the injury, and, in the case of a bone, no apparent change of texture ; but the piece of tissue is killed in the midst of the hving parts ; its recovery, by the re-estabhshment of its relations with the blood, is not possible : it cannot even be absorbed. II. Among the instances of indirect mortification of parts, the most numerous are those in which nutrition is made impossible by some defect either (1) in the quantity, or (2), in the movement, of the blood. Defects in the quantity of blood have been already noticed as lead- ing to death of parts (p. 24). The following are the chief general methods of the events : — The main artery of a part may be closed by pressure, or by some internal obstruction. Thus, sometimes, sloughing of the foot, or leg, follows ligature of the femoral artery for popliteal aneurism ; or sloughing of part of the brain may follow ligature of the common carotid artery ; and in this case the difierence, and yet the close rela- tion, between the death of a part and its degeneration, are well shown (compare pp. 24 and 109). Thus, also, through equal internal obstruc- tion of main arteries, sloughing may follow blows which crack the internal and middle coats, and let them fold inwards across the stream of blood : ' or, the blocking of masses of fibrine, washed from the left valves of the heart, and arrested in the iliac or some other artery : ^ or the closure of inflamed arteries. Portions of tissue may similarly perish when, by injury, or by pro- gressive ulceration or absorption, all their minute bloodvessels are destroyed, and their supply of blood cut off. Thus necrosis may follow the separation of periosteum from the surface of a bone ; when it is either violently stripped off, or raised by effused blood, or by suppura- tion beneath it. Thus, also, sometimes, as an abscess approaches the surface, the thinned skin dies ; and, not like a-n inflamed part, but as one deprived of nutriment, it shrivels and is dried. Such sloughing is more common in perforating ulcers of the stomach or intestines ; in the ' Two such epecimens are in the Museum of St. Bartholomew's (Series 13: 119. 120). 2 See Dr. Kirkes's essay in Mcd.-CMr. Trans, xxxv. 342 MOETIFICATION : course of wtiGh., when tilceratioii lias destroyed a porfcion of the subperi- toneal tissue and its bloodvessels, the peritoneum, hitherto fed by them, perishes, and is separated as a greyish or yellowish-white slough. In like manner, ulceration, in its progress, may so undermine or intrench a part, that at length it dies through defect of blood ; thus, often, small fragments of bone are detached in strumous disease of the tarsus and other parts. And, similarly, through mere defect of the blood, the centre of a tumour may slough; and here, again, is manifest the relation between the death, and the more frequent degeneration, of an imper- fectly nourished part. The effect of pressure constantly maintained on a part may be a similarly produced mortification : the part may die because its blood is pressed from it and not renewed; but more commonly, as we see in bed-sores, inflammation ensues, and the death of the part has a double or mixed origin. Senile gangrene, also, is without doubt, in many cases, due, in a' measure, to defective quantity of blood ; but it is a more complicated example of mortification than any of the foregoing, and I shall therefore again refer to it. I have said that parts may die through defective movement of blood. It may be present in sufficient or excessive quantity ; but it may be fatally stagnant. So far as the proper elements of the tissue are con- cerned, there may be little difierence in their modes of death, or in their subsequent changes, in these two sets of cases; but, as seen in the mass, the tissue dead through defect of blood is very different from that dead through stagnation of blood. In the former, we find little more than its own structures dried and shrunken or disorganised ; in the latter, the materials of abundant blood, and often of substances exuded from the congested vessels, he mingled with the proper structures, having died with them. Hence, mainly, the differences between the mortifi- cations distinguished as the dry and moist gangrenes ; or as the cold and hot, the white and the black, gangrenes ; these being, respectively, the technical terms for parts dead through defect, or through stagna- tion, of blood. This stagnation of blood may ensue in many ways. The simplest is when a part is strangulated : as the contents of a hernial sac may be. J£ the strangulation is sudden and complete, the stagnation is equally so, and the death of the part follows very quickly, with little excess of blood in it. But, if the strangulation be less in degree, or be more slowly completed, the veins suffer more in the gradual compres- CAUSES or MOETIFICATION. 343 sion than the arteries do : the vessels of the part thus become gorged with blood, admitted into them in larger quantity than it can leave them, and so mortification ensues after intense congestion or inflammation of all the tissues.' Mere passive congestion of the vessels of a part may, in enfeebled persons, lead to mortification : but this is a rare event, for unless a part be injured, or of itself already degenerate, it may be maintained by a very slow movement of the blood. The congestion which more commonly leads to mortification is that -sihich forms part of the inflammatory process. It is, perhaps, to be regretted that the cases of this class should have been taken as if they were the simplest types of the process of mortification, and that the process should have been studied as an appendage, a so-called ter- mination, of inflammation : for, in truth, the death of an inflamed part is a very complex matter ; and in certain examples of it, all the more simple causes of mortification may be involved. Thus — (1) the in- flammatory congestion may end in stagnation of the blood, and this, as an indirect cause of mortification, may lead to the death of the blood, and that of the tissues that need moving blood for their support. But — (2) a degeneration of the proper textures is a constant part of the inflammatory process ; and this degeneration may itself proceed to death, while it is concurrent with defects in the conditions of nutrition. And — (3) the exudation of fluid in some inflamed parts may so com- press, and by the swelling so elongate, the bloodvessels, as to diminish materially the influx of fresh blood, even when little of that already in the part is stagnant. All these, and perhaps other, conditions may concur in the mortifl- cation of an inflamed part; and their united force is commonly the more effective, by being exercised in a previously defective or degene- rate condition of the inflamed tissue. The second of them, I think, has been too little considered ; for by it, more than by any other event, we may understand the sloughing that ensues in the inflamed parts of enfeebled persons. The intensity of an inflammation is not, alone, a measure of the probability of mortification ensuing in its course ; nei- ther is mere debility ; for we daily see inflammation without death of parts in the feeblest patients with phthisis and other diseases : rather, when mortification happens in an inflamed part,, it seems to be through the occurrence of the disease in those that have degenerate tissues be- ' Tiis difference in the effects of constrictions of parts is particularly described by- Sir B. C. Brodie : Lectures on Surgery and Pathology , p. 304. 3-i4 MORTIFICATION : cause of old age, or defective food or ottier materials for life, or throngli habitual intemperance. It is as if the deatli of the part were the con- sequence of the defective nutrition, which concurs with the rest of the inflammatory process, being superadded to that previously existing in the part. To the same occurrence we may, in some measure, ascribe the mortification of parts after comparatively slight injuries in the aged and intemperate : already degenerate, they perish through the addition of what, in healthier persons, would have led to only some degeneration, or to the inflammatory process, in the injured part. Such oases as these, also, stand in no distant relation to those of the mortification that ensues in inflammation after injuries. And with these we may pro- bably class the similar effects of intense cold. Cold alone does not, in general, directly kill a part, whether in cold or in warm-blooded ani- mals : the death that ensues appears to be the result of inflammation in the part that was cold or frozen. Such may be the explanations of the local death that may occur in inflammation ; but, in many more cases of what appear as mortifications in inflamed parts, the death is the first event in the process, and the inflammation appears as its consequence ; or else the death and the inflammation are coincident in different parts of the same tissue. To these cases I shall again refer. In senile gangrene we commonly find a very large number of con- ditions ministering to the death of the afTected part. First, occurring, as its name implies, in the old, and often in those that are old in struc- ture rather than in years, it affects tissues already degenerate, and at the very extremity and most feebly-nourished part of the body. I thiuli that, in some oases, its beginning may be when the progressive degeneration of the part has arrived at death. But, if this do not happen, some injury or disease, even a very trivial one, kills that which was already nearly dead ; as a severe injury might kill any part, how- ever actively alive. Now, when death has thus commenced, it may in the same manner extend more widely and deeply, with little or no sign of attendant disease ; the parts may successively die, blacken , and become dry and shrivelled ; in this case the senile gangrene is a dry one. But more commonly, when a portion of a toe or of the foot has thus died, the parts around or within it become inflamed, and in these, degenerate as they were already, the further degeneration of the inflammatory process is destructive ; and thus, or in this extent, by progressive in- flammation and death, the gangrene, moist though senile, spreads. In either case the extention of the gangrene is favoured by many other CAUSES OF MORTIFICATION. 345 things ; especially by tlie defective muscular and elastic power, and by the narrowing or obstruction, of the degenerate arteries of the part ; by the defective movement of the blood, readily inducing a passive con- gestion or stagnation in parts of its course ; by an enfeebled heart ; by the blood being, like the tissues, old, and doubtless, like them, defec- tive ; and by the aptness of the slow-moving blood to coagulate in the vessels. All these favour the occurrence and extension of the senile gangrene : one or more of them may, sometimes, be the eflB.cient cause of it : but my impression is, that it is essentially, and in the first in- stance, due, either to senile degeneration having reached its end in local death, or to the fatal superaddition of an inflammatory degeneration in a part already scarcely living. III. In the foregoing cases, we seem able, in some measure, to ex- plain the occurrence of mortification. But there are yet many cases in which explanation, except in the most general and vague terms, is far more difl&cult. In some, the local death is to be ascribed to defec- tive quality of the blood, or to morbid materials in it. The very rapid decomposition of the body after death in advanced cases of uraemia, and in some cases of septicsemia or putrid infection following injuries, may suggest how barely the blood was adequate to the maintenance of the composition of the tissues during life. And its inadequacy seems illustrated by the mortification that sometimes follows puncture of anasarcous limbs in cases of disease of the kidney. To the instances of sloughing of the cornea observed in animals, and more rarely in men, whose food is deficient in nitrogen ; and those of mortifications of the extremities that have ensued after eating rye with ergot, may prove the general principle, — that certain parts, even small and circumscribed parts, may die through defects or errors of the blood which yet do not quite hinder its maintaining the rest of the body. They may, thus, be types of a large class of cases, in all of which the death of a portion of tissue seems to ensue through some wrong in the blood by which their mutual influence is destroyed ; of which cases, therefore, we may say that as there are morbid conditions of the whole blood in which local inflammations may have their origin, so are there others in which local deaths have theirs. Boils and carbuncles seem to be examples of this kind of mortifica- tion, especially when they are connected, as necrosis also sometimes is, with diabetes. The sloughs, so often separated from them, are pale and bloodless ; they are not portions of tissue that have died in conse- quence of stagnation of blood in them : they are white sloughs in the 346 MOETIFICATION : midnt of inflamed parts. In boils, the first event of the disease may appear in the small central slongh ; in such cases the surrounding in- flammation may appear to be the consequence of the slough ; but, much more probably, it is the result of a lesser influence of the same morbid condition of the blood. In the idiopathic sloughing of the subcutaneous tissue of the scrotum, the local death is evidently, in some cases, the first event of the disease. To this class, also, of mortifications in con- sequence of morbid conditions of the blood, we must refer, I presume, the cases of hospital gangrene ; those of the most severe and most rapidly extending traumatic kind ; those of the sloughings of mucous membranes and other parts, that sometimes ensue in typhus, scarlet fever, and other allied diseases, when they deviate from their ordinary course ; the sloughing of syphilitic sores, and many others. Lastly, we may enumerate among the causes of death of parts the defect of nervous force : but the examples of this have been related in a former lecture (p. 33) ; ' and it only needs, perhaps, to be said here that this defect may mingle its influence with many other more obvious causes of mortification. When a part is severely injured, its nerves sufier proportionate violence, and their defective and disordered force may add to the danger of mortification ; in the old, not the blood, or the tissues alone, are degenerate, but the nervous structures also ; and defective nervous force may be, in them, counted among the many con- ditions favourable to the senile gangrene ; and so, yet more evidently, the sloughing of compressed parts is rapid and severe when those parts are deprived of nervous force by injury of the spinal cord, especially if the injured cord inflames. While the causes of mortification are so manifold, while it is, in fact, the end of so many different affections, it is not strange that the characters or appearances of the dying and dead parts should be ex- tremely various. The changes in them (independent of those produced by great heat, caustics, or other such disorganising agents) may be referred to three chief sources : namely, (I) those that ensue in the dying and dead tissue ; (2) those in the blood, dying with the tissues and often accumulated in them in unnatural abundance ; (3) those ' There are yet many cases which I can neither explain nor classify ; such as those from the effects of animal poisons, malignant pnstule, peculiar gangrenes of the skin, and many others. On all these, and, indeed, on the whole subject of mortifications, the reader will find no work that he am study with so much profit as the lectures of Sir E. C Brodie. CHARACTERS OF MORTIFICATION. 347 which are due to the inflammation or other disease or injury, which has preceded the death of the part, and of which the products die with the tissue and the blood, and change with them after death. But, though we may thus classify the morbid changes in mortified parts, yet we can hardly enumerate the varieties which, in each class, are due to the previous diseases of the part, or to external conditions ; such as differences of temperature, of moisture, and others. All the chemical changes which, in life, are repaired and unobserved, are here cum.ulative ; all those external forces are now submitted to, which, while the parts "were living, they seemed to disregard ; so exactly were they adjusted in counter- action. It is, therefore, only in typical examples that mortifications can be well described. The technical terms applied to them have been already mentioned ; and ' dry ' and ' moist ' signify the chief differences dependent on the quantity of blood and of inflam- matory products in the dead parts. 'Dry gangrene' is usually preceded by diminished supply of blood to the part ; ' moist or humid gangrene ' by increased supply, and often by inflammation ; the former more slowly progressive is usually a ' chronic,' or, as some have called it, ' cold gan- grene ; ' the latter an ' acute or hot gangrene.' Among the examples of mortification due to defective supply of blood, and therefore classed as dry gangrenes, great differences of appearance are due to the degrees in which the dead parts can be dried. As it may be observed in the integuments of the leg, for example, it may be noticed that, in the fiirst instance, the part about to die appears livid, or mottled with various dusky shades of purple, brown, or indigo, through which it seems to pass as its colours change from the dull rud- diness of stagnant or tardy blood towards the blackness of complete death. It becomes colder, and gradually insensible ; its cuticle sepa- rates, and is raised in blisters by a serous, or more or less blood-coloured, or brownish fluid. Then, as the cuticle breaks and is removed, the subjacent integument, hitherto kept moist, being now exposed to the air gradually becomes drier ; withering, mummifying, becoming dark brown and black, having a mouldy rather than a putrid smell ; it is changed, as Kokitansky says,^ like organic substances decomposed with insufacient moisture and with separation of free carbon. Such are the changes often seen in the dry senile gangrene, and in that which may follow obstruction of the main arteries in young persons : but, very generally, as the interior parts of the limb cannot be dried so quickly as ' Fathologische Anatomie, i. p. 237. 348 MORTIFICATION : the exterior, and are, perhaps, less completely deprived of their supply of blood, they, or portions of them, become soft and pntrid, while the integuments become dry and musty. In other cases of mortification similarly caused, the dead parts, though deprived of blood, cannot become dry ; either they are not ex- posed to air, or they are soaked with fluid exuded near them. In these instances the sloughs maybe dark ; but they are commonly nearly white ; and hence one of the grounds for the technical distinction of white and black gangrene. Such white sloughs are commonly seen when the peritoneum mortifies, after being deprived of blood by ulcera- tion gradually deepening in the walls of the digestive canal ; and, sometimes, in the integuments over an abscess, when the cuticle has not previously separated. If this have happened, the dead and under- mined integument may become dry and horny ; but if the cuticle remain, it is commonly white, soft, and putrid. The typical examples of the moist gangrene are those which occur in inflamed parts, and chiefly in consequence of inflammation ; and to which, therefore, the names of ' acute ' and ' hot ' gangrene have been applied. "We must not reckon among these the cases in which the death of the part precedes, or has a common origin with, the inflamma- tion ; for in these, as in boils, carbuncles, and hospital gangrene, the slough is commonly bloodless, white or yellowish-, or greyish- white, and, if it were not immersed in fluid, would probably be dry and shrivelled. The mortification that occurs during inflammation, and as in part a consequence of it, finds the tissues full of blood, and often of lymph and serum, which all perish with them. If such a process be watched in an inflammation involving the in- teguments, or in senile gangrene rapidly progressive with inflammation, or, as in the most striking instance, in the traumatic gangrene follow- ing a severe injury of the limb, the parts that were swollen, full, red, and hot, and perhaps very tense and painful, become mottled with overspreading shades of dusky brown, green, blue, and black. These tints, in mortification after injuries, may, sometimes, seem at first like the effects of ecchymoses ; and often, after fractures of the leg, a further likeness between the two is produced by the rising of the cuticle in blisters filled with serous or blood-coloured fluids at the most injured parts. But the coincident or quickly following signs of mortification leave no doubt of what is happening. The discoloured parts become cold and insensible, and more and more dark, except at their borders, which are dusky red ; a thin, brownish, stinking fluid, issues from the CHAEACTERS OF MOHTIFICATION. 349 exposed integuments : gas is evolved from similar fluids decomposing in tlie deeper-seated tissues, and its bubbles crepitate as we press them ; the hmb retains its size or enlarges, but its tissues are no longer tense ; they soften as in inflammation, bnt both more rapidly and more thoroughly, for they become utterly rotten. At the borders of the dying and dead tissues, if the mortification be still extending, these changes are gradually lost ; the colours fade into the dusky red of the inflamed but still living parts ; and the tint of these parts may afford the earliest and best sign of the progress towards death, or the return to a more perfect hfe. Their becoming more dark and dull, with a browner red, is the sure precursor of their death ; their brightening and assuming a more florid hue, is as sure a sign that they are more actively alive. Doubtless the varieties of colour indicate, respectively, the stagnation and the movement of the blood in the parts which, thus situated, may, according to the progress of their inflammation, be added to the dead, or become the apparatus of repair.' The interior of apart thus mortified corressponds with the foregoing description. All the softer tissues are, like the integuments, rotten, soft, putrid, soaked with serum, and decomposed exuded fluid ; ash- coloured, green, or brown ; more rarely blue or black ; crackling with various gases extricated in decomposition. The tendons and articular cartilages in a mortified limb may seem but little changed ; at the most they may be softened, and deprived of lustre. The bones appear dry, bloodless, and often like such as have been macerated and bleached ; their periosteum is usually separated from them, or may be easily and cleanly stripped ofi'. But these harder and interior parts of a limb, either die more slowly, or more slowly manifest the signs of death, than do those around them ; for not only do they appear comparatively little changed, but often when all the dead soft parts are completely separated from the living, the bone remains continuous, and its medul- lary vessels bleed when it is sawn off. Usually, also, after complete spontaneous separation of the mortified part of a limb, the stump is conical ; the outer parts of it having died higher up than the parts in its axis. Another appearance of mortified parts, characteristic of a class, is > Among the products of decomposition on the surfaces of wounds, are Uttle filaments and flocculi of soft orange, or hrownish-yellow substance, often seen, but particularly described first by Zeis {Memoires de la Soc. de Biologie. Annie 1855). They are shreds of connective tissue (generally) mingled with fatty and molecular matter, which may be coloured, and with crystals of cholestearine. 350 MORTIFICATION : presented after they have been strangulated. I have mentioned the difference which in these oases depends on whether the strangulation have been suddenly complete, or have been gradually made perfect. In the former case the slough is very quickly formed, and may be ash- coloured, grey, or whitish, and apt to shrivel and become dry before its separation. In the latter case, as best exemplified in strangulated hernia, the bloodvessels become gradually more and more full, and the blood more dark, till the walls of the intestine, passing through the deepest tints of blood-colour and of crimson, become completely black. Commonly, by partial extravasation of blood, and by infiltration with inflammatory products, they become also thick, firm, and leathery — a condition which materially adds to the difSculty of re- ducing the hernia, but which is generally an evidence that the tissues are not dead ; for when they are dead, they become not only duller to the eye, but softer, more flaccid and yielding, and easily torn, like the rotten tissues of other mortified parts. The canal, which was before cylindrical, may now collapse ; and now, commonly, the odour of the intestinal contents penetrates its walls. I have spoken of the death of the blood as coinciding with that of the part in whose vessels it is enclosed. Very commonly, when this happens, coagulation of blood ensues in the vessels for some distance above, i.e. nearer to the heart than, the mortified parts. Hence, as it has been often observed, no bleeding may occur from even large arteries divided in amputations above the dead parts of sloughing limbs. It remains now to speak of the phenomena which ensue when gan- grene ceases, and of which the end is, that a separation of the dead parts from the living takes place. As for the dead parts, they only continue to decompose, while, if exposed to a dry atmosphere, they gradually shrivel, becoming dryer and darker. But more important changes ensue in the living parts that border them. The first change that occurs in this process (the whole of which may be studied as the most remarkable instance of the adapta- tion of disease for the recovery of health), the first indication of the coming reparative process, is a more decided limitation and contrast of colour at the border of the dying part. As we watch it in the integu- ments the dusky redness of the surrounding skin becomes more bright, and paler, as if mingled with pink rather than with brown ; and the contrEist reaches its height when, as the redness of the living part brightens, the dead whiteness or blackness of the slough becomes more SEPARATION OF MORTIFIED PARTS. 351 perfect. The touch may detect a corresponding contrast — the living part, tnrgid with moving blood, feels tense and warm ; the dead part is soft, or inelastic, cold, and often a little sunken below the level of the living. These contrasts mark out the limits of the two parts — they constitnte the ' line of demarcation ' between them. The separation of the dead and living parts, which remain con- tinuous for various periods after the mortification has ceased and the line of demarcation is formed, is accomplished by the ulceration of the portions of the living tissues which are immediately contiguous to the dead. At this border, and (in parts that are exposed), commencing at the surface, a groove is formed by ulceration, which circumscribes and intrenches the dead part, and then gradually deepening and converging, undermines it, till, reaching its centre, the separation is completed, and the slough falls or is dislodged by the discharge from the surface of the nlcerated living part. Commonly, before the border of the integu- ments ulcerates, it becomes white and very soft, so that, for a time, a dull white line appears to divide the dead and living parts. Closely following in the wake of this process of ulceration is one more definitely directed towards repair. As the ulcerated groove deepens day by day around and beneath the dead part, so do granula- tion-cells rise from its surface ; so that, as one might say, that which was yesterday ulcerating, is to-day granulating ; and thus, very soon after the slough is separated, the whole surface of the living part, from which it was detached, is covered with granulations, and proceeds, like an ordinary ulcer, towards healing. There is, I believe, nothing in the method of thus separating a dead part, thus ' casting off a slough,' which is not in conformity with the general process of ulceration. When a portion of the very interior sub- stance of an organ dies, and is separated, there may be doubt, as in some nearly corresponding cases of ulceration, whether the clearing away of the living tissue adjacent to it be effected by absorption, or by disintegration and mingling with the fluid in which, after separation, the dead piece lies. We may have this doubt in such oases as the sloughing of subcutaneous tissues in carbuncles not yet open, or in phlegmonous erysipelas, or in the cases of internal necrosis ; in which, without any external discharge, pieces of dead tissue are completely detached from the living tissue around them : and I do not know how such doubt can be solved. But the separation of superficial or exposed dead parts might be studied as the type of the ulcerative process, of which indeed, it is in disease the usual beginning, and with the more 3.'>2 MORTIFICATION : advantage, because tlie sloughing of parts of limbs affords illustrations of the process in tissues in which it very rarely happens otherwise. Especially it shows the times at which, in different tissues, ulceration may ensue, and hereby the times during which, under similar condi- tions of hindered niitrition, the tissues may severally maintain life. The process which I have exemplified by the mortification of soft parts has an exact and instructive parallel in necrosis or mortification of bone ; but there are in the phenomena of necrosis some things which deserve a brief mention, because of their clearly illustrating the general nature of the process following the death of a part. Thus (1) we find in bones a permanent evidence of the increase of vascularity of the tissues around a dead part ; for, in specimens of necrosis, the bone at the border of the dead piece has always very numer- ous and enlarged Haversian canals, in which, as well as in the enlarged lacunae, an abundant growth of cells, which fill their cavities, takes place. By the formation of pus from these cells, the dead bone is separated, or, as it were, floated off.^ (2) We may often see that the reparative process, on the borders of the living part, keeps pace with, or rather precedes by some short interval, the process by which the living and the dead are separated ; for new bone is always formed in and beneath the periosteum at the border of the living bone, while the groove around the dead piece is being deepened, or even before its for- mation has commenced. (3) Instances of necrosis show some of the progressive changes that lead to the formation of the groove of separa- tion. The bone at the very junction of the living and the dead be- comes, first, soft and ruddy, as an inflamed bone does. Its earthy matter, as Mr. Hunter described, is flrst (by absorption, as we must suppose) removed in a larger proportion than its animal basis. This basis remains, for a time, connecting the dead and the living bone, both of which retaining their natural hardness, appear in strong contrast with it : but soon this also is removed, and the separation is completed. (4) From some cases of necrosis, also, we obtain evidence on a ques- tion about the removal of dead tissue. It is asked whether dead tissue may not be absorbed, and so removed. Examples of necrosis show that, in the large majority of cases, the separation of dead bone is accomplished entirely by the ulceration or absorption of the living bone around it ; but that, in certain cases, especially in those in which ' J. Goodsir, Of. cit. ; E. Kuiss, Op. cii. ; Virchow, Cell. Fathologie. SEPARATION OF MORTIFIED PARTS. 353 pieces of bone, though dead, remain continuous or in tight contact^ with the living, the dead bone may be in part absorbed, or otherwise removed, not indeed in mass but after being disintegrated or dissolved. (5) In cases of necrosis we find the best examples in which the dead and living parts remain long united and continuous. A piece of dead bone, proved to be dead by its blackness, insensibility, and total absence of change, may remain even for months connected with living bone: and no process for its separation is established, till the patient's general health improves. (6) Lastly, in the death of bone, we may see a simpler process for the separation of the living tissues than that which is accomplished by ulceration. In superficial necrosis, the periosteum, at least in those parts in vrhich its own tissue does not penetrate so as to be continuous with that of the bone, separates cleanly from the sur- face of the dead bone, retaining its own integrity and smoothness, and leaving the bone equally entire and smooth. No observations have yet been made, I believe, vrhioh show how this retirement of one tissue from another is effected, or how the bloodvessels that pass from one to the other are disposed of. Another method of separation without the ulcerative process is observed when teeth die, especially in old persons. Their sockets enlarge, apparently by mere atrophy or absorption of their walls and margins ; so that the teeth-fangs are no longer tightly grasped by them, but become loose, and project further from the jaw. ' See Mr. Savory's paper in Medico- Chirurgical Transactions, xlyii. Also the account of a case by Dr. Cleland in British Med. Journal, February 22, 1868, in which a portion of a dead parietal bone was absorbed, without suppuration, apparently by the pressure of subjacent granulations. 354 SPECIFIC DISEASES: LECTURE XX. SPECIFIC DISEASES. It would be far beyond the design of these lectures, intended only for the illustration of the General Principles of Pathology, in its relations with Surgery, if I were to enter largely on the consideration of the diseases named specific. It will be sufficient, I hope, and certainly will more nearly correspond with the rest of my plan, if I describe the general features of specific diseases, and their general import ; and if I point out, though only in suggestions, how we may more effectually study them; how many things relating to them, which we are apt to dismiss with words, may be subjects of deeper, and perhaps nsefnl, thought. The term ' specific disease,' as employed in common usage and in its most general sense, means something distinct from common or simple disease. Thus, when a ' specific inflammation,' or a ' specific ulcer,' is spoken of, we understand that these present certain features, in which they differ from what the same person would call ' a common,' or a ' simple ' 'inflammation,' or 'ulcer.' The specific characters of any disease, whether syphilis or hydrophobia, gout or rheumatism, typhus, small-pox, or any other, are those in which it constantly deviates from the characters of a common or simple disease of the same general kind.' Our first enquiry therefore, must be, — what are these common diseases, which we seem to be agreed to take as the standard by which to measure the specific characters of others ? ' It may not be unnecessary to guard Bome students at once from the suspicion, which the terms in common use may suggest, that there is a correspondence between the species of diseases and those of living creatures as studied in natural history. There is really no likeness, correspondence, or true analogy between them ; and if nosological systems, framed after the pattern of those of zoology, lead to the belief that they have any other resemblance than that of the modes of briefly deacribiag, and of grouping double names, they had better be disused. COMMON DISEASES. 355 I believe that, in relation to inflammatory diseases and their conse- qaences, onr chief thoughts conceraing such standards for comparison are derived from the affections which follow injuries by violence, or by inorganic chemical agents, by heat, or any other frequently applied causes of disease. When such a blow is inflicted as kills a por- tion of the body, its consequences afford a standard with which we may compare all other instances of mortification and sloughing ; and ■when, among these, we find a certain number of examples which difier, in some constant characters, from this standard, wc place them, as it were, in a separate group, as examples of a specific disease. Or, again, when a part is submitted to such pressure as leads to its ulceration, we regard the disease as a common, simple, or standard ulcer ; and b}'- their several constant differences from it, and from one another, we judge of the various ulcers which we name specific. In like manner, our standard of common or simple inflammation seems to be derived from the processes which follow violence, the application of heat, the lodg- ment of foreign bodies, or the application of certain chemical stimulants. And the standard of common or simple fever is that which ensues in a previouslj^ healthy man, soon after he has received some such local injury as any of these agents might produce. Now, it is very reason- able that we should take these as the best examples of common or simple disease: the best, I mean, for comparison with those that may be called specific. For not only can we produce some of these common diseases when we will, and study them experimentally, but they mani- festly present disease in its least complicated form ; least specified by peculiarities either in its cause or in its subject. Only, in adjusting our standards of disease from them, it is necessary that we should take the characters presented by all or by the great majority of instances ; since the consequences of even the simplest mechanical injuries are apt to vary according to the peculiar constitution of the person injured. The terms simple and specific are sometimes applied in equal con- tradistinction, to tumours. Here we have no such standard of accidental or experimental disease ; but that which seems to be taken as the measure of simplicity in a tumour, is the conformity of its struc- ture with some of the natural parts of the body. The more a tumour is like a mere overgrowth of some natural structure, the more ' simple ' is it considered: and the specific characters of a tumour are chiefly those in which, whether in texture or in mode of life, it differs from the natural parts. When, however, a tumour is diseased, — for instance, when a cancer ulcerates,— the specific characters of the ulcer are 356 SPECIFIC DISEASES: estimated by comparison with tlie characters of common or sunple ulcers. Such are, in the most general terms, the standards of common or simple diseases. The title ' common ' applied to them is, in another sense, justified by the features which they present being, for the most part, common to them and to the specific diseases. For, in the specific diseases, we do not find morbid processes altogether difierent from those which are taken as standards, but only such processes as are conformed with them in all general and common features, but differ from them by some modification or addition. In other words no specific disease is entirely peculiar or specific ; each consists of a common morbid process, whether an infiammation, an ulceration, a gangrene, or any other, and of a specific modification or plan in some part thereof. Let us now see what these modifications, these specific characters, are ; and here, the history of tumours being for the present postponed, let me almost limit the inquiry to a comparison of the inflammatory affections of the two kinds, and select examples from only such as are, by the most general consent, called specific ; as syphilis, gout, rheuma- tism, the eruptive fevers, and the like. 1. Bach specific disease constantly observes a certain plan or con- struction in its morbid process ; each, as I just said, presents the phe- nomena of a common or simple disease, but either there is some addition to these, or else one or more of these is so modified as to constitute a specific character ; a peculiarity by which each specific disease is distinguished at once from all common and from all other specific, diseases. Thus, we see a patient, with, say, two or three annular or crescentic ulcers on his legs ; and, if we can watch these, they are, perhaps, healing at their concave borders at the same time as they are extending at their convex borders. Now, here are all the conditions that belong to common ulcers ; and, in difierent instances, we might find these ulcers liable to the variations of common ones, as being more or less inflamed or congested, acute or chronic, progressive or stationary; but we look beyond these characters, and see, in the shape and mode of extension of these ulcers, properties which are not observed in common ones ; we recognise these as specific characters ; we may call the ulcers specific ; or, because we know how commonly such ulcers occur in syphilis, and how rarely in any other disease, we call them syphilitic ulcers, and treat then\ with iodide of potassium or some other specific, that is, specially curative, medicine. Another patient has, say, numerous small. CHAEACTEE OF SPECIFIC DISEASES. 357 round, dusky, or light brownish-red, shghtly elevated, patches of in- flammation of the surface of his skin ; on many of them there are small, dry, white scales ; and some of them may he arranged in a ring. Herei again, are the common characters of inflammation ; but they are pecu- liarised in plan and tint of redness, and in general aspect ; and because of these we regard the disease as specific, and call it psoriasis, and, because of the additional peculiarity of dusky or coppery redness, and of the annular or some other figurative arrangement, we suspect that it is syphilitic psoriasis. Or, we look through a series of preparations of ulcerated intestines ; and we call one ulcer simple or catarrhal, another typhous, another dysenteric, a fourth tuberculous : all have the common characters of ulcers ; but these are, in each, peculiarly or specifically modified in some respect of plan ; and the modifications are so constant, that without hearing any history of the specimens, we may be sure of all the chief events of the disease by which each ulcer was preceded. Or, among a heap of diseased bones, we can select those whose pos- sessors were strumous, rheumatic, syphilitic, or cancerous ; finding in them specific modifications of the results of some common diseases, such as new bone, i.e. ossified inflammatory deposits, ari-anged in peculiar methods of construction, or at particular parts ; or ulcers of pecuhar shape and peculiar method of extension. I need not cite more examples of the thousand varieties in which the common phenomena of disease are modified in specific diseases. In some, the most evident specific characteristics are peculiar affections of the movement of the blood, as in the cutaneous erythemata ; in some, affections of certain parts of the nervous centres, as in tetanus, hydrophobia, and whooping-cough ; in some, peculiar exudations from the blood, as in goat and the inoculable diseases ; in some, peculiar structures, as in variola, vaccinia, and other cutaneous pustular erup- tions ; in some, destruction of tissues, as in the ulcers of syphilis, the sloughs of boils and carbuncles ; in some, peculiar growths, as in cancer ; in some, or indeed in nearly all, peculiar methods of febrile general dis- turbance ; but, in each of all the number, the phenomena admit of dis- tinction into those of common disease, and those in which such disease is peculiarly modified, or by which, if I may so say, it is specificated. The morbid process thus modified may be local or general. Usually, in specific diseases, both local and general morbid processes are con- current, and both are, in a measure, specific ; but, although we can scarcely doubt that there is in every case an exact and specific corres- pondence between the two, yet, at present, the general or constitutional 358 SPECIFIC DISEASES: affections of many different specific diseases appear so alike, that we derive our evidence of specific characters almost entirely from the local part of the disease. The premonitory general disturbances of the ex- anthemata, or the shghter disorders preceding cutaneous eruptions are, severally, so alike, that, except by collateral evidence, we could seldom do more than guess what they portend ; their specific modifications of common general disturbance are too slight for us to recognise them with our present knowledge and means of observation. 2. Observing the causes of specific diseases, we find that some, and these the most striking examples of the whole class, are due to the in- troduction of peculiar organic compounds, — morbid poisons, as they are generally called, — into the blood. Such are all the diseases that can be transmitted by inoculation, contagion, or infection. AU these are essentially specific diseases ; each of them is produced by a distinct substance, and each produces the same substance, and by a morbid process separates it from the blood. In most of these, also, as well as in many of which the causes are internal and less evident, the local phenomena are preceded by some affection of the whole economy • the whole blood seemis diseased, and nearly every funcbion and sensation is more or less disturbed from its health; the patient feels ' ill all over,' before the local disease appears ; i.e. before the more distinct and spe- cific morbid process is manifest in the place of inoculation, or in some other part. Herein is a very general ground of distinction between the specific and the simple or common diseases : in the latter, the local phenomena precede the general or constitutional; in the former, the order is reversed. We might, indeed, expect this to be a constant difference between the two ; and perhaps it is so ; for though many exceptions to any rule founded on it might be adduced, yet these may be ascribed to the unavoidable sources of fallacy in our observations. Thus, every severe injury, every long-continued irritation, excites at once both local and general disease ; and the latter may be evident before the former, and may not only modify it, but may seem to pro- duce it. On the other hand, the insertion of certain specific poisons, e.g. that of the venom of a serpent or of an insect, gives rise so rapidly to specific local disease, that this seems to precede all constitutional affection. Notwithstanding such exceptions as these are, or seem to be, this contrast between specific and common diseases, in regard to the order in which the local and constitutional symptoms arise, is so usual that the terms specific and constitutional are often employed as convertible CHARACTER OF SPECIFIC DISEASES. 359 terms in relation to disease. But this is not convenient ; for some specific diseases are, or become, local ; and some constitutional diseases are not specific. 3. A character very generally observed in specific diseases is an apparent want of proportion between the cause and the effect. In common disease, one might say that, on the whole, the quantity of local disease is in direct proportion to the cause exciting it — whether violent injury, heat, poison, or any other. Numerous exceptions might be found, but this is, on the whole, the rule.' In specific dis- eases there is no appearance of such a rule ; we cannot doubt its exis- tence, but it is lost sight of. Thus, in smallpox, measles, hydrophobia or syphilis, the severity of the disease is not, evidently, proportionate to the cause applied ; a minimnm of inoculated viius engenders as vast a disease as any larger quantity might. 4. I have said that there is generally a correspondence between the local and the constitutional characters of a specific disease : but this is only in respect of quality : in respect of quantity there is often such a want of correspondence between the two as we rarely or never see in common diseases. In general, the amount of common inflamma- toiy fever after an operation bears a direct proportion to the injury, and the amount of hectic fever to the quantity of local disease (here, again, are numerous exceptions, but this is the rule) ; but in specific diseases it is far otherwise. In syphilis and cancer, the severest de- fects or disturbances in the whole economy may co-exist with the smallest amounts of specific local disease ; and, as Dr. Robert Williams^ has well said, ' It may be laid down as a general law, that when a mor- bid poison acts with its greatest intensity, and produces its severest forms of disease, fewer traces of organic alteration of structure will be found than when the disorder has been of a milder character ; ' a rule which may find its most striking instance in pyaemia. 6. To specific diseases belong all that was said, in a former Lec- ture (pp. 13 et seq.), of the symmetrical diseases, and of seats of elec- tion : such phenomena occur in degenerations, but, I think, in no common diseases, 1 I am tempted to say here, that, in pathology, we must admit the existence of many rules or laws the seeming exceptions to which are more numerous than the plain examples of them. This, however, is not enough to invalidate the truth of the laws ■ it could scarcely bo otherwise in the case of laws, the exact observance of which requires the concurrence of so many conditions as are engaged in nearly all the phenomena studied in pathology. 2 Elements of Medicine, i. p. 12, i560 SPECIFIC DISEASES: 6. The local process of a specific disease of nutrition is less apt than, that of a common one to be nearly limited to the area in which, in the first instance, the cause of disease was applied. Specific diseases are peculiarly prone to spread — that is, to extend their area. They also, among the diseases of nutrition, are alone capable of being erratic, i.e. of disappearing from the part in which they were first manifest, while extending thence through other jDarts continous with it ; and they alone are capable of metastasis, i.e. of suddenly ceasing in one locality, and manifesting themselves, with similar local phenomena, in another. 7. In all the particulars mentioned in the last preceding, and in some of the earlier, paragraphs, specific diseases manifest a peculiar character, in that they seem capable of self-augmentation ; no evident fresh cause is applied, and yet the disefise increases : witness the seemingly spontaneous increase of manifest local disease in secondary and tertiary syphilis, or in the increasing eruption of eczema or of herpes, or the extension of a carbuncle, or the multiplication of secon- dary cancers. In some of these there may be, as there is in the com- mon cellulitis extending from a wound, whose decomposing discharges spread and infect by infiltration, a continuous extension by local in- fection or growth ; but in some of them this is impossible, and in others as in carbuncle, it may be usually observed that an increase of the con- stitutional disturbance precedes an increase of the local disease. 8. Specific diseases alone are capable of transformation or meta- morphosis. As we watch a common disease, its changes seem to be only those of degree ; it appears increasing or declining, but is always the same, and a continuous disease. But in many specific diseases we see changes in quality or kind, as well as in quantity. In syphilis, for example, a long series of diseases may occur as the successive conse- quences of one primary disease different from them all. They are all, in one sense, the same disease, as having a single origin ; but it is a disease susceptible of change in so far as it manifests itself at difierent times, not only in different parts, but in different forms in each, and in forms which are not wholly determined by the nature of the tissue affected. The successive phenomena of measles, scarlet fever, and many others, may, I think, be similarly expressed as metamorphoses or transformations of disease. 9. A similar transformation of specific diseases may take place in their transference from one person to another, whether by inheritance,' ' It might seem as if none but specific diseases eonld be hereditary ; but many tumours are so which we cannot well call specific : Buch as the cutaneous cysts or ■wens, and fatty and cartilaginous tumours. CHARACTER OF SPECIFIC DISEASES. 361 or by infection or contagion. A parent witli one form, of secondary syphilis may have a cliild with another form, the child of a parent with scirrhous cancer may have an epithelial, a colloid, or a medullary can- cer : the inoculation of several persons with the matter from one pri- mary syphilitic sore may produce somewhat different forms of the pri- mary disease and very different consecntive phenomena ; the same con- tagion of small-pox, measles, or scarlet fever, may produce in different subjects all the moditioations of which those diseases are severally cap- able ; the puerperal woman, or the patient who has sustained a severe accidental or surgical injury, may modify, or, as it were, colour with the peculiarities of her own condition, whatever epidemic or other zymotic diseases she may incur.' 10. Lastly, time is a peculiarly important condition in many of the specific diseases. If we except the period of calm or incubation, which usually occurs between the infliction of an injury and the beginning of an evident reparative process — a period of which the length is, in general, proportionate to the severity of the injury — there are few of the events of common diseases that are periodic or measurable in time ; there are none that are regularly intermittent or remittent ; none that can be compared, for regularity, with the set times of latency of the morbid poisons of the eruptive fevers, or the periods in which they run their course, or change their plan or chief place of action. Neither are there, in common diseases, any periods of latency so long as those which elapse between the application of the specific cause, and the ap- pearance of its specific effect, in the eruptive fevers, syphilis, tetanus, or hydrophobia. Such, briefly, are the chief general characters of the diseases which are commonly named specific, or described as having something specific in their action. In some of them, chiefly such as depend on distinct morbid poisons, whether miasma or virus, or matter of contagion, all these characters may be observed ; and these are the best types of the class. In others, part only of the same characters concur. I do not pretend to define the exact boundary of what should be called specific, and what common, in diseases ; but it seems reasonable that any dis- ease, in which the majority of the characters just enumerated are found, should be studied as one of the class, and that its phenomena should be interpreted, if possible, by the rules, or by the theory, de- rived from the more typical members of the same class. ^ See Carpenter ; Br. and For. Med.-Chir. Review, Jan. 1853, quoting from Simpson, in Monthly Journ. of Med. Sc. xi. and xiii. 362 SPECIFIC DISEASES: The theory of specific diseases, in its njost general terms, is, that each of them depends on a definite and specific miorbid condition of the blood ; that the local process in which each is manifested is due to the disorder produced by the morbid blood in the nutrition, of one or more tissues ; and that, generally, this disorder is attended with the accumu- lation, and leads to the discharge, or transformation, of some morbid constituents of the blood in the disordered part. It is held, also, that, in some specific diseases, the morbid condition of the blood consists in undue proportions of one or more of its normal constituents ; and that in others, some new morbid substance is added to or formed in the blood. In either case, the theory is, that the phenomena of each spe- cific disease depend chiefly, and in the first instance, on certain corres- ponding specific materials in the blood : and that if characteristic morbid structures be formed in the local process, they are organs in which these morbid materials are incorporated. Now in regard to certain diseases, such as some of those that can be communicated by inoculation, these terms are scarcely theoretical ; they may rather be taken as the simplest expressions of facts. For example (as I have already said, p. 328), in either syphilis, vaccinia, glanders, or small-pox, especially when produced by inoculation, we have demonstration (1.) of a morbid condition of the blood ; (2.) of the definite and specific nature of that condition, in that it is, and may be at wiU, produced by the introduction of a definite substance into the blood, and manifests itself in a local disease which, within certain limits, has constant characters ; and (8.) of the same substance being accumulated and discharged, or for a time incorporated in the morbid structures, at the seat of the local disease. And it seems important to mark, that all which is thus seen in some specific diseases, and is assumed for the explanation of others, is consistent with facts of phy- siology : especially with those referred to in a, former Lecture (pp. 18 et seq.), as evidences, that certain normLil organs of the body are formed in consequence of the presence of materials in the blood, which, in relation to them, might be called specific, and which they, in their formation, take from the blood, and incorporate in their own struc- tures.' ' Abundant illustrations of the same general laws, of both healthy and morbid formation of structures incorporating specific matorialb from the blood, are supplied by the action of medicines -whose operation ensues in only certain organs (Lectures ii. and iii.) Dr. Robert Williams {I. u. p. 8) has justly said, ' The general laws observ- able in the actions of morbid poisons are, for the most part, precisely similar to those which govern medicinal subiit.iDccs, or only differ in a few minor points.' The subject THEOBY OF SPECIFIC DISEASES. 363 The proof of the theory of specific diseases is scarcely less complete for all those thatareinfectioas or contagious, but cannot be communica- ted by inoculation s— such as typhus, measles, erysipelas ; and scarcely less for those Tvhich are neither infectious nor contagious, but depend, like cholera and. ague, on certain materials which are introduced into the blood, and produce uaiform results, though they are not proved to exist in the products of the morbid processes. For other diseases, classed or usually regarded as specific, such as gout, rheumatism, car- buncle, boil, the various definite, but not communicable, cutaneous eruptions, hydrophobia, tetanus, and many more, the evidences of the theory are less complete. Yet they seem not insufScient ; while we have, in many of these affections, proofs of the accumulation and separ- ation of morbid substances at the seats of local disease, and while, in all, the chief phenomena are in close conformity with those of the diseases which are typically specific. -Relying on the similarity of all the menabers of the group of specific diseases, on the sufl&ciency of the terms of the theory for the expression of the facts concerning them all, and on the evidences more or less complete which each of them supplies for its truth, we seem justified in adopting the same tlieory for them all.' But now, if we may hold this theory to be true for some specific diseases, and not unreasonable for the rest, let us see how, in its terms, we can explain or express the chief characters of these diseases ; such as their periodicity, metastases, and metamorphoses, the apparent in- crease of the specific substance in the blood, and the others just enume- rated. This may be done while tracing the probable history, or, as I would call it, the life, of the morbid material in the blood, and in the tissues.^ is too extensive for discussion here. It is admirably treated by Mr. Simon in his Lectures on Fathohgy ; the work, which, together with that of Dr. Eobert Williiims, may be .studied with more profit in relation to all the subjects of this lecture than any I have yet read. ■ Virchow regards every enduring change in the circulating juices as derived from fixed points of the body, from single organs or tissues, and looks for ' localisation for the different dyscrasi* ; ' that is, for definite tissues from out of which the blood derives its disturbance. It may be reasonably granted, that any diseased organ or tissue must, through the nutritive changes which take place between it and the blood, constantly act as a centre or focus, from which a disturbance affecting the entire mass of blood may arise ; and all the Instances in which this is proved are evidences in support of the theory of specific diseases which is here maintained. ^ Several of the characters of specific diseases are already explained, in the terms of this theory, in the earlier LecLures ; namely, their specificforms and construciions (w 18 23 46); symmetry and seats of election (pp. 13 rt seq.) ; extension and errantry (p. 15, note). 364 SPECIFIC DISEASES: Specific morbid materials, or at least their chief constituents, may enter the body from without, by inoculation, contagion, or infection : or they may be formed in the blood, or added to it -within the body ; in other words, some morbid materials are inserted, others are inbred, in the blood ; with some, probably, both modes of introduction are possible. Doubtless, an important difference is thus marked between two chief groups of the specific diseases ; but it is not within m.y present purpose to dwell on it ; for only one general history can as yet be written for the whole class of morbid materials on which the specific diseases depend : and although this may be best drawn from the instances of those that are derived from without, i.e. from such as are called morbid poisons, yet it would probably be as true, in all essential features, for those that are inbred. When a morbid poison is inoculated — for example, when the matter from a syphilitic sore, or from a vaccine vesicle, is inserted in the skin — it produces a specific eflFect both on the tissue at the place of insertion, and on the blood, as soon as it, or any part of it, is absorbed : in other words, it produces both a local and a constitutional change ; and in both these effects its history must be traced. I. First, respecting the local change : of which, with another design I have already spoken (p. 329). It is not proved by anything that can be seen immediately, or even within one or two days after the inoculation. The place of inoculation remains, for a time, apparently unaffected : and yet that a pecuhar change is being wrought in it is clear, for it pre- sently becomes the seat of specific disease, the materials of which disease are supplied by blood that nourishes healthily all other parts, even such parts as may have received common injuries at or near the time of the inoculation. The inoculated part, therefore, is not merely, injured, but is peculiarly altered in its relation to the blood, which now nourishes it differently from all the rest of the body. The change of the blood is proved, if not by general febrile or other disturbance, yet by the specific character of the presently ensuing disease, and by the consecutive secondary disease, or by consecutive immunity from later disease of the same kind. If further proof be needed of the specific local change produced in the inoculated part, it may be furnished by the analogy of the more visible eflPects of certain animal poisons, — such as those of venomous serpents and insects. None of these appear to be simple irritants ; the the consequences of their insertion are not like simple inflammations, but are peculiar, and constant in their peculiarities. The bite of a bug MOEEID MATERIALS IN BLOOD AND TISSUES. 365 or a flea will not, I hope, be thought too trivial for an illustration, and its specific characters may be compared with the common consequences of a prick of a needle made at the same time. In less than a minute after the bite, the bitten part begins to itch ; and quickly after this, a wheal or circumscribed pale swelling, with a nearly level surface, and a defined border, gradually rises and extends in the skin. It seems to be produced by an oedema of a small portion of the cutis at and around the bite ; it is not a simple inflammatory swelling ; it is, from the first, paler than the surrounding skin, which may be healthy or slightly reddened by afflux of blood : and the con- trast between them becomes more striking, as the surrounding skin becomes gradually redder, as if with a more augmented fulness of the bloodvessels. Thus, for some minutes, the wheal appears raised on a more general, and less defined, vascular swelling of the surrounding and subjacent tissues ; but, after these minutes, and as the itching sub- sides, the wheal, or paler swelling, becomes less defined, and the more general swelling appears gradually to encroach on it and involve it. Then all suhsides : but only for a time ; for in about twenty-four hours a papule, or some form of secondary inflammation, appears, with renewed itching, at the seat of the puncture, and this after one, two, or sometimes more days, gradually subsides.^ And all this time the needle-puncture has been healing unobserved, because unobservable. Now, the first pale and circumscribed swelling at any of these bites may serve to illustrate the immediate eiFects of a morbid poison on the tissues at and around the seat of inoculation. In the area of such a swelling the tissues are, by the direct contact or influence of the venom, altered in their nutritive relation to the blood. So I believe, immedi- ately after the insertion of syphilitic, vaccine, or other virus, there ensues a corresponding specific alteration of those parts of the sur- rounding tissues which afterwards become seats of the specific local disease.' ' Some persons are so happily constituted, that they do not thus, or with any other discomfort, suflfer the consequences of insect-bites ; but I think the description I have given will be found generally true for cases in which the bitten part is left undisturbed ; the fortunate exempt may illustrate the rarer exceptions from the usual influence of the severer morbid poisons. « The direct influence of animal poisons on the tissues appears to be well shown in the effects of the bites of the viper and rattlesnake. Sir B. C. Brodie particularly noticed this in a man bitten by a rattlesnake {Lectures on Pathology and Surgery, p. 345). The primary local, though widely extended, effect of the poison was a sloughing of the cellular membrane, which began ' immediately after the injury was received.' The poison ' seemed to operate on the cellular membrane, neither in the direction of 366 SPECIFIC DISEASES : I will not be sure tliat the secondary inflammation which usually appears on the day after any of these bites, is to be ascribed in some measure to an influence exercised by the virus on the blood ; though, indeed, this will not seem impossible to those who are considerate of the effect of the minutest portion of vaccine virus, and of the intense constitutional disturbance excited by the other venoms. But, whatever be thought on this point, the occurrence of a new and difierent inflam- mation in the bitten part proves that it did not return to perfect health when its first afiection subsided ; it proves that some altered material of the virus, or some changing trace of its efiects upon the tissues, re- mained, altering their relation to the blood, and making them alone, of all the parts of the body, prone to specific disease. The bitten part thus, in its interval of apparent health, instructively illustrates the state of parts after inoculation with syphilitic or vaccine virus. In them, as in it, we must suppose that some virus, or some specific effect, pro- duced by a virus on the tissues, remains during all that period of latency, or incubation, as it is called, which intervenes between the inoculation and the appearance of the specific disease. Wliatever be the state thus indirectly induced in the inoculated, or bitten, part, let it be noted as one constantly changing. The tissues of the part, like the rest of the body, are engaged in the constant mutations of nutrition ; and the morbid material in the part is pro- bably, like every organic matter, in constant process of transformation. Some of the local phenomena of specific diseases indicate these pro- gressive changes in the part itself; but they can scarcely be traced separately from those that are occurring in the morbid material absorbed in the blood. The local and peculiar change produced by the direct effect of the morbid poison is essential to the complete manifestation of some specific diseases. In many others, as in typhus, variola, acute rheumatism, and gout, the morbid condition of the blood is sufficient to determine the local disease in tissues previously healthy. But it is, perhaps, true for all, that the existence of some part whose nutrition is depressed, whether through simple or specific injury, is very favourable to the manifestation of the constitutional disease (see p. 329). Thus, I shall the nerves, nor in that of the absorbents, nor in that of the bloodvessels.' His account has been recently confirmed in a more quickly fatal case. Many years ago, one of my brothers was stung by a weeverfish {Trachinus Draco) ; he had intense pain at the part and up the arm, and I remember that next day, though no severe inflammation had intervened, there was a little black slough at the puncture, as if the venom had completely killed a piece of the skin. MORBID MATERIALS IN BLOOD AND TISSUES. 367 tave to mention cases of cancer in wLich tlie constitutional condition, or diathesis, seems to have been latent till some local injury brought a cer- tain part into a state apt for the cancerous growth, — the diathesis, as one may say, waited for the necessary local condition. In like manner, cases sometimes occur in which constitutional syphilis is justly pre- sumed to exist, but in which it has no local manifestation till some part is appropriated for it by the effects of injury. T know a gentle- man, who, for not less than five years after a syphilitic affection of the testicle, had no sign of syphilis, except that of generally feeble health ; but he aacidentally struck his nose severely, and at once a well-marked syphilitic disease of its bones ensued. In another case, syphilitic disease of the skull followed an injury of the head. In similar cases, ulcers like those of tertiary syphilis have appeared in healing operation- wounds. I lately saw a gentleman who had long suffered with dia- betes, a condition with which, as is well known, boils often coincide. He, however, had none, till he accidentally struck his leg, and the injury was quickly followed by a succession of more than twenty boils near the injured part. And, in like manner, as I have stated in a for- mer Lecture (p. 330), even variola and measles may have their in tensest local manifestations in injured parts. I need not dwell on the importance of cases such as these, for caution against supposing that the diseases which seem to originate in local injury are only local processes. The most intense constitutional affections may appear, almost irrespective of locality, able to manifest themselves in nearly every part ; but the less intense may abide unob- served, so long as all the tissues are being maintained without external hindrance cr interference; they may be able to manifest themselves only in some part whose normal power of maintenance is disturbed by • injury or other disease. It may, generally, also, be noticed that the more intense the constitutional affection, and the less the need for preparation of a locality for its manifestation, the less tenacious is it of its primary seat. Contrast, for example, in this respect, the fugaoity of acute rhumatism or goirt with the tenacity of chronic rheumatism in some locality of old disease or injury. II. Respecting, secondly, the changes which a morbid material, inoculated and absorbed, may undergo in the blood, these may be enumerated as the chief; — increase, transformation, combination, and separation or excretion. Here, again, one assumes for an example such a morbid material as may be inoculated ; but it will be plain that most of what is said, in the following illustrations, might also be said of 368 SPECIFIC DISEASES: those that are otherwise introduced into the blood ; and further, that the particulars of the life of these morbid materials are generally con- sistent with those of ordinary constitnents of the blood. (a) The increase of the morbid material in the blood is illustrated in syphilis, small pox, vaccina, glanders. In any of these, the inocu- lation of the minutest portion of the virus is followed by the formation of one or more suppurating structures, from which virus, similarly and equally potent, is produced in million-fold quantity. So, the matter of any contagion working in one person may render his exhalation capable of similarly affecting a thousand others. , The increase is thus evident. The effect of the inoculated morbid poison may be compared with that of a ferment introduced into some azotised compound, in some of the materials of which it excites such changes as issue in the production of material like itself. What are the materials of the blood thus changed and converted to the likeness of the morbid poison we cannot tell. The observations of Dr. Carpen- ter,' showing how peculiarly liable to all contagious and other zymotic influences they are whose blood is surcharged with decomposing azotised materials, may well lead us to believe that it is among these materials that many of the morbid poisons find the means of their increase. And, as Mr. Simon^ argues, it seems nearly sure that certain of these poisons, in their increase, so convert some material of the blood, that they wholly exhaust it, and leave the blood for a long time, or for life, incapable of being again affected by the same morbid poison. The increase of the morbid material, however effected, explains these characters of specific diseases : — the apparent disproportion between the specific cause and its effect (p. 359) ; the want of correspondence, in respect of quantity, between the local and the constitutional pheno- mena (p. 359) ; the seeming capacity of self-augmentation (p. 860). (&) The transformation of a morbid material is indicated by the di- versity of the successive manifestation of a single and continuous specific disease. Thus, in syphilis, the primary disease, if left to its unhindered course, is followed, with general regularity, by a series of secondary and tertiary diseases. The terms often used would imply that these diseases are due to a morbid poison, which is, all along, one and the same. But identity of causes should be manifested in identity of effects ; the succession of morbid processes proves a succession of changes, either in the agent poison, or in the patient. They may be in ' Loc. cit. p. 160. ' Leefures on Surgical Pathology, p. 262. TRANSFORMATION OF MORBID MATERIALS. 369 the latter ; but, regularly, thej are in the former : for, on the whole, the succession of secondary and tertiary syphilitic diseases is uniform m even a great variety of patients. We may, therefore, believe, that the regular syphilitic phenomena depend on the ti-ansformations of the morbid poison ; their irregularities, on the peculiarities of the patient, whether natural or acquired from treatment. The transformation here assumed is self-probable, seeing the analogy of successive transformations in all organic hving materials. It is nearly proved by the diiferent properties, in regard to communica- bility, of the syphilitic poison at different periods : in the primary dis- ease communicable by inoculation, but not through the maternal blood to the foetus ; in the secondary, having these relations reversed ; in the tertiary, not at all communicable. In like manner, such facts as that the material found in the vaccine vesicle, on the eighth day, is better for fresh vaccinations than that taken earlier or later, prove successive tiansformations, — periods, we may say, of development, ma- turity, and degeneration, in the material of the virus. Many similar phenomena of transformations in the morbid poisons may be cited ; and if it may be accepted as a general occurrence, it will explain many of the phenomena of specific diseases. The period of in- cubation or latency of a disease may correspond with the transforma- tion preceding the effective state of the morbid poison, with its periods of development. The prodromata, the precursive constitutional affec- tions, and the Fuccessive stages of the disease, indicate the continuctis transtormations and varying influences of the same ; just as every difference of organic construction indicates a difference in the yet un- formed materials used in it. The increasing disturbance of the general health probably implies that the morbid poison increases while being, transformed ; that it grows with its development. The periodicity of all these events (p. 361) is a sign that the transformations of morbid poisons, like those of all other materials in the living body, are, in ordinary circumstances, accomplished in definite times. The sequelis of specific diseases indicate yet further transformations, or, more pro- bably, that the changes of the morbid poison have left the blood in a morbid state, through the exhaustion of some of its natural constitu- ents, or through the presence of some complemental material. (c) The combination of a morbid poison with one or more of the normal materials of the blood is indicated by the fact that when the same specific disease, produced even by the inoculation of the same matter affects many persons, it may present in each of them certain B B 370 SPECIFIC DISEASES: peculiar features. And these personal peculiarities, as they might be called, indicate modified qualities of the disease ; not merely such differences of quantity as might be explained by assuming that each person has, in his blood, a different quantity of such material as may be convertible into the morbid poison. Difference of quantity may ex- plain (as Mr. Simon and Dr. Carpenter have shown) differeace of in- tensity of specific disease, and difference of liability to epidemic influence ; but it does not explain the varied method of the same disease in different persons. For this, I believe, we must assume that the specific material of each disease may be, in some measure, modified by its combination with one or more of those normal materials of the blood which have, in each person, a peculiar or personal character (see pp. 11, et seq.) By such combination, we may best explain those characters of specific disease, which appear in its changes in transmission from one person to another (p. 360) : such as the varieties of syphilitic sores, and the varieties of their consequences in different persons inoculated from the same source ; the change in the form of secondary syphilis or of cancer in transmission from parent to offspring ; the several peculi- arities in the results of the same miasm when affecting ordinary per- sons or puerperal women, or those who have survived injuries. A remarkable instance, exemplifying, I think, as well the changes in the morbid poison itself, as its various effects on difierent persons, has been told me by my friend Mr. Huxley. One of the crew of H.M.S. Rattlesnake, after slightly wounding his hand with a beef-bone, had suppuration of the axillary lymphatic glands, with which typhoid symptoms and delirium were associated, and proved fatal. His illness began the day after the ship left Sydney, where all the crew had been remarkably healthy. A few days after his death, the sailor who washed his clothes had similar symptoms of disease in the axilla, and for four or five months, he suffered with sloughings of portions of the areolar tissue of the axilla, arm, and trunk on the same side. Near the game time, a third sailor had diffuse inflammation and sloughing in the axilla ; and after this ' the disease ran, in various forms, through the ship's company, between thirty and forty of whom were sometimes on the sick-list at once.' Some had diffuse cellular inflammation, some had inflammation of the lymphatic glands of the head, axilla, or lower extremities ; one had severe idiopathic erysipelas of the head and neck ; another had phlegmonous erysipelas of the hand and arm after an acci- dental wound ; others had low fever, with or without enlargement of SEPAEATION OF MORBID MATEEIALS. 371 glands. ' Finally, the disease took the form of mumps, which affected almost everybody on board.' The epidemic lasted from May to July. The ship was at sea the whole time, and, in the greater part of it, in the intense cold of a southern winter. (d) The separation of the material of a specific disease may probably be accomplished in many different ways, and may be regarded as the final purpose (if we may venture to trace one) of the greater part of the morbid process. It is evident in the inoculable products of sores and •pustules; in the infectious exhalations of the skin, pulmonary, and other surfaces in the exantliematous and other fevers ; in the deposits in and near gouty joints. Analogy with these cases makes it, also , pro- bable that the specific materials of several other diseases are separated from the blood accumulated at the seats of the local morbid process ; whence, if no organisms incorporating them be constructed, they may be re-absorbed after tiansformation. And it is nearly certain that the w.aterials of most specific diseases may be excreted with the natural evacuations in the course of the disease, and this, either in their ma- ture state, or after transformation, or in combination with the con- stitutents of specific medicines. The results of such separation or excretion are also various. Some- times, it seems as if the whole of the morbid material were (after various transformations) removed, and Ihe blood left healthy : as in small-pox, vaccinia, cured primary syphilis. Sometimes part of the morbid material, transformed or combined, so as to be incapable of excretion, remains in the blood, and produces secondary phenomena or sequete of the disease. Sometimes, the production of the morbid material continues, notwithstanding the separation of what is already formed : as in the increase of the cancerous diathesis during the growth of cancers. Generally, in whatever manner the separation be accom- plished, it is attended by such disturbance of the natural functions of parts, that serious disease is superadded to that which is the more di- rect consequence of the presence of the morbid material in the blood. And lastly, a local disease which owes its origin, and, for a time, its maintenance, to a specific morbid condition of the blood, may persist after that condition has ceased ; the blood may regain its health by the separation of the morbid material, but the part diseased in the process of separation may so continue. Now, however, the disease may be wholly local, and curable by local treatment. Thus may the theory of specific diseases be applied in explanation li B 2 372 SPECIFIC DISEASES : of their phenomena. I will only add that, in assuming all this of the changes occurring in morbid materials in the blood, we really assume little more than we believe of the organisable materials introduced, as nutriment, into the blood. If we could trace these, in their changes, first in the chyle and blood, and then in some complex tissue, then in the lymph and blood again, and again through the tissue of some ex- cretory gland, we should trace a career of changes not less numerous, not less definite in method and in time, not less influential in the economy, than those which I have assumed for morbid materials in the blood. Only, the increase of the morbid material, and the apparent independence of its changes, are not imitated in the normal events of life. GENEEAL CHAEACTEES OP TUMOUES, 373 LECTURE XXI. GEKKIiAL CTTAEACTEES AND CLASSIFICATION OF TUMOUES. The class of diseases whicli includes the tumours may be reckoned as a part of the great division named Hypertrophies or Overgrowths. All its members consist in additions to the organized materials of the body, and appear to be expressions of a morbid excess of the formative process ; but, in the case of each hypertrophy, the mode is peculiar in which this excess is manifested. If we compare any tumour with one of the hypertrophies that are least m orbid, with one of those, for instance, in which the excessive growth is adapted to some emergency of disease, as an hypertrophy of the heart is adapted to some emergency of the cir- culation, we shall, I believe, always see between them this chief differ- ence : that, to whatever extent the adapted hypertrophy may proceed, the overgrown part maintains itself in the normal type of shape and struc- ture ; while a tumour is essentially a deviation from the normal type of the body in which it grows, and, in general, the longer it exists the wider is the deviation. A striking illustration of this contrast may be found in some of the cases of fibro-muscular tumours that grow into tlie cavity of the uterus.' Such a tumoui' may resemble in its tissues the substance of the uterus itself, having well-formed muscular and fibrous tissues ; and, so far -as the structures formed in excess are con- cerned, we might regard the tumour as the result of an hypertrophy not essentially different from that which, at the same time and rate, may take place in the uterine walls around it. But an essential differ- ence is in this ; the uterus, in its growth around the tumour, maintains a normal type, though excited to its growth, if we may so speak, by an abnormal stimulus : it exactly imitates, in vascularity and muscular development, the pregnant uterus, and may even acq^uire the like power ; ' Such as (e. a.) No. 2682 in the College Museum. Eespecting the conditions in which the changes in the uterus here described are likely to occur, see Eokitansky, FathologUche Anatomic, iii. 546. 374 GE^fERAL CHARACTERS OF TUMOURS. and at length, by contractions, like those of parturition, may expel the tnmour, spontaneonsly separated. But the tumour imitates in its growth no natural shape or construction; the longer it continues, the greater is its deformity. Neither may we overlook the contrast in res- pect of purpose, or adaptation to the general welfare of the body, which is as manifest in the increase of the uterus as it is improbable in that of the tumour. Herein we seem to discern an essential diiFerence between the over- growths of tumours, and those accomplished by any exercise of the normal power of nutrition in a part. This power, capable of augmented exercise in any emergency, is yet not a mere capacity of production ; neither is it dependent upon circumstances for the fashion of its pro- ducts ; identical with that which effected the development of the germ, it is equally bound to conformity with the proper type of the part or species in which it is exercised. An equal contrast may, in general, be drawn between the class of diseases that include tumours, and all the others that issue in a morbid excess of nutritive formation. We may take, as the example of these, the inflammatory diseases attended with much production of new tissue, and say (reserving certain conditions, p. 320) that in these there is an excessive exercise of formative force — an hypertrophy. But between such diseases and tumours we shall rarely fail to observe the following differences : — 1st. The accumulation and increase of lymph in inflammation appear chiefly due to the morbid state of the parts at, or adjacent to the place of production. We have, I think, no evidence that the lymph of inflam- mation increases by any inherent force, any attraction of self-organising matter ; but the increase of all, or nearly all, tumours, is ' of themselves :' they grow as parts of the body, but by their own inherent properties, and depend on the surrounding parts for little more than the supply of blood from which they may appropriate materials. A tumour, there- fore, as a general rule, increases constantly ; inflammatory products generally increase only so long as the disease in the adjacent parts con- tinues. 2nd. The materials severally produced in excess, in these two cases, have difl"erent capacities of development. The inflammatory product, in whatever part it lies, has scarcely more than the single capacity to form, in the first instance, connective tissue : the material that begins or is added to a tumour may, indeed, assume this form, but it may as- sume any one of several other forms. aENERAL CHARACTEES OF TUMOURS. 375 But, 3dly, tlie most striking contrast is in the events subsequent to this first organising of the two materials. The later course of organised inflammatory products, like that of the organised material for repair after injuries, is usually one of constant approximation to a healthy state. As newly-formed parts, they gradually assimilate themselves to the shape and purpose, if not to the tissue, of the parts among which they lie ; or they are- apt to waste, degenerate, and be removed. Their changes tend ever towards a better state ; so that, in the whole course of productive inflammatory diseases, some can see nothing but an ' effort of nature ' to avert or repair some greater evil.' It is very difi'erent with the class of diseases to which tumours belong : it is in their very nature to proceed to further and further deviation from the proper type of the body. The structure of tumours may, indeed, be like that of some of the natural parts : it may be identical with that of the part in which they lie : in this respect they may be called homologous ; but considered in their life, they are not so ; for, commonly, they are grow- ing while the tissues far and near around them are only maintaining their integrity, or are even degenerating, or undergoing absorption from the pressure of the abnormal growth. 1 think that it is only in the consideration of this activity and partial independence of the life of tumours, and of the diseases allied to them, that we shall ever discern their true nature. We too much limit the grounds of pathology, when, examining a tumour after removal from the body, we only now compare it with the natural tissues. The know- ledge of all its present properties when dead may leave us ignorant of the property which it alone, perhaps, of all the components of the body, had prior to its removal, — the property of growing. And so, if we can ever attain the knowledge of the origin of a tumour, it may avail little, unless it supply also the explanation of its progress. If, for example, what is very improbable could be proved, namely, that tumours have their origin in the organisation of extravasated blood, or of an inflam- matory exudation, still this greater problem would remain unsolved : — • How or why is it, that, in ordinary cases, these materials, when organ- ised, gradually decrease, and assimilate themselves to the adjacent parts ; while, in the assumed formation of tumours, they gradually increase, and pursue, in many cases, a peculiar method of development and ' There are, indeed, cases in which organised lymph and scars continue to grow ; but these are quite exceptional, and are to be regarded as diseases of the same class as tumours, peculiar only in respect of the materials in which they are manifested. 376 GENEEAL CHARACTEES OF TUMOUKS. growth ? Why is it that, assuming even a similarity of origin, the new- formed part manifests, in the one class of cases, a continuous tendency towards conformity with the type of the body ; in the other, a contin- uous deviation from that type in shape and volume, if not in texture ? How is it that, to take an extreme case, we can ever find, as in a spe- cimen ' at St. George's Hospital, fatty tumours of considerable size in the mesentery of a patient from whom, in the exfcremest emaciation of phthisis, nearly all the natural fat was removed ; or, as in a case re- lated by Schuh,^ huge lumps of fat, on the head, throat, and chest of a man whose abdomen and legs were extremely thin ? I do not pretend to answer these questions ; hut T think that in them is the touchstone by which we may tell the value of a pathology of this great class of diseases. It is not in the likeness or in the unUke- ness to the nainiral tissues that we can express the true nature of tumours : it is not enough to consider their anatomy ; their physiology, also, must be studied ; as dead masses, or as growths achieved, they may be called like or unlike the rest of a part ; but, as things growing, they are all unlike it. It is, therefore, not enough to think of them as hypertrophies or overgrowths ; they must be considered as parts over- growing, and as overgrowing with appearance of inherent power, irrespective of the growing or maintenance of the rest of the body, discordant from its normal type, and with no seeming purpose. To all this, I know, it may be objected that tumours, and other like growths, may cease to grow, or grow unequally, and yet be tumours still. But this is only in appearance opposed to what I have said, which is no more than that the best or only time, in which we may discern the true difference of these from other growths is the time of their active increase. As we can have no complete idea of any living thing, unless it include the recognition of its origin, and of its passage through cer- tain phases of development and growth ; so must our thoughts of these abnormities be imperfect or untrue, unless we have, regard to their development, and growth, and maintenance, as independent parts. But, indeed, the cessation of growth in tumours and the allied diseases often affords evidences of their peculiar nature, confirmatory of that deduced from their increase. Such cessation may occur when they have attained a certain regular size ; as in the painful subcutaneous tumours, the osseous tumours on the phalanges of great toes, and some others, which, perhaps always, cease to gi-ow when they have reached a limit of dimen- ' Y 7 1 , Museum of St. Geoige's Hospital. ' Die Erl;enntnhs der Pseudoplaamcn, 101. Wien, 1851. GENEEAL CHARACTERS OF TUMOURS. 377 sions that appears as natural and constant for them as the average stature is for the individuals of any species. Or, the cessation of growth may occur vrhen the tumour degenerates or wastes ; as when a fibrous tumour calcifies, or when a mammary glandular tumour is absorbed. But it is to be observed that these events are, or may be, as irrespective of the nutrition of all the rest of the body, as the development and growth of the tumour were ; and that, except in the comparatively rare event of the absorption of a tumour, there is, in no case, an indication of return to the normal type or condition of the body ; there is no improvement, as in the organised lymph formed in the inflammatory process, no adaptation to purpose, no assumption of a more natural shape. In all these events, therefore, as well as in their growth, the nearly independent nature of the tumour is shown : while forming part of the body, and borrowing from it the apparatus and the materials necessary to its life, the tumour grows or maintains itself, or degene- rates, according to peculiar laws. The characters of which I have been speaking belong to a larger number of abnormities than are usually called tumours ; they belong, indeed, to a large class, of which tumours form one part or section, while the other is composed of certain morbid enlargements of organs, by what is regarded as merely hypertrophy ; such as that of the pros- tate, the thyroid gland, and others.' Now the distinction between these two divisions of the class must, I believe, be an arbitrary one ; for the two are so little unlike, that, really, it is in these hypertrophies of glands that we may hope to find the truest guidance to an insight into the nature of tumours. In speaking of cysts from the walls of which vascular growths may ' The class may seem to include, also, those abnormal states of the foetus which are attended with excessive growth or development of organs or members, yet cannot be ascribed to a fusion of two germs ; and, indeed, in the ease of certain bony growths the line cannot be drawn, without artifice, between monstrositiefe by excess and tumours. But, in the large majority of cases, there are sufficient characters of distinction between them; for 1st, the congenital excesses of development present a more complex structure, and are more conformed to the plan and construction of the body, than anything that can be reasonably called a tumour. And, if it be said that this higher organisation is no more than is consistent with the period of formation, which is in embryo-life, when the force of development is greatest ; then, 2ndly, we may note this difference, that the congenital excesses are usually limited for their increase to the period of natural growth of the body. They commonly cease to grow when or before the body has attained its full stature: they conform to its methods and times of development, growth, and decay. 378 GENERAL CHAEACTEES OF TUMOtTES. spriBg and fill their cavities, I sLall have to describe that these intra- cystic growths are, ia their best state of structure, close imitations of the gland in vsrhich they occur. In relation to tumours, the most in- structive examples of this fact are in the cystic tumours of the breast, of which the general structure has been especially illustrated by Dr. Hodgkin and Sir B. 0. Brodie, and the microscopic characters by M. Lebert and Mr. Birkitt. Among these, a series of specimens in the Museum ' may illustrate every stage of the transition, from the simple cyst, to the cyst so filled vfith gland-substance as to form a solid tumour, — the chronic mammary, or mammary glandular tumour. Now a near parallel with the history of these mammary tumours is presented by the ohservations of Frerichs^ and Rokitansky ^ on the intra-cystic growths which occur within the substance of enlarging thyroid glands, i.e. of increasing bronchoceles. lu these, masses of new-formed thyroid gland- tissue are found imbedded, and inclosed in coverings or capsules of con- nective tissue, within the proper though increased substance of the gland. In like manner, as Rokitansky first showed, it is not unusual in enlargements of the prostate gland, to find distinct masses of new structure imitating that of the prostate, which lie imbedded and incap- suled in the proper substance of the gland. Moreover (and here is a closer contact between these hypertrophies and tumours), these growths of new gland-tissue may appear, not only in the substance of the en- larging thyroid and prostate glands, but external to and detached from the glands. Such outlying masses of thyroid gland are not rare near bronchoceles ; lying by them hke the little spleens one often sees near the larger mass. Near the enlarged prostate, similar detached outlying masses of new substance, Hke tumours in their shape and relations, and like prostate gland in tissue, may be sometimes found. A very large and remarkable specimen of the kind was sent to me by Mr. Wyman.^ It was taken from a man, sixty-four years old, who, for the last four years of his Hfe, was unable to pass his urine without the help of the catheter. He died with bronchitis ; and a tumour, measuring 2i inches by 1^, was found, as Mr. Wyman described it, ' lying loose in the bladder, only connected to it by a pedicle, moving on this like a hinge, and, ' Mus. Coll. Surg.Xos. ]68, 169, 170, 172, ett. ' Ueber Gallcrt- oder CoUoid-geschwiilste. G-ottingen, 1847. ' Zur Anatoniie des Kroffes ; and Tlebtr die Cyste, in the Denkschr. der K. Akcdemie der Wissenschaften. Wien, 18i9. * The specimen is in the Jluseum of St. Bartholomew's Hospital (Series xxix. 25). A remarkable tumovir of the same kind, but imbedded in the substance of the prostate, is in the museum of the Middlesex Hospital. GENERAL CHARACTERS OF TUMOURS. 379 wlien pressed forwards, obstraoting the orifice of the urethra.' Now, both in general aspect and in microscopic structure, this tumour is so like a portion of enlarged prostate gland, that I know no character by which to distinguish them. The relation of these new-formed isolated portions of thyroid or pros- tate gland is so intimate, on the one side, to admitted tumours, such as the chronic mammary, and, on the other side, to the general hypertrophies of the glands, that we cannot dissociate these diseases without great violence to nature. Clearly these are all essentially the same kind of disease : yet, to call them all tumours would be to do as much violence to the conventional use of terms which have become not merely the expressions, but the guides, of our thoughts. The best course seems to b^ to make an arbitrary division of this group. In accordance, then, with the arbitration of custom, we may assign the name of Tumours to such examples of these morbid growths or growing parts, as, 1st, are isolated from the surrounding parts by distinct investing layers of tissue ; or, 2ndly, though continuous with the nataral parts, are abruptly oir- cumsoribed in the greater part of their extent ; or, 3rdly, are formed of new materials infiltrated and growing in the interstices of natural parts. General Classification. — If the group of what are to be called tumours may be thus inclosed, we may next proceed to divide it into smaller parts. And, first, it seems proper to arrange tumours in three divisions, two of which, characterised by possessing certain extreme or opposite properties, may be named Innocent and Malignant, whilst a third intermediate group may be named Recurrent. I would employ the terms innocent and mahgnaut still, because, though not free from obiections, they imply a more natural and a less untrue division than any yet invented to replace them. But in using these terms it may be well to remember that the distinction between innocent and recurrent and malignant tumours is probably one, not, or not only, of visible structure, but of origin and vital properties ; it is, therefore, less falsely expressed by terms implying quality of nature than by such as refer to structure alone.' ' The principal division of tumours, according to their physiological rather than their anatomical characters, has not been retained without a careful reconsideration of 380 MALIGNANT TUMOUES. Malignant Tumours. — The chief distinctions are to be traced in cer- tain characters which, in the maHgnant tumours or cancers (for these terms are synonymous) are superadded to those already cited as belong- ing to the whole class. And, 1st, the intimate structure of malignant tumours is, usually, not like that of any of the fully developed natural parts of the body, nor like that which is formed in a natural process of development, repair, or degeneration. Many of the cells of cancers, for example, may be somewhat like gland-cells, or like epithelium- cells ; yet a practised eye can distinguish them, even , singly. And much more plainly their grouping distin- guishes them . they are heaped together disorderly, and seldom have any lobular or laminar arrangement, such as exists in the natural glands and epithelia, or in the innocent glandular or epithehal or epider- mal tumours. These innocent tumours are really imitations, so far as their structure is concerned, of the natural parts ; and the existence of such imitations in any tumoui-s makes the diversity — heterology, as it is called — of the malignant tumours, appear more evident. Still, this rule of dissimilajity of structure in malignant tumours is only general. The other properties of malignancy may be sometimes observed in tumours that have, apparently, the same structure as those that are generally innocent. I shall have to refer to cases of fibrous tumours which, in every respect of structure, were like common fibrous tumours, and yet returned after removal, and ulcerated, with infection of adjacent parts, and appeared in internal organs. These, with some others, must be regarded as malignant, though in structure resembling innocent tumours and natural tissues. On the other hand, there are some innocent cartilaginous tumours, vrith structures as different from the whole matter, and a just regard to the opinions of those who hold that such a foundation of classification cannot he stable. It is believed that any one who, with equally large opportunities for both methods of study, will examine, with equal care, the manners of life, and the structures after death, of large numbers of tumours, will find not less constancy in the one than in tlie other. In a very large majority of cases certain structures coincide with certain manners of life ; and for all these the clinical foundations for classification (if it may be so called) would coincide with the anatomical. In a few cases there would be no such coincidence ; in a few, classification on either foundation is very difficult ; in still fewer it may be at present impossible. But for all cases, so long as the anatomical foundations for classification are not nearly perfect, the utility of a clinical division and momenclature of the great groups of tumours must justify the retention of names which, by custom and contrasted meanings, tell the facts which are, in daily practice, the most important to be Jin own. MALIGNANT TUMOURS. 381 those that exist in our natural tissnep, as cancer-cells are from gland- cells or from epithelial cells. The two sets of cases, though both be exceptional, supply sufficient grounds for not preferring such terms as ' homologous ' and 'heterologous ' before ' innocent ' and 'malignant,' if the former are meant, as they commonly are, to apply to the structure of the several growths. 2nd. Malignant growths may have the character of infiltrations; i.e. their elementary structures may be inserted, infiltrated, or diffused in the interspaces and cavities of the tissues in which they lie. Thus, in its early state, a malignant tumour may comprise, with its own proper elements, those of the organ in which it is formed ; and it is only in its later life that the elements of the tissue or organ disappear from it, gradually degenerating and being absorbed, or possibly, yield- ing themselves as materials for its growth.' Thus, a hard cancer of the mammary gland includes in its mass a part, or even the whole, of the gland itself, as if there were only a con- version of the gland-tissue : and one may find, within the very sub- stance of the cancer, the remains of the lactiferous tubes involved in it, and, with the microscope, may trace in it the connective tissue that separated the gland-lobes and the degenerate elements of the epithelial contents of the tubes and acini. But among all these lie the proper cells of the cancerous growth, and these usually increase while the original structures of the gland decrease. So, too, in medullary can- cerous disease of the uterus, the uterus itself, or part of it, is in the tumour, and gradually disappears, while the medullary m.atter, diffused or infiltrated in it, is growing. The malignant growths may, I say, thus appear as infiltrations ; but they are not always so. Thus, though the hard cancer of the breast is, commonly or always, an infiltration of cancerous substance in and among the proper structures of the gland, yet the hard cancer of the bones is often a distinct tumour, such as has no mixture of bone in it, and may be enucleated from the cavity or shell of bone in which it lies. So too, while the medullary cancer of the uterus plainly consists in an infiltration or insertion of new material in the substance of the organ, ' See, on this last-mentioned point, Eokitansky, Pathol. Avatomie, i. 121. If, in such a case, the removal of the original textures he quicker or more considerable than the production of the new morbid substance, there may be no swelling or risible tumour ; yet, since the new material increases, the essential character of a growth is obserTed. Such growth without swelling is often noticed in hard cancers of the breast and of the bones. 382 MALIGNANT TUMOUES. that of the hreast is usually a separate tumo-ar, and altogether discon- tinuous from the surrounding parts. • Many other instances of similar contrast might be cited ; still the fact that their elementary structures may be thus infiltrated in the tis- sues they afiect is a characteristic feature of malignant tumours. I think it is rarely imitated in cases of innocent tumours. 3rd. It is also generally characteristic of malignant tumours that they have a peculiar tendency to ulcerate, their ulceration being pre- ceded by softening. One can, indeed, in this particular, only observe a graduated difference between the innocent and the malignant diseases ; for certain innocent tumours, if they grow very rapidly, are apt very rapidly to decay ; and they may suppurate and discharge their ichor and debris with foul and dangerous ulceration. Thus the quickly- growing cartilaginous tumours may imitate in these respects malignant growths ; so may large fibrous tumours when they soften and decay. Or, again, when an innocent tumour grows more rapidly than the parts over it can yield, they may waste and ulcerate, and allow it to protrude ; and it may now itself ulcerate and look very like malignant disease. This may be seen in the protruding fibrous tumours that ulcerate and bleed ; or, in a more striking manner, in the protruding vascular growths that have sprung up in the cystic tumours of the breast. Or, once mere, the characters of readiness to ulcerate may be imitated by innocent tumours after injuries, or in exposure to continued irritation ; for they resist these things with less force than the similar natural parts do. Hence, sloughing and ulcerating fibrous, erectile, and other tumours, have been often thought cancerous, and so described. The respective tendencies to ulcerate can, therefore, be counted only as constituting differences of degree between the innocent and maUg- nant tumours. We may speak of a hability in the one case, of aprone- ness in the other. 4th. The softening that often precedes the ulceration of malignant growths, can hardly be considered separately from, the minute account of their structure. I therefore pass it by, and proceed to their fourth distinctive character, which is to be noticed in the modes of their ulcera- tion. This is, that the ulcer which forms in, or succeeds, a maUgnant growth, has no apparent disposition to heal ; but a morbid substance ' Nos. 2787, 2796, and others in the College Museum; andNos. 15 in Series xxxii. and 28 in Series xxxv , of that of St. Bartholomew's, illustrate these contrasts. On the difference between infiltrations and, cutyrowtlis, seep. 389. MALIGNANT TUMOURS. 383 like that of which the original growth was composed, forms the walls or boundaries of the ulcer ; and as this substance passes through the same process of ulceration which the primary growth passed through, so the malignant ulcer spreads and makes its way through tissues of all kinds. In contrast with this character of malignant growths, it is observ- able that beneath and around an ordinary nicer of the natural tissues, or of an innocent tumour, we find the proper tissues uncha;iged ; or, perhaps infiltrated and succulent with recent lymph, or the materials for repair ; or somewhat indurated with lymph already organised. The base and margins of a cancerous ulcer are themselves also cancerous ; those of a common ulcer are infiltrated with only reparative or inflam- matory material. In like manner, if ulceratioia extend through an in- nocent growth, it may destroy it all, and no similar growth will form in the adjacent parts, replacing that which has been destroyed : but, in the aloeration of cancer, while the cancerous matter is being constantly discharged, by sloughing or ulceration, from the surface, new matter of the same kind, and in more abundance, is being formed at some distance from the surface ; so that, in a section through an ulcerated cancer, one does not arrive at healthy tissues till after passing through a stratum of cancer. .5th. Malignant tumours are, again, characterised by this — that they not only enlarge, but apparently multiply or propagate themselves ; so that, after one has existed for some time, or has been extirpated, others like it grow, either in widening cii'cles round its seat, or in parts more remote. Mere multiplicity is not a distiuctive character of maliguant diseases ; for many innocent tumours may be found in the same person. But in the conditions and circumstances of the multiplicity there are character- istic difE'erences. Thus, when many innocent tumours exist in the same person, they are commonly, or always, all in one tissue. A man may have a hundred fatty tumours, but they shall all be in his subcutaneous fat : many fibrous tumours may exist in the same uterus, but it is so rare, that we may call it chance, if one be found in any other part in the same patient : so, many cartilaginous tumours may be in the bones of the hands and feet, but to these, or to these and the adjacent bones, they are limited. There is no such limitation in the cases of multiplicity of malignant tumours. They tend especially to aflFect and to extend along the lymphatics connected with the part in which they first arise ; but they 384 MALIGNANT TUMOUES. are not limited to these. TLe breast, the lymphatics, the skin and mus- cles, the liver, the lungs, may be all, and at once, the seats of tumours. Indeed (and here is the chief contrast), it is more common to find the many malignant tumours scattered through several organs or tissues than to find them limited to one.^ Moreover, if there be a multiplicity of innocent tumours, they have generally a contemporary origin, and all seem to make (at least for a time) a commensurate progress. But the more ordinary course of ma- lignant tumours is, that one first appears, and then, after a clear interval of progress in it, others appear ; and these are followed by others, which, with an accelerating succession, spring up in different parts. 6th. A sixth distinctive character of malignant tumours is that, in their multiplication, as well as in their progress of ulceration, there is scarcely a tissue or an organ which they may not invade. In regard to their multiplicity, I have just illustrated their contrast in this point with the innocent tumours ; and a similar contrast is as obvious in the characters of the ulcers. It is seldom that a common ulcer extends, without sloughing, from the tissues it has first affected into any other ; rather, as a new tissue is approached, it is thickened and indurated, as if to resist the progress of the ulcer. But before a cancerous ulcer the tissues in succession all give way, becoming first in- filtrated, and then, layer after layer, degenerating and ulcerating away with the cancerous matter. One may see this very well in bones. Specimens are to be found in nearly all museumf, of tibiee (for example) on the front surfaces of which new bone is formed, in a circumscribed round or oval layer, a line or two in thickness. This bone, which is compact, hard, smooth, and closely united with the shaft beneath it, was formed under an old ulcer of the integuments of the shin. But, on the other side, specimens are found, which show that when a cancerous ulcer reaches bone, at once the bone clears away before it ; and a cavity with abrupt, jagged, eaten-out edges, tells the rapid work of destruction. ^ Neither are spe- cimens rare, showing the progressive destruction of more various tissues ; such as a cancer of the scalp making way by ulceration through the " A case quoted in the Assoc. Med, Jour. Nov. 30, 185S, from the practice of Dr. E. W. Smith, offers a remarkable exception to this rule A woman, with obeolfte scirrhous caucer of the breast, had secondary scirrhus in nearly every part of the skeleton, and scarcely a trace of it in any other structure, ' In the College Museum, Nos. 3082'3-3a; 3267-8, and many others, illu-'trate these points. INNOCENT AND KECUEEENT TUMOURS. 385 pericranium, skull, and dura mater, and then penetrating deeply into the brain ; ' or one in the integuments of the shin going right through the tibia, and deep into the muscles of the calf.^ Such are the general characters of malignant tumours. Innocent Twmours. — The characters of innocent tumours are the opposites or negatives of malignant tumours. Thns : innocent tumours have not a structure widely different from that of a natural tissue; they do not appear as infiltrations displacing or overwhelming the original tissues of their seat ; they do not show a natural proneness to ulcera- tion : nor is the ulceration, which may happen in one through injury or disease, prone to extend into the adjacent parts : they do not appear capable of multiplying or propagating themselves in distant parts : they do not grow at the same time in many different tissues. Becurrent Tumnurs. — Of recurrent tumonrs the chief distinctive characters are that, like innocent tumours, their structures resemble those of the natural tissues, but of those tissues -usually in an incomplete, rudimental, or embryonic state, or in conditions that may be likened to malformations ; that they have a tendency to depart the more widely from the adult type of structure, the more frequently they recur ; that they do not appear as infiltrations ; that their ulceration, to which, how- ever, they are more prone than most innocent tumours, is not apt to extend into adjacent parts : but that, like malignant tumours, they do sometiines appear in organs distant from their first seat, and are ex- ceedingly prone to be repeatedly re-formed at their original seat after complete extirpation. The distinctive value of each of the characters which I have assigned to malignant disease may be depreciated : indeed, I have myself lowered it, by showing that each of them may be absent in tumours having all the other features of malignancy, and that certain of them may be ob- served occasionally in tumours that in other respects appear non-malig- nant. But objections against each chara,cter, separated from the rest, are of little weight against the total value of all these characters of malignancy, or of a majority of them, concurrent in one case. Similar objections might be made against even the classifications of natural his- tory : and none but such as are disposed to cavil at all nosology, could ' Museum of St. Bartholomew's, vi. 57. '' Museum of the College of Surgeons, 232. 386 CLASSIHCATION OF TUMOUKS. fail, in watching a series of cases of tumours througli many years, to observe that the great majority of them could be classed according as, in their conrse, they did or did not present the characters that I have enumerated. Some cases wonld be fonnd in which one or two of the signs might be wanting, or, if I may so speak, misplaced ; bnt, putting these aside, aa exceptions to be regulated by future inquiry, and looking broadly at the whole subject, no one could doubt that this division of tjumours into innocent, malignant, and recurrent, may be justly made, and that the outward marks by which they are discriminated are expres- sions of real differences in their properties and import. In what these differences may consist I shall not discuss till I have completed my account of each kind of tumour. For the present I will say only, that I think malignant tumours are local manifestations of some specific morbid states of the blood ; and that in them are incorpo- rated peculiar morbid materials which accumulate in the blood, and which their growth may tend to increase. All their distinctive charac- ters are, I think, consistent with this view : and the absence of the same characters in the innocent tumours may lead us to believe that they are usually local diseases, the result of some inexplicable error of nutrition in the part that they affect, and only in the same measure dependent on the state of the blood as are the natural tissues, which require, and may be favoured by, the presence of their appropriate materials of nutrition. Or when, as sometimes happens, an innocent tumour begins its growth during, or soon after, some general disease, we may suppose that it owes its first formation to an abnormal condition of the blood ; but that, when the blood recovers its health, the tumour subsists or grows on the nourishment supplied by the normal materials of the blood. Instances of tumours thus constitutional in their origin, but subsisting as local diseases, will be mentioned in the general history of cancers. It may be best to speculate no farther, either on this point, or on the origin or determining causes of tumours. I could speak certainly of very little connected with these points, unless it were of the error or insufficiency of all the hypotheses concerning them that I have proposed to myself, or have read in the works of others. One of these alone seems to need disproof : namely that tumours, whether innocent, recur- rent, or malignant, are due to the organisation of effused blood, or of some inflammatory or other exudation, or of the material of repair. The great objections to this view are as follows : — 1. It is an almost infinitely small proportion of injuries that are followed by the growth of tumours. 2. In a large majority of cases of tumour, no injury or previous local CLASSIFICATION OF INNOCENT TUMOURS. 387 disease is assigned, even by the patients, as the cause of the growth. In 200 cases, taken indiscriminately from those I have recorded, no local canse whatever could be assigned for the growth of 155 tumours, of which 64 were innocent and 91 malignpnt ; of the remaining 45, re- ferred by the patients to previous injury or disease of the part, 15 were innocent and 30 malignant tumours. 3. Blood extravasated, and the products of the inflammatory and reparative processes, are not indiffe- rent materials, such as would pursue this or that direction of develop- ment, according to chance, or some imaginary influence exercised on them. They have a proper tendency to assume the form of connective or osseous tissue. They do not become, when their history can be traced, either fatty, or perfectly cartilaginous, or glandular tissue, such as we find in tumours. 4. No intermediate conditions have been yet found between blood, or lymph, and a tumour. And, lastly, all the facts relating to injuries, as favouring, or determining, the growth of tumours, are explicable on the supposition that the injury impairs for a time the nutrition of a part, and diminishes its power of excluding ab- normal methods of nutrition. Narrowing, now, the objects of consideration to the Innocent Tumours alone, I will speak very briefly of their classification. A first subdivision of them may be made, according to the usual ai-rangement, into the Cysts, or Cystic Tumours, and the Solid Tumours. There are, indeed, not a few instances in which the two divisions overlap, or are confused. Thus, on the one side, in cases to which I have already referred, a solid growth may spring from the inner wall of a cyst, and, enlarging more rapidly than the walls do, may fill the cavity, and come in contact and unite with the walls ; and thus may be traced a complete series of gradations from the cystic to the sohd tumour. On the other hand, cysts may be formed within solid tumours, and, increasing more rapidly than the solid structure, may reduce it to scarcely more than a congeries of cysts, or to one great cyst. Such changes are illustrated sometimes in fibrous tumours of the uterus ; and I think, also, in the tumours which Sir Astley Cooper called ' hydatid disease ' of the testicle. But though there are these instances of confusion, yet the division is very convenient, and is probably deeply and well founded. Next among cysts, some are filled with a simple fluid, containing no organised matter, and resembling one or other of the fluids of serous c c 2 388 CLASSIFICATION' OF INSOCSNT TUMOUES. cavities. These may be called Simple, or Barren, or, in most instances, Serous Cysts. Other cysts contain organised substances, and may be named, as a group, Proliferous ; and the several members of the group may be de- scribed, according to their contents, as Glandular, Cutaneous, Sebaceous, Dentigerous, and the like. Of the solid innocent tumours, no method of arrangement at present appears reasonable but the old one, which is founded on their likeness to the natural tissues. On this ground they may be arranged in. the following chief divisions, with names, as specific names, expressing their several resemblances — viz. Fatty, Fibro-Cellular, Fibrous, Car- tilaginous, Osseous, Myeloid, Glandular, Vascular or Erectile, and Papillary. And, again, under each of these may be arranged certain varieties, including instances that, in some uniform manner, deviate, without quite departing, from the usual characters. Thus, as varieties of the Fibrous tumours, may be named the fibro-cystic, fibro-calcareous, and fibro-muscnlar tumours, and so on. In each assnmed kind or group of these solid tumours, moreover, we must make a division, according to their modes of growth, and of connection with the adjacent parts. Some among them are only in- termediately connected with the adjacent parts ; a layer of tissue at once separates and combines them, and, by division of this layer, such a tumour may be cleanly and alone removed from the surrounding parts ; it may be enucleated or shelled-out from them. Thus, with a common fatty tumour, or a fibrous tumour of the uterus, if we cut along one part of its surface, we may, with a blunt instrument, detach the whole mass, by splitting the layer of connective tissue which, like a capsule, incloses and isolates it. These are what we commonly accept as the proper or typical tumours, these which are ' discontinuous hypertrophies.' Other growths resemble these in every character, except in that they are connected with the adjacent parts by continuity of similar tissue, and thus appear as growths, not in, but of, the parts. Thus we cannot exactly isolate a polypus of the nose or of the uterus : the over- grown part cannot be enucleated, because the proper tissue of the nasal mucous membrane, or of the uterine wall, is continued into it ; the tissue of the growth is here not only uniform, but continuous, with that of the adjacent parts. So, too, with epulis : the gum itself, or the periosteum of the jaw together with the gum, seems, by its own exces- sive growth, to form the tumour ; and in other fibrous tumours on TUMOURS AND OUTGEOWTHS. 389 bones, the fibres of the periosteum appear to be in the growth, and to form part of it. Such growths as these might be named ' continuous hypertrophies ' or ' outgrowths ; ' and I will, in general, observe this distinction wher- ever the same tissue is, in different cases, found in both forms of growth ; calling the discontinuous masses, tumours, the continuous ones, out- growths. Thus, answering to the common fatty tumour, we find the pendulous and continuous fatty outgrowths of the neok or the abdominal walls ; answering to the fibro-oellular tumour that grows, as a discon- tinuous mass, in the scrotum or beneath the labia, we have the cutaneous outgrowths or enlargements of these parts ; to the fibrous tumours of the uterus answer the fibrous polypi or continuous outgrowths of its substance. All these instances of clear distinction might lead us to think that a strong definition-line might be drawn to divide the whole class of innocent overgrowths into tumours and outgrowths. But when we come to the tumours of bone and periosteum, and to the erec- tile tumours, we find the distinctions vanishing, and in many instances no longer possible. It may seem as if these ' outgrowths ' needed distinction from the ' infiltrations ' which were spoken of as peculiar to malignant diseases. The distinctions between them are well marked. In the outgrowth the new material is like that with -ivhich it is connected, or like its normal rudiment, so that it is as if the tissue were itself outgrown ; but, in the infiltration, the new material is dissimilar from that in the interstices of which it is placed. And in the outgrowth the materials of the original part appear to be at least maintained, if they are not increased ; but in the infiltration they degenerate and waste. We may compare, for this contrast, the cancerous diseases of the skin, with the cutaneous outgrowths of the labia, nymphre, prepuce, or scrotum. In thus briefly indicating that which appears still the most rea- sonable method of classifying tumours, I have referred to difBculties which have appeared to some to be insuperable objections to any at- tempt at an arrangement of these diseases. I will therefore state, so far as I can, what is the real weight of these objections. First, it is said, such classifications cannot be well made, because, between each two assumed kinds or groups of tumours, intermediate examples may be found, transitional, as it were, from one species to the other : the one, it is said, ' runs into ' the other ; or, as Mr, Abernetiy expressed it, ' diseases resemble colours in this respect, —that a &w of 390 CLASSIFICATION OF INNOCENT TUMOURS. the primary ones only can be discriminated and expressed, whilst the intermediate shades, though distinguishable by close attention and comparative observation, do not admit of description and denomination. This is exactly true : but Mr. Abernethy seems to have felt that his sentence supplied the answer to the objection against classification by structure, which it expressed ; for as he did not, because of the inter- mediate tints, refuse to name and arrange the primary colours, so neither did he, nor need we, hesitate to name and classify diseases, and among them the principal forms of tumours. Moreover, the objection that structures may be found intermediate between those belonging to the chief forms of tumours, may be as well made against the use of names and systems for the natural tissues. There are no strongly outlined characters defining any of the natural tissues that are ever imitated in tumours ; intermediate and confusing forms are found everywhere. The various forms of fibro-cartilage, for instance, fill up everypossiblegradationfromcartilage to fibrous tissue : between the looser and denser forms of connective tissue, between ten- dons, aponeuroses, and fasciae, between epithelium and simple mem- brane, there are, in the natural tissues, the narrowest gradations. Yet we name and arrange the natural tissues with some truth and much utility ; and so we may the tumours that resemble them. Another objection against this classification of tumours is made on the ground that there are some in which two or more different tissues are mingled. Thus, tumours may be often found, in which fat and fibro-cellular tissue, or fibrous tissue and organic muscle, or cartilage and glandular tissue, or other combinations, meet together. But, among these, some are imitations of natural combinations of tissues, as the fibrous and organic muscular tissues of the uterus are imitated by the fibro-muscular tumours in its walls ; and of the othei-s, it need only be remembered that such combinations do occur, and these may be put aside from any interference with arrangement, by making a series of mixed tumours, or by adding to the description of each species the combinations into which it may enter. Tet another objection is made, that the characters of tumours are not constant, and that many must be reckoned as examples of one spe- cies, which are not much, if at all, like one another. This diversity of characters is, indeed, the great difficulty with which the pathology of tumours has to contend ; but the diversity is ' ' An Attempt to form a Classification of Tumours according to their Anatomical StrnettTO.' Surgical Works, ii. ed. 1815. DIVEESiTY OF CHARACTER OF TUMOURS. 391 •not to be called inconstancy : it is due to the fact that each tumour has, like each natural tissue, its phases of development, of degeneration, and of disease. Now, we have scarcely yet begun the study of the variations to which, in each of these phases, the several tumours are liable. We may have learned, for example, the general characters of cartilaginous tumours, as they grow in the most favourable conditions ; but how little do we know of the various aspects these may present when they fail of due development, or fall into various diseases, or vari- ously degenerate ! Yet all these changes have to be studied in the history of every tumour ; and it would be as reasonable to charge any natural tissue with inconstancy, because it is altered in development and disease, as to hold that the similar diversity of tumours is an ob- jection to their classification according to their structure. However, while I put this aside as an objection against classifica- tion, let me not be thought to underrate it as a difiiculty ; it is the great difficulty with which we have to contend. The work we have to do is not only to distinguish each kind of tumour from all other kinds, but, and in order to this end, to distinguish, as I may say, each kind from itself, by learning in each all the changes occurring in the various stages of its life. The difficulty of such a task cannot be exaggerated, while we consider the rarity of the objects to be studied ; but it must be overcom.e before we can cease to speak of ' anomalous tumours,' and of ' strange distempered masses,' or, which is more important, before we can, even after the removal of a tumour, speak with certainty of the issue of a case. It is owing to this diversity of structure which the same tumour may at times exhibit in various parts of its substance, that, not rarely, the examination of a mere fragment is insufficient to enable us to pronounce an opinion on the characters of the entire mass. Moreover, the careful study of the diiFerences which each kind of tumour may present, according as its component structures are in various stages of development, or of degeneration, or disease, must be a check on the giving of new names to tumours that only appear not like to those well known and well named. As we do not give different specific names to embryonic and to mature cartilage, or to healthy and to diseased connective tissue, so neither should we give a new name to any tumour till we have reason to believe that it is not composed of the elements of some ordinary tissue in some rudimental or morbid state. I cannot doubt that most, or all, of the tumours that in recent years have received new names, may be referred to and regarded as varieties of some of the older kinds, if they are but studied with this ?92 SIMPLE OE BAEREN CYSTS. LECTURE XXII. SIMPLE OR BAEREN CYSIS. The Cysts, or Cystic Tumours, to which I shall devote this lecture and the next, form a very numerous group, and have only or barely these characters in common ; namely, that each of them is essentially a cyst, sac, or bag, filled with some substance which may be regarded as entirely, or for the most part, its product, whether as a secretion, or as an endogenous growth. We may conveniently arrange cysts under the titles ' simple ' or ' barren,' and ' compound ' or ' proliferous ; ' the former containing fluid or an organised matter, the latter containing variously organised bodies. Among the simple or barren cysts, which may occur either singly or many together (multiple), we find some that contain a fluid like that of one of the serous membranes ; such are certain mammary cysts, and those of the choroid plexus : some are full of synovia-like fluid, as the enlarged bursse : others are full of blood, or of colloid or some peculiar abnormal fluid : while others, forming the transition between the barren and the proliferous cysts, contain more highly organic secretions, such as milk:, or mucus, or salivary or seminal fluid. These several forms we may arrange with names appropriate to their con- tents; as Serous, Synovial, Mucous, Sanguineous, Colloid, Salivary, Seminal, and others. Among the cysts, whether barren or proUferous, it is probable that at least three modes of origin may obtain. 1st. Some are formed by the enlargement and fusion of the spaces or areolae in connective or other tissues. In these spaces fluids coUect and accumulate ; the tissue around becomes condensed ; and, gradu- ally, the boundaries of the spaces are levelled down and walled in, tUl a perfect sac or cyst is formed, the walls of which continue to secrete. Thus are produced the bursas over the patella, and others ; and to this GENERAL HISTORY OF CYSTS. 393 ■we may refer, at least in some cases, the formation of cysts ia tiimours, and, perhaps, in other parts. 2dly. Some, and probably the larger nnmber of cysts are formed by dilatation and growth of natural ducts or sacculi ; as are those sebjiceous or epidermal cysts which, formed by enlarged hair-follicles, have permanent openings ; and the cysts, formed by dilatation of mucous follicles. Such, also, are certain cysts, containing milk and other fluids, that are formed of enlarged portions of lactiferous tubes ; such the ovarian cysts formed by distended and overgrown Graafian vesicles ; and such appear to be certain cysts formed of dilated portions of bloodvessels shut off from the main streams. 3dly. Other cysts may be due to the enormous growth and expan- sion of new-formed elementary structures, having the characters of cells or nuclei, which pursue a morbid course from their origin, or from a very early period of their development. It might, on some grounds, be desirable to classify the cysts accord - ing to their respective modes of formation ; separating the 1st and 2d groups, the ' secondary cysts,' which are derived by growth or expan- sion of normal parts, from the 3d group — ^the so-called ' primary,' or the ' autogenous ' cysts. But, at present, I believe, such a division cannot be made ; for of some cysts it is impossible to say in which method they originate, and, in some instaaces, either method may lead to an apparently similar result. Thus, some sebaceous or epidermal cysts are clearly formed of overgrown hair-follicles ; others seem of distinct autogenous origin. Some ranuliB are formed by dilatation of the submaxillary duct, obstructed by calculi or otherwise ; others probably by abnormal development of mucous cysts, which are formed by a dilatation of the mucous glands of the floor of the mouth, or possibly of a bursa between the muscles of the tongue.' Some, and probably the majority of the cysts in the mammary gland are certainly dilated portions of ducts ; others seem to be abnormal transformations of the elementary structures of the gland. But in each of these cases it may be impossible, when the cyst is fully formed, to decide what was its mode of orio-in : whether by growth of parts once normally formed, or by transformation of elementary and rudimental structures. Of the three modes of the formation of cysts to which I have ' See Fleischmann, in Schmidt's Jahrbucher, 1841, B. 32; and Frerichs, TJeher GaUert- oder CoUoidgesohwulste, Gottingen, 1847, p. 37. The existence of a bxiraa as a normal structure ia this locality is somewhat douhtful. See Virohow, Die TcranJcJiaften Greschwiilste, i. p. 274. 394 GENEEAL HISTORY OE CYSTS. referred, tlie first two — namely, that which is accomplished by expan- sion of areolar spaces, and that by dilatation and growth of ducts or vesicles — scarcely need an explanation. If it were not for some conTenience in surgical practice, we should not retain many of the cysts thus formed in the list of tumours ; for their growth appears, in most instances, to be due only to the accu- mulation of the contents of the obstructed tube or sacculus, and to be exactly adjusted to this accumulation, and commensurate with it. Thus it is in the cases of ranula with obstruction of the submaxillary duct, and the similar dilatations of the pancreatic duct ; in the cystif orm dila^ tation of the obstructed Fallopian tube ; in the dilated hair -follicles ; in bursffi ; and in some others. These are all conventionally reckoned among cysts, and arranged with tumours. But several of the like kind are not usually so reckoned ; such as the cyst-like gall-bladder, dilated with thin mucas, when the cystic duct is completely obstructed ; the dilatation of the body of the uterus, filled with serum (hydrometra) after closure of the os uteri ; the distended sheath of a tendon ; and others. Convenience and common usage have decided what cysts may be grouped with those which alone, we may anticipate, will be classed with tumours when pathology becomes more accurate and strict. Con- venience alone, also, decides for the omission, from, so vague a class as this, of the sacs or capsules that are formed round foreign bodies and solid tumours, and of the sacs that may be formed on the free surfaces of extravasated blood or inflammatory products. The walls of these cysts are usually constructed of fine, well- formed connective tissue, of which the filaments are commonly mingled with elastic fibres, and are variously interwoven in a single layer, or in many that are separable. The membranous walls are, in general, rather firmly connected with the adjacent parts, so that the cysts cannot easily be removed entire ; and from these parts they derive the bloodvessels that usually ramify copiously upon them. They are usually also fined with epithelium, which is generally of the tessellated form. In some cases, however, a ciliated epithelial lining is found. M. Giraldes' tells me that the cysts which so often occur in the antrum are commonly lined with ciliary epithelium. Friedreich ' and Eberth ^ describe cysts with a similar lining in the Uver : Virchow' refers to a case by Luschka, where, in the interior of an ovarian cyst, papillary growths, covered by ' Virchow'e Archiv, xi. p. 466. 2 Idem, March 1866. ' Idem, xi. p. 469. GEWEEAL HISTOEY OF CYSTS. 395 ciliated epithelial cells, were found. Athol Johnson ^ relates a case of fibro-cystic disease of the testicle, some of the cysts in which had a ciliated epithelial lining, and Eberth ^ has described a cyst in the pos- terior lobe of the brain which had a similar epithelium. For the third method of cyst-formation enumerated above a more detailed account may be required. But it must be admitted that patho- logists do not at this time attach so general an importance to this mode as was done some years ago. For many of the appearances seen on cutting into a multiple cystic tumour in a gland, which were sup- posed to be due to enlargement of its elemental structures, can be ac- counted for as easily on the supposition that they are owing to dilatations of its ducts or other normal parts. Still there are cases in which cysts form, often in considerable numbers, where it is not easy to see how they can have arisen by growth or expansion of the normal parts, and in which, therefore, for the present at least, a primary or autogenous origin may be assumed. The observations of Mr. Simon ^ and of Rokitansky,* on cystic for. mations in the kidney, are those on which the theory of the development Pig. 50. of cysts from enlargement of the cells, or primary anatomical elements, of a part is chiefly based. I shall best describe this theory by giving • Med. Times and Gaz., Feb. 16, 1856. ' Virchow's Archw, March 1866. « On Subacute Inflammation of the Kidney ; « Ueber die Ci/ste ] Wien, 1850. Bledioo-Chirwrgical Trans, xxx. 396 GENERAL HISTORY OF CYSTS. an abstract of some of Rokitansky's obssrvatlons, with a copy (Pig. 60) of one of his outline sketches of the minute structure of the cystic disease of the kidney. In a portion of a granular and cystic kidney, nests (as Rokitansky calls them) of delicate vesicles, from a size just visible to that of a millet-seed, niay be seen imbedded in a reddish-grey or whitish sub- stance. These differ in size alone from the larger cysts to which one's attention would be sooner attracted ; and, on the other side, it is only in size that they differ from many much smaller. For if a portion of such a nest be examined with the microscope, one finds, together with the debris of the kidney, variously diseased it may be, a vast number of vesicles or cysts that were invisible to the naked eye. The most striking of these have a wall consisting of layers of fibres scattered over with curved nuclei (a), and are filled with granulated nuclei, or, more rarely, with round or polyhedral cells, some of which may contain a molecular or granular pigmental matter (cZ). In many of these cysts the nuclei or cells are reduced to an epithelial lining of the cyst ; and in some even this is absent, and the ' barren ' cyst is filled with a clear or opaline adhesive fluid. From the size just visible to the naked eye, such cysts vary to y^th of an inch in diameter ; and, together with these, are cysts whose walls (though their contents are like those of the others) consist of a structureless hyaline membrane ; and these lie in a stroma which is equally simple, but seems to develope itself gradually into a fibrous structure circumscribing the cysts. Moreover, one finds, in the same specimens (as in the lower part of Fig. 50), structures of the most various dimensions, which, except in size, agree completely with the last-mentioned simple and structureless vesicles, and show every grade of size down to that which is just larger than a nucleus. The smallest of these contain a clear fluid, or are slightly granulated : in the larger there is a central nucleus, and to this are added a second, a third, and a fourth nucleus, and so on till there appear several, which fill up the commensurately enlarged vesicle (e, e, e, etc.) Now, in such a nucleus seems to lie the nucleus of the history of development of those autogenous cysts, not in the kidney alone, but in any part in which they may occur. A nucleus grows to be a cyst, whether a simple or barren one, or one that has an en- dogenous production of nuclei, or cells, or any other structures.' ' Thongh we have retained in the text Rokitansky's description of cjst-formation, by enlargement of the primary anatomical elements in the kidney, yet it is necessary GENEEAL HISTORY OF CYSTS. 397 Rokitansky has traced all the phases through which such cysts may pass. The simple cyst- wall is capable, not only of growing hut of acquiring the laminar and nucleated fibrous tissue which we find in its full estate ; acquiring these, we may presume, just as more normally, the simple nucleated membranous wall of a new bloodvessel acquires, as it grows, the textures that belong to its more perfect state. Such might be the least abnormal course of any cyst ; but from this it may deviate ■ — thickening, acquiring continually new layers, calcifying, and in other ways showing the signs of degeneration or disease. The contents, also, of the cyst may assume even yet more various forms : to narae only the extremes — tbey may retain the simple state of liquid ; or with liquid there may be a simple, or a specially secreting, epithelial layer ; or a series of successively enclosed nuclei or cells may be formed within that which first enlarges ; or the contents may acquire the structure of well-organised glands, or of cancer, or some other tissue ; and between these extremes, according to conditions which we have no power to trace or explain, they may pass in any of the manifold ways of wrong, the ends of which I shall have to describe. Important as this history of cysts may be in its direct bearings on their mode of development, yet this is not all that we m.ay observe in it. For I cannot but think we may discern in their history an image of the first form and early progress of many innocent solid tumours also. For, as the cyst is traced from the mere nucleus, onwards to its extreme size or complexity of structure or contents, so, it is very probable, from the numerous correspondences between them, that these solid tumours also have a similar beginning in some anatomical element, or tissue- germ ; or in some group of such germs, which, in their development, multiplication, and growth, may aggregate together, and then may appropriate, or exclude for absorption, the intervening substance. Thus, in the form of erring nuclei and cells, we may, I think, almost apprehend the structural origin of these cysts and sohd tumours. For it would be difficult to understand how the contents of certain that we should state that most of tha appearances may be equally well explained on the supposition that the urinifeious tubules "have become locally obstructed, and dilated into cysts, above or between the points of obstruction, as has been pointed out both by Dr. Gairdner and Dr. George John&x>n, and by Otto Beckman (Virchow's Arckiv, ix.). Similarly cystic disease in the thyroid gland, which was also regarded as due to expansion of the cells and nuclei, has been referred by Dr. Billroth (Miiller's Archiv, 1856, p. 144) to a constriction and subsequent dilatation of tubular structures, similar to those formed in the original development of the gland. 398 ORIGIN OF INNOCENT TUMOURS. cysts could be like to the secretions or structures of the glands in which they occur, unless they were produced by a transformation of some of the normal structures of the gland. The likeness also which commonly exists between a solid tumour and the tissue in which it is imbedded, is due to its descent by pro- liferation of nucleated corpuscles from the pre-existing cells and nuclei of the part ; though here, as in the case of the origin of new cell- forms in inflammatory products (pp. 232, 248), the corpuscles of the blood may wander possibly into the part, and participate in the formation of the tumour. When these anatomical elements are perverted from their normal course in the first beginning of a tumour, they multiply and grow, and whilst conforming generally with the part in minute structure and composition, yet they more and more widely deviate from it in shape and size. Thus fibrous tumours spring from periosteum and other forms of connective tissue ; adipose and fibro-cellular tumours arise in the subcutaneous or submucous areolar tissue ; cartilaginous, myeloid, and osseous tumours in connection with the bones ; glandular tumours with glands, etc. And as the connective and adipose tissues, bone and cartilage, have a close morphological relation to each other, we need not be surprised to find that tumours largely composed of adipose tissue, or in the construction of which bone and cartilage have an important share, are not unfrequently found developed in the con- nective tissue. Of all the tissues, indeed, the connective tissue, and its morpho- logical derivatives, are thoseinwhich the tendency to tumour-formation is most usually exhibited. When tumours form in the substance of muscles or of nerves, the new growths are usually in connection with the fibrous sheath, or with the septa, which lie between the fasciculi, and do not, as a rule, exhibit any important increase in the proportion of the proper muscular or nervous texture. Such are the facts, and such the speculations, that we may entertain respecting the origin, or, at least, the smallest visible beginning of a cyst or an innocent solid tumour. Need I add that if even this be true, we are yet far from the explanation of the cardinal point in the pa- thology of tumours — their continual growing ? Why should these detached tissue-germs, or any less minute and less isolated portion of an organ, grow, while all other germs and parts that are most like them remain unchanged ? I have already confessed my ignorance. I will endeavour now to illustrate the histories of particular forms of the simple or barren cysts. GASJiOUS CYSTS. 399 1. The first that may be enumerated are Gaseous Cysts. I know, indeed, concerning them only the specimens placed by Hunter in his Museum ; ' but these should be admired, or almost venerated ; for their histories include the honourable names of Hunter, of Jenner, and of Cavendish. Mr. Hunter says of them, — ' I have a piece of the intestine of a hog, which has a number of air-bladders in it.' . . . 'It was sent to me by my friend Mr. Jenner, surgeon at Berkley, who informed me that this appearance is found very frequently upon the intestines of hogs that are killed in the summer months.' . . . 'Mr. Cavendish was so kind as to examine a little of this air; and he found "it contained a little fixed air, and the remainder not at all inflammable, and almost completely phlogisticated." ' ^ What a relic have we here ! Surely, never, on an object so mean to common apprehensions, did such rays of intellectual light converge, as on these to which were addressed the frequent and inquiring obser- vations of Jenner, the keen analysis by Cavendish, and the vast com- parison and deep reflection of John Hunter ! Surely, never were the elements of an inductive process combined in such perfection ! Jenner to observe ; Cavendish to analyse ; Hunter to compare and to reflect. 2. The Serous Cysts, or Hygromata, are, of all the order, the most abundant. The term includes nearly all such as have thinly liquid, or honey-like contents, of yellow, brown, or other tint. Their most frequent seats are, by a hundredfold majority, in or near the secreting glands or membranes, or the so-called vascular glands ; but there is scarcely a part in which they may not be found. Their frequency in connection with secreting structures has led some to hold that they are all examples of perverted epithelial or gland-cells ; but their occurrence in such parts as bones, and in the connective tissue between deep- seated muscles and nerves, and in fibrous tumours, makes it sure that they may originate independently of gland-cells. ^ Of this numerous group of serous cysts, however, T will speak at present of only such as may best illustrate their general pathology, and are of most importance in surgical practice ; and I will, to these ' Museum of the Coll. of Surg., No. 153-4. ^ See Hunter's WorTcs, iv. p. 98, and Description of PI. xxxvii. ' Some very interesting specimens of serous cysts in bones are in the Museum of St. George's Hospital. They are described by Mr. Caesar Hawkins, in his Lectures on Tumours in the Medical Gazette, xxi. xxii. ; and in a Clinical Lecture in the same, XXV. p. 472. See also a remarkable case by Vanzetti, in Schuh {Psetido-plasmen, 175). 400 SEEOUS CYSTS. ends, refer cHefly to the cysts in the neck, the mammary gland, and the gums. Serous r.ysts in the neck form what have been called ' hydroceles of the neck,' and are well exemplified by a specimen in the Museum of the College.' This is a single oval cyst, with thin, flaccid, membra- nous walls, which even now, after shrinking, measures more than six inches in its chief diameter. It was successfully removed by Mr. Thomas Blizard from between the platysma and sfcemo-mastoid muscles ; and a part of it is said to have passed behind the clavicle. It was filled with a clear brownish fluid. Such cysts, but various in size and other characters, are more apt to occur in the neck than in any other part of the body. Many are single cysts like this ; but others are multiple, having many cavities, whether separate or communicating ; and in some cases very nume- rous cysts, even hundreds, are clustered in one comparatively firm mass. In situation, too, they are various. In some cases they lie in the front of the neck ; in others, at one or both sides : they may He by the lower jaw, over the parotid, by the clavicle, or anywhere or every- where in the mid-spaces, or they may extend from lower jaw to clavicle, and even pass across the middle line anteriorly to the opposite side. And in any of these situations they niay occur either in the subcuta- neous tissue, or they may be placed beneath the platysma and superficial layer of the cervical fascia, and may extend very deeply among the structures of the neck, and adhere to them so closely, and so thinly cover them, as scarcely to conceal them when laid open. Their date of origin is often obscure, in many, perhaps in the majority of cases, they are met with in young children, and are indeed congenital, and to this form the name ' hygroma colli cysticuna con- genitum ' has been given. But they may be first observed at any later period of life. Some years ago. Sir W". Lawrence removed a collection of four large cysts ' Mus. Coll. Surg. 1 16. ilany well-marked examples of the disease in all its forms are recorded by Dr. O'Beime {VvMin Jour, of Med. and C%em. iSc. vi. p. 834) ; Sir W. Lawrence (Med.-Chir. Trans, xvii. p. 44) ; Mr. Caesar Hawkins {Med.-Chir. Trans, xxii. p. 231) ; Mr. Liston {Practical Surgery, p. 330, ed. 1846) ; Wemher {Die angeborenen Cyden-Hygrome, Giessen, 1843) ; Von Ammon {Die angeborenen Chirurg. Krankheiten) ; Gurlt (Die Cynten GescJmuhte des Raises, Berlin, 1855); Storch {Journal fur Kinderkrank. 18fl); 3ir. T.Holmes {Lancet, 1864,1.); Mr. T. Smith {St. Bartlwl. Bqjorts, ii. p. 16). SEROUS CYSTS. 401 from over the parotid gland and mastoid region of a man, twenty- eight years old, who had observed their beginning only seven years previously. Three of these were iilled with serum, and one with pus. Of course, in snc a variety of forms, there must be more than one kind in the group of cysts that are thus, for mere convenience, placed together. The variety of origins, indeed, to which cysts in the neck may be traced, gives them peculiar interest in relation to the genera] pathology of cysts.' Some are evidently connected with the thyroid gland ; though, being developed singly, and growing to a very large size, their relation to it may be at length obscured, and they may appear during life quite isolated. A woman forty-eight years old was under Mr. Vincent's care in St. Bartholomew's Hospital, in July 1841, with a tumour in the front of her neck as large as the head of a child two years old. The tumour contained fluid, which was twice withdrawn with a trocar. At the first time the fluid looked like semm, but coagulated sponta- neonsly ; at the second, it was mixed with blood. After the second operation the cyst inflamed and discharged grumous and sanious pus ; but it also enlarged quickly, and the patient died unexpectedly, and rather suddenly, sufibcated. The preparation ^ displays a cyst occupy- ing nearly the whole right lobe of the thyroid gland : its walls are nearly two lines in thickness ; its cavity was full of lymph, pus, and blood ; and the sudden death was due to a discharge of a great part of its contents into the pharynx and larynx, through an ulcerated aperture into the former. A somewhat similar case as regards the place into which the cyst discharged its contents, thongh without fatal termination, has recently been recorded by Mr. Savory.^ Besides these cysts which lie within the thyroid gland, some that ' Some of the congenital cysts in the neck are not so simple in structure as the hygromata described in the text. Examples of these more complex forms are the cases described by Gilles {Be Hygromatis Ct/sticis Cmgenitis, Bonn, 1852), in which not only cysts, but adipose and fibrous tissues, bone, and in one case even a tooth, were developed. These growths are probably more of the nature of monstrosities by excess, and are allied to some form of those congenital cysts which are occasionally found connected with the sacrum and coccyx. For a, description of these coccygeal cysts, a lecture by Sir J. Y. Simpson (Med. Times and Gaz., July 2, 1859) ; an essay by Dr. Grlaser (Virchow's ArcMv, 1858) ; and the elaborate treatise. Die angeborenen Gesehwillste der Kreuz-beingegend, Leipzig, 1862, by Dr. Braune, may be consulted. 2 Museum of St. Bartholomew's Hospital, Series xxii. No. 16. 3 Lancet, November 24, 1866. D D 402 SEROUS CYSTS. lie near to it are very probably of tbe same nature ; cysts formed ia some outlying portion of the gland, snob as I referred to in the last lecture. But of tbis mode of origin we can scarcely have a proof wben the cyst is fully formed and largely grown. Other of these cysts in the neck appear to be transformations of vascular tumours — i.e. of erectile vascular growths or nrevi. I shall refer to this point again ; it is made probable by the close connection which some of these cysts have with large deep-seated veins ; by the occasional opening of bloodvessels into their cavities ; and by their sometimes distinctly forming portions of vascular nsevi. A girl, three and a half years old, was under Sir W. Lawrence's care, in 1849, in St. Bartholomew's Hospital, with a large soft and obscurely fluctuat- ing tumour covering the greater part of the left side of the neck, and the lower part of the cheek. Such a swelling had existed from birth, but it had of late enlarged very much. It was composed of a cluster of close-set cysts, containing spontaneously coagulable fluid ; but at its apper part a firmer portion of its mass consisted of a collection of tortuous and dilated bloodvessels like those of a nsevus. The exami- nation made of it by Mr. Coote,' after its removal, was such as to leave little doubt in his mind that it had origin in or with a nssvous growth ; and other cases to which I shall refer in speaking of erectile tumours, have confirmed this view, especially some of those which are published by Mr. Hawkins. But more commonly these cystic tumours have no connection either with the thyroid and other gland-structures in the neck, or with erectile vascular growths. They are seated in the connective tissue, either immediately subcutaneous, or in its deeper intermuscular por tions. At their first formation the cysts are too minute to be recognised by the naked eye, and perhaps arise from expansions of the corpuscular elements, or of the juice-canal system which permeates the connective tissue ; but as they grow, through increase in their fluid contents, they form distinct rounded spaces. With their further growth the inter- mediate membranous walls may atrophy, and the cavities of two or more cysts may intercommunicate, and the remains of their walls may present a trabecular appearance.^ Some cysts which form in the neck, more especially those which ' Lecture by Sir W. La-wrence, in the Medical Times, November 30, 1850. * Julius Arnold in Virehow's .drc^ii), xxsiii. ; and the specimen (2554, b) in the Anatomical Museum of the University of Edinburgh presented by Dr. Cappie, and dissected by Dr. Chiene {Edin. Med. Journal, March 1867). SEROUS CYSTS. 403 grow at or near the front of the larynx, possess fluid, contents of peculiar viscidity, ropy, or honey-like, and deriving a peculiar aspect from including abundant crystals of cholestearine. In the College Museum there is such a cyst,' attached to the hyoid bone of a sailor, who was between fifty and sixty years old, and in whom it had existed nearly as long as he could remember. It contained a brownish- yellow, grumous, honey -like fluid, with abundant crystals of choles- tearine. In 1849, Sir W. Lawrence had, at St. Bartholomew's Hospital, a patient, thirty-five years old, on the left side of whose neck, directly over and closely attached to the thyro-hyoid membrane, was a smooth oval tumour, abont an inch in length, which had slowly increased for five or six years ; but its bulk and deformity alone were inconvenient. He freely cut into it, and let out a thick honey-like fluid, in which large groups of crystals of cholestearine were visible even with the naked eye. The cyst, after the incision, suppurated, and then the wound healed, and the patient left the hospital quite well ; but I saw him some time after with an appearance as if some remains of the cyst were again filling. Gysts in or near the gums, and with contents like the last described, are not nncommon, lying usually behind the reflection of the muoons membrane from the gum to the cheek. Their occasional large size, and their thick tough walls obscuring the sense of fluctuation, may make them at first look formidable. A woman, thirty-eight years old, was under my care in 1849, in whom, at first sight, I could not but suppose something was distending the antrum, so closely was the deformity of the face due to such diseases imitated. But the swelling was soft and elastic, and projected the thin mucous membrane of the gum of the upper jaw, like a half-empty sac. I cut into the sac, and let out nearly an ounce of turbid brownish fluid, sparkling with crystals of cholestearine. The posterior wall of the cyst rested in a deep ex- cavation on the surface of the alveolar border of the upper jaw ; an adaptation of shape attained, I suppose, as the result of the long-con- tinned pressure of the cyst, which had existed six years. At nearly the same time a young man was under my care with a similar swelling of larger size, which he ascribed to an injury of the gum or alveolar border of the upper jaw only six months previously. ' Mua. Coll. Surg. 148. D D 3 404 SEROUS CYSTS. In neither of the cases coald I find any disease of the maxillary bone ; but it sometimes exists in intimate connection with these cysts, and som.etimes the fang or socket of the nearest tooth is diseased. I lately saw a lady in whom a small cyst of this kind had existed twenty-seven years, almost daily discharging and refilling. It had its origin in a blow, by which the two median npper incisors were loosened. One of them was again firmly fixed ; the other had remained slightly loose, and its crown was dark. Oysts in the mammary gland form a very important group. Every variety of them may be found here ; but I will speak at present of only the serous cysts. Some of these cysts are dilated ducts, or portions of ducts grown into the cyst-form. During lactation, cysts thus derived may be filled with milk, and may attain an enormous size, so as to hold, for example, a pint or more of mUk.' In other cases they may contain the remains of milk, as fatty matter, epithelial scales, etc. ; or they may be filled with transparent watery fluid, without coagnlable matter ; ^ but much more commonly they contain serous fluid, pure, or variously tinged with blood or its altered colouring matter, or various green, or brown, or nearly black fluids.' The complete proof of the origin of some, and probably the greater number, of these cysts as dilated portions of ducts is, that by pressure they may be emptied through the nipple, or that bristles may be passed into them from the orifices of tubes. But although these facts may be often observed, yet I agree with Mr. Birkett in thinking that others of the cysts in the mammary gland are formed in the man- ner of the renal cysts, to which, indeed, they present many points of resemblance. The most notable instances of mammary cysts are those in which the whole of the gland is found beset with them. This may occur while the proper substance of the gland appears quite healthy ; ^ but I think it is more commonly concuiTent with a contracted and partially indu- ' See a case by M. Jobert de Lamballe, in the Med. Times, Jan. 4, 11, 1846; and a collection of cases ley Mr. Birkett, in one of which ten pints of milk were evacuated {Diseases of the Breast, p. 201). ^ Brodie: Lectures on Pathology and Surgery, p. 155. ' Their various contents are well shown in Cooper's Illustrations of Diseases of the Breast, pi. i. ; and a fuU account of all the diseases of this class is given by Mr. Birkett in his work already cited. * Two such cases are described by Sir B. C. Brodie {Lectures on Pathology and Surgery, p. 139). SEROUS CYSTS. 405 rated state of the gland : a state wMcli, independent of the cysts, appears similar to cirrhosis of the liver, and has, I think, been named cirrhosis of the mammary gland. Its coincidence with cysts proves its nearer relation to that shrivelled and contracted state of the granu- lar kidney with which the renal cysts are so commonly connected ; or, when the cysts are formed by partial dilatation of the ducts, to the shrivelled, indurated state of the lung that may coincide with dilatation of the bronchi. The cysts in these cases are usually of small size, thin-walled, full of yellow, brown, green, and variously deep-coloured fluids : fluids that are usually turbid, various in tinge and density, but not usually much denser than serum. They do not lie in groups, but are scattei'ed through, it may be, the whole exteilt of the gland ; and their walls, though thin, are tough and tense, and very closely adherent to the surrounding gland-substance. Similar Small cysts are sometimes found in connection with hard cancer of the breast ; and in this case they have been called by Mr. Hunter and others ' cancerous hydatids,' but their proper relation in such cases appears to be, not with the cancer but with the coincidently shrivelled gland. And it is an accidental co- incidence of a, cyst with scirrhous cancer, that gives rise to the dis- charge of bloody, or other fluid, from the nipple, which has been thought a sign of cancer. Where no such cyst is involved in the can- cer, no discharge from the nipple is observed. In this disease of the mammary gland there is no reason to believe a malignant nature, ihough the coincidence with calncer appears not rare. Yet the diagnosis between it and cancer is rfot stltvays clear, and many breasts have been removed in this uncertainty. I once saw such a case, and it ended fatally. A woman, fifty years old, had, in her left breast, just below the surface of the mammary gland, a small, smooth, oval, and movable tumour. It felt firm, but not hard ; but, external to it, in a line extending towards the axilla, were two Or three small round ' knots,' scarcely so large as peas, and quite hard. In the axilla was an enlarged gland. The breast was soft, flaccid, and pendulous. The tumour vras sometimes painful, and a serous and bloody fluid often flowed from the nipple. The patient's youngest child was sixteen years old,, and the tumour had been noticed six months, having arisen with- out evident cause. There was doubt enough about the diagnosis of this case to suggest that the tumour should first be cut into. An in- cision exposed the cavity of a cyst full of dark, turbid, greenish fluid, and near it many more cysts. Similar cysts pervaded the Ivhole extent 406 SEROUS CYSTS. of the gland, and the whole breast was therefore removed. Many of the cysts coram tinicated with lactiferous tubes, from which bristles could be passed through the nipple.' In this case one comparatively large cyst existed, with many of much smaller size. Usually, indeed, one cyst has a great predominance over others, or even exists alone. Sometimes, in such instances, the removal or laying open of one large cyst has been sufficient ; but in other cases, smaller cysts neglected have enlarged, and the disease has appeared to recur. ^ The single cysts of the mammary gland may become enormous. I know not what boundary may be set to their possible size ; but I find one case in which nine pounds of limpid ' serosity ' were produced in three months in the breast of a woman thirty years old.' In this case the walls of the cyst were thin, a,nd the fluid serous ; and the fact illustrates a general rule, that the cysts which contain the simplest fluids, and which have the simplest walls, are apt to grow to the largest size : thickening of cyst- walls, and, much more, their calcification,^ are here, as elsewhere, signs of degeneracy, and of loss of productive power. It would appear as if any cyst of the mammary gland might, after some time of existence in the barreb state, become prolific, and bear on its inner surface grovrths of glandular or other tissue. But of these proliferous cysts I will speak in the next lecture.* 3. Of Stnovial Cists I need say very little. Under the name may be included all the abnormal burssB, dropsies of the synovial sheaths, or ganglions, as they ate called. In these, again, three methods of for- mation probably obtain. Some, of which the best example is the dis- 1 In the Iduseilm of the Middlesex Hospital is a breast from a. woman in whom both mammary glands were thus diseased. In the College iluseum, Nob. 151 and 152 best illustrate the disease; ' Sir B. C. Brodie, loc. cit. p. 146, note. ' Case by M. Marini, cited by M. B6rard, Diagnostic IKfferentiel des Tumeurs du Sein, p. 86. * For a case in which the walls of a cyst in the breast were calcified, and crackled like those of ossified arteries, When pressed, see Berard, loc. cit. p. 56. ' Having in view only the illustration of the more general pathology of these cysts, I have not referred to more special instances of them. Examples' enough are to be found in all the works here quoted. Neither have I mentioned any analysis of the contents of serous fiysts ; for few have been made, and these few were made on such various materials, that no general account of them can be rendered. Several are cited in Simon's Medical Chemistry; and in Frerichs' TIeber GalUrt-oier CoUoidgesclMillste, pp. 7-9, etc.; and by Virchow, in the Verhandhmgen der med.-i:hijs. Muller's Archw, 1850, p. 207. 2 Die Diagnose der Bbsartigen Geschwi'dste, p-p. 185, 191. 430 VARIOUS PEOLIFEROUS CYSTS. opening, suggesting that it may haTe had its origin in a cystic mnoous or sebaceoTis gland.' In the College Museum, No. 167, is a thick- walled cyst, from the cheek of an old woman, which contains two large lobed, and pedunculated masses, so like some of those found in the mammary cysts that we can hardly doubt their glandular nature. All these specimens, however, need more minute examination ; at present they only make it probable that any cyst originating in or near a secreting gland may be the parent, or the habitation, of an endogenous glandular growth. To this account of glanduliferous cysts it must be added, that their characters may be closely imitated by cysts formed in parts altogether unconnected with secreting glands. It is not, indeed, probable that the contained growths in such cysts are glandular ; yet they present characters like the softer growths that are found in the mammary cysts. I found one of these proliferous cysts beneath the gracilis and ad- ductor longus muscles of a woman twenty-five years old. It was a large spheroidal mass, which felt as if held down tightly on the front of the pelvis, and had pushed the femoral vessels a little outwards. It lay too deep to form a clear diagnosis of its nature ; it was assigned to no distinct cause ; it had been noticed for only seven months, but when first seen was ' as large as a tea-cup.' I removed it witliout much difficulty ; for it was not closely adherent to the parts, except to a small portion of the front of the pubes, where it rested on the adductor brevis. The patient has since remained well for more than seven years. The tumour was spheroidal, about four inches in diameter, and con- sisted chiefly of cysts, from two of which six or eight ounces of turbid serous fluid escaped when they were cut across. One of these cysts was thickly lined with pale, brownish, fibrinous substance, like that which one finds in old hsematoceles ; and this appeared as fibrine on minute examination. Another was nearly filled with a ruddy mass, in most parts soft and succulent, like blood-stained gelatine. Iiluch of this mass was also hke fibrine-clot,^ith^abundant corpuscles ; but the ' See also an account of a specimen in the same Museum, by Mr. Hawkins : Medical Gazette, xxi. p. 951 ; and Proe. of Pathol. Soc. ii. p. 340. I suppose there is some relation between these and the subcutaneous warts and condylomata described by Hauck and Kramer ; but X have not seen what they refer to. (See Simon : HauthtniJcheiten, p. 22o.) VARIOUS PROLIFEROUS CYSTS. 431 layers of it next the cyst- walls were firmer tlian the central parts, and contained all the forms that one finds in common granulations develop- ing into connective tissue. The microscopic likeness to granulations was, in these parts, exact. The rest of the tumour, including some large portions between the cysts, consisted of connective tissue more or less perfectly developed.' A similar tumour was removed by Sir W. Lawrence from the exactly corresponding part of a woman fifty years old, in whom it had grown slowly, and without pain, for nine or ten years. It gave the sensation of a firm fatty tumour, as large as an egg, but when removed was found to be a bilocular cyst. Each cavity contained, together with serous fluid, a soft, reddish, gelatinous-looking mass, like a polypus in one, and solid and folded in the other. The cyst-walls were tough, pure white, formed of connective tissue, and polished on their inner surface. The intra-cystic growths consisted of a structureless, or dimly granular, or fibrillatiag blastema, with abundant oily molecules, granule- cells, and corpuscles, like nuclei, imbedded in it. And to these two instances, since the disease seems very rare, I may add a third. A girl, twenty-three years old, under the care of Sir W. Lawrence, had a pyriform pendulous tumour in her neck, about 2j inches long. Its surface was ulcerated, Jivid, and painful, and bled occasionally. Its history was doubtful ; but it had existed for at least a year. On removal, it appeared to have grown in the subcutaneous tissue, and to be composed of a collection of cysts closely and irregularly packed, and, for the most part, filled with lobed, soft, cauliflower-like growths from parts of their walls. It closely resembled, in its general aspect, the collections of prolifeTOUs cysts, with soft iutra-cystic growths in the mammary gland. In microscopic structure the intra-cystic growths appeared composed entirely of corpuscles, like those of lymph or granulations ; but my record of the examination, made several years ago, is too incomplete for a clear account of them. I believe that all the cysts that I spoke of, before these that contain vascular growths, may be regarded as completely void of the characters of malignant disease ; at least I have met with no evidence contrary to this statement, except in certain cases of proliferous ovarian cysts, to which I shall presently refer. And, in general, the reputation of inno- cency is deserved by the glanduliferous cysts also. Yet there are many cases which show that such tumours may have any exceeding tendency ' The tumour is in the Miiseum of St. BartholomeVs Hospital. 432 EECUREIifG PEOLIFEEOUS CYSTS. to recnr after removal ; and when a mammary proliferous cystic tnmonr lias soft and succulent, or gelatine-like growths, or cyst-walls, it may be always expected to prove recnrrent (see Lectnre xxix.). A healthy robust woman, thirty-seven years old, was under Sir W. Lawrence's care with a very large protruding tumour in her right breast. This had been slowly increasing for ten years, but, till lately, had given little uneasiness, except by its bulk, and had not hindered her nursing. The greater part of the breast and the tumour were removed in 1844. It weighed 7^ pounds, and was a well-marked example of that form of 'sero-cystic sarcoma,' in which the cyst-walls, as if altered by inflam- mation, or imperfectly formed, are soft, succulent, and glistening, with solid growths of similar substance, lobed and fissured. Many cysts in it still contained serous fluid. Its appearance when recent, and even now as preserved,' leaves no room for doubt as to its nature. The patient remained well for fifteen months ; then a tumour be- gan to grow under the scar, and quickly increased. After nine months' growth. Sir W. Lawrence removed this also, with all the surrounding tissues. It was a pale, pinkish, and yellowish mass, like soft size or jelly. It was lobed and folded, and included some irregular spaces, containing a fluid like mucus, or half-melted jelly. It was like the solid parts of the tumour last removed, and consisted of a pellucid dimly fibrillated blastema or basis-snbstance, in which were imbedded nuclei and abundant granule-cells, of various forms. The sketches and account of these, which I drew at the time, make me stiU snre that they had none of the characters of cancer-cells, but were like nuclei of ordinary form, or elongated, many of which were changed by fatty or granular degeneration. After this second operation, the patient remained well for seven months, and fully regained her stout robust appearance. But now a third tumour appeared ; a fourth soon after ; and both grew rapidly, till, after two months. Sir W. Lawrence removed them, and all the parts bounding them. They were, in every respect, exactly Kke those removed in the last operation, and near them lay another not discerned before the removal. Erysipelas following this operation proved fatal, and no post-mortem examination could be obtained. Now in the first of these operations some portion of the mammary gland was left. It is possible that some cysts already existed in this portion, and were subsequently developed into the second tumour, ' In the Museum of St. JBartholomew's, Series xxxiv. Nos. 19 and 20. EECUBEING PEOLIPEROTJS CYSTS. 433 which, therefore, might not deserve to be called a recurring tumoar, although, indeed, it appeared under the scar of the former operation, and not in the place where gland- substance was left. But, after the second operation, there is little probability that any gland remained ; and we may, with as little doubt, regard the third tumour as an in- stance of recarrence or repetition ; i.e. of reappearance of the disease in an entirely new growth. Sir B. C. Brodie' has related two cases of single recurrence of tumours very closely resembling that just now described ; and the lia- bility to recurrence which Sir W. Lawrence's case presented is sur- passed by one recorded by M. Lesauvages,^ whose description of the tumours he removed accords so closely with what was observed in the foregoing case, and in three similar cases which have been under my care, that I can have very little doubt they were of the same nature. The patient was sixty-three years old. The first tumour of the breast, which was of great size, was removed in February 1832 ; a second ap- peared, and was removed before the healing of the first wound ; a third in May ; a fourth in September of the same year ; a fifth sprang up, and was removed in February 1833 ; a sizth in May ; in a seventh operation, in June of the same year, three tumours were removed ; but from the same spot two more arose, and these grew rapidly, and the patient died. Now if, as I believe, all these cases, and others that 1 have seen, were examples of the proliferous cystic disease of the breast, they prove such an inveterate tendency to recurrence in this disease, as is scarcely surpassed by any even of the well-marked malignant tumours. Unfor- tunately, no examination of any of the cases was made after death ; so that it is not possible to say whether the more characteristic features of malignant disease existed, such as the concurrence of similar disease in internal organs. The same defect does not exist in a most remark- able case related by Dr. Cooke.^ The patient was about forty years old when, in April 1847, six ounces of a glairy brown fluid were drawn from a cyst in her breast, which formed part of a large tumour that had been growing for seven months, and felt in some parts firm, in others soft and fluctuating. Occasional tappings were subsequently employed but after five or six weeks the integuments inflamed and sloughed over the cyst, and a profuse discharge of similar glary fluid ensued. > Lectures 071 Pathology and Surgery, p. 145. 2 Archives Gm. de Medecine, Fevrier 1844, p. 186. ' Medical Times and Gazette, August 7, 1852. 434 CUTANEOUS PROLIFEROUS CYSTS. ' Fangoid masses ' soon protruded, and in July 1847 Dr. Cooke removed the whole disease. It weighed 3J pounds, and consisted of fungoid masses of various degrees of firmness, with a central cavity lined by a vascnlar membrane. In December of the same year a small enlarge- ment on the scar was removed. In March and in October of the next year (1848) renewed growths were again removed. In 1849 the dis- ease again returned, and was extirpated in June 1850. This was ' a nainiatnre representation of the tumour removed at first ; ' and it was examined by Mr. Birkett, who reported of it, that, ' in a stroma of fibrous tissue cysts appeared, containing a yellow tenacious fluid. The follicular terminations of ducts of glands and nucleated corpuscles were very distinctly seen in the fibrous tissue ; within these follicles were clearly seen the elements of the epithelium of glands.' The patient re- covered rapidly from this last operation, and no recurrence of the dis- ease in the breast again ensued ; but in June 1851 she began to suffer with what proved to be cancer of the peritoneum, liver, pleura, pelvic organs, and lumbar and thoracic lymphatic glands. When she died, in November 1851, abundant cancerous disease was found in all these parts ; but the seat of former disease in the breast was healthy, and, as Mr. Birkett especially remarks, all the lymphatic glands connected with the breast were, as they always had been, nnafiected, while all those connected with the cancerous parts in the pelvis and elsewhere were the seats of cancer. The fact last mentioned makes it improbable that the cancerous disease with which this patient died was continuous with, or a part of, the disease which had been manifested in the breast. Rather, we may believe that the two affections were essentially distinct, and that the first was, like the others I have related, an example of recurring pro- liferous cystic disease. It may be inserted here, that the mode of growth observed in the glandular proliferous cysts may be imitated by genuine cancerous diseases. Cancerous growths may be found in cysts under at least two condi- tions ; namely, in cj-sts that of themselves appear innocent, and in cysts produced within cancers. Of the former mode of growth we have the examples in ovarian cysts, to which I just referred ; and herein are perhaps the only un- exceptionable instances of the transformation of an innocent iuto a malignant tumour. The second mode of production of intra-cystic cancers is best CUTANEOUS CYSTS. 435 shown in some examples of medullary tumours of the testicle. In these' we may see a repetition, so far as the plan is concerned, of the intra-cystic production of thyroid gland substance. The great mass of the medullary disease includes smaller masses, incapsuled with connec- tive tissue, and commonly presenting a lobed and laminated form, at once reminding us of the intra-cystic glandular growths, and justifying the application to them of the principles of Dr. Hodgkin's theory of the growth of cancers. In these medullary testicles the intra-cystic medullary growths have usually filled the cysts and coalesced with their walls. In rare cases one can discern how the growths spring up as spheroidal, or as pedunculated, branching, and grouped processes from the interior of the cysts. This condition was peculiarly well shown in a case of cancer of the clitoris, in which the whole of that organ was occupied or concealed by a cancerous mass inclosing several distinctly walled cysts, which were half filled with small, soft, and lobed cancer- ous intra-cystic growths. 2. I proceed to the consideration of the cutaneous proliferous cysts ; i.e. of cysts within which, in the typical examples, a tissue grows, having more or less the structure and the productive properties of the skin. Instances of these in a perfect or typical state are rare. In the large majority of cases the cutaneous structure, if it were ever present, has degenerated Or disappeared ; and we recognise the relations and import of the cysts only through their containing epidermal and seba- ceous materials, of which the natural production is a peculiar attribute of the tissues of ^he skin. Among the parts in which these skin-bearing cysts may be found are some that have no natui-al connection with the skin. (1.) They are frequent in the ovaries ; one or more Graafian vesicles enlarge and grow, and then produce in their interior a growth of skin, with its layer of cutis, subcutaneous fat, epidermis, and all the minute appended organs of the proper hairy integument of the body. The general likeness of the interior of these cysts to ordinary skin had been often noticed ; but the first minute demonstration of it was by Kohl- rausch ^ whose observations have been fully confirmed by others as well > As in Mu3. Coll. Surg. No. 2396. ' MuUer's Archiv, 1843, p. 365. A careful descrirtion of the structure of these skin-bearing cysts in the ovary, by Dr. Steinlein, may be found in the Zeitsch.f. Eat. F F 2 436 CUTANEOUS CYSTS. as by myself. Among the specimens in the College Museum, one (No. 164 a) presents all the textures of a hairy piece of skin growing on the interior of one of the cavities of a large mnltilocular ovarian cyst. Of the other divisions of the same cyst, some contained fatty matter and loose hair ; others, various fluids ; others, secondary and tertiary cysts. Another specimen in the College Museum (No. 2624) shows very well the origin of these skin-bearing cysts. It is an ovary, with a cyst, the small size of which, as well as the structure of its walls, and the mode in which they are connected with the surrounding substance of the ovary, leave no doubt that it is a simply enlarged Graafian ves- icle. Tet it contains some hairs, and a small mass of fat, resembling the subcutaneous fat, with its tough connective- tissue partitions. (2.) Cutaneous proliferous cysts may form in the subcutaneous tis- sue. They are, indeed, rare in this tissue in naan, except in cases of congenital growths. In the little cysts about the brow, or in or near the orbit, the inner surface is often perfectly cutaneous ; and Lebert ' has detected in such cysts all the minute structures and organs of the skin.^ Most of these cysts are first observed at or soon after birth. Some similar specimens of cysts lined with skin are in the Museum of the College.' These were taken from the subcutaneous tissue of a cow and of an ox : and, in some of them, the inner surface of the cyst could hardly be distinguished from the outer hairy integument of the animal. ■* (3.) Besides these, the common seats of cutaneous cysts, perhaps any part or organ may, in rare instances, present them ; for the records of surgery and pathology furnish abundant instances of aberrant cysts containing hair and fatty matter, such as we must class with these in which the cutaneous structure and products are more perfect. The most siugular and frequent of these rarer examples are in the testicle,^ Md., ix. p. 146. Dr. C. G-. Eitchie has also described a case in his Contributions to Ovarian Physiology and Pathology ; London, 1865. ' Abhandlimgen, p. 99, et. sej. The structure is well shown in 'So. 158 in the College Muieum. ^ Mr. H. Walton, in his ' Eemarts on Tarsal Tumoiu's ' {Med.-Ohir. Trans, xxxvii. p. 7, 1854), suggests that the name of Meibomian cysts should be given to the so-called tarsal tumours. He considers them to be dilated and grown IMeibomian glands, with cuticular, or sebaceous, or degenerate, or puriform contents, and sometimes with vascularised and perhaps glandular intra-cystie growths. ' Nos. 161, 163, etc. * In Mus. St. Bar. (Series xxr. 62) is a specimen of a cutaneous cyst, containing hair, obtained from the scalp. See Med. Times and Ga=., Dec. 16, 1853. * See Prof. Goodsir, in Northern Journal of Medicine, June, 1845; and Anatomical Memoirs, ii. p. 506. SEBACEOUS CYSTS. 437 the lung,' tlie kidney,^ the bladder,''' and under the tongue,* and with- in the skull or brain. Those in the brain are of chief interest. I found cue ' many years ago in an elderly man. While he was in St. Bar- tholomew's Hospital with an ulcerated leg, he suddenly died ; and the only probable cause of death appeared to be a mass of granular fatty matter mixed with short stiff hairs, which lay in the tissue of the pia mater under the cerebellum. A yet more remarkable cyst from a child two and a half years old, in whom it appeared to have been congenital, is in the Museum of St. George's Hospital, in Mr. Osesar Hawkins' collection. It was situated within the layers of the dura mater, close to the junction of the superior longitudinal sinus with the torcular Herophili. Its contents were pearly, and consisted of epithelial cells, in the midst of which a lock of hair, curled up and about one inch in length, was found. A foramen in the supra-spinous part of the occipital bone opened into a depression on the inner surface of the bone in which the cyst was lodged. This case has been fully described by Dr. John W. Ogle.^ A case of a closely similar character, met with in a child set. twenty-three months, but in which there was no defect in the ossifica- tion of the occipital bone, has been described by Professor Turner.' (4.) It is perhaps only during the vigour of the formative forces in the foetal or earliest extra-uterine periods of life, that cysts thus highly organised and productive are ever formed. In later life imperfect imi- tations occur, which may be classed with the proliferous cysts, and are named sebaceous, epidermal, or cuticular cysts — the proper atheroma of Virchow and other German pathologists— or a iven as each cyst is popu- larly termed. We cannot tell, in any advanced case of such a cyst, whether the more complicated structures of the skin ever existed ; if they did, they have degenerated before the cyst became of distinct size ; yet the retained likeness is sometimes shown in the fact that, when such cysts are laid open to the air, they do not granulate, but assume ' Kolliker, in the Zeitschriftfiir imssensoh. Zooloc/ie, ii. p. 281 . Cloetta in Virchow's Archiv, xx. p. 42, 1860. ' Mus. Coll. Surg. 1904. -'• Mus. CoU. Surg. 2626. ♦ Schuh, Psetidoplasmen, T). 154; and Mus. St. Bartholomew's, Series xxxv. No. 25. Hutchinson, Med. Times and Gaa., Dee. 31, 1853, ' Mus. St. Bartholomew's, Series -fi. 56. ° Trans. Path. Soc. vi. p. 12 ; and British and Foreign Med. Chir. Bev. 1865. ' St. Bartholomew's Hospital Reports, p. 62, 1866. The preparation is No. 2549 A, Edinburgh University Anatomical Museum. 438 SEBACEOUS CYSTS. for their internal surfaces the characters of the adjacent and now con- tinuous skin.' Of these sebaceous or epidermal cysts, it is interesting to notice the frequent hereditary origin. Perhaps, in the majority of cases, the bearers of these have known one or more members of their family similarly endowed. They are certainly more commonly hereditary than are any forms of cancer. I have already referred to the double mode of origin of the epider- mal cysts. Sir Astley Cooper first observed that some among them could be emptied by pressing their contents through a small aperture in the cutis over them, and hence concluded that they are all examples of hair-follicles distended with their secretions, and overgrown. This is probably true of the cysts on the face, trunk and limbs, in a great majority of which the external aperture may be found, but in those on the scalp such an aperture is rarely if ever seen, and the greater part are closed on all sides alike, and are apparently new formations.^ I suspect that those cases are equally or more rare, of which Lebert and Bruns have described instances,* characterised by the existence of a slender cord, traceable from the cyst to the skin, and formed of the obliterated duct of the enlarged and obstructed hair-follicles. The characters of these epidermal cysts may be extremely various, in regard not only to their walls, but to their contents. Their walls may be thin, pliant, and with delicate connective tissue ; or laminated, thick, and hard, with tough fibrous tissue ; or they may be calcified ; and I believe a general rule may be connected with the differences in ' See Home, Hunter's Works, iii. p. 635 ; and a remarkable case ty Mr. Green, in the Medical Gazette, ii. p. 346. ' Mr. South especially notices this in his edition of Chelius's Surgery, ii. p. 698. See also Walther, in VogeVs Pathol. Anat, p. 224. Professor Porta, in an essay devoted to the consideration of follicular sebaceous tumours {Dei Tumori Folluiulari Sebacei, Milano, 1856), supplies some statistical information respecting the frequency of occurrence of the different kinds of cysts. He has met with 384 specimens ; 23 patients, having from 2 to 20 cysts each, supplied 72 of the specimens. Of the 384 cysts, 270 were on the head and face, 11 4 on other parts of the body, 257 were subcutaneous ; 127 (including 37 encysted hydroceles) were deepseated, 41 were congenital, the others originated at various times of life, and had various progress. Of the 384 cases, 238 were examples of cutaneous cysts of new formation, 78 (including those of encysted hydroceles) were cases of hygroma, 15 were hsematoid or sanguineous cysts, 9 calcareous cysts, 4 echinococcus cysts, 14 suppurated cysts, and 26 were such sebaceous follicular cysts as he has made the chief subject of his essay. Of these last named he describes cases of a kind of cutaneous tumour of the face, composed chiefly of numerous hair- follicles, or sebaceous glands, arranged in groups and all moderately enlarged (see his PI. iii.) ' Virchow's Archiv, viii. H. ii. p. 222. SEBACEOUS CYSTS. 439 these, as in other cysts, namely, that the thin- walled arc the most pro- ductive, grow most rapidly, and are the seats of most active change. Wernher has described' in many of these cysts an inner wall, imbedded in the substance of which, especially when thick and nodular, are collec- tions of laminated epidermal capsules, and in some instances all the other usual contents of epidermal cysts. Iii the later stages of the growth the capsules may become enclosed in thin cysts, which may afterwards split, and gradually discharge their contents into the main cyst-cavity, in which case they are found as heaps of epidermal struc- ture set on the surface of the outermost layer of the epidermal contents of the main cyst. When thus emptied, the inner surface of the inner layer of the cyst- wall has cavities or reticulated depressions, corres- ponding to the emptied-out collections of epidermal structures. It may be, however, a question whether the interpretations put by Wern- her on these collections of epidermal structures within the innermost layer of the cyst- wall — viz. that they are first formed, and subsequently encysted — is the correct one. It is more probable that they are abor- tive or imperfect follicular structures, representing the completely- formed follicles, glands, etc., of the best and most perfect cutaneous cysts. Among the contents of these cysts we may observe extreme varie- ties. The chief alone need be referred to. And 1st, we find successive productions of epidermis, formed in layers on the inner wall of the cyst, and thence successively shed, and pushed inwards towards its centre. A section of such cysts (which were particularly described by Sir Everard Home from the Hunterian specimens) presents layers of white soft epidermis, like macerated epidermis of the heel or palm. The external layers are commonly quite regular, white, and flaky ; but the internal are more disorderly, as if degenerate, broken-up, or liquefied, and mingled with less organ- ised productions. 2ndly. A peculiar appearance is given to contents like these, where, among the layers of epidermal scales, abundant crystals of cholestea- rine are mingled. They hence derive an appearance like that of the masses to which Miiller' has given the name of Cholesteatoma, or lami- nated fatty tumour, ; and, indeed, the few well-marked examples of this disease which I have been able to examine, as well as Miiller's own account, make me think that what he named cholesteatoma is only a ' Virchow's Archiv, viii. p. 221, ^ On Cancer, p. 155. 440 SEBACEOUS CYSTS. combination of layers of epidermal scales with crystals or choles- tearine.' The appearance produced by such a combination is quite peculiar. It forms nodular masses of soft and brittle substance, like wax or spermaceti, the surfaces of which are bright and glistening, like mother- of-pearl, whence Virchow has called it ' pearly tumour ;' while their sections are finely laminated. It is a rare disease ; the most frequent seats of well-marked specimens appearing to be in ovarian cysts, and sometimes in cystic tumours in the testicle,^ or in the scalp. ^ The characters are well shown in the contents of a small ovarian cyst in St. Bartholomew's Hospital. Striking examples are figured by Oru- veilhier ■* but the want of microscopic examination leaves their consti- tution uncertain. 3rdly. In the opposite extreme to these cysts, in which the cuticular product is most perfect, we find an innumerable variety of contents, of bufiF, and ochre-yellow, and brownish materials, that seem to consist mainly of degenerate cuticle mingled with sebaceous secretions. The microscope finds in them a confused mass of withered scales, granular fatty matter, clustered and floating free, cholestearine-crystals, and earthy matter in free molecules, or enclosed within the cells or scales. And all these may be fioating in a turbid liquid, or retained in some soft tenacious mass, or clustered in hard nodular and pointed masses, projecting like stalactites from the old cyst- walls f and sometimes the fatty contents may have such a honey-like consistency as to deserve the name of meliceris. One more phase pf this disease deserves especial notice — that in which the cyst ulcerates, and its contents protrude. An inflammation in or about the sac often appears the inducement to this change ; and sometimes the inflammation itself can be traced to nothing but dis- turbance of the general health. The probability that it may thus arise makes the caution very valuable which Dr. Humphrey^ gives concern- ing the removal of all tumours. 'It is always well' (he says) 'to bear in ' See also an account of such a case by Mr. W. Adams, in Proc. of Fathol. Soc. 1850-1. Other writers since Miiller have applied the name of cholesteatoma more vaguely. ' VirchoVs Archiv, \in. p. 371. ' Volkmann, in VirchoVs Archiv, xiii. p. 46, 1858. * Anatomie Pathol., ii. p. 6. " College Museum, 157 A and 2297. A most remarkable specimen is in the Museum of Guy's Hospital, which was removed from an old man's thigh. " 'Lectures on Surgery,' p. 135; from the Provincial Medical and Surgical Journal. SEBACEOUS CYSTS. 441 mmd that persons are most likely to consult us respecting these, or other growths of the like kind, when they are out of health, and conse- quently unfit to bear an operation ; they do so because the tumour is then most productive of pain and annoyance.' A distressing instance of the truth of this occurred to myself seve- ral years ago. A strong but very intemperate man came to me as an out-patient, with an ulcerated sebaceous cyst, about three-quarters of an inch in diameter, just below and to the right of the umbilicus. Pie had observed a tumour here for sixteen years ; but he had scarcely thought of it till, five weeks before I saw him, it had grown quickly, and in the last fortnight had ulcerated. I saw no reason to be very cautious in such a case ; so slit the tumour and removed it, as well as the thickening and adhesion of the parts around would allow. In the evening, having returned to his work and some intemperance, hsemor- rhage ensued from a small cutaneous vessel, and before he reached the hospital he lost more than a pint of blood. I tied the artery, and applied solution of alum to the rest of the wound, for its whole surface was oozing blood, and he was admitted into the hospital. The next day he became very feverish, and he appeared as if he were going to have typhus, which was then prevalent. But from this state he par- tially recovered ; and then abscesses formed in his groins, and dis- charged profusely. Nothing improved his health, and three months after the operation he died, apparently exhausted by the continual discharge from the abscesses, and with both external epigastric veins and parts of the femoral veins full of old clotted blood — the consequence of slow phlebitis. Cases like this, or ending fatally much sooner than this did, with erysipelas or more acute phlebitis, have occurred to many surgeons. They need no comment to make them instructive. I beheve the contents thus protruded from cutaneous cysts may become vascular. I have not seen this event, but it seems certain in a case observed by Mr. James Reid. A woman, eighty years old, had numerous cysts in her scalp. They were like common sebaceous cysts ; and three of her daughters had cysts like them. Two years and a half before her death, one of the cysts, which had not previously appeared different from the rest, inflamed. It was opened, and sebace- ous matter was discharged from it. The opening did not heal, but ulcerated, and a small hard lump remained under the ulcer for a year, when, after erysipelas of the head, it begaa to grow, and rather quickly increased to a mass nearly five inches in diameter, which occasionally 442 DENTIGEKOUS CYSTS. bled profusely. The mass has the appearance of the firm contents of a cuticular and sebaceous cyst, and contains abundant epidermal cells ;' so that there can be scarcely a doubt that it had its origin, in the con- tents of such a cyst. Recently MM. Guyon and Thierry ^ have described epidermic cysts forming in connection with the mucous membrane of the palate and gums of young children, in the interior of which an abundant laminated epithelium was found. Sebaceous cysts sometimes form in the external auditory meatus, or even in the tympanum. They appear, as Mr. Toynbee has shown,^ to have the peculiarity of growing inwards rather than towards the surface ; when in the meatus, they cause, by their continued pressure, absorption of the petrous bone ; but when in the tympanic cavity, the effect is to induce caries of the bone, and even to give rise to fatal cerebral symptoms, unless they are remedied by removal through an opening in the tympanic membrane, after the manner practised by Mr. Hinton. 3. Concerning cysts containing teeth, a few words must suffice. They are of two kinds. Some, occurring in the ovaries, and more rarely in other parts, bear, with one or more teeth, the products of skin, as hair, epidermis, etc.* These may be regarded as diseases of the same general group with the cutaneous proliferous cysts ; and the great formative power which they manifest is consistent with their occurring only in embryonic or foetal life, and in the ovaries, in which, even independently of impregnation, one discovers so many signs of great capacity of development. Other dentigerous cysts occur within the jaws. In some cases cysts are hollowed out in the substance of the upper or lower jaw, and are lined with a distinct membrane, to some part of which a tooth is ' Museum of St. Bartholomew's Hospital, Series xxxv. No. 57. Probably the case ■was similar which is related by Mr. Abemethy in his Essay on Tumours, p. 117- Such cases have peculiar interest in relation to the question of the possible origin of certain epithelial cancers in these cysts. This will be referred to in Lecture xxxii. 2 Archives de Physiologie,-^. 5Z(); 1869. ' Med.-CUr. Trans., 1864. * A very remarkable specimen is in the Museum of St. Bartholomew's Hospital (Malformations, A 177). It was presented by Mr. Kingdon, and is described by Dr. Gordon in the MeA, Chir. Trans, xiii. In the anterior mediastinum of a woman twenty-one years old, a tumour, probably of congenital origin, contained portions of skin and fat, serous fluid, and sebaceous matter, and two pieces of bone, like parts of upper jaws, in which seven well-formed teeth were imbedded. In an ovarian tumour, more than 300 teeth were once found ; in another ease, a piece of bone, like part of an upper jaw, with 44 teeth. See Lang, in the essay cited below, p. 11. DENTiaEROTTS CYSTS. 443 attached. I believe these are examples of tooth-capsules, from which the teeth, though perfectly formed, at least in their crowns, are not ex- truded, and which therefore remain, becoming filled with fluid, and growing larger.^ In other cases, that which appears as a cyst is the antrum, distended with fluid, and having a tooth imbedded in some part of its wall, and projecting into its cavity.^ In the most remark- able case of the kind. Professor Baum removed a tooth from each antrum of a woman thirty-eight years old. The distension of the antra, with excessive thickening of their lining membranes, and thinning of their osseous walls, and with accumulations of purulent fluid, had been in progress for thirty years, and produced horrible deformity of the face. The operation was completely curative. ' Two such cases are in the Museum of St. Bartholomew's, Series i. 119, 119 A. I saw a third cured by Mr. Wormald by cutting away part of the cyst, and removing the tooth. '' The principal cases are collected in two essays, for which I have to thank Professor Baum : namely, Lang, Ueber das Vorkommen von Zdknen, im Sinus Maxillare, Tiibingen, 1844; and Glasewald, De Tumore guodam utriusque Antri Highmori, Gryphise, 1844. Three good cases, also, are related by Mr. Salter in the Guy's Hospital Beports for 1859. 444 FATTY TUMOUES. LECTUEE XXIV. FATTT TUMOUES : FIBEO-CELLTJLAE TUMOUES : MYXOMA : GLIOMA : HYDATID MOLE : CYLINDROMA. Among the solid tumours, the first that may be considered is the Eatty or Adipose tumour — the Lipoma of some, the Steatoma of others ; the most simple in its texture, the most like the natural parts, the least liable to variations ; a morbid growth so well known, that I can scarcely hope to impart any interest to an account of it. Among the growths commonly included as fatty tumours, we find examples of both the forms of morbid hypertrophies of which I spoke in the twenty-first Lecture. There are both continuous and discon- tinuous morbid hypertrophies of fat ; both fatty outgrowths and fatty turuours, more properly so called.^ The Fathj Outgrowth is thus described by Sir B. 0. Brodie, in his well-known lecture upon fatty tumours. He says, — ' There is no dis- tinct boundary to it, and you cannot say where the natural adipose structure ends, and the morbid growth begins These tumours feel like fat, but they may be distinguished from common fatty tumours by their baving no well-defined boundary, and by their being less soft and elastic. Such deposits may take place in any part of the body ; but I have seen them more frequently in the neck than anywhere else.' ^ Doubtless the case will be familiar to you by which Sir B. Brodie illustrates this account, — the case of a footman, with an enormous double chin, and a great mass of fat extending from ear to ear, who was cured by the liqiior potassce. The case already cited from Schuh's essay (p. 376) was of the same kind. I can add nothing to this account, except the mention of a singular case of fatty growth connected with the heart of a sheep.^ The right ' M. Lebert (Abhandlungen, p. 112) distinguishes tlie fatty tumoiirs, according to their degrees of isolation, as Lipoma circumscriptum andL. diffusum. ' Lectures on Patholoc/y and Surgery, p. 275. ' Mus. Coll. Surg., 1529. FATTY TUMOURS. 445 ventricle is nearly iilled with, a lobalated mass of fat, distending it, and pressing back the tricuspid valve. The left auricle and ventricle arc similarly nearly filled with fatty growths, and fat is accumulated on the exterior of the heart, adding altogether about twenty-five ounces to its weight. The textures of the heart itself appear healthy, though it is the seat of all these fatty growths. The discontinuous Fatty Tumours, of which alone I shall now speak, present a tissue exactly or very nearly resembling the normal fatty or adipose tissue of the animal in which they grow. Certain differences may, indeed, be sometimes found between the fat of a tumour and that of the part in which it lies ; such as the larger size of the tumour's cells, its less or greater firmness at the same temperature, and the usual crystallising of the margarine ; but I believe there are no greater differences than may bo found in the natural fat of different parts of the same person. It would be superfluous to describe or delineate the minute characters of this well-known tissue : it is only in its arrangement that the tumours have any peculiarity worth notice. It is, in all, composed essentially of clustered oil-cells ; but these are, in some tumours, placed in a uniform mass, smooth on its surface, and only obscurely partitioned ; in others, arranged in oval or pyriform lobes, projecting on the surface, easily separable by splitting their connective-tissue partitions ; and in some of these it may be dissected into thin layers, which are wrapped in each lobe, one within the other, like the leaflets of a bud. Moreover, any of these forms, whether ' simple,' or 'lobed,' or ' involuted,' may be either deeply embedded in the tissues, or 'pendulous.' Fatty tumours are, I believe, always invested with a capsule, or covering of connective tissue ; and of these capsules, since they exist with most of the innocent tumours, I may speak now once for all. The capsule, then, of such a tumour is usually a layer of fibro-cellular, areolar, or connective tissue, well organised, dry, and containing bloodvessels proportioned to the size of the tumour. It appears to be formed of the connective tissue of the part in which the tumour grows, increased, and often strengthened, in adaptation to the bulk and other conditions of what it encloses. It grows with the tumour, invests it, and at once connects it with the adjacent tissues, and separates it from them ■ just as, e.g., similar connective tissue does each muscle in a limb. Its adhesion to both the tumour and the parts around it is more intimate than that of its layers or portions to one another ; so 446 FATTY TUMOURS. that, when such a tumour is cut into, it may be dislodged by splitting its capsule, and leaving some of it on the tumour, and some in the cavity from which the tumour is extracted. This, at least, can be easily done, unless the tumour has been the seat of inflammation, which may thicken the capsule and make all its parts adherent to one another, and to the tissues on either side of it. As Schuh observes, when a fatty tumour is just under the skin its capsule is usually more closely connected with the skin in the interspaces between the lobes than in any other part, so that the skin appears dimpled over it, especially if one squeezes the tumour at its base, and presses it up to make the skin tense. In the capsule, the bloodvessels that supply the tumour usually first ramify. One principal artery, indeed, commonly, but not always, passes straightway into the tumour at its deepest part, but the rest branch in the capsule, especially in any thicker parts of it that lie in the spaces between projecting lobes of the tumour. Hence, with the partitions of the tumour that ar&«derived from the capsule, the blood- vessels pass into its substance. The capsules of these fatty tumours may vary somewhat in thick- ness and toughness ; and so may the partitions that proceed from them into the mass. They are usually very delicate ; but they are sometimes thick and strong, and give a density and toughness which approach to the characters of a fibrous tumour. To such examples of fatty tumours deviating from the common type, Miiller^ has assigned the name of Lipoma mistnm ; and Vogel,^ Gluge,' Rokitansky,'* and some others, call them ' Steatoma,' and ' lardaceous tumour ' (Speck- geschwiilst).^ Fatty tumours usually occur singly ; but there are many exceptions to this rule. Two or three in the same person are not rarely seen, and a hundred or more may exist. Sir B. C. Brodie mentions such cases ; and I am acquainted with a gentleman who has borne, for nearly twenty years, firm tumours, f eehng like fatty masses, in the subcutaneous tissue of his trunk and aU his limbs. They are usually stationary, but sometimes one grows a little, or one diminishes, or a new one appears, ' On Cancer, p. 153. ^ Pathologische Anatomic, p. 179. ^ Pathologische Anatomic. * Pathologische Anatomic, i. p. 283. " Miiller also gives the name of Lipoma arborescens to the pendulous fatty processes with synovial membrane that are clustered about chronic diseased joints. Sir B. C. Brodie {Lecturer, I. e.) describes a form of fatty tumour, -which I have not yet seen, in which the tumour is covered "with a double layer of memljrane like a 'serous sac. FATTY TUMOURS. 44,7 Some time ago, I saw a woman, fifty years old, in wtom a large number of similar tumours had been growing for about ten years in the subcutaneous tissue of the arms, thighs, and haunches. They were all small and firm, and felt like tumours of mixed fatty and tough con- nective-tissue. The most frequent seats of fatty tumours are the trunk, and the part of the neck and limbs that are nearest to it ; but they may occur in any part where fat naturally exists, and they are not limited even to these.' It is, perhaps, impossible to say why they should affect one locality of fat rather than another Their rarity in the human mesentery and omentum, and the fat about the internal organs, is remarkable. I have never seen one in the recent state in any of these parts ; and I know only two or three specimens in museums.* In the College Museum (No. 194) is a bilobed mass of fat, enclosed in a thick capsule, and attached by a long pedicle to the intestine of an ox. In the trunk and limbs, they appear less frequent in the parts in which the natural fat, though abundant, is subject to least variations in its quantity ; such as the palms and soles,^ and the bones ; and they are rarely, if ever, formed in parts of or near the trunk where very little fat naturally exists, as the eyelids* and the greater part of the scrotum. Fatty tumours have, indeed, been found in the scrotum ;' and one very remarkable case is ' Miiller(Ora Cancer, p. 153) describes one between the optic nerves and corpora albicantia ; and Eokitansky (i. p. 282), including both the tumours and the outgrowths , refers to examples of Lipoma in the submucous tissue of the stomach, intestines, and bronchi ; in the subserous tissue of the pleura, peritoneum, dura mater, and cerebral ventricles ; and in the lungs, liver, and kidneys. A very remarkable case of pendulous fatty tumour of the pharynx and larynx is related by Mr. Holt. Trans. Pathol. Son. V. p. 123. ^ One, referred to in Lecture xxi., is in the Museum of St. George's Hospital. Other cases are related by Vogel (Path. Anat. tab. sxii. fig. 1) ; Gluge (I.e. Lief vii).); Lebert {Phys. Pathol, ii. p. 105). Professor Turner has seen a well-marked fatty tumour, the size of a large walnut, growing in the submucous tissue of the large intestine, and projecting into the cavity of the gut at the angle of junction of the two segments of the ileo-csecal valve, which were in consequence much dis- placed. They are not rare in the corresponding parts of horses and other domestic mammalia (Fiirstenburg : Die Fettgeschwiilste und ihrer Metairwrphose ; Berlin, 1851). ' M. Folin has related (C B. de la Soc. de Biologic, t. iv. p. 71) a case of a fatty tumour as large as a pullet's egg on the anterior and external aspect of the middle finger of a man about fifty years old. It adhered firmly to the sheath of the tendon, which was opened in removing it. In the St. Bartholomew's Hospital Museum there is now a specimen of a fatty tumour from the palm. Series xxxv. No. 68. * Cases of fatty tumours in or encroaching on the orbit are recorded by Mr. Hutchinson in the Med. Times and Gaz., December 16, 1853. ^ Gluge mentions one in the labium of a woman seventy years old. It was pyriform, and looked like a hernia [Path. Anat. Lief. viii. Taf i. fig. 1). 448 FATTY TUMOUES. related by Sir W. Lawrence and Sir B. C. Brodie : bnt, perhaps, such tmnours have not begnn to grow in the part in which they were at length found ; they may have grown or shifted into it. This shifting of fatty tumours is worth notice ; for the fact may be used in the diagnosis of them when they occur in the groin or scrotum, or other unusual place. A patient was under Mr. Lloyd's care, in 'St. Bartholomew's Hospital, with a strange-looking pendulous fatty tumour in the peri- neum. It hung like a pocket-flask between his scrotum and thigh ; but he was quite clear that it was in his groin ten years before, and that it had gradually shifted downwards. It was removed, and no pedicle or other trace of it remained in the groin. I find also a case by Mr. Lyford,' in which a large fatty tumour began to grow in the abdominal wall, midway between the spine of the ilium and the pubes, and thence, as it increased, gradually moved downwards, and was excised from the upper and inner part of the thigh. And thus, in Sir W. Lawrence's case, the tumour began to grow in the spermatic cord, and thence had partly extended and partly shifted into the scrotum behind the testicle, where it was ex- tremely difl&cult to decide its nature. For in the layer of fat outside the peritoneum small fatty tumours (Jiernie graissettse) not unfrequently grow, which may extend along with the cord, down the inguinal canal, and, in their position at least, simulate that of an inguinal hernia. Similar fatty growths may sometimes be seen, more especially in old women, projecting through the saphenous opening in the situation of a femoral rupture.^ The fatty tumours usually lie in the subcutaneous tissue, extending in it between the skin and the deeper fascia ; but they may extend more deeply. Mr. "Wormald removed one, from which distinct lobes or pro- longations passed between the fasciculi of the trapezius muscle, and expanding below them, were constricted by them. In the case of a great fatty tumour ' of the neck, removed by Mr. Listen, the operation was made formidable by the lobes of fat extending deeply to the trachea and oesophagus. Professor Turner saw in the body of an old woman a well- marked fatty tumour between the greater and lesser pectoral muscles. It was compressed and smooth, and had a strong capsule. In rare ' Med. Gaz. iv. 348. '' See an account of some eases -which occurred in the dissecting-rooms of the University of Edinburgh. MoniUy MedicalJournal, JIarch 1870. 3 Mas. Coll. Surg. No. 190. FATTY TUMOURS. 449 cases, fatty tumours may be altogether deeply seated: I found one resting on the lesser trochanter of the femur, growing up by the side of the pectineus muscle, but not prominent externally. Vogel mentions the case of a woman who had several fatty tumours, one of which was so closely connected with the nasal bone and the nasal process of the superior maxillary bone, that it was necessary to remove these with it. Mr. Aberncthy also refers to a fatty tunaour, removed by Mr. Cline, which adhered to the capsule of the hip-joint,' and Mr. Ooote has recently removed a congenital fatty tumour which passed deeply towards the neck of the radius.^ In the Museum of the Middlesex Hospital is a fatty tumour one and a half inches long, which was re- moved from beneath the tongue, where it looked like a ranula ; in the College Museum' is one taken from the substance of the tongue ; and Virchow has related^ a case of numerous fatty tumours occurring in the nerves and other parts. Such are some of the chief facts respecting the structure of this kind of tumours. Of their life I need say little. Their usual seat is in the adipose tissue, and their development is, probably, like that of the natural fat ; and in them, according to C. 0. Weber,* the gradual production of fat cells out of connective-tissue corpuscles may be traced. Their growth is, as a rule, slow, and usually without pain or any affection of the adjacent parts. But they often grow capriciously, having uncertain periods of acceleration and arrest, of which no ex- planation can be given. The extent of growth cannot well be measured, for fatty tumours have been cut out that weighed between fifty and sixty pounds ; and such as these, after twenty, or even fifty years, were still growing, and might have continued to do so as long as the patient lived. I believe the largest in London is that in the Museum of St. Thomas's Hospital, which was removed from a man's abdomen by Sir Astley Cooper, and weighed 37 lbs. 10 oz.^ One, almost as heavy, which weighed 37 lbs., was recently removed by Mr. Holden, from the back of a man aged sixty-seven.'' One of the most formidable is that in the College Museum, removed by Mr. Liston from a man's neck,* ' See also Brodie, I. c. ; Simon, Lectvrcs on Fathology; and others. 2 Brit. Med. Journal, Jan. 1, 1870. ^ No. 1Q65. ■■ Archw, xi. iii. p. 281. 1857. » Virchow's Archiv, xv. p. 61. 1859. « Medico- Chinirg. Trans, ix. p. 440. ' St. Bartholomew's Honpital Beporls, iv, 1868. No. 190. G G 450 FATTY TUMOUES. where it bad been growing for twenty-two years. A parallel to it is drawn in tlie splendid work of Auvert.' Thongh pain is not a common symptom, yet oases sometimes occur in which pain and weakness of the part are associated with fatty tumours. An interesting group of cases, occurring in the practice of Mr. Syme, has recently been recorded by Mr. Annandale.'^ Little is known of the degenerations to which fatty tumours may be liable. Their diseases have some points of interest. They may be par- tially indurated. The chief mass of a tumour may be foand with the characteristic softness, pliancy, and inelasticity of fat ; but in its sub- stance one or more lumps, like hard knots, may be imbedded. So far as I have seen, these depend on induration, contraction, and a propor- tionate increase of the connective tissue of the fat : and the change is probably due to slow inflammation of the tumour. It may be sometimes traced to frequent pressure. A laundress had a fatty tum.our, as large as a foetal head, above her ilium, aind portions of it were as hard to the touch as cartilage, and appeared to move so freely in the soft fat-tissue about them, one might have thought them loose bodies, or fluid within cysts. Where these were, the patient had been in the habit of resting her linen-basket. The indurated parts of a fatty tumour may be the seats of bone- like formations. This is, I believe, very rare ; and I have seen only the single specimen in the Museum of St. Bartholomew's Hospital ; ' but Auvert describes the same change,^ and two cases have been described by Mr. Annandale, in which calcareous nodules were found in the midst of fatty tumours. Cysts also may form in fatty tumours. In the case with partial in- durations just mentioned, I found, in another part of the tumour, a cyst with thin and partially calcified walls, which contained a glutinous and greenish oily fluid. I presume it is to tumours of this kind that Gluge gives the name of Lipoma colloides. Suppuration and sloughing may occur in these tumours ; but they are, on the whole, very rare events, except in large pendulous tumours, ' Obs. Med.-Chir. tab. li. See, for a list of the largest elsewhere recorded, Mr. South's edition of Chelius's Surgery, ii. pp. 691-2. In the Cleveland (U.S.) Medical Gazette, August 1859, is an account of a 'Mammoth Tumour ' of the abdomen and hip by Dr. Delamater. It appears to have been composed chiefly of fat, and was estimated at 276 lbs. weight. - British Medical Journal, Feb. 22, 1868. ' Series xxxv. 1 1 . ■i Tab. xvi. A case also by Mr. T. Smith in the Trans. Vathol. Soc. ix. p. 384. FATTY TUMOURS. 45 1 which have grown too large to be effectively nourished through their bases of attachment. Pathologically these changes have little interest ; but in practice they are more important, as being almost the only way in which external fatty tumours are likely to lead to death. Even in these oases, however, they show no real imitation of malignant disease.' I once, indeed, saw a case in which the end of a pendulous fatty tumour m a woman's permeum was so ulcerated that it looked like cancerous disease ; but after a week's rest in bed, during which the patient men- struated, it lost its mahgnant aspect. It now acquired (what the ulcers over and in fatty tumours commonly present) clean, inverted, and over- hanging, wedge-shaped, granulating edges. It is seldom that a fatty tumour recurs, but Mr. Curling has seen a case in which one was four times recurrent, and it was found that the stalk of the tumour, which lay beneath the pectineus muscle, con- tained a quantity of young, growing, connective tissue.^ Lastly, respecting the causes of these tumours few things can be more obscure. Nearly all knowledge on this point is negative. The growth may have followed an injury, and we may call this the cause of its formation; but we can give no explanation why such an event as an injury, which usually produces only a transitory impairment of nutri- tion, or a trivial inflammation, should, in these cases, give rise to the production of a new and constantly-growing mass of fat. Fibeo-Cellulae Tumodes. Under this name I propose to consider the tumours which, in their minute structure and their general aspect, resemble the fibro-ceUular, areolar, looser, and more rudimentary form of connective tissue of the body. So far as I know, before the time when these lectures were first published, no general account of these tumours had been given. The first distinction of them was made, I believe, by Sir W. Lawrence,^ who described an admirahle example in his paper on Tumour's ; and they are briefly but accurately described by Mr. Csesar Hawkins,'' as a softer and more elastic form of the fibrous tumour. Miiller ^ refers to them by the name of Cellulo-fibrous tumour ; and he has also given the name of ' On the possible conjunction of fatty tumoiirs and malignant disease, see Sir B. C. Brodie's Lectures, p. 282 ; and the same on the combination of fatty and mammary glandular tumours, 2 Fath. Trans. SMui. 186. ' Medico- Chirm-g. Trans, xvii. p. 14. * Medical Gazette, xxi. p. 925. " On Cancer, p. H. a o 2 4-52 FIBEO-CELLTJLAE POLYPI. Collonema to an example of this kind of ttunour. Billrotli ' states that a Collonema is a connective-tissue tumour with extremely delicate fibres and possessing a gelatinous consistence. Vogel ^ speaks of them as connective-tissue tumours (Bindegeweb-geschwiilste), and compares their tissue with that of the cutis ; and Rokitansky ; ^ points to them as a variety of 'gelatinous sarcoma.' Recently Virchow lias described, by the name of Myxoma, or Mucous tumour, a variety of the fibro-cel- lular tumour, in which the tissue is of extreme delicacy, and re- sembles the embryonic connective tissue or the tissue of the vitreous humour. As in the fatty tumours, so in this, we find instances of both out- growths and tumours ; i.e. of both continuous and discontinuous over- growths. The former are, indeed, abundant and often described ; for among them, as being formed chiefly of over-growing fibro-cellular tis- sue, are the most frequent forms of polypi of mucous membranes, and of hypertrophies of skin or cutaneous outgrowths. 1. Nearly all the softer kinds of Polypi, growing from mucous mem- branes, consist of rudimental or more nearly perfect fibro-cellular tissue, made succulent by serous or synovia-like fluid infiltrated in its meshes : the firmer kinds of polypi are formed of a tougher, more compact, dryer, and more fibrous or fascia-like tissue. Of the softer kind, the best examples are the common polypi of the nose : mucous, gelatinous, cr vesicular polypi, as they have been called. These are pale, pellucid, or opaque-whitish, pendulous outgrowths of the mucous membrane of the nose, — most frequently of that which covers the middle of its outer wall. They are soft and easily crushed, and in their growth they adapt themselves to the shape of the nasal cavity ; or, when of large size, pro- ject beyond it into the pharynx, or, more rarely, dilate it. As they increase in size, so in general does the part, by which they are continuous with the natural or slightly-thickened membrane, become comparatively thinner, or flatter : their surfaces may be simple and smooth, or lobed ; they often hang in clusters, and thus make up a great mass, though none of them singly may be large. A clear ropy fluid is difiused through the substance of such polypi, and the quantity of this fluid, which is generally enough to make them soft and hyaline, appears to be increased when evaporation is hindered ; for in damp weather the polypi are always larger. Bloodvessels enter their bases, and ranaify with wide-extending branches through their substance, ac- ' Entwick. der Blutgefasse, p. 44. ' Pathologische Anatomic, p. 185. ' Fcth. Anat. i. p. 336. FIBEO-CELLULAR POLYPI. 453 companying nsually the larger and more opaque bundles of fibro-oeHu- lar tissue. Cysts full- of synovia-like fluid sometimes exist witbin tbem. On microscopic examination these polypi present delicate fibro-cel- mlar tissue, in fine undulating and interlacing bundles of filaments. In the interstitial liquid or half-liquid substance, nucleated cells appear, imbedded in a clear or dimly granular substance ; and these cells may be spherical, or elongated, or stellate ; imitating all the forms of such as occur in the natural embryonic fibro-cellular tissue : or, the mass may be more completely formed of fibro-cellular tissue, in which, on adding acetic acid, abundant nuclei appear. In general, the firmer the polypus is, the more perfect, as well as the more abundant, is the fibro- cellular tissue. The surface is covered with ciliary epithelium, exactly similar to that which invests the healthy nasal mucous membrane, and supplies the most convenient specimens for the examination of active ciliary movement in human tissues. Glands which resemble in form the natural glands of the nasal mucous membrane occur in the super- ficial part of the polypus, and in the larger polypi make up a large part of their substance. In one case Billroth ' saw nerve fibres in a polypus. The soft polypi that grow, very rarely, in the antrum, and other cavities communicating with the nose, are, I believe, justlike these.^ And those of the external auditory passage are, in structure, not essen- tially different. All that I have been able to examine appeared com- posed of rudimental fibro-cellular tissue ; but they are generally more vascular, firmer, and less succulent than the nasal mucous polypi. Baum, Meissner, Billroth, andForster have all seen ciliated epithelium on the surface of these aural polypi, and the two last have found distinct and tolerably large papillse on them. They are also much more prone to inflammation and to superficial ulceration, perhaps through being so often connected with disease of the tympanum or its membrane. Mucous polypi not unfrequently grow in connection with the mucous membrane of the uterus. They consist partly of connective tissue and ' Ueber den Bau der Schleim-polypen, Berlin, 1855. 2 Schuh, FseudoplasTnen, p. 75. Billroth (p. 14) describes and figures a good instance of polypus of the antrum, which he considers to be a very rare affection. But Luschka (Virchow's Archiv, B. iv. p. 419, 1865) states that these polypi are not so rare as is usually supposed. He has found them five times in about sixty bodies examined. He considers them to be hypertrophies of the submucous connective tissue covered by its mucous membrane. Forster has given beautiful figures, illustrating the structure of a polypus from the antrum, in pi. 25 of his Atlas. 454 EIBEO-CELLULAE POLYPI. - partly of the glands of the uterine macons membrane, ' and possess an epithelial investment. Sometimes they are not much larger than a pea, and sessile, but at other times they possess long peduncles, and hang down into the vagina, or even project beyond the external labia. A large, deeply-lobed, soft, and nearly clear polypus in the urinary bladder, the only specimen I have seen in the recent state, ^ was com- posed, in part, of very fine filamentous fibro-cellular tissue, and, in greater part, of granular or dim homogeneous substanee,with embedded nuclei. Over the substance which these formed, there was an immense quantity of tesselated epithelium, with large scales, like those of the epithelium of the mouth ; indeed, so abundant was this, that it formed the chief constituent of the smaller lobes of the polypus. Once, also, I have been able to examine a polypus of the rectum, which, being soft and succulent, might have been classed with these ; but it was com- posed almost entirely of gland textures. It was like a disorderly mass of such tubular glands, lined with cylindriform epithelium, as are found in the mucous membrane of the rectum. These were heaped to- gether with some intersecting fibro-cellular tissue, and with abundant viscid fluid, like synovia or thin mucus. The polypus was spheroidal, about two- thirds of an inch in diameter, and attached, by a pedicle nearly an inch long, to the anterior wall of the rectum ; it received so abundant a supply of blood through the pedicle, that I think excision would have been very unsafe, unless I had first tied the base of the pedicle.^ 2. The best examples of Cutiueous Odtgeowths, of which, as I have said, a second division of the fibro-cellular outgrowths is composed, ' See Eokitansk/s Essay in Zeitsch. der GeseUschaft der Aerste zu Winn, Sept. 1860. ^ Museum of St. Bartholomew's, Ser. xxviii., No. 30 ; described by Mr. Savory in the Medical Times, July 31, 1852. Mr. Birkett has, in Trans. Med.-Chir. Soc. xli. 1858, described a polypus of the bladder which ' resembled in every anatomical particular the succulent fibrous growth termed nasal polypus.' ' Other eases of mucous and glandular polypi of the rectum may be found recorded by M. Forget in the Union Medicate, June 21, 1853; by Harpeck in a pamphlet Se poly pis recti, 1855; by Forster in his Atlas, Taf. xxv., and by Billroth in the essay already quoted. Billroth has also described cases of mucous polypi of the larynx and trachea : of the female urethra and of the uterus. He refers also to two cases of mucous polypi of the lachrymal sac. Ebstein has described (Eeichert und du Bois Eeymond's Archiv, 1864, p. 94) cases of polypi connected with the mucous membrane of the stomach. Polypi of the vagina should also be classed along with the above, as examples of mucous polypi. Sir C. Locock has stated that he had often seen a single little niucous polypus attached to a uympha, or some part of the wall of the vagina in children, either at birth, or in later life. CUTANEOUS OUTGROWTHS. 455 arc those wliicli occur in the scrotum, prepuce, labia, nymphas, clitoris and its prepuce, and not unfrequently in the lower limb.' These, which reach their maxim-nm of growth in the huge ' elephantiasis scroti ' of tropical countries, consist mainly of overgrown fibro-cellular tissue, which, mingled with elastic tissue, and with more or less fat, imitates in general siructure the outer compact layer of the cutis. Their tissue is always closely woven, very tough and elastic ; in some cases it is compressible and succulent, as if anasarcous, and it yields, on section, a large quantity of serous-looking fluid ; in others, it is much denser, interlaced with strong, shining bands, like those of a fascia ; in others, it is meshed with intervening lobes of fat ; and in others, is uniformly solid and glistening, yellowish, or with an ochre tinge, like udder. In some cases the subcutaneous tissue possesses a reticulate, spongy, or even cavernous texture, and presents an appear- ance not unlike that of erectile tissue. In a characteristic specimen of this kind, which has recently been described by Mr. T. Smith,'' great en- largement of the veins on the back of the affected limb was associated with a venous, cavernous texture, which everywhere occupied the overgrown subcutaneous tissue. Sometimes elephantiasis may coexist with an obstructed and dilated condition of the lymphatics situated in the connective tissue of the part. The dilated lymph vessels in some of these cases •* have contained a quantity of a milky, chyle-like fluid. The diversities of external form are numerous. In some, as, most commonly, on the nymphse and prepuce of the clitoris, the masses are suspended by comparatively narrow pedicles ; thus, also, are suspen- ded most of the small cutaneous outgrowths that are common on the trunk and limbs ; in some the bases are very broad, as in the nose, in which, moreover, the growth of skin is generally associated with acne and dilatation of its minute bloodvessels : in some, as in the elephanti- asis scroti, a large extent of skin appears uniformly afi'ected. Again, in different instances, they are lobed, or less deeply subdivided, or smooth, or warty and tuberculated on their surfaces : healthy or dark- 1 I suppose that the disease named Mollu.scum simplex should be classed -nnth these ; but I have never seen a good instance of it The best accounts that I have read are by &. Simon : Die Hautkrankheiten, pp. 50 and 219, and Jacobovies Du Molltiscum. Another form of disease sometimes thus named consists in morbid changes of very numerous hair-foUieles. See a case by Dr. Bealo in Trans. Pathol. Soc. vi. 313. « St. Bartholomew's Hospital Reports, v., 1869. » Dr. Carter, Med.-CUr. Trans, xlv. Papers by Drs. Day, Cholmelcy, and others, in Clinical Society's Transactions, i. 1869. 466 FIBEO-CELLULAH TUMOUES. ened epidermis covers them ; and the sebaceous glands and hair-folli- cles sinking beneath their surfaces, as in the healthy skin, are not un- frequently considerably enlarged. In the elephantiasis of the extremities and of the scrotum not only the isolation, but even the circumscribed appearance, of a tumour is lost ; the affection is classed with the dis- eases of the skin rather than with tumours, and, in morbid anatomy, is perhaps not to be distinguished from the consequences of chronic or re- peated inflammations of the integuments. In all cases, however, let the external form be what it may, there is such uninterrupted continuity be- tween the several tissues of the overgrowth and those of the healthy cutis, that the disease might be taken as the type of the ' continuous over- growths.'' Fibeo-Cellulak Tumours, properly so called, are much rarer than the outgrowths of the same texture which I have just described. They are also rare, in comparison with other tumours ; and this is singular, considering the abundance of the fibro-cellular tissue naturally existing, its general diffusion, its easy formation after injuries in disease, and even in and about other tumours. I can in no wise explain the fact ; but it is certain that for ten tumours formed of fat or cartilage (tissues which are rarely produced iu other diseases), we do not find more than one formed of flbro-oellular tissue. The form in which the fibro-cellular tumours are most frequently seen is that of oval or round masses of soft, elastic, close, and pliant tissues smooth and uniform, or, when they grow among yielding parts, deeply and variously lobed. Their exterior surface is connected with the ad- jacent parts by a capsule of connective tissue, which generally splits ' Well-marked speoimens of cutaneous outgrowths are in the Museum of the College, Nos. 2283 to 2290, 2466-7; 2708 to 2714; and in that of St. Bartholomew's, Ser. xi. 18, 19 ; Ser. xxviii. 18 ; and Ser. xxxii. 36, 37. I lately cut one from a man's nates (a very unusual place of growth), which weighed upwards of eight pounds. It had been growing for twenty years, and formed a great pendulous mass, on which he used to sit, its base covered the whole region of the glutei muscles. As examples of cutaneous outgrowths, ought also to be enumerated those cases of a peculiar form of tumour of the skin which Professor Valentine Mott has described by the name of ' Pachyder- matocele 'in the Med.-Ghir. Trans, xsxvii. 1854. Of the five cases recorded, one returned twice after removal. Other cases of cutaneous outgrowths are recorded by Mr. 0. Pemberton in Med. Times and Gaz. July 1856. "With the cutaneous outgrowths ought perhaps to be included those curious cases which constitute the Keloid of Alibert, and which appear to consist of a fibrous development in the subcutaneous areolar tissue. Fuller information on this subject may be found in Dieberg's pamphlet. Be Tuinoribus Celoidibtis, Dorpat, 1852, and in a paper by Dr. Addison in Trans. Med.-Chir. Soc. xxxvii. 1854. FIBRO-CELLULAE TUMOUES. 457 readily. When liandled they feel peculiarly tense and elastic ; their outer surface may shine like a thin sac full of fluid. On their sections we see opaque white bands, intersecting a shining succulent basis-substance of serous yellow or greenish-yellow tint. Through this basis the bands course in circles or wavy lines, or form complete par- titions ; or, in the smaller lobes of the tumour, they run without order, only forming white marks on the yellow ground-colour, but giving no appearance of grain, or of regularly fibrous structure. The peculiar yellow colour of the basis-substance of these tumours makes them look at first like fat ; it is due, however, not to fat, but to a serous, or synovia-like, or very viscid fluid, which is infiltrated through the substance of the tumour. The mass is just like anasar- cous areolar tissue — most of all like the subcutaneous areolar tissue of the back, as one sees it dissected in a dropsical body. When such a tumour is cut through or sliced, the clear yellow fluid oozes from it, or may be abundantly pressed out ; in alcohol the sanae fluid coagulates ; in both cases, the filamentous tissue contractiug, becomes denser and more compact, and more uniformly opaque white, like that of the softer varieties of fibrous tumour. It is to these last-named tumours, indeed, that the fibro-cellular have the nearest relations, and into them that they ' pass ' through gradational specimens ; but there is just the same difference, as well as just the same relation, between these kinds --..iS?i Pig. 58. of tumours as there is between the embryonic and the natural fibro- cellular and fibrous tissues ; and there is a similar propriety in distin- guishing them. Fig. 1)8. Microscopic elements of a fibro-cellular tumour, with cells in various stages of elongation and attenuation. Magnified about 450 times. 458 MYXOMA. Examined witli tlie microscope, the fibro-cellular tumours display the filamentous appearance characteristic of that tissue after which they are named. In many cases parallel, soft, undnlating filaments are found collected iu fasciculi, which interlace, and from which single filaments can often be traced out (Fig. 58) ; or, where this is not seen, the texture looks filamentons through markings or wrinkles on the surface of a more homogeneous snbstance. The best developed and most filamentous tissue is in the intersecting white bands ; but similar tissue is nsually present everywhere. In many instances elongated, or attenuated corpuscles, or abundant nuclei, appear among the fila- ments, or imbedded in the more homogeneous substance, and acetic acid rarely fails to bring into view such nuclei in crowds. In the softer, looser, and more succulent varieties of these fibro- cellnlar tumours, which on section have a jelly-like, flickering appear- / ; ance, and to which the name of Myx- I I I ''' n oma or Mucous tumonr, employed by 'I i'Ul ! ' V J Virchow, is more especially applicable, '' '' the structure of the tumour closely resembles the embryonic connective tissue, or the Whartonian jelly of the umbilical cord.' When cnt into, these tumours are seen to be soaked with a clear yellow fluid which readily drains away. Under the microscope, well- marked, ronnded, oval, elongated, or even branched corpuscles are easily Fig. 69. recognised, whilst the intermediate material is indistinctly fibrUlated, and the filaments of the connective tissue are imperfectly formed. The homology of these tumours, in respect of tissue, is thus as per- fect as that of the fatty tnmours. In chemical analysis they may yield gelatine from the well-formed fibro-cellular tissue ; but I believe they yield much more albuminous matter from their imperfectly-developed tissue, and from the serous fluid that is soaked in them. Fig. 59. From a characteristic specimen of a Myxoma. This tumour was removed by Dr. Joseph Bell from the male perineum close to the urethra. Preparation *2584, Anatomical 3Iuseum, University of Edinburgh. ' These will be again referred to in the chapter on Eecurrent Tumours. FIBEO-CELLULAE TUMOURS. 459 Fig. 60. In general, there is nearly complete uniformity ttrougli the whole mass of one of these tumours. Often times, however, different portions are more or less cedematous (if I may so call them) ; and, which is more remarkable, portions of cartilage, sometimes parti- ally ossified, may be found in or over them. I have thrice seen this. In the first case nodules of cartilage were em- bedded in a fibro-cellular tumour that grew in the ball of the great toe ; in the second (a similar tumour from the thigh) (Pig. 60), a portion of its surface, and one of its chief partitions, were formed of cartilage partially ossified ; in the third, a similar tumour from the thigh was thinly, but completely, encased with bone.' More- over, besides these differences dependent on mixtures of other tissues with those proper to the tumours, some may be found which are due to parts of the tumour being immature or imperfectly developed, and from this imperfect state degenerate. I have lately seen two such specimens, of which one was removed from the inner and deeper part of a gentleman's ham by Sir W. Lawrence ; and the other, seated between the superficial and deep muscles of a woman's forearm, was removed by Mr. Gay. The former was of three years', the latter of two years', growth. Both were of oval form, deeply lobed, very soft, loosely connected by a thin capsule with the adjacent healthy parts, and about eight inches in chief diameter. Partitions, proceeding from the capsule, and including large bloodvessels, intersected the tumours, which were mainly composed of a bright serous-yellow, flickering, but tenacious substance, half pellucid like size-gelatine. Opaque-white lines traversing this substance, gave it the general appearance of the softest and most succulent fibro-cellular tumours, or of the common mucous polypus of the nose. Fig. 60. Section of a fibro-cellular tumour intersected -w^ith cartilage and partially encased with bone : reduced one-half. Series xxxv. No. 72. ' All these specimens are in the Mueeum of St. Bartholomew's Hospital. Series XXXV. Nos. 72, 74, 94. 4G0 FIBEO-CELLULAE TUMOUES. These characters, which were commoii to large portions of both tumours, were, however, in some lobes of each, \'i'idely deviated from. In the tumour from the ham, some lobes were suffused and traced over with bright crimson and vermilion tints, and looked like lumps of size and vermilion ill-mixed for an injection. Other lobes had patches of buff-coloured or ochrey soft shreddy substance, or consisted almost wholly of such a substance. In the tumour in the forearm there was less appearance of vascularity, but the ochrey substance was more abun- dant, and parts of some lobes seemed liquefied in a turbid thick fluid of ochre or buff-yellow tint. In other portions it had a greenish-yellow hue, as if infiltrated with dried-up pus ; in others, it was nearly white and brain-like ; in others, it had mingled shades of pink and grey. But various as were the aspects of these tumours, so that with the naked eye it would have been extremely difficult or impossible to discern their kind, yet, in all parts, they showed microscopic structures characteristic of the fibro-cellular tissue in an immature state. Serous or synovia- like fiuid oozed from them, but none that was pulpy or cream-like. The serous- coloured parts consisted mainly of well- formed fibro-cellular tissue, or of a clear imperfectly fibrillated blastema, with closely imbed- ded corpuscles like nuclei. Many of these corpuscles were clear, but many were granular, as if with fatty degeneration, or appeared changed into small granule masses. In the buff and ochre-coloured parts, simi- lar tissue or blastema was sprinkled over, or was quite obscured, with minute shining black-edged molecules, like oil-particles, and with drops of oil. In other parts, some nuclei appeared hke those of very soft car- tilage ; in others, crystals of cholestearine were mingled with the oily matter. In the greenish-yellow parts, also, were corpuscles, like shri- velled pus-cells, mixed with fatty particles and debris ; and again, in other parts, cells elongated like those of granulations. No specimens could illustrate better than such as these the necessity of learning, as I have already said, to distinguish, in each tumour, the exceeding varieties presented, in the phases of development, of prema- ture degeneration, and of disease. The most frequent seats of fibro-cellular tumours appear to be the scrotum, the labium or the tissues by the side of the vagina, and the deep-seated intermuscular spaces in the thigh and arm. They may occur, also, in other parts ; but either they particularly affect these, or else a singular chance has shown them to me in these situations with unusual frequency. PIBEO-CELLULAE TUMOUKS. 461 In the scrotum I haye been able to examine two oases, and have found records or notices of many more. The first case is represented in a large specimen in the Museum of St. Bartholomew's (Series xxxv. No. 70), and in a drawing (327) made shortly after the parts were re- moved. The patient was a carpenter, seventy-four years old ; and, when he was under Mr. Stanley's care, the tumour had existed four years. It was a huge naass, about a foot long, and six or seven inches wide, filling the scrotum, and drawing over it all the adjacent integuments. A collection of fluid, like a hydrocele, was at its lower part, a large hernial sac was above it, and the scrotum was thick and oedematous. The obscurities these complications threw upon the diagnosis of the tumour, the doubt how far the hernial sac might extend, the patient's age, and his aversion for any operation, were sufficient to dissuade from active interference. The patient died about half a year after leaving the hospital. The tumour had attained the weight of twenty-four pounds ; the testicle, with a distended tunica vaginalis, lay pressed down below it, and the hernial sac was quite clear of it above. It was easily separable from the surrounding tissues, into which many lobes extended far from the chief mass, and on section appeared partitioned into lobes of various sizes and shapes. It had all the characters which I have described as be- longing generally to these tumours, varied only by the unequal collec- tions of blood or of serum, or by its various firmness of texture in its several portions. A similar case was brought to St. Bartholomew's by Mr. 0. B/. Thompson, to whom I am indebted for the history. The patient was a parish-clerk, seventy years old, a sickly-looking man, and the tumour had been nine years in progress before his death. It was first noticed as a hardness just above the testicle ; but as it constantly increased in size, it filled the whole scrotum, displacing the adjacent integuments, and looking at first sight like an enormous hydrocele. Its surface was uneven and lobed, in some parts feeling hard and brawny, in some soft and fluctuating. For many years it was inconvenient only by its size and weight ; but, about a month before death, one of its prominent parts sloughed, and haemorrhage took place from it. After this, more extensive sloughing took place and more considerable hemorrhage and the patient sank. The tumour had the same characters as the last, except in the part that was sloughing, which was denser and more compact, and of a dark blood-stained colour, likr congested liver. This might have been thought 462 FIBEO-CELLULAB TtTMOUES. cancerous ; bat with the microscope I fonnd only fibro-cellular tissue infiltrated with inflammatory exudation and blood ; in other poi-tions, unmixed fibro-cellular tissue.' To these cases I might add one related by M. Lesauvages,^ in which the tumour, in a man seventy years old, weighed at least 44 pounds and was of such a size that, as the patient sat with it resting on his thighs, it reached to his sternum and beyond his knees. And another of the same kind is related by Dr. OTerrall, which he removed successfully ; but, excellent as the surgery of this case was, its pathological complete- ness is marred by the suspicion that a small portion of it was of can- cerous structure, and by finding of a ' solitary, hard, circumscribed tuber ' in the patient's liver, when, some months after complete recov- ery from the operation, he died with phthisis.^ Of the similar tumours growing by the vagina, the best instance that I know is that recorded by Sir W. Lawrence.* A portion of the tumour is in the Museum of St. Bartholomew's Hospital (Series xxxv. No. 19) ; and, though altered from its fi.rst condition, it proves the identity of the disease with that of which I have been speaking. The patient was a lady, 28 years old, and the tumour, suspended from the labium and buttock as far as the coccyx, reached near to her knees, was as broad as her two thighs, and measured 32 inches in its greatest circumference. It had been growing four years, and produced no incon- venience except by its weight and bulk. It was soft and lobed, and the skin was loosely connected with it. Sir W. Lawrence removed the greater part of this tumour ; but a portion which advanced into the labium and along the side of the vagina could not be eradicated : this ' The two foregoing cases are published by Mr. Thompson in the Medical Gazette, May 30, 1851. ^ Arrhivcs Gen. de Med. ix. p. 212, 1845. M. Lesaiivages refers to another very probable ease in which Bayle removed the tumonr. It was of three or four years' growth, and as large as a head. The patient died, without return of the disease, seven or eight years afterwards. ' I am indebted for these particulars, beyond what were published in the Dublin Journal of Medical and Chemical Science, i. 1846, to the kindness of Dr. O'Ferrall. Mr. Guvlmg (On Lipases of the Testis, p. 51) refers to two cases of small 'fibrous' tumours removed from the scrotum, in one of which the tumour was supposed to be a third testicle. These were probably of the kind here described. So, probably, were those referred to by Schuh {Psetuloplasmen, p. 69), in one of which a fatty tumour was combined with one of several 'fibroid' tumours in a scrotum. Other cases in the scrotum are also described by Jfr. Hutchinson in the Med. Times and Gazette, December 31, 1853. And in the Lancet, July 1856, is recorded a ease in the practice of Sir W. Fergusson where the tumour recurred in the scrotum. * Medico-Chirurgical Transactions, xvii. p. 11. FIBRO-CELLULAK TUMOURS. 463 was therefore cut across ; and, when it had grown again, was removed in a second operation two years afterwards. The patient then recov- ered perfectly, and lived without any return of the disease, more than twenty years after the operation. Sir W. Lawrence's account of the tumour, and its present appearance, leave no doubt that it was of this fibro-oellular kind. A similar specimen, weighing more than 10 pounds, was removed by Mr. Liston from a patisnt thirty years old, in whom it had been growing many years, and a portion of it is in the Museum of the Col- lege (No. 2715). Many of smaller size have been removed from the same part ; ' and I have met with two which have presented the same disease in another phase. A woman, thirty-four years old, had a tumour pendulous from the right wall of the vagina and the right nympha. It was a large flask- shaped mass, about five inches in diameter, attached by a pedicle about one inch and a half in length and thickness, over the upper part of which the orifice of the uretha was arched. All the lower part of the tumour was sloughing, and discharging an offensive ichorous fluid. The upper half was covered with healthy mucous membrane, and felt uniformly tough, pliant, and elastic. The patient had noticed this disease for three or four years. . It began as a tumour, projecting into the vagina from beneath its right wall, and in this situation acquired a large size before it protruded ex- ternally. It was punctured, and then grew more rapidly ; but the pro- trusion did not take place till about ten days before I saw the patient. After this protrusion it enlarged very quickly, and, with the sloughing, the general health sufiered severely. I removed the tumour, dissecting it out with little diiSoulty, and the patient remained well for at least ten years. It presented a well-marked instance of a very cedematous and sloughing fibro-cellular tumour, and microscopic examination found abundant inflammatory exudation mingled with the rudimental fibro- cellular tissue. At nearly the same time I saw a case essentially similar to tliis ; but the tumour was suspended from, the labium, and the patient was ' Sir "W. Lawrence, I. v., refers to one by Mr. Earle. Cases are also described by Sir B. C. Brodie, Med. Gaz. i. p. 484 ; Mr. Csesar Hawkins, Med. Gaz. xxi. p. 925 ; Mr. Cnrling, Froceedings of the Pathological Society, Part ii. p. 301 ; and (probably) by Dr. O'Ferrall, Dublin Journal, i. p. 520, and iv. p. 337. A specimen from a case by Mr. Keate is in the Museum of St. George's Hospital. 464 FIBRO-CELLULAE TUMOURS. about sixty years old. And this last fact is, perhaps, worth notice ; inasmuch as, with this exception, all the cases of the fibro-cellular tumour by the vagina that I have met with have occurred in young women, while all the similai' tamours in the scrotum have been in old men. The occurrence of such tumours as these in the scrotum and labium may make it necessary that I should particularly say they are not the same disease as are the cutaneous growths which form the pendulous tumours — the elephantiasis, as it is sometimes called — of the same parts, and which I have already briefly described. The main differences are : — 1st. That these fibro-cellular tumours may be separated or enucleated from the tissues among which they lie; whereas the cutaneous growths have no definite boundary, but are continuous with the proper tissue of the scrotum, or labium, or nympba : the two diseases have the common differences between tumours and outgrowths. 2nd. In the growth of the fibro-cellular tumours, the surrounding parts, including the skin, or the mucous membrane, grow in adaptation to the tumour, but often defectively, or, at the most, only normally ; but in the cu- taneous outgrowths all the tissues take part, and the proper tissue and appended organs of the cutis are nearly as much exaggerated as the fibro- cellular substance. And 3rdly. In the tumours, fibro-cellular tissue is the highest form attained, or, at most, a small quantity of elastic tissue is mingled with it ; but, in the outgrowths, all the component structures of the skin and subcutaneous tissue are increased. The two diseases are thus different. Still, the fact is significant that the parts most liable to the cutaneous outgrowths are also those in or near which the fibro-cellular tumours most frequently occur ; and it may be noted that, among those parts in which fatty tumours are most rare, the fibro-cellular are the most common. For examples of fibro-cellular tumours removed from deep inter- muscular spaces, I may refer to two specimens already described, and to two others in the Museum of St. Bartholomew's Hospital. One of these was removed twelve years ago, by Mr. Stanley, from an elderly man ; it lay under the vastus internus muscle, and was easily dislodc/ed from the cavity in which it was imbedded ; it was a smooth, spheroi- dal mass, thinly inoapsuled, and the bright yellowish colour of its sur- face made it to be regarded as a firm-textured fatty tumour (Series XXXV. No. 33) ; but the microscope found little or no fat in it, and its IIBRO-CELLULAE TUMOURS. 465 present aspect leaves no doubt of its nature. The patient died after the operation, and had no similar disease in other parts. The second of these specimens was removed by Mr. Savory, from beneath the tensor vaginte femoris of a man thirty-eight years old. It was of uncertain date, but had been observed about five months ; it ■was firm, elastic, smooth, moveable, and painless. In the operation it was easily removed from its resting-place on the rectus muscle and the inferior spine of the ilium ; the patient recovered perfectly, and has re- mained well for nearly two years. This tumour was a smooth oval mass, measuring about 6 inches by 3^ (Series xxxv. No. 72). Both in general aspect and in microscopic characters it might have been taken for a type of the species, except for the peculiaiity of its being at one end capped with a layer of cartilage and cancellous bone, and having nodules of cartilage set along the course of one of the chief partitions between its lobes (Fig. 60). To these specimens I may add another, in the College Museum, of which Mr. Hunter has left the record that it was taken from the thigh, and had been supposed to be an aneurism.' These seem to be the most common seats of the fibro- cellular tumours, but I have preserved specimens from other parts. One was removed by Mr. Stanley from the sole of the foot, where, surely, we might have expected a fatty rather than any other tumour. The patient was a healthy man, forty-one years old, and the deeply bilobed and very prominent tumour lay in the subcutaneous tissue over the metatarsal bones, with small lobular prolongations extending among the deeper-seated tissues. It was of eight years' growth, and nodules of cartilage were imbedded in the pliant and oedematous fibro-cellular tissue of many of its lobules. Another of these specimens was removed by Mr. John Lawrence, with the testicle, within the tunica albnginea of which it appears to be entirely enclosed. The patient was a healthy-looking man, thirty- seven years old, and the tumour had, in seven years, grown to a mea- surement of nearly six inches by four. "When first removed, it was to the eye exactly like a fatty tumour, but it contained no fat, and was a ' Two remarkably good cases have been recorded by Prof. Santesson in Hygeia (translated in Dublin Journal, xx.). They lay just external to the peritoneum, between it and the rectus and transrersalis muscles, and both were examples of very rapid growths. I removed in January 1870 «. large tumoiir of this kind from beneath the gracilis muscle of a man aged sixly-three — {British Med, Journal, Jan. 1870). H H 466 FIBRO-CELLULAE TUMOURS. typical specimen of fibro-cellnlar tamonr in a very oedematous or ana- sarcous state. A tklrd was removed from over tte upper part of a girl's saphena vein, by Mr. Skey. It was completely encased in bone ; but its mass was perfect soft and elastic fibro-cellnlar tissue. A fourth, specimen is a tumour which I removed from the orbit of a man forty years old, in whom it had been growing for about eighteen months. It has the general and microscopic characters of the species, but is very soft, and is composed of a cluster of small masses, looking almost like a bunch of small gelatinous polypi of the nose.' A fifth is an oval bilobed tumour, about half-an-inch in diameter, which I removed from a young man's tongue, in the very substance of which, near its apex, it had been growing for three years. It was firmer than most of the others, yet succulent, and formed of an ob- scurely filamentous tissue, abundantly nucleated. The specimens to which I have now referred will be sufficient, I think, to justify the giving a distinct name to the kind of tumour of which they are examples. There may be found, indeed, many speci- mens that will connect these with fibrous tumours ; but, as I have al- ready said, if we may, among the natural tissues, distinguish the fibro- cellular, areolar, or looser, from the fibrous, tendinous, or denser, form of connective tissue, so should we make a corresponding distinction of the tumours that are respectively like them. I need only add a few words respecting the general history of these tumours. They have been found, I believe, only in or after the adult period of hfe, and in persons with apparently good general health. Their causes are wholly unknown. Their development appears to be like that of the natural fibro-ceUular tissue, which, in the myxomatous form of these tumours, does not pass beyond the embryonic stage. I ' Three cases of tumour in the orbit, which, I think, must have been like this, are described by Schuh (p. 63) under the names ' Zellgewebsschwamm,' 'Fungus cellulosus.' Besides the specimens, above described, which are all in the Museum of St. Bartholomew's, I have seen two removed from the scalp, both of which, before removal, were supposed to be cutaneous cysts ; and one of large size situated in the scalp has also been described by Mr. Flower {Lancet, Oct. 27, 1860). A tumour removed by Dr. Humphry (iecteres on Surgery, p. 1 87) from a finger, and one described by Lebert {Phys. Pathol, ii. p. 173) as a fibrous tumour of the neck, were probably of this kind. In other localities, as in the bones, the nerves, and the mammse timiours belonging to this group have been described, and, for an account of such cases, I may refer to the elaborate treatise on tumours by Professor Virchow (Die Krankhaften Geschwiihte, i. Lecture y.) GLIOMA. 467 have often found in them abundant cefla lengthening and attenuating themselves as in the organising of lymph or granulations. These I am disposed to regard as proper rudimental parts of the growth ; for they are often peculiarly well marked, and have no appearance of being pro- duced in disease. The growth of these tumours is quick in comparison with the average rate (so far as we can roughly estimate it) of innocent tumours. They often enlarge very quickly ; but this enlargement is probably not growth, but swelling, through increase of the oedematous eflFasion (and this difference between growth and swelling may be usefully remem- bered in the diagnosis of many tumours). The growth is usually pain- less ; but about the vagina is apt to be too rapid for the superjacent tissues. Its possible extent is very great. I have mentioned one tumour of 44 pounds' weight, and another of 24 poimds, which was still growing. Of the diseases of these tumours nothing has been yet observed, except the sloughing and suppuration that occurred in one of the cases I have mentioned. As to their nature, all that has been said implies that they are completely innocent ; and I have seen no sufficient reason to doubt that they generally, or always, are so. Once, indeed, I think such a tumour recurred after removal ; and once, in the testicle, a small growth of medullary cancer existed near, but separate from a laro-e fibro- cellular tumour : but these are the only suspicious cases I have known. Closely allied, and in particular to the myxoma or more rudimentary form of fibro-cellular tumours, is a group of tumours to which Virchow has given the name of Glioma. These tumours occur iu the nervous centres, more especially in the substance of the brain, though they are sometimes found in the auditory nerve and in the retina. In a former lecture, p. 112, the presence of a very delicate connective substance or nenroglia was described as forming a constituent part of the nervous centres. It consists of a dimly granular matrix, which sometimes ex- hibits a faint appearance of fibrillation, and contains multitudes of smaU pale, round or oval, corpuscles (Pig. 12). It supports the bloodvessels and the proper nervous structures which enter into the formation of the brain and spinal cord. Sometimes this neuroglia increases in quantity in a particular locality, and by this local increase a tumour is produced, which, on microscopic examination, is found to be chiefly composed of small cor- H H 2 468 HYDATID MOLE. puscles similar to those of the neuroglia itself, thongli sometimes they m.ay assum.e a caudate or even a stellate form. A stroma with faint fibrillae, arranged in very regular networks, is sometimes to be re- cognised between these cells, and in this stroma capillary bloodvessels are found. When these vessels are numerous they may rupture and occasion haemorrhage into the substance of the tumours. In some cases the gliomatous tumour has a firm consistence, and the stroma then consists of a more compact substance, in which distinct fibrill® may be seen, which often lie parallel to each other, and can sometimes even be isolated in distinct threads.' Fig. 61. It is well known that the chorion sometimes assumes a very re- markable appearance. The vilK on its surface swell out, and are borne on long, slender, and often branching pedicles (Fig. 61). To this ap- pearance the name of Hydatid Mole is given. The nature of these so-called hydatids has excited con- siderable discussion. From their cyst-like character, I at one time supposed that they were a cystic disease of the villi of the chorion, and, following the description of Mettenheimer,^ regarded them as examples of cyst formation by dilatation of primary anatomical elements ; and produced by an ex- pansion of the cells which normally exist both on the surface and in the substance of the villi. Gierse and H. Meckel considered^ that the disease was a swollen condition of the villi due to an accumulation of fluid in the loose tissue in their interior, and this view has been adopted by Dr. Graily Hewitt.* Virchow, on the other hand, regards the enlargement of the viUi as occasioned by a hypertrophy of their proper tissue, which he compares with the mucous tissue of the vitreous humour. Hence he includes the hydatid mole in his group of myxomata or mucous tumours.' There ' For a more detailed account of these tumours, consult Virchow: Die KranHiaftm Gesckvmlste, ii. Lecture XVIII, An illustrative case is described by Dr. Lauchlan Aitken, Ed. Med. Journal, September 1868. ' Muller's Archiv, 1850, p. 417. ' Verhandl. der Gesellsch. fur Geburtshiilfe in Berlin, 1847, * Trans. Obstet. Soc. London, i. 1859. = See also a case of hyperplasia of the ehorionic villi by Dr. A. D. Sinclair, Proc. CYLINDROMA. 469 cau be no doubt, however, but that cysts not unfrequently form in these hyperlrophied villi, and there is reason to believe that these cysts may be derived from vesicular expansions of the normal cells of their tissue (Kg. 62). It seems probable, however, that these cysts are not the essential characters of the disease, but merely arise as secondary formations in its pro- gress. /KX Fig. 62. In this place, also, it may be well to refer to certain tumours, in which peculiar cylin- drical structures are formed, for which Bill- roth has proposed the name of Cylindroma.' The structure and affinities of these tumours have given rise to considerable difference of opinion, for their characteristic appearance under the microscope is due to the presence of bodies which cannot be said to occur as normal tex- tures. At one time it was supposed that the peculiar cylindrical structures were indicative of a distinct and special kind of tumour, but further observations have shown that they may exist in tumours which occur in different regions of the body, and which may be entirely innocent, or recur in the scar after operation. Thus, they have been seen in tumours of the orbit, the nose, the antrum, the humerus, the loins, and of the parotid, in an epulis, and in spreading cancroid ulcers. These cylinders usually present a transparent, colourless, glassy character. They branch and frequently anastomose, are varicose, and swell out iuto knob-like ends. Not unfrequently they radiate from a common centre, and give off branches in a cactus-like manner : sometimes globular or bladder-like bodies occur, and whilst these and the cylinders may at times seem perfectly structureless, yet in other cases they may be filled with roundish, or radiate, or spindle-shaped cells. These Massachussets Mediccd 8oc. i. 1869, which is ascribed to increasedformation of mucous tissue. ' Various other tames have also teen given to these tumours. Meckel termed them oyliEdrical ■ cartilaginous tumours (Schlaucli-knorpel-geschwulst) ; Forster, mucous cancroids(Sch]eim-cancroid); Friedreich, cylindrical sarcouia(Schlauchsarcom); Henle, Siphonoma. 470 CYLINDROMA. peculiar structures appear to be modifications of a rudimental connective or mucoTis tissue, and, according to Thiersch and Liioke, are occasioned by a metamorpliosis of the stroma of the tnmonrs in which they are found. It has also been supposed that they have some genetic relation with the juice-canals, or the rootlets of the lymphatic vessels which arise in the connective tissue.' ' The literature of these tumoTirs may be studied by the aid of the following references : — W. Busch {Chirurg. Beobacht. Berlin 1854) ; von Graefe in his Archiv, i. p. 416, and von EeekUnghauseu in the same Archiv, xii. p. 62; Billroth {Uiitersuch. i'ther die Bntmcl. der Blutgefasse, Berlin 1856, and 'Vhokoyi's Archiv, 1869); H. V. Meckel (Charite Annalen, vii.) ; Henle in his Zeitschrift, iii. 130 ; Volkmann (VirehoVs Archiv, xii. p. 293) ; Porster {Atlas, Taf. xxx.) ; Liicke in Virehow's Archiv, 1866, and in Billroth n. von 'Ei^ha.'s Handbuch ii. p. 21 ; Bottcher in same Archiv, xxxviii., and Koester in vol. xl. FIBROUS TUMOURS. 471 LECTURE XXV. FIBROUS ITJMOUES — MYOMATA NETJEOMATA — PAINFUL SUBCUTANEOUS TUMOURS. The name of ' fibrous tumour,' or ' Fibroma,' appears tbe best, among the sixteen or more, by whicli different writers have described the tumours whose chief characteristic is their likeness to the natural fibrous, tendinous, or denser form of connective tissue of the body. This, at least, seems the best for a general designation ; and to those among them which are constructed of more than one elementary tissue we may give such names as ' fibro-muscular,' ' fibro-elastic,' 'fibro- cartilaginous,' etc. The most frequent and notorious examples of the species are the fibrous tumours, or fibrous bodies, of the uterus; the 'hard, fleshy tubercle of the uterus,' as it was described by Dr. Baillie. From these, chiefly, the general, though not all the microscopic, characters of the species may be described. First, however, the usual distinction must be drawn between the tumours and the outgrowths of the same structure. The uterus presents examples of both. The FiBEOUS PoLtPl of the uterus, more properly so-called, are con- tinuous outgrowths of and from the substance of the uterus ; the mucous membrane and the muscular and fibrous tissues of the uterus, growing, in variety of proportions, into its cavity and that of the vagina. The fibrous tumours are discontinuous growths of similar tissue in or near, not of, the substance of the uterus.' The distinction is often difficult to make during life ; for the pen- dulous, polypoid, and narrow-stemmed outgrowth may be imitated, in all its external characters, by a tumour growing near the surface of the ' The distinction is expressed by M. Cruveilliier {Anatomic Fathologigue) by the terms ' corps fibrenx implant^,' and 'corps fibreux non impknteS;' but the 'corps fibreux ' of the breast, which were described by him, and led to the 1-enowned discussion at the French Academy of Medicine, were, for the most patt, mammary glandular tumours, and nearly solidified proliferous cysts. 472 FIBKOUS POLYPI. uterus, and projecting into its cavity, with a gradual thinning invest- ment of-its muscular and mucous tissues. On dissection, however, or in such a section as the adjoining diagram (Fig. 63) may represent, the continuity of the polypus or outgrowth, A, and the discontinuity of the more commonly occurring tumour, B, may generally be discerned, even in specimens which, like two in the Museum of St. Bartho- lomew's Hospital, are, in external appearance, exactly alike (xxxii. 12 and 34). _ , Similar differences exist among what are f 'li ^f^t\ ff classed together as fibrous tumours of bone or I??* l^ . * JtrA periosteum ; some, as we shall see, are tumours ; * ' ' * '^ ^ some are outgrowths, and the line of distinction cannot be well drawn. Fibrous outgrowths are also, sometimes, found in the form of polypi suspended in the pharynx, or in the chambers of the nose, or in some of the cavities communicating with them. But I have not been able to examine any of these minutely in the recent state ; and I have seen so few in any condition, that I cannot tell whether some or even many, of them are not separate fibrous tumours, projecting the mucous membrane, and pendulous, as fatty tumours often are, when they grow just beneath the cutis. Neither the description of Schuh, accurate as it is in other points, nor any other that I remember, decides this. The same uncertainty exists as to the relations of the extremely rare fibrous polypi of the oesophagus and larynx. The fibrous structure of all these growths is well marked, but comparatively soft and elastic, and intermediate between the structures proper to the typical examples of the fibro-cellular and the fibrous tumours. Fibrous polypi have also been described springing from the wall of the rectum' into the canal of the gut, and even projecting out- side the orifice of the anus. Fig. 63. Diagram-sections of an uterine outgrowtli (a) and of an uterine tumour (b). Both are like polypi, but the former is continuous with the substance of the uterus ; the latter is discontinuous. See eases by Dav 534 EXOSTOSES OF THE GREAT TOE. and, which is more singular, one from a cod-fish. In this specimen', a disk-shaped mass of bone, two inches in diameter, extremely heavy and compact, is attached to the inner surface of the superior maxillary bone. In the texture of these very hard, bony tumours connected with the bones of the skull and the lower jaw, we may observe an instance of the general rule of likeness between tumours and. the parts most near to them ; for their bone is like no other natural bone so much as the internal table of the skull, or the petrous bone, or inferior maxilla. The same likeness is observable in the osseous tumours that are frequent on the last phalanx of the great toe, which alone now remains for me to speak of.'' No adequate explanation, I believe, can be offered for the occur- rence of these growths. They may be sometimes referred to injury, yet the effects of injury to the great toe are so inconstant, that we cannot refer to injury, as other than an indirect cause of the growth of tumours, so singularly constant as these are in all their characters, and so nearly without exception limited to the one toe of all that are exposed to injury. They grow almost always on the margin, and usually on the inner margin, of the end of the last phalanx of the great toe ; in only one specimen have I seen such a tumour springing from the middle of the dorsal surface of the phalanx ; and, in only two, similar tumours from the last phalanx of the little toe. Growing up from the margin, they project under the edge of the nail, lifting it up, and thinning the skin that covers them, till they present an excoriated surface at the side of the nail. Their growth is usually very slow, and when they have reached a diameter of from one-third to one-half of an inch, they commonly cease to grow, and become completely osseous. They are among the tumours whose independence is shown not only by abnormal growing, but by the staying of their growth when they have attained a certain natural stature. I believe that they are not uniform in their method of development. In some specimens, I have seen no cartilaginous basis ; the bone appeared to form in fibrous tissue, as it were following, and at length ' Ko. 1039. A similar specimen is in the Museum of the Boston (U.S.) Medical Society. 2 Mus. Coll. Surg. 787-8-9, 790. Preparations 566 to 672 in Anatomical Museum of the University of Edinburgh. In four of these preparations the exostosis projected from the dorsal surface of the last phalanx, in the remainder from the margin of the bone. OSSEOUS GEOAVTHS IN UPPER JAW. 535 overtaking, the fibrous growth. In another, the outer part of the tumour was formed of a thin layer of fibrous tissue, and between this and the growing bone was a layer of cartilage, which had externally the stellate nuclei, and internally the nuclei of ordinary form, among which the processes of bone were extending. Whichever way the bone is formed, it is, like that of the phalanx itself, cancellous but very hard, and with small spaces, and com- paratively thick cancelli or laminas bounding them. The outer layer, too, is rough and ill-defined, so that the growth looks like a branch from the phalanx, and, like a branch, is apt to sprout again when cut away, unless at least the end of the bone on which it grows be removed with it. The account of osseous tumours would be very incomplete, if there were not added to it some notice of those growths which are most like them, though they may lie beyond the range of any reasonable or con- venient definition of tumours. Among these are certain growths of the bones of the face, tumour-like in their most prominent parts, and yet unlike tumours in that their bases of connection with the bones are very ill-defined, and that from their bases the morbid changes, in which themselves originated, extend outwards, on the same or even to other bones, gradually subsiding. In no instances can it be plainer than it is in these, that a nosological boundary of ' Tumours ' must be an arbitrary one. Such growths as these are not very rare in the superior maxillary bone. Its ascending process may become enlarged and prominent, with an ill-defined hard swelling, very slowly increasing, and sometimes stopping short of any considerable deformity. But a much more formid- able disease exists when a large portion of the bone, or the whole antrum, is involved ; especially, because this is apt to be associated with diseases in the adjacent bones. An extreme case is shown in a specimen in the College from the Museumof Mr. Langstafi".' Two large masses of bone, of almost ex- actly symmetrical form and arrangement, project from the upper jaws and orbits, and have partially coalesced in the median line. They are rounded, deeply lobed, and nodular ; nearly as hard and heavy as ivory; perforated with numerous apertures, apparently for bloodvessels. They proiect more than three inches in front of the face, and an inch ' Mus. Coll. Surg. 3235 A. 536 OSSEOUS GROWTHS IN UPPER JAW. on each side beyond the malar hones ; they fill both orbits, the nasal cavities, and probably the antra, and they extend backwards to the pterygoid plates. Part of the septum of the nose, and the alveolar border of the jaw, are almost the only remaining indications of a face. The disease appears to have begun in the superior max- illary bones, and thence to have spread over the bones of the face ; similar disease, in a less degree, existing in the bones adjacent to the chief outgrowths. The patient who was sixty years old, believed the disease had been eighteen years in progress, and ascribed it to re- peated blows on the face. He suffered much pain in the face, eyes, and head. His eyes projected from the orbits ; the right, after suppura- tion and sloughing of the cornea, shrivelled ; the left was accidentally burst by a blow. During the last two years of his life he occasionally showed symptoms of insanity, and at last he died with apoplexy of the cerebral membranes. The disease very rarely attains so horrible a state. More commonly it is almost limited to the antrum, when it may exist with little deformity. In the Museum of St. Bartholomew's (i. 62) is a specimen in which both the antra appear nearly filled by the thickening and in- growing of their walls ; only small cavities remain at their centres. The new bone is hard, heavy, and nearly solid ; yet it is porous or finely cancellous, and is neither so compact nor so smooth on its cut surface as that of the ' ivory exostosis.' The same disease is manifest in a less degree upon the outer surfaces of the maxillary bones, and on the septum and side walls of the nose. The disease has a manifest tendency to conceutrate itself in the maxillary bones ; so much so, that if a case be met with where only one of these bones is diseased, it may be removed with a fair prospect that the disease will not make progress in the adjacent parts. I believe, indeed, that this has been done with a satisfectory result, in a case where already slight increase of some of the bones near the maxillary was observable : and there was good reason to anticipate the same re- suit, in a case on which Mr. Stanley operated. The patient was a girl, fifteen years old, in whom enlargement of the nasal process of the superior maxillary bone had been observed for eight years, and was still increasing. It had as yet produced no pain, and no deformity of the cheek, the orbit, or the palate ; but it was regularly increasing ; and it coald be certainly expected to increase even more in width of base than in prominence (this being the common tendency of the disease), it was thought right to remove the superior maxilla, while OSSEOUS GROWTHS IN UPPEE JAW. 537 yet the disease was limited to it. The patient died, ten days after tlie operation, with erysipelas. The specimen displays exactly the same disease as do those last described. It sometimes happens that growths like these spontaneously perish, are separated with the ordinary phenomena of necrosis, and thus are naturally cured. Such an event was observed in a case under the care of Mr. Stanley. A man, thirty-seven years old, was admitted with a slight convex, smooth prominence of the nasal process of his right superior maxillary bone, which he had observed increasing for two years, but which of late had not increased or given him any inconvenience. Indeed, he cam.e to the hospital not for this, but for a swelling of the right gum and the mucous membrane of the hard palate, through fistulous openings, in which one could feel exposed dead bone. These had existed for a month. The swelling of the nasal process was so characteristic of the disease I am describing as to suggest at once the existence of such a growth ; but the suppuration and necrosis threw obscurity on the case ; and it was only watched and treated according to such iudications as arose, till, after four months, the whole of the mass of bone with which the antrum had been filled up was separated and pulled away. The appearance of the sequestrum, a nearly spherical laass of hard, heavy, and finely- cancellous bone, an inch or more in diameter, leaves no doubt of the nature of the disease.' The great cavity which remained, opening widely into both the mouth and the nose, gradually contracted, or was filled up, and the man recovered perfectly. A similar event, I imagine, happened in a man who exhibited him- self at most of the hospitals in London, twelve years ago, with a great cavity where all his right upper jaw-bone and his turbinated bones had once been, and through which one could see the movements of his pharynx and palate. This he said had been left after the separation of a great tumour of bone. The growths of this kind seem to merge gradually into elevations of cancellous porous bone, which may be found on various parts of the bones of the skull, but of the exact pathology and relations of which we have, I believe, no clear knowledge. Specimens of them are in the Museum of the College, and the Museum of St. Thomas's Hospital is peculiarly rich in them. In some there are great thickenings of one or both tables of the skull, raising up bosses of new bone from haK-an-inch ' The specimen is in the Museum of St. Bartholomew's Hospital. Series i. No, 260. 538 HEREDITABY OSSEOUS TUMOURS. to an incli in depth, on one or both the parietal bones, or on the occi- pital or frontal. In some, aU the bones of the face are involved in similar changes. In some, similar elevations are prodnced by growth of bone between the tables of the sknll, which themselves remain healthy. But as yet, I believe, we can only look at these as strange and un- instructive things. The last form of bony growths that I shall mention comprises the instances in which numerous exostoses occur in the same patient, and the examples of what has been called the ossific diathesis or dyscrasia. In the large majority of cases, both cartUaginous and osseous tumours occur singly : a few exceptions might be found among such as I have been describiag, yet the rule is generally true. But in certain instances a large number of the bones bear outgrowths which, at least in external shape, are like tumours. These are commonly regarded as of constita- tional origin. Some, indeed, appear to be so in the sense of con- stitutional disease, which implies a local manifestation of some morbid condition of the blood ; but others can be so called only in that sense, by which we intend some original and inborn error of the formative tendency in certain tissues or organs. Of these last we may especially observe that the tendency to osseous overgrowths is often hereditary, and that its result is a symmetrical deformity. A boy, six years old, was in St. Bartholomew's Hospital, several years ago, who had symmetrical tumours on the lower ends of his radii, on his humeri, his scapulae, his fifth and six ribs, his fibulas, and internal malleoli. On each of these bones, on each side, he had one tumour ; and the only deviations from symmetry were that he had an unmatched tumour on the ulnar side of the first phalanx of his right forefinger, and that each of the tumours on the right side was rather larger than its fellow on the left. The swelling on the little boy's fore- finger was an inconvenience to him, and at his parent's request Mr. Lloyd removed the finger. The swelling consisted of an outgrowth or projection of healthy- looking cancellous bone, fall of medulla, and coated with a thin layer of compact tissue ; its substance being regularly con- tinuous with that of the phalanx itself. I saw this child's father, a healthy labouring man, foi-ty years old, who had as many or even more tumours of the same kind as his son's ; but only a few of them were in the same positions. All these tumours had existed from his earliest childhood ; they were symmetrically placed, and ceased to grow when he attained his full stature ; since that time they had undergone no apparent change. Kone of this man's direct DISTINCTIVE CHAEACTEKS OF OSSEOUS TUMOURS. 539 ancestors, nor any other of Ms children, had similar growths ; but four cousins, one female and three male children, of his mother's sisters, had as many of them as himself. Many similar cases of symmetrical and hereditary osseous outgrowths might, I believe, be adduced ; ' and all their history suggests that they are to be regarded as related not less closely to malformations or mon- strosities by excessive development, than to the osseous tumours or outgrowths of which I have been speaking. Indeed, at this point the pathology of tumours concurs with that of congenital excesses of develop- ment and growth. We must distinguish from such cases the instances of multiple ossifications of tendons, muscles, and other tissues, that are occasionally met with ; for these only imperfectly imitate the forms of tumours, and are probably connected with such; a morbid condition of the blood as really may deserve the name of ossific dyscrasia or diathesis. Before ending, it may be proper to point out the chief distinctions between the osseous tumours and those growths which are connected with other tumours springing from the bones ; for, under the vague name of osteo- sarcoma, many include together, and seem to identify all growths in which bone is mingled with a softer tissue. The growths that may chiefly need distinction are those of osteoid cancers, and the bony skeletons of certain medullary tumours of bone. Osteoid cancers are probably examples of firm, or hard, or fibrous can- cers, ossified : and the best marked among them present an abundant formation of peculiarly hard bone. The distinctions usually to be observed between these hard osteoid cancers and the hard osseous tumours are mainly in these particulars : — (a) the osteoid mass, in its mid substance, may be compared with chalk, the osseous with ivory ; the one is dull and powdery, the other bright, and wholly void of friability ; (6) the osteoid is new bone infiltrated, as it were, in some softer tissue, or in the tissue of the original bone, which disappears as it increases ; the hard osseous tumour is a distinct growth, attached in a comparatively small part of its extent to the bone on which it grows ; (c) the outer surface of an osteoid growth is porous and rough, and, if laminated, its lamin* have their edges directed outwards ; while the 1 See Mr. Stanley's Treatise on Diseases of Boties, p. 152; and Mr. Hawkins's ' Lectures on Tumours of Bones ' {Medical Gasette, xxt. p. 474). Also a case reported in Med. Times and Gaz. July 9th, 1853, from St. Bartholomew's Hospital, by Mr. J. Hutchinson. 540 DISTINCTIVE CHARACTERS OF OSSEOUS TUMOURS. outer surface of a hard osseous tumour is smootli and compact, aud if laminated, the surfaces of its lamdnas are directed outwards ; (d) lastly, the minute characters of bone are far less perfect in the osteoid than in the osseous growth : bone corpuscles existing, indeed, but small, round, irregular, with very small if any, canaliculi, and imbedded in a porous, chalky-looking, basis substance. And, secondly, for distinction between the softer osseous skeletons of medullary cancers, and the cancellous osseous tumours, we may chiefly observe that (a) the bone in cancers is more dry and friable than the cancellous bone of the osseous tumours ; and (6) the bone in cancellous growths has no medulla, the interspaces between its laminas being filled with cancerous matter : while medulla is a constant con- stituent, I believe, of all the cancellous osseous tumours. Such are the chief differences generally to be observed between the bone of innocent and that of malignant tumours ; differences which it is well to establish, since the fact is suiSciently confasing, that any nor- mal tissue should be formed in subordination to the growth of cancers. The subject will be again adverted to in the lecture on Osteoid Cancer. MYELOID TUMOURS. 541 LECTURE XXVII. PART IL MYELOID TDMOUES. The Tnmonra for which I venture to propose the name of Myeloid (/juE\(i)o//f, marrow-Tike) were first distinguished as a separate kind by M. Lehert.' Before his discovery of their minute structure, they were confounded with fibrous tumours, or included among the examples of sarcoma,^ and especially of osteosarcoma. M. Lebert gave them the ' Physiologie Pathologique,iS. p. 120; and Abhandlungen,p. 12S, Archives Generales de Medecine, Jan. 1853. ^ The term Sarcoma has recently been revived by Tirchow, and other pathologists in Germany, and employed to designate a group of tumours, ' the tissues forming which belong to the series of connective substances, but which are distinguished from the tumours formed of the connective tissues by the preponderating development of the ceE-elements.' The tissae of granulations formed during the inflammatory irritation of the connective tissue is regarded as the normal prototype of those tumours. The following varieties of sarcoma have been described : — u. Tumours with spindle-shaped cells, the fibro-plastic cells of Lebert (Spindel- zellen-sarcoma. Recurrent fibroid tumours, Fibro-plastic tumours). b. Tumours with colossal, many-nucleated, or myeloid cells (Riesen-zellen-sarcoma, Myeloid tumours). t. Tumours with small round cells like the lymph or white blood-corpuscles, or pus, or granulation-cells (Rund-zellen-sarcoma, Granulations- sarcoma, Glio- or Lympho- sarcoma). d. Tumours with stellate cells, and a gelatinous, shiny, intercellular substance, not unlike the material found in a myxoma (Myxo-sarcoma). 0. Tumours with round or variously-shaped cells, most of which are of large size, and are usually imbedded in a fibrous matrix. In structure no well-defined character distinguishes these tumours from Carcinoma. /. Tumours in which the cells contain a considerable proportion of pigment, which is most frequently found in the cells described in the last group, in the tumours with round and with fusiform cells (Pigment-sarcoma, Melanoma). In all these forms an intercellular substance occurs, which may be either homo- geneous or fibrous, or which may present a delicate, net-like or trabecular structure, such as is found in a lymphatic gland. But the tumours classed under the name of sarcoma vary also greatly in their general characters, and in the localities in which they grow : pendulous growths from 542 MYELOID TUMOUBS. name of ' fibro -plastic,' having regard to tlieir containing corpnsclea like the elongated cells, or fibro-oells, which he has called by the same name, and to which I have so often referred as oconrring in the mdi- mental fibro-cellnlar and fibrons tumours, and in developing lymph and granulations; and he includes in his account some tumours which are composed entirely of these elongated fibro-plastic corpuscles, and which ought rather to be regarded as a rudimental fibro-cellular, or fibrous, or recurring fibroid tumour. But the more characteristic constituents of these tumours, and those which more certainly indicate their structural homology (i.e. their likeness to natural parts) are peculiar many-nucleated corpuscles, which have been recognised by Kolliker' and Robin* as constituents of the marrow and diploe of bones, especially in the foetus and in early life. It seems best, therefore, to name the tumours after this their nearest affinity, and I would restrict the term Myeloid to those tumours in which these many nucleated corpuscles are a constant and essential constituent. On similar grounds, they must be regarded as having a nearer relation to the cartilaginous than to the fibrous tumours ; for both the many-nucleated medulla-like corpuscles and the elongated cells, are (like those of cartilaginous tumours) identical with normal rudimental bone-textures. Moreover, as I have already said (p. 525), portions of myeloid structures are sometimes mixed with those of car- tilaginous tumours, and they are sometimes developed into naturally constructed cancellous and medullary bone. The structures of this oTOup of tumours are, indeed, essentially similar to those found in granulations which grow from, and may be transformed into, bone and the gum ; soft fleshy warts on the skin ; myeloid tumours of the bones ; tumours in muscles and fasciae ; tumours in the female hreast ; clusters of enlarged lymphatic glands, have all been grouped under this head. After a careful consideration of the matter, we are inclined to think that the group is too vague, and is made to embrace tumours which are too diverse both in consistence, colour, vascularity, structure, mode of growth, seat, course, and eifects on the patient to be included under one common term. We are not prepared, therefore, to employ the term Sarcoma in the classification of tumours, for we believe that the morbid growths, which have been ranked under that name, may be more satisfactorily and precisely arranged under one or other of the heads employed in these lectures. For further information on sarcoma, consult Vircliow, Die KranTehaften Geschumlste, ii. Lecture XLX. Billroth, Die Allgemeine CMntrgische Pathohgie und Therapie, Berlin, 1868 ; Liicke in Billroth und von Pitha's Handbuch der Chirurgie, ii. ; part i., 1869. ' Mikrosk. Anatomie, ii. pp. 36i, 378. ^ CoiKptes Eendtis de la Socieii de Biologic, i. p. 150, ii. p. 8; and Memoires p. U3. MYELOID TUMOUES. 543 to a section of snch granulations some specimens bear, even to the nn- aided eye, no small resemblance. The myeloid tnmonrs may perhaps, like the oartilaginons, be found in other situations than in connection with the bones ; but they are far more frequent in or upon the bones than in any other tissue. I have seen the characteristic myeloid cells in the mammary .gland, and I think in the neck, near the thyroid gland ; Dr. Wardell' records a case of myeloid tumour in the brain ; Dr, Moxon^ reports that a soft pul- taceous material found in a case observed by Dr. Allbutt, where the lung was converted into a fibrous substance, mingled with plates of bone, fnrnished an example of myeloid. M. Lebert mentions many other parts as occasionally containing tumours belonging to his ' fibro- plastic ' group, especially the eyelids and conjunctivae, the subcutaneous tissue, the cerebral membranes, and the uterus. As usually occurring in connection with the bones, a myeloid, like a fibrous, tumour may be either enclosed in a bone whose walls are ex- panded round it, or, more rarely, it is closely set on the surface of a bone, confused with its periosteum. The sketches on p. 484, of fibrous tumours within and upon the lower jaw, might be repeated here for myeloid tumours ; and the two kinds are about equally common in the same positions, both within and upon the upper jaw. When enclosed in bone, the myeloid tumours usually tend to the spherical or ovoid shape, and are often well defined, if not invested with distinct thin capsules ; seated on bone, they are, as an epulis of this structure may exemplify, much less defined, less regular in shape, and often deeply lobed. They feel like uniformly compact masses, but are, in different instances, variously consistent. The most characteristic examples are firm ; and (if by the name we may imply such a character as that of the muscular substance of a mammalian heart) they may be called ' fieshy.' Others are softer, in several gradations to the softness of size- gelatine, or that of a section of granulations. Even the firmer are brittle, easily crushed or broken ; they are not tough, nor very elastic like the fibro-cellular or fibrous tumours ; neither are they grumous or pulpy ; neither do they show a granular or fibrous structure on their cut or broken surfaces. They are usually moderately vascular, and when resting on hollows in bone, and covered with periosteum, they commonly pulsate. But this pulsation is due, not to their own vas- cularity, but to the arteries beneath them in the hollow in the bone. It ' Trans. Path. Soc. xix. 31, : ', ' ^ Med.-Ckir. Trans, xlix, 544 MYELOID TUMOURS. is similar to the pulsation of pns or other liquid iu a vascular bony cavity. On seetion, the cut surfaces appear smooth, uniform, compact, shining, succulent, with a yellowish, not a creamy, fluid. A peculiar appearance is commonly given to these tumours by the cut surface pre- senting blotches of dark or livid crimson, or of a brownish or a brighter blood-colour, or of a pale pink, or of all these tiats mingled, on the greyish- white or greenish basis-colour.' This is the character by which I think, they may beat be recognised with the naked eye, though there are diversities in the extent, and even in the existence, of the blotching. The tumour may be all pale, or have only a few points of ruddy blotch- ing, or the cut surface may be nearly all sufiiised, or even the whole substance may have a dull Modena or crimson tinge, like the ruddy colour of a heart, or that of the parenchyma of a spleen.^ Many varieties of aspect may thus be observed in Myeloid tumours ; and, beyond these, they may be even so changed that the microscope may be essential to their diagnosis. Often, they partially ossify ; well- formed cancellous bone being developed in them. Cysts, also, varying considerably both in number and size, and filled with bloody or serous fluids, may be formed in them, occupying much of their volume, or even almost excluding the solid texture.^ In the last case, the recognition of the disease is very difficult. I amputated the leg of a woman twenty-four years old for what I supposed to be a cancerous tumour growing within the head of the tibia. She had had pain in this part for eighteen months, and increasing swelling for ten months ; and it was plain that the bone was expanded and wasted around some soft growth within it. On section, after removal, the head of the tibia, including its articular surface, ap- peared expanded into a round cyst or sac, about 3^ inches in diameter, the walls of which were formed by thin flexible bone and periosteum, and by the articular cartilages above. Within, there was little more than a few bands or columns of bone, among a disorderly collection of cysts filled with blood, or blood-coloured serous fluids. The walls of most of the cysts were thin and pellucid ; those of some were thicker, ' Lebert says the greenish-yellow colour that they may show depends on a peculiar sort of fat, which he calls Xanthose {Ahlimidl. 127). ^ I believe that many of what hare been named spleen-like tumours of the jaws have been of this kind. The colour they present is not due only to blood in them ; more of it is appropriate to their texture, as that of the spleen is, or that of granu- lations ; and it may be quickly and completely bleached with alcohol. ' 3Iany cases described as cystic tumours in bone were myeloid tumours, thus nearly replaced by cysts. Specimens illustrating this are in the Museum of St. Bartholomew's. MYELOID TUMOURS. 545 soft, and brownisli-yellow, like the substance of some medullary cancers, a likeness to whick was yet more marked in a small solid portion of tumour, wliicli, tbough very firm, and looking fibrous, was pure white and brain-like. None wbo examined this disease with the naked eye alone felt any doubt that it was an example of medullary cancer, with cysts abundantly formed in it. But, on minuter investigation, none but the elements which I shall presently describe as characteristic of the myeloid tumours could be found in it : these, copiously imbedded in a dimly-granular substance, appeared to form the substance of the cyst-walls, and of whatever solid material existed between them. The white brain-like mass was, apparently, composed of similar elements in an advanced fatty degeneration ; neither in it, nor in any other part, could I find a semblance of cancer-cells. The patient was alive many years after the amputation. I have not seen another specimen deviating so far from the usual characters of myeloid tumours as this did ; but I think that, as in this, so in any other variation of general aspect, the microscopic structures would suf&ce for diagnosis ; for there is no other morbid growth, so far as I know, in which they are imitated. They consist essentially of cells and other corpuscles, of which the following are the chief forms :— 1. Oval, lanceolate, or angular cells, or elongated and attenuated, like fibro-oells, or caudate or spindle-shaped cells (Note, p. 541), hav- ing dimly dotted contents, with single nuclei and nucleoli (Fig. 83 a). Fig. 83i 2. Free nuclei, sticli as rinay have escaped from the cells ; and, among these, some that appear enlarged and elliptical, or variously angular, or Fig. 83. Microscopic structures of myeloid tumours. A, Elongated cells, or fibro- plastic cells (Lebert). B, A cluster of many-nucleated cells. Magnified about 350 times. N N 5J:6 HISTOKY OF are elongated towards the same shapes as the lanceolate and caudate cells, and seem as if they were assnming the characters of cells. 8. The most peculiar and characteristic form ; — large, round, oval or flask-shaped, or irregular cells and cell-like masses, or thin disks, of clear or dimly-granular substance, measuring from ^-J^ to -^-^-^^ of an inch in diameter, and containing from two to ten or more oval, clear, and nucleolated nuclei (Fig. 83 B ; see also Kg. 85). By various patholo- gists in Germany these large cells have recently been called colossal or giant cells Biesen-zellen, Note, p. 641). Corpuscles such as these, irregularly and in diverse proportions imbedded in a dimly-granular substance, make up the mass of a mye- loid tumour. They may be mingled with molecular fatty matter ; or with many cells Hke those of granulations ; or the mass they compose may be traversed with filaments, or with bundles of connective tissue and bloodvessels; but their essential features (and especially those of the many-nucleated corpuscles) are rarely obscured. Myeloid tumours usually occur singly ; they are most frequent in youth, and very rare after middle age ; they generally grow slowly and without pain, and generally commence without any known cause, such as injury or hereditary disposition. They rarely, except in portions, become osseous ; they have no proneness to ulcerate or protrude ; they seem to bear even considerable injury without becoming exuberant ; they may (but I suppose they very rarely) shrink, or cease to grow ; they are not apt to recur after complete removal, although their recur- rence has been in more than one case observed ; ' nor have they, in general, any featul'es of malignant disease, although myeloid structures have occasionally been found mingled with the ordinary structures of medullary cancer.' I may illustrate these general statements by abstracts of some of the cases I have recorded, selecting for the purpose those which were, on any ground, the more remarkable.^ ' See the cases related in the note, p. 653. 2 Cases by Mr. Cock, in Trans. Fath. Soc. viii. 389, and at p. 346 of the same volume a case is related by Mr. J. Hntchinson, in "which the upper end of the shaft of the humerus and several enlarged infra-axiUary glands were removed on account of a myeloid tumour of the humerus. Thickening and fungous growths appeared a few weeks after in the operation wound, and five months after the operation the patient died. The last-formed growths disclosed well-marked cancerous structure, and several deposits of soft cancer were found in the right lung. ' The specimens obtained from all the following cases are in the Museum of St. Bartholomew's. (Series i. iSTos. 273, 275.) MYELOID TUMOUES. 547 A lad, eighteen years old, was under Mr. Stanley's care, fifteen years ago, with a tumour occupying the interior of the symphysis, and immediately adjacent parts, of his lower jaw-bone. It had been ob- served gradually increasing for eight months without pain, and in its growth had disparted the walls of the jaw, hollowing out a cavity for itself, and projecting into the moath through one of the alveoli. Mr. Stanley removed the portion of the jaw, from the first left true molar to the first right premolar tooth. The tumour presented the greenish and greyish basis, blotched with crimson and various brownish tints, and the characters of firmness, succulenoy, and microscopic texture, which I have described as most distinctive of the myeloid tumours. It was the specimen from which some of the microscopic sketches were made, and might be considered typical. This patient was in good health, with no appearance of return of the disease, twenty years after the operation. Sir "W. Lawrence had under his care a woman, twenty-one years old, with a tumour in the alveolar part of the front of the upper jaw. This was of about twelve month's duratiohj and had sometimes been very painful. It was seated in the cancellous tissue between the walls of the alveolar and adjacent portion of the upper jaW, projecting slightly into both the mouth and the cavity of the nose, and raising their mucous membranes after passing through the wasted bonci After cutting away the front wall of the jaw, the tumour was cle&red out from all the cavity in which it lay imbedded. It was in all microscopic characters Hke that last mentioned, and resembled it in general features, except in that it had in every part the dark raddy Colour of a strong heart. There was no reappearance of the disease for two years after the perfor- mance of the operation, such as Would have occurred in the case of a malignant tumonr, if an attempt had been made to remove it without the bone in which it was growing.' I'he patient was then lost sight of, so that no further history can be givenj A woman, twenty-two yfearfi old, was under Sir W, LaWrence's care, in March 185] , from the alveolar part of whose right jaw, growths which were regarded as examples of epulis, had been four times re- moved in the previous thirteen months. In the fourth operation, in August 1860, the growth was found to extend through the socket of ' I hare had several opportUDities of observing that rectirrence does not happeti when myeloid tumonrs are cleanly excavated from the cavities of hones in *hich they grow The excavation is in most cases a far better operation than the removal t>i th6 bone or its affected portion. N N 2 548 HISTORY OF the first molar tootli into the antrum, or into a cavity in the jaw. It was wholly removed (as it was thought), and the wounds healed soundly ; but nine weeks afterwards a fresh growth appeared, that seemed to involve or arise from nearly the whole front surface of the right upper jaw-bone : it was firm, tense, and elastic, but not painful, pro- jecting far on the face, as well as into the nostril, and into the cavity of the mouth at both the gum and the hard palate. This swelling, under various treatment, rapidly increased : and in December 1850, a similar swelling appeared at the left canine fossa, and grew at the same rate with that of earlier origin. Of course the co-existence of two such swellings led to the fear, and in some minds to the conviction, that the disease was cancerous ; and the more, because, at nearly the same time with the second of these, two soft tumours had appeared on the parietal bones. Still, the patient's general health was but little impaired ; and when the mucous membrane of the hard palate ulcerated over the most prominent parts of the tumours, neither of them protruded, or bled, or grew more rapidly. In April 1851, the growth of the tumours appeared to be very much retarded, and for the next month was hardly perceptible ; and the patient being very urgent that something should be done to diminish the horrible deformity of her face. Sir W. Lawrence, in May, cut away the greater part of the front and of the palatine and lower nasal parts of the right upper jaw, and removed from the antrum all that appeared morbid, including, doubtless, nearly every portion of the tumour. The excised portion of the jaw-bone was" involved and imbedded in a large, irregularly spherical tumour, composed of a close textured, shiningj soft, and brittle substance, of dark greyish hue, suffused and blotched with various shades of pink and deep crimson. It was not lobed, but included portions of cancellous bone, apparently new-formed, and was very closely adherent to all the surrounding parts. To the microscope it exhibited all the characters that I have described above ; and the many-nucleated corpuscles were remarkably well defined and full. They composed nine-tenths of the mass, and were arranged like clustered cells. The patient perfectly recovered from the efiects of the operation ; and, to every one's surprise, the tumour on the left upper jaw, which had been in all respects like that removed from the right side, gradually disappeared. It underwent no apparent change of texture, but simply subsided. The swellings on the parietal bones, also, the nature of which was not ascertained, cleared away ; and when the MYELOID TUMOURS. 549 patient was last seen, in 1868, she appeared completely well, and no swelling could be observed. No case could better show than this did the conformity of the myeloid tumours with the general characters of innocent growths ; on the other hand, the following might well have been regarded as a malignant disease, if its structure and limitation to a single part had not been considered. A farmer's boy, fifteen years old, was under Mr. Stanley's care, in the winter of 1851, with a large tumour covering the upper part of his head, rising to a height of from one to two inches above the skull, extending nearly from ear to ear, and from the occipital spine to the coronal suture. This had been in progress of constant growth for three years, and was believed to have originated in the effects of re- peated blows on the head. The head now measured 21 inches in cir- cumference, and 1 6^ inches over its transverse arch. Just before his admission he had become blind in one eye, and nearly so in the other ; his gait was unsteady ; he had severe pains in and about the forehead, but his intellect was not affected, and he appeared in good general health. The scalp over the tumour was exceedingly tense, and, at the most prominent psirt, rather deeply ulcerated. The temporal and oc- cipital arteries were very large and tortuous : the corresponding veins felt like large sinuses. In the last two months of his life, while in the hospital, his blindness became complete ; he lost nearly all power of hearing, and suffered severe paroxysms of headache. A large portion of the scalp and of the subjacent tumour sloughed, leaving a great suppurating cavity in the still growing tumour. At length, two days before death, convulsions ensued, which were followed by coma ; and in this he died. The tumour covered all the surface of the skull in the extent above mentioned, rising gradually from its circumference to a height of two inches at and about its central parts. A similar growth of somewhat less dimensions existed within the corresponding parts of the interior of the skull, including the dura mater and longitudinal sinus, and deeply impressed the cerebrum. And, again, material similar to that forming these growths was infiltrated in and expanded the included parts of the bones of the vault of the skull. From both surfaces of these bones osseous spicula and thin lamellae extended into the bases of other corresponding parts of the tumour. The adjacent sketch (Fig. 84), from the preparation in the Museum of St. Bartholomew's (Series i. 550 HISTOEY OF 293), sliows the relations of this singular growth to the skull and brain, as seen in a transverse section. The extra-cranial portion of the tumour had a nearly uniform dense and elastic textnre, of dull yellow colour mingled with white. Its cut surface appeared smooth, without distinct fibrous or other structure, and to the unaided eye looked like the firmest medullary cancer, involv- ing the pericranium, and partially exposed by ulceration of the scalp. The intra-cranial portion was soft, easily crushed and broken into pulp, Fig. 84. purple, streaked with pale grey and pink tints. It looked obscurely fibrous, and was intersected by shining bands derived from the dura mater and falx involved in it. To the naked eye it was like a softer medullary tumour, and was closely connected with the impressed sur- face of the brain, in the substance of which, just beneath it, was a large abscess. Different, however, as the two parts of the tumour appeared, there was no corresponding difference in their microscopic elements ; these ■were essentially the same in both parts ; and though the tumour was so like cancer in its general aspect, yet its minute structures were not cancerous. They were chiefly as follows :—(!.) Regular, oval, and well-defined cells, about -g-J-g- of an inch in diameter, containing dimly- granular or dotted substance, in which many oval nucleolated nuclei were imbedded (Fig. 85, a). They corresponded exactly with the cor- puscles characteristic of the myeloid tumours ; but they had more dis- tinct cell-walls than I have seen in any other case, and some had even double contours, as if with very thick cell- walls. (2.) Irregular masses or fragments, of various sizes and shapes, having the same apparent MYELOID TUMOURS. 551 substance as the contents of the cells, and containing similar numerous imbedded nuclei, but no defined cell- walls (Fig. 85, b). In these also, the identity- with the constituents of myeloid tumours was evident. (3.) More abundant than either of these forms were bodies like the many- nucleated cells, but having on their walls, as it were wrapped over them one or more elongated caudate nucleated cells (c). They seemed to be formed like the peculiar corpuscles in epithelial cancers, in which one finds cells or clusters of nuclei invested with layers of epithelial scales concentrically wrapped round them. Their borders presented two or three concentric lines, as if laminated ; between these were one or more nuclei ; and often the innermost of the lines was bayed inwards towards the cell-cavity, leaving a space in which a nucleus was lodged. Some- times, from the circumference of such bodies, one could find curved, nucleated, elongated, spindle-shaped cells dislodged (d). In most in- stances these laminated cells were filled with the dimly-granular pro- toplasm and the many nuclei ; but in some there were clear spaces, that seemed to contain only pellucid liquid. The elongated cells that could be sometimes detached from these laminated cells agreed, in general characters with the remaining principal constituent of the growth ; — namely (4.) narrow, long, caudate and fusiform cells with out-swelling nuclei, like those of developing granulations, and such as I have des- cribed as constant elements of the myeloid tumours. All the minute structures just described were found closely com- pacted, and making up with free nuclei and granular matter the mass of both portions of the tumour ; and the only apparent difi'erence was, that in the intra-cranial portion they appeared more generally to con- tain granules, and to be mixed with granule-cells and granule-masses, as if this part of the tumour were more degenerate than the ,other. I fear that even so abbreviated a record of this case as I have Fig. 85. Microscopic elements of the myeloid tumour of the skull described in the text. Magnified 350 times. 552 HISTOEY OF ventured to print may seem Tery tedious ; but it is not for its own rarity alone tliat tlie case is important. It would be difficult to find a tumour more imitative of cancer than this was in its mode of growth, its infiltration of various tissues, its involving of important parts, its apparent dissimilarity from any natural structures. And yet it certainly was not cancer ; the microscopic elements were like those of natural parts ; not a lymphatic or any other organ was afiected by similar disease, and death seemed to be due solely to the local effects of the growth. But while these, and many other cases, may be enough to prove that the myeloid tumours are generally of innocent nature, yet I suspect cases may be found in which, with the same apparent structures, a malignant course is run. Of such suspicious cases the two following are examples : — A woman, fifty years old, was under Mr. Stanley's care, in 1847, with an irregular, roundish, heavy tumour, between two and three inches in diameter, in her left breast. It projected in the breast, and the skin over it was red and tense, and at one part seemed to point, as if with suppuration. Some axillary glands were enlarged but not hardened. This tumour had existed about nine months, had been the seat of occasional pain, and was increasing. It was considered to be a hard cancer ; but on the removal of the breast, was found to be a distinct growth, completely separable from the mammary gland, which was pressed aside by it. Its character was obscured by suppuration in many points of its substance : yet after a careful examination of it in the recent state, and a repeated examination of the notes and sketches that I made of its sti-uctures, I can only conclude that it was a myeloid tumour suppurated, or, possibly, mingled with cancer. Eighteen months after the removal of her breast, this patient returned to the hospital, with a large ulcerated tumour in the lower part of her left axilla, which had begun to form as a distinct tumour six months after the operation. This was like a large flat ulcerated cancer ; it often bled freely. Her general health was deeply affected by it, and she died in two or three months after her readmis- sion. The malignant character manifested in this case was yet more decidedly marked in another. A man, fifty-three years old, of healthy appearance, was under Sir W. Lawrence's care with an oval tumour, extending, under the mastoid muscle, from the angle of the jaw to the MYELOID TUMOURS. 55S clavicle. Bloody sorum oozed from it througli three small apertures in the integuments. The anterior part of the tumour felt as if con- taining fluid ; the posterior part felt solid, firm, and elastic. He had observed this tumour for ten months, having found one morning, when he awoke, a lump nearly as large as an egg, which regularly increased. In two months it had become very large ; it was punctured, and about one-third of a pint of reddish serum was discharged from it. In the succeeding eight months it was tapped thirty-four times more, about the same quantity of similar fluid being each time evacuated. It was also six times injected with tincture of iodine, twice traversed with setons, and in. various other ways severely treated. The only general result was, that it increased, and seemed to become, in proportion, more solid. When admitted, all parts over the tumour were extremely tense and painful, and cerebral disturbance appeared to be produced by its pressure on the great bloodvessels of the neck. It was freely cut into, and the surface which was exposed presented well-marked cha- racters of the myeloid tumours such as I have described. Some small portions that were removed enabled me to confirm this with the microscope. The elongated, and the many-nucleated cells, were, to all appearance, decisive. The incision of the tumour produced temporary relief ; but the tumour continued to grow, and death occurred nearly twelve months from its commencement. In examination after death, the solid portion of the tumour, formed five-sixths of its bulk, the rest consisting of a suppurating cavity. The microscopic characters of the solid part were exactly like those of the portions removed during life, though the substance appeared firmer and whiter than before, and yielded, when scraped, a creamy fluid. Four small masses of similar substance were found in the lungs ; and a similar material was diflused in one cervical gland.' ' In the Trans. Path. Soc, ix. p. 367, a case is communicated by Mr. Henry, in -which a myeloid tumour, the size of an orange, was removed by amputation through the shoulder-joint. Some six weeks afterwards a rapidly-growing recurrent tumour appeared. The patient died three months after the operation. The recurrent tumour contained the characteristic myeloid bodies. Secondary myeloid deposits were found in both lungs. See also a case by Dr. Wilks, in x. p. 244, which is again referred to in a note on p. 577. In the Lancet for November 11, 1865, a caseis recorded in which a myeloid tumour recurred six times. A collection of cases of myeloid tumours, several of which occurred in the practice of Sir B. Brodie, by Mr. H. Gray, may be found in Med.-Chir. TVans. xxxix. 1856; and in the Trans. Path. Soc. vii. et seq. cases are related by Dr. Bristowe, Mr. C. Hawkins, and Mr. B. Childs, and others. 554 HISTORY OF MTELOID TDMOUES. Now, in botli these cases, and especially in the last,' the whole history of which seems full of anomalies, there were certainly such features of dissimilarity from the usual general characters of the myeloid tumours, that, although the microscopic characters appeared identical, yet they are not enough to prove even the occasional malignancy of the disease ; they are enough to make us cautious ; enough to induce us to study this disease very carefully, as one of those that may, in different conditions, or in different persons, pursue very different courses ; appearing in some as an innocent, in others as a malignant disease. The use of such terms as ' semi-malignant,' ' locally malignant,' ' less malignant than cancer,' and the like, in relation to growths of this kind, involves subjects of singular interest in pathology as well as in practical surgery. But I will not now dwell on them. The whole subject may be more appropriately discussed in the lectures on malignant tumours, ' Which last, I am disposed to believe, may be regarded as an anomalous thyroid glandular tumour with cysts. Many nucleated bodies, like those of the myeloid tumours, are constituents of the thyroid gland. GLANDULAE TUMOURS. 555 LECTURE XXVIII. PART I. GLANDULAR TTTMOTIRS. The name Glandular tumour, Adenoid tumour, or Adenoma, may be applied to ttose tumours whicli, in their structure, imitate the glands, whether the secreting glands, the lymphatic glands, or those organs which, because they have no open ducts, we name the ductless glands. The most frequent example of these glandular tumours is the kind which imitates, and occurs in or near, the mammary gland. Other tumours of the same general kind are more rarely found in the lips, and in or near the prostate and the thyroid glands. New formations of gland structure may also take place in connection with the sebaceous and sweat glands, so as to cause tumours in the skin. In some of the forms of mucous polypi of the antrum, nose, larynx, uterus, or rectum, as has already been stated on pp. 453, 454, mucous glands are produced, and, in the proliferous cystic tumours of the ovary, gland-structures ai-e formedin great abundance (p. 422). Enlargement of the lymphatic glands, apparently from new growths of gland-substance, may also take place. In this place I do not intend to do more than sketch such gland-tumours as may be clearly recognised ; namely, the mammary glandular tumour, the labial, the prostatic, the thyroid, and the lymphatic glandular tumours. Some of the pathology of these tumours has been already sketched in the account of the glandular proliferous cysts (pp. 378 and 424). To that account I may again refer, so far as to the point at which it is believed that an intra-cystic growth has completely filled the cyst in which its growth began (p. 425). In the glandular tumours occurring in the breast, we find some- times one circumscribed mass, composed half of a proliferous cyst, and 556 MAMMARY GLANDTJLAE TUMOURS. half of a solid glandnlar tumour ; ' sometimes two such growths lie apart, yet in the same gland (Fig. 55) ; and often we find such struc- tures as we doubt whether to call proliferous cysts nearly filled, or mam- mary tumours (Fig. 57). If aR the mammary and some other glandu- lar tumours are of intra-cystic origin, it must be admitted that many of them very early lose the cystic form, and contiuue to grow as solid masses ; for we find them solid even when they are very small ; and they are traced growing from year to year, yet apparently maintaining always the same texture. I shall speak now of the soUd tumours alone ; and, first, of the Mammaet Glandtjlae Tdmoiies — ^the chronic mammary tumour of Sir A. Cooper ; the pancreatic tumour of Mr. Abernethy ; ^ the fibrous tamour of the breast of M. Cruveilhier ' and Mr. Syme.* Sir Astley Cooper may be said to have had a good insight into their nature, when he called them ' chronic mammary,' and said they were • as if nature had formed an additional portion of breast, composed of similar lobes.' ' The analogy of their structure was also recognised by Sir W. Lawrence.^ But I believe nothing more than this general like- ness had been observed, till these tumours were examined with the microscope by M. Lebert,^ who found in them the minute glandular structure imitative of the mammary gland, and recognised many of their relations to the proliferous cysts. Mr. Birkett,' by independent and contemporary observations, made on the great collection of these tumours in Guy's Hospital, confirmed and extended the conclusions of M. Lebert, and has cleared up much of the obscurity that existed previous to his inquiries. Both these gentlemen apply such terms as ' Imperfect Hyper- trophy of the mammary gland ' to these tumours : but, highly as I esteem their observations (and not the less, I hope, because they correc- ted errors of my own'), I would rather not adopt their nomenclature, J Mus. CoU. Surg. 177-8, ' The mammary tumoiir described "by Mr. Abernethy was probably a medullary cancerous disease. ^ Anatomie Pathol, xxri. pi. 1 ; and JBuU. de I'Acad. de Midecine, ix. p. 429. ' Principles of Surgery. ' On Diseases of the Breast, p. 5i. " On Tumours; in Med.-Chir. Trans, xvii. p. 29. ' Physiologie Pathologique, ii. p. 201. ' On Diseases of the Breast, p. 124. ' In the Catalogues of the Museums of the College and of St. Bartholomew's Hospital these tumours are classed with the fibro-cellular. In most of the specimens that I had examined the conuectire tissue was very abundant, audi thought too lightly of the glandular tissue which I found mingled with it, and which in some cases has a less proportion, relative to the connective tissue, than in others. MAMMARY GLANDULAR TUMOURS. 557 since if we do not call these ' tumours,' 1 hardly know to what innocent growths the term could be applied. Nearly all innocent growths are imperfect hypertrophies, in the same sense as these growths are ; nay, these are, in many respects, the very types of the diseases to which the name of tumours is by general consent ascribed, and which can be dis- tinguished, even in verbal definition, from what are more commonly regarded as hypertrophies. The mammary glandular tumours may be found in any part of the breast ; over, or beneath, or within the gland, or at its border. Their most rare seat is beneath the gland ; their most common at its upper and inner part, imbedded in, or just beneath, its surface. They are usually loosely connected with the gland, except at their deepest part where their capsules are generally fastened to it ; but the connection permits them to slide very easily under the finger, and to be peculiarly movable in all directions. The tumour is commonly of oval shape ; superficially, or sometimes deeply, lobed or nodular ; firm, or nearly hard, elastic, and often feeling like a cyst tensely filled with fluid. The parts around appear quite healthy. The mammary gland is pushed aside ; but it undergoes no other change than that of atrophy, even when stretched over a tumour of the largest size. The skin under distension may grow slightly livid but else is unchanged. The veins, if the growth of the tumour be rapid, may be dilated over it, as over or near a cancer of the breast. The tumour is usually invested with a complete capsule, isolating it from the surrounding mammary gland, and often adhering less to it than to the gland. This capsule may appear only as a layer of connective tissue, like that round any other innocent tumour ; but it is not unfrequently more perfectly organised in layers, and smoother on its inner surface conditions that we may perhaps ascribe to its having been a perfect cyst within which the glandular growth originated, and which the growth has only lately filled. In some cases, the wall of the cyst may atrophy, and, if the tumour lies next the surface of the skin, the gland- ular growth may protrude and assume a fungous character. On section, these tumours present a lobed construction, ia which it is sometimes not difl&cult to discern the remains, or the imitation of the plan, of the lobed, or foliated and involuted intra-cystic growths. In some the connective tissue partitions among the lobes converge to- wards the centre of the mass, as if they were the remains of clustered cyst- walls ; or, there may remain a cavity in the centre of the tumour as if clustered cysts and growths had not quite filled up the space. In 558 MAMMAEY GLANDULAR TUMOURS. some, however, no such plan is discernible ; the whole mass is dis- orderly lobed, and its lobes have the shapes derived from accidental mutnal pressnre, and are bounded by loose partitions of connective tissue. In structure, as in constrnction, these tumours may present several variations ; but they may be artificially arranged in three or four chief groups. Some are really very like the normal mammary gland in an inactive state. These have a pure opaque- white, and soft, but tough and elastic tissue ; they are lobed, and minutely lobulated, with undulating white fibres. Such an one is well shown in a specimen from Sir Astley Cooper's collection,' in which, moreover, his injection of the blood- vessels shows a moderate vascularity, about equal to that of the sur- rounding normal-gland substance. We might take such as this as the examples of the medium form of this kind of tumour; and the other chief or extreme forms are represented by those which deviate from this in two directions. In one direction we find much softer tumours ; ^ these, though closely textured, are soft, brittle, or easily crushed ; their cut surfaces shine, or look vitreous or haK translucent ; they are uniformly greyish- white, or have a slight yellowish or pink hue, which deepens on exposure to the air; or they may look like masses of firm, but flickering jelly; and commonly we can press from them a thin yellowish fluid, like serum or synovia. Such as these have the usual lobed and lobular plan of construction ; and I think the intersecting partitions commonly extend from a firm, fibrous-looking central or deep part, towards the circumference of the tumour. These softer tumours have a tendency to recur. In the other direction from the assumed average or medium form, we find firmer tumours. These have a drier and tougher texture ; they are opaque, milk-white, or yellowish, like masses of dense con- nective tissue, lobed, and having their lobes easily separable ; as in the great specimen, weighing seven pounds, in the College Museum (No. 208). To such as these varieties we might add many, due not merely to intermediate forms, but to the degrees in which the intra-cystic mode of growth is manifested ; or to the development of cysts, which may ' Mus. Coll. Surg. No. 2772. In this specimen theie is also a peculiar warty growth in the skin over the tumour. ' Sv.ch as No. 2774 in the College Museum. MAMMARY GLANDULAR TUMOURS. 559 take place as well ia this new gland-tissue as in tlie old ; or to the various contents of these cysts, whether liquids or organised growths.' I believe we cannot at present always connect these various aspects of the tumours with any corresponding varieties iu their histories. Neither, I think, have any investigations ptoVed more of the corres- ponding varieties of microscopic structure, than that, as a general rule, the tougher any tumour is, and the slower its growth has been, the more it has of the connective, mingled with its glandular, tissue ; while the more succulent and vitreous one is, and the more rapid its growth, the less perfectly is the glandular tissue developed. The microscopic structures may ho best described from a medium specimen : from such an one I made these illustra- tive sketches. The patient was thirty- three years old ; the tumour had been noticed seven months, and was ascribed to a blow ; it was painful at times, and increasing ; and it had the several cha- racters that I have already described The patient has remained well since its removal. In such a tumour one finds, in thin sections, traces of a minute lobular or acinous form ; the miniature, we might say, of that which we see with the naked eye. The lobules may be merely placed side by ^^S- 86. side, with little or no intervening tissue ; their form may appear to depend on the arrangement of their contents, and these may seem scarcely bounded by membrane. But, I think, more commonly, especially in the firmer specimens, the plan of lobules or acini is mapped out by partitions of filamentous looking tissue, fasciculi of Fig. 86. Minute structiires of a mammary glandular tumour, described in the text: magnified 350 times. The microscopic examinations of several specimens may be foiind in Lebert {Phi/s. Pathol, ii. 190; and Abhandlungen, p. 269); Birkett, On Diseases of the Breast, pi. 2, 3, 4, etc. ; and Bennett, On Cancerous and Cancroid Gi'O'Wths, p. 52. f t3 Q > I believe these include the chief examples of Miiller's Cysto-sarcomata. One of these tumours containing simple cysts would constitute his cysto-sarcoma simplex ; the cysts being proliferous with gland growths would make his cysto-sarcoma proliferum seu phyllodes. 560 MAMMARY GLANDULAR TXTMOUES. wliich, curving and variously combined, appear to arcli over, and to bound, each acinus or lobule. But great varieties appear in the quantity of tbis tissue ; it may be nearly absent, or it may so predomi- nate as to obscure tbe traces of the essential glandular structure. This proper gland- structure consists of minute nucleated cells and nuclei, clustered in the lobular form, or in that of cylinders or tubes, and often, or perhaps always in their most natural state, invested with a simple, pellucid, limitary membrane. Thus, the likeness is striking between the structure of such a tumour and that of an inactive mammary gland, such as that of a male, as Mr. Birkett has pointed out. We have here what maybe compared ■with the round or oval cseoal terminations of the gland-tubes clustered together, and often seeming grouped about one trunk-tube ; and in these we have the simple membrane and the gland-ceUs and nuclei within ; only, the main duct is wanting, and the communication with the ducts of the proper gland. It is as if the proper secreting structure of a gland were formed without connection with an excretory tube ; tho tumour is, in this respect, like one of the glands without ducts.* The mammary glandular tumours are singularly variable in all the particulars of their life. They sometimes grow quickly; as did the largest figured by Sir A. Cooper, which, in two years, acquired a weight of a pound and a half. In other cases their growth is very slow ; I have known one ^ which, in four years, had not become so much as an inch in diameter. In some instances they remain quite stationary, even for many years. One ' was removed from a woman twenty-seven years old : it was observed for fourteen years, and in all that time it scarcely enlarged ; yet after this it grew so rapidly, that, in six months, it was thought imprudent to delay the removal. Cases of this arrest or extreme retardation of growth must have been seen by most surgeons ; but there are few cases so striking as one related by M. Cmveilhier, in which a lady had, for more than twenty years, three of these tumours in one breast, and one in the other. She died in con- sequence of the treatment employed against them, and after death no similar disease was found in any other part. ' In one of these tnmouTs, removed from a breast in which lactation was going on, Billroth noticed that milk was secreted by the gland-like lobules of the tumour. — Virchow's ArcMv, 18o9,XTiii. ' Museiun of St. Bartholomew's, Series xxxiv. No. 23. ' Mus. Coll. Surg. 207 b. MAMMARY GLANDULAR TUMOUES. 661 Equal variations exist in regard to pain. Commonly these tnmours are painless ; but sometimes tiey are the seats and sources of intense suffering ; even of all that suffering which is popularly ascribed to cancer, but which cancer in its early stages so very rarely presents. The irritable tumour of the breast, as Sir A. Cooper named it, was in most of his cases a mammary glandular tumour ; ' and the character of the pain, like that of the painfal subcutaneous tumour (p. 491), is such as we may name neuralgic. A tumour,^ evidently glandular, was taken from the breast of a woman twenty-five years old, where it had been growing for two years ; it had often been the seat of the most intense pain. I referred to a similar case while speakiug of neuralgic tumours (p. 493), and I removed a similar tumour from the breast of a young lady, who begged for its removal only that she might be relieved from severe suffering. In all these cases the minute glandular structure was well marked. A peculiarity of these tumours is, that they not unfrequently disappear ; an event very rarely paralleled in any other tumour. They are most likely to do this in cases in which any imperfection of the uterine or ovarian functions, in which they may have seemed to have their origin, is repaired by marriage, or pregnancy, or lactation. And the fact is very suggestive ; since, in many cases, it appears as if the discontinuous hypertrophy, which con- stitutes the tumour, were remedied by the supervention of a con- tinuous hypertrophy for the discharge of increased functions of the gland. On the other side, these tumours often continue to grow indefinitely, and they may thus attain an enormous size. One was removed by Mr. Stanley, which, after twelve years' progress, in a middle-aged woman, measured nearly twelve inches in length, and weighed seven pounds. It was pendulous ; and, as she sat, she used to rest it on her knee till the integuments began to slough. Mr. Stanley merely sliced it ofF cutting through the pedicle of skin ; and the patient remained well for at least seven years. The tumour was one of the firmest and most filamentous of the kind.^ In the College Museum is a tumour * of the same kind, but ' Under the same name, however, he included some that "were more probably ' Painful subcutaneous Tubercles ' : see his PI. viii. Figs. 2, 4, 5, 7. 5 Mus. St. Bartholomew's Hospital, Series xxxir. No. 22. ' Mus'. Coll. Surg. No. 208. ' ibid. No, 216. 562 MAiniARY GLAIfDULAR TUilOUES. softer and mucli more succulent, whicli was removed by Mr. Listen from a woman forty-fonr years old, and which weighed twelve pounds. Respecting the origin of these tumours, little more, I believe, can be said than that, occurring most conamonly, though not always, in young unmarried or barren women, their beginning often seems con- nected with defective or disordered menstruation. The law which, if we may so speak, binds together in sympathy of nutrition the ovaries and the mammary glands, the law according to which they concur in their development and action, is not broken by one with impunity to the other. The imperfect office of the ovary is apt to be associated with erroneous nutrition in the mammary gland. I have seen only one specimen of a mammary glandular tumour in a male. A portion of it was sent to me by Mr. Sympson, and its cha- racters were well marked. It was removed by Mr. Hadwen, from a countryman, twenty-five years old, in whom it had been growing irregu- larly and occasionally diminishing or disappearing, for about five years. When removed, it formed a circular, fiattened, and slightly lobulated tumour, 3^ inches in diameter, and an inch in thickness, invested with a distinct connective tissue capsule, which loosely connected it to the adjacent tissues. There are, I believe, no facts to suggest that the glandular tumours are, as a rule, other than innocent. More than one may grow in a breast at the same or several successive times ; but I have not known of more than three either at once or in succession. Neither am I aware of any facts which prove what is commonly believed, that, after a time, these tumours may become cancerous. Such things may happen ; and, on the whole, one might expect, that if a woman have a tumour of this kind in her breast, cancer would be more apt to affect it as a morbid piece of gland, than to afiect the healthy gland. But, I repeat, I know no facts to support this ; and some that I have met with are against it. Thus, in the Museum of St. Bartholomew's, is a portion of breast,' from a woman thirty-two years old, iu which there lie, far apart, a small mammary glandular tumour that had existed four years, and a hard cancer that had existed four months. A second specimen' shows a hai-d cancer and a proliferous cyst, in the breast of a patient, who died some time after its removal, with recurrence of the cancer ; and I believe that they are not counterbalanced by any of an opposite kind. ' Series xxxiv. No. 17. - ^JIiis. St. Bartholomew's Hospital, Series xxxiv. No. 16. MAMMARY GLANDULAR TUMOURS. 503 And yet, wliile all tlie characters of innooent tumours are generally, if not always, observed in these, there are facts concerning a seeming connection between mammary glandnlar tnmonrs and cancer wlaicli must not be passed by here ; though they may need to be again stated in the last lectures on cancer. It has sometimes happened that a glandular tumour has been re- moved from a breast, and, within a short time, the same breast has be- come the seat of cancer.' I believe that the explanation of such cases as these may be, that a woman, prone to cancer by some constitutional condition, or, especially, by hereditary disposition, had (as any other might) a glandular tumour in her breast, and that the operation for re- moving this tumour inflicted a local injury, and made the breast apt to be the seat of cancer. Such events may prove only an accidental con- nection between the glandular tumours and the cancer ; but they are enough to suggest great caution in operating on the breast of those who may be suspected to be, by inheritance, peculiarly liable to cancer. But, again, cases sometimes occur in which, I think, the mammary glandular tumours supply examples of what I have already suggested as probably, a general truth : namely, that the children of a cancerous parent, or those in whose family cancer is prone to occur, are apt to have tumours which may be like innocent tumours in their structure, but may resemble cancers in a peculiar rapidity of growth, and aprone- ness to ulceration and recurrence after removal. A striking instance of this occurred in Sir. W. Lawrence's practice. He removed the breast of a lady, from one of whose sisters Mr. Aston Key had removed a breast said to be affected with ' fungoid ' disease, whose mother had died with well-marked hard cancer of the breast, and in other mem- bers of whose family cases of cancer were believed to have occurred. The breast removed by Sir W. Lawrence comprised a huge sloughing a.ud ulcerating mass of yellowish, soft, flickering substance, like the softest of these mammary glandular tumours, or like the very soft pellucid growths which I have described as occurring in some of the proliferous cysts of the breast. The diseased state of the mass (in con- sequence of esoharotics having been recklessly used) was such, that minute examination showed little more than the absence of distinct cancer-structure. During the healing of the wound, and for some > See such a case, by Mr. Erichsen, in the Lancet, Feb. 14, 1852; and tlie history of a series of preparations in the Catalogue f.f the Museum of St, Bartholomew's, i. p. 446, Series xixxt. No. 28. o 2 564 LABIAL GLANDaLAR TUMOURS. months after it, fresh growths repeatedly appeared. Some of these which I have examined were yellow, pellucid, soft, viscid, almost like lumps of mucus, or of half-melted gelatiue, imbedded in the tissues of the integuments or scar. With the microscope I found only granules and granule-masses, with elongated nuclei, themselves also granular, set in abundant pellucid substance. I found no sign of cancer-structure or of gland-structure. The substance resembled that which I have mentioned (p. 429) as found in some of the imperfect proliferous mam- mary cysts. Now, after repeated removals of such growths as these, the wounds completely healed, and the patient has remained well, and in good general health, for eighteen months. At nearly the same time, a third sister of this family was under Sir W. Lawrence's care, and he removed one of her breasts, in which was a great mass, which had grown quickly, and was chiefly composed of well-marked glandular tissue, either in separate solid growths, or in- closed in proliferous cysts. But some parts also of this tumour were soft, pellucid, and gelatinous ; and others were as soft, but opaque and dimly yellow. In the firmer parts, the glandular texture was as dis- tinct with the microscope as with the naked eye : in the softer parts no such structures were seen, but abundant free cells and nuclei, of most various and apparently disorderly shapes ; some elongated, like small shrivelled fibro-cells ; some flattened, like small epithelial cells. I would not venture on an opinion of what these were or indicated: I think they were not cancerous, and the disease has not returned. The main fact of all the cases is, that three daughters of a cancerous mother had mammary tumours ; in two, at least, of them the structure was probably not cancerous ; and yet the rapid growth, the recurrences in one of them, and the defective or disordered modes of growth in both, were such as marked a wide deviation from the common rules of mam- mary glandular or any other innocent tumours, and a deviation in the direction towards cancer. Labial Glandular Tomoues may be briefly described, for their general characters correspond closely with those of the foregoing kind ; or, they may appear intermediate in character between the foregoing and those tumours which I described as lying over or near the parotid gland, and as consisting of mixed glandular and cartilaginous tissue. Their likeness to these tumours over the parotid was manifest to Sir. W. Lawrence, who has recorded a case of labial glandular tumour.' ' lifedico-Chimrgical Transactions, s.-^W. p. 28. LABIAL GLANDULAR TUMOURS. 565 The most marked case of labial glandular tumour that I have seen ■was that of a healthy-looking man, some years ago under the care of Mr. Lloyd. A tumour had been growing in his upper lip for twelve years. It was not painfal, but the protrusion of the lip was inconvenient and ugly, the swelling being an inch in diameter. It was imbedded in the very substance of the lip, both the skin and mucous membrane being tensely stretched over it. Its form was nearly hemispherical, its posterior surface being flattened as it lay close on the gums and teeth, its anterior convex and smooth. Its whole substance was firm, tense, and elastic. Mr. Lloyd removed the tumour with the mucous membrane over it, leaving the skin entire. The tumour was firm, slightly lobed, yellowish- white, smooth. In general aspect it resembled the mixed tumours over the parotid, but in minute structure it presented as perfect an imitation of lobulated or acinous gland-structure as any' mammary glandular tumour. Its tubes and their dilated ends had distinct limitary membrane, and were filled with nudlei and nucleated cells, like those of the labial glands (Fig. 87). I heard some months after- wards that another tumour was growing in the same lip ; but the patient was lost sight of. Such a recurrence, even if it really hap- pened, -Vrould be no sufficient evi- dence of malignancy. I removeci a similar tumour from the upper lip of a man about thirty years old. It had been regularly growing for four years withbut pain, and projected far externally, reaching to the same distance as the end of his nose. This had a texture of glandular kind, but less distinctly © @ Fig. 87. Fig. 87. A, structure like the csecal terminations of gland-ducts in an acinus ; B, a separate portion of gland -like tube ; c, separate gland- cells, and free nuclei; from the labial glandular tumour described in the text, a and ij magnified 300 times ; c magnified 400 times. 566 PEOSTATIC GLANDULAE TUMOTJES. marked ttan. that in the former case. Moreover, in the centre of the mass was a portion of bone ; a pecnliarity which existed also in Sir W. Lawrence's case, and which may add to the probability of relationship between these tnmoni-s and the mixed glandular and cartUaginons tumonra over the parotid. Lastly, I may again refer to a specimen in the Musenm of St. George's Hospital, in which, in one tumour, a cyst and what looks like one of these glandtdar growths are combined (see p, 429).' Peostatic Glaudulak Tuhotjes were briefly referred to in the first lecture on tumours (p. 378), as examples of the abnormal growths by which tumours appear to be connected with simple hypertrophies of organs ; and I can add little to what was then said of them. We owe to Rokitansky ^ the knowledge that the tumours in the prostate gland which were commonly, and till lately even by himself, regarded as fibrous tumours, are composed of tissues like those of the prostate gland itself. In enlarged prostates they are not unfrequently found. In cutting through the gland, one may see, amidst its generally lobed structure, portions which are invested and isolated by connective tissue, and may be enucleated. Such portions have, I believe, been sometimes removed as tumours, or as portions of prostate gland, in operations of hthotomy. They lie imbedded in the enlarged prostate, as, sometimes, mammary glandular tumours lie isolated in a generally enlarged breast. They look like the less fasciculate of the fibrous t:umours of the uterus : but to microscopic examination, they present such an imitation of the proper structure of the prostate itself, that we cannot distinguish the gland-cells or the smooth muscular fibres of the tumour from those of the adjacent portions of the gland. Only their several modes of arrangement may be distinctive.' The Thteoid Glanddlae Tumours were similarly refeired to in the same lecture and on p. 397 (note). Their history is merged in that of bronohoceles,* with whichthey are usually associated, whether imbedded ' Billroth relates a case in which one of these tumours grew in conoection with the mucous membrane of the cheek, about one inch from the angle of the mouth. It was removed, and twice recurred after the first extirpation. Tirchow's Archiv xvii. p. 374. 2 Ueber die Cyste, 18i9 ; and Anatomie des Kropfei. ' Sir H. Thompson describes, in his work On the Enlarged Prostate, both the fibro-muBCular enlargement and the increase in the glandular structure. * The pathology of bronchocele has been discussed with great completeness by Virehow in his twenty second lecture on Tumours. THYROID GLANDULAR TUMOURS. 567 as distinob masses in the enlarged gland, or lying close by it, but dis- continuous. In appearance, botb to tlie naked eye and under the microscope, they have a strong resemblance to the structure of the normal thyroid gland. But they are very apt to exhibit an abundant cyst-formation in their interior, whioh is due to a dilatation of the gland- vesicles, which become filled with a more or less gelatinous ma- terial. Mr. Stanley removed a tumour from the neck of a woman sixty-two years old. It Lad been observed for fifty years ; for the first thirty of which it was like a little loose ' kernel ' under the skin, and scarcely increased. In the next ten years it grew more quickly, and in the next ten more quickly still ; and now, the skin over it ulcerated, and it pro- truded and occasionally bled, but was never painful. It looked like an ulcerated sebaceous cyst, seated upon the subcutaneous tissue at the lower part of the neck, just in front of the trapezius. No cause could be assigned for it. On section it appeared as a solid tumour with a thin connective- tissue capsule, partitions entering from which divided it into distinct round lobes. Its proper substance was soft, elastic, glistening, yellow- ish, blotched and streaked with brownish-pink and blood-colours. It was, to the naked eye, like a piece of bronchocele, with such an arrange- ment of its parts as would exist when numerous cysts ai'e filled with the glandular growth, and compacted. And the general impression hence derived was confirmed by microscopic examination, which showed that the tumour consisted chiefiy of round and oval bodies, or minute sacculi, from y^^ to ^-jf of an inch in diameter, filled or lined with nu- cleated substance, or wdth nuclei imbedded in a dimly molecular blastema, and not nucleolated. These bodies were closely apposed, but frequently appeared separated by thin filaments, or connective-tissue partitions. The nuclei were very uniform, circular, about ir,^-,,- of an inch in diameter, and ia general aspect like the nuclei of vascular glands or lymph glands. Numerous similar nuclei appeared free ; and some appeared imbedded in a dimly molecular blastema, which was not enclosed in cysts or sacculi, or divided by partitions of connective tissue. I have seen no other tumour like this, nor any natural texture that it resembled, except the thyroid gland, and it is probable that it was produced by an enlargement of one of those isolated S,ccessory portions of thyroid-gland substance, which one sometimes sees detached from the main body of the gland. 568 XYMPHOIU TUMOUES. Lymphoid Tumouks. The term Lymphoid tumour may be employed to express those new formations which, in their essential structure, are composed of cor- puscles like the round, pale corpuscles that form the characteristic cell- elements of the lymphatic glands. Used in this sense, the term is equivalent to that of Lymphoma employed by Virchow. It includes not merely cases of enlarged or hypertrophied lymphatic glands, but all new growths composed of lymphoid elements, whether such elements do, or do not, normally exist in the localities of the morbid growths. Here, as in the last two kinds of tumours, we may in practice, but cannot in pathology, distinguish between the mere hypertrophy and the tumour, between the mere overgrowth and the new growth. Enlargement of the lymphatic glands, from a numerical increase of their anatomical elements, more especially their characteristic corpuscles, is indeed not an uncommon occurrence. The glands in the neck, loins, mesentery, and roots of the lungs, are those which are most frequently affected. As these glands lie in groups, and as most of the glands in the same region enlarge at or about the same time, a swelling, some- times of considerable size, is produced. When cut into, the glands are seen to possess a semi-elastic consistence, and a greyish or reddish-yellow fleshy colour. Microscopic examination shows that the pale lymph-corpuscles are greatly increased in numbers, the alveoli in which they lie are enlarged, and to some extent also, an enlargement and multiplication of the con- nective-tissue corpuscles of the trabecular framework has taken place. This hypertrophy of the lymphatic glands is sometimes found in conjunction with hypertrophy of the spleen, and is often associated with that condition of the blood termed leucooythEemia, in which the white corpuscles are greatly in- creased in number. Lymphatic glandular enlargement is also specially to be studied in Kg. 88. SCROFULA AND TUBERCLE. 569 surgical pathology, in its relations to scrofula and tubercle. In children these glands are most frequently affected ; in adults, they are next to the lungs in order of frequency ; and at all ages the lymphatic glands are liable to be secondarily affected in consequence of tubercular disease in other parts or organs. Without entering into any discussion of the much-disputed question, whether scrofula and tubercle are, or are not, different diseases — whether the former, as Virchow believes, arises in the glands, from pre-existing lymphatic elements, the latter from proliferation within the connective tissue — there seems to be little doubt that in both cases the new formation is in its early stage composed of lymphoid corpuscles, such as are represented in Fig. 88. Both in scrofula and tubercle the new-formed , , , corpuscles exhibit a remarkable tendency to shrivel ® ^ (^^ g, »M up, degenerate, and become abortive. In Fig. 89 •.S^='|.,©V' ^^ the smaller, withered, kind of corpuscles, and the ^.^.9 ^^ ff^y free nuclei (6), so frequently met with in tuberculous ' feffi matter, derived from the atrophy or breaking down „. . of the larger, more fully formed, tubercle-corpuscles (a), are represented. As this degeneration advances, the diseased glands acquire a soft, yellow, cheesy character, and softening or liquefaction of their substance occurs. The softening is usually central, and thence extending, may affect the whole morbid substance. The result of the change is not a homo- geneous liquid ; but, rather, a mixture of thin, turbid, yellowish-white liquid, and portions of soft, curd-like, cheesy substance, like fragments of tubercle softened by imbibed fluid. And as in the case of tubercle, inflammation often precedes the tubercular change, the Hquid products of the inflammation of whatever remains of the gland-subStance, or its capsule, and the surrounding parts, are commonly added to the liquid. The mixture constitutes the tuberculous, or, as it is generally Called scrofulous pus, of which the chief characters, as distinguished from those of ordinary inflammatory pus, are, that it has an abundant thin, yellowish, and slightly turbid liquid, with white, curdy flakes, that quickly subside when it is left at rest. The liquefaction of the tuberculous matter in the glands usually leads to its discharge ; and this is efiected, in the case of the cervical and other similarly placed glands, by ulceration, which differs from that for the opening of common abscesses, chiefly, in being slower and 570 LYMPHOID ItrMOITRS. attended with less vivid and less concentrated inflammation. There is^ therefore, less disposition to point : the skin is, proportionally, more widely undermined, more extensively thinned, Thus gradually, by thinning and inflammation deprived of blood, the inflamed skin over the gland whose contents are Uquefied, may perish, and form a dry parchm.ent-like slough, very slowly to be detached. More oom.monly, however, one or more small ulcerated apertures form in the skin, and let out the fluid. If the undermined skin be freely cut, its loose edges are apt to ulcerate widely ; if it be only punctured and allowed to subside gradually, it usually contracts and recovers its healthy state. The cavity left by the discharge of the liquefied matter, and of the fluids mingled with it, may heal up like that of an ordinary abscess ; but it does so slowly, and often imperfectly, enclosiQg portions of tuber- culous matter, which soften at some later, and often at some distant period, and lead to a renewal of the process for discharge. However, such retained portions, or even the whole of what has been formed, and perhaps liquefied, ill a lymphatic gland, instead of being discharged, may degenerate farther, and be absorbed ; or may wither and dry up into a fatty and calcareous concretion. Such chalky masses, even of large size are frequently found in bronchial and mesenteric glands that have been seats of tuberculous disease in childhood ; and similar mate- rial, but usually in small fragments, is often discharged from healing tuberculous abscesses in the neck. Whether by healing after discharge, or by calcification of the re- tained tuberculous matter, the recovery from the disease of the lymph- atic glands is often complete and permanent. The original substance of the gland may be wholly destroyed ; or, portions of it may remain indurated and fixed closely to the scar or the calcareous concretion. In connection with the mucous membranes in various parts of the body, collections of lymphoid corpuscles, infiltrated in a reticular mesh of connective tissue, are met with as normal constituents of the texture, without being aggregated in the form of glands. They form a tissue to which Professor His has given the name of adenoid. The solitary and Payer's glands of the intestinal tract, the tonsils, and the adenoid tissue ia the posterior wall of the nasal part of the pharynx,' are amongst the best marked examples of this kind of tissue. ■ Under some patho- logical conditions a numerical increase of the lymphoid corpuscles in ' Luschka in Schultze's Archiv, iv. 1868. LYMPHOID TtJMOUES. 571 these localities may take place, and swellings be produced, wliicli in their structure closely resemble an bypertrophied lymphatic gland. But there are other localities, again, where apparently no lymphoid corpuscles exist as normal structures, yet in which they may be produced and sometimes in considerable numbers. Virchow has especially studied these new formations in the liver and kidney. In the former organ they arise in the connective tissue of Glisson's capsule, and extend into the interlobular spaces. In the kidney, also, they are infiltrated with- in the matrix-substance which surrounds the capsules of Malpighi, and the uriniferous tubules. Dr. Murchison has recently recorded two cases ' in which lymphoid corpuscles had been produced in considerable numbers within the liver, and in one of these cases similar corpuscles had formed in the kidney, intestine, heart, mesentery, and extra-peri- toneal tissue generally. Dr. Church has also described a case,^ where the spleen was unusually small, in which lymphoid corpuscles bad been produced in large numbers in the mesentery and extra-peritoneal tissue. In the diffusion of such quasi- lymphatic elements in the connective tis- sue of various parts and organs, a considerable resemblance may be found between these cases and the results arrived at by Dr. Sanderson ^ and Dr, Wilson Fox,* from their inoculating experiments on the artifi- cial production of tubercle in guinea-pigs and rabbits. But in the expe- rimental inquiry the new-formed corpuscles rapidly passed into the well-known cheesy metamorphosis, a form of degeneration which does not appear to have been set-up in the cases described by Drs. Murchi- son and Church. When the lymphatic glands enlarge from a numerical increase of their corpuscles, and when this hypertrophy is not attended by an in- crease in the white corpuscles of the blood, as in leucocythEemia, and does not show a tendency to the caseous degeneration, as in scroihila, the name Lympho-sarcoma has been applied by Yirchow to express this form of lymphoid tumour. By some pathologists the term has been extended so as to embrace all new formations of lymphoid tissue whether they occur in the lymphatic glands or not, in which the leuco- cytheemic condition of the blood and the caseous degeneration are not met with. It is well known that in the mediastinum thoracis growths not un- frequently occur by the sides of the pericardium, and around the roots of the lungs, which are of great clinical interest. These growths have ' Pathological Transactions, xx. ^ Ibid, xx. p. 375. » Ibid. xix. p. 456. * Artificial Production of Tubercle : London, 1868. 572 LYMPHOID TTJIIOUES: ■nsually been described as a carcinomatons affection of this region. Vircbow bas, bowever, pointed out tbat many of tbese tumours closely resemble in structure the lympbatic glands. Tbis view of tbeir struc- tural affinity is confirmed by a recent examination of one of tbese growths, the microscopic structure of which is given ia tbe accompany- ing Figure 90. The tumour was composed of multitudes of smaUj pale, round corpuscles, which closely resembled the corpuscles of a lym- pbatic gland. Under a high magni- fying power nuclei could be recognised in the centre of many of these cor- puscles. Traversing tbe tumour were bands of delicate connective tissue which crossed each other at various angles, and formed a loose network, ia the meshes of which the lymphoid cor- puscles were collected in large num- bers. It is difficult to say ia what texture tbese mediastinal growths take their rise. It may be in the mediastinal lympbatic glands, or in tbe connective tissue, or, as bas been suggested by Vircbow and Dr. Church, in the remnants of the thymus gland.^ Pig. 90. From a lymphoid mediastinal tumour, in the Anatomical Museum, University of Edinburgh . It occurred in a woman eetat. thirty-seven, and formed a thick grcwth around the pericardium. The glands in the neck and mediastinum were much enlarged. The ca,se ia desciihei in the Edinb.' Med. Jour. March 1870, by Dr. E. H. Clay, as a fibro-nucleated or cancroid growth in the pericardium. In the Trans. Path, Soc. XX. p. 102, Dr. Church has described a mediastinal tumour, which 'consisted almost entirely of small nucleated cells, indistinguishable from those met with in lymphatic glands.' Fig. 90. ' "Whether the lymphoid corpuscles, when they are produced in parts in which they do not exist as normal constituents of the texture, may not to some extent have migrated from the lymph or bloodvessels, is a question which, for the present at least, must be left undetermined. VASCULAR TUMOURS. 573 LECTURE XXVIII. PART II. EEECTILB OK VASCOLAB TUMOURS — PAPILLARY TUMOURS. The Erectile or Vascular Tumours, or Angeioma, include most of the diseases wliich are described as vascular naevi. Among them, also, are the growths to which John BeU gave the name of aneurism by anasto- mosis, and those which have been called Telangeiectasis. They are tumours which consist almost entirely of vessels which are held together by a small proportion of intermediate connective tissue. They are pro- duced either by an unusual development of the vessels normally present in a locality, or by a growth of new vessels. The name ' erectile tumour ' has, of late years, come into general use, as expressing a principal fact concerning the best-marked examples of this disease — namely, that they resemble very closely in their tex- ture that of the erectile or cavernous tissue. The likeness which these tumours bear to the erectile tissue, as exem- plified in the corpus cavernosum penis, is sometimes, in general appear- ance, perfect. A well-marked specimen is in the Hunterian collection,^ from which the adjoining sketch was made (Pig. 91). It was removed from under the lower jaw, and its cut surface displays a close network, or sponge, of fine smooth, shining bands and cords, just like those of the corpus cavernosum penis, only less regular in their arrangement. The opportunities of examining such tumours in the recent state are rare ; and they are usually spoiled by the operations for removing them ; but what I have seen, and the descriptions which others have recorded, leave little doubt that this imitation of erectile tissue is a frequent character among them. John Bell's account ^ of the aneurism by anastomosis, which is by ' Mus. Coll. Surg. 301 A, ^ Principles of Surgery/, i. p. 456, et seq. 574 VASCULAR TUMOUES. Fig. 91. far the most vivid and exact, in relation to the history of the disease, that has yet been published, accords vfith this statement. Although he had chiefly in view the arterial var- iety of these tnmours, yet of one he says, ' The substance of it was cellu- lar, stringy, and exactly resembling the corpora cavernosa penis . . • the cells were filled with blood from the arteries, which entered ^K^SBFJU/IS'^Sft^^^fi' ^^^ tumonr in all directions. ^^i^MimMtt^NllMK ^°^^^^ ^^ compares to a sponge W^m^JM'm^l^ablfkm soaked in blood; and the descrip- tions of other examples, though less explicit, imply the same. The descriptions by Mr. Wavdrop ' and Mr. Caesar Hawkins,^ and the more minute accounts of structure by Mr. Goodsir,' and Mr. Liston,* and Rokitansky,' confirm this view ; and neither Mr. Birkett's,^ nor any other that I have met with, is discordant from it. The essential structures of the disease are derived from such a growth of bloodvessels, or rather of blood-spaces, that, in imitation of erectUo tissue, the whole mass seems formed of cells or spaces, opening widely into one another ; and, in extreme cases, no remains exist of the walls of the vessels, except those narrow bands and cords that bound and intersect the cell-like spaces. The amount of the tissue which remains between the blood-spaces depends on the seat of the tumour, and the extent to which the compression and absorption of the intermediate tissue has proceeded. It seldom exists in any very distinct form, but a case has been described by C. 0. Weber, in which abundant fatty and fibrous tissue occupied the intervals between the dilated blood- spaces ; and in some other cases smooth muscular fibres have been seen in the meshes of the cavernous strncture. The division, often made, of erectile or vascular tumours into such Fig. 91. Section of an erectile tumour in the College Museum, described above. It is drawn one-third larger and rather coarser than natural. ' Med.-C'hir. Trans, ix. p. 201, and PI. vi. ^ Medical Gazette, xxxvii. p. 1027. ' Monthly Medical Journal, 1845. Anatomical Memoirs, \i. 1868. * Med.-C'hir. Trans, xxvi. p. 12.5. ' Pathologische Anatomic, i. 276. ' Med.-Chir. Trans, xxx. p. 193. SMVl MATEKNi; 575 as are named, respectively, ' capillary,' ' arterial,' aad 'venous,' is con- venient, and probably well founded. Tbe most frequent examples of subcutaneous nsevi, and the more frequent superficial nsevi, wliicli are like them in structure, though different in position, are such as may be called ' capillary ; ' understanding, only that they probably affect minute arteries and veins as well as capillaries. But, on the one hand deviating from these specimens, we find that in some cases the enlarge- ment of arteries far exceeds, in proportion, that of the veins ; the swel- lings pulsate, and are florid and overwarm, and, if injured, throw out arterial blood. These constitute the ' arterial ' form of the disease : the ' aneurism by anastomosis.' And, on the other hand, are tumours formed mainly of dilated, sacculated, and overgrowing veins ; to these arteries of comparatively small size pass, while from them proceed very large veins : and they are subject to changes of size in all the events that affect, not the arterial, but the venous,' part of the circulation. Now, I believe that, in a majority of cases, the arterial and the ve- nous form of the disease are constituted by a dilatation of large branches of one or the other kind, being superadded to such a condition of the smiall vessels and capillaries as exists in the common or ' capillary ' erec- tile tumours. But I have, also, no doubt that, in rarer instances, arte- rial tumours are formed by arteries alone, convoluted, or anastomising in a heap, whence, as from an arterial ' rete mirabile,' normal arteries proceed and lead to capillaries. And, on the other hand, there are, doubtless, venous tumours, which are formed of veins alone, and through which, since they are seated altogether beyond capillaries, the blood passes (according to Rokitansky's comparison) as it passes through a portal vein. The Capillary Yasoular Tumours, or nsevi materni (Telangeiectasis of the German pathologists), consist of closely-arranged minute blood- vessels. In the bright red superficial naevi, the vessels which lie in the papillse of the skin are dilated, tortuous, and convoluted, so that, in- stead of a single loop being present in each papilla, the vessels form a network. In the subcutaneous blue-coloured nffivi, the vessels which are enlarged are those of the sweat-glands, the hair follicles, sebaceous glands, and subcutaneous fat-lobules. The characters of the subcuta- neous uEevi may be gathered from the following specimen which I exam- ined. A child, two years old, which had a nsevus of this kind on the side of the chest, died exceedingly emaciated after measles and diarrhoea. 576 N^VI MATEENI. The tumour had grown from birfch-time, and had appeared as one of the most ordinary subcutaneous naevi or erectile tumours ; soft, com- pressible, dimly blue as seen through the skin, swelling in forced expi- ration, thinly scarred over its centre, in consequence of an ulcer which had spontaneously formed and healed. After death it had shrunk into a very thin layer of brownish tissue between the emaciated skin and the fascia covering the serratus magnus. It was well defined, and could be dissected out cleanly from the adjacent parts. Its surfaces and sections had a distinct lobular arrangement, many lobes projecting from its borders, and those within it being separated by connective-tis- sue partitions derived from the tough skin and fascia between which the tumour lay. In its shrunken state, it most resembled, in its obvious characters, a piece of parotid gland ; being pale brown in colour, lob- ulated, soft, but tough, and yielding but little blood on pressure. About six small collapsed veins proceeded, in a tortuous course from the surfaces and borders of the tumour. Its arteries were too small to be distinct. Examined with the microscope, the whole mass appeared composed of bloodvessels interlacing in white and yellow fibrous tissue, which probably belonged to the natural subcutaneous structure. No parenchymal cells or abnormal forms of tissue were found ; the disease seemed to be of the bloodvessels exclusively. The vessels, which were very difficult to extricate, in any length, from the matted tissue about them, were of all sizes, from 2Wo to ^-g of an inch in diameter ; but I think none were larger. Nearly all of them were cylindriform ; a few were unequal, or varicose, or sacculated, with small pouches projecting from their walls (Fig. 92). I could not discern their arrangement ; but they did not appear to branch often ; neither am I sure that they differed in structure from the normal vessels of subcutaneous tissue, except in that they were, considering their size, of less complex structure : they were as if minute vessels were enlarged without acquiring the perfect form of those which they equalled in ca- libre. In some parts I found long cords of connective tissue, which probably were obliterated bloodvessels. I have examined other tumours resembling this, but in less favour- able conditions. From all, however, as well as from the descriptions of others, I believe the common structure of this form of erectile tumour is a collection of minute bloodvessels, dilated, and closely ar- ranged within a limited area of some natural texture. In the subcnta- neous tissue, arteries usually appear to pass into the vasculax mass fronai the under surface of the skin ; and veins radiate from it, larger than CAPILLARY VASCULAR TUMOURS. 577 Fig. 92. the arteries and more numerous, but scarcely exceeding the proportion between the normal cutaneous veins and arteries. Within the tumour (which thus, as well by the relation of its vessels as by their minute- ness, justifies the epithet 'capillary') it is probable that some of the vessels are always sacculated or varicose. Virchow's ' account of this state exactly confirms what I have described ; and, with more detail, Robin ' describes an erectile tumour in which, along the track of the vessels, nu- merous little culs-de-sac existed, which the blood might be made at will to enter and quit, by alternately pressing and let- ting free a piece of the tumour on the field of the microscope. These could be seen on vessels as small as ^\ of a milli- metre in diameter : they were generally smaller at their connection with the vessels than at their other ends, and were commonly twice as long as the vessels were wide. But although the vessels within the tumour be thus dilated, yet, as a general rule, in this form of the disease, the dilatation (if there be any) in those proceeding to and from the tumour extends but a short distance from it : the arteries enlarge (if at all) only just before they enter the tumour ; the veins regain their calibre soon after they leave it : and hence the general safety with which John Bell and many others have cut out such tumours, when they attended to the rule he Jays down with such emphatic repetition, that in treating such a tumour we are ' not to cut into it, but to cut it out.' However, this limitation of enlargement to the vessels within and near the tumour, is not so usually observed in the next two forms of the disease, as in this which I have just described. The characters of the Arterial Erectile Tumour may be learned from a specimen which I examined from a man who died under the influence Pig. 92. Bloodvessels of the erectile tumour described in the text (iffus. St. Bar. Series xxxv. No. 89). Magnified about 200 times. ' ArcMofilr Pathol. Anatomic, iii. p. 437. Ib Lebert ; Physiologie Palholngique, ii. p. 9 r P 578 AETERIAL VASCULAE TUMOURS. of chlorofonn at St. Bartholomew's Hospital. He was twenty-three years old, and the disease occupied the external ear, the adjacent subcn- taneons tissues, and part of the scalp. The back of the auricle, in nearly the whole extent, was puffed out by a superficially-lobed, soft, easily compressed, and elastic swelling, which all pulsated fully and softly. Two similar and continuous lobes of swelling were under the scalp above and behind the auricle ; and these were well-defined above, but gradually subsided below. The skin covering the swelling was for the most part dusky purple, but except where it was scarred, appeared of healthy texture ; the skin of the interior of the auricle and its fibro- cartilage also appeared unaffected, except in the turgescence of the bloodvessels. A posterior branch of the superficial temporal artery passing by the front of the swelling, and a branch of the posterior auri- cular artery passing behind it, felt large, and pulsated strongly ; the common carotid artery, also, on this side, pulsated more fully than that on the other. A distinct soft bruit was audible, synchronous with the pulsation in the tumour ; and distinct pulsatile movement was visible. This disease had been noticed like a very small pimple when the patient was four years old. It had from that time regularly increased. On four occasions severe bleeding had taken place from it, through an ulcer in the skiu over it, or through a prominent part over which the skin was extremely thin. After the first of these bleedings a piece of the swelling had been tied, and had sloughed away. A month before the patient's death, Mr. Lloyd had tied and compressed the branch of the temporal artery and two other principal arterial branches at the borders of the swelling ; and by this and subsequent treatment had diminished the size of the tumour and the fulness of the pulsation in and around it. Much of the tumour had been spoiled by this treatment, but enough remained to show that a great part of its substance was like that last described, and probably, like it, consisted of minute bloodvessels col- lected in a soft spongy mass. But, while the veins proceeding from the swelling were of no considerable size, the arteries passing to it and within it were very large, convoluted, and thin- walled. This was espe- cially observed in the posterior auricular artery, which had not been interfered with in the operations. A lobe of the swelling (as it seemed) had pulsated strongly below and behind the lobule of the ear ; and it was for the operation of tying this that the chloroform was given to the patient. This proved to be only a part of the posterior auricular artery, which, from a short distance beyond its origin, was large, and more collapsed and flattened than the other branches of the external ca- ARTERIAL VASCULAR TUMOURS. 679 rotid. At the beginning of its enlarged part, this artery was from a line to a line and a half in diameter ; and from this point its trunk, as well as its branches (which were not unnatural in either number or anastomosis), were tortuous and coiled up in heaps, which had felt during life like pulsating masses. The dilatation of the arteries was uniform, not sacculated, though in jDarts^the suddenness of the curves made it appear so. The small intervals between them were filled either with the natural connective tissue, or with the minute bloodvessels that composed the chief mass of the tumour. I believe that this specimen presented a fair example of the ordinary structure of the arterial form of vascular or erectile tumours ; and that they consist, essentially, of the minute vessels of a limited portion of tissue enlarged and closely clustered, so as to form a tumour, in the substance, as well as about the borders, of which are arteries, much more enlarged, and convoluted into pulsating heaps. In these tumours the veins are comjiaratively small, and the diflBculty of transit for the abundant blood flowing into them, doubtless adds materially to the ful- ness of the tumours, and of the jjulsations seen and felt in them. The existence, and even the preponderance, of the minute vessels in such tumours was manifest in a specimen sent to me by Dr. Orme- rod (Mus. St. Bar. Series xxxv. No. 91). A healthy woman, about sixty years old, had for many years a pendulous growth in the lower and inner part of the left axilla. Lately it had grown quickly to the size of the closed hand. It was dark, hard, and knotty, with a distinct pulsa- tion, and hung on a pedicle in which a large artery could be felt. A ligature was tied on the pedicle, and a few hours after another was applied, and the pedicle was cut through. The tumour was gorged with blood, ecohymosed, and too much damaged for complete examination. Its general aspect was like that of the pedicled outgrowths of skin ; but nearly its whole mass consisted of minute bloodvessels confusedly arranged and of various sizes. Their walls showed nuclei, which were generally shorter than those of healthy arteries ; but in many instances were placed, as in them, regularly in layers, the external lying longitudinally, others within these transversely, and, still within these, others that were obliquely or variously placed. Besides the bloodvessels, I could find in the tumour only a compara- tively small quantity of connective tissue ; and Dr. Ormerod's examina- tions made when the tumour was more recent, had similar results. Some I think, have described the arterial tumours as formed by the convolutions of a single artery ; and the characters of the swelling p p 2 580 VENOUS VASCULAR TUMOURS. formed by the trunk and commencing branches of tbe posterior anricular artery, in t'ae first of these cases, make me ready to believe that this description may be sometimes tme. But I think that, more commonly, many branches of arteries are engaged in the tumour. Such was the case in the tumour of the ear, and in an instance recorded by Mr. Coote.' Arteries of the lip, which, in their natural state, might not have had a greater diameter than a large pin, were dilated for about an inch of their course into sinuses or canals, and were equal in diameter to the adult radial artery. Similar to this was a very formidable case, cured by compression, under the care of Mr. Lloyd. The temporal, supraorbital, and occipital arteries, aU exceedingly dilated and tortuous, converged to a large pulsating swelling over the sagittal suture, the general char- acters of which agreed exactly with what I have described. The Venous Vascular Tumours are those to which the term cavernons is especially applicable. In the venous tumours the veins are very large, the arteries comparatively small. Of this kind of tumour the following case presented a good example. A man, thirty- two years old, was under the care of Sir W. Lawrence. He had a hoof-shaped tumour projecting from the middle of the outer part of his thigh. It was from six to eight inches in diameter, and looked like some strange outgrowth of skin. Its base rested on the fascia lata ; it was covered with skin, which was healthy, except in one excoriated place, and adhered closely to it. It was firm, but com- pressible and elastic, and by long-continued pressure could be reduced to nearly half its size, as if by squeezing blood from it. Several small arteries pulsated at its base ; and very large veins, like tor- tuous sinuses, converged from it towards the upper part of the saphena vein. The patient was in feeble health, apparently through the effect of a life in India, where, in the army, he had received a wound by a mnsket- ball, to which he referred as the cause of the growth of this tumour. Before the wound, he believed the part was quite healthy. The injury appeared superficial, and he was absent from duty only two days ; but, six months afterwards, he observed a small tumour, and this, growing constantly and with severe pain, had increased in ten years to the present mass. The skin had been slightly ulcerated for twelve months, and severe hremorrhages had occurred from the ulcerated part, reducing his already diminished strength. ' Medical Gazette, xlv. VENOUS VASCULAR TUMOUES. 581 Sir W. Lawrence cut away the whole tumour. Its connections were slight, except to the skin covering it ; the arteries at its hase bled freely, bat for a short time ; the great veins bled very little. A section through the tumour showed that, while some parts of it appeared solid and close- textured, like a mass of firm connective tissue, the greater part was like the firmest cavernous or erectile tissue. Sections of bloodvessels of various sizes and in various directions, were so thick-set, that the surface looked aU reticulated and grooved with them. The general colour of the tumour, which seemed to have almost emptied itself of blood during the operation, was nearly white ; but in some parts it had a pale ruddy tinge, and in a few was blotched with small rusty and ochry spots. The microscopic examination was less instructive than the general aspect of the tumour. Its tissue was very hard to dissect, and displayed (as its chief constituent) matted and crooked fibres, like those of close- textured, longitudinal, striated membrane of bloodvessels, with shrivelled nuclei imbedded in membrane, some of these nuclei being round, some oval, and some very narrow and elongated. I think the obscurity of the microscopic appearances was due to the tenacity with which the bloodvessels were imbedded in the elastic fibrous or nucleated tissue ; it seemed impossible to eitricate complete vessels ; and one obtained by dissection only fragments of their walls confused with the intermediate tissues. Other cases of venous nsevi, which I have been able to examine less completely, have confirmed the foregoing account, especially in regard to the small size of the arteries in comparison with the veins, the genera,lly dilated and varicose state of the latter, and the imitation of the characters of erectile tissue, which appears always more marked in the venous than in the other forms of vascular tumours. Such ate the principal facts that I can site regarding the structure of the vascular or erectile tumours of the walls of the bloodvessel. From these few facts some general considerations may be derived. That which is common to all the vd;SCular or erectile tumours is an over-extension of bloodvessels or blood-spaces within a circum- scribed area. Their chief varieties depend (1) on the kind of vessels affected, and (2) on the nature of the tissue in which these vessels lie. The varieties of the first class have been pointed out ; but all of theta alike present the singular instance of the apparent primary growth of bloodvessels. In all other tumours, as in all abnormal pro- ducts, the formation of bloodvessels appears to be a consequent 582 GEOWTH OF VASCULAR TUMOUES. and subordinate process. As in tlie natural development ot parts, so in what is morbid, organisation to a certain point precedes vascularity, and the formation of bloodvessels follows on that of the growths into which they pass. Bat here the case appears reversed. The calibre of the bloodvessels increases, and the solid tissues between them diminish ; all the growth of an erectile tumour is an enlargement of bloodvessels, with diminution of the tissues in which they ramify ; or, rather, it is often an enlargement, not of bloodvessels, but of blood- spaces ; for though, in the first stages of the disease, the walls of the vessels may grow, and elongate, so that the vessels become tortuous, yet, after a time, the walls waste rather than grow ; apertures seem to form through mutually apposed bloodvessels, and at length, while the blood within, the tumour increases, the bloodvessels containing it diminish, together with the parts in which they ramify. Hence, at last, in place of branching and anastomosing tubes, there is only a network formed of the remains of their walls. This is an increase of blood-spaces rather than of bloodvessels ; so far as solid tissue is concerned, we might call it a wasting, rather than a growth ; no new materials seem to be added, but step by step the bloodvessels are dilated, and the intervening tissues clear away, leaving room for more and more blood. Such a fact constitutes a great contrast between these and any other diseases named tumours. And yet perhaps we may properly regard these as being overgrowths of bloodvessels, comparable vriih the over- growths of the various other tissues illustrated in the preceding chapters. And their relation to such overgrowths seems, sometimes, distinctly proved in the gradations of morbid changes that connect them with mere enlargement of bloodvessels. If we examine different specimens of these tumours, or sometimes even the condition of the vessels ad- jacent to one of them, we may observe a regular gradation from the erectile tumour, through clusters of dilated and tortuous vessels, to that which we regard as merely the varicose condition of the veins or arteries. Such transitions are well shown in some of Cruveilhier's plates, and in a remarkable case by Dr. Hake and Mr. Image ;' as well as in two of the cases that I have related. In relation to the nature of the tissues in which this overgrowth of bloodvessels may take place, we may hold that there are two chief classes of cases. In the first class, and these include the greater part of the common erectile tumours of the skin, and of the other parts in ' Medico-Chimrgical Transactions, xxx. p, 109. GENERAL CHARACTEES OF VASCULAR TUMOURS. 583 "whicli these tumours are seated, tHe bloodvessels normally present in the part are aiFected, or new vessels arise in the part, which subsequently- become affected. In either case the vessels dilate and become sacculated ; the intermediate tissue, and even the walls of the vessels atrophy ; and fenestra are formed, so that communications take place between adjacent vessels. ^ In the second class of cases, though these are probably rare, spaces arise in the connective tissue of a part, which afterwards become filled with blood and connected with the general system of vessels of the region. ^ The skin and subcutaneous tissues are the localities in which the erectile tumours by far the most frequently occur ; and though they may affect any part of the surface, yet the integuments of the head, face, and neck, are more especially apt to be their seat. In the cavity of the orbit also erectile tumours have not unf requently been described ; and though there is good reason to think that the symptoms observed in a large number of these cases are referable to other diseases,^ rather than to a vascular tumour, yet some cases still remain in which evidence of the occasional existence of erectile tumours in this locality seems to be satisfactory.* The muscles are very seldom the seat of these tumours,^ but in the Museum of St. Bartholomew's is a preparation in which an erectile growth, not surrounded by an investing capsule, had form.ed in the substance of a muscle ; and in a case of intra-muscular erectile tamour recorded by Mr. De Morgan the tumour possessed au envelope of connective tissue.^ In the bones,^ the parotid gland,' the ' Vircliow, Arckiv, vi. p. 526 ; Esmaroh and Maier in the same Archiv, vi. p. 34, and viii. p. 129. '' Eokitansky, 8itz. Bericht der Kais. Akad., 1862 ; also Luschka, in VirchoVs Archil:, vi. p. 458. Vircho-vr regards this case of Luschka's not as a trae cavernous vascular tumour, but as an alveolar myxoma, the blood spaces in which were offshoots of the vessels lying in its trabecular framework. = Mr. Busk, Trans. Med.-Chir. Soo. London, xxii.; and Mr. Niuineley in the same, xlii. ; Dr. Joseph Bell in Edinb. MontUy Med. Journal, June 1861. ' Case by Von Grafe, quoted in Virchow, Die Kranjchaften Gesahvimkte, Lecture = Mr. Listen, Med. CUr. Trans, xxyi. 120; Mr. Coote, loo. cit., and Cruveilhier XXX. pi. 5. = Medioo-Chirurgical Review, Jan. 1864. Much information on the occurrence of vascular tumours in muscles is contained in this paper. ' Among these may be included, probably, most of the cases described under the name of Aneurism of Bone and Osteo-Aneurism. I am far from convinced that, in all the cases thus entitled, the bloodvessels of the bone were primarily or chiefly diseased. My impression is that in many oT them the disease was really medullary cancer or myeloid tumour of the bone with large development of vessels, and that in some it was such a blood-cyst as appears to be sometimes formed in the course of a myeloid or cancerous disease. " Mr. Gascoypu, Trans. Path. Soc, ±i. 584 GENERAL CHAEACTERS OF A'ASCULAR TUMOURS. liver, kidney, spleen, brain,' uterus and supra-renal capsules,^ erectile tumours have been described. As I bave bitberto cbiefly bad in view tbe subcutaneous erectile tumours or naevi, so I will now, in describing tbe general characters of tbe disease, refer to them alone for examples. Even of these, indeed, it is difl&cult to give a general account, since we can make only an artificial distinction between such as may bear this name, and those extended dilatations of cutaneous vessels which, with little or no swell- ing, form the cutaneous nsevi, port- wine spots, and the like. These are, evidently, essentially the same disease ; the terms, cutaneous and sub- cutaneous naavi, respectively applied to them, imply only their difiTerence of seat ; they have no real difference of nature, and are very often asso- ciated. But, if we include only such as are for the most part or wholly subcutaneous, then it ma.y be said that they are generally round or oval, disk- shaped or spheroidal, but are often difiTuse and ill-defined, the morbid state of tbe bloodvessels in which they consist gradually merg- ing into the healthy state of those beyond them. Sometimes, and especially in those of most venous character and of longest duration, the mass is circumscribed by connective tissue, which forms a kind of capsule, is penetrated by the bloodvessels passing to and from, the tumour, and is very intimately connected both with the surrounding parts and with the tumour. The dilatations of the vessels with the cavernous spaces are lined by an epithelium continuous with that lining the arteries and veins which pass into and out of the tumour. The vascular tumours are remarkable by their frequent beginning before birth, and their especially quick growth in early childhood. Beyond all comparison, they are the most common of congenital tumours. Hence, mother-spot is almost synonymous with nsevus, and nsevus with erectile tumour. But they may begin, or acclerate their growth, at any period of life. I have seen one of which no trace exis- ted till the patient was twenty-five old ; and another in which rapid growth began, for the first time, when the patient was past fifty. Dr. Warren mentions a case of erectile pulsating tumour about the angles of the eyes and forehead, which began in a girl seventeen years old. Many others, no doubt, have seen similar cases. Their origin is generally unknown ; but, as one of the cases I have related shows, they may commence in the results of injury ; or, rather, ' Virchow, op. cit., refers to various cases in the liver, brain, etc. ^ Dr. Payne, in Trans. Path. Soc. xx. p. 205. SUBCUTANEOUS NiEVI. 585 a tumour may originate in injury, and in this tumour an exceeding formation of bloodvessels may ensue. Their growth is uncertain ; they may seem at rest for many weeks after birth, and then grow quickly, and then again may stay their growth ; and, having attained a certain size, may remain therein limited, or may decrease or disappear, the vessels, in whose enlargement the growth consisted, regainingtheir natural calibre or becomingobliterated. Frequently two or more exist in the same person. There are not many observations on the recurrence of these tumours ; but Mr. Annandale relates^ that he has seen in Mr. Syme's practice three cases of vascular recurrent tumours in the cheek, in two of which cases the tumour recurred three times. Their maintenance of life, if I may so term it, is not strong. They are miich more apt than the natural tissues are to slough or ulcerate after injury ; and, in general disturbances of the health, they may perish altogether. I know of a case in which a large subcutaneous nrevus in a child's forehead sloughed, while another on its back, of much less size, was in process of sloughing after the application of nitric acid. Similar apparently spontaneous sloughings have occurred during, or in the debility following, measles or scarlatina. Such events may be connected with the extreme slowness of the movement of blood in the tumours ; for though they contain abundant blood, they probably transmit it very slowly. Venous tumours not unfrequently contain clots of blood and phlebolithes ; such, probably, as would form only where the circulation is most slow ; and even in the arterial tumours the full pulsation seems to indicate a retarded stream. The diseases of the vascular tumours are of mnch interest ; especi- ally two amongst them — namely, the formation of cysts, and that of malignant structures in their substance. I just referred to the formation of cysts in erectile tumours, when speaking, in Lecture XXII., of serous cysts in the neck, and of sangui- neous cysts. The history of the changes by which an erectile tumour becomes in part, or wholly, cystic is very incomplete ; for the oppor- tunities of observing them, except when they are accomplished, are rare. The principal facts are, that, next to the erectile tumours, those that are composed of clusters of serous or sanguineous cysts appear to be the most common congenital form, and that in some cases the two forms appear in one mass. I referred in Lecture XXII. (p. 402) to ' Edinburgh Medical Journal, Dec. 1865. 586 DISEASES OF VASCULAE XUMOUES. STicli a case as recorded by Mr. Coote. Mr, Caesar Hawkins/ also, had before described similar eases. He says of one, ' yon may sec, in addi- tion to the usual vessels, thab several apparent cells exist. Some of these were filled with coagnlnm ; their structure appeared identical with the other veins, of which, they constituted, as it were, anenrismal pouches. . . . There were, however, beside these, some other cysts, which contained only serous fluid, and which were, to all appearance, close-shut sacs — serous cysts — their size being about that of peas.' In other instances, no erectile or nsevous structure can be found, but the communication existing between one or more among a cluster of cysts and some large bloodvessel, makes it probable that they had the same origin. Thus, Mr. Coote traced a vein, as large as a radial vein, opening into the cavity of a cyst, which formed one of a large cluster removed by Sir W. Lawrence from a boy's side. The mass formed by these cysts had existed from birth ; some of them contained a serous fluid, others a more bloody fluid. In another similar cluster,^ removed from a boy's groin, one cyst appeared to communicate with the femoral vein, or with the saphena at its junction with the femoral. In one case mentioned by Mr. Hawkins,^ when a cyst in the neck was opened, arterial blood gushed out. In another, the patient died with repeated haemorrhages from a cyst in the neck, and this cyst was found after death to be one of several, into some of which the bloodvessels of the isthmus of the thyroid gland opened. It is difficult to interpret the formation of such cysts in naevi, or in connection with them or with veins. It may be that, as Mr. Hawkins believes, cysts are formed in these, as they may be iu many other tumours, and that gradually, by the absorption produced by mutual pressure, they are opened into communication with one or more of the veins, or of the sacs connected with the veins. Or, as Mr. Coote sug- gests, it may be that certain of the dilatations of the vessels are gradually shut oflF from the stream of blood, so as to form shut sacs ; and that after this their contained blood is absorbed, and replaced by serous Juid. Lastly, respecting the production of cancerous disease in the tissue of erectile tumours, it seems to be generally regarded as a frequent event, and these are commonly believed to afford the most frequent instances of malignant growths supervening on such as were previously ' Mudko-CMrurgical Transactions, xxii.; and Medical Gacette, xxxvii. p. 1027. * The specimen is in the Museum of St. Bartholomew's Hospital. ' Clinical Lecture?, in the Medical Gasette, xjtviii. p. 838. LYMPHATIC VASCULAR TUMOUES. 587 innocent. I -will not donbt that such events have happened. In one case recorded by Mr. Phillips,' the transition appears to have been very clearly traced. Tet, I think that in many of the cases which have gained for erectile tumours their ill repute, a clearer examination would have proved that they were, from the beginning, very vascular medullary cancers, or else medullary cancers in which blood-cysts were abundantly formed. Or it may be that the erectile tumours have been presumed to be liable to cancer, through having been supposed to share in the peculiar liability of the pigmentary nssvi, or moles, to be the seats or melanosis. LympJiatic Cavernous Vascular Tu-nwurs. — Oases in which one or more of the lymphatic vessels of a part have been dilated, and in which the dilatation either was or was not associated with expansion of the lymph-spaces within the lymphatic glands, have occasionally been des- cribed. These cases have already been referred to (p. 458) as produc- ing a form of elephantiasis. But other, though rarely seen, cases have been observed, in which not merely had a dilatation of the normal lymph- vessels of a region taken place, but an actual new formation of such vessels had apparently occurred. A tumour had been in this manner produced, which, in its structure, was similar to the venous cavernous tumour, except that the spaces did not contain blood, but a fluid which closely resembled lymph. Tumours of this kind have been named cavernous lymph-angeioma, or lymph-vascular tumours. Like the cavernous blood-vascular tumours, they possess the property of erectility. These growths seem more especially to affect the tongue^ocoasioning one of the forms of makro-glossie — the lips, the cheeks, and the eyelids. They are usually congenital. Billroth has described an illustrative case, in the lower lip, where a semi-globular tumour was composed of a cavernous tissue, ihe bars of which consisted of connective tissue, which contained many elastic fibres and bloodvessels. The spaces were lined by an epithelium. They contained a clot with a serous fluid, in which small corpuscles like those of lymph were found.' ' On Vascular Tumours, in the Medical Gazette, xii. p, 10. 2 Btitrage zur Pathologisohen Histologie, 1858. — This subject is fully discussed by Virchow, Die Krankhaften Geschwiilste, iii. p. 487. Consult also Th(5ophile Anger, Bes Tumeurs Erecliles Lymphatiques, Paris, 1867. Eeichel describes, in Virchow's Archiv 1869, p- 497, a case of congenital cystic cavernous lymph-angeioma in the perineum, close to the scrotum, in an infant set. one year and five months. 588 PAPILLARY TUMOUES. 1*APILLAET TuMOtTES. By the name papillary tumour, or Papilloma, certain new growths whicli occasionally project from the free surface of the akin, the mucous, serous, and synovial membranes, may be designated. They may be occasioned either by a hypertrophy of normal papillse, or may be entirely new formations in the part. These growths, in their general form and arrangement, have many points of resemblance, but on an enlarged scale, to the papillae which, in various localities, con- stitute natural projections from free surfaces, more especially from the skin and mucous membranes. To some extent these papillary growths, in whatever locality they may be found, correspond ia structure with each other. Their basis substance is formed of connective tissue, which is continuous with that which normally exists in the part ; whilst the free surface is covered by an epithelium which may vary in its thickness, and in the number of its layers, according to the seat of the tumour. Bloodvessels, and even nerves, enter into the interior of the papilla3. When a number of these new papillary growths become aggregated together, they may form a tumour of some size. Of the cutaneous papillary growths, the best known example is the common wart, which in many persons forms in such nlimbers on the skin of the hands. These warts consist in an excessive development in length and thickness of both the dermal and epidermal structures which constitute the papillae of the skin. The condylomatous growths which sometimes form in the region of the prepuce, and about the labia and anus, are excessive developments of the same character ; and when they exhibit a very irregular, subdivided surface, they present the well-known cauliflower appearance. The anatomical characters which distinguish these simple warts and condylomata from cancerous growths of the skin, in which the papillae are enlarged, will be referred to in the lecture on epithelial cancer. The horn-like structures which are occasionally seen projecting from the skin of the face and head, are also papillary growths in which an excessive increase in the epidermal investment has taken place. These horns are usually bent or twisted, and when removed have a great tendency to be reproduced. Various of the mucous memhranes are also liable to be affected with abnormal papillary growths. Many of the mucous polypi, already PAPILLARY TUMOURS. 589 described (p. 453), are complicated -with, papillary formations. Some- tim.es the new-formed papilte are scattered irregrdarly over a consider- able tract of the mncous surface, so as to give it a villous, velvety appearance, though at others they are aggregated into the form of a distinct tumour. The bladder, colon, and rectum, are more especially the seats of villous or papillary growths, which in some cases seem to be simple and innocent in their nature,' though in others they possess a malignant character, and will be more appropriately considered in the section on villous cancer. The papillee are recognisable to the naked eye, and impart a distinct villous appearance to the mucous surface, from which they spring. They divide and give off lateral sprouts or branches ; they are vascular, and the epithelium which invests them usually corresponds in form with the normal epithelium of the part. In these simple papillary growths the tissues are not infiltrated with cancerous elements. Papillary growths also sometimes project from the mucous mem- brane of the larynx in connection with, or in the immediate neighbour- hood of, the vocal cords. ^ The florid and highly vascular growths which frequently occur at the orifice of the female urethra are papillary formations in which bloodvessels exist in considerable numbers, so that they are allied to the vascular tumours. The vessels are, however, arranged in loops, and are not as a rule dilated. Wedl describes ^ in one case, that the vessels were arranged as in the vasa vorticosa of the eyeball. The epithelium, in the cases I have examined, was tessellated and abundant. Papillary growths from serous surfaces are extremely rare, but there is one locaHty in particular in which they grow, and where they may form very distinct tumours. The investigations of Professor von Luschka* into the anatomy of the Pacchionian bodies have proved that those bodies are nothing more than an enlarged condition of the villi which normally grow from the surface of the visceral arachnoid, or from the inner serous surface of the dura mater ; and it would seem that at times the villi may increase so much in size and numbers as to > air Sibley Tram. Path. Soc, vii. pp. 214 256; Mr. Sliaw, idem, v. p. 200; Sir H. Thompson, yiii. p. 262 ; Mr. Bryant, xi. p. 153 ; Dr. W. 0. M'Intosh in Mm. Med. Journal, January 1866. „ , ,, 2 Prof, von Bruns has recorded {Vrdundzwanzig neiie Beobachtungen von Polypen des Kehlkopfes, Tahingen, 1868) several eases where he had been able to remove the 3 Translation p 409, by the Sydenham Society, of his Tvork on Pathological Histology. ' ^Mulhv',Arahiv,m2. .'590 PAPILLAHY TUMOURS. form well-marked tumours. Professor Clelanll has recently described ' two cases, in one of wHcli a tumour as large as a small orange, in tte other as large as a walnut, projected from the inner surface of the dura mater. Whilst the surface of each tumour was in part smooth, it was to a large extent papillary or villous. Dr. Cleland concludes from the examination of these tumours, that they were produced by a morbid enlargement of the villous growths from which the Pacchionian bodies are themselves derived. A villous or papillary tumour has been recorded by Dr. Moxon,^ growing into the sub-arachnoid space from the free surface of the pia mater covering the pons Varolii. Papillary growths from synovial membranes do not fall to be con- sidered in a course of lectures on tumours. ' Glasgow Medical Journal, July 1863. * Trans. Path. Sac. xix. p. 21. EECUERENT TUMOURS. 591 LECTURE XXIX. EECDEEENT TTJMOUES. Is the course of these lectures on tumours, I have pointed out, under the head of each class, that, after the complete removal of one no growth of a similar nature is likely to recur in the same, or in any other part. And this is certainly the rule for the vchole class of innocent tumours, and a character by which they are seen to be essentially different from cancers, amongst which recurrence, after removal, in the same, and in other parts, is the rule. I have, however, had to mention, in connection with most of the groups into which the innocent tumours have been divided, instances in which recurrence took place after complete extirpation. As this is so important a character, and one which possesses so much interest both clinically and pathologically, we may fairly be justified in grouping these tumours under the separate head of Recurrent, and devoting a lecture to their consideration. Almost every form of tumour may occasionally present examples of recurrence, so that the distiuguishing term I have employed must be understood to express, not the possession of any specific form or structure, but rather a peculiar tendency manifested in the life of the tumour. Por it may be accepted as a well-established fact, both in physiology and pathology, that apparent similarity of structure between two or more diSerent parts is not of itself sufficient to determine functional correspondence. The examination, therefore, of any texture, either morbid or healthy, cannot be regarded as complete if it is limited to a mere determination of its form, appearance, and structure. Its growth, development, tendencies, influences upon the individual in whom it occurs, in short, its life, must be attended to. Its teleological as well as its morphological aspects are to be considered. I have already described (p. 432) instances in which proliferous cysts recurred after removal. At p. 461 a case of recurrence of a fatty tumour has been referred to, and on p. 620, et seq., several cases have been mentioned, in which cartilaginous tumours not only 592 EECUERENT TUMOURS. returned in the same part, but even appeared in distant organs. Recurrence and secondary deposits of the myeloid tumours have now- been described in more than one instance (p. 552),' and the mammary glandular tumours have occasionally returned after removal (p. 563). The fibro-cellular tumours, more especially in the soft gelatinous form which has recently been termed myxoma (p. 458), also present addi- tional illustrations. Although the various instances of recurrent tumours which have been recorded, present many diversities of structure, yet they may be said generally to have possessed the characters of incomplete develop- ment, to have exhibited an undue preponderance in the cell-elements which they contained, and to have presented the embryonic or mdi- mental, rather than the perfect state of the natural tissues. And this rule of persistent or arrested embryonic structure in the recurrent tumours is so general, that in practice it is advisable to speak with hesitation of the ultimate result of any case in which a tumour is found to be composed of mdimental tissues, This similarity in structure to embryonic texture becomes more strongly marked after each removal and recurrence. A tumour which, at first, might be not unlike the normal fibrous or glandular texture in which it grew, after repeated removal and recurrence becomes softer, more succulent, and in its later growths may seem to the naked eye little more than like masses of yel- low or ruddy soft gelatine with bloodvessels. The later are usually much more rapid in their progress than the earlier growths : they are generally less well defined, penetrating farther and more vaguely among the interstices of adjacent parts, and more quickly protruding through the skin or scars over them, And in these characters the later-formed tumours assume more of the character of malignancy than the earlier. In the case I relate on p. 596, the last tumour was, in general aspect, hardly to be distinguished from brain-like tumour, though in microscopic characters essentially like its predecessors. In one of Professor Gluge's cases the transitions to completely malignant characters appeared yet more sure. Mr. Syme also expresses a similar transition : describing, as the usual course of ' Dr. Wilks also has recorded a case {Path. JVans. x. p. 244) of a man whose leg was amputated hy Mr. Cock for a large myeloid tumour of the head of the fibula. Two years afterwards a recurrence took place in the stump. Eemoval was again performed, and a few days afterwards the man died of pleurisy. At the post-mortem examination, secondary myeloid tumours, of considerable size, were hanging pendulous from the exterior of the lungs, but not infiltrating their substance. But the more frequent result of amput itions for recurrent tumours of the limbs has been an apparently final remedy. EECUREENT TUMOURS. 593 the cases he has seen, that, after one or two recurrences of the tnmour, the next now productions present a degeneration of character, excite pain, proceed to fungous ulceration, and thus in the end prove fatal. So that, although there be cases in which this evil career has not been run, yet I think we may regard these tumours as approximating to cha- racters of malignancy, not only in their proneness to recurrence after removal, but in their aptness to assume more malignant features the more often they recur. Whatever be the truth concerning the supposed transformation of an innocent into a malignant morbid growth, I think it can hardly be doubted that in the cases of some recurring- tumours the successively later growths acquire more and more of the characters of thoroughly malignant disease.' But this evil result does not by any means follow as a necessar_t consequence of the repeated recurrence of the tumour, for there are many cases now recorded in which the patient retains, to all appearance, perfectly good health, and shows none of that cachexia which would almost certainly exist in a patient who had suffered ^repeated recur- rences of cancer. No more striking example could be adduced in illustration than the case related by Dr. Douglas Maclagan, and de- scribed further on, in which the tumour appeared nearly forty years ago, recurred, and was removed altogether four times, with consider- able intervals between each recurrence, and yet the patient is still in perfect health. The recurrence of these tumours takes place, not merely in the same organ or tissue, but in loco — in the place in which they originally occurred — in the cicatrix, or closely adjacent to the scar of the first operation wound. And here, again, do they possess a character by which they are distinguished from the malignant tumours, which in their recurrence may multiply not only in the same part but in distant organs. Cases certainly have been recorded, more especially of some cartilaginous tumours (p. 521), in which growths of the same nature arose in distant parts, as the lungs, but in them there is distinct evi- dence of the growth being propagated either directly by the veins or along the lymphatics into the veins, and then into the pulmonary artery and its minute branches. In their tendency to recur in loco, in the undue preponderance of > An illustration is presented by a remarkable case, of which specimens are described in Cat Mus. St. Bartholomew's, Series xxxv. Nos. 28, 29. Other examples are adduced in the recurring proliferous cysts, p. 432, and in a case of recurring fibroid recorded by Mr. Hulke, Med. Tim's and Gazette, Nov. 29, 1 862. Q Q 594 EECUERENT FIBROID TUMOURS. their cell- constituents, and in their rudimental or embryonic struc- tural characters, these recurrent tumours correspond with many of the tumours which Virchow has grouped together under the general term Sarcoma. Thus we have in these recurrent tumours characters which connect them on the one hand with the innocent, and on the other with the malignant tumours, so that the plan I have adopted of placing them in a group intermediate -between those two great divisions seems not in- expedient. And this relation to, and partial possession of, the characters common to the two divisions, appears to be in some measure accounted for by these recurrent tumours being so frequently found in members of cancerous families. I have seen several cases in which these tumours occurred in the descendants or near relatives of those who are, or have been, cancerous, and I have heard and read of others like them ; from which I have been led to form the opinion, that, amongst the members of families in which cancer has manifested itself, there is a peculiar liability to the production of tumours, which will recur after repeated and complete excisions, though they are neither cancerous in structure, nor attended with similar disease in the lymphatic or other organs ; nor with any cachexia but such as may be ascribed to their gradual in- fluence upon the constitution.' With these general remarks on the group of recurrent tumours, I shall now proceed to a special and more detailed account of the tumours which I have termed Recurrent Fibroid : and among which the most numerous and striking examples of recurrence have been found, al- though the general characters of the group are equally well marked in other tumours where rudimental structures occur. In their structural characters the recurrent fibroid tumours correspond with the spindle- celled sarcomata of Virchow. A brief account of some cases of this tumour may best illustrate it. The first I saw was from a gentleman, sixty years old, under the care of Mr. Stanley. In 1846 a tumour was removed by Mr. Cockle from, the upper and outer part of his leg. It lay close to the tibia, was as large as a filbert, and was considered fibrous. Some months afterwards another tumour was found in the same place, and, when as large as a walnut, was removed by Mr. Hamilton, of the London Hospital, who cousidered it ' decidedly fibrous.' In October 1847, Mr. ' For a more detailed account of the relations of recurrent to cancerous tumours, I may refer to a paper in the Medical Tones and Gazette, Augiist 22, 1857. RECURRENT FIBROID TUMOURS. 595 Stanley removed from the same place a third tumour ; and this T ex- amined minutely. It had the shape, and nearly the size, of a i^atella, and the note that I made of its general appearance was, that it was ' very like those fibrous tumours which are whitest, most homogeneous, and least fasciculate and glistening ; ' and that ' without the microscope I should certainly have called it a fibrous tumour.' The microscopic examination, however, showed peculiar structures (Fig. 93). The tumour was composed almost entirely of very narrow. Fig. 93. spindle-shaped, elongated, caudate, and oat-shaped nucleated cells, many of which had long and subdivided terminal processes. Their contents were dimly shaded ; and in many instances the nuclei ap- peared to swell out the body of the cell, as in the most elongated granulation-cells. With these cells were scattered free nuclei, and grumous or granular matter, such as might have been derived from disintegrated cells. Very little filamentous tissue was contained in any part of the tumour. Now, in the extirpation of the third tumour, the parts around it were very freely removed, the periosteum was scraped from the tibia, and every assurance seemed to exist that the whole disease was cleared away. But, in June 1848, two small tumours appeared in the subcu- taneous tissue just below the seats of the former operations. These also were removed, and these had the same fibrous appearance, and the same minute texture, as the preceding. Some months only elapsed before in the same place another tumour grew ; i.e. a sixth tumour. The patient, despairing of remedy by operations, allowed this to grow till November 1850, by which time it had acquired a diameter of be- tween four and five inches, and protruded as a large soft fungoid mass from the front of the leg. Two profuse haemorrhages occurred from Fig. 93. Microscopic elements of a reciiTring fibroid tumour described above. M.igiiified about 400 times. Q Q 2 596 EECUKRENT FIBROID TU3IOUI15. it, and made him earnestly beg that his limb might be removed to re- lieve him from the extreme misery of his disease. The amputation was performed, and he died in a few days. The tnmonr' appeared confused with the thin skin over it. It rested below on the mnscles of the leg, bnt was not mixed with them, except at a scar from the former operations. The tnmour was milk- white, soft, and brain-like, except where discolonred by eflfased blood, and in the exposed parts was soft, pulpy, and grumous. One would certainly, judging by its general aspect, have called this a brain-like medullary cancer ; and yet it had essentially the same microscopic characters as the tamours I first examined from the same patient : only, the narrow, elongated, candate cells were very generally filled with minute shining molecules, as if from fatty degenera.tion connected with the protrusion and partial sloughing of the mass. Unfortunately no examination of the body was made after death, and it conld only be guessed, from the absence of emaciation, and of all other indication of general loss of health, that no similar disease existed in internal organs. In another case of the same kind, I assisted Mr. Stanley, in May 1848, in the removal of a tumour from the shoulder of a gentleman twenty-eight years old. It had been growing under the deltoid for six months, was loosely connected with the surrounding parts, and was about three inches in diameter. It had the general aspect of a common fibrous tumour : firm, tough, white, traversed with irregular bands. It was easily and completely removed, but was not examined with the microscope. The wound of the operation healed well ; but, two months afterwards, a second tumour appeared under the cicatrix. This was removed with some of the adjacent muscles, and other tissues. It was like the first, only less tough, and more lobed, and elastic ; but under the microscope, instead of appearing fibrous, it was found to be composed almost entirely of elongated and caudate nucleated cells, very like those described in the last case, "and mixed with free nuclei and granular nfiatter. In March 1849, a third tumour was removed from the same part, which had been noticed two months, and again presented the same character ; it was indeed greyer, and less firm, and more shining and succulent on its cut surfaces, but the differences to the naked eye were not great, and the microscopic structure was the very same as in the former instance. ' Iq the Museum of St. Baitholomew'e, Series xxxv. No. 97. EECUREENT PIBEOID TUMOUES. 597 In October 1849, another tnmour had formed, and, after it had resisted various methods of treatment, Mr, Stanley removed it, by a fourth operation, in December. This had again the same chaiacter. In the course of 1850, a fifth tumour appeared in the same part, and this, after growing slowly for an uncertain time, ceased to in- crease, and has now been for a long time stationary, without in any way interfering with the patient's health. He is pursuing an active occupation, and, but for the tumour, might be thought a healthy man. In a third case, Mr. Syme removed, in 1839, a tumour which, without any knoAVn cause, had been growing for a year, over the an- terior part of the first right rib of a gentleman forty-eight years old. Two years after the operation, another tumour appeared in or near the same part, and was removed by Mr. Syme in 1843. A third was re- moved'by him in 1847 ; and a fourth in 1849. After another distinct interval of apparent health, a fifth tumour appeared, and grew quickly, and was removed by the same gentleman in 1851. In one of these, an account of which was pubhshed by Mr. Syme, Dr. Hughes Bennett found microscopic structures similar to those of the fibro-plastic tu- mours of Lebert;! similar, therefore, I have no doubt, to those de- scribed above. The patient recovered from the last operation, as from all the previous ones, quickly and favourably; but the wound had scarcely healed when two more tumours appeared beneath the scar, like the preceding ones, except in that they grew more rapidly. One of these tumours was so firmly fixed at the clavicle that no further operation could be recommended. In six months' growth the tumours, at first distinct, had formed a single mass, deeply lobed, of oval form, measuring a foot in one direction, and about ten inches in the other, It covered, and felt as if tightly fixed to, the middle half of the clavicle, and thence extended downwards over the chest, and outwards towards the axilla. It felt heavy, firm, tense, and elastic. The skin, thinly stretched over it, and by its tension appearing as if adherent,' was generally florid, but in some parts livid, and over the most prominent lobes ulcerated ; but the principal ulcers were super- ficial, covered with healthy-looking granulations, discharging thick pus, having no cancerous or other specific character : only one of them ' Monthly Journal of Medical Science, x. p. lO-l. Probably this refers to the elongated cells alone. I have not, in any of these tumours, found the large many- nucleated cells which occur in most of the tumours named flbro-plastic by M, Lebert. 598 EECUKRENT PIBROID TUMOURS. had a thin slough. Such were the characters of ths disease when I saw it in February 1852, and it was very striking, as evincing one of the contrasts between this form of tumour and any rapidly-growing ulcerated cancer, that the patient's general health was scarcely affected. He was still a florid sturdy man ; and he fed, slept, talked, and moved about as a man in health might do. He suffered scarcely any pain; but, within the last month, the ulcerated surface of the tumour had Hed severely. The tumour was now submitted to compression, with Dr. Neil Amott's apparatus ; and with some advantage, inasmuch as its growth was retarded, and the htemorrhage was prevented, so long as the pressui-e was maintained. Twice, however, on the instant of removing the apparatus, I saw arteries as large as the radial throw blood in a jet far from the trunk. The bleeding was in this respect such as I have never seen from the proper vessels of any other tumours, and was like that described as occurring in the first of these cases. It would be useless to tell, at any length, the later history of this case. The tumour increased constantly to the time of the patient's death in July 1862 ; but, in the last two months, several small portions of it sloughed away, and it gradually shifted lower down on the chest, leaving the clavicular region, so that at the time of death it lay movable on the musfles, and could be removed, ' as a common fatty tumour might be,' without dividing any important part : death seemed due to mere exhaustion, consequent on the discharge from the tumour, and the pain to which, as it extended farther into the axilla, it gave rise. Dr. Ross, to whom I am indebted for an account of the conclusion of the case, could find no indication of disease in any internal organ. Only the tumour was allowed to be examined after death ; and Dr. Ross wrote to me of it, in addition to the account of the absence of any deep connection or infiltration of adjacent tissues, that ' its texture was pretty hard, like that of a fibrous tumour, but not nearly so dense or crisp as scirrhus. It scarcely gave out any blood on being cut into ; but here and there was to be seen, on the surface of a section, the open mouth of a vessel, just as in a section of liver. All the textures behind, forming the bed of the tumour, appeared quite healthy. A portion of the tumour, kindly sent to me by Dr. Ross, was, after hav- ing lain in spirit, milk-white, firm, elastic, of very close texture, breaking and tearing with a coarse fibrous grain. It had, most nearly, the as- pect of a very firm fibro-cellular tumour altered by spirit. When scraped it yielded little or no fluid, bat white shreds, in which, together with much that looked like withered tissue or debris, there were abun- EECUEEENT FIBEOID TUMOURS. 599 dant slender awn-sbaped corpuscles, such as are sketched in Fig. 94. Tliey looked dry and shrivelled, containing no distinct nuclei, but mi- nute shining particles, as if themselves were outgrown nuclei. With these, also, were numerous broader and shorter corpuscles, of the same -■ \D I"ig. 94. general aspect, but enclosing oval nuclei ; and yet more numerous smaller bodies, like shrivelled, oval, elongated, free nuclei, dotted, and contain- ing minute shining particles. The whole mass appeared made up of corpuscles of these various shapes, irregularly or lineally imbedded in a substance that was nearly structureless or imperfectly fibrillated. Only in a few places, perhaps in the partitions of the lobes, there was a very small quantity of fine connective tissue. I think there can be no doubt that this case was essentially of the same kind as the former two ; and the constancy of their peculiarities in both history and structure appears sufficient to justify the placing them in a separate group and under a separate title^ But these are not the only cases to be cited. Professor Grluge has given a good general account of the history of such tumours as these, as examples of the forms transitional to cancer. He names them ' albuminous sarcoma ; ' a term one hears frequently used, without, perhaps, any clear meaning ; yet generally, I think, with the suspicion that the growths to which it is applied are not wholly innocent. Among the cases which he cites, one coincides exactly with those I have detailed. A major, forty-five years old, fell from his horse in 1843. Six or seven weeks afterwards, a tumour appeared over his scapula. It was removed, but after some months returned. Between 1843 and 1848, four such tumours were removed from the same part. In 1848, the patient was under the care of M. Seutin, who removed the Fig. 94. Microscopic structures of the recim-ing fibroid tumour described above. Magnified 450 times. 600 EECUERENT FIBEOID TUMOUES. fifth, tumour ; and Gluge's description of this, including the expression that in colonr and consistence it was like the muscular tissue of the intestinal canal, leaves little doubt that it was like the less firm of the specimens that I have been describing. In the last of these five operations, and in one previously, the removal of the tumour was followed by free cauterisation of the wound ; yet the last account published by Professor Gluge was, that in April 1849, a sixth tumour had appeared in the same part ; and he has informed me by letter that in 1850 the patient died. A case which, in its conclusion, is the most instructive of all that have been recorded, is related by Dr. Douglas Maclagan.' A girl, twenty-two years old, had a tumour, of three years' growth, on the left lumbar region, about an inch from the spine. In 1832, it was about as large as a jargonelle pear, iirm, but elastic and movable, and below it was a portion of indurated skin. The tumour and diseased skin were removed, and the former ' possessed most of the ohai'acters of a simple fibrous tumour.' After about twelve months the disease returned in the soar. Three little tumours formed, and these, with the scar, were removed freely in February 1834. ' The extirpated mass bore a striking resemblance to that previously removed.' Between twelve and eighteen months later, a third gTOwth appeared, which, after creasing for a year and a half, was removed. ' It had the same elas- tic feel and fibrous appearance ; and the semi-transparent pinkish grey colour was the same as in the original tumour.' In March 1857, Dr. Maclagan sent me a portion of another tumour cut out from the same place in this patient, by Mr. Spence. ' This specimen presented to the naked eye exactly the same appearance which the former tumours did.' On microscopic examination it was exactly after the type of the recurrent fibroid tumours, and in naked-eye appearance just like the others that I have seen. In November 1868, Professor Spence ex- cised from the right breast of this woman a tumour of the size of half a small melon. It was hard, almost stony, and painful, and the nipple was retracted ; but the axiUary glands were not enlarged. The section of the tumour was concave ; its colour dullish white with yellowish spots, and it contained a cyst, which had smooth vascular walls and puriform contents. The tumour had in part a well-defined outline, but in part it was blended with the surrounding fat and areolar tissue. The cell-forms making up the chief part of the tumour were circular, ' Edmhurgh Medkal and Surgical Juurual, xlviii. 1837. EECUEBENT FIBEOID TUMOUES. 601 or oval, or caudate, or irregularly stellate, and ttey lay in an ill-defined trabecular structure. Througli the courtesy of Dr. Maclagan I am enabled to state, that at this date (January 1870) there has been no recurrence of the tumour, either in the breast or in the loins. The woman is now in her sixtieth year, and in the enjoyment of good health. Dr. Maclagan has added the account of another case, in which the essential features were quite similar. Another, which I believe must be referred to this group, is accurately described and figured by Dr. Hughes Bennett.' Some cases have occurred in the practice of Sir J. T. Simpson, iu which fibrous tumours, growing from the cervix uteri into the vagina, and removed by operation, have recurred after an interval of some time. When cut into, these recurrent uterine tumours do not exhibit the concentric appearance so characteristic of the ordinary fibrous tumour of the uterus, but have much more of a granular aspect. In one case the tumour recurred three times, and the tumours removed on the second and third occasions were exami- ned microscopically by Professor Turner. In the second tumour the fibro-muscular structure was recognised, more especially in and near the pedicle of attach- Fig. 95. ment. But when the tumour was well teased with needles, numerous pale, round, oval, caudate, and spindle-shaped nucleated corpuscles, similar to those just described as met with in the recurrent fibroid tumours, were also recognised. The nuclei of the spindle-shaped cells Fig. 95. Microscopic structure of the recurrent fibroid uterine tumour described in the text. ' On Catweroiis and Cancroid Growths, p. 87. Cases of recurrent fibroid tumours have been recorded by Mr. Birkett in Guy's Hospital Reports, Series iii. iv. ; Mr. Hutchinson, Med. T. and Gaz., August 20, 1853 ; Billroth, Virchow's Archiv, viii. 1855: Verneuil, Mem. de la Soc. de Biologie, 1865; Mr. Callender, Trans. Path. Soc, ix. p. 327 ; Dr. Roberts, Beale's Archives, October 1861 ; Mr. Annandale, Edin. Med. Journ., p. 432, 1862 ; Mr. C. Heath and Mr. Hulke, Med. T. and Gas., November 18, 1862. 602 FIBEO-JSUCLEATED TUMOURS. ■were rouud or oval, and not rod-like as in the contractile mnscular fibro-cells. In the last tumour removed, the muscular tissue could not be re- cognised, and the connective tissue was very sparing. The tumour was chiefly composed of spindle-shaped nucleated cells, such as are drawn in 6, Fig. 95. These cells, as at a, lay in close contact with each other. In some localities, as at c, the nuclei were imbedded in a dimly granular protoplasm, in which no well-defined differentiation into distinct corpuscles was seen. Numerous so-called free nuclei, as at d, were visible in the field of the microscope, which closely resembled in form and appearance the nuclei within the fusiform cells, and had probably escaped during the dissection of the various specimens ex- amined. The tumour was a characteristic example of the recurrent fibroid tumour, or spindle-celled sarcoma. FiBEO-NUCLEATED TUMOUES. Dr. Hughes Bennett' has given the name of Fihro-nucteated to certain tumours, first described by himself, which have I think a very near affinity with those which I have been considering. They are, indeed, of so rare occurrence, that we cannot as yet be sure of many things concerning them ; but their most usual characters seem to be, as assigned by Dr. Bennett, a general resemblance to the fibrous tumours ; a tendency to return in the part from which one has been excised ; an absence of disposition to affect lymphatics or more distant parts ; and a texture ' consisting of filaments infiltrated with oval nuclei.' The first three characters are repetitions of those belonging to the recurring fibroid tumours ; the last is not so ; and yet the difference of structure is such as may consist with a very near natural relationship. The history of these cases is important, especially because, like the last described, they seem to occupy a kind of middle ground between innocent and malignant tumours. They are among the diseases which are often spoken of as ' semi-malignant,' ' locally malignant,' or ' less malignant than cancer: ' terms which are generally used in relation to what are deemed exceptional cases, but which may appear to have a real meaning if ever we can apply them to well-defined groups of tumours. The most characteristic of the cases described by Dr. Hughes Bennett tvas that of a lady twenty-five years old, from whom, when she ' On Cancerous and Cancroid Growths, p. 176, etc. HBEO-NUCLEATEU TUMOUES. 6U3 was eighteen, a tamour of four years' growth, was removed from the left thigh, nearly in front of the great trochanter. After its removal there remained a small hard knot in the scar ; bn.t no change ensued in this for six years. Then it began to enlarge and increase, and in a year increased to the size of a small almond-mit. Jt was superficial, quite movable, and intimately adherent to the skin. It was hard and dense ; and its cut surface was smooth, slightly yellowish, and yielded no juice on pressure. It appeared to consist of fine filaments, among which oval bodies, like nuclei with nucleoli, were everywhere infil- trated. Here and there large oval rings appeared, marked by con- verging irregular lines, and, in a few places, oval spaces surrounded with concentric marks, like sections of gland-ducts. The only well-marked case that I have yet seen was that of a boy, ten years old, on the palmar aspect of whose forearm a small indentation was noticed at birth. This part was slightly wounded when he was two years old, and from that time a tumour began to grow. When he was four, the tumour was removed (of course completely) by Mr, Sands Cox, but the wound did not heal before another growth appeared. This increased at first slowly, but at last quickly ; and when the boy came under my care, it formed an oval swelling rising to nearly an inch and a half above the surrounding skin, and measuring from three to three and a half inches in its diameters. The skin over it was very thin, adherent, tense, and florid, and at the centre ulcerated, and superficially scabbed ; the ulcerated surface was granulated, like one slowly healing. The mass felt firm and elastic, and at its borders very tough, like the tissue of a cicatrix ; little cord-like branching processes extended from its borders outwards in the deeper substance of the cutis ; and above the principal mass another, like a small flattened induration of the skin, was felt. The growth was not painful, and the general health appeared -good. Some axillary glands were slightly enlarged. I removed the whole disease, witli all the surrounding skin that appeared in any way unhealthy, and large portions of the fascia of the forearm and of the intermuscular septa, to which the base of the growth adhered intimately, and which were indurated and thickened. The wound very slowly healed; the enlargement of the axillary glands subsided ; and the patient remained well for about twelve years after the operation. The tumour was intimately adherent to all the parts adjacent to it, yet was distinct and separable from them. Its section was smooth and shining, of stone-grey colour, shaded with yellowish tints. It was 604 FIBRO-NUCLEATED TIBIOTJES. GS) ^ lobed ; but in its several lobes was nniform, and with no appearance of fibrous or other structure : but intersected irregularly by white and buff- yeUow branching lines, where the microscope found a fatty degeneration of the tissue. In texture the tumour was firm, but easily breaking and splitting in layers, shell-Kke ; with the microscope it appeared to be composed of two materials — namely, nuclei, and a sparing granular or molecular substance in which they were imbedded. These, as sketched in Fig. 9G, were so hke those represented by Dr. Bennett, as to leave little doubt of the similarity of the two cases ; only there was less appear- ance of fibrous structure, and less of texture like that of the glands. The nuclei were, generally, of regular elongated oval shape, from -rsVff ^° j^^ "of an inch in length, and generally bi-nucleolated ; compara- tively few were broader, or reniform, or irregular. They were very thick- set in a molecular basis-substance, and in many parts (perhaps in all that were not disturbed) they appeared as if arranged in overlaying double or triple rows, which radiated to a distance from some point, or from some space of round or elongated oval form. These spaces, if they were such, appeared full of molecular matter. It would be wrong to endeavour to draw mauy conclusions from so small experience as yet exists on these tumours.' I will only express or repeat my behef that these are examples of a form of tumour which will be found most nearly related to the recurring fibroid tumours. They have been included by Virchow in his group of spindle-celled Sarcoma. Fig. 96. A, Nuclei ; jj, nucleated structure of the tumour described above. A magnified 450 times ; b about 230 times. ^ Fig. 96. ' A recurrent tumour removed by Mr. Xunn from the female breast (Trans. Path. Soc. xix. p. 380) is apparently a tumour of the fibro-nucleated form. SCIEEHOUS CANCEE.. 605 LECTURE XXX. SCIEEHOUS OE HARD CANCER. PART I. ANATOMY. The foregoing lectures on tumours have comprised the histories of the Innocent and the Recuerent Tumours ; and in the first of them I related the characters generally appertaining to the Malignant Tumours, or Cancees, which it now remains to descrihe. For an account of this class of tumours it will, I hope, sufS.ce if, after reference to the first of these lectures, I describe, in order, each of the chief forms in which cancers occur, and then gather such conclusions as may be drawn respecting the general pathology of the whole class, and the relations of the several forms to each other, and to other tumours. The chief forms of cancer are named severally Scirrhous, Medullary, Epithelial, Melanotic, Heematoid, Osteoid, Colloid, and Villous. These, at least, are the names most frequently applied to them. The degrees of difference between the diseases to which they are severally applied are not nearly equal ; and, probably, under certain of them, two or more diseases are included which are sufiiciently diflPerent to justify their separation witK distinct names. But these are points which, having just mentioned, I may leave to be discussed in the account of each ftirm of cancer, or in the concluding lecture. First, I will speak of Scirrhous or Hard Cancer. Being both more frequent and more obvious than any other form of cancer, this was, to the beginning of the present century, the type and chief example of the disease ; and so, in regard to its physiology, and many particulars of its structure, it may still remain. It has received many names,' such as scirrhus, scirrhoma, and others, expressing that ' Enumerated by Dr. Walshe : On Cancer, p. 10. 606 SCIEEHOUS CANCER hardness of texture wliich is its distinctive and especial cliaracterisfic ; or sncli as Carcinoma reticulare, implying certain minute peculiarities of structure. I believe, however, that these peculiarities are too in- constant and accidental to justify the division that they suggest : I will therefore include them all under the name of Scin-hous or Hard Cancer ; and will use these terms for all stages of the disease, avoiding that which seems always a confasing distinction in which, before ulceration, the disease is called Scirrhus, and after it, Cancer. I will describe the Scirrhous Cancer first, as it occurs in the breast, because here the disease is far more frequent than in any other part, and presents, openly, most of its varieties of appearance according to its successive stages, and the accidents to which it is exposed. The scirrhous or hard cancers in the breast are very far from being so uniform that they may be briefly described. I believe that they are always primary cancers ; always infiltrations ; and almost always seated, in the first instance, in some part of the mammary gland ; but, when we compare their other characters in any large number of specimens, we find in them many and great diversities. Probably, therefore, it will be best if I describe first and chiefly the ordinary characters of the disease ; the form in which it is most frequently seen, when it has not been changed by softening, ulceration, or any other morbid process. I can then add to this description, by way of comparison, some accounts of the principal deviations from the more usual form ; and, in the next part of the lecture, can give the history of the changes that ensue in the progress of scirrhous cancers towards destruction, or in their much rarer regress. Most frequently, the scirrhous cancer of the breast appears as a hard mass occupying the place of the mammary gland, or of some portion of it. In the cases I have collected it has not been more frequent in one breast than in the other. It is least frequent at or near the inner mar- gin of the mammary gland ; but with this reservation, it is not much more frequent in one than in another part of the gland, or in any part than in the whole. While part of the gland is cancerous, the rest is, commonly, healthy ; but, according to the age and condition of the patient, it may be more or less atrophied and withered ; or excess of fat may be accumulated round it ; or it may contain numerous small cysts, or one or more large cysts, most confusing to the diagnosis : or, more rarely, it may be the seat of mammary glandular tumour (p. 662), or of some morbid change OF THE BREAST. 607 of sfcracture. As yet, however, I believe, no connection can be traced between any of these conditions and the growth of cancer, unless it be that it is peculiarly apt to happen in breasts that are being defectively nourished. The hardness of the cancer, as compared with that of other tumours, is in most cases extreme : it is about equal to that of a lum.p of fibrous cartilage, and is associated with a corresponding rigidity, weight, and inelasticity. Cases, however, are not unfrequent, especially when the cancer grows quickly, in which the mass is less hard,' — very firm rather than hard, — about as flexible and elastic as the body of an unimpregna- ted uterus. The size of a hard cancer is seldom very great. In most eases it is rather smaller than the part of the gland which it occupies was when healthy ; so that, e.g., if half a mammary gland become cancerous, and half remain healthy, the latter may be two or three times larger than the former ; or, if the whole gland become cancerous, it may be reduced to less than half its natural size. The exceptions to this diminution in the size of the cancerous gland are, I believe, in cases of very rapid growth, in which the cancer-material seems to be added more rapidly than the materials of the gland can be removed. The shape of the hard cancer, also, depends chiefly on the part of the gland that it affects. Generally, it may be said that when the cancer does not extend beyond the limits of the gland, it does not much deviate from the shape of the aflPected part ; only, it gathers up, as it were, the gland-lobes into an irregular lump, in which their outline is not lost, but blunted. Hence, according to their seats, we may observe different shapes of hard cancers of the breast. At the anterior surface of the gland it is usually convex or obliquely shelving; at the posterior surface it is flat or slightly concave, resting on the pectoral muscle ; iu the middle, or thick substance, of the gland it is commonly rounded and coarsely tuberous, knotted, or branched ; at the borders it is often dis- coid, or else is peculiarly apt to extend from them, in a mass reaching to the adjacent skin (Fig. 97) ; and when the whole gland is affected, the cancer has commonly a low conical shape, or is limpet-shaped, with the nipple set on the top of the cone (Fig. 98).' ' The terms 'ramo.se,' 'tuberous,' and 'infiltrated,' have been applied to specify the hard cancers, according to their shapes ; but the shape appears so little connected with any other oliaracter of the disease, — it seems so nearly accidental, — that it cannot bo adopted for a ground of specific appellation. Moreover, there is no reason for especially calling the cancers that aifectthe whole gland, infiltrated ; for all the hard cancers of the breast are infiltrations in less or more of its structure. 608 AXATOMY OF SCIEEHOUS From, any such cancerous lump, processes, like crooked, gnarled, and knotted branches, may extend outwards in correspondence with the outlying lobes or processes of the gland. But shapes like these are comparatively rare, and scarcely less so are the instances in which Fig. 97. portions of the gland, after becoming cancerous, are detached from the chief mass ; or those in which, in the same gland, more than one cancer forms at the same time. Such oases do, however, happen ; and Fig. 98. I have known the smaller detached cancers nearly escape removal in operations. As we dissect towards the surface of a hard cancer, especially of one of which the growth is not very rapid, we m.ay observe that rela- tion of the tissues around it which is so characteristic : I mean their contraction towards it, and their progressive absorption. It is as if, in its progress, the cancer were always growing more and more dense, by the contraction and compacting of its substance, and by the absorption of the tissues it involves ; and as if, in this concentric contraction, it drew all parts towards itself To this it is due, that, even from the first, and when it is yet very small, a hard cancer in the breast feels as Fig. 97. Section of a hard cancer, extending from a border-lobe of the mammary gland to the superjacent skin, and affecting both these and the intervening tissues. Natural size. Fig. 98. Section of a hard cancer of a whole mammary gland. Half the natural size. CANCER OF THE EEEAST. 609 if it could only be moved with the gland around it ; it does not slide or roll under the finger as a mammary glandular tumour does. To this, also, is due the slight dimpling of the skin over the nearest adjacent part of the cancer, even long before the two have become adherent ; and to this we must ascribe the more numerous depressions, seaming and wrintling the surface of the breast, and making it appear lobed, when, in a case of cancer occupying the whole of a large and fat breast, many parts of the skin are drawn inwards. To the continuance of this contraction and absorption, also, are due the sinking down of the retracted nipple, and the uplifting of the superficial fibres of the great pectoral muscle ; and then the deeper furrowing and the adhesion of the sunken skin or nipple, and the firm conjunction of the pectoral muscle with the deepest portion of the cancer. Sometimes one finds bands of tough tissue extending from the retracted parts of the skin to the surface of the cancer. These are commonly supposed to be always cancerous, — ' claws,' or outrunners from the cancer ; but the supposition is only sometimes true ; they often consist of only the connective tissue between the lobes of the subcutaneous fat, condensed and hardened. A scirrhous cancer in the breast has no distinct or separable capsule of connective tissue investing it : the proper tissues of the breast, that are in contact with its surface, adhere to it very intimately ; and the more so, the more slowly it has grown. The general boundary between them is, indeed, distinct to the sight ; yet it is not easy to dissect out the cancer ; and, at certain parts, it is evident that the tissues around the cancer are continuous with some of those within it. Especially, we can often see that the lactiferous ducts pass from the nipple, or some healthy portion of the gland, right into the substance of the cancer. When we out through an ordinary scirrhous cancer of the breast, such as I am chiefly describing, the surface of the section becomes at once, or in a few minutes, slightly concave. This is a very character- istic appearance, though not a constant one : I know no other tumour that presents it. In all others, I think, the surface of the section either rises and becomes slightly convex, especially at its borders, or remains exactly level. In well-marked scirrhous cancer, the cut surface becomes concave, sinking in towards its centre, through the persistence I suppose of that tendency to contraction, to which, during life, we B E 610 ANATOMY OF SCIRRHOUS Lave to ascribe the traction of tlie surrounding tissues, and which is now no longer resisted hj them. The cancer seldom appears, on its cut surface, divided into lobes : it is one mass, variously marked perhaps, biit not partitioned ; neither has it any distinct grain or fibrous plan of structure ; its toughness and tenacity are complete, and in every direction equal. It has generally a pale greyish colour, and is glossy and half-translucent ; often it is slightly tinged with a dim purple hue, or, in acute cases, may be more deeply and more darkly suffused. Very often too its greyish basis is marked with brighter whitish lines, like interlacing bundles of short straight fibres, and with minuter ochre-yellow lines, or small yellow spots, and with various transverse and oblique sections of ducts. The explanation of these various appearances, and of the minuter characters of the cancer, can be understood only by recollecting (what all the foregoing description will have implied) that the cancerous mass is composed not only of structures proper to the cancer, but of more or less of the tissues of the mammary gland, or other parts, among which the cancer-structures are inserted. And the differences implied in the words ' more or less,' may be considered as explaining many of the differences of appearances that hard cancers present. The consideration of the influence of cancer-formations on the tissues that they occupy belongs, more properly, to the general pathology of the disease ; but I must here just refer to the main facts concerning it. As I have said, the formation of a scirrhous cancer of the breast consists in the production of peculiar structures — cancer-cells and others — in the interstices of the proper tissue of the part (see Fig. 99) . Virchow has Hkened it to a tumour possessing an alveolar structure, in the alveoli of which are lodged cells possessing the character of epithelium ; and an almost similar comparison has been given by Rindfleisch. Thus, then, we have, in any such cancer of the breast, a mixture of cancer-substance and breast-substance. But among many cancers we should find many diversities in the proportions of these two substances, which diversities are determined, first, by the original pro- portions in which the two substances are mingled ; and, secondly, by the degrees of wasting, and other changes, that may occur in either or both of them. For example, a large quantity of cancer-substance may occupy so small a portion of the gland, that this portion, spread CAJICBR OF THE BREAST. 611 out as it is in the substance of the cancer, may be scarcely discernible and the cancer may look lite a completely isolated tumour ; or, on the other hand, the whole of an atrophied gland may be condensed within a comparatively small cancer. Moreover, after the original proportions of the two substances are determiaed, they may not remain the same ; for their subsequent pro- portions of increase or of decrease may be different. Generally, as the cancer-substance increases, so the involved structures of the breast dimiuish or become degenerate, till they can hardly be recognised, and the cancer is where the natural structure was : a complete ' substitu- tion,' as M. Lebert names it, is thus accomphshed. But the original tissues do not thus disappear at any given rate, or all in the same rate or order. The gland-lobules, I think, waste very early : I have never found them clearly marked within a scirrhous cancer. The larger gland-ducts remain much longer ; their cut orifices may be often seen on the section of the cancer, or they may be traced right into it from the nipple, or fragments of them may be found in microscopic exami- nations. The small gland-ducts, with their contents, often appear, in branching buff and yellow-ochre lines, imbedded in the substance of the cancer. The fat of the breast is commonly quickly wasted : we find sometimes portions of it encircled by the cancer, and sometimes its yellow tinge is diffused through parts of the cancer, as if they were thoroughly mingled : but both these appearances are limited to the superficial and more lately formed portions of the growth ; they are always lost in the central and older parts. There is the same gradual disappearance of the elements of the skin when it is involved ; so that we might say that the regular process in the formation of a cancer of the breast is, that as the cancer-substance increases, so the natural tissues involved by it degenerate and waste. I repeat, we might say this if it were not for the fibrous tissue that intervenes among the lobes and ducts of the gland ; for this seems either to waste more slowly than any other part, or to remain unchanged, or even in some cases to increase with the progress of the cancer. To these conditions of the fibrous tissue I shall again refer. Now if to the progressive varieties that may arise through these changes in the involved tissues of the breast, we add that parts of the proper cancer-substance may degenerate or waste, or may vary in their method of development, while other parts are merely increasing, we may apprehend, in some measure, the meaning of those great varieties of appearance which we find in any large series of cancers.. They are B K 2 612 fflCROSCOPIC ANATOIMY mainly due to the different modes and measures in whicli the consti- tuents of the cancer-substance and of the original tissues are first mingled together, and then increased, degenerated, or absorbed. After this necessary explanation, let me return to the description of the mingled mass. We find, as I have said, in any ordinary cancer of the breast, a greyish basis, which contains the proper elements of the cancer, but which is or may be intersected by visible fibres, ducts and yellow lines or spots, which belong chiefly or entirely to the textures of the breast. One may usually press or scrape, from the cut surface of such a cancer, a pale greyish, thick, and turbid fluid, which is easily diffused through water, and is much more abundantly yielded when the cancer has been macerated for a day or two in water. It is not creamy, but rather like thick gruel, and is usually composed of a mixture of the proper cancer- substance, and of the softened tissues of the breast, and the contents of the bloodvessels and remaining gland-ducts. It is called the ' Oancer-Juice,' and what is left after it is expressed is called the ' Stroma ' of the cancer (see, further, p. 617). I should state, how- ever that about the central and deeper parts, or sometimes in the whole masses of the hardest cancers, no such fluid can be obtained : they yield, to pressure or scraping, only a small quantity of yellowish fluid, like turbid serum. The remaining description of the Scirrhous cancer must be, chiefly, from its microscopic appearances. In very thin sections it is not difficult to see the infiltration, or in- sertion, of the cancer-substance in the inter- stices of the affected tissues. It may be most clearly seen ia sections of any part of the skin recently invaded by the cancer, for here, in the meshes of the reticulated con- nective tissue, the cancer-particles are quite distinct, filling every interval, and not ob- scured by the debris of the gland- ducts and their contents. I am not aware of any more Yiff, 99. orderly plan of arrangement of the materials of the cancer than that which may be ex- pressed by saying that they fill the interstices of whatever tissue they may lie in. They may either expand these interstices, when they ac- Fig. 99. Cancer-cells filling interstices among the bundles of the connective tissue, in the skin of a breast. Magnified about 200 times. OF SCIREHOUS CANCER. 613 cumulate quickly and abundantly, or, wlien they shrivel and degenerate they may allow the tissues to collapse or contract. The elementary structures of the cancer substance, thus infiltrated in the breast, are chiefly two : — namely (1), certain cells and other corpuscles ; and (2), a nearly homogeneous intercellular substance in which these lie imbedded. We may study these, but, it must be admit- ted, in some confasion and uncertainty, in the material obtained by the pressure from the cancer. The intercellular substance presents, I believe, no peculiar features. As obtained by pressure, it is made very impure by the admixture of blood and other fluids ; and it would be unsafe to describe it more minutely than as a pellucid or dimly granular substance, which in cer- tain cases, yet I think rarely, assumes an appearance of fibrous texture. The corpuscles of hard cancer are chiefly nucleated cells. In ordinary cases, and where the cancer has not been deflected from its normal course, their characters are constant and peculiar, and may be described as for the types of ' cancer-cells ' (Fig. 100). Fig. 100. In shape they are various. Usually a large majority are broadly oval, or nearly round : in some specimens, indeed, all may have these forms ; but, in other specimens, though these prevail, yet many cells have one or more angles, or out-drawn processes, and some are pyriform, some fusiform, some reniform, some nearly lanceolate. It would be useless to describe all the shapes that may be found, for we can, at present, neither explain them nor connect them with any corresponding differences in the general structure or history of the can- cers in which they severally occur. But we may observe, asBruch and others have done, on this multiformity as a feature of malignant structures : I know no innocent tumours, except the cartilaginous, in which it is imitated. In size, the hard cancer-cells range from -^^-^ of an inch to -^ of an inch in diameter. Their medium and most frequent sizes are from Fig. 100. Cells and free nuclei of scirrhous cancer: from cancerous breasts. Magnified about 600 times. 6H MICROSCOPIC ANATOMY TTTtro to xTOTF • ^lie smaller dimensions are usnally found in the cancers of quickest growth. In structure and general aspect they most nearly resemble, I think, the secreting gland-cells. Examined immediately after removal, and without addition of water, they appear clear and nearly pellucid ; but changes quickly ensue, which water accelerates, and which bring them to the characters more generally ascribed to cancer-cells. They become nebulous, or dimly granular, or dotted, as if containing minute mole- cules ; and they look no longer quite colourless, but very lightly grey- ish or yellowish. The cell-wall is, if it can be seen at all, peculiarly thin and delicate ; but it is often impossible to discern any, and my be- lief is that the cancer-cells are often only cell-shaped masses of some soft though tenacious substance, within which are nuclei. The nuclei in hard cancers are more constant in their appearances than the cells, and, I think, are even more characteristic. They are always comparatively large, having an average long diameter of about ■^oVfT of an inch, and varying from this size, much less than the cells do from theirs. They are regular, oval, or nearly round, clear, well- defined, scarcely altered by commencing decomposition or by water, or any moderately diluted test substance. A single nucleus is usually contained in each cell ; two nuclei in a cell are frequently found, but not in all specimens of hard cancer ; more than two are rare : when more than one are found in a cell, they are generally smaller than those that are single. Among the materials of a hard cancer, a certain number of free nuclei are usually found. It may be difficult to prove that these have not escaped from cells during the examination ; but I think they are naturally free nuclei, for they are often larger than those contained in cells, and they sometimes deviate from the common shape, after methods which are more often noticed among the corpuscles, of medullary can- cers, and which will be more fully described in the next lecture. Each nucleus has one, two, or rarely more nucleoli, which, like itself, are large in comparison with the ordinary proportion between nucleoli and cells, and are peculiarly bright and well defined. These seem to be the normal elements of hard cancer ; and such as we find them in the breast, such are they, but less mingled and confused with other forms, in the hard cancers of the skin, the bones and other organs. Indeed, these characters are so nearly constant and so pecu- liar, that an experienced microscopist can very rarely hesitate in form- OF SCIEEHOUS CANCER. 615 ^^^^j^i^ mg tipon them a diagnosis of the cancerous nature of any tumour in whicli they are observed. But it would seem as if hard cancer seldom long maintained an un- disturbed course ; for we seldom find these structures without finding also cells mingled with them, in which degeneration or disease has taken place. Some of them are withered (Fig. 101) ; some contain minute oily particles ; some are completely filled with such particles, or are transformed into granule-masses (Fig. 102) ; and with these we always find abundant molecular and granular matter, in which, as in the debris of cells, the nuclei lie loose. This debris too, let me add, is always increased when the cancer is kept for a day or two before examination, and when water acts upon it. The loss of clearness by the cancer- cell, of which I have already spoken (p. 614), is only the first of a series of changes in the course of which the material of the cell breaks up into molecular and amorphous debris : fragments of it may hang about the nuclei ; but finally the cells are completely disintegrated, and the nuclei, comparatively unchanged, are set free. Among the tissues of the breast itself which are in- volved by the cancer, the gland lobes, I have already said, are quickly removed ; but their debris may contri- bute to the molecular matter which is mingled with the proper corpuscles of the cancer. The larger gland ducts involved in the cancer often appear thickened ; and their contents, which are usually a thick, turbid, greasy fluid, present abundant granule- masses, withered cells like the epithelial cells of ducts, fragments of m.embrane, free nuclei shrivelled and deformed, molecular and granular matter : all these being, I suppose their natural contents, degenerate and disintegrated. Characteristic appearances are produced chiefly or in great part by the smaller gland-ducts and the fibrous-tissue inclosed in the cancer. The former chiefly constitute that which has been named the ' reticulum ' of hard cancer. In one form of the reticulum, which is the most characteristic, and, indeed, the only one to which the name can properly apply, we see fine, Pig. 101. Withered hard cancer-cells, "with debris. Fig. 102. Hard cancer-cells, showing the progress of fatty degeneration. 616 MICEOSCOPIC ANATOMY brandling, and variously interlacing and netted lines, of an opaqne- TV'Hte, bufif, or ochre-yellow line. They appear as if formed of thickly sprinkled dots. They traverse the very substance of the cancer ; and when the cancer occupies but a small portion of the mammary gland, these netted lines are found only in that part of it which corresponds with the gland substance. In the other and rarer form of what is also called ' reticulum,' we find larger dots or small masses of ochre-yellow substance, such as are compared to seeds. These lie more widely scattered in the substance of the cancer, and may be often pressed from it, like the comedones or retained white secretion from obstructed hair-foUicles. I believe that these yellow ' seed-like bodies,' which are apt to be confounded with the degenerate contents of the larger ducts, are always small portions of the cancer degenerated and softened or partially dried. We find in them abundant granule-cells and granule-masses, some entire, some in frag- ments : fragments, also, of granular and nebulous blastema (as it seems), and often of nucleated membrane : and these lie in molecular and granular matter diffused in liquid, with minute oil tirops, and often with crystals of cholestearine. But with these products of complete degeneration, we may commonly find, also, cells of which the great majority are either degenerate, filled with fatty matter, like granule- cells, or disintegrated ; or else (when the substance is drier) shrivelled and dried up, like the lymph and pus corpuscles that we may find in. chronic inflamed lymphatic glands (Figs. 101, 102). Similar to these in their component structures are the larger masses of friable yellow substance, like tuberculous deposits, which -are rarely found in hard cancers ; but are very frequent in the medullary cancers. These appearances of yellow spots — whether seed-like or in larger masses — are not exclusively found in the breast or in glandular structures : they may be seen in any hard cancer, and are yet more frequent in soft cancers in all organs. Lastly, respecting the connective tissue involved in the cancer. We sometimes meet with a cancer of the breast which, having just involved the skin, shows us the interlacing bundles of cutaneous fibres spread out or expanded by the insertion of the cancer-structures among them (as in Fig. 99). The skin in such a case appears thickened, and its section is glossy, grey, and succulent, like that of hard cancer, but dimly marked with whitish fibrous bands. In other and more frequent cases the marks are absent, and the fibrous and elastic tissues of the skin are not to be found ; we may presume that they have been absorbed OF SClERHOtrs CANCER. 617 as the cancer- structures increased. I think this removal of the fibrous and elastic tissues is the more frequent event, both in the skin and in the gland ; yet in some of the hardest cancers, and in the central hardest part of others, the fibrous tissue of the gland — all that which encompasses the gland-tubes and becomes proportionally abundant when the secreting structures waste — aU. appears to be even increased and condensed or indurated. The fibrous tissue found in these cancers has been commonly con- sidered as a new-formed proper caaoerons structure. I would not deny that part of the cancerous material produced in a breast may be de- veloped into fibrous tissue ; but I am sure that in the large majority of cases, the fibrous tissue which is found in a cancer of the breast is only that which belonged to the breast itself, and which, involved in the cancer, may now be either wasted or increased. For the fibrous tissue in hard cancers of the breast is not like morbid or new tissue, nor like that which is found in really fibrous cancers, but is hke the natural connective tissue, either healthy or indurated and condensed. It is also generally mixed with fibres of elastic tissues, such as are inter- mingled with the natural areolar tissue, but never, T think, occur among the proper constituents of cancer, and are very rare in even the more highly organised of the innocent tumours. I may add, in confirmation of this view of the nature and origin of the fibrous tissue in cancers of the breast, and that when hard cancer occurs in organs which have little or no fibrous tissue — such as cancellous bone, the brain, the liver, or the lymphatic glands — it presents little or none of the same tissue ; however hard it may be, it is formed almost entirely of cor- puscles.' The difference in this respect is often, indeed, very striking between the hard cancer of the breast and that of the corresponding axillary glands. Both may be equally hard and manifestly identical in nature ; yet while the cancer of the breast may include abundant fibrous tissue, that in the glands may have scarcely a trace. I have dwelt the more on this point because the current method of describing all cancers as composed of a peculiar ' stroma,' the meshes of which are filled by a peculiar ' cancer- juice,' appears to me very decep- tive and often incorrect. The expressions, as they are commonly used imply that the fibrous tissue or stroma, and the cells and other materials which form the juice, are alike proper and essential to the cancer. But I believe that in the large majority of cancers of the breast the ' See, respecting the hard cancer of the brain, a case well described by Dr. Eedfern (Monthly Journal, Deo. 1850). 618 ACUTE AND CHRONIC CANCEE. only 'stroma,' the only substance that woiild remain, after removing aU tliat is cancerous, ■would be the structures of the breast itself. And so, in other cancers, my belief is that if we except the rare examples of the really fibrous, and osteoid cancers, to which I shall hereafter refer, there are few in which more than a very small quantity of fibrous tissue is formed. In the foregoing description I have had in view, almost exclusively, the forms of scirrhous cancer which are most frequent in the breast : instances of the ordinary or typical charactei'S of the disease. But as I said at the outset, the deviations from these medium forms are neither few nor inconsiderable, even though we do not count among them any of the varieties of appearance which are due to degeneration, or to dis- ease of the cancerous structure, or to varying conditions in the parts about the mammary gland. And, first, varieties appear which m.ay be referred to different de- grees of activity or intensity of the disease. The examples which I have hitherto chiefly described might hold a middle place in a series at the opposite ends of which would be those of what may be called the ' acute ' and the ' chronic ' cancers. The well-marked examples of the former kind are distinguished, not only by rapid progress, but by structure. They are scarcely to be called hard — they are, at the most, firm, tense, and elastic ; and they may even, though not morbidly softened, present a deceptive feeHng of fluctuation. Their cut surfaces do not become concave ; they are suc- culent, and yield abundant fluid upon pressure ; they are often suffused with vascularity, especially about their borders. The quantity of can- cer-structure in them is very large, in proportion to the quantity of gland in which it has its seat. Hence the section of an acute cancer appears more homogeneous, and its growth produces a m.anifest en- largement or swelling, the morbid material expanding the tissues around and involved within it. The surrounding tissues, also, are less closely connected with the cancer than they usually are, and it may appear like a distinct isolated tumour, rather than an infiltration. In all these conditions the acute scirrhous cancers approximate to the characters of medullary cancers : and perhaps the expression is not unjust, that they are examples of an intermediate form of the disease. And the approximation is shown, in some other characters, especially in their more rapid growth ; in their usually aSecting those whose mean ACUTE AND CHRONIC GANCEE. 619 age is below that of the subjects of the harder and more chronic cancers : and in the signs of larger supply of blood. In the chronic hard cancers the opposites of all these characters are found. The cancerous mass is comparatively small ; and, as time passes, it often seems to shrink and contract rather than increase. It is intensely hard, knotted, and dry ; the adjacent tissues appear tight drawn to it, and firmly adherent ; and on its cut surface, which usually appears deeply concave, it may show more of the increased and indu- rated fibrous tissue of the breast than of the proper cancer substance. All the history of the chronic cancers accords with these signs of inac- tivity : they occur generally in those that are beyond the mean age, or much below the average state of nutrition ; they are attended with no increase of vascularity ; and if the skin becomes involved in one it is only ruddy or palely livid at the very seat of adhesion. The tissues of the breast itself usually appear to suffer a corresponding atrophy ; the gland commonly shrivels, and the skin becomes lax and wrinkled, or else is filled out with superabundant fat accumulating round the shrink- ing gland. Either of these forms of cancer may afiect, in some cases, the whole gland ; in others, only a portion of it. The characters of both are most marked when they occupy the whole gland, for now the enlargement attending the acute cancer, and the shrinking that accompanies the chronic, are most manifest. In general, the respective characters of the acute and the chronic cancer are consistent throughout all their course : yet cases are not rare in which a scirrhous cancor has shown all signs of rapid progress at the beginning of its career, but, after a time, has inexplicably retarded its course, and passed into a, chronic state. Nor, on the other hand, are those rare in which patients are seen dying quickly, because a can- cer which has been slowly and almost imperceptibly progressive for several years, at length assumes the rapidity and destructiveness of an acute inflammation. A second series of scirrhous cancers, deviating from the usual forms consists of cases in which the nipple and the skin or other tissues of the mammary gland are peculiarly afiected. Commonly the scirrhous cancer extends from the mammary gland to the nipple and areola, involving these as it may any other adjacent part. When seated at or near the centre of the gland, it commonly draws down the nipple, which descends as it were into aroundpitsunk 620 CAXCEE OF NIPPLE AKD SKIN". below the general level of the breast. As it extends, also, the cancer- structnres deposited in the nipple make it hard, or very firm and elas- tic, inflexible and comparatively immovable. But the changes which thns usually occur later, or in a less degree than those in the gland, may commence or predominate in the nipple or the areola. The former may be found quite hard and rigid ; or, in the place of the latter, there may be a thin layer of hard cancerous substance, with a superficial ulcer, like an irregular excoriation, while the structures of the gland itself are yet healthy. In other cases we find the skin, over and about the mammary gland exceedingly afiected. In a wide and constantly, though slowly widening area, the integuments become hard, thick, brawny, and almost inflexible. The surface of the skin is generally florid or dusky, with congestion of blood ; and the orifices of its follicles appear enlarged, as if one saw it magnified,^it looks like coarse leather. The portion thus affected has an irregular outline, beyond which cord-like offshoots or iso- lated cancerous tubercles are sometimes seen, like those which are com- mon as secondary formations. The mammary gland itself, in such cases, may be the seat of any ordinary form of scirrhous cancer ; but I think that at last it generally suffers atrophy, becoming, whether cancerous or not, more and more thin and dry, while the skin contracts, and is drawn tightly on the bony walls of the chest, and then becomes firmly fixed to them. I might add to the account of these deviations from the ordinary forms of cancer of the breast, notices of some others ; but these may sufiice, and if it be remembered that each of these, as well as of the more common forms, is liable to change by the various degenerations and diseases of the cancer, enough vf iU. have been said to illustrate the exceeding multiformity in which the disease presents itself in the breast. Something, however, must be added respecting the characters of scirrhous cancers in other parts of the body ; and from these I vriM select chiefly those parts in which it has the greatest surgical interest, or has received the least attention from morbid anatomists. In the Lymphatic Giands the scirrhous or hard cancer appears very frequently as a secondary disease ; iadeed, there are few cases in which cancerous patients reach their average of life without affection of the glands connected with the organ primarily diseased. As a primary disease, scirrhous cancer of the lymphatic glands is SCIERHOUS CANCER OF LYMPH-GLINDS. 621 rare : the cancer which most commonly appears first in them is the medullary ; especially, I think, that of the firmer kind.' Bat a speci- men is in the Museum of St. Bartholomew's,^ which shows well-marked scirrhous cancer in an inguinal gland. The gland is increased to an inch and a half in length, and, while retaining its natural shape, nearly the whole of its proper texture appears replaced by structures exactly resemLling, in hardness and all other properties, the ordinary scirrhous cancer of the breast. It was removed by Sir W. Lawrence from a lady who remained well about three years after the operation, and in whom the disease then recurred in another inguinal gland, which was also removed, and presented the same characters. They were equally marked in the progress through destructive ulceration which ensued in a primary scirrhous cancer of the axillary glands, also observed by Sir W. Lawrence. I have seen other instances in inguinal glands forming exceedingly hard swellings in and below the groin; but I have had no opportunity for minute examination of them. Similarly, I have seen cases of primary scirrhous cancer in axillary and in cervical lymph- glands. Cases sometimes occur in which the disease in the glands may be so nearly coincident with that in the organ to which they are related, that we may believe the gland-cancer to be primary, though not alone. And sometimes the disease in the glands greatly preponderates over that in the organ, even though its primary seat was in the latter. All these, however, are rare events in comparison with the second- ary cancerous affection of the lymph-glands. The ordinary course is, that after the scirrhous cancer has existed for a time (the length of which seems at present quite uncertain) in the breast or any other oro-an, the lymphatic glands in and near the route from that organ towards the thoracic duct become the seats of similar disease. I shall speak elsewhere of the probable method of this extension of the cancer to the glands. Its effects are shown in a process which, in all essential characters, imitates that preceding it in the organ primarily diseased. Usually the cancerous structures are formed, in the first instance, in separate portions of one or more glands. The separate formations ap- ' The Index will, I hope, in some measure correct the disadvantage, which is here evident, of separating the accounts of the different forms of cancer in the same organ. The disadvantage is, I think, more than compensated by the avoidance of confusion in the descriptions of the different forms ; and in the Index the reader will find, under the title of each chief organ or tissue (so far as they are here described), the references to all the forms of cancer occurring in it. 2 Series xxi. 2. 622 SOIERHOUS CANCER OP TEE SKIN. pear as masses of very firm and hard wtitisli or greyish. snbstaBce, of rounded shapes, imbedded in the glands, and contrasting strongly, as well in texture as in colour, with their healthy remaining portions. But, as the separate portions in each gland enlarge, they gradually coalesce till the whole natural structure of the gland is overwhelmed and re- placed by the cancer. Similarly, the same changes ensuing at once in many glands, they form a large and still increasing cluster, and at length coalesce in one cancerous mass, in which their several outlines can hardly be discerned. The minute texture of the scirrhous cancer of lymphatic glands differs, I believe, in nothing that is important from that already des- cribed in the cancer of the breast. Only, in microscopic examinations, we find the proper structure of the lymphatics, in the place of those of the mammary gland, miugled with the cells and other constituents of the cancer. Neither is there any essential difference in the mode of formation of the cancerous material ; it is, in both alike, an infiltration, though circumscribed. Occasionally, it is said (but I have never seen it), the secondary cancer of the lymphatic glands is soft and medullary, while that of the organ primarily diseased is scirrhous. Very often, before becoming cancerous, the lymphatic glands enlarge without hardening — through ' simple irritation,' as the expression is. From this condition they may subside after the removal of the primary cancer, or when correspond- ing 'irritation' in it is relieved. But the condition, whatever it may be, is probably not one of mere slight inflammation ; for glands which may have thus subsided, or which have not been visibly afiected, may become the sole or primary seats of recurrent cancer, even two or more years after the removal of the primary disease. There seems to be a peculiar state of liability to cancer, long retained in lymphatic glands, sometimes testified by enlargement, but often not discernible except in its results. Scirrhous cancer of the Skin is another of the affections commonly occurring secondarily, yet sometimes appearing as a primary disease. Its occurrence, when the disease extends continuously from the mam- mary gland is already described. In a similar manner it may be found extending from lymphatic glands, or any other subcutaneous organ ; and I have described (p. 620) how it sometimes precedes and surpasses in extent the scirrhous cancer of the breast. But its most frequent appearance, in connection with cancer of the breast, and that which is SCIEEHOUS CANCER OF THE SKIN. 623 imitated when it occurs as a primary disease in other parts of the skin, is in tubercles or rounded hard masses. Such tubercles are generally grouped irregularly, but in constantly widening areas, about the primary disease in the breast ; in other parts, and as primary cancers, they may be single or numerous. They are almost incompressibly hard, tough, circumscribed masses or knots ; they are usually of oval, flat, or biconvex form, or, when large, are tuberous or lobed ; they are imbedded, as infiltrations of cancer-structures, in the exterior compact layer of the cutis. They are generally equally promi- nent above, and sunken beneath, the level of the surface of the skin ; and this condition is commonly acquired as well by those which com- mence Uke little prominent papulae, as by those which at first appear like knots just subcutaneous. The skin covering them is thin, tense, and shining ; it is usually of a deep, ruddy, pink colour, tending to purple or brownish red, or it may seem tinged with brown, like a pigment mark. This change of colour extends a little beyond the border of the cancerous mass, and then quickly fades into the natural hue of the skin. Such cancers are movable vpith, but not in, the surrounding skin, and even with it the mobility is very limited when they are large and deep. They may be found of various sizes ; in cir- camscribed masses, ranging from such a size as can just be detected by the touch, to a diameter of two inches ; or, when diffused in the skin, occupying it in an expansion of hardly limited extent. The minute structures, equally with the general characters, of the scirrhous cancers of the skin, are, in everything, conformed with those a,lready described ; and the characters of cancer-cells, and their mode of disorderly insertion in the interstices of the natural tissues, are in no parts more distinct.' In general, I think the scirrhous cancers of the skin have a chronic course, not painful or soon ulcerating ; but, as primary diseases, they are too infrequent for a general history of them to be written at present. I have seen only four examples of them independent of previous cancer in other parts. In one of these the seat of disease was ' In the foregoing account I have not had in Ti6\y that which is commonly called the ' cancerous tubercle of the face,' and which so often occurs as the precedent of the destrnctive process constituting the so-called 'cancerous ' or ' cancroid ulcer' of the face in old persons. I have not been able to examine minutely one of those tubercles before ulceration, but all I have seen of the materials forming the base and margins of the ulcers which follow them, and all the characters of their progress, make me believe that no cancerous structure, whether scirrhous, epithelial, or any other, exists in them. I shall revert to this subject in the lecture on Epithelial Cancer. 624 SCIRRHOUS CANCER IN THE MUSCLES. nearly the whole skin of the front of the left side of the chest of a woman seventy-three years old ; in another, it was in the skin of the leg, in the form of cancerous tubercles abont the knee, of a woman set. sixty-five : in another, an elderly man's scalp had two large, hard, cancerous masses in it ; in a fourth, the disease wss in the scrotum of a man fifty-three years old ; but I believe the elementary structures of scirrhous cancer were mingled with others resembling those of the more frequent epithelial soot-cancer of the same part.' In the Muscles scirrhous cancer is commonly associated with its most frequent form in the skin : that, namely, in which it occurs in groups of tubercles about the primary disease of the breast. We may, indeed, draw a close parallel between the secondary cancers in the skin and muscles respectively ; for in both parts alike we find, in some cases, discrete cancerous tubercles, in others extensively diffused cancerous formations ; and in the muscles, as in the skin, the latter form occurs, especially when the disease extends continu- ously : the former when it is multiplied contiguously to its primary seat. I have never seen a primary scirrhous cancer in a muscle, and only once have seen such a cancer forming a distinct isolated tumour in an intermuscular space. It may be doubted, indeed, whether this tumour were the primary disease ; yet, because of the exceeding rarity of s cirrhous cancers in any other form than that of infiltrations of the textures of parts, it deserves mention. It was taken, after death, from a man fifty-four years old, in whom it had been observed for a month, and who died, exceedingly emaciated and exhausted, with similar disease in his axillary and bronchial lymphatic glands, his lungs, muscles, occipital bone, and other parts. This tumour was about four inches in length, oval, surrounded by a distinct capsule of connective tissue, and seated between the brachialis anticus and biceps muscles, outspreading both of them. It had the same hardness, weight, and density, and the same microscopic cell- structures, as the ordinary scirrhous cancers of the breast ; it was milk-white, slightly sufiused ' This specimen is in the Museum of St. Bartholomew's. Cases of cancer of the skin are related by Lehert, "Walshe, and others, in their appropriate chapters ; but it is not clear that any of them were primary scirrhous cancers. Those which were not epithelial cancers appear to have been either medullary of the firmer sort or (inLebert's cases) melanotic. All these forms of cancer are more frequent in the skin, as primary diseases, than that which I have described : they wiU all be considered in the following lectures. SCIERHOUS CANCER OF THE BONES. 625 ■with pink and grey, and distantly spotted and streaked -with ochre tints. The other cancerons masses had for the most part the same characters ; but some, which by their size and positions might certainly be considered as of latest production, were soft, and like the most frequent medullary cancers. In the Bones, as in the muscles, the scirrhous cancer seldom, if ever, occurs except as a secondary disease : the primary cancers of bones are, I think, always either medullary, osteoid, or colloid. The structures of the scirrhous cancer may be infiltrated or diffused among those of the bone, or they may form distinct masses ; but in neither case do they so increase as to form considerable tumours. In some of the cases of infiltration, the cancerous substance is diffused through the cancellous tissue of the bone, while its walls are comparatively little changed : in others all the bony structures are expanded into an irregular framework of plates and bands, the interstices of which are filled with cancerous substance, hard, elastic, grey, and shining.' On the other hand, when separable cancerous masses are formed, they are usually round or oval, or adapted to the shape of the inner walls of the bone, within which they are, at least, for a time confined. They generally appear as if, while they were growing, the original bony textures around them had gradually wasted or been absorbed, making way for their further growth.^ And thus the growth of the flfeirrhous cancer, with absorption (whether previous or consequent), of the bone around it, may colitinue till not only the medullary tissue, but the whole thickness of the wall is removed, and the cancer day project through and expand beyond it, or may alone fill the periosteum, retaining, with very little change, the originalshape and size of the bone.^ In both these sets of cases the cancer-cells are ahke, and they form, without fibrous tissue, a hard, or very firm, elastic, greyish substance, ' Nos. 822-3 in the College Museum are examples of the first form ; and No. 5 (Appendix) in that of St. Bartholomew's may exemplify the second. The latter specimen was taken from a case in which a cancerous femur was broken eight months before death, and the new boiie, with which it was repaired, was infiltrated with cancer as well as the original textures. 2 See, respecting the occasional 'preparatory rarefaction' of bones, previous to cancerous deposits in them, the excellent observations of Walshe (p. 556) and Virchow {Archiv, i. 126). 3 As in Nos. 817-8-9, in the Museum of the College, and in several specimens lately added to that of St. Bartholomew's, Series i. 292, 306. S S 626 SCIEEHOUS CANCER OF THE EECTUM. stining, and sometimes translncent, sometimes with an obscure fibrous appearance. The likeness to the common hard cancer of the breast is complete, in both general and microscopic characters ; and not less complete the contrast with the usual forms of the medullary cancer, which, as I have said, is the more frequent primary disease of the bones. Intermediate speci- mens may, indeed, be found ; yet, on the whole, the contrast between medullary and scirrhous cancers is as well marked in the bones as in any other part.' The bones thus cancerous become liable to be broken with very slight forces ; and to these condi- tions a certain number of the so-called spontaneous fractures in cancerous patients may be assigned. But some are due to the wasting and degenerative . JA'ffl atrophy which the bones undergo during the progress of cancer, and which seems to proceed to an extreme more often than it does in any other equally emacia- ting and cachectic disease. W] The scirrhous cancer of the Intestinal Canal is exemplified most frequently in the rectum, where it, very remarkably, has a ' seat of election,' at from three to four inches from the anus, in the sigmoid flexure of the colon, and, sometimes in a very striking Kg. 103. form, in the ileo-csecal valve. It appears, usually, as an infiltration of hard cancer structures in the submucous tissue, with lobed and nodular outgrowths projecting in bosses into the cavity. The cancer is usually of annular form, and occupies the whole circum- ference of the intestine, in a length of from half-an-inch to an inch. It may, at the same time, or in other instances, occur externally to the muscular coat, and in this case is usually not annular, but in separate tubercles, which, until ulceration ensues, project with flattened. Fig. 103. Section of a humerus with scirrhous cancer, as described ahove. Mils, of St. Bartholomew's, Series i. No. 290. ' Medullary cancer may appear as a secondary disease in the bones, as well as in any other parts, after primary scirrhous cancer in the breast. The cases I have examined would mate me think that the scirrhous cancer is, in these events, the more frequent : but M. Lebert (Traiti des Maladies Cancereuses, p. 714) describes none but soft cancers as occurring in the bones, whether primarily or secondarily. SCIEEHOUS CANCEE OF THE EECTUM. 627 and sometimes centrally depressed, round or oval surfaces, into the cavity of the iatestine. Very rarely (it is said) it may affect the whole circumference of a large extent of the rectum, and may in the same extent involve many adjacent parts. It sometimes happens that the scirrhous cancer of the submucous tissue is associated with growths of softer medullary cancer into the cavity of the intestine, or with formations of colloid cancer. The mingling of these forms is certainly more frequent in the digestive canal than in any other part. But that which is most remarkable in the scirrhous cancers of the rectum, as an example of those of other portions of the canal, is derived (especially in its chronic forms) from the tendency which the cancer has here, as in other parts, to contract and condense, and adhere to the parts around it. To this it is due, that, when an annular cancer of the rectum exists in the submucous tissue, even the exterior of the bowel appears constricted ; instead of swelling, the bowel is, even externally, smaller at the cancer than either above or below it : and the stricture, or narrowing of the canal, which might be trivial if it depended only on the cancer- ous thickening of the coats, is made extreme by the contraction of the coats around and with the cancer. The same conditions which, in hard cancer of the breast, produce retraction of the nipple and pucker- ing of the skin over the morbid growth, here produce contraction of the muscular and peritoneal tissues around the growth, and a concen- tric indrawing of the growth itself With similar likeness to the hard cancers of the breast, those in the intestine (in the rectum, for example) give rise to close adhesion of the tissues round them to other adjacent parts. Thus the cancerous part of the rectum may be fixed to the promontory or front surface of the sacrum quite immovably ; or the colon may become united to the urinary bladder, or to some other portion of the intestinal canal. Kg. 104. Scirrhous cancer of the rectum, showing the constriction of the peritoneal and muscular coats around the cancer of the submucous tissue. Museum of St. Bartholomew's. s 9 ^ Fig. 104. 628 FIBEOUS CANC'EK Many otter important facts in tiie Mstory of this afiection are con- nected witli the dilatation and hypertrophy of the intestine above the stricture ; the final paralysis of the dilated part, and the phenomena of ileus chiefly due thereto, -with displacement of the diseased part by the weight of fsBces accumulated above it ; the occasional variations of the degree of stricture, according to the afEu:x of blood swelling the diseased part, or its ulceration or sloughing decreasing it, and so for a time widening the canal ; but these I need only enumerate, while I can refer to Rokitansky' for ample accounts of them all. The large intestine is, probably, next to the mammary gland and the stomach, the organ in which the well-marked scirrhous cancer is most frequently found as a prim.ary disease. It very rarely, indeed, occurs secondarily, except when extending to the intestine continuously from some adjacent part ; and in this case, as it usually affects, at first, only part of the circumference of the intestine, it may become much more extensive without producing stricture ; for the unaffected part of the wall may dilate so as to compensate, for a time, for the contraction of the diseased part. Moreover, when it is a primary disease, the can- cer of the intestine is one of the forms in which the disease may exist longest without multiplication, although often, even in its early stages, it is associated with exceeding, and seemingly disproportionate, ca- chexia. I have spoken of the occurrence of fibrous tissue in the scirrhons cancers of the breast, and have said (p. 617) that this appears to be no proper element of the cancer, but the natural connective tissue of the part involved in the cancer, and often increased and condensed. If this be always so, and if, as I have also said, little or no fibrous tissue be found in cancers affecting organs which naturally contain none, it will follow that the name Carcinoma fibrosum is not well applied to any ex- amples of hard cancer described in the foregoing pages. Tet there are cancers which contain not only abundant but peculiar fibrous tissue ; and these may well be called ' fibrous cancers,' and may be considered as a distinct form or species, unless it should appear that they are always associated, as secondary diseases, with scirrhous cancers of the more ordinary structure ; so that we may suppose that the same material is, in one organ, developed into fibrous tissue ; in others, at the same time, into cancer-cells. The most remarkable examples of hard cancers with fibrous struc- ' Patholcgische Anatomie, iii. 276 and 282. IN THE OVARIES. 629 tures, tliat I have yet seen, have been in the ovaries of certain patients with common hard cancer of the breast or stomach.' In these cases, the place of the ovary on either or on both sides is occupied by a nodulated mass of uniformly hard, heavy, white, and fibrous tissue. The mass appears to be, generally, of oval form, and may be three or more inches in diameter ; its toughness exceeds that of even the firmest fibrous tumours ; and its component fibres, though too slender to be measured, are peculiarly hard, compact, closely and irregularly woven : they are not undulating, but, when they can be separated singly or in bundles, they appear dark-edged, short, and irregularly netted. With these I have found only few and imperfect cancer-cells ; with more numerous nuclei, elongated and slender. They are not mingled with elastic or other ' yellow element ' fibres. Bat fibrous cancers are not found in the ovaries alone. Peculiar stiff-fibred tissue is sometimes contained, together with less abundant cancer-cells, in the hard cancers connected with periosteum. So I have seen it in the pelvis, and in the unossified parts of osteoid cancers, where neither its relations nor its minute textures were such as to suggest that it was morbidly increased periosteum. However, the occasions that I have had of examining truly fibrous cancers have been too few to justify any conclusion respecting the propriety of separating them, as a distinct form, from the scirrhous cancers. And I cannot complete my own imperfect observations with the records of other pathologists ; for I think that none have endeavoured sufficiently to discriminate between the two kinds of fibrous tissue that may be found in cancers; namely, that which is developed during the growth of the cancer, and that which is derived from the original fibrous tissue of the afiected organ, whether in its natural state, or increased, condensed, indurated, or otherwise morbidly changed. Tet the distinction is an essential one : for the former is truely cancer-structure, the latter is only the structure in the interstices of which the cancer has its seat. A similar distinction will have to be made, in a future lecture, between the osseous tissue that grows so as to form the framework, or interior skeleton, of certain medullary cancers of bone, and that which is the chief constituent of osteoid cancers : the one is a morbid growth of a bone affected with cancer ; the other is the proper cancer- structure ossified. ' Museum of the College, No. 240, 2636; and of St. Bartholomew's, xxxi. 17, and probably, xxxii. H 630 AGE AND SEX IN THEIE LECTURE XXX. SCIREHOtJS OR HAED CANCBK. PART II. PATHOLOGY. The former part of tkis lecture being devoted to an account of the structures of the chief examples of scirrhous cancers, I propose, in this second part, to consider their history, their mode of life, their pathology as contrasted with their anatomy. And here, even more nearly than in the former part, I will limit myself to the histories of those of the breast ; for concerning the primary scirrhous cancers of other parts, we have too few data for any general history. First, concerning the conditions favourable to the origin of these scirrhous cancers : — (a.) They exist, in great preponderance, in women. Probably, of every 100 cases of scirrhous cancer of the breast, 98 occur in women ; and, I believe, it is chiefly this that makes cancer, on the whole, more frequent in women than in men, for in nearly every other organ common to both sexes the greatest frequency is found in men. (6.) The age of most frequent occurrence of scirrhous cancer of the breast is between 45 and 50 years. Nearly all records, I think, agree in this. The disease has been seen before puberty ; but it is ex- tremely rare at any age under 25 ; after this age it increases to between 45 and 50 ; and then decreases in frequency, but at no later age becomes so infrequent as it is before 20. The following table, drawn from the records of 158 cases, of which the diagnosis cannot be reasonably questioned, will illustrate the fore- going statement : — ' ' This and many of the following tables are drawn from a. general tahle of 365 cases of cancers of all kinds. Of the whole number, nearly half were observed by myself. Of the remainder, I have derived about 50 from the records of the Cancer RELATIONS TO SCIIIEHOUS CANCER. 631 2 cases were first observed between 20 and 25 years of age. 4 9 26 83 40 17 11 9 6 1 158 In another series, of 276 cases observed by myself, tbe numbers were : — 26 )) 30 30 )) 35 35 j> 40 40 )) 45 45 )> 50 50 )) 55 55 ») 60 60 J) 70 70 )j 80 above 80 jween 20 and 30 years o f age 5 30 „ 40 . 41 40 „ 50 . 122 60 „ 60 . 65 60 „ 70 . 35 70 „ 80 8 These numbers may represent the absolute frequencies of the oc- currence of scirrhous cancer of the breast at different ages. But it is more important to know the relative freqnencies in proportion to the number of women living at each of the successive periods of life. To ascertain this, I have added to the cases in the first preceding table those tabulated, in a nearly similar manner, by Mr. Birkett' and M. Lebert ; ^ making a total of 354 cases originating between the ages of 20 and 80 years. Then, comparing the number of cases in each de- wards in the Middlesex Hospital, for access to which I am much indebted to the surgeons of the Hospital : more than 60 were very kindly communicated to me by Dr. Humphry ; others I owe to Mr. Lowe and Dr. Paget : nearly all the rest were collected from the works of Wardrop, Langstaif, Baring, Bruch, Bennett, and Sedillot. The ages assigned in this table are those at which, in each case, the disease was first observed hy the patient ; and no case is included which was recorded only, or chiefly because it was an example of the disease occurring at an unusual period of life. ' On Diseases of the Breast, p. 218. 2 Bes Maladies Cancereuses, p. 354. The particulars of both these tables accord very nearly with those given above ; but the numbers of cases below 20 and above 80, in Mr. Birkett's table, are very large ; probably because he has included cases that were recorded on account of their rarity in respect of the p.itients' ages. 632 AGE AND SEX IN THEIE cetinial period of life, witli the number of women alive in tte same period ia England and Wales (according to tHe Population Returns for 1841), it appears that the comparative frequencies, relatively to the whole number of women, may be stated in the followiag numbers ; — Ages. 20 to 30 Eelative frequency of the origin of hard cancer. 6 30 „ 40 . 40 40 „ 50 . 100 50 „ 60 . 76 60 „ 70 . . 38 70 „ 80 . 32 In other words, the proportions between these numbers may re- present the degrees in which the conditions of women's Uvea, at the successive decennial periods, are favourable to the first growth of scirrhous cancer in the breast. One is naturally led to suppose that the great liability to cancer of the breast between 40 and 50 years of age, and, especially, the maximum between 45 and 50, are connected with some of the natural events that are then occurring in the nearly related reproductive organs ; such as the cessation of the menstrual discharge, and of the maturation of ova ; or else with the wasting and degeneracy of the mammary glands. And yet it is difiicult to prove such a connection with any single event of the period. The event which is generally regarded as most important is the cessation of the menstrual discharge. But I find that among 52 women with scirrhous cancer of the breast, in whose cases this point is noted, 27 were still menstruatiug for at least a year after their dis- covery of the cancer ; and 16 had ceased to menstruate for a year or more previous to it ; so that less than ^ of the whole number afforded examples of the cessation of the catamenia and the discovery of the cancer occurring within the sam.e year. The following table shows the ages at which menstruation ceased in 400 women,' and the ages at which hard cancer of the breast was first detected by an equal number : — ' From Dr. Gray's tables, in the Medical Times, 1845. The numbers in the third column are obtained by doubling those in a table of 200 cases, collected from those of M. Lebert and Mr. Birkett, as well as from my own. RELATIONS TO SCIRRHOUS CANCER. 633 Ages. Below 35 Cessation of menstruation. 9 First otservation of the eancer. 36 35 to 40 51 62 40 „ 45 140 78 45 „ 60 159 101 Above 50 41 123 400 400 AU these calciilations are sufficient to prove the great influence whidi the events of life, at and about the time of the cessation of the menstrual process, exercise in the production of the cancer ; but they do not prove that the defect of that process has more influence than others of the coincident events. This is conflrmed by the observation that, in 75 cases of cancer of the breast, commencing between the ages of 40 and 65, the disease began in 48 before the cessation of the cata- menia ; 12 about the time of their cessation ; 15 after it.^ I think we may most safely hold that the aptness of this time of life for the deve- lopment of hard cancer is chiefly due to the general failure of the pro- cess of maintenance by nutrition, which usually has at this time its beginning, and of which the most obvious natural signs are in the diminution of the powers of the reproductive organs. It is in favour of this view, rather than of any especial influence of the reproductive organs, or of change in the mammary gland, that the ages of increasing frequency of scirrhous cancer in the male breast,^ and of primary SciiThous cancer in other organs, coincide with the results of the far more numerous cases in the female breast. This would hardly be so if it were the condition of the female breast itseK, or of any nearly related organ, that alone or chiefly de- termined the greater frequency of the cancer at particular periods of life. (c.) To these conditions of sex and age, as favouring the production of scirrhous cancer, we may add an hereditary disposition, and the effects produced by injury or previous disease. The influence of these conditions is not generally, but is often very clearly, manifested. In 88 patients with scirrhous cancer (including four men and four cases ' Contribution to the Statistics of Cancer, by Mr. W. M. Baker, Med.-Chir. Trams. vol, xlv. 1862. * The four men in whom I have seen hard eancer of the breast were respectively 40 44 48, and 52 years old at the discovery of the disease. 634 INFLUENCE OF OTHER CONDITIONS ON of the cancer of other organs than the breast), 16 were aware of can- cer having occurred in other members of their families. In 40 tabnlated by M. Lebert only 6 could be deemed hereditary.* It might thus be believed that not more than 1 in 6 patients with scirrhous cancer can be reckoned as having hereditary tendency thereto, but the proportiQn is larger if calculated from a larger number of private patients. The family histories of hospital patients are scarcely worth collecting.* (fZ.) So, with regard to the effects of injury and previous disease, I find that, aruong 91 patients, only 16, i.e. less than one-sixth, ascribed the hard cancer to injury or any such local cause. The proportion is so small (it is less even than that of the patients with other tumours, who ascribe them to the same cause '), that we might be disposed to deny the influence of injury altogether, if its consequences were not, in a few cases, so manifest and speedy. (e.) The influence of the single and married states is shovni by Mr. Baker (loc. cit.) in a table of 260 cases of cancer of the breast, in which the proportions were — Single . . . 23'0 per cent. Married . . . 72-4 „ Widow . . . 4-6 „ The percentage of single women in cases of cancer of the breast is therefore smaller than that in the female population generally.* (/.) I pass by some other conditions supposed to be favourable to the occurrence of scirrhous cancers; such as mental distress, particulai' occupations and temperaments. Concerning all these, the evidence at present gained is insufficient to justify any numerical conclusions. But respecting one point much discussed — namely, the general health of women at the time when hard cancer is first found in them — I would observe that a remarkable majority present the appearance of good ' The difference in the proportions of M. Lebert's cases and in mine is probably due to my having reckoned as hereditary three cases in which members of the patient's families had had cancers of the lip. These would be excluded as only 'cancroid' by M. Lebert ; and so excluded, and added to the non-hereditary cases, they make the proportions very nearly equal in both our estimates. ^ See one of Mr. Baker's tables in the Lecture on the General Pathology of Cancer. ' See p. 387. Of 79 tumours not cancerous, 15 were ascribed to injury or previous disease ; i.e. 1 in nearly 6 j. * See Insurance Guide and Handbook. London, 1857. THE DEVELOPMENT O'F SCIRRHOUS CANCER. 635 health. I find that in 91 cases in which I have notes on this point, no less than 66 patients presented the general characters of I'obust or at least good health ; 9 were of uncertain or moderately good health ; and only 16 were sickly or feeble.^ It does not follow that all these were manifestly ill when the cancer began to form ; but, granting that it may have been so, it would still appear that scarcely more than one-fourth of the subjects of hard cancer are other than apparently healthy persons. Trom all this it is evident, that, except in relation to in- heritance and the comparative liabilities of diflFerent ages, we have little knowledge of the events that are, in any sense, the predisposing causes of hard cancer. Indeed, so insignificant in their whole sum are those that are already ascertained, that, in a large majority of oases, the patient finds the cancer by some accident. She chances to touch her breast attentively, or she feels some pain in it, or her friends notice that it is smaller or larger than it used to be ; and now, already, there is a cancer of, it may be, large size, of whose origin no account whatever can be rendered. The fact last mentioned may explain why we so rarely have an opportunity of seeing what a scirrhous cancer is like at its very be- ginning. I have examined only three that were less than half-an-inch in diameter. All these were removed within two months of their being first observed, and all had the perfect cancerous structure, such as I have described as the type. I believe they illustrated what is generally true — namely, that the cancerous structure has, from the first, its peculiar hardness. The formation of it appears to be attended with gradually increasing induration ; only, in the cases in which, from the beginning, it aSects the whole glands, and those in which it acquires even more than usual hardness, by the gradual predominance of the in- creased and indurated fibrous tissue. From the extreme of smallness the cancer grows ; but at various rates, in different cases and even in the same case at diff'erent times. I believe no average rate of increase can be assigned. Cases sometimes occur, especially in lean, withered women, whose mammary glands share in the generally pervading atrophy in which two, three, or more years pass without any apparent increase in a cancer ; and the progress even of ulcerated cancer is, in such patients, sometimes scarcely per- ' From one of Mr. Baker's tables {loc. cit.) it appears that only 5'2 per cent of the patients Trith scirrhous cancer of the breast were in bad health at the first observation of the disease. 636 GROWTH OF SCIPEHOUS CANCER. ceptible, even in the lapse of years. On the other hand, cases are found sometimes of most rapid increase. I saw such an one some time ago. A scirrhons cancer grew in five months from the size of the tip of a finger to a mass five inches in diameter. This was in a woman thirty-two years old, in whom the disease began while she was suckling, and immediately before, even while snckling, she again became pregnant. Extensive and speedy sloughing followed this rapid growth, and she died in seven months from the first observation of the disease.' Still more rapidly in a case under the care of Mr. Savory, within three weeks after the removal of a cancerous breast, the other mammary gland, which appeared quite healthy at the time of the operation, became com- pletely infiltrated with scirrhous cancer. We may very probably connect this singularly rapid progress of a scirrhous cancer during pregnancy or lactation with the condition of determination of blood to the breast in which it occurred, and to the early age of the patient — for, as a general rule, though malignant tumours may, in their plan and mode of growth, deviate never so widely from the normal tissues, yet for their rate of increase they are dependent in a certain measure upon the supply of blood and the general activity of the nutritive processes. Hence it needs to be always borne in mind, that among the cancerous they who seem most robust may succumb most quickly ; while the aged and the withered commonly live longest and with least discomfort. The increase of a scirrhous cancer appears to be by gradual super- addition of new particles on the surface of the mass already existing, and in the interstices of the tissue immediately bounding it. It is a nice question to determine how far from a mass of cancer already formed, say in the breast, the parts to be next added to it will be formed. Practice professes to have settled this in the rule held by some, that the whole mammary gland should be removed when only a portion of it is mani- festly cancerous. But whatever be the facts on which this rule is founded, they may be explained by the advantage resulting from the re- moval of all the part in which the cancer would be most apt to recur : they do not prove that cancer is already present in the part of the breast that appears healthy. It is, indeed, rare to find more than one cancerous mass in a mammary gland. I do not remember to have seen it more than four times in about 100 cases : and in one of these the second cancer appeared to have been detached, not to have grown ' This was the same case as that related by Mr. Gay, in the Proc. of Pathol. Soo. J851-2, p. 444. ULCERATION OF SCIRRHOUS CANCER. 637 separately from the principal nlasa. I have looked with microscopic help at the tissues close by a hard cancer, and have found, I think, cancer-cells one or two lines distant from the apparent boundary of the chief mass, as if the disease had already begun where neither the naked eye nor the finger could have discerned it. Beyond this little distance I have not found reason to believe that cancerous matter in any form exxsts in the parts of a cancerous mammary gland that appears healthy.' After an uncertain time and extent of growth of hard cancer, Ulceeation almost constantly follows. This may ensue in various ways ; it may be accelerated or retarded by many extraneous circum- stances, according to which, also, its characters may vary ; but there are two modes of ulceration which are especially frequent, arid are al- most natural to the course of the cancer. In one of these the ulceration begins superficially, and extends inwards ; in the other the changes leading to ulceration begin in the substance of the cancer, and thence make progress outwards. The superficial mode of ulceration is commonly observed when the cancerous growth has slowly reached and involved the skin. The best examples are those in which the cancer first affects a border lobe of the gland. From this, as it grows, it extends towards the skin, occupy- ing as it extends the subcutaneous fat and all the intervening tissues (Fig. 97). The skin, as the cancer approaches, whether raised or de- pressed towards it, adheres closely to its more prominent parts or to its whole surface. It becomes now, while cancerous matter infiltrates it, turgid with blood, thin, tense, and glossy, fiorid or dusky red, or livid or pale ruddy brown ; the congestion does not extend far, nor very gradually fade out, as in an inflamed integument, but is rather abruptly circumscribed, just beyond the adhesion of the skin to the cancer. In the next stage, the surface, in one or more plac'es, appears raw, as if excoriated •; or else, by some sudden stretching, it is cracked ; or a thin yellow scab forms over part of it, which, being removed, exposes an excoriated surface, and is soon reproduced. After a time the ex- coriated or the cracked surface appears as a more certain alcet ; scabs ' Several pathologists have, however, stated that cancer-structures are infiltrated amongst'tisBues which surround the actual cancerous tumour, and -which to the naked eve may appear to be perfectly healthy (Bennett On Cancerous and Cancroid Growths, 103 jVan der Kolk ' On the Formation and Extension of Cancer-cells.' £r. and For. Med.-Chir. Bev., April 1855, p. 390). 638 tJLCERATION OF SCIBEHOUS CAN-GEE. DO longer form, btit a copious, acrid, thin fluid exudes. The ulcer is apt to extend Tery widely ; and if there have been more than one, they soon coalesce ; bat they very rarely extend deeply, and their surfaces rarely appear otherwise than pale, hard, dry, and inactive. The growth of the cancer continues, as usual, after the ulceration ; and with the growth and the involving of more skin, the ulceration is generally com- mensurate. Now, the ulcer thus formed has, in itself, no so-called specific characters : examined by itself, it has not the features assigned to the cancerous ulcer ; we recognise its nature through that of the mass be- neath it. And yet there is much in the occurrence of this form of ul- ceration that is characteristic. For we may always notice, that though it is afiected as if by the destruction of the skin, and is not unlike the ulceration that ensues over a great firm tumour that has stretched the skin to its extreme of tolerance ; yet its occurrence is determined, not by the bulk of the cancer and the tension of the skin, but by the ad- hesion and confusion of the skin with the Cancer. As the cancer ap- proaches the skin, so the skin, without any stretching, becomes thinner and thinner; then its residue becomes cancerous ; and then, at length, it is excoriated. The cancer, exposed through the superficial ulcer, is not apt to be exuberant : it does not become or throw out ' fungous growths ; ' it manifests no peculiar tendency to further ulceration. Granulations' of ordinary aspect, or such as are only too pale and hard, may cover it, and it may often scab, or even skin oyer ; or, if it deepen itself, it may be with no assumption of cancerous shape, but Eke a common chronic ulcer deepening by sloughing or acute inflammation. Ear difierent from this, though sometimes superadded to it, is the form of ulcer of the breast which begins in the substance of the cancer. I will not now enter upon the discussions about the softening of can- cers (as a normal tendency of their structure), or upon those about their interior suppuration : I will only state that, in certain cases of sciiThous cancer, we find cavities filled and walled-in with softened and disintegrated cancerous matter. In these the dull, ochre-yellow, soft materia], consists mainly of degenerate cancer-cells and their debris. It may be mingled with an ill-formed pus ; and as these mingled materials increase and enlarge the cavity, so, finally, they are discharged by ulceration. Their discharge leaves in the solid mass of cancer a deep excavated ulcer, a cavity like that of a widely open abscess, except ' These granulations are formed of cancer-structiu-es ; yet, let it he otseryed, tley take the shape of such as are formed in the healing of any common ulcer. ULCERATION OS" SClERHOUS CANCER. 639 in that it is all walled-in witli cancerous matter, the remains of the solid mass. Then, as the walls of this cavity ulcerate on. their internal surface, and at the margin of the opening into it, so their outer surface is increased by superaddition of the cancerous matter ; i.e. as one part of the cancer wastes, by ejection of its nlcerating surface, so is another part increased. Hence the ulcer constantly enlarges : but the ulcera- tion does not destroy the cancer ; that increases the faster of the two, extending more and more, both widely and deeply, and involving differ- ent tissnes more and more continually, to the end of life. In all its course it yields a thin, ichorous, and often irritating discharge, that smells strongly, and almost peculiarly. In all its later course, when not disturbed, this form of cancerous ulcer has certain characteristic features, which are chiefly due to the concurrent processes of ulceration at one surface, and of predominating fresh formation at the other surface, of the cancer. Thus the edge of the ulcer is raised by the exuberant formation of cancer in and beneath the boundary of skin: exuberance of the growth necessarily everts the margin, which is too rigid to stretch ; and the margin thus raised and everted is hard, nodular, and sinuous, because the growth under it, like the primary cancer, is formed after a knotted tuberous plan. The base of the ulcerated cavity is similarly hard and knotted, or covered with hard, coarse, cancerous granulations. Lastly, when we cut through such an ulcer, we divide a thick layer of cancer, infiltrated in the subjacent tissues, before the knife reaches any noi-mal struc- tures. It would be vain to try to describe all the various and dreadful forms of ulcer that follow the acute inflammations and sloughings of scirrhous cancers, or all the aggravations of the disease by haemorrhage from the ulcerating surface, or by obstructions of the lymphatics or the veins. As I passed by the effects of these accidents of the disease, in describing its structure, so, much more, must I now. Only I would state that these are the events which produce, in cancerous patients, the most rapid and the most painful deaths. When inflammation is averted from it, a cancerous ulcer may exist very long, and make slow progress, without extreme pain or disturbance of the health ; it may be no worse a disease than the ' occult ' cancerous growth ; and ten or more years may pass with the health scarcely more impaired than at the beginning. Sir B. Brodie ' has related two such cases ; and I may ' Lectures on Surgery and Pathology, p. 211. 640 tTLCEEATION OP SCIEEHOUS CANCEE. add to them one wMch I saw in a cook, who for eight years had hard cancer of the breast. During five of these years it had been ulcerating, and yet none of those with whom she lived was aware that she was diseased. Such cases of arrest of cancer are, however, only rare exceptions to the general rule of that progress towards death, the rate of which is far less often retarded than it is accelerated by such accidental inflam- mations of the cancer as I have already referred to. Still more rare are the exceptions in which an ulcerated cancer heals. Such cases, however, may be met with, especially among the examples of the more superficial ulcer. The ulcers may be skinned-over (as any common ulcer usually is), and the cancerous mass beneath it may waste and be condensed, so that the disease may be regarded as obsolete, if not cured. The conditions under which this healing and regress of the ulcer- ated cancer may take place are, I beHeve, as yet quite unknown. In the following case they seemed to be connected with the development of tuberculous disease, as if the patient's diathesis had changed, and the cancer had wasted through want of appropriate materials in the blood. I removed the breast of a woman twenty-five years old, including a large mass of well-marked scirrhous cancer of three months' duration. She appeared in good general health, and could assign no cause for the disease. The progress of the cancer had been very rapid ; it had lately afiected the skin near the nipple ; and all its characters were those of the acute form. The axillary glands had been enlarged and hard, but had subsided with rest and soothing treatment. Six months after the operation, and after the patient had been for four months apparently well, cancerous disease reappeared in the skin about the scar, and in the axillary glands. In the skin it rapidly increased ; numerous tubercles formed, coalesced, and ulcerated ; and the ulceration extended till it occupied nearly the whole region of the scar, and often bled profusely. Thus the disease appeared progressive for twelve months after its reappearance ; but at the end of this time the ulcer began to heal, and in the next six months a nearly complete cicatrix was formed ; only a very small unhealed surface remained, like an excoriation covered with a scab. The disease in the axilla, also, nearly subsided ; one hard lump alone remained of what had been a large cluster of hard glands. But even dufing and after the healing of the cancerous ulcer she lost strength, and became much thinner, and at length, gradually ULCERATION OF SCIRREODS CANCER. 641 sinking, slie died nearly two years after tlie operation, and six months after the cancer had so nearly healed. In the examination after death I found, in the situation of the scar of the operation, a low nodular mass of the very hardest and densest cancer, extending through the substance of the scar and the pectoral muscle, and nearly all covered by thin scar-like tissue. In the axilla was one hard cancerous gland, and in the liver were many masses of cancer as dense and hard as that on the chest. In all these parts the cancer-structures appeared to be condensed and contracted to their extreme limit. The lungs contained no cancer, but were full of groups of grey suc- culent tubercles and greyish tuberculous infiltration in every part except their apices, where were numerous small irregular tuberculous cavities. The other organs appeared healthy. The contrast was very striking, in this case, between the appear- ances of active recent progress in the tuberculous disease, and of the opposite course in the cancerous disease found after death ; and I can hardly doubt that, during life, the progress of the one had been at first coincident, and then commensurate, with the regress of the other. This case illustrated the two modes of healing that may occur in cancer ; — namely, the formation of a scar over the ulcer, and the shrivel- ling of the cancerous mass. The first appears to be accomplished according to the ordinary method of the healing of ulcers : the second is probably similar to the contraction and induration of deposits of in- flammatory lymph. So far as I know, the process of superficial healing has not been minutely examined in relation to the changes ensuing in the elementary structures of the cancer. Only, one sees cuticle form- ing on the surface of apparently cancerous granulations. In the process of shrivelling the cancerous mass becomes smaller, denser, drier, and harder ; it contracts and draws in more tightly the adjacent parts ; it yields no turbid ' juice,' but a thin serous-looking fluid may be scraped from it in very small quantity. One finds in such fluid, sparingly dis- tributed, cancer-cells and nuclei, with molecular and granular debris- like matter • but (in the breast) the chief mass of the shrivelled cancer seems to consist of the proper tissues of the organs indurated and condensed. We cannot doubt that, during such a change, cancer-cells and other elemental structures are absorbed ; but the changes prepara- tory thereto are not, I think, satisfactorily explained. T T 642 PAIN. Such may serve as a general history of the progress of a scirrhous cancer in the breast. Let me add a brief notice of the pain, cachexia, and some other of its accompaniments. Among the many inconstancies in the life of cancers, none, I think, is more striking than that which relates to the attendant pain. One sees cases, sometimes, that run through their whole career without any pain. In a case of deeply ulcerated cancer of the breast, the patient, who had also a cluster of cancerous axillary glands, begged that the disease might be removed, but only because it was ' such a terrible sight.' It had never once given her the least pain. In another case a patient, from whom a cancer involving the whole mammary gland was removed, was quite unaware of any pain or other affection in her breast till, a few weeks before the operation, some of her friends observed its diminished size. The largest hard cancer of the breast that I have yet removed was equally painless. Another patient, who died with rapidly progressive and ulcerated cancer, had not a pain in its two years' duration. On the other hand, we sometimes meet with cases that quite exem- plify the agony which is commonly regarded as the constant accompani. ment of hard cancer. In such a case the patient could ' wish herself dead,' for the sake of freedom from the fierce anguish of her pain, — pain as if a hot dart were thrust swiftly through her breast, or right through her chest, — pain, startling with a sudden pang, and then seem- ing to vibrate till it fades out slowly ; or sometimes more abiding pain, likened to the burning and scalding of hot water, or of molten lead. With such resemblances as these do patients strive to describe the agonies, which are indeed beyond description, and of which the peculiar intensity is perhaps best evidenced by the fact, that the sufferers almost always thus liken them to some imaginary pain, and not to anything that they have felt before. The memories of those who have suffered even the pains of childbirth supply no parallel to that which is now endured ; the imagination alone can suggest the things with which it may be compared. Now, although both these classes of cases be exceptions from the general rule concerning the painfulness of cancer of the breast, yet they are interesting, both for their own sakes, and because they illus- trate the natare of the pain attending tumours ; they show that it is, in great measure, personal, according to constitution, and independent of the merely mechanical condition of the parts ; that it is not due to pressure on the nerves, or to their tension or displacement, but rather CACHEXIA. 643 must be considered as a subjective sensation, a neuralgia, duo to some unknown morbid state of nerve-force. That this is so is nearly sure from the fact, that if we compare the most painful and the least pain- ful cancers with each other, we may find their structure and relations exactly similar. Any of the forms that I have described may in one case be attended with intense pain, in another may exist without dis- comfort. They may present no other difference than the immense difference of painfulness. However, as I have said, both the very painfal cancers and those that are always without pain are exceptional cancers. The more general rule seems to be : (1) that in the early part of its course (for instance, in ordinary cases for the first year or year and a half) the scirrhous cancer of the breast is either not painful at all, or gives only slight and occasional pain, or is only made painful by handling it ; (2) that during this time its pain has usually no peculiar character ; is not generally lancinating, but more often, and especially after manipulation, is dull and heavy ; (3) that after this time the cancer becomes pro- gressively more painful, and the pain acquires more of the darting and lancinating, character ; (4) that the pain is generally increased when the cancer grows quickly, and more constantly when it is inflamed or ulcerating, or about to slough ; (5) that the pain is yet more intense when the cancer is progressively ulcerating, and now adds to its lancinating character, or substitutes for it, the hot burning or scalding sensation. With the advance of the local disease the signs of general disorder of the health usually increase ; and the cancerous ' cachexia,' which may at first have been absent or obscure, is established. It would be very difficult to describe this state exactly, and much more so to analyse it. The best description of its most frequent characters is, I think, that by Sir Charles Bell : ' — ' The general condition of the patient is pitiable. Suffering much bodily, and everything most frightful present to the imagination, a continual hectic preys upon her, which is shown in increasing emaciation. The countenance is pale and anxious, with a slight leaden hue ; the features have become pinched, the lips and nostrils slightly livid ; the pulse is frequent ; the pains are severe. In the hard tumours the pain is stinging or sharp ; on the exposed surface it is burning and sore. Pains, like those of rheumatism, extend over the body, especially to the back and lower part of the spine ; the hips ' Medieo-CMrurgical Transactiofis, xii. 223. T T i! 644 MULTIPLICATION. and shoulders are subject to those pains. Successively the glands of the axilla and those above the clavicle become diseased. Severe pains shoot down the arm of the affected side. It swells to an alarming degree and lies immovable. ' At length there is nausea and weakness of digestion : a tickling cough distresses her ; severe stitches strike through the side ; the pulse becomes rapid and faltering ; the surface cadaverous ; the breathing anxious;. and so she sinks.' This vivid sketch is generally true of, perhaps, a majority of the cases of hard cancer of the breast ; but I doubt whether any one of the signs of cachexia here indicated is constantly present. Even ema- ciation is not so ; for many die, exhausted by the suffering and discharge, in whom fat is still abundant, or appears even increased about the cancer itself. This want of constancy adds greatly to the difficulty of analysing the phenomena of the cachexia. We can see little more than that they include two miagled groups of symptoms : of which one may be called ' primary,' depending on the increasing morbid and peculiar cancerous condition of the blood, and the other ' secondary,' depending on the local disesise and the effects produced on the blood by its pain, discharge, haemorrhage, and various accidents. In the con- fusion of symptoms thus arising analysis seems impossible. The last concomitant of the scirrhous cancers of the breast, that I need now speak of, is their multiplication ; but I will here only enu- merate the methods in which this may happen ; for its explanation belongs to the general pathology. These, then, are the methods : — First, and most frequently, the disease extends to the lymphatic vessels and glands, or to their contents ; for it seems most probable that, as Mr. Simon has suggested, its progress is along the continuity of the lymph from the breast to the glands. (2) Next, I think, in order of frequency, are the multiplications of the cancer in the same region ; not, indeed, in the same gland, but in the skin and muscles near it, and then in areas gradually widening round it. (3) It is less frequent for the scirrhous cancer to appear second- arily in the similar tissue of the opposite breast. Indeed, its multipli- cation, if it may be so considered, is less frequent in this direction than in that of some organs of more different texture, especially the Hver, the lungs, and the bones. These, among parts distant from its primary seat, are by far the most frequent seats of secondary disease j but with DUKATION. 645 these, or, much more rarely, alone, nearly every tissue has been found affected.' The structures of many examples of these secondary cancers are already described (p. 625, etc.) It is often said that the cancers which appear as secondary to the schirrus of the breast are of the meduUary kind ; an error which I think must have arisen from the belief that the scirrhous cancer is always fibrous. I have already explained that it very rarely is so ; and only appears to be so when it grows in parts containing fibrous tissue ; and that what has been generally deemed the fibrous structure of the cancer is usually that of the organ in which it is seated. The secondary cancers are, usually, in all points conformed to the primary, and consist, like them, essenti- ally of cells compacted into a hard mass. They may appear fibrous when growing in fibrous organs ; but, inasmuch as their more usual seats are in organs that naturally contain little or no fibrous tissue, they are more commonly formed of cell-structures alone. The change from hard to soft cancer is rare ; it may, however, take place, especi- ally in the latest growths ; and it is the best illustration of the affinity between the two forms of the disease. To end this history of the scirrhous cancers of the breast, I must speak of their duration. There is a striking contrast between the certain issue, and the uncertain rate, of their progress. Cases are on record in which life has been ended in four months, and others in which it has been prolonged to twenty-five years ; but I am not aware of a single clear instance of recovery : of such recovery, that is, as that the patient should live for more than ten years free from the disease, or with the disease stationary. The nearest approach to this that I have yet seen was in the case of a woman, from whom, at fifty- one years of age, I removed a cancerous breast of two years' duration, and numerous axillary glands. She lived and worked hard for eleven and a half years without any apparent return of the disease, and died with progressive muscular atrophy of the tongue and pharynx. After death no trace of cancer was to be found, except a few very hard white masses in the liver and gastro-hepatic omentum. Mr. Birkett gives cases of yet longer intervals before recurrence. Among 150 patients four lived more than twelve years free from disease. ^ ' M. Lebert has given a table of the relative frequencies of secondary cancers in flifferent organs after primary disease in the "breast. It is drawn from 23 autopsies, Mr. Birkett has given a similar table of 37 cases examined after death. ' British Medical Journal, September 29, 1866. 646 DURATION OF SCIRRHOUS CANCER. 12 tJ 18 „ 18 jy 24 „ 24 jj 30 „ 30 }j 36 „ 3 )> 4 years. 4 5» 6 „ 6 » 8 „ 8 10 J) )) 10 „ 20 „ The average duration of life, from the patient's first observation of the disease, is a little more than four years. In 66 cases, tabulated vrithout selection, I find it something more than 49 months.' Among 61 of these 7 died in between 6 and 12 months. 10 2 12 6 3 1 The cases are too few to allow of many conclusions ; but they suffice at least to show that the average duration of life in these cancerous patients would afibrd a wrong estimate of the probable duration of life in any single case ; since the number who live be- yond the average is far less than that of those who die within it, and the mean average is raised by the lives of those few who survive long periods. It seems at present impossible to estimate many of the conditions which determine the duration of life; but none among them seems more weighty than the age at which the disease commences. There are, indeed, many exceptions to the rule, yet, on the whole, the earlier the disease begins the more rapid is its course. Thus, among those who lived not more than 18 months, I find that the average age at which the disease was first observed was 43 years. Among those who live between 18 and 36 months, it was 61 years ; and among those who lived between 3 and 8 years, the average at the commencement of the disease was 56"7 years.' ' I say ' sometliing more,' because I have reckoned-in the eases of five patients -who are stUl living more than 49 months from the first observation of the disease. In the table on this page six similar cases are reckoned -with those from which the general average is derived. Of the patients already dead, the average duration was, for those in this table, 49-36 months ; for those in the next table, 48-9 months. The difference is fer less than I believed it to be when the lecture was delivered : I was deceived at that time by using too small a number of cases, and a table containing some cases that were recorded only because they were examples of rarely long life. ^ The average for those who lived for more than 8 years was only 45 years. But this will not materially invalidate the rule as stated above, if, as I suspect, these long lives owe their unusual duration to something interfering with the more normal pro- DUEATION OP SCIERHOUS CANCEE. 647 In all the cases frota wliicli the foregoing deductions were made the disease ran its course uninterrupted by operative treatment. In 47 cases, in which the cancer was once or more removed by operation, the average duration of life, after the first observation of the disease, was again something more than 49 months. I believe, there- fore, that the removal of the local disease makes no material difference of the average duration of life ; but if the following table be compared with that on the preceding page, it will seem probable that the course of the more rapid cases is retarded by the operation. Among 41 of those patients who are already dead — 4 died in between 6 and 12 months. 4 12 )J 18 „ 2 18 •>•> 24 „ 6 24 J) 30 „ 3 30 »J 36 „ 11 3 }} 4 years, 8 4 n 6 „ 2 6 J) 8 „ 1 8 J) 10 „ 1 10 ») 20 „ It would seem, I repeat, as if the course of cancerous disease, that otherwise would be very rapid, were retarded by the removal of the growth ; for, while in some respects the two tables closely correspond, it may yet be noticed that the proportion of those who die within two years is 36 per cent, of those in whom the disease is allowed to run its course, and only 24 per cent, of those from whom the growth is once cr more removed. The number of cases from which this is concluded is indeed small ; but other facts might lead us to expect the same, espe- cially that in general the most rapidly fatal cases are those in which the local disease has the greatest share in the death. Moreover, tables by Mr. Baker (loc. cU.') prove that, by a better selection of cases for operation than had been made in the instances from which the above tables were constructed, much better results may be obtained. Thus in 84 cases, of which by far the greater number occurred after' the publication of the first edition of these lectures, and on which no operation was performed, the average duration of life was gress of the disease; and if, as is also probable, the deaths from cancers commencing in those whose average age is near sixty are often prevented or accelerated by the other diseases which destroy so large a proportion of persons living to that age. 648 EFFECTS OF REMOVAL OF SCIEKHOUS CANCEE. •43 montlis ; and ia 62 cases on whicli operations were performed, the average was 55-6 montlis. Mr. Sibley's tables indicate a still greater difference ; tlie average in cases of removal of tbe breast ' being 56 '6 montlis, and of non-removal 32-25 months. The constitutional part of the cancerous disease, little, if at aU, affected by the removal of the local part, manifests itself by the recur- rence of cancerous growths in or near the seat of operation, or in the lymphatics of the breast, or in some more distant part. In 74 cases, comprising 21 collected by M. Lebert, and 53 by myself, the periods of recurrence after the operation were as follows : — ' Between 1 and 3 months in 23 cases. 3 „ 6 JJ 22 6 „ 9 )3 8 9 „ 12 )) 6 2 » 24 )J 7 2 , 3 years in 3 8 „ 4 )) 1 4 „ 6 n 2 6 ., 8 >> 2 The table confirms the view that the removal of the local has little influence on the constitutional element of the disease ; for even if we believe that many of the cases, reported as recurrences between 1 and 3 months, were examples of continuous, rather than of recurrent, local disease, still the small proportion of cases in which recurrence was delayed more than twelve months after the operation might suggest the belief, that after an operation the constitutional disease continues and increases, till it manifests itself in recurrent local disease, in about the same time as it might have appeared in some secondary cancer, if the operation had not been performed. And this might still be concluded even from, the results of the better-selected cases from which Mr. Baker's tables were constructed, for those show that 42 per cent, of the recur- rences occurred within six months of the operation. The recufrent local disease appears generally to be less intense than the primai-y. This is probable, both from the fact mentioned at page ' Med.-Chir. Trans, xlii. ' Since the first edition, a patient has liv^ed 9j years after operation ■without any sign of recurrence, and perh.ips the case mentioned at p. 645 may be considered as another instanci' of recurrence delayed licj-crd eight years. .See also Mr. Birkett's Tables {he. cit.) EFFECTS OF REMOVAL OF SCIRRHOUS CANCER. 649 647, respecting the smaller proportion, of rapidly fatal cases in those submitted to operation, and from the fact that when recurrent cancers are removed, the second recurrences sometimes ensue more slowly than the first did. In 12 cases in which recurrent cancers of the breast were removed, I find that the period of second recurrence, i.e. the interval between the second operation and the reappearance of the disease, was Between 1 and 3 months in 4 cases. jj 3 „ 6 „ 3 „ 17 6 „ 12 „ 1 „ „ 2 „ 3 years in 2 „ » 5 )) ' j> 2 ,, And, among these late-recurring cases, is one in which the first recurrence was after 24 months, the second after 60 ; another of first recurrence in 12 months, and a second in 84 ; and another of first recurrence in 2 months, and a second in 24. It is believed by some that the cancer of the breast (and they would say the same of other cancers) is in the first instance a local disease ; and that the constitutional disease which is manifested by recurrence after operation, or by multiplicity of cancers, or by ca- chexia, is the consequence of the slowly acting influence of the local If this opinion were true, it has been supposed that we ought to find the average interval between removal of the disease and its recur- rence bearing an inverse proportion to the time of duration of the cancer before removal.' No such proportion, however, exists ; nor does it even appear that recurrence is, on the whole, later after early, than after delayed, operations. The following table shows the times of recurrence in 66 cases, in which the removal of the cancer was effected within various periods, from three months to fotir years, after its first appearance : — Time of operation. Under 3 months . T: Within 6 months. . 4 ime of Recurrences. Between 6 and 12 months. 2 More than 12 months. 2 No. of Cases. 8 Between 3 and 6 months . 6 2 2 9 „ 6 „ 12 „ . 6 4 6 14 „ 12 „ 24 „ . 9 1 3 13 ,. 24 „ 48 „ . 7 3 2 12 ' But here is a fallacy. The ' time of duration ' cannot be exactly ascertained; and long before a cancer is tangHile or visiblu it may be as potent to infect the blood as at any later time. 650 EFFECTS OF KEMOVAL OF SCIERHOUS CAlfCEE. The following table shows that the duration of life is not greater after early than after late operations : but this is, doubtless, because the most acute cancers are, on the whole, the most early removed : — Average duration Number Time of operation. of life after the of operation. Cases. Under 3 months 20 months 4 Between 3 and 6 months 12 jj 6 „ 6 „ 12 „ . 39 it 8 „ 12 „ 24 „ . . 17 J) 8 „ 24 „ 48 „ . 21 11 5 Lastly, I can find, in the cases I have collected, no confirmation ol the received (and possibly true) opinion, that when some of the axillary lymphatic glands are cancerous, and are removed with the cancerous breast, the recurrence of the disease, and its fatal termination are more speedy than after operations iu which the breast alone is removed, the glands appearing healthy. In 20 cases of removal of the breast alone, the average time of recurrence was eight months, and that of death twenty-four months, after the operation : while ia 10 cases of the removal of the breast with some axillary glands, the recurrence ensued, on an average, in thirteen months, and the death in twenty-four months after the opera- tion. I find as little clearly recorded evidence for the similarly un- favourable opinion generally entertained of the effects of the removal of cancers adherent to the skin, or already ulcerated. I greatly doubt the value of this opinion. The recurrences and deaths after these ' unfavourable ' cases are indeed sure and speedy ; but yet they are not more so than those are which follow the operations for cancers of equal duration, but neither ulcerated nor adherent. The foregoing facts, relating to the influence of the removal of cancerous breasts on the progress of the disease, and on the duration of life, may be considered from two points of view — the pathological and the practical. Mere pathology may study these operations as so many experiments for determining the mutual influences of the local and the constitutional elements of the cancerous disease ; or, the questions entertained by some respecting their priority; or, the EFFECTS OF REMOVAL OF SCIRRHOUS CANCER. 651 share taken by each in destroying life. I trust that the tables T have given may be of some avail for the settlement of these and other similar questions, to "which I shall again refer in the concluding lectures. But at present few of the facts which mere pathology can gather from inquiries such as these, are sufficiently clear or pronounced to serve for guidance in the practice of surgery, in which we have to deal with single cases, not with many at once, and in which each case presents many questions that cannot yet be solved by general statements. In deciding for or against the removal of a cancerous breast, in any single case, we may, I think, dismiss all hope that the operation will be a final remedy for the disease. I will not say that such a thing is impossible ; but it is so highly improbable that a hope of its occurring in any single case cannot be reasonably entertained. The question then, is, whether the operation will add to the length or to the happiness of Hfe. The conclusion from the foregoing tables might be that the length of life would be nearly the same whether the local disease were removed or not. But such a conclusion cannot be' unconditionally adduced for the decision in a single case. The tables do not include cases in which the operation was fatal by its own conse- quences ; yet these are not few. In 235 operations for the removal of cancerous and other diseased breasts, I find 23 deaths ; and probably this mortahty of ten per cent, is not too high an estimate for cases that are not carefully selected. With careful selection, I believe the mor- tality to be not less than five per cent. "We have to ask, therefore, whether it is probable that the operation will add to the length or com- fort of life, enough to justify the incurring this risk from its own con- sequences. The question must be answered from the results of experience, not from what may seem deduoible from a doctrine concerning the origin and nature of cancer ; for whether we hold cancer to be at first local, or at first constitutional, the result of operations would be the same unless we could detect a cancer before it has had time to affect the blood. Judging from experience, I cannot doubt that the answer to the question of operation should be often affirmative — 1. In cases of acute scirrhous cancer the operation may be rightly performed: though speedy recurrence and death may be expected, its performance is justi- fied by the probability (see p. 654) that it will, in some measure, pro- long life, and will save the patient from dreadful suffering. 2. On 652 EFFECTS OF EEMOVAL OF SCIEEHOUS CANCEE. Bimilar grounds, the operation seems proper in all cases in which it is clear that the local disease is destroying life by pain, profuse discharge, or mental anguish, and is not accompanied by evidences of such cachexia as would make the operation extremely hazardous. 3. In all the cases in which it is not probable that the operation will shorten life, a motive for its performance is afforded by the expectation that part of the remainder of the patient's life will be spent with less suffer- ing, and in hope instead of despair ; for when they are no longer sen- sible of their disease, there are few cancerous patients who will not entertain and enjoy the hope of long immunity, though it be most un- reasonable and not encouraged. On the other side, there are many cases in which the balance is clearly against the operation — 1. In well-marked chronic cancers, es- pecially in old persons, it is so little probable that the operation will add to either the comfort or the length of life, that its risk had better not be incurred. These are, indeed, the cases in which the operation may be longest survived ; but they are also those in which, without operation, life is most prolonged and least burdened. 2. In cases in which the cachexia, or evident constitutional disease, is more than proportionate to the local disease, the operation should be refused : it is too likely to be fatal by its own consequences, or possibly by accele- rating the progress of cancer in organs more important than the breast. On similar grounds, and yet more certainly, it should not be per- formed when there is any reasonable suspicion of internal cancer. 3. If there be no weighty motives for its performance, the operation should be avoided in all patients whose general health (independently of the cancerous diathesis) makes its risk unusually great : in all, for example, who are very feeble, very fat, over-fed, intemperate, or in any of those conditions which make persons unfavourable subjects for surgical operations.' The above rules leave unconsidered a large portion of the cases of scirrhous cancer of the breast ; and I fear that, at present, no other statement can be made concerning the cases which do not fall within such rules as these, than that each must be decided, by weighing the probability that the operation will prove fatal, or, by weakening the patient, will accelerate the progress of the constitutional disease, against the probability of its adding to the comfort, and thereby to the length, of life. The first of these probabilities must be estimated by the same ' See ' Lectures on the Eisks of Operation^,' in the Lancet, 1867. EFFECTS OF REMOVAL OF SCIRRHOUS CANCER. 653 general principles by which we reckon the dangers of all capital opera- tions : the estimate of the second may be, I hope, assisted, though it cannot be settled, by the evidence collected in the foregoing tables. In every case we should keep in view the twofold method of destruction by this disease. It may destroy life by its consequences as a local dis- ease ; or by its primary and specific cachexia, which niay be progressive independently of the local afieotion. Usually, indeed, its local and con- stitutional parts mutually affect and aggravate each other, and both contribute to the fatal issue ; but, since they do not always contribute in the same proportions, our object should be to ascertain, in each case, which will contribute most, — the local disease, which the operation can remedy, or the constitutional, which, if at all affected by the operation, is as likely to be made more intense as to become less so. 654 MEDULLAKY CANCEE. LECTURE XXXI. MEUULLAEY CANCEE. PART I. ANATOMY. Eeom the long list of names which Dr. Walshe, with his usual profound research, has found assigned to this disease, I select that of Medullary Oais'cer, because it has been sanctioned by the longest usage, and by many of the best pathologists. It is true that the term ' medullary ' is vague and unmeaning ; yet even this seeming defect may have some advantage, since, after long custom, we may now employ the word, as ■we do inflammation, cancer, and many others, without any reference to their original naeaning, and therefore without any danger of too much limiting our thoughts to the likenesses which they express. The very precision and fixity of such terms as encephaloid, cerebriform, cephaloma, and the like, are objectionable, by directing the mind to a single character of diseased structures, and that an inconstant one ; for the likeness to brain is observable in only a portion of the tumours to which the names of brain-like and its synonyms are applied. The boundaries of the group of medullary cancers can be only vaguely drawn ; for although, on the whole, and as a group, they have peculiarities both of structure and of history, which sufficiently distin- guish them from the scirrhous and other cancers, yet, define them by whatever character we may, a series of specimens might be found filling every grade between them and each of the other chief forms. The tei-m 'soft cancer,' often applied to them, expresses their most obvious, though not their mcst important, distinction from the scirrhous or hard cancers, and, used comparatively, it might, for the present, suffice for the definition of the group. But, in the group thus defined, there are included many forms that appear widely different from each other ; and there is, as Rokitansky has well said, no disease of which the examples present more deviations from any one cardinal character. It might be MEDULLARY CANCER. 655 riglit to arrange the examples of some of these deviating forms under distinct titles ; but, at present, it may be more useful to make no other division of the group, than into such as may be called, respectively, soft and Jirm medullary cancers. In any large series of specimens, the softer kinds would constitute about two-thirds, the firmer about one- third of the whole number. The former would include such as are described as encephaloid, brain-like, milt-like, pulpy, placental, etc. ; the latter would be such as have been called mastoid, solanoid, nephroid, apinoid, etc. Certain transitional specimens would be found in the series, which might be arranged in either division, or between the two ; but these, though they may prove that there is no specific distinction between the two chief divisions, do not invalidate the utility of speaking of them separately. The medullary cancers, whether soft or firm, may grow either as separable tumours or as infiltrations. In the former condition, they are most frequent in the intermuscular and other spaces in the limbs, in the testicle, the mammary gland, and the eye : rarely, they are thus found in the bones. In the latter condition, they most frequently occupy the substance of the uterus, the digestive canal, the serous membranes, the periosteum, and the bones. We have, herein, the first point of contrast, in addition to that of their consistence, between the medullary and the scirrhous cancers. The latter are almost always infiltrations of natural parts : the former appear, in nearly equal frequency, as infiltrations, or as distinct growths, of cancer-substance. The contrast is equally marked between them in regard to their respective seats and allocations. Of every 100 primary hard cancers, I believe that not less than 95 would be found in the breast ; and there is no other organ in which they are not very rare. But, among 103 tabulated instances ■ of medullary cancer in external parts, the seat of primary disease was in the ' It need hardly be said that this table, containing no cases of medullary cancer in the uterus or other internal organs, is not intended to prove anything concerning the relative frequency of the disease in each part of the body. I know no records by -which this could be proved. Its only purposes are, to show the contrast between medullary and scirrhous cancers in relation to their usual seats in external parts, and to indicate the kind of cases from which manv of the other tables in this lecture are derived. 656 SOFT MEDULLARY CAXCLE. Testicle .... in 29 cases Bones (most frequently in the femnr) . ;,2i „ Limbs (especially in the intermuscular spaces) „19 „ Eyeball or orbit „io „ Breast . . . . . )) ' J) Walls of the chest or abdomen I! 5 „ Lymphatics . . . . . >> ■* IJ Various other parts . . . . H 8 „ 103 Let me now, for general examples, describe such Soft Medtjllaet Cancees as often occur in the intermuscular spaces of the limbs or trunk. To the touch they present a pecuHar softness, or a deceptive sense of the slow fluctuation of some thick liquid ; so that, even to the most experienced, their diagnosis from collections of fluid is often doubtful ; and the achievement of experience in relation to them is caution rather than knowledge. In shape, these tumours are commonly round, oval, or spheroidal, fitting the adjacent parts. But they maybe variously lobed; and when they are so, these following things may be noticed in them, as well as in the firmer kinds. (1.) Their lobes are peculiarly apt to extend into muscular and other interspaces, far away from their chief mass. Thus, in the foot, they may track through the interosseous metatarsal spaces, or between bones of the tarsus ; or, about the hip or knee, portions may extend deep down to the immediate coverings of the joint ; or from behind the ankle-joint, they may reach, with the flexor tendons, far into the sole of the foot. (2.) Thus deepening as they grow, parts of these tumours may acquire unexpected deep-seated attachments. It is frequent to find them so attached in the neck, even when, in their beginning, they were easily movable tumours, or such as patients call 'kernels.' (3.) In the same extension, they are much more apt than other tumours are to grow round, and completely enclose, important vessels and nerves. I have thus seen, in one case, the phrenic nerve, in another the pneumogastric, in another the femoral artery, in others the carotid artery and jugular vein, passing right through medullary can- cers which, at first, appeared freely movable and not deeply fixed, and even now had no characters of iufiltration. The parts around a separable medullary cancer are generally only extended, as they might be round an innocent tumour. They are SOFT MEDULLAEY CANCEE. 667 usually not contracted, or adherent, as those next to a scirrhoTis cancer are. Even sucli a tissue as the glandular substance of the testicle may be cleanly separated from the surface of a medullary cancer, round which it has been stretched. Sometimes, however, the parts near the principal tumour contain smaller detached growths ; and more rarely they are infiltrated with cancer. When a distinct capsule exists around a medullary cancer, it is usually composed of connective tissue, forming a very thin layer, from the interior of which partitions may pass, intersecting the substance of the tumour, or investing its several lobes. Generally, such a capsule contains numerous tortuous bloodvessels ; and is tensely filled, so that, as soon as it is cut, the tumour protrudes or, when very soft, oozes out, like a thick turbid fluid. It is, usually, easy to separate the capsule, or part of it, from the surrounding tissues ; but it may be closely adherent and, I think, generally is so in the cases of medullary cancers in the breast. In section, the soft medullary cancers usually appear lobed ; and the partitions between the lobes, derived from the investing capsule, are often so complete that they may appear like separate cysts filled with endogenous growths. The lobes are of various sizes and shapes, through mutual compression, and they may even seem very differently constructed. The material composing these cancers (when not disordered by the effects of hemorrhage, inflammation, or other disease) is a peculiar, soft, close-textured substance, having very little toughness, easily crushed and spread out by compression with the fingers. It is very often truly brain-like, most like fcetal brain, or like adult brain partially decom- posed and crushed. Many specimens, however, are much softer than brain ; and many, though of nearly the consistence of brain, are unlike it, being grumous, pulpy, shreddy, or spongy, like a placenta, with fine soft filaments. Very few have a distinct appearance of fibrous or other regular structure. In colour, the material may be white, but most commonly, when the cancer is fresh, it is light grey (like the greyness of the retina after death). The tint is usually clear ; it is in many cases suffused with pale pink or lilac, or with a deeper purple ; and, in nearly all, is variegated with effused blood and full bloodvessels, whose unequal abundance in different parts of the tumour produces a disorderly mottled appearance. Masses of bright yellow or ochrey substance also, like u V 658 VASCULARITY OF MEDULLAEY CANCEES. tubercle, are often found in or between the lobes, as if compressed by them, while withering and drying in the midst of their growth. When pressed or scraped, the soft medullary cancers yield abundant ' cancer- juice,' a milky or cream-like, or some other turbid material, oozing or welling up from their pressed mass. There is no better rough test for the diagnosis of meduUary cancers than this is ; and the substance thus yielded is generally diffusible in water, making it uniformly turbid, not floating: in course shreds or fragments. When the greater part of the softer and liquid substances is thus pressed out, there remains a comparatively small quantity of tissue, which appears filamentous, with abundant bloodvessels, and, to the naked eye, is spongy and flocculent, like the tissue of a placenta. This is the so-called ' stroma ' of the cancer ; and it differs from that which, in the scirrhous cancers, has been so named (p. 617), in that it is not part of the tissue in which the cancer has its seat, but is probably formed during the growth of the cancer, and is as truly part of the cancer as the cells and other corpuscles are. Such are the most general or normal characters of the soft medullary cancers. It would be vain to attempt to describe all the varieties to which they are subject by the mingling of cysts within or on the surface of their mass ; by hsemorrhage into their substance ; by inflammation ; and by the various degenerations of their proper substance, of the ex- travasated blood, and of the inflammatory products. There are, I think, no other examples in which the diseases of the products of disease are so frequent, so various, or so confusing, as in these. It is in the medullary cancers alone that the bloodvessels have been minutely studied, and in these alone that it is easy to distinguish the vessels of the cancer itself from those of the organ in which it is seated. M. Lebert and his colleagues have made numerous injections, displaying arteries, capillaries, and veins, arranged in networks of various closeness, in the substance of medullary cancers of the ovary, omentum, uterus, and other parts. They have thus disproved the belief that the vascular system of these tumours is exclusively either arterial or venous. I may add, that the minute bloodvessels, though, in proportion to their size, they are thin-walled and easily torn, have the same structures as those in other new-formed parts.' ' Dr. Westhoff, in a thesis, Mikrosk. OnderzoeMngen over de Ontaarding von Aderen en Zenuwen iti Kanker,' 1860, wHch is analysed in the Bublin Quarterly Journal, Nov. 1860, makes it probable that the impossibility of injecting veins in some cancers. is due to their being fiUed with cancerous matter which stops the injection after it has tra- versed the capillaries. VASCULARITY OF MEDULLARY CANCERS. 659 In some medullary tumours we may notice a remarkable abundance of even large bloodvessels. Next to tbe proper cancer-corpuscles, they may appear to be tbe cbief constituent. Tbe cancer tbat contains them may tbus appear in many respects like an erectile tumour, and may often vary in size according to tbe fulness of its bloodvessels. Wben bloodvessels are chiefly arterial, the whole mass of the tumour may have a soft full pulsation — a condition which is peculiarly apt to be found wben the tumour is in part imbedded in, or supported by, bone, and in part held down by fibrous tissue, such as that of the perios- teum.' To the same abundant vascularity of these tumour we may ascribe not only their liability to internal apoplectic heemorrbage,^ but the great bleedings that may ensue when they protrude through ulcers, or are wounded. I have twice seen the difficulty of distinguishing a medullary cancer of the testicle from a heematocele enhanced by the fact, that when the swelling was punctured with a trocar, blood flowed in a full stream through the canula, and continued so to flow till the canuia was withdrawn. The size of the swelling was not diminished, as that of a hasmatocele would have been, by the abstraction of the blood ; and in both cases it proved to be a large medullary cancer, very vascular and very soft. So, when such tumours are cut into in the limbs, the vessels that bleed are far larger and more numerous than in any other tumour, except the erectile. Tbe vessels, moreover, often appear defective in muscular power ; for, as Mr. Hey' noticed, the bleeding from them scarcely decreases even when a tourniquet compresses the main artery of the limb. It is as if they could not contract so as to close themselves, even when the force of the blood is diminished to tbe amount with which it traverses the anastomosing channels. Lastly, we may connect with the great vascu- larity and rapid growth of these soft tumours, the large size of the veins near them ; though this is not peculiar to them, but is found, I think, with nearly all tumours that grow rapidly and to a large size. Lymphatics have been injected in two specimens of medallary cancer of the stomach and of the liver, by Schroeder van der Kolk.* ' See Mr. Stanley's paper on the ' Pulsating Tumours of Bone,' in the Med. Chir. Trans, xxviii. 303. SimilaT pulsation may often he observed in myeloid and in fibrous tumours similarly placed in connection -with hones. 2 It is chiefly to the medullary tumours changed by internal, and prone to external, hsemorrhage, that the name of fungus haematodes has been applied. 3 Observations in Surgery, p. 258. * Lespinasse : De vasis novis pseudomembranarum, 1842, p, 41. TT TJ 2 660 MEDtTLLARY CANCKROUS INFILTEATION OF BONE. In both instances the vessels passed into the very substance of the cancer. Of nerves, I believe that none have been fonnd in these or in any other cancers, except such as they have involved in their growth. The same structures which alone form the separable medullary cancers may be infiltrated among the natural structures of parts. Thus infiltrated, the natural structures are expanded and rarefied; sometimes, indeed, they seem to be, in a measure, thus changed, even before the cancerous material is deposited among them.' Pinally, most of them disappear, as in the infiltrations of scirrhous cancer ; and the cancerous mass may now seem like a separately growing tumour ; or, when its material is very soft, it may appear as a quantity of creamy liquid, collected, like the pus of an abscess, in a defined cavity. Exceptions to the general rules of the wasting of the infiltrated tissues are often observed in the fibrous tissues and the bones : both these may increase during soft cancerous infiltrations. Medullary cancers may be found in the articular ends of bones, forming distinct tumours round which the walls of the bone are ex- panded in a thin or imperfect shell. But more commonly the cancer is infiltrated. In these cases, it usually occupies, at once, the can- cerous tissue, the wall of the bone, ajid the periosteum ; and it seems probable that the disease begins simultaneously in all these parts ; or, at least, that when they are affected in succession, it is not generally by extension from one to the other. Hence we commonly find that a tumour surrounds the bone, or, in the case of a flat bone, covers both its surfaces ; and that the portion of bone thus invested is itself infiltrated with cancer, which is collected most evidently, but not ex- clusively, in its cancellous tissue. When a medullary tumour thus surrounds a long bone, it is usually of unequal thickness : when both surfaces of a flat bone are covered, the tumour is usually biconvex lens- shaped, and is, on both surfaces, of nearly equal extent. The periosteum may seem to be continued over a medullary cancer thus placed ; but is really, with the exception of a thin outer layer, involved in it, and intersects its substance. The intersecting portions of periosteum chiefly traverse the exterior tumour, extending from the layer which invests its surface to the wall of the bone. They form branching and decussating shining bands, which to the microscope present a perfect fibrous tissue, infiltrated with the cancerous materials. They may, also, be much increased by growth, so as to give the section ' Walshe, loc. dt. p. 55.5. MEDULLARY CANCEROUS INFILTRATION OP BONE. 661 of the tamour an appearance of ' grain,' or of a tissue with fibres set vertically on the bone. Or, the periosteal tissue thus growing may ossify. In this event, it forms, in a large majority of cases, a light, spongy, and friable growth of bone, which is like an internal skeleton of the cancer. Most of the specimens of ' spongy ' or ' f ungona ' exostoses are such skeletons of cancers, examined after the maceration and removal of all the morbid structures that filled their interspaces. The new bone is often formed in thia plates and bars or fibres, the chief of which extend outwards, at right angles to the surface of the bone on which they grow ; they may pass deeply into the substance of the cancer, but they seldom reach its outer surface : no medalla is formed with them ; and they sometimes form a denser and harder tissue, like that which belongs to the osteoid cancers (see p. 539). In the walls or compact substance of the bone thus inclosed by cancer, it is common to find the laminse separated by cancerous deposit, mingled with a ruddy, soft material like diploe. In other cases, the structure of the walls is rarefied, and converted into a light, soft, and porous or finely spongy tissue, whose spaces contain cancer-structures. The Haversian canals, also, may be enlarged ; cancerous matter being fornaed within them. Sometimes a peculiar appearance is derived from an unequal separation of the laminae of a bone's walls ; large spaces being found between them like cysts, which may be filled with blood or softened cancer. Lastly, in the diploe or cancellous tissue, a corresponding state exists. The soft cancerous material excludes the medulla, and, com- monly, its formation is attended with a disturbed growth of the bony cancelli, so that they form a finely spongy, dry and brittle structure, or more rarely a dense and hard structure, resembling the skeleton of the external mass of cancer.' It remains that I should describe the Firm Medullaet Cancbes. In all their general relations— as to seat, shape, size, and connec- tions — these correspond with the softer kind. Like them, they may be separate masses, or infiltrated ; may have distinct investing capsules', or may extend indefinitely in the proper substance of organs; like ' I have twice seen a formation of very firm fibrous-substance, like the basis of the osteoid cancers, in the cancellous tissue of bones that were surrounded with very soft medullary cancer. I have also seen a light brittle skeleton formed in the cancer external to a bone, of which the cancellous tissue was converted into hard osteoid substance. 662 FIRM MEDULLARY CANCERS them, they are apt to affect a certain part or place rather than a single tissue ; or may be the seats of various degeneration or disease : their only pecnliarities are in their own strncttires.' They are firm masses : not hard, like scirrhous cancers ; but, firm elastic, tense, compact, and moderately tough ; they are as tough as the more pliant examples of fibrous cartilage, and merge into exact likeness to the less hard and more elastic scirrhous cancers. They are not evidently fibrous, but tear or split as very firm coagulated albu- men might. Their cut or torn surfaces appear peculiarly smooth, compact, shining, and sometimes translucent : in some instances, they are uniforra and without plan; in some more regularly and minutely lobed, or even imitating the appearance of any gland, such as the mammary or parotid, in which they He. Sometimes they present a strongly-marked grain, as if from fibres : but this results, I believe, from a peculiar fasciculate and linear arrangement of elon- gated cells. In colour, the firm medullary cancers are hardly less various than the sofber kind. They may be pure white ; but more often are white, tinted or streaked with pale pink or yellow ; or they may be in nearly every part buff-coloured or grey ; or these tints may be mingled and mottled with blood-colour, though not so deeply, or with such effusions of blood, as are frequent in the softer tumours. On pressure, especially after contact with water, they generally yield a characteristic creamy or greyish fluid, which sometimes ap- pears strangely abundant, considering their firmness of texture. In a few instances, however, this character is wanting ; the firmest tumours may give only a thin turbid fluid. Among the points of contrast, in the descriptions of medullary and scirrhous cancers, is the wider range of variety exhibited by the former in the original characters of its growth. For the diversities which I have been describing are not to be referred to changes ensuing in different stages of the same disease : the firmer cancers do not gradually become soft, nor the soft become firmer ; they are not to be connected (as the chief varieties of scirrhous cancer may be) with the acute or chronic progress of the disease, or with its different modes of ' Generally, I think, -when they affect bones, the osseous tissue is apt to soften and waste, rather than to grow as it does in the soft medullary cancerous affections. Cer- tainly, the firm medullary cancers rarely have internal skeletons, and I have seen a case in which, with firm medullary and osteoid cancer of the humerus, all the other bones of the arm and hand were so soft that they could be broken or cut with one's nail. MICROSCOPIC ANATOMY OF MEDULLARY CANCER. 663 growth, or with the diflferences of age in which it occurs ; rather, the pecuhar features of each specimen, and of each chief group, appear to be original and constant — provided they are not affected by degenera- tion or disease. Now, equal diversities exist in the microscopic structures of medullary cancers. There are, indeed, certain characters to which nearly all are conformed : the microscopic diagnosis is there- fore seldom difficult, very seldom doubtful; yet many varieties of appearance need to be learned, both that the disease may be always recognised, and that we may, if possible, hereafter accurately divide the inconveniently large group into smaller ones. At present such a division is impracticable : for we can only sometimes trace a corres- pondence between a peculiarity of microscopic structure, and one of general aspect, in the tumours ; but it should be a chief object of future inquiries. The varieties exist in both the corpuscles and the basis, stroma, or intercellular substance of the cancers. Among the corpuscles, the most frequent, and that which seems the normal form, is that of nucleated cells, which, in all es.sential characters, are like those of hard cancer (p. 613, Pig. 100). Examples of such cells may be found in nearly every specimen, although, in certain instances, other forms may predominate over them. There is, I believe, no mark by which they may be always distinguished from, the cells of hard cancers. They may be softer, less exactly defined, more easily disintegrated by water, flatter than the cells of scirrhous cancer are, but there is in these things no important distinction. The only constant difference is in the modes of compacting, and in the relations of the cancer-materials to the natural structures in which they are placed. Cells such as, in scirrhous cancers, are closely placed, with a sparing, firm, intermediate substance, or are tightly packed among the contracted structures of a mammary gland, are in the medullary cancers more loosely held together, in a more abun- dant and much softer or liquid intercellular substance. The chief varieties of microscopic forms in medullary cancers may be described as affecting, severally, the nuclei, the cells, and the inter- cellular substance ; and it may be generally understood that each pecu- liar form may occur in combination with a predominant quantity of the ordinary or typical cancer-structures, or may, in rarer instances, form the greater part, if not the whole, of a cancerous mass. (a.) Nuclei imbedded in a soft, nebulous, or molecular basis-sub- stance or protoplasm, may compose the whole of a very soft medullary cancer. Appearances of cells may be seen among them, because of the 664 MICfiOSCOPIC AlfATOMY OF MEDULLARY CANCEE. ~5aa?' Pig. 105. adhesion of the basis-substance to them : and appearances of many nu- cleated cells, when fragments of the basis are detached in which several nuclei are imbedded. But certainly, in many instances, formed cells are rare or absent. The nuclei (Fig. 106) are like those of the typical cancer-cells (p. 613) ; they are oval or round-oval, having a long diameter of from ^^^^ to ao'bo °^ ^^ inch, bright, pellucid, perfectly defined, largely, and often doubly nucleolated. It is in the structures thus formed that the minute bloodvessels of cancer may be best exam- ined without injection ; for the soft material in which they ramify may be washed away from them, so as to leave them nearly alone, and fit for examination as transparent objects. (fe.) Nuclei (Fig. 106), which may be considered as grown or deve- loped, are often mixed, in various proportions, with other cancer- structures. Some, retaining the usual shape, as much larger than the average ; others, rarer and more peculiar, are elongated, narrow, strip-like, caudate, or pyriform. Some of these are very small, slender, and apparently of simple structure ; others, more nearly acquire the size and other characters of cells. Their contents are not so simple and pellucid as those of ordinary nuclei ; in the smaller they are darkly dotted or granular, but no contained par- ticles appear larger than common nucleoli. lu others, larger, oval, pellucid corpuscles, Kke small nuclei, are contained ; and these seem to be formed by the enlargement of the nucleoli, which thus approach or attain the characters of nuclei, while the nuclei that contain them are advanced to the condition of cells. Most com- monly, the cells, that thus seemed formed out of nuclei, are singly nucleated ; but two or three nuclei are found in a few of large size. Fig. 105. Nuclei of soft medullary cancer, imbedded i n a molecular basis-sutstance, or protoplasm, without cancer cells. Magnified 500 times. Fig. 106. Various grown and developed nuclei of medullary cancer, as described in the text. Magnified 500 times. Fig. 107. Dotted nuclei of medullary cancer, described in the est. Magnified 500 times. Fig. 106. MICROSCOPIC ANATOMY OF MEDULLARY CANCER. 665 (c.) In a few specimens of medullary cancer of the breast and of the parotid, I have found the chief constituent to be free or clustered nuclei, of round or round-oval shape (Kg. 107), from y^Vir *" sirffTr of an inch in diameter, well-defined, but not darkly, nebulous or molecular rather than pellucid, and appearing to contain four, five, or more shining gra- nules, but no special or distinct nucleolus. They might have been taken for large corpuscles of inflammatory lymph, but that neither water nor acetic acid affected them. They were imbedded in a small quantity of molecular basis, and sometimes arranged in groups, imitating the shapes of acini of glands. A few of smaller size but similar aspect appeared to be within cells. (d.) In a remarkable case, at St. Bartholomew's Hospital, a woman, sixty-seven years old, had two very large and several smaller tumours connected with the skull, a tumour in the lower part of the neck and sirailar small growths in the lungs. They were all very soft, close-textured, white, or variously coloured with extravasated blood, enclosing large cavities filled with bloody -p- jQg fluid. Except that they yielded no creamy fluid till after they were partially decomposed, one could not hesitate to call them medullary cancers. But they were composed, almost exclusively, of round, shaded nuclei, with three or four minute shining particles, and in general aspect very like the dotted corpuscles of the spleen. Many of these were free ; but more, I think, were arranged in regulaj" clusters or groups of from five to twenty or more, composing round, or oval, or cylindriform bodies (Fig. 108). A few similar nuclei were enclosed singly in cells in the cancerous growths in the lungs. Such are the chief varieties in the nuclei of medullary cancers. Scarcely less may be found in cells, mingled, let me repeat, in diverse proportions, with cells or nuclei of typical form, and rarely surpassing them in number. (e.) Besides those varieties in the shapes of cells, which were des- cribed among the microscopic characters of hard cancers (p.613), and which are equally, or with yet more multiformity, found in these, we may note the occasional great predominance of elongated caudate cells in some examples of medullary cancers. I have hitherto observed this Fig. 108. Clustered nuclei of a meduUary cancer, described in the text. Mag- nified about 400 times. 666 MICROSCOPIC ANATOMY OF MEDULLARY CANCER- in none but some of tlie firmer specimens of the kind. Many such contain only typical cancer-cells : but in some the caudate and variously elongated cells predoijainate, and, by their nearly parallel and fasci- culate arrangement, give a fibrous appearance to the section of the tumour. The adjacent sketch (Fig. 109) is from the cells of a very firm tumour that grew round the last phalanx of a great toe.' Its cancerous nature was proved not only by its structure, but by its recurrence after amputation, and by similar secondary disease of the inguinal glands. I found scarcely any cells but such as are drawn. Some wisre narrow, tongue-shaped, broad and rounded or truncated at one end, and at the other elongated and tapering. Some were elongated at both ends ; some oat-shaped ; some very slender, with long awn-shaped or cloven processes. All these had large, oval, well-defined, clear nuclei, like those of ordinary cancer-cells, and with distinct nucleoli. Their texture, also, appeared to resemble that of common cancer-cells ; they differed only in shape, being, in. this, most like the cells of recurring fibroid tumours (pp. 596, 601). (/.) In two instances I have found cancers which, by their general characters and history, should be called firm medullary cancer, and which were, in great pai't, composed of much smaller, narrower, and proportionally more elongated cells than those last described. One of these was a large deep-seated tumour behind the inner ankle and in the sole of the foot, enclosing the posterior tibial and plantar vessels and nerve, and the flexor tendons. In the other case, the primary tumour involved the gum and larger part of the front of the lower jaw ; and similar secondary disease was diifused through part of the right lobe of the thyroid gland, and, in small masses,- in both lungs. All the tumours were very firm and elastic ; the fluid that they yielded was not creamy, but viscid and yellowish. The tumour on the foot was grey, shining, minutely lobed, intersected with opaque-white fibrous bands, and in its own tissue appeared fibrous. That on the jaw was greyish. white, sufiused with pink, glistening, but with no appearance Kg. 109. Caudate and variously elongated cells of a firm medullary cancer, des- cribed in the text. Magnified 460 times. ' Mus. Coll. Surg. 252 ; and of St. Bartholomew's, Series xxxv. No 54. MICEOSCOPIC ANATOMY OF MEDULLAEY CANCEE. 667 Pig. 110. of fibrous or other texture. In all much molecular matter and granular debris, cancer nuclei, and a few cells of ordinary form were found ; but their essential structures were (as in fig. 110) very small, narrow, and elongated cells and nuclei. The cells were of various shapes ; some sharply caudate, some swollen in the middle, some abruptly truncated. They looked wrinkled and very pellucid. They measured, generally, about -j-rinr ^^ ^^ i'^^'li ^^ length. Some had elongated clear nuclei ; in others no nuclei appeared. Many free nuclei had the same shapes as these cells, and of many corpuscles it was hard to say whether they should be called cells or nuclei. (g.) Sometimes one meets with cells, in medullary cancers, in which nuclei are not at first discernible. They are round, large, nebu- lous ; they contain many minute granules ; and when water is added, it diffuses their contents, and may display a round nucleus, smaller, and more nebulous or granular than those of the typical cancer-cells. (A.) Cells containing more than one nucleus not unfrequently occur in medullary cancers. They may be seen in various stages of endoge- nous production, with two, or four, or many nuclei, and in this last case, as in the large ceUs in Fig. Ill, broods of young cells may be seen contained within a parent cell. I have not found, in medul- lary cancers, any structures similar to those of the laminated cysts or capsules which occur in epithelial cancers. Such are the chief varieties of the cor- puscles of medullary cancer : these, at least, are what I have found them presenting in their natural state. Much might be said respecting the changes efiected in them by the fatty and other degenerations and diseases, and about the confusion brought into the microscopic diagnosis by the granular masses, free granular matter, and various debris hence derived. But for these I must refer to the last lecture, and to the general account of degene- Fig. 111. Fig. 110. Small elongated cells and nuclei, -with nuclei of ordinary shape, from a firm medullary tumour, as described above. Magnified 500 times. Fig. 111. Endogenous production of nuclei and young cells in the cells of ;i, medullary cancer. 668 MICROSCOPIC AifATOMY OF MEDTJLLAEY CANCEE. rations already given.* It remains that I ahoxJd speak of the sub- stance with which the cells are associated — the basis, intercellular substance, or stroma. I need not repeat what has been said (p. 617) respecting the ' stroma, so-called, of a cancerous infiltration, — that it is only the tissue of the organ in which the cancer is seated. What I have now to describe is the substance which is proper to the cancer, and in which the cancer- corpuscles are suspended or imbedded. (a.) The cells and nuclei of medullary cancers may be suspended in liquid alone : and the two, Kke a collection of iluid rather than like a tumour, may be infiltrated in tissues, or, more rarely, may be contained in small cavities. This is not unfreqnently the case in veiy rapid pro- ductions of cancerous matter, especially in secondary deposits. The liquid (cancer-serum, as it had been named) is turbid ; it dims trans- mitted light, and has a finely molecular appearance. With the cancer- corpuscles, and usually with granular matter, it makes the ' cancer- juice ; ' the peculiar thick, creamy liquid, tinted with yellow, grey, pink, or purple, and easily diffusible in water. The quantity of corpuscles in proportion to the liquid is various ; it may be so small, and the corpus- cles themselves may be so lowly developed, that the liquid may appear the chief constituent of the cancer. (6.) The same kind of liquid which, in the cases just referred to, forms the only material suspending the corpuscles, exists, also, in the solid medullary cancers: it is the liquid of the 'cancer-juice.' But in the more solid growths it appears to be diflPased through some solid tissue, or in the interspaces of a kind of spongy texture. This, which may be more properly called a stroma of medullary cancer, is in its simplest form a nearly pellucid substance, having either no trace of structure, or only imbedded roundish or elongated nuclei ; but some- times it appears fibrillated. (c.) When medullary cancer is formed in bone or periosteum, these tissues may, as I have said, grow excessively, and make for it a fibrous or osseous skeleton (p. 661). Or, in other cases, new fibrous or osseous tissue may be formed in the cancer, and may be as a stroma for the can- cer-cells. Medullary cancers thus composed are the chief examples of transition-forms to the scirrhous cancers, on the one hand ; and, on the other, to the osteoid cancers, in which the cancer-cells are wholly or nearly superseded by an imperfect ossific production. ' Or, -with more adrantage, to Lebert's admirable account of the changes of the cancer-eeUs, in his Traiti Pratique, p. 23. MIOEOSCOPIC ANATOMY OF MEDULLARY CANCER. 669 ((^.) Sometimes a framework, enclosing and supporting cancer- cells, appears to be formed by elongated fibro- cells arranged in series of commnnicating lines. But, more commonly, a framework is con- structed of delicate pellucid or nucleated membrane, with filamentous tissue. In the last case one obtains from a medullary cancer, after ex- pressing as much as possible of its ' juice,' a kind of sponge, flocculent and shreddy, constructed of membrane and filamentous tissue, with bloodvessels, and stiU- adhering cancer-particles. One thus sees that, even in the minuter parts, the substance of the growth is intersected with such partitions as are visible with the naked eye, separating its larger lobes. Eokitansky has given ' the following description of the structure and development of the framework or stroma of medullary cancer. In certain examples of such a stroma or skeleton, two interlacing networks, or meshed structures, maybe seen (Figs. 112, 113). One of these (6) consists of slender bands, beams, or tubes (Fig. 112, c) of a hyaline substance, which contains oblong nuclei, and may be in part fibrillated or transformed into filamentous connective tissue. The other and younger structure (a) is composed of larger opaque bands or beams, which are made up of nucleated cells, with elementary granules, and variously perforated. These form a network interlacing with that formed by the hyaline structures. Moreover, with these opaque beams, formed of the same structures, and projecting from them, or from the hyaline structures, there are hollow flask-shaped or villous processes or out-growths (Fig. 113). Many of these pass through the apertures or meshes in the networks, projecting through them with free ends ; and the apertures with which many of them are perforated, enlarging by absoi-ption, give them the appearance of netted hollow bands or cords. Some of these same processes, also, appear pellucid, hyaline, and nu- cleated at their bases or pedicles of attachment, or through more or less of their length. These several conditions of the stroma indicate, Eokitansky says, that it is constructed on that plan of ' dendritic vegetation,' of which the type and best example is in the villous cancers. The growth of the stroma takes place at first in the form of hollow, flask-shaped, bud- ding, and branching processes or excrescences, which are composed of hyaline membrane, and filled with nucleated cells and grannies. These processes constantly increase, throwing out fresh ofishoots of the same > Ueber die Entwickelung der Krebsgeriiste, 1852, from the Siizungsberichtc der Kais. Akademie. 670 STROMA OP MEDULLARY CANCER. shape as themselYes first had. At the same time the cells, or part of the cells, within the processes uBite or fase their cell- walls, while their Fig. 112. nuclei remain and are elongated. Thns the texture of the growing stroma becomes hyaline, nucleated, and filamentous ; and, as apertures Fig. 113. Figs. 112 and 113. Development of cancer-stroma, described in the text. Mag- nified 90 times. From Eokitansky. The formation of these branching hyaline pro- cesses seems to be not unlike that -which takes place in the production of the structures met with in Cylindroma, p. 469. STEOMA OF MEDOLLARY CANCER. 671 are formed in it by partial absorption of its textures, it becomes also meshed and reticulate or sponge-like. Fresh dendritic vegetations arising on the same plan, from the network thus formed, pass with in- terlacements through its meshes ; and, by repetition of the changes just described, increase the stroma and the complexity of its construction. The production of cancerous elements is commensurate with the growth of the stroma, and they fill all the interstices, as well as, in some cases, the tubules of the networks . The foregoing descriptions, though illustrated by only a few exam- ples, might sufiice, I believe, for the medullary cancers of nearly all parts. Yet it maybe useful, if, after the example of the other lectures, I describe some of the peculiarities which this form of cancer presents in certain organs — making a selection on the same grounds as in the last lecture (p. 620) . In the Testicle the medullary cancer is usually of the softer kind : the firmer kind is not uncommon, but examples of the scirrhous, or any other form of cancer, except the medullary, are of exceeding rarity. The medullary cancer commonly appears as a regular oval or pyri- form mass, which the toughness of the enclosing fibrous coat of the testicle permits to grow to a great size without protrusion. As the fibrous texture is distended by the growth, so it commonly also in- creases in thickness. The surfaces of the tunica vaginalis are generally partially adherent; and what remains of the cavity, usually at its upper part, is filled with serous or blood-tinged fluid. Part, or the whole, of the glandular tissue of the testicle may, I think, be always found outspread on the surface of the tumour : the epididymis, often the seat of similar disease, is generally flattened and expanded. Separate medullary cancers may lie near, especially in the loose areolar tissue of the spermatic cord : or the growth may perforate the tunica albuginea, and extend exuberantly about the testicle in the sac of the tunica vaginalis, or in the loose tissue of the scrotum : or, without communication, part of the cancer may be within, and part around, the tunica albuginea.' The general characters of the cancer- structure in the testicle are ' Mr. Prescott Hewett showed me a specimen in -which a healthy testicle "was sur- rounded hy medullary cancer. Examples of similar cancers in the spermatic cord, the testicles being healthy, are in the College Museum, No. 2462-3 : some affecting the undescended testicles are related by Mr. Amot {Med.-Chir. Trans, xxx. p. 9), and by Dr. Eayrer in Min. Month. Med. Jour. March 1863. 672 MEDULLABY CANCEK OF THE EYE. usually conformed to tHe type already described, yet these points may be considered worthy of note : — (1.) Sometimes the lobes of the can- cerous mass are severally so invested with connective tissue that they may have the appearance of cysts filled with endogenous cancerous growths.' (2.) Portions, or whole lobes, of the tumour, degenerate and withered into a yellow substance, like tuberculous or ' scrofulous ' matter are usually seen, especially near the central parts of the cancer. (3.) Large cavities full of blood may exist, and add to the difficulty of the diagnosis from haematocele. (4.) The conjunction of m.edullary cancer with cartilage is more frequent in the testicle than in any other part (see p. 623). (5.) The disease very rarely affects both testicles, either at once or in succession. The medullary cancer of the Eye so rarely deviates from the general characters of the disease, and, since Mr. Wardrop's first account of it, has been described, in all works on Ophthalmic Surgery, so much more fully than would here be reasonable, that I shall advert to only two points which it illustrates : — (1.) It is especially apt to present, either in parts or throughout, the melanotic form ; a fact which we can hardly dissociate from that of its growth near a seat of natural black pigment, and which illustrates the tendency, even of cancers, to conform them- selves, in some degree, to the structures of ad jacent healthy parts. (2.) It shows a remarkable disregard of tissue in its election (if it may be so called) of a seat of growth. I fally agree with M. Lebert in his denial of the opinion that either the retina, or any other tissue of the eyeball, is in all or even in a large majority of cases the place of origin of the cancer. Rather, we have here, a striking instance of what may be called the allocation of cancers ; of their growth being determined to certain places rather than to certain tissues. Any of the tissues within or about the globe of the eye, or any two or more of them at a time, may be the primary seat of the cancer ; and, probably, each of them is more liable to be so than any similar tissue elsewhere is : the locality, therefore, which they all occupy, may be assumed as that to which the cancerous growth is directed, rather than any of the tissues themselves. And so it appears to be, when, after extirpation, the can- cer returns, as if with preference, in the same locality, although the whole of the first growth, and of the tissues which it occupied, is re- moved - ' Mus. Coll. Surg. No. 2396. MEDULLARY CfANCER OF THE BREAST. 673 Tke Breast is among the parts which, are most rarely the seats of medullary cancer I cannot tell exactly the proportion which the cases of medullary bear to those of scirrhous cancer ; but I think it is not greater than five to ninety-five in this conntry ; an infrequency which seems the more remarkable by its contrast with the occurrence of the disease abroad. In France, according to M. Lebert,^ about one-fifth of the cancers of the breast are ' soft and encephaloid.' In America, Dr. J. B. S. Jackson has assured me that the proportion is not less than one-fifth ; and I gather, from the records of German writers, that it is with them about the same. I have never seen, in the recent state, a medullary cancer of the breast which had a brain-like or any other usual appearance : ^ but I have observed four cases of what must be regarded as medullary cancer, though widely deviating from the usual characters, and not resembled by any of the same kind except some of those occurring in the brain. They may be worth description, because they are with difficulty dis- tinguished from scirrhous cancers, on the one hand, and from mammary glandular or cystic tumours, on the other. If a general description may be drawn from these few cases, it may be to the following eSect, The tumours are separable masses, closely connected with the sur- rounding mammary gland or fat, but not incorporated with them, and having, in some instances, distinct thin capsules, — a character at once distinguishing them from all the scirrhous cancers of the breast that I have yet seen. They are, generally, seated on or near the surface of the gland, ' floating ' as mammary glandular tumours often do. The skin over them is upraised, thin, and tense ; not depressed, or morbidly adherent, or itself cancerous ; but when ulceration is at hand, becom- ing livid, then ulcerating sparingly, and then everted with the protrud- ing and outgrowing tumour. The tumours are oval, flattened, rounded, or nodular ; firm, sometimes very firm, but not hard or very heavy like scirrhous cancers, and at or about their centres they feel like cysts tensely fiUed with fluid. They may grow quickly, and to much larger size than scirrhous cancers ; are not remarkably painful ; and are often associated with the formation of large serous cysts. Their general history is that of ordinary medullary cancers. With these characters alone, the diagnosis of such medullary 1 Des Maladks Canoereuses, p. 326. '' I do not so consider two specimens in the Museum of St. Bartholomew's, Series xxxT. 28 29, removed from the front of the chest after amputation of the breasts on account of extreme hypertrophy. X X 674 MEDULLARY CANCEE IN THE SUBCUTANEOUS TISSUE. cancers of the breast is very diflBcult; all these equally belong to mammary glandular tumours or proliferous mammary cysts. But the same disease may exist in the axillary lymphatic glands, forming quickly-growing masses, apt to be much larger than those in scirrhous cancer. And, if ulceration ensue in the tumour, it becomes exuberant, with lobed and coarsely-granulated firm growths, discharging offensiye ichor, and sometimes profusely bleeding. When such tumours are removed, they are found, as already stated, separable from the mammary gland ; it is pressed away by them, but is itself healthy. The section of the tumour is minutely lobed, with lobes or ' granulations ' closely grouped, like those of a mammary glandular tumour. Their texture is close, more or less firm, easily crushed, shining on the cut surface. In colour, they are greyish, varied with dots and irregular lines of yellow (which do not follow the course of the gland-ducts), or, in parts, suffused with livid or deeper purple tints. Parts of them, or even whole lobes, may be soft, shreddy, pale- yellow, like tuberculous infiltration ; and these seem to be portions that are degenerate and withered, like the tuberculoid materials in other medullary cancers. They yield, not a creamy fluid, but a turbid grey- ish, or viscid yellowish one. In microscopic examination traces of a glandular acinous plan may be again observed : the corpuscles of the tumour being arranged in round or oval groups, which lie in the meshes or alveoli of a stroma, formed of delicate connective tissue in which numerous young cells are infiltrated. These corpuscles present such forms as have already been described on pp. 665, 666, and in them endogenous cell-multiplication in various stages of development may be observed. In the Subcutaneous Tissue, or deeper areolar layer of the skin, the medullary cancers, while generally conformed to the type, exhibit these peculiarities : — (1.) They are apt to assame the melanotic state ; a fact allied to that already mentioned of the cancers of the eyeball. (2.) While, in nearly all other external parts, the medullary cancers appear as single growths, they are here very often multiple. Such nu- merous cancers may grow after one affecting some distant organ ; or may be fir.st formed below the cutis. In the latter case, many may appear coincidently ; or, when in succession, none seem to be conse- quences of the growth of their predecessors ; they all have the charac- ters of primary cancers, of ' cancers d'emblee.' In some cases all the MEDULLARY CANCER OF LYMPHATIC GLANDS. 675 tumours appear in a single region of the body. In an old man, lately under Sir. W. Lawrence's care, two medullary cancers were removed from the scalp, and four remained in it. In a case, which I shall presently detail, a large number were seated on one arm and shoulder, but scarcely any appeared elsewhere. In some cases, on the other hand, they appear at about the same time in many and distant parts; and in some, though limited at first to a single region, they grow suc- cessively in other parts more and more widely distant. Such was the event in a remarkable case by Dr. Walshe, ' In this aptness to be the seat of many medullary tumours, the sub- cutaneous tissue agrees most nearly with the serous membranes and the liver and other glands. The separable tumours are generally isolable, oval, discoid, or lens-shaped ; very rarely, I believe, they are pedun- culated : they do not commonly grow to a great size, or tend to ulcer- ation or protrusion, unless after injury. But there seems no limit to their number ; it is as if the force of the disease, which, in other instances, is spent in a single enormous growth, were here distributed among many. (3.) It is chiefly among these examples of multiple medullary can- cers that the occasional disappearance of a cancer, as if by absorption, may be observed. The old man referred to, as under the care of Sir W. Lawrence, was admitted because one of the tumours in his scalp was largely and foully ulcerated. The removal of it was deferred on account of the other tumours, and especially on account of one behind the ear ; but in the course of about a month this almost wholly disap- peared ; the largest of those remaining was now removed ; and during the healing of the wound the rest nearly disappeared, becoming grad- ually smaller and firmer. So, in the case of multiple tumours of the arm, before the patient died, the whole of the smaller tumours were completely removed during the sloughing and suppuration of the larger. The Lymphatic Glands, so rarely the seat of primary scirrhous can- cer, are often primarily affected with medullary cancer. They are, in- deed, less frequently so affected than they seem to be ; for, in some in- stances, when the disease seems primary in them, it is only because of its predominance over that in the organ with which the glands are con- ' Medical Times and Gazette, Aug. 21 and 28, 1852. In his treatise on Cancer, Dr. Walshe gives a full analysis of all the cases previously published. See also the singular case recorded by Mr. Ancell {Med.-Chir. Trans, xxv. p. 227). X X 2 676 MEDULLAEY CANCER OF LYMPHATIC GLANDS. nected. But, in more instances than these, the glands are first, and for a time exclusively, afiected. The most frequent seats of such primary disease are the cervical, inguinal, lumbar, axillary, and mediastinal glands : in a few very rare instances nearly the whole lymphatic system has quickly become cancerous. The primary cancer of the lymphatic glands usually affects, from the first, more than one gland ; often, it extends through a whole group, and so many tumours form in a cluster, that one may doubt whether all of them are in glands. They may present any of the various forms of medullary cancer ; and these peculiarities may be noticed in their course : — (1.) They are rarely well marked in the first instance ; they appear like merely enlarged glands ; their constant and accelerating increase may alone suggest the suspicion of the nature of the disease. (2.) Cysl^formation is frequent in connection with them. Especially, I think, in the neck, one may find serous cysts, in elderly persons, resting on clusters of cancerous glands, and the cysts may be often evac- uated, and win fill again, while the main disease makes insidious pro- gress deep in the neck. (3.) Partial suppurations may occur in the cancerous glands, rendering the diagnosis for a time still more difBcult. (4.) It is especially among the cases of cancerous lymphatics that we may find those occurrences of deep connection, and of enclosing of large nerves and bloodvessels, to which I have referred (p. 656). (6.) Can- cerous lymphatic glands often give a faUacious support to the belief that innocent tumours are apt to become cancerous; for the glands sometimes enlarge before the cancerous disease is established in them ; and since, in their simple enlargement, they are like simple tumours, there is an appearance of transmutation, when in such a state they be- come the seats of cancer. In the RECTrM, and in other parts of the digestive canal, I have already said that growths of medullary cancer may coexist with scir- rhous cancer. Whether in this combination or alone, or with epithe- lial forms, the medullary disease may appear in at least three dis- tinguishable aspects : — (1.) It consists sometimes in difiuse infiltration of creamy, white, or greyish cancerous substance in the submucous tissue, the mucous membrane being, for a time, healthy, but raised into the canal with low unequal elevations. (2.) Much more commonly, larger and more tuberous circumscribed masses grow in the submucous tissue, projecting and soon involving the mucous membrane, then exu- berant through ulcerated apertures in it, and often bleeding. (3.) MEDULLARY CANCER OF RECTUM. 677 Witli nearly equal frequency the disease has its primary seat iu the mncous membrane. Here it forms broad, circular, or annular growths, of a soft, spongy, and shreddy substance. They are but little raised above the level of the mucous membrane, unless it be at their margins, which are usually elevated and overhanging, and when ulcerated, sinuous and everted. They are very vascular, justifying Rokitansky's expression, that the bloodvessels of the affected part of the membrane have assumed the characters of those of an erectile tissue. They might produce little stricture of the canal, if it were not that they are, I think, frequently associated with thickening and contraction of the tissue external to them. It hardly needs to be added that in whichever part of the intestine the disease commences it extends to the rest, and from them to the sur- rounding tissues : exemplifying here as everywhere the coincident pro- cesses of destruction and of more abundant forniation.^ ' When I have omitted all description of the medullary cancers of the uterus, lungs, brain, and many other organs in which they frequently occur, it will not, I hope, be forgotten that my purpose is only to illustrate the general pathology of the disease by the best examples which I have been able to study. To have entered further on the special pathology of cancer in each organ would have been beyond my purpose, and quite superfluous while the great works of Walshe and Lebert can be consulted. 678 MEDULLARY CANCER. LECTURE XXXI. MBDULLAET CANCKR. PAKT II. FATHOLOGr. The general history of medullaiy cancers presents tlie best marked type of malignant growths. Among all tumomrs, they appear, in at general view, the most independent of seat and of locality ; the most rapid in growth ; the most reckless in the invasion of diverse tissnes ; the most abundant in multiplication : they have the most evident con- stitutional diathesis ; they are the most speedily fatal. All these facts will be illustrated by comparison of the following sketch with the cor- responding histories of the other forms of cancer. (a.) Among the conditions favouring the production of medullary cancer, the peculiarities of the female sex, though not without influence, appear far less powerful than they appear in the history of scirrhous cancers. The peculiar liabihty of the uterus so much surpasses that of any of the male organs of generation, that women are certainly, on the whole, more liable than men are to this form of cancer. But when the medullary cancers of the generative organs of both sexes are left out, the majority of the remaining cases are found among males. (6.) The medullary cancer is prone to occur at an earlier age than any other form ; it is, indeed, almost the only cancerous disease that we meet with before puberty. The three localities in which, according to M. Lebert,^ cancer occurs at the lowest mean age are (in the order of their liability), the eye, the testicle, and the osseous system. To these, while confirming his observation, I would add the intermuscular spaces, and other soft parts of the trunk and limbs. The mean age of the occurrence of cancer in these parts is under 40 ; in all other parts it is above 40, and in most of them above 50. Now the four localities named above are those in which the medullary and melanotic cancers almost alone occur as primary affections. ' Traite Pratique, p. 140. See also one of the tables in Med.Chir. Trans, ilv. p. 393. INFLUENCE OF AGE. 679 From a table ' of 164 primary medullary cancers of the bonea, soft parts of the trunk and limbs, the eye and orbit, the testicle, breast, and yarious other external parts, I find that the ages at which they oc- curred were as follows : — Before 10 years of age Between 10 and 20 . 20 „ 30 . 30 „ 40 40 „ 60 . 60 „ 60 . Above 60 . . . Breast Soft parts of Umbs and trunk Lymph- atic glands and other parts Bones Eye and Orbit Testicle Total 2 2 3 2 6 3 3 6 2 1 3 2 2 3 4 12 11 6 11 4 6 15 1 4 2 1 5 3 4 2 12 17 8 3 25 21 33 32 30 20 10 7 23 10 54 31 46 171 The striking contrast between this table and that of the 158 cases of scirrhous cancer (p. 632) needs little comment. Of the scirrhous cancers, not one occurred before the age of 20 ; of the medullary can- cers, more than a fourth began before that age : of the former, nearly half commenced their growth between 40 and 60 years of age ; of the latter, little more than a sixth : of the former, nearly three-fourths com- menced after 40 ; of the latter, little more than one-third did so. The following table, also, may be compared with that at p. 632. It shows, by similar calculations, the relative frequencies of medullary cancers in external parts, in proportion to the number of persons living at each of the successive decennial periods of life. The greatest fre- quency is between 40 and 60, and reckoning this as 100, the following numbers may represent the frequencies of the beginning of medullary cancers at other decennial periods : — to 10 years . . 31 38 69 79 100 99 44 10 20 20 30 30 40 40 50 60 60 Above 60 ' The table is constructed jErom nearly equal numbers of M. Lebert's cases and my o\ra • and it may be worthy of remark, that in the case of every part the average age is higher in his cases than in mine. 680 IVIEDITLLAIiy CANCEE: HEREDIT.AJIY TENDENCY. The chief points which this table may illustrate are — (1), that the maxinmm of frequency, in proportion to the number of persons Hving at the several ages, occurs between 40 and 50, as well for the meduEary as for the scirrhous cancers of estemal parts ; but (2) that there is a gradual ascent to this maximum from the earliest period of life, and then a more gradual descent from it. I believe, however, that if we could reckon the frequencies of medullary cancers of internal organs, we should find no such dimimi- tion after the age of 50. Rather, it would appear that (in consequence chiefly of the frequency of cancer of the stomach, rectum, and bladder in advanced life) the frequency of medullary cancers, in proportion to the number of persons living, continues to increase up to the latest age. There are, I believe, no tables in which the medullary are separated from other cancers of internal organs ; but from those of the cancers of the uterus and stomach given by Lebert, and of the lungs by Walshe (of which, doubtless, the majority were medullary cancers), the pro- portionate frequencies at successive periods appear to be as follow. (For comparison's sake, the proportion between 40 and 50 years is still counted as 100.) to 10 years ..... 10 „ "20 „ (cancers of the lungs alone) 20 „ 30 30 „ 40 40 „ 60 50 „ 60 60 „ 70 70 „ 80 3 15-7 51 100 204 236 (cancers of the stomach almost alone) . . 250 There are no data from which we could exactly reckon the relative frequencies of medullary cancer in each part of the body ; but there can, I think, be little doubt that it is a disease which, on the whole, becomes constantly more frequent, in proportion to the number of persons living at each successive period of life, from the very earliest to the latest age. (c.) The influence of hereditary tendency is probably about the same in medullary as in scirrhous cancer. Among thirty- two patients, five were aware of cancer having occurred in other members of their families, and of these five, four reported that two members of their res- pective families had died cancerous. INFLUENCE OF INJURY. 681 (d.) Among fifty-seven patients with medullary cancer of external parts, seventeen gave a clear history of previcas injury or disease of the part affected ; in seven the history was doubtful. Certainly it would be impossible to prove, in many of these cases, that the cancer was in any sense consequent on the injury after which it formed ; and yet, while we find that a third of the patients with medullary cancers ascribe them to injury or previous disease, while less than a fifth of those with simple tumours, or with hard cancers, refer them to such cause (p. 634), we cannot fairly doubt that these local accidents have influence in determining the place and time in which the medullary cancerous disease shall manifest itself. The influence of injury is very clearly shown in certain cases, in which there is no appreciable interval between its immediate ordinary consequences and the growth of a medullary cancer in the injured part. For example, a healthy boy was accidentally wounded in the eye. It had been perfectly sound to this time ; but, within a few days after the injury, a medullary tumour grew from the eyeball. It was removed three weeks later ; but it quickly recurred, and destroyed life. A boy fell and struck his knee. It had been perfectly healthy ; but the inflammatory swelling (as it was supposed) that followed the fall did not subside : rather, it constantly increased ; and in a few weeks it became probable that a large medullary tumour was growing round the lower end of the femur. Amputation proved this to be the case. Again, a sturdy man at his work, slipped and strained, or,perhaps broke, his fibula. Three days afterwards he had increased pain in the injured part, and, at the end of the week, swelling, which, though carefully treated, constantly increased. Eight weeks after the injury the swelling was found to be a large medullary growth around and within the shaft of the fibula ; and the limb was amputated. We must, I suppose, assume the previous existence of a cancerous diathesis in the persons in whom these rare consequences of accidental violence ensued ; nevertheless their cases prove, as I have said, the in- fluence of local injury in determining the time and place in which the cancer will be manifested ; and they may make us believe that, in many cases, in which a clear interval elapses between the injury and the appearance of the cancer, the effect of the violence, though less immediate, is certain. (e.) Although I know of no numerical evidence to support it, yet I think the general impression must be true that medullary cancer is 682 MBDULLAKY CA:NCEE : peculiarly liable to occur in tbose who have many of the features of the fair strumous constitution ; in persons of fine complexion, light hair and eyes, pale blood, quick pulse, and of generally delicate or feeble health. Scirrhous cancer appears most frequent in those who have the opposite characters of temperament. A difference also exists in re- lation to the general health of those in whom the two forms of the dis- ease are severally observed. I mentioned (p. 635, note) that 96 per cent, of the subjects of scirrhous cancer appear to have good general health at and soon after its first appearance : the proportion of those in the like condition with medullary cancer is about 89 per cent ; the remainder have presented from the very beginning a loss of weight and of muscular power, accelerated action of the heart, quick breathing, paleness, and general defect of health. In the growth of medullary cancer we may chiefly observe these three things — (1) their multiplicity in certain cases ; (2) their generally rapid rate of increase ; (3) the occasional complete suspension of growth. I have referred to their multiplicity in the subcutaneous tissue, but again notice it, to mention the observation of Rokitansky,' that medullary cancers are sometimes developed in great number in the course and among the phenomena of a very acute typhoid fever. I do not know what their greatest rate of increase may be ; but it has in several cases exceeded a pound per month, and, except in the instances of some of the cartilaginous tumours (p. 503), it is, I believe, unequalled by any other morbid growth. In general, the more rapid the growth the less is the firmness, and the less perfect the development of nuclei and cells, in the medullary tumour. Their rapid increase commonly indicates, not a special capacity of growth or multiplication of cells in the tumour already formed, but an intense diathesis, an ample provision of appropriate materials in the blood. The growth ia by simple increase : the materials once formed do not normally change their charact-ers ; there are no stages of crudity or maturity ; the disease is, in its usual and normal course, from first to last the same. But while these things justify the expression that the medullary is, on the whole, the most acute form of cancer, yet there is, I believe, none in which arrest or complete suspension of progress is so apt to occur. These cases have occurred within my own observation. — A man ' Fathologische Jiiatomie, i. 373. SUSPENSION OF GEOWTH. 683 thirty-eiglit years old, had a slight enlargement of one testicle for fifteen years, and its rate of increase was often inappreciable. At the end of this time rapid growth ensued. On removal, -well-marked medullary and melanotic cancer was found, and was the only apparent source of the enlargement. He died soon after the operation with recurrence of the disease. A man, forty-two years old, had a large increasing medullary tu- mour of the ilium. He had also a tumour in the upper arm, which had grown slowly for seTon years, and had been stationary for three years. When he died, the tumour in the arm had as well-marked characters of medullary cancer as that of the ilium, or of any other of the several parts in which similar disease was found.' A man, thirty-five years old, had numerous medullary tumours in his right upper arm, shoulder, and axilla, all of which had commenced their growth within three months, and were very quickly in creasing. One, which appeared to be in every other respect of the same kiud, had been stationary for twelve years in the groin, and another nearly as long in the neck. Sir Astley Cooper removed a gentleman's testicle for what was believed to be medullary cancer. He remained well for twelve years, and then died with certain medullary cancer in the pelvis. Dr. Baly had a patient who had observed for several years a tumour connected with two of his ribs. It had scarcely enlarged, till shortly before his death ; then it quickly increased, and, at the same time, nu- merous medullary cancers appeared about it and in more distant parts. ^ Cases such as these occur, so far as I know, in no cancers but those of the medullary and melanotic kinds. They seem to be quite inexpli- cable ; and as yet no facts have been observed which would show a pecu- liarity of structure in the arrested cancers corresponding with the strangeness of their life. As the medullary cancers grow, the parts about them generally yield, and some among them grow at once in strength and in extent, and for a time retard both the increase and the protrusion of the tumour. Be- cause the skin over a medullary cancer is not often infiltrated (as that > Museum of St. Bartholome-w's, Series i. Nos. 235 to 240. Case related ty Mr. Stanley in Med.-Chir. Trans, xxviii. p. 317. ^ The tumour on the ribs is in the Museum of St. Bartholomew's, Series xxxt. No. 103. It appears an ordinary medullary cancer, with a hard bony skeleton. 684 MEDULLARY CANCER : over a hard cancer usually is), Vfe do not often see the kinds of ulcer described in the last lectnre (p. 637). Neither is there, in medullary cancers generally, any remarkable proneness to ulceration. The usual course is, that, as the tumour grows, the skin and other parts over it become thinner and more tense ; then, as the growth of the tumour is more rapid than theirs, they inflame and ulcerate, and a hole is formed over the most prominent part of the tumour. There is nothing specific or characteristic in this ulceration ; it is only such as may ensue over any quickly-growing tumour ; but the continued rapid increase of the cancer makes it protrude and grow exuberantly ; it throws out fongns, as the expression is. The exuberant growth, exposed to the injuries of the external world, inflames, and hence is prone to softening, bleeding, ulcerating, and sloughing.' These may keep down its mass ; yet it may grow to a vast size, having only its surface ulcerated ; lower down, it usually adheres to the borders of the apertures in the skin, and over- hangs and everts them. This is usually the case with the huge out- growths of medullary cancer that have protruded from the eyeball, after penetrating through ulcers of the overstretched cornea or sclerotica. And similar exuberant growths are often seen when medullary cancers have penetrated the walls of various cavities or canals : thus, e.g., they grow along the canals of veins when they have entered them by, it may be, a single small orifice. In the cases of diffuse infiltration of an exposed superficial tissue (e.g. of the mucous membrane of the stomach or rectum) the cancer usually ulcerates widely with the tissue it affects, and herein imitates more nearly the characters of the ulceration in scirrhous and epithelial cancers. Through the constantly deepening cachexia, with which the increase in the medullary cancers is usually commensurate, and which is aug- mented by the various influences of the local disease, the usual course of the medullary cancer is uniformly towards death ; and rapidly thither, even when the grovfth does not involve parts necessary to life. And yet, as Rokitansky has observed,^ there is no form of cancer in which spontaneous natural processes of healing so often occur. Doubtless nearly all the reputed cases of the cure of cancer have been erroneously ' Li Series xxxv. No. 60, in the Museum of St. Bartholomew's, is a large medullary tumour whicli had grown in the subcutaneous tissue of the back, and, after the skin over it had ulcerated, was in one mass squeezed out through the opening, while the patient was endeavouring to raise herself in bed. " Loc. cit. p. 375. DEGENERATION. 685 SO regarded ; yet instances may be easily gathered of at least temporary cure ; and these are important in relation to the general pathology of cancer, since they afford the best examples of the effects of its degener- ations and diseases.' The degenerations of medullary cancer are chiefly three : withering, fatty, and calcareous degeneration. Its chief diseases are equal in num- ber : hasmorrhage or apoplexy, suppuration, and sloughing. A medullary cancer may gradually decrease, becoming harder, as if by shrivelling and condensing, and at length may completely disappear. I have mentioned such cases at p. 675 ; and I have seen the same happen after partial removal of cancers. A firm medullary tumour was seated deep in the substance of a young woman's parotid gland. Its removal with the knife could not be safely completed ; about a fourth part of it was left behind, and the wound was left to heal in the ordinary manner. It healed quickly, enclosing the remains of the tumour ; but after some time all the ap- pearance of swelling subsided, and no renewed growth ensued till after a lapse of three months, when it was renewed, but not more rapidly than before. A woman's humerus was amputated, with a large mass of firm medullary cancer surrounding its neck and the upper part of its shaft. The same disease existed in all the muscles about this part of the bone; and the patient was so exhausted, that the dissection necessary for the removal of the whole disease could not be completed. Large portions of it were left in the deltoid and great pectoral muscles. In two months after the operation, however, the wound had very nearly healed and no trace could be felt of the masses of the cancer in the muscles. Nor did any perceptible recurrence take place till more than four months after the operation. At that time renewed growths ap- peared at the scar, and in the thyroid gland, and quickly increased. To these cases I might add at least three in which I have known portions of cancerous growths left in the orbit after incomplete opera- tions • in all of which complete healing ensued, and one, two, or three months elapsed before any renewed growth was evident in the portion of disease that was left. In all these cases the disappearance of the ' A probable instance is related by Pirogoflf {Klinische Chirurgie, i. p. 45). It was in a middle-aged man. The tumour grew to a great size, and appeared connected with the periosteum of the ribs ; it ulcerated, sloughed in portions, and finally healed. The patient remained well for two years, at least. 686 MEDULLARY CANCER: cancer may have been due in part to the disease and rapid degeneration excited in it by the injury of the operation and its consequences ; and in all, the growth was renewed within three months of the disappear- ance : a fallacious hope was in all excited, and bitterly disappointed. Bat I shall have presently to refer to a case in which the removal of cancers was independent of local injury. It is most probable that fatty degeneration coincided with the wasting and absorption of cancer which occurred in the preceding cases: for it seems to be the most frequent change when growth is hindered. I have already referred to the fatty degeneration which, in medullary cancers, as in other tumours, may give an appearance of baff or ochre- yellow lines or minute spots scattered, as a reticulum, through their substance. I have also described (p. 658) the similar but larger dege- neration which ensues in those portions or lobes of medullary cancers that are found as tuberculoid masses (phymatoid, of Lebert), yellow and half-dry, among the other portions that appear actively progressive. In both cases it is probable that the altered substances are incapable of further growth : but the change, being only partial, does not materially affect the progress of the whole mass. But, though more rarely, a whole mass (especially when many exist, as in the liver) may be found white, or yellowish- white, soft, partially dried, close-textured but friable, and greasy to the touch — in a state of what Rokitansky has called ' saponification.' In such cases, many of the cancer-cells and nuclei have the characters of the granular or fatty degeneration, and may appear collapsed and shrivelled ; and they are mingled with abundant molecular matter and oil-particles of various sizes, and often with crystals of cholestearine or with coloured granules. All the analogies of such changes in other parts imply that cancers thus degenerated must be in- capable of increase ; they are amongst those which may well be called as by Hokitansky, obsolete. But I am not yet sure that these gradual changes have been ever followed by absorption of the altered cancer- substance, and by healing : ' the disease ceases but does not dis- appear : and usually, while one mass is thus changing, others are pro- gressive. The calcareous degeneration is much more rare than the two pre- ceding. It is fully described by Dr. Bennett^ and by Rokitansky,' and ' The supposed cases of healing of cancer of the liver, reported as having occurred at Prague, admit of other explanations. (See Lebert, Traite Pratique, ^ 72). " On Cancirous and Cancroid G-rowlhs, p. 214. » Loc. at. p. 352. FUNGUS H^MATODES. 687 IS in all essential characters similar to that which so often occurs in degenerating arteries, calcified inflammatory products, etc. The earthy- matter, in minute granules, is commonly mingled with fatty matter, and, according to the quantity of fluid, is like more or less liquid or dry and hardened mortar : if hardened it lies in grains, or larger irre- gular concretions, in the suhstance of the tumour. Its indications are the same as those of the fatty degeneration with which it is usually mingled.' Among the diseases of medullary cancers their proneness to bleeding may be mentioned. Hence their occasionally abundant hsemorrhages when protruding, and the frequent large extravasations of blood in them, variously altering their aspect as it passes through its stages of decolorisation, or other changes. The extreme examples of such bleed- ing cancers constitute the Fungus Hsematodes. Acute inflammation also is frequent, especially in such as are ex- posed through ulcers. It may produce not only enlargement of the bloodvessels and swelling of the tum.our, but softening, suppuration, and, I believe, other of its ordinary effects. The softening may be com- pared with that which occurs in inflammation of any natural part, like which, also, it is, I believe, often attended with a rapid fatty degenera- tion or a disintegration of the cancer-structures. Thus degenerating, and whether with or without suppuration, a medullary cancer may be completely removed. By sloughing, also, a medullary cancer may be wholly ejected ; and this event is more likely to happen than with any other kind of cancer, because no other is common in the form of an isolable mass. I might collect several cases in which it has occurred, but none is more remark- able than this.^ — A strong man, forty- six years old, under Sir W. Lawrence's care, had a large firm medullary cancer deep seated in his thigh, of about nine months' growth, painful and increasing. In an attempt to remove it, the femoral artery was found passing right through it ; its connections, also, appeared so wide and firm, and ' I have little doubt that the melanotic cancer might he truly descrihed as a pig- mental degeneration of the medullary cancer (except in the few instances in which epithelial cancers are melanotic). But part of another lecture will be devoted to this. The same lecture will comprise the colloid or alveolar cancer ; and I shall have oc- casion to mention in it the frequent occurrence of cysts in medullary cancers, some of which might perhaps be described as a cystic disease of the cancers. 2 The case is fully reported by Mr. Abernethy Kingdon, in the Medical Gazette, 1850. 688 MEDULLARY CANCER : bleeding ensued from vessels of so great size,- that the operation was discontinued after about half the surface of the tumour had been nnco- Tered. The tumour sloughed, and gradnally was completely separated. It came away with nearly three inches of the femoral artery and vein that ran through it. ISTo bleeding occurred during or after the separa- tion, and the cavity that remained in the thigh completely healed. The man regained an apparently good health for a few weeks ; then the disease, returning in the thigh, proved quickly fatal. In the following strange case, nearly all the methods of spon- taneous temporary cure which I have been illustrating were exem- phfied : — A tail, healthy -looking man, thirty-six years old, came under my care in July 1850. In October 1849 he thought he strained his shoulder in some exertion, and soon after this he noticed a swelling over his right deltoid muscle. It increased slowly and without pain for nine months, and was thought to be a fatty tumour, or perhaps a chronic abscess. About the beginning of July, other tumours appeared about the shoulder ; and, when I first saw him, there was not only the tumour first formed, which now covered two-thirds of the deltoid, but around its borders were numerous smaller round and oval masses ; in the axilla was a mass as large as an egg ; over the brachial vessels lay a series of five smaller tumours, and a similar series of larger tumours over the axillary vessels reaching under the clavicle. A small tumour of several years' date lay at the border of the stemo-mastoid muscle ; and one, which had been noticed for twelve years, was in the right groin. All these tumours were soft, pliant, painless, subcutaneous, movable, more or less lobed. There could be very little doubt that they were medul- lary cancers, and their complete removal seemed impossible ; but it was advised that, for proof's sake, one should be excised. I therefore re- moved one of those near the chief mass. It was composed of a soft greyish substance, with a pale purple tinge, lobed, easily reduced to pulp, and in microscopic structure consisted almost wholly of nucleated cells exactly conformed to the very type of cancer-cells. The operation was followed bj- no discomfort ; and, a few days after it, the patient left the hospital, still looking healthy, but, I supposed, doomed to a rapidly fatal progress of the disease. At home, near Dover, he was under the care of Mr. Sankey. In a few days after his return, the skin over the largest tumour cracked, and a thin discharge issued from it. Four days later he was attacked with sickness, diarrhoaa, and abdominal pain, and in liis writhings he hurt TEMPORARY CURE. 689 his arm. Next day, tliree or four more openings had formed over the great tumour, and the scar of the operation-wonnd reopened ; the tu- naour itself had rapidly enlarged. From all these apertures pus was freely discharged, and in a day or two large sloughs were discharged or drawn through them. With the sloughing, profuse hssmorrhage several tiroes occurred. All the upper part of the arm and shoulder was undermined by the sloughing, and a great cavity remained, from which, for three weeks, a thin foetid fluid was discharged, but which then be- gan to heal, and in twelve weeks was completely closed in. While these changes were going on in the tumours over the deltoid and in those near it, that in the axilla was constantly enlarging. It be- came ' as large as a hat,' and early in September it burst ; and through a small aperture about six pints of pus were rapidly discharged. A great cavity, like that of a collapsed abscess, remained ; but it quickly ceased to discharge, and healed. In the same time all the tumours over the brachial vessels disappeared ; they did not inflame or seem to change their texture ; only, they gradually decreased and cleared away, and with them that also disappeared which had been in the groin for twelve years. It need hardly be said that during all this time of sloughing and suppuration the patient had been well managed and amply supported with food and wine and medicine. About the end of October he ap- peared completely recovered, and returned to his work. I saw him again in January 1851. He looked and felt well, and, but that his arm was weak, he was fully capable of work as an agricultural labourer. Over the lower half of the deltoid there was a large irregular scar ; and this appeared continuous posteriorly with a small mass of hard tough substance, of which one could not say whether it were tissues indurated after the sloughing, or the remains of the tumour shrivelled and har- dened ; whatever it was, it was painless and gradually decreasing. No traces remained of the other tumours in the ai-m, except a small mass like a lymphatic gland in the middle of the upper arm. In the axilla there was a small swelling like a cluster of natural lymphatic glands. The tumour also remained at the border of the sterno-mastoid muscle, and was rather larger than in July. In February 1851 the swelling of the axilla began to increase ; its growth became more and more rapid. By the end of March the arm was greatly swollen ; he sufiered severe pain in and about it ; his health failed ; he had dyspnoea and frequent vomiting, and died with pleuro- pneumonia on April 20. The tumour in the axilla (the only one found T T 690 MKDULLAHY CANCEK: after death) was about eight inches long, oval, lobed, soft, vascular, and brain-like, and consisted chiefly of small apparently imperfectly-formed cancer-cells. So in a case with Mr. PhiUips, a lady nearly seventy had a great tumour in the lymph-glands behind the left stemo-mastoid ; many lymph-glands near it and the other side ; and some in the groins were large, hard, and to all appearance cancerous. The great tumour, about three inches in diameter, had sloughed on its surface when I first saw it, and appeared as if being excavated. And with continued sloughing its excavation went on, tiU in a month, when I again saw her, it was completely cleared out, leaving a deep granulating cavity that reached down to the front of the spine. While this had been going on, all the other glands had been becom- ing smaller, and many had disappeared. But the apparent good was of only some weeks' duration. Then renewed growth ensued, and the pa- tient died as with the ordinary increase of cancer. In another case, I saw a very large medullary cancer of the undes- cended testicle entirely disappear three times before its final fatal in- crease and infection of the lumbar lymph-glands. In this case the changes seemed due to the influence of liquor potassae with iodide of po- tassium. Such cases as these need little comment. They illustrate the spon- taneous removal, and so far the healing of medullary cancers by ab- sorption, by inflammation and abundant suppuration, and by sloughing. They show the absorption of the cancerous matter, doubtless in an alteredstate, accomplished without evident injury to the economy. And they illustrate the cancerous diathesis quickly re-established, after being, we must suppose, suspended or superseded for a time, during the re- moval of its products. It is scarcely possible to give general illustrations of the pain and other phenomena attendant on the progress of medullary cancers ; for these are variously modified by the many organs in which it may have its primary seat. The history of some of the medullary cancers which grow as distinct tumours, may teach us that the pain is not an affection of the cancer itself, but of the organ which it occupies. Such cancerous tumours, in the subcutaneous areolar tissue are, I believe, rarely the sources of pain ; often they are completely insensible ; yet the same kind of tumours seated among the deeper parts of Hmbs, or inclosed in the testicle, or in bone, seem to be usually painful, and often severely so. The difference indicates that the varying pain is not of the cancer, but of the part it fills. PAIN AND CACHEXIA. 691 The cachexia is, in the later periods of the disease, too much varied by the disturbed functions of the organs specially affected to admit of general description. But it is chiefly in this form of cancer that, early in the disease, and even while the local affection seems trivial and in- volves no important part, we often find the signs of the general health being profoundly affected ; the weight and muscular power regularly diminishing, the complexion gradually fading, the features becoming sharper, the pulse and breathing quicker, the blood more pale. Such events are, indeed, inconstant, both in the time of their occurrence and in their intensity ; but in many cases they are far too striking to be overlooked ; the defective nutrition of the early stages of phthisis is not more marked : the evidence is complete for the proof of a distinct can- cerous cachexia, which is indeed commonly indicated and may be measured by a cancerous growth, but which may exist in a degree with which neither the bulk nor the rate of increase of the growth is at all commensurate. To estimate the general duration of life in those who have medullary cancers, those cases alone should be reckoned in which parts whose functions are not essential to life are affected' — such as the bones and soft parts about the trunk and limbs, the testicle, the eye, and other external organs. From a table of fifty cases of medullary cancers in these parts (including eight cases of cancer of the bones by M. Lebert, in all of which the disease pursued its course without operative inter- ference, I find the average duration of life to be rather more than two years from the patient's first observation of the disease.' Among 45 of these patients — 6 died wdthin 6 months 7 „ between 6 and 12 months 1 )) 71 12 „ 18 „ 4 71 )1 18 „ 24 „ 7 )J fi 24 „ 36 „ 7 3» 17 36 „ 48 „ 3 ,,moretlian48 7) from the com- mencement of the disease. A comparison of this table with that at p. 646 will show, in striking ' I have not reckoned in this table the exceptional cases referred to at p. 682 in •which the disease appears to have been suspended for some years. But I have included five cases in which the patients were still living beyond the average time. In the forty-five already dead, the average duration of life was 23-8 months. T T 2 692 MEDULLAEY CANCER: contrast -witli the history of scirrhous cancer, the rapidity of this forta in running its fatal career ; a rapidity which is certainly not to be as- cribed to the earlier exhaustion produced by haemorrhage, discharge, pain, or other local accidents of the disease, but is mainly due to the augmenting cachexia. The same comparison wUl show how small is the proportion of those in whom the disease lasts more than four years; and there seem to be no cases parallel with those of scirrhous cancer which are slowly progressive through periods of five, ten, or more years. I have mentioned instances of the apparent suspension of the disease ; but these are different from the cases of constant slow pro- gress, the rarity of which supplies an important fact in diagnosis, in the great probability that a tumour is not a medullary cancer, if it have been increasing for more than three years without distinct manifesta- tion of its cancerous nature. The effect of removing medullary cancers is, on the whole, an in- creased average duration of hfe ; but chiefly, I believe, because in a few cases the operation is long survived, and, in some, death, which would have speedily ensned, is for a time arrested. Thus, in forty-six cases in which external medullary cancers were removed by excision, or amputation of the affected part, the average duration of life was something more than twenty-eight months.' Among fifty-one cases (including nine cases of extirpated cancer of the eye, from M. Lebert) these were the several times of death, reckoning, as before, from the first observation of the disease by the patient : — 1 13 7 11 3 Within 6 months . Betwee n 6 and 12 months >j 12 JJ 18 „ . J) 18 J) 24 „ . )j 24 J) 36 „ . J) Above 36 48 )J 48 „ . The comparison of this table with that on p. 691 will show that the only notable contrast between them is in their first and last lines. If the operation be recovered from, the regular course of events brings about the renewal of cancerous growth, either near the seat of the former growth, or in the lymphatics connected therewith, or, more ' Two of Mr. Baker's tables show a greater adrantage derived from operations, piobably because of a better selection of cases. The average duration of life in 32 cases not submitted to operation was 20 months; in 16 cases operated on, 33'4 months. DURATION OF LIFE. 693 rarely, in some distant parts. In tMrty-eight cases of medullary cancer, afifecting primarily the same external organs as aflForded the cases for the former tables, I find the average period of recurrence after the operation to have been seven months. I have reckoned only those cases in which a period of apparent recovery was noted after the operation ; all those oases are omitted in which the disease was not wholly re- moved, or in which it is most probable that the same disease existed unobserved in lymphatics or other internal organs at the time of operation. Tet the average rate of recurrence is fearfully rapid. It was observed in between — 1 and 3 months in 18 cases. 3 „ 6 „ 11 „ 6 „ 12 „ 4 „ 12 „ 24 „ 3 „ 24 „ 36 „ 2 „ Among the fifty-one cases in the table on page 692, those of five patients are included, who were living without apparent return of disease, for periods of three, three and half, four and a half, five, and six years, after operation ; and I have referred, already to one case in which a patient died with cancer in the pelvis twelve years after the removal of a testicle which was considered cancerous. Of cases more near to recovery than these I can find no instances on authentic record. The cases I have been able to collect supply little that is conclu- sive respecting the diflferent durations of life, according to the age of the patient, the seat of the cancer, and other such circumstances. In children under ten years old, the average duration of life, with medullary cancers of external parts, is, I believe, not more than eighteen months ; after ten years, age seems to have little or no influence. According to the part affected, the average duration of life appears to be greater in the following order : — the testicle, the eye, the bones, the soft parts of the Umbs and trunk, the lymphatics ; but the difierence is not consider- able. It is the same, I beHeve, with the results of operations ; recur- rence and death occur, on the whole, more tardily after amputations for medullary cancers of the bones and soft parts of the limbs, than after extirpations of the eye or testicle ; but there are many obvious reasons why we cannot hence deduce more than a very unstable rule for practice. The previous duration of the disease seems, also, to have little influence on the time of recurrence after the operation : the only general rule seems to be, that the rapidity of recurrence corresponds with that of the progress of the primary disease. 694 MEDULLAEY CANCER: Now, respecting the propriety of removing a medallary cancer in any single case, mnoh that was said respecting the operation for scir- rhons cancer of the breast might be repeated here. The hope of finally curing the disease by operation should not be entertained. Such an event may happen, but the chance of it is not greater than that of the disease being spontaneously cured or arrested ; and the chance of any of these things is too slight to be weighed in the decision on any single case. The question in each case is, whether life may be so prolonged, or its sufferings so diminished, as to justify the risk of the operation. In general, I think, the answer must be afSrmative wherever the disease can be wholly removed, and the cachexia is not so manifest as to make it most probable that the operation will of itself prove fatal. (1.) The number of cases in which the patients survive the opera- tion for a longer time than that in which, on the average, the disease runs its course, is sufficientto justify the hope of considerable advantage from the removal of the disease. On the other hand, the number of chronic oases of medullary cancer is so small, that no corresponding hope of a life being prolonged much beyond the average can be reasonably held if the disease be left to run its own career.' (2.) The hope that the removal of the cancer will secure a con- siderable addition (two or more years, for example) to the length of life, will be more often disappointed than fulfilled. But, even when we do not entertain this hope, the operation may be justified by the belief that it wiU avert or postpone great suffering. The miseries attendant on the regular progress of a medullary cancer, in any external part, are hardly less than those of hard cancer of the breast ; they are such, and in general, so much greater than those of the recurrent disease, that un- less it is very probable that an operation will materially shorten life, its performance is warranted by the probability of its rendering the rest of life less burdensome. (3.) A motive for operation in cases of supposed medullary can- cers may often be drawn from the uncertainty of the diagnosis. This is especially the case with those of the large bones, for the removal of which the peril of the necessary operation might seem too great for th e ' The difference here stated may seem opposed hy the tables in the foregoing pages. I must therefore state that, at p. 683, I have referred to all the cases of chronic or suspended medullary cancer that I have ever seen or heard of ; but tha t the cases of operations surviving for more than three years, mentioned at page 693, were not selected on this account, but occurred in the ordinary course of observation. EESULTS OF OPERATION. 695 probability of advantage to be derived from it. I have referred to cases of cartilaginous and myeloid tumours o£ bone (pp. 603, 644, 647), in -wMoli during life tbe diagnosis from medullary cancers was, I believe, impossible. In all sncb. cases, and I am sure ttey are not very rare, the observance of a rule against tlie removal of tumours or of bones believed to be cancerous, would lead to a lamentable loss of life. All doubts respecting diagnosis are bere to be reckoned in favour of operations. 696 EPITHELIAL CANCER. LECTURE XXXII. EPITHELIAL CANCEB. PAET I. — ANATOMY. EpiTHELiiL Cancer lias its primary seat, witt very rare exceptions, in or just beneath some portion of skin or mucous membrane. Its most frequent locality is the lower lip, at or near the junction of the skin and mucous membrane ; next in order of frequency it is found in the tongue, prepuce, scrotum (of chimney-sweeps), labia, and nymphaa : more rarely it occurs in very many other parts — as at the anus, in the interior of the cheek, the upper Kp, the mucous membrane of the palate, the larynx, pharynx, and cardia, the neck and orifice of the uterus, the rectum and urinary bladder, the skin of the perineum, of the extremities, the face, head, and various parts of the trunk. In the rare instances of its oc- currence, as a primary disease, in other than integumental parts, it has been found in the inguinal lymphatic glands (as in a case ' which I shall relate), in bones,^ the dura mater, and in the tissues forming the bases or walls of old nlcers. By extension from any of its primary seats, an epithelial cancer may occupy any tissne : thus, in its progress from the lip, tongue, or any other part, muscles, bones, fibrous tissues, are alike invaded and destroyed by it. As a secondary disease, or in its recurrence after removal by operation, it may also have its seat in any of these tissues at or near its primary seat ; but it more commonly affects the lymphatic glands that are in anatomical connection therewith ; and, very rarely, it has been found iu internal organs, the lungs, liver, and heart.' ' Mus. St. Bartholomew's, Series xxi. No. 6. ^ By Virchow in the tibia, in the Wiirzhurg Verhmdlungen, i. 106 ; and by C. 0. Weber in the lower jaiv, Chir. ErfaJirungen, 343. ' In the lungs and in the heart, in the Museum of St. Bartholomew's, Series siv. No. 61. In the liver once, by Eokitansky (Pathol. Anat. i. 386). In the lungs and in the liver, in the Museums of Berlin and "SViirzburg (Virchow, loc. cit., and in his ANATOMY. 697 The essential anatomical character of the epithelial cancer is, that it is chiefly composed of cells, which in most cases bear a genera 1 re- semblance to those of tesselated, or scaly epithelium, such as lines the interior of the lips and mouth, and that part of these cells are inserted or infiltrated in the interstices of the proper structures of the skin or other affected tissue.' But when it occurs in connection with mucous membranes which are covered by columnar epithelium, the new cells have the cylindrical form of this kind of epithelium. The epithelial cancers of the skin or mucous membrane from which, as types, the general characters of the disease must be drawn, present many varieties of external shape and relations, which are dependent, chiefly, on the situation in which the cancerous structures are placed. They may be either almost uniformly diffused among all the tissues of the skin or the mucous membrane, predominating in only a small degree in the papiUce ; or the papillse may be their chief seat ; or they may occupy only the sub-integumental tissues. As a general rule, in the first of these cases, the cancer is but little elevated above or imbedded below the normal level of the integument, and its depth or thickness is much less than its other dimensions ; in the second, it forms a promi- nent warty or exuberant outgrowth ; in the third, a deeper seated flat or rounded mass. These varieties are commonly well marked in the first notice of the cancers, or during the earlier stages of their growth ; later, they are less marked, because (especially after ulceration has Archiv, iii. p. 222). Oh. Eotin has described, under the title Epithelioma of the Kidney [Gaz. des Hopitaux, 1855), a well-marked case of epithelial cancer of the kidney, but under the same title he describes a case which appears to have been no- thing more than blocking up with epithelium and dilatation of the urine tubes. In a case described by Mr. Sibley in the Path. Trans, x. p. 272, in which the tongue was affected with epithelial cancer, a post-mortem examination disclosed a peculiar con- flition of the right supra-renal capsule. It was enlarged and converted into a firm, almost fibrous-looking, cream-coloured substance, in which ' large numbers of cells, closely resembling epithelial cancer-cells, were found.' The other viscera were healthy. ' In assigning these two conditions as the essential characters of epithelial cancers namely, both the constraction with epithelial cells, and the insertion of such cells among the original, though often morbid, textures of the affected part — I make a group of diseases less comprehensive than either the 'Cancroid' of Lebertand Bennett, or the 'Epithelioma' of Hannover. These excellent pathologists, and many others following them, would abolish altogether the name of epithelial cancer, and place the cases which are here so designated in a group completely separate from cancers, as ex- emplified by the scirrhous and medullary forms. It is not without much consideration that I have decided to differ from such authorities; but I believe that the whole patho- logy of the diseases in which the two characters above cited are combined is, with rare exceptions, so closely conformed to that of the scirrhous and medullary cancers, that they should be included under the same generic name. 698 SUPERFICIAL EPITHELIAL CANCEBS. coTnTTienced) an epithelial cancer, which has been superficial or exabe- rant, is prone to extend into deep-seated parts ; or one which was at fisrt deeply seated may grow out exuberantly. Moreover, when ulcer- ation is in progress, a greater unifornuty of external appearance is found ; for, in general, while all that was superficial or exuberant is in process of destruction, the base of the cancer is constantly extending both widely and deeply into the sub-integumental tissues. I believe that it wUl be useful to describe separately the external characters of the two principal varieties of epithelial cancer of the in- teguments here indicated ; and (while remembering that mingled, transi- tional, and intermediate specimens may be very often seen), to speak of them as the superficial or outgrowing, and the deep-seated, forms of the disease.' Among the examples of the superficial epithelial cancers, the greater part derive a peculiar character from the share which the papillae of the skin or mucous inembrane take in the disease. These being enlarged, and variously deformed and clustered, give a condylomatous appearance to the morbid structures, which has led to their being called papillary or warty cancers, and which renders it sometimes difiBcult to distinguish them from common warty growths. According to the changes in the papillaB, numerous varieties of external appearance may be presented : I shall here describe only the chief of them." In the most ordinary examples of epithelial cancer of the lower lip, or of a labium, or of the scrotum in the soot-cancers, if they be exam- ined previous to ulceration, one can feel an outspread swelling, and an unnatural firmness or hardness of the affected skin. The width and length of the swelliug are much greater than its thickness. The diseased part is enlarged ; the Hp, for example, pouts, and projects like one overgrown ; and the swelling is slightly elevated, rising gradually or abruptly from its borders, and having a round or oval or sinuous outline. Its surface, previous to ulceration, may be nearly smooth, but • I believe that either of these forms may occur in any of the parts enumerated as the usual seats of epithelial cancer ; hut they are not both equally common in every such part. The superficial, and especially those which have the chaiacters of warty and cauliflower-lite outgrowths, are most frequently found on mucous surfaces, espe- cially those of the genital organs ; the deep-seated are more frequent in the tongue than elsewhere ; those in the extremities and in the scrotum have usually a well- marked warty character, and are rarely deep seated. Other particulars might, I believe, be stated, but I am unwilling to state them unsupported bv counted numbers of cases. VAEIETIES. 699 more often is coarsely granulated, or tuberoulated, or lowly warty, like the surface of a sypMlitic condyloma, deriving tMs character usually from the enlarged and closely clustered papiUffi. The surface is generally moist with ichorous discharge, or covered with a scab, or with a soft material formed of detached epidermal scales. The firmness or hardness of the diseased part is various in degree in different instances : it is very seldom extreme ; the part, however firm, is usually flexible and pliant, and feels moderately tense and resilient on pressure. Com. monly, it is morbidly sensitive, and the seat of increased afflux of blood. Its extent is, of course, various ; but, before ulceration, the disease makes more progress in length and breadth than in depth ; so that when, for exam- ple, it occupies the whole border of a lip or of a labium, it m.ay not exceed the third of an inch in thickness. In the form of epithelial can- cer just described there may be no considerable enlargement of papillae, or it may only appear when the growth is cut through. But, in many instances (espe- cially, I think, in the epithelial cancers of the prepuce, glans, and integuments of the extre- mities), the changes of the pa- pillae are much more evident. In some, as in the adjacent sketch, one sees a great extent of surface covered with crowds and clusters of enlarged papillse set on a level or slightly elevated portion of the cutis. Singly (when the ichor and loose scales that fill their intervals are washed away), they appear cylin- driform, flask-shaped, pyriform, or conical : clustered, they make nodu- lated and narrow-stemmed masses. They may be in one or in many Kg. 114. The papillary character is well shown in this specimen of soot-cancer of the hand, in the Museum of St. Bartholomew's (Series xi. 6). The history of the case is in Pott's Works by Earle, iii. 182. The patient was a gardener, who had been employed in strewing soot for several mornings ; the disease was of five years' duration. 700 VARIETIES OE EEITHELIAL CANCEBS. groups ; or groups of them may be scattered round some large central ulcer. They appear very vascular, and their surface, thinly covered with opaque white cuticle, has a pink, or vermilion, or brightly florid hue.' In other instances, or in other parts, a large mass is formed, the sur- face of which, when exposed by washing away the loose epidermoid cells which fill up its inequalities, is largely granulated or tuberculated, and is planned out into lobes by deeper clefts. Such growths are up- raised, cauliflower-like ; and, with this likeness, m.ay be broken through the clefts, into narrow- stemmed masses, formed each of one or more close-packed groups of enlarged, tuberous, and clavate papillae.^ The surface of such a growth shows, usually, its fuU vascularity ; for if it be washed, it appears bare, and, like the surface of common granula- tions, has no covering layer of cuticle. It may be florid, bleeding on slight contact, but, more often it presents a dull or rusty vermiUou tint, rather than the brighter crimson or piuk of common granulations, or of such warts as one commonly sees on the prepuce or glans penis. Occasionally, we meet with an epithelial cancer having the shape of a sharply-bordered circular or oval disc, upraised from one to thi-ee lines above the level of the adjacent skin or mucous membrane, and imbedded in about the same depth below it. The surfaces of such disc- shaped cancers are usually flat, or slightly concave, granulated, spongy, or irregularly cleft ; their mai'gins are bordered by the healthy integu- ments, raised and often slightly everted by their growth. Such shapes are not nnfrequent among the epithelial cancers of the tongue, of the lining of the prepuce, and of the scrotum. I removed such an one also from, the perineum, and have seen one in the vagina. Sometimes, again, an epithehal cancer grows out in the form of a cone. I examined such an one removed from the lower lip, which was half-an-inch high, and nearly as much in diameter at its base. Its base was a cancerous portion of cutis ; its substance was firm, grey, com- posed of the usual elements of epithelial cancers imbedded among con- nective tissue outgrown from the skin : the subcutaneous tissue was healthy. In another instance an exactly similar cancer grew on a chim- ney sweep's neck ; ^ and in both these cases, the growth being covered ' Museum of St. Bartholomew's, Series i. 42, 126, 127, etc., and Series xi. 6. Mus. Coll. Surg. 2301, 2607, 2608, etc. 2 Museum of St. Bartholome-w's, Series xxx. 35. Mus. Coll. Surg. 2609. ' Mus. of St. Bartholomew's, Series xxxv. No. 99. In the next year the sam patient was in the hospital with a cancerous wart of the scrotum. PEDUNCULATED EPITHELIAL CA^GER. 701 with a thick laminated black and brown scab, was, at first, not easy to distinguish from syphilitic rapia ; that in the neck might even have been confounded (as some, I believe, have been) with one of the horns that grow sometimes from the skin. Mr. Curling ^ describes a similar growth, three-quarters of an inch long, on the scrotum of a chimney- sweep ; and has copied, from one of Mr. Wadd's sketches, a represen- tation of a horn two and a half inches long similarly formed. Lastly, we may find epithelial cancers as narrow-stemmed or even pendulous growths from the cutis. I have seen such on the lower lip, and at the anus, like masses of very firm exuberant granulations, two inches in diameter, spring- ing from narrow bases in the cutis, or deeper tissues, and far overhanging the adjacent healthy skin. And I lately examined one of this kind, which was removed from the skin over the lower border of the great pectoral muscle. It was exactly like the specimen sketched in Eig. 115." Fig. 115. It was spheroidal, about an inch in diameter, rising from the skin with a base about half as wide : it was lobed, deeply fissured, and subdivided like a wart, with its component por- tions pyriform and mutually compressed. Its surface was pinkish, covered with a thin opaque white cuticle, which extended into and seemed to cease gradually in the fissures. Its substance, composed almost wholly of epithelial cancer-cells, was moderately firm and elastic. It was but little painful. A thin strong-smelling fluid oozed from it. The patient had noticed a small unchanging wart in the place of this growth for ten or twelve years. Without evident cause it had begun to grow rapidly, and had become redder and discharged flaid six weeks before its removal.^ It is almost needless to say that a much greater variety of shapes than Fig. 115. Section of a narrow-based outgrowing epithelial cancer. It was ex- tremely vascular, and had grown in the place of a dark mole, or pigmentary nsevus, on the wall of the abdomen. Two growths had been previously removed from the same part. ' Treatise on Diseases of the Testicle, p. 522. The specimen is in the Mus. Coll. Surg. 2469. In the Museum of St. Bartholomew's, Series xxviii. No. 61, is an in- stance of very large soot-cancer, in which, at the borders of the ulcer, there are spur- shaped, sharp-pointed processes, doubtless cancerous papillae, some of which are from I to ^ an inch in length. ^ The cauliflower excrescence of the uterus may be most nearly compared with the extremely exuberant epithelial cancers such as are described above. 702 WAETY CANCEES. I have here described may be derived from the different metiiods and degrees in wMcli the papillee are deformed, enlarged, and involved in tie eancerons disease. All, and more than all, the shapes of common warty and condylomatons growths may be produced. But the same general plan of construction exists in all ; namely, a certain portion of the skin or mucous membrane is infiltrated with epithelial cancer- structures : on this, as on a base more or less elevated and imbedded, the papillEe, variously changed in shape, size, and grouping, are also cancerous ; their natural structures, if we except their bloodvessels, which appear enlarged, are replaced by epithelial cancer-cells. And herein is the essential distinction between a simple or common warty or papillary growth, and a cancerous one or warty cancer. In the former the papillae retain their natural structures ; however much they may be multiplied, or changed in shape and size, they are either merely hyper- trophied, or are infiltrated with organised inflammatory products ; how- ever abundant the epidermis or epithelium may be, it only covers and ensheaths them. But in the warty cancer the papilte are themselves cancerous ; more or less of their natural shape, or of the manner of their increase, may be traced : but their natural structures are replaced by cancer-structures ; the cells, like those of epithelium, lie not only over, bnt within, them.' To describe the interior structure of the superficial cancerous growths, we may take as types the most common examples of cancers of the lower Up — those in which the papillae are indeed involved, enlarged, and cancerous, bnt not so as to form distinct or very pro- minent outgrowths. The surface of a vertical section through such a cancer commonly ' I described the papillary origin and construction of these cancers in 1838 (Medical Gazette, xsiii. 284), but was not then aware of their minute structure. Later exam- inations have made me sure that the true distinction between them and other papil- lary growths is as above stated. But it is to be observed that cancerous growths may appear papillary or warty, though no original papillse are engaged in their formation. Thus when papillary cancers are deeply ulcerated at their centres, the base of the ulcer, where all the original papillse are destroyed, may be warty, like its borders where the cancerous papillse are evident. Some of the most- warty-looking epithelial cancers are those which grow from the deep tissues of the leg after old injuries. This may be only au example of cancerous growths imitating the construction of adjacent parts, but in some instances (as in cysts, and on the mucous membrane of the gall-bladder and stomach), the warty cancers are probably examples of the dendritic mode of growth. It must also be a question at present, whether some of the most exuberant cancers of the skin are not to be ascribed to this mode of growth. It is, to say the least, ex- tremely difficult to trace their origin from once-natural papillse. EPITHELIAL CANCER OE LIPS. 703 presents, at its upper border, either a crust or scab, formed of ichor, detached sc8,les, and blood ; or else a layer of detached epidermoid scales forming a white, crumbling, pasty substance. This layer may be imperceptible, or extremely thin : but it may be a line or more in thick- ness ; and it enters all the inequalities of the surface on which it lies. Its cells or scales are not regularly tessellated or imbricated like those of the epidermis or a common wart, but are placed without order loosely connected both with one another and with the subjacent vascular structures, and may be easily washed away. Such a layer must be regarded, I presume, as formed of epithelial cancer-cells, detached or desquamated from the subjacent vascular and more perfectly organised substance of the cancer. This substance presents, in most cases, or in most parts, a greyish or greyish-white colour, and shines without being translucent. It is firm and resilient, close-textured, and usually void of any appearance of regularly lobed, granular, or fibrous construction, except such as may exist near its surface, where close- set and uniformly elongated vertical papillse may make it look striped. The greyness and firmness are, I think, the more uniform and decided the slower the growth of the cancer has been. In the acute oases, especially of secondary formations, or when the cancer has been inflamed, or ulceration is in quick progress, the out surface may be opaque white, or of some dull yellow or ochre tint, streaked and blotched with blood ; or it may, in similar cases, be soft and shreddy, or nearly brain-like ; but these appearances are very rare. The grey substance of epithelial cancers commonly yields to pressure only a small quantity of turbid yellowish or greyish fluid ; but with rare exceptions, one may squeeze or scrape from certain parts of the cut surface, as if from small cavities or canals, a peculiar opaque- white or yellowish material. It is like the comedones, or accumulated epithelial and sebaceous contents of hair-follicles ; or even more like what one may scrape from the epidermis of the palm or sole after long maceration or putrefaction. This material, which is composed of structures essentially similar to those of the firmer substance of the cancer, but differently aggregated, supplies one of the best charac- teristics of the disease. It may be thickly liquid, but more often is like a soft, half-dry, crumbling, curdy substance : pressed on a smooth surface, it does not become pulpy or creamy, but smears the surface, as if it were greasy : mixed with water, it does not at once diffuse 704 SUPERFICIAL EPITHELIAL CANCEE OF INTEGUMENTS. itself, so as to make the water tiniformly turbid, but divides into minute visible particles.' The quantity of this softer material is extremely various in different instances of epithelial cancer. According to its abundance and arrange- ment, the grey basis-substance may appear differently variegated ; and the more abundant it is, the more does the cancer lose firmness, and acquire a soft, friable, and crumbling texture. In many cases the soft substance appears, on the cut surface, like imbedded scattered dots, or small grains : these being sections of portions contained in small cavities. But, as the quantity increases, and the cavities containing it augment and coalesce, so the firmer substance becomes, as it were, cribriform ; or when the softer substance is washed away, it may appear reticulated or sponge-like, or as if it had a radiated or plaited structure. Or, lastly, the soft substance may alone compose the whole of the can- cer ; but this, I think, is vary rarely the case, except in secondary formations and in the lymphatic glands. Vertical sections of the more exuberant and the more distinctly papillary epithelial cancers present essentially the same appearance as I have just described. The upper border, corresponding with the ex- posed part of the growth, may be overlaid with thin scab, or crust, or epidermoid scales, detached and disorderly, or may be bare, like that of a section of common granulations. The cut surface is generally grey, succulent, and shining, with distinct appearances of vascularity. Por- tions of it may yield the peculiar soft crumbling substance like macerated epidermis ; but this is, I think, generally less abundant than in the less exuberant and deeper-set specimens, and is more often arranged in a radiated or plaited manner. The vertical sections of the superficial epithelial cancers of the in- teguments display many important differences, in relation to the depth to which the cancer-structures occupy the proper tissues of the skin or mucous membrane. In some, only the papillae, or the papillas and the very surface of the tissue on which they rest, appear to be involved. The enlarged papillae in such cases usually retaining their direction and their cylindrical or slenderly conical shape, appear like fine grey stripes or processes ' In these are its distinctions from the 'juice' of either schirrous or medullary cancers. But it maist be remembered that, in the rare instances in -which epithelial cancers are very soft, they may yield a creamy or turbid greyish fluid. It can hardly be necessary to give a caution against confounding the peculiar material described above with that which may be pressed from milk-ducts involved in scirrhous cancers (compare p. 615). SUPERFICIAL EPITHELIAL CANCER OF INTEGUMENTS. 705 vertically raised on the liealtliy white tissue of the integument, or on its surface rendered similarly grey by cancerous infiltration. And the outlines of the papillae are commonly the more marked because of their contrast with the opaque white substance formed by the epidermoid scales which cover them and fill up all the interstices between them. In such cases the cancerous material may be more abundant on the surface than in the substance of the papillae or corium ; and often the whole morbid substance is brittle, and may be separated from the corium which bears the papillse. But more frequently, and almost always in such cases of epithelial cancers when they are removed in operations, the cancerous structures ■ are more deeply set. They occupy the whole thickness of the integu- ment, or reach to a level deeper than it. The base or lower border of the diseased mass rests on, or is mingled with, the subcutaneous or submucous tissues, whatever these may be — fafc, muscular fibres, or any other. The lateral borders usually extend outwards for some distance on each side, beneath the healthy integument which bounds the up- raised part of the diseased growth, and which is usually raised and everted so as to overhang the adjacent surface. In nearly all these, also, while the surface and central parts of the cancer are being de- stroyed by ulceration, its base and borders are, at a greater rate, ex- tending more deeply and widely in the subcutaneous or submucous tissues. The bases of the most exuberant and most distinctly papillary can- cers are rarely, in the early periods of their growth, either deeply or widely set in the integument. They rarely, I believe, occupy more than the thickness of the portion of the skin or mucous membrane from which the growths spring : they sometimes occupy less. But, in their later growth, and especially when ulceration is progressive, the same deeper and wider extension of the base of the cancer ensues as I men- tioned in the last paragraph. All the foregoing description will have implied that the proper structures of the diseased parts are mixed up with the cancer-structures inserted among them ; the condition of parts is here exactly com- parable with that of other cancerous infiltrations. (Compare p. 610.) The boundaries of the cancer, as seen in sections, usually appear to the naked eye well defined ; yet it is often easy to see portions of the natural tissues extending into it, these being continuous with those portions among which the cancer-structures are infiltrated. This is especially evident when, as in the lip or tongue, the superficial muscular 706 EPITHELIAL CANCER: fibres are involved. Pale red bands may then he traced into or within the cancer ; and the microscope will prove, if need be, their mnscular structure. Or when these cannot be traced, yet we may find the con- nective tissue of the involved skin or mucous membrane. Concerning the changes that ensue in the tissues thus involved in the deeper parts of epithelial cancers, I believe that what was said of those in cancerous breasts (pp. 610 and 616) might be here nearly re- peated, regard being had to the original differences of the tissues in the respective cases. In general, the natural structures in these cases appear not to grow ; gradually, but not all at the same rate, they de- generate and are removed, till their place is completely occupied by the increasing cancer-structures, and an entire substitution is ac- complished. So, too, what was said of the stroma of scirrhous cancers of the breast might be repeated. These epithelial cancers have no stroma of their own ; their proper structures are sustained by the remains of the original textures of the afiected part. And, as in the scirrhous cancers, so in these ; when they grow very quickly, they occupy a comparatively small area of the original tissues, and may appear like nearly distinct tumours. In the most exuberant epitheHal cancers, and in those that are pro- minent, like warts or condylomata, there is more growth of the natural tissues ; those, not of the papillee alone, but of the basis of the skin or mucous membrane, may be traced into the outgrowth, forming a stroma for the cancer-structures, and surmounted by the cancerous papUlaa, Such a stroma may be well traced in many soot-cancer- warts : the connective tissue extends from the level of the cutis, in vertical or radiating and connected processes among which the cancer-cells lie ; and one may compare them with the osseous outgrowths that form an internal skeleton of a cancer on a bone (see p. 660). The tissues bordering on the superficial epithelial cancers appear generally healthy, but they are often increased in vascularity, and succulent. The adjacent corium also may appear thickened, with its papillffl enlarged, and an unusual quantity of moist opaque-white cuticle may cover them.' This condition is, however, not frequent, neither is it peculiar to the environs of cancer ; changes, essentially similar, are often observed around chronic simple ulcers of the integuments.* ' M. Lebert (Traite pratique, p. 618) quotes from M. FoUin, that the tissues around the disease are often 'infiltrated with epidermis in a difiuse manner.' ^ On some of the diseases of the papillie of the cutis {Medical Gazette, xxiii. p. 285). The multiform appearances of epithelial cancers which I hare described may be still more varied by the consequences of degeneration and disease. But it would DEEP-SEATED VARIETIES. 707 The deep-seated epithelial cancers remain to be described. In the progress of all the preceding -varieties of the superficial form of the disease, especially when their surfaces are ulcerating, we may trace a constant sub-integnmental extension of their bases, in both width and depth ; an extension which is more than commensurate with the destruction at the surface, and in the course of which no tissue is spared. Now, the same cancerous infiltration of the subcutaneous or submucous tissues, which is thus the common result of the extension of the disease from the surface, may also occur primarily : that is, the first formation of epithelial cancers may be in masses of circum- scribed infiltration of the tissues beneath healthy skin or mucous membrane. The same condition is more frequent in the epithelial cancers that form, as recurrences of the disease, near the seats of former operations, or, as secondary deposits, about the borders of pri- mary superficial growths. In comparison with the superficial form, the primary deep-seated epithelial cancer is a very rare disease ; yet it is frequent enough for me to have seen, within the same year, three cases, which I will describe ; for they were all well-marked examples. A chimney-sweep, thirty-two years old, died suddenly, suflTocated, in the night after his admission into St. Bartholomew's. He had had cough for six months, and aphonia and dyspncea for two months. A scrotal soot-cancer had been removed from his brother in the previous year. I found a wide-spread layer of firm substance, exactly like that of the majority of epithelial cancers, under the mucous membrane of the larynx, iuvolving the left border of the epiglottis, the left arytenoid cartilage, the intervening aryteno-epiglottidean fold, part of the right arytenoid cartilage, and the upper and posterior third of the left ala of the thyroid cartilage. In all this extent, the diseased substance lay be- neath the mucous membrane, which, though very thinly stretched over some parts of it, appeared healthy, was covered with ciliated epithelium wherever I examined it, and could everywhere be separated in a distinct layer.' All the submucous tissues were involved ; the cartilages, as it were buried in the growth, appeared less changed than the softer parts. be too tedious to describe them minutely, -while, as I believe, they are essentially similar to the consequences of the same affections in the scirrhous and medullary can- cers, of -which I have already given some account. ' The specimen, and those referred to in the two folio-wing cases, are in the Museum of St. Bartholomew's. ?; z 2 708 DEEP-SEATED FOEMS OF EPITHELIAL CANCER. The surface of the growth, as covered with the mucous membrane, was lowly lobed, or tuberculated, raised from one to two lines above the natural level ; its border was in many parts sinuous. The cancerous substance was firm, elastic, compact, greyish and white, shining, variously marked on its section with opaque- white lines. It appeared wholly composed of the usual minute structures of epithelial cancers, including abundant laminated epithelial cap- sules. All the epithelial structures were of the scale-Uke form, though collected in the tissues under a membrane covered with ciliated epithelium. A man was admitted into the Hospital, in a dying state, with a large firm swelling between the lower jaw and the hyoid bone, the increase of which had produced great difiB.culty of breathing and swallowing. After his death, the greater part of the swelling was found to be due to cancer of the deep tissues of the tongue, and of the fauces and lymphatic glands. A section of the parts (as in Fig. 116) showed that the muscular and other structures of the posterior two-thirds of the tongue were completely occupied by a firm cancerous infil- tration : but the raucous membrane of the tongue was entire ; its various papillary struc- tures were healthy and distinct ; it was only tight-stretched and adherent on the surface of the cancer. From the-base of the tongue the cancer extended backwards and downwards on both sides of the fauces, and as far as the vocal cords, preserving in its whole extent the characters of a massive in- filtration of aU the submucous tissues. It was covered with healthy- lookiug mucous membrane in every part, except just above the right vocal cord, where it protnded slightly through a circular ulcer less than half-au-inch in diameter. The substance of the disease presented, to the assisted as well as to the unaided sight, and touch, the weU-marked characters of epithelial cancers. The lymphatic glands were similarly diseased. A gentleman, sixty-four years old, had, on the upper part and right side of his nose, a flat, lowly lobsd or tuberculated growth, an iuch in Fig. 116. DEEP-SEATED FOEMS OF EPIIHELIAL CAKCEB. 709 diametorg, radnally rising above the level of the adjacent skin to a height of one and a half or two lines. It was covered with skin, which was very thin and adherent, and florid with small dilated bloodvessels, like those in the skin of his cheek. The base of the growth rested on the bones ; it feli like an infiltration of all the thickness of the deeper part of the skin and subcutaneous tissues, and moved as one broad and thick layer of morbid substance inserted in the skin. In its middle and most prominent part was a fissure nearly a line in depth, with black, dry borders, from which a very slight discharge issued. It was very painful, and, beginning from no evident cause, had been ten weeks in regular progress. I removed this disease, and found in its centre a small, roundish mass of soft, dark, gmmous substance, like the contents of a sebaceous cyst.' Around the cavity in which this was contained, all the rest of the disease appeared as am outspread infiltration of firm yellowish and white cancerous substance in the tissues under the [stretched and ad- herent but entire skin. It extended as deep as the periosteum of the nasal bones. Soft, crumbling, and grumous substance could be scraped from it ; and it yielded well-marked elements of epithelial cancer, with numerous laminated capsules. During the healing of the operation- wound, a similar small growth appeared in the adjacent tissues. It was destroyed with caustic by Mr. Hester, and the patient remained well for at least ten years after the operation. Besides cases such as these, which may suffice for a general de- scription of the disease, many might be cited of what may be regarded as an intermediate form, in which both the skin or mucous membrane and the subjacent tissues are simultaneously affected, but the latter to a much larger extent than the former. Such cases are far from rare in the lower lip and tongue. They are characterised by the existence of a roundish, frm, or hard and elastic lump, deep set in the part, and well defined to the touch, with its surface little, if at all, raised, and having at some part of its surface either a portion of cancerous integu- ment, or a small ulcer or fissure. Now these cases of deep-seated epithelial cancers have much inte- rest, as well in practice as in their bearing on the pathology of the disease. They are instances of the disease of which it is impossible to speak as of mere augmentations of the natural structures ; there is in ' Mr. Hester and Mr. Eye, who saw this ease some weeks before I did, told me that it presented, at first, all the characters of a common setaceous cyst ; and I think it quite prohahle that it was an example of epithelial cancer formed in and around such a cyst. 710 ULCEEATIOK OF EPITHELIAL CANCEE. them no trace at all of the assumed homology of epithelial growths ; there is in them no progressive formation of epithelial cells gradually penetrating from the surface into the substance of the cutis ; their pro- gress, or a part of it, is from the deeper parts towards the surface. The epithelial cancers in or near the integuments are so prone to ulceration, that the occasions of seeing them as mere growths are com- paratively rare. The state in which they are usually shown to us is that of progressive ulceration of the central and superficial parts, with more than equal growth of the bordering and deeper parts. In this state, indeed, they present the type of that which is commonly de- scribed as the cancerous ulcer, a type which is observed also in some examples of the scirrhous cancer (p. 638), and more rarely in the me- dullary. In the superficial first- described form of the disease, the ulceration, usually begins either as a difiused excoriation of the surface of the can- cer, the borders of which are alone left entire, or else as a shallow ulcer extending from some fissure or loss of substance at which the disease commenced. The discharge from the excoriated or ulcerated surface usually concretes into a scab, or a thicker dark crust, beneath which, as well as beyond its edges, ulceration gradually extends in width and depth. A nearly similar method is observed, I believe, in the earliest ulcer- ation of the papillary and other more exuberant epithelial cancers. The central parts ulcerate first, and the ulcer, from this beginning, deepens and widens, destroying more and more of the cancer-structures ; but its rate of destruction is never so quick as that of the increase of the borders and base of the cancer. In the deep-seated epithelial cancers, other methods are observed in the first ulceration. Sometimes the skin or mucous membrane over them, becoming adherent and very thin, cracks, as it may when adhe- rent over a scirrhous cancer (p. 637). Such a crack may remain long with little or no increase, dry and dark, and scarcely discharging ; but it is usually the beginning of ulceration, which extends into the mass of the cancer. In other cases, with inflammation of the cancer, its cen- tral parts may soften and perhaps suppurate ; and then its liquid con- tents being discharged (sometimes with sloughs), through an ulce- rated opening, or a long fissure, a central cavity remaios, from the un- even walls of which ulceration may extend in every direction. And, again, in other cases, especially, I think, in secondary formations, and in those under the scars of old injuries, the cancer protrudes, through ULCEEATION OF EPITHELIAL CANCEE. 711 a sharply-bounded ulcer, in the soxmd integument or scar, and grows ex- uberantly, with a soft, shreddy surface, like a medullary cancer, or with a firmer, warty, or fungous mass of granulations. But though the beginnings of the ulcers be thus, in different instances, various, yet in their progress they tend to uniformity. The complete ulcer is excavated more or less deeply, and is usually of round, or oval, or elongated shape. Its base and borders are hard, or very firm, because, as one may see in a section through it, they are formed by cancerous substance infiltrated in the tissues bounding it. The thickness of this infiltration is commonly in direct proportion to the extent of the ulcer, from a line to half-an-inch or more : we may feel it as a distinct and well-defined indurated boundary of the whole ulcer, hindering its movement on the deeper tissues. The surface of the base of the ulcer is usually concave, unequal, coarsely granulated, nodular, or warty : it is fiorid, or, often, of a dull vermilion, or rusty red colour j it bleeds readily, but not profusely ; and yields a thin ichorous fluid, which is apt to form scabs, and has a peculiarly strong, offensive odour, something like that of the most offensive cutaneous exhalations. The borders of the ulcer, or some parts of them, are generally elevated, sinuous, tuberous, or nodulated ; frequently, they are everted and, to a less extent, undermined. They derive these characters, chiefly, from the cancerous formations beneath the skin or mucous membrane that surrounds the ulcer. These formations may be in a nearly regular layer, making the border of the ulcer like a smoothly rounded embank- ment ; but oftener, though continuous all round the ulcer, they are un- equal or nodular, and then corresponding nodules or bosses, from a line to nearly an inch high, may be raised up round the ulcer, or some part of it. Moreover, these upraised borders may so project as to overhang both the base of the ulcer and the adjacent healthy surface of the skin or mucous membrane ; they thus appear, at once, undermined and everted. When they are everted, healthy skin is usually reflected under them, and continued beneath them to their extreme boundary. When the papillary character of the primary growth was well marked, the borders of the ulcer often present, instead of the characters just described, a corresponding papillary or warty structure : for in these cases, the cancer continues apt to afi'ect especially the papillaa, and widening areas of them become its seat as it extends. And, even at the base of the very deep ulcers, the cancerous granulations, though rising from the tissues far deeper than papillae, may have a similarly warty construction. 712 MICROSCOPIC STRUCTURE Of EPITHELIAL CANCER, The characters of the nicer here described are generally retained, however deep, and into whatever tissues, the cancer may extend. For the proper tissues of the successively invaded parts, at first infiltrated with cancer-structures, seem to be quickly disparted and then removed : even the bones rarely produce any out-growths corresponding with those that are found in medullary cancers ; they become soft, are broken up, and at length utterly destroyed. Epithelial cancers thus extending produce the changes described, as characteristic of malignant ulceration, in p. 382 ; and by similar extension (especially in the affections of the lymphatic glands), they lay open great bloodvessels more often than any other ulcers do. I have seen three cases in which the femoral ar- tery was thus opened by ulceration extending from the epithelial can- cerous inguinal glands. The minute component structures of the epithelial cancers are alike among all the varieties of construction and external shape that I have now described ; and, if we omit the proper textures of the part affected, they may be thus enumerated : (a.) epithelial cancer-cells ; (&.) nuclei, either free, or imbedded in blastema or protoplasm ; (c.) endogenous or brood-cells ; (d.) laminated epitheUal capsules, or epithelial globes. Prom each of these, by degeneration or other change, several apparently different forms may be derived. The proportions, also, in which they are combined are various in different specimens ; but I believe that diversities of appearances to the naked eye, are not so connected with these proportions, as with the methods of arrangement, the degrees of degeneration of the component structures and the mingling of the pro- ducts of inflammation in the cancer. (a.) The most frequent cells (Fig. 117, a), and those which may be regarded as types, are nucleated, flattened, thin and scale-like. They are, generally, round or round-oval ; but they seldom have a regular shape ; their outline is, usually, at some part, linear, or angular, or ex- tended in a process. Their average chief diameter is about y-J-^y of an inch ; but they range from ^^ to , ^^j^, or perhaps beyond these limits. In the clear, or very palely nebulous, cell-contents, a few minute granules usually appear, either uniformly scattered, or clustered, as in an areola, round the nucleus. The nucleus is usually single, central, and very small in comparison with the cell, rarely measuring more than -3-5^7 o^ ^^ ™ch in its longest diameter : it is round or oval, well defined, and subject to no such varieties of shape and size as the cell. It is usually clear and bright, MICROSCOPIC STRUCTUEE OF EPITHELIAL CANCEE. 713 and is often snrronnded by a narrow clear area ; it may contain two or more minute granules, but rarely has a bright distinct nucleolus. But many of the cells may deviate widely from these characters : the most various and (if the term may be used) fantastic shapes may be found mingled together. The younger cells are generally smaller, A B C Kg. 117. rounder, more regular, less flattened to the scale-like form, clearer, and with comparatively large nuclei. The older (as I suppose) appear drier and more filmy ; they are often void of nuclei, and like bits of membrane in the shape of epithelial scales (b) : they are flimsy, too, so that they are very often wrinkled or folded and rolled up, so as to look fibrous (c), and not unlike the elongated epithelium-scales so often seen on the dorsum of the tongue. Independently of difierences of age, some cells are prolonged in one, two, or more slender or branching pro- cesses ; some are very elongated (as d) ; some are void of nuclei ; some, within their pale borders, present one or two dimly-marked concentric rings, as if they had laminated walls. To these varieties may be added such as depend on the progressive degeneration of the cells. The most frequent (besides the withering which, I suppose, is shown in the shrivelled flimsy scales without nuclei Fig. 118. iust mentioned) is the change like fatty degeneration in other cancer- structures. One of the most frequent effects of such degeneration is that the place of the nucleus is occupied by a circular or oval group of Fig. 117. Various epithelial cancer-celle or scales. Magnified 360 times: referred to in the text. Fig. 118. Cells and free nuclei of epithelial cancer, in states of fatty degeneration. Magnified 350 times. 714 MICEOSCOPIC STEDCTUEE OF EPITHELIAL CANCER. minute oily-looking molecules, some bright with black borders, some dark (Fig. 118). Others, like these, or larger, are generally scattered through the cell. With the progress of the degeneration, all trace of the nucleus is lost; the molecules increase in number and in size, till the whole cell or scale appears filled with them, or is transformed into an irregular mass of oily-looking particles, differing in shape alone fi-om the common granule-masses of fatty degenerations. (6.) Nuclei, either free or imbedded in a dimly molecular or granu- lar protoplasm, are commonly found mingled with the cells. I believe they occur in the greatest abundance in the most acute cases. They may be just like the nuclei of the cells ; but, usually, among those that are free, many are larger than those in the cells ; and these, reach- ing a diameter of more than ^^^(, of an inch, at the same time that they appear more vesicular and have larger and brighter nucleoli, ap- proximate very closely to the characters of the nuclei of scirrhous and medullary cancer-cells. Indeed, I have seen many nuclei in soot-can- cers, which, if they had been alone, I could not have distinguished from such as are described at page 614 : yet all the other structures of these specimens were those usual in epithelial cancers, and between the different characters of nuclei there were all possible gradations. The free nuclei, like the cells, may be found in all stages of degeneration (Fig. 118). (c.) Those which are named brood-oells, or endogenous cells, pre- sent many varieties of appearance, which may be regarded as the results of one or more nuclei, enclosed within cells, assuming, or tending to assume, the characters of nucleated cells (Fig. 119).' In some cells a nucleus appears very large, clear, pellucid, spherical : it loses, at the same time, its sharply-defined outline, its boundary becomes shadowed, and it looks like a hole or vacant space in the cell (a). Thus enlarging, the nucleus may nearly fill the ceU, and appear as a pellucid vesicle. I think, however, that such nuclei rarely grow to be cysts ; for cysts con- taining serous"or other fluids are very rarely found in epithelial cancers. Neither have I seen instances of free nuclei changed, as those in the cells are.^ ' We owe the atility to interpret these appearances, which illustrate many things interesting in the general physiology of cells, almost entirely to Yirchow (in his Archiv, iii. 197) and Eokitansky, loc. cit. The vesicular spaces which sometimes form not only in cancer-cells, as described in the text, hut in the cells of other parts, as in the thymus, Virchow has since described by the name of physalides (brood-cavities), whilst to the cells in which these spaces arise, he has given the name of physaliphores. ' Virchow, however {Wiir^hurcf Vtrhandl. i. 100), mentions having found in a, MICROSCOPIC STRUCTURE OF EPITHELIAL CANCER. 715 The enlarged nucleus may remain completely pellucid or barren ; but often granular matter appears to fill it ; and, as often, one or two corpuscles form in it, wbicli now appear as its nuclei, and make it as- sume tbe cbaracter of a cell, endogenous witbin tbe first or parent-cell (b). The sketches show many of the appearances that may be hence derived ; and others may be thus explained. When a cell contains two nuclei, one only of these may enlarge or become inflated (if I may use such a term for that which fills with liquid, not with air) ; the other may be then pressed against the wall of the cell. Or both nuclei may alike proceed to the gi-ade of cells, and two cells, flattened at their place of mutual compression, appear within the parent-cell (c) : or a second- Fig. 119. ary nucleus, i.e. one formed within an enlarged nucleus, may enlarge like its predecessor, and become like a pellucid cavity, or may become a secondary cell, and contain its tertiary nucleus ; hence, possibly, the concentric appearance above mentioned may be referred to the series of successively enclosed cell- walls (d). And changes such as these may equally occur with more than two nuclei : a cell of any grade, primary, secondary, or later, may be filled with a numerous ' brood ' of nuclei, in which all the above-described changes (but not the same in aU) may be repeated. (d.) The laminated capsules, as I have called them ( ' globes epider- miques ' of Lebert), are the most singular structures of the epithelial cancers (Fig. 120). They are not, indeed, peculiar to this disease ; for I have found exactly corresponding structures in the contents of an epidermal and sebaceous cyst ; and Virchow says these are common in all accumulations of epidermis.' But, I believe, they are not so frequent or so well marked in any other morbid growths as they are in nearly every epithelial cancer. Their great size at once attracts the eye ; they are visible even to Kg. 119. Epithelial caneer-cells, with endogenous development of nuclei, as de- scribed in the text. Magnified 350 times. cauliflower excrescence of the uterits, alveoli which, after the plan of proliferous cysts, contained secondary papillary growths. ' AroMv. iii. 200. 716 MICEOSCOPIC STEUCTUEE OF EPITHELIAL CANCER. the unaided sigU, especially when the softer curdy material of the cancer, in which they are generally most abundant, is pressed out on glass. They appear, at first sight, like spherical or oval cysts, from tW ^ siiy oi an inch in diameter, walled in by irregular fibrous tissue, and containing granular matter, nuclei, or cells, obscurely seen within them (Fig. 120, c). They may be clustered together in a mass or a A D Fig. 120. long cylinder (d) ; but, by breaking them up, or looking more closely, it becomes evident tha,t the appearance of fibrous tissue is due to one's seeing the edges of epithelial scales, which, in successive layers, are wrapped round the central space. Such scales may be broken off, in groups of two, three, or more, retaining the curved form in which they have lain (Fig. 120, a). When detached, they generally appear like the driest and most filmy of the epithelial scales composing the rest of the cancer (b) ; often they are folded, and look fibrous even when separated ; their nuclei are shrivelled, or not visible ; their contents are often, granular. As they lie superposed, they appear closely compacted ; but not unfrequently granules are distinct iu the outer laminar spaces, or on the inner surface of detached pieces. The contents filling the central spaces in these laminated capsules are extremely various ; sometimes granular and oily particles diffused in some nebulous material ; more often, along with these, cells or nuclei (c, d). Sometimes one cell is thus enclosed, sometimes two or more, and these not scale-like, but oval or round and plump, having distinct and generally large nuclei : or a crowd of nuclei may be enclosed : and briefly, these nuclei may appear in any of those various states which I described just now in the account of the endogenous epithe- Fig. 120. Laminated epithelial capsules, described in the text. Magnified about 250 times. MICROSCOPIC STRUCTURE OF EPITHELIAL CANCER. 717 Fig. 121. lial cells. Indeed it is probable that tbe last sentence of that descrip - tion (p. 716) might begin the history of the development of these capsules; for I know no method of ex- plaining them, except that taught by Rokitansky, and illustrated by the dia- grams copied here (Fig. 121).' In one of the simplest cases, we may suppose a nucleus largely inflated and filled with a brood of (say four) second- ary nuclei, which proceed to the formation of secondary cells (Fig. 121, a). If, now, only one of the nuclei of these secondary cells becomes enlarged, it will not only extend its own cell's wall into contact with that of- the cell containing it, but will at the same time press the three other cells into similar contact, and thus appear invested with laminated epithelial scales. Such a state, with the nuclei of the investing scales, is shown in B. A greater complexity of similar events is shown in C, in which, among a very large number of second- ary endogenous nuclei, many are persistent as nuclei, while others, developed to nucleated cells, are laminated around them. But, among the nuclei, two are represented as enlarged and containing tertiary ' broods ' of nuclei, among which the same changes have ensued as in the preceding generation. And it is evident that if any in the group A had now singly enlarged, the rest, with all the cells and nuclei around them, must have arranged themselves or been compressed into imbricar- ted scales, so as to form a large laminated capsule. The component structures now described appear to be disorderly placed in the mass of epithelial cancer, in the interstices of the natural structures, or of their remains, and even apparently within muscular fibres.^ The laminated capsules are, I believe, most abundant in the softer substance, but they are not confined to it. The texture of the mass is such as makes it very difiicult to obtain a sufficiently thin sec- Fig. 121. Diagrams of the production of the laminated epithelial capsules, from Eokitansky. ' From his. essay, Ueber die Cyste ; Fig. ii. C. 0. Woher in Virchow's Arohiv, vol. xv. 1859. 718 MICEOSCOPIC STEUCTUEE OF EPITHELIAL CANCEE. tion with tlie structures undisturbed ; but ia sections of scrotal cancers I liave seen tbe laminated capsules imbedded at distant intervals among the simpler epithelial structures, and the turgid large capillaries as- cending towards the surface and forming near it simple or undulating loops. The epithelial structures appear to be in contact with the walls of the bloodvessels, supported by a wide and scanty mesh-work of connective tissue growing up from the adjacent tissue of the scrotum. In whatever part or organ they may be found, there is a remarkable uniformity in the characters of the epithelial cancer- structures. Devi- ations, however, from such as I have described as the normal struc- tures are sometimes met with. I have once seen a melanotic epithehal cancer : it grew in the deeper part of the cutis and in the subcutaneous tissue, under a dark pigmentary nsevus or mole, in a woman who had many similar moles on various parts of her body : a thin layer of the cutis with its covering of dark epidermis, extended over the cancer, and was slightly raised by it. The epithelial shape and texture of the cancer-cells were well marked, but most of them contained melanotic matter ; in some, a quantity of brownish molecular matter was either diffused or collected about the nucleus or its place ; in some, with similar mole- cular matter, there were two, three, or more brown corpuscles, from the size of mere molecules to that of blood-cells. Materials like those within the epithelial cells existed, also, more abundantly as an intercel- lular substance. Cells Kke cylindriform epithelium cells may also be mingled with the more usual form. I have seen this in a case of large ' cauliflower- excrescence ' of the uterus, in the very substance of which the cylindri- form cells were found. I have found them also in cancer of the lowest part of the rectum. Bidder describes a similar occurrence in a cancer of the stomach ' and duodenum : and Rokitansky,^ in the same parts. Other cases have also been described by Mr. Hutchinson,^ Forster,'' Billroth,' and Liicke.^ Indeed, the imitation of the cylindriform epith- elium in some of the cancers affecting parts in which it is normal, is sufficiently frequent to justify the giving them the name of cylindriform epithelial cancers. Hannover to the same form gives the name Epithe- lioma cylindricum. I believe, also, that cases may be foumd in which the cancer-ceUs, or part of them, have characters intermediate, or transitional, between > Miiller's ArcUv, 1852, p. 178. ' Tleher den Zottetijerebs, pp. II, 18. ' Path. Trans, -riii. p. 524. » Atlas, pi. 28, fig. ."5. " HanMuch, p. 721. s In BiUrotk u. Von Pitha's Handbuch, ii. part i. p. 213, MICEOSCOPIC STRUCTURE OF EPITHELIAL CANCER. 719 those of the epithelial and of the scirrhous or medullary diseases. I have mentioned the existence of the large free nnolei (p. 714), and the full plump cells in the capsules (p. 71S) in epithelial cancers ; and I believe that I have seen cancers with all their cells of intermediate shape. But the point is very difficult to determine. Toung epithelial cells are less flattened and scale-like, and have larger and clearer nuclei, than those of completed formation : in these characters they approach to the appearance of the other cancer-cells ; and if in a quickly-growing mass, they occur alone, tliey may produce a fallacious appearance of an intermediate form of cancer. Moreover, two forms of cancer may be mingled in one mass. Lebert and Hannover have satis- fied themselves of this : and such a specimen as they describe may have deceived me. As yet, therefore, I can have only a belief in the exis- tence of such intermediate forms. The foregoing description has been drawn, almost exclusively, from cases of epithelial cancer in integumental parts, and the varieties which it may present in different localities are so slight and inconstant, that such references as I have already made to them may suffice. But cer- tain examples of the disease, in other than integumental parts, need sep- arate description. The Lymphatic Glujds, in anatomical relation with the primary seat of an epithelial cancer, usually become similarly cancerons in the progress of the disease ; and, I think, sooner or later in that progress, in direct proportion to its own rapidity, following in this the same rate as in other cancers. Prom the glands nearest to the primary seat, the disease gradually extends towards the trunk, yet seldom reaches far. I have known the whole line of cervical glands affected in epithelial cancer of the tongue ; and the lumbar glands may become diseased with the penis or scrotum ; but, much more often, the proximate cluster of glands alone becomes cancerous, and those more distant are swollen and succulent, but contain no cancerous matter. In some cases the diseased glands appear in a large cluster, forming one lobed mass ; in others, a chain of small glands is felt, snch as one might not suppose to be cancerous, except for their hardness. The can- cerous elements in the glands resemble those in the primary disease ; indeed I have found even slight modifications of general character in the one, exactly repeated in the other.' They are inserted among the ' In one case of epithelial cancer of the tongue, and in another of the larynx, I found the lymphatic glands affected with what, according to both general and micro- 720 EPITHELIAL CANCEE IN LYMPHATIC GLANDS. natural structures of the gland. At. first, I think, they usually appear iu circumscribed masses,^ occupying only a certain part of the gland . but these, gradually increasing, at length exclude, or lead to the re- moval of, the whole of the original tissues. The diseased glands are enlarged, hardened, smooth-surfaced, and usually retain their natural connection with the surrounding tissues. On section, part or the whole of the gland presents the same appear- ance as a section of primary epithelial cancer ; and, generally, the opaque white crumbling substance, like scrapings from macerated epi- dermis, is abundant. One can remove masses of it, and leave only the capsule of the gland, or some remains of gland- substance that bounded the spaces that it filled. Glands thus diseased are not unfrequently the seats of acute inflam- mation, in which, with fatty degeneration of the cancer-cells, suppura- tion may ensue : they may discharge the pus, as from a common bubo, and may continue many days thus suppurating. But the end of this is, that large and deep cancerous ulcers, such as are already described, form Ln them and the adjacent tissues, and the progress of these is often more serious than that of the primary disease. I have seen two examples of primary epithelial cancer in lymphatic glands. One I will relate, both for its own interest, and because it illustrated many of the foregoing statements. The man, who was a patient in St. Bartholomew's Hospital, was a sweep, forty-eight years old : his skin was dusky and dry, and many hair-folholes were enlarged by their accumulated contents ; but he had no appearance of cancer, or wart of any kind, on the scrotum or penis ; yet his inguinal glands were diseased, just as they commonly are iu the later stages of scrotal soot-cancer. On the right side, over the saphenous opening a cluster of glands formed a round tuberous mass, more than an inch in diameter. It felt very firm, heavy, Hi-defined, and as if deep-set. Over its most prominent part the skin was adherent, and ulcerated, and a soft dark growth protruded through it. Above this mass were three glands en- larged, but not hardened. On the left side, below the crural arch, one gland was enlarged to a diameter of half-an-inch, and hard ; and four scopio cliaracteTS, could only be regarded as firm medullary cancer. It is possible that in these eases, the primary disease was of mixed kinds — medullary and epithelial — just as there are examples of mixed cartilaginous and medullary tumours, in which only the medullary disease is repeated in the lymphatic glands (see p. 523). But I found no evidence of this mixture of diseases in the primary growth ; and I think it equally possible that the cases may be compared with tlie rare instances of secondary medullary, associated with primary scirrhous cancer. EPITHELIAL CANCEE IN THE LUNGS. 721 others felt similarly but less diseased. All ibese -were movable under the skin. This disease had been observed in progress for fifteen weeks, having begun in the right groin as a hard lump under the skin, like those ■which vs^ere now in the left groin, and which had commenced to enlarge somewhat later. The ulceration in the right groin had existed for a week. I removed all the glands that seemed diseased. The chief mass from the right side appeared, on section, lobed, soft, greyish, mottled with pink and livid tints. The same changes, but with increased firmness, were seen in the largest gland from the left side ; and the material pressed from both these (a turbid, grumous, and not creamy, substance) contained abundant epithelial cancer-cells. The other glands were not evidently cancerous ; but, during the healing of the operation on the right side, a gland, which I had thought it unneces- sary to remove, enlarged and became hard : it was destroyed with chloride of zinc, and then the wounds healed soundly. The patient re- mained well for at least six years. The Epithelial Cancer of the Lungs, which I referred to (p. 796) as having once seen, occurred in an old man whose penis was amputa- ted eighteen months before death. The disease soon returned in the inguinal glands, and I received these and the lungs for examination. The other organs were reported healthy. A cluster of three or four glands was compressed in a large mass, of which a part protruded through an ulcerated opening in the skin. On section, nearly the whole of the gland-substance appeared replaced by the peculiar and oft-mentioned whitish, half-dry, friable, substance, with greyish mottlings and streaked with bloodvessels. In this substance all the structures of epithelial cancer, with abundant laminated capsules, were perfectly distinct : they might have been taken as types. In the lungs there were about twenty masses of similar cancerous substance ; and of one large mass, at the root of the right lung, I could not be sure whether it were in the lung itself or in a cluster of bronchial glands. They were nearly all spherical, or flattened under and in the pleura, and measured from ^ of an inch to nearly 3 inches in diameter. Their substance was opaque- white, marbled with pale yellow and pink, intersected by lines of grey and black (belonging apparently to the in- volved interlobular tissue of the lungs), and marked with bloodvessels. They were compact, but brittle and crumbling under pressure ; several of the largest were softer and more friable at their centres than else- where and the largest three had great central cavities, filled with soft- 3 A 722 EPITHELIAL CANCER IN HEAUT : AND UTEEUS. ened cancerous matter and pus : they miglit liave been called ' cancerous vomicae ; ' but tbey were completely bounded by layers of cancer, rough, and knotted on their inner surfaces, and had no communication with air-tubes. From one mass an outgrowth projected into, and had grown within, a bronchial tube : from another a similar growth exten- ded into a pulmonary artery. The crumbling, brittle texture of these masses, and the absence of creamy ' juice ' in even the softest parts, might have sufficed, I believe, to declare that these were not masses of scirrhous or medullary cancer : but the microscopic examination left no doubt. Their minute structures accorded exactly with those in the inguinal glands : not a character of the epithelial cancers was wanting.' Epithelial Cancer in the Heaet is illustrated in the Museum of St. Bartholomew's.^ A man, fifty-eight years old, had a granulated and warty epithelial cancer, which covered the anterior and inferior third of his eye, and was firmly combined with the conjunctiva and parts of the sclerotica and cornea. Mr. Wormald removed the eyeball with all the disease. Two years afterwards the man died with a large tumour over the parotid gland ; and a mass of cancer, about an inch and a half in diameter, was imbedded in the substance of the apex of the right ventricle and septum of the heart. The mass is soft and broken at its centre, and has the microscopic structures of epithelial cancer. In the Uteeus, and the adjacent part of the Vagina, the epithelial can- cer may be found with ordinary characters, such as were described at the beginning of the lecture ; but its more remarkable appearance is in the form of the ' Cauliflower-Excrescence.' Only a part, however, of the cases to which this name has been ascribed have been epithelial can- cers : of the rest some were medullary cancers, and some, perhaps, simple non-cancerous, warty, or papillary growths (see p. 589). My own observations of this disease have only sufficed to confirm (wherever I could test them) those far more completely made by Vir- chow,' whose results, approved by Lebert, and consistent with the best ' Portions of the lungs, Series xiv. No. 61, and of the inguinal glands, Series xxi. No. 6, in this and in the last-described ca.'ie, are in the Museum of St. Bartholomew's. • Series xii. 60. In the Catalogue the disease is described as medullary cancer, but I have since examined microscopically both it and the primary growth (Series ix. No. 17) ; and they are certainly epithelial cancers. ' Wureburg. Virhandl. 1850, i. 109. They were chiefly made in the cases de- scribed by Mayer in the Virhandl. der Gesellsih. fur Gehurtshulfe in Berlin, 1851, p. 111. EPITHELIAL CANCER IN UTEEUS AND VAGINA. 723 earlier records, I shall therefore qnote : — ' Oue must distinguish three different papillary tumours at the os uteri — the simple, such as Fre- richs' and Lebert^ have seen ; the cancroid ; and the cancerous ' [i.e. the epithelial-cancerous and the medullary-cancerous] : — the first two forms together constitute the cauliflower-growth. This begins as a simple papillary tumour, and at a later period passes into cancroid [epithelial cancer]. At first one sees only on the surface papillary or villous gro-wths, which consist of very thick layers of peripheral flat, the deeper cylindrical, epithelial cells, and a very fine interior cylin- der formed of an extremely little connective tissue with large vessels. The outer layer contains cells of all sizes and stages of development ; some of them forming great parent-structures with endogenous cor- puscles. The vessels are, for the most part, colossal, very thin-walled capillaries, which form either simple loops at the apices of the villi, between the epithelial layers, or towards the surface develop new loops in constantly increasing number, or, lastly, present a reticulate branching. At the beginning of the disease the villi are simple and close pressed, so that the surface appears only granulated, as Clarke describes it ; it be- comes cauliflower- like by the branching of the papillEe, which at last grow out to fringes an inch long, and may present almost the appearance of an hydatid mole. ' After the process has existed for some time on the surface, the cancroid alveoli begin to form deep between the layers of the muscular and the connective tissues of the organ. In the early cases I saw only cavities simply filled with epithelial structures ; but in Kiwisch's case there were alveoli, on whose walls new, papillary, branching growths were seated — a kind of proliferous arborescent formation.' It will be evident, from this description, that the cauliflower-excre- scence, in the two conditions distinguished by Virchow, illustrates the usual histoi'y of the most exuberant epithelial cancers (p. 700) : it might be taken as the principal example of the group. That which he calls the ' simple papillary tumour ' is an excessive papillary outgrowth of epithelial cancer ; the later stage of the same, when it ' passes into cancroid,' is the usual extension of such a cancer into deeper parts, — a continuous growth of the same thing in a new direction. For the papillary structures, composed, as Virchow says, of epithelial cells with bloodvessels and a very little connective tissue, are the essential characters of the epithelial cancerous outgrowths ; and I believe that the same composition has never been seen iu any papillary or warty ' Jenaische Annalen, p. 7. ^ Abhandlunffen, pp. 37, 160. 3 A 2 724 CAULIFLO-WEE EXCEESCENCE. growths, tliat did not, if time were allowed, proceed to the formation of epithelial structures in the deeper parts, and thence through the usual progress of malignant disease. Before entering on the pathology of epithelial cancers, it will be useful to refer briefly to the morbid anatomy of the diseases with which they have most affinity, and from which it is most necessary to dis- tinguish them, — at least, as clearly as we can. These are, on the one side, the scirrhous and medullary cancers ; and, on the other, certain rodent ulcers and warty growths of scars.' The descriptions in former lectures of the scirrhous and medullary cancers of the skin and subcutaneous tissue may suffice for the distinc- tion from them (compare pp. 619, 622, 674). The Bodent Ulcer is the disease which has been described under various names : such as cancerous ulcer of the face, cancroid ulcer, ulcere rongeant, ulcere chancreux du visage, der flache Krebs, moos- artige Parasit, ulcus exedens, noli me tangere. In its earliest appear- ance, on its most frequent seat, it has been called cancerous tubercle of the face. It has been confounded by many with different forms of cancer ; yet it is distinct from them in structure as well as in history, and had better be described by some name which may not add to the yearly increasing confusion that arises from the use of terms expressing likeness to cancer. Sir B. C. Brodie thus describes the most frequent characters of the disease :' — ' A man has a soft tubercle upon the face covered by a smooth skin. He may call it a wart, but it is quite a different thing. On cutting into it you find it consists of a brown solid substance, not very highly organised. A tumour of this kind may remain on the face unaltered for years, and then, when the patient gets old, it may begin to ulcerate. The ulcer spreads slowly but constantly, and, if it be left alone, it may destroy the whole of the cheek, the bones of the face, and ultimately the patient's life ; but it may take some years to run this course. So far these tumours in the face, and these ulcers, are to be considered as malignant. Nevertheless, they are not like ' The whole of the subject is admirably illustrated by Mr. Caesai Hawkins, in papers in the Medico-Chir. Trans, xix. aid xxi., and in the Medical GazMe, xxviii. xxix. Indeed, I can add nothing to his account, except such conclusions as are de- rived from microscopic examinations of the diseases. One of Mr. Hawldns' lectures relates to chcloid growths ; but to these it seems unnecessary to refer ; if they could be confounded with any form of cancer, it would be with scirrhous cancer of the skin. ^ In his Lectures on Pathology and Surgery, p. 333. EODENT ULCER, 725 fungus hsamatodes or cancer ; and for this reason, that the disease is entirely local. It does not aifeot the lymphatic glands, nor do similar tumours appear in other parts of the body.' The constantly progressive ulceration is a character in which this disease resembles cancer, especially epithelial cancer. The likeness in this respect may indicate some important affinity between them, but the differences between them are greater ; for not only is the rodent idcer usually nnUke that of any cancer in its aspect, rate, and mode of progress, but the tissues bounding it, and forming its base and walls, never contain any epithelial or other cancerous structure ; they are infiltrated with only such structures as may be found in the walls of common chronic ulcers. The most usual characters of the rodent ulcer, whether on the cheek, the eyelids, upper lip, nose, scalp, vulva, or any other part, are as follows :' — It is of irregular shape, but generally tends towards oval or circular. The base, however deeply and unequally excavated, is usually, in most parts, not warty or nodular, or even plainly granulated ; in contrast with cancerous ulcers, one may especially observe this absence, or less amount, of up-growth. It is, also, comparatively dry and glossy, yielding, for its extent, very little ichor or other discharge, and has commonly a dull reddish-yellow tint. Its border is slightly, if at aU, elevated ; if elevated, it is not commonly or much either everted or undermined, but is smoothly rounded or lowly tuberculated. The immediately adjacent skin usually appears quite healthy. The base and border alike feel tough and hard, as if bounded by a layer of indurated tissue about a line in thickness. This layer does not much increase in thickness as the ulcer extends ; and herein is another chief contrast with cancerous ulceration : in the progress of the rodent ulcer we see mere destruction, in the cancerous we see destruction with coincident, and usually more than commensurate, growth. It is only in the rarest cases that a growth is associated with rodent ulcer. In one such case, a gentleman about fifty -five years old had, for nine years, a well-marked rodent ulcer of the ear, which was several times partially healed. At length, a firm spheroidal growth, nearly an inch in diameter, appeared ' The parts enumerated were tlie seats of disease in the cases from which I have drawn my description, and in which it is, I believe, most frequent ; but it is not cm- fined to them. Lebert refers to cases of it, in his account of the cancroid of the uterus, and suggests that the simple chronic, or perforating, ulcer of the stomach is a disease of the same nature. Considering, however, the age and circumstances in which this ulcer most frequently occurs, it may rather be compared with lupus. 726 WARTY GEOWTHS OF SCABS. in the subcntaneous tissue at the border of the ulcer. I cut off the upper half of the ear with the adjacent growth, expecting to find that it was an epitheUal cancer : but it had no cancer-structures ; only such corpuscles as I have always found in the borders and bases of the rodent ulcers. The patient died fifteen years after the operation, with- out any appearance of recurrent disease. This indurated substance at the base and borders of the nicer appears, on section, very firm, pale greyish, uniform or obscurely fibrous ; Kttle fluid of any kind can be pressed from it. It is com- posed of the same elementary structures as common granulations are, and these, in the deeper layers, are inserted among the tissue on which the ulcer rests. I have examined very carefully six of these ulcers, re- moved by excision, and hare never seen in or near them a structure resembling those of epithelial or any other form of cancer. Lebert's observations, I believe, fully coincide with mine ; though he classes the disease with epithelial cancers, under the general name of Can- croid. Mr. Jonathan Hutchinson, also, has made several examina- tions of pieces cut, during life, from the margins of rodent ulcers, and always with the same result ; they never contained structures re- sembling those of epithelial or any other cancer. Thus the anatomical distinction between this disease and cancer is evident, and they are equally different in pathology ; the rodent ulcer, so far as it has yet been observed, is never attended by similar disease in the lymphatics or any other part ; and if completely removed or destroyed, it does not recur. The Warty Growths on Scars (Cancers of Cicatrices) are usually well- marked papillary epithelial cancers, which grow in the place of scars remaining after injuries or common ulcers. Mr. Hawkins,^ who has given a very full account of their general characters and progress, describes cases in the scars of burns, gunshot- wounds, floggings, and ulcers. All that I have seen were on the lower extremities, and con- nected with scars after repeated injuries or bums.' The description already given of the warty epithelial cancers may suSice for these. They usually exemplify very well the wide-spread growth and cancerous change in the papillse ; the enlargement, at first ' Medical Gazette, xxi-iii. S72 ; and iled.-Chir. Trans, six. See, also, the Bublin Quarterly Journal, 1850-51. ^ They are amply illustrated in the Museum of St. Bartholomew's, Series i. and xxxT. -to. Several cases are described by Mr. Stanley {Treatise (m Diseases of the Bones, p. 360). WAKTY GROWTHS OF SCAES. 727 probably simple, aad afterwards 'witli cancerous formation, in the papillae of tbe adjacent skin ; tlie deep extension of the disease to the periosteum, and tbenoe onwards, even to tbe complete penetration of the bones and other subjacent tissues ; and, at a late period, the can- cerous disease of the lymphatic glands. But it is important to be aware that this disease niay be closely imitated by warty growths and ulcers, in and about which no cancerous matter can be found. I esiimiued very carefully such an ulcer with prominent growths on the front of a man's leg. It was seated in the middle third of the leg, in the place of a large old scar after a scald, and the greater part of the ulcer pre- sented high, lobed, and nodulated, hard granulations. No one doubted, before the amputation, that the disease was the usual form of cancer ensuing in these conditions ; yet no cancer-structure could be found. In whichever part I examined, I could find only inflammatory products, and such corpuscles as compose ill-developed or degenerate granula- tions upon common ulcers. Similar warty diseases very closely resem- bling, to the naked eye, the epithelial cancers, and often, like them, ulcerating, are not very rare on the lower lip ; and I have seen them on the tongue.' I think some of the diversities of opinion respecting the nature of these warty growths and ulcers may be due to the want of distinction between those which are, and those which are not, epithelial cancers. Certainly, the opinion that epithelial cancer is thoroughly curable by operation, and is altogether a much less mahgnant disease than the other varieties of cancer, is due in great part to warty growths and ulcers having been considered cancerous which were not so. To the naked eye and during life, the two diseases may be very much alike ; but the diiFerence in their respective minute structures is clear, and in- dicates essential difference of nature. ' The growths described by some of the German pathologists, by the name of destructive papillary tumour of the skin, are doubtless the same as these ulcerating warty growths. 728 EPITHELIAL CANCER. LECTURE XXXir. EPITHELIAL CANCEK. PAET II. — I'ATHOLOGT. Among all the cancers, the epithelial present the general or constitu- tional features of malignant disease in the least intense form. They commence at the latest average period of life ; they appear to be most dependent upon local conditions ; they are least prone to multiplication in internal organs. And yet I believe that in a large survey of them, none of the features of malignant disease, as exemplified in the scirrhous and medullary cancers, will be found wanting : the difference is one of degree, not of kind. (a.) A large majority of the cases of epithelial cancers occur in males. In 105 cases, affecting parts common to both sexes, 86 were in men and 19 in women. In the cases affecting the sexual organs them- selves, I think the proportion is nearly equal ; unless we reckon the scrotal soot-cancers, which for obvious reasons, we should more properly exclude. (6.) A few cases are on record, transmitted from book to book, in which what were probably epithelial cancers occurred before adult life. Sir James Barle saw a scrotal soot-oancer in a child eight years old ; ' so did Mr. Wadd ; * and M. Lebert ' examined a ' cancroid ' growth at the vulva in a child three and a half years old, in whom it was almost congenital. But cases such as these cannot be taken into our estimate of the influence of age in determining the access of the disease. In the • Port's Works by Earle, iii. p. 178. ^ Curling on the Diseases of the Testis, iii. p. 528. ' Traits Pratique, p. 676. Hannover {Das Epithelioma, p. 104) quotes from Freriehs a case in which the disease exten led from the ear through the petrous bone in a male nineteen years old. HEBEDITABY DISPOSITION. 729 following table I have included no cases that were recorded merely or chiefly on account of the patients' ages :■ — ' No. of Gases, 9 22 Age. 20 to 30 30 „ 40 40 „ 50 50 „ 60 60 „ 70 70 „ 80 40 32 30 10 143 If now, as in the last two lectures (pages 633, 679), we calculate from this table the frequency of epithelial cancer in proportion to the number of persons living at each of the successive periods, it may be represented by the following numbers (100 being, as before, taken to express the frequency between 40 and 50) : — 20 to 30 years . 12 30 „ 40 „ 41 40 „ 60 „ 100 60 „ 60 „ 119 60 „ 70 „ . 163 70 „ 80 „ 111 "We may probably deduce from this calculation, which is confirmed by Mr. Baker's tables,' that the conditions favourable to the production of epithelial cancers regularly increase with the increase of age ; for the apparent diminution after 70 may be reasonably ascribed to the comparatively small proportion of persons beyond that age who are re- ceived into hospitals, or who are under such surgical treatment as to have their cases recorded. The proportions expressed by the foregoing general tables are nearly true for the epithelial cancers of each part most liable to be affected ; the only notable peculiarities, I believe, are that the mean age of its ' The table includes cases from Lebert, Hannover, and others. But I have omitted both from it and from the preceding one, Lebert's cases of ' cancroid ' of the face. They were examples of rodent ulcers, aad their contrast with epithelial cancers (of the ]ip for example), is well shown, in that the average age for their coming under opera- tion is 17 years later, and the proportionate frequencies in the two sexes are reversed. The ages assigned in the above table are, with few exceptions, those at which the disease was first observed bt/ the patients. ' Med.-Chir. Trans, xlv. 730 EPITHELIAL C.il^CEE : occurrence is lowest in the sexual organs and highest in the integu- ments of the head, face, eyelids, and upper extremities. (c.) An hereditary disposition to soot-cancer has been several times observed ; as by Mr. Earle,' in a grandfather, father, and two sons ; by Mr. Hawkins,^ in a father and son ; by Mr. Cusack,^ in a mother and son ; by myself (twice) in two brothers. But all the per- sons here referred to were engaged in the same trade, and their expo- sure to the same exciting or predisposing cause of the disease diminishes the value of the facts as indications of hereditary predispo- sition. I have no certain record of other epithelial cancers occurring in many members of the same family ; but among 66 patients with epithelial cancer, 10 were members of families in which other members have had scirrhous or medullary cancers, and two were sweeps, whose brothers had similar soot-cancers. Among 160 instances of cancer, in most of which the point was in- quired into, though none were collected for the sake of it, these cases ■were found : — (1 ) A man had medullary cancer of a toe : his father had cancer of the lip. (2) A woman had repeated epithelial cancers of the labia : her sister, her father's sister, and her mother's brother's daughter, had cancer of the breast. (3) A man had epithelial cancer of the lip, whose grandmother had cancer of the breast. (4) A gentleman had epithelial cancer of the interior of the cheek : his aunt died with cancer of the breast. (5) A woman had medullary cancer of the breast : her mother had cancer of the uterus, and her uncle cancer of the face. (()) A woman had scirrhous cancer of the breast, whose mother's uncle had cancer of the lip. (7) Of another woman with similar cancer, one cousin had cancer of the lip, another cousin cancer of the uterus. (8) A third woman had scirrhous cancer of the breast whose grandfather had cancer of the lip.* The proportion of these cases (only ^\j- of the whole number) may seem too small to be even suggestive : jet it is too large to be referred 1 MM.-Ckir. Trans, sii. 305, ^ Medical Gazette, xxi. 842. ' Quoted by Mr. Curling ( On Diseases of the Testis, p. 328). ■■ Dr. "Warren mentions this: — A grandfather died Tiith a cancer of the lip. His son and two daughters died with cancer of the breast. One of his grandsons and one of his granddaughters had also cancer of the breast {On Tumours, p. 281). It may be objected by some, that the cancers of the lip here referred to were not epithelial. I assume that they were, because of the exceeding rarity of any other kind in the lip : indeed, I have not yet seen one, or a complete record of one, in which the microscope did not find the epithelial structures. Again, in 103 cases of inherited cancer collected by Mr. Baker, 13 sho\fed changes in form similar to these. — St. Bartholomew' s Hospitai Reports, a. -p. 132. INFLTJENCE OF INJURY AND PREVIOUS DISEASE. 731 to chance. Let it be contrasted with, these facts : — (1) I have found that among 116 patients ' with cancer, only one was aware of any member of the same fam.ily having had a simple tumour. This was a woman with scirrhous cancer of the breast, from whose sister a mye- loid tumour of the breast had been removed. (2) Among 77 patients with non-caneerous tumours, 10 were aware of near relations having had similar diseases : but among the same IT , the only cases of family connection with cancer were the following : — (a) The cases of recur- ring and disorderly-growing mammary tumour related at p. 663 ; (V) the case of anom.alous cartilaginous tumours at p. 507 ; (c) that of the same woman whose case was just raentioned as one of myeloid tumour of the breast ; five years after its removal, she and her sister were at the same time in St. Bartholomew's with scirrhous breasts ; (d) that of a lad with mixed cartilaginous and glandular tumour over his parotid gland, whose grandmother had cancer of the breast. Now of these oases the first two must be regarded, I believe, as instances of a cancerous dis- position, modified and gradually ceasing in its transmission from parent to offspring (see p. 563, etc.) : the third is a very anomalous one, exemplifying the formation of a most rare tumour in the breast, not long before it became cancerous ; the fourth alone is an instance of an ordinary simple or innocent tumour growing in one who had a cancer- ous relation. I have referred to these cases, not to suggest that when cancer has occurred in one or more members of a family, the rest are peculiarly unlikely to have innocent tumours, but to show, by contrast, that the proportion of cases in which epithelial and other cancers occur in the same family is, relatively, considerable. For if that proportion were the result of chance-coincidences or errors in observation, an equal or nearly equal proportion of coincidences should have appeared in the opposite set of cases. But the contrast between the two sets of cases is remarkable ; and I believe the facts may be justly regarded as evi- dence for the close affinity between epithelial and other cancers, and as an illustration of the modification which the cancerous and other dia- theses may undergo in their hereditary transmission. (■(£.) Among 34 patients with epithelial cancers, 19 were aware of iniury or previous morbid condition in the affected part : a much larger 1 These -were part of the 160 mentioned aboye ; but I hare here reckoned only the cases recorded by myself, because it is probable that, even if, among the others, any instances had occurred of innocent and malignant tumours in the same family, they would not have been mentioned. The bearing of these oases on the question of the local or constitutional origin and nnture of cancer is considered in the 34lh Lectum, 732 EPITHEUAL CANCER. proportion than is found among patients labouring under tumours of any other kind, except melanoid cancers of the skin. In certain cases, injury by violence appears as the exciting cause. But the histories of epithelial cancers differ from those of others in that the kind of injury which is most effective in their production is such as is often inflicted — ^frequent blows or slight wounds on the same part ; hurts of sears and other seats of old injury. It is as if it were necessary that the part should be considerably changed in structure before it is appropriate for a cancerous growth. It agrees with this, that in the majority of cases, patients assign as the cause of the disease, not injury, or not it alone, but some former disease, especially such as arises from long-continued irritation of a part. Thus epithelial cancers arise sometimes in old ulcers, as on the legs, or, as I have known, in perineal urinary fistula ; sometimes, iu those of more rapid progress, as I once saw in a case of necrosis of the hard palate, and once in a case of necrosis of the angle of the lower jaw ; and as Frerichs describes, in an ulceration of the internal ear, following scarlet fever. The majority of the epithelial cancers of the prepuce and glans occur in those who are the subjects of congenital phymosis, and in whom we may assume the frequent irritation of the part by decomposed secretions. In some rare cases, a mole or pigmentary nasvus becomes the seat of the disease. But, among all the things referred to by patients, none are so frequently named as ' warts.' ' The affections thus named are not usually such as are commonly called warts. They are not usually like the warts (Verrucae, or Condy- lomata elevata) that grow on the genital organs during gonorrhoeal or other similar irritation ; nor Kke such warts (Verrucse vulgares) as are common on the hands of young people before puberty (p. 588) ; nor like the condylomata (0. lata) of syphilis. Such papillary growths as these may, I believe, precede epithelial cancer ; but I think they rarely do so. The general condition of the ' wart ' is, I think, that a small por- tion of the cutis is slightly indurated ; its papillas are generally in some measure enlarged : and it is covered with a darkish dry crust, or with a scab ; or, if the part be very moist, with a soft layer of detached scales.^ The induration of the cutis, and the predominance of the 1 It is implied here that the form of cancer assumed in or by warts is always the epithelial. Some cases by Mr. Butcher {Dublin Quart. Jour, of Med. Sc., Nov. 1856) appear to be instances of medullary cancer originating in warts. 2 Such as these are well described by Schuh {Pseudcplasmen, p. 46), under the title ' barky warts.' With the same intimation of likeness, Dr. Warren (Om Tumours, p. 27) called the disease ' Lepoides. INFLUENCE OF INJUEY AND PEEVIOUS DISEASE. 733 crust or other covering (which apparently constitutes more of the disease than either the induration or the papillffi), mark the chief differ- ences between this disease and any of the ' warts ' just referred to. The induration which patients often describe as ' a little hard knot,' is usually attended with elevation, but sometimes with contraction and depression of the piece of cutis. The crust consists, for the most part, of epidermal scales held together by dried secretion, or, in its deepest layers, forming a whitish, friable sabstance, and fitting between the papillae. It is easily detached and quickly removed ; and, when it is re- moved, the subjacent cutis does not usually appear raw or bleeding, but is tender, florid, and as if covered with a very thin glossy layer of epider- mis. When a moister yellow scab covers the induration, the surface beneath it is usually more inflamed and excoriated, and the papillse are more enlarged. Such incrusted warts as these are very common, especially on the faces of old persons ; the large majority of them lead to no further trouble ; ' yet some become the seats of epithelial cancers, and some of rodent ulcers. A similar affection often precedes the epithelial cancer of the lower lip. Some slight violence often applied, such as that of a short pipe habitually supported by the lip, or the frequent slight rending of the surface of a dry scaly lip, or one much exposed to the weather, leads to a ' little crack ; ' this scabs over, and after repeated removals and re- newals of the scab, there is a ' little hard lump,' or ' a sort of wart,' with a head or crust. And such a wart might be as often innocuous on the lip as on the face, if it were not that the lip is in the unhappy singu- larity of being within easy reach at once of the fingers, the teeth, the tongue, and the other lip ; so that when it is as yet but slightly diseased it is never left at rest. A similar drily scaled or incrusted warty change of the cutis often, I believe, precedes, the chimney-sweep's cancer ; and I suspect that the true influence of the soot in this disease is not that its contin- ued contact determines the growth of cancers, but (at least in part) that it produces a state of skin which provides an apt locality for epithelial cancer in persons of cancerous diathesis. How it does this I cannot imagine : but this is only one of many things unexplained in this strange disease ; for the whole of the peculiarities of the chim- ney-sweep's cancer — its dependence on soot, while coal-dust is wholly ' Virchow (in his Anhiv, vi. p. 553) says that the small hairy knots, -yhich ara so frequent on the faces of old persons have exactly the structure of the cutaneous cavernous tumours. But these, I think, are not peculiarly apt to be seats of epithelial cancer. 734 EPITHELIAL CANCEE. inoperative (for the disease is unknown among colliers) ; its compara- tive frequency in England, especially in certain, but not all, large towns, while in other countries where soot is abundant it is hardly seen ; its selection of the scrotum for its most frequent sea*", — all these,' and many like facts in its history, appear completely inexplicable. Still, it is certain that scaly or incrusted small warts, such as I have been des- cribing, are very common in chimney-sweeps. In many of them, even when they are thoroughly cleaned, the whole skin is dry, har. h, and dusky ; and, before operation for the removal of scrotal cancers in them, it is a common question whether one or more warts or scaly pat- ches near the chief disease should be removed with it. Nor are such warts confined to the scrotum ; they may exist on every part of the trunk and limbs ; and I have seen sweeps so thick-set with them, that a hundred or more might have been counted. Such are some of the numerous morbid states, one or other of which may, in the majority of cases, be assigned as predisposing apart to be- come the seat of epithelial cancer. Expressions are sometimes used, implying that the part does not become the seat of a new morbid struc- ture, but that its mode of action is changed, or that the change is only due to the extension and deepening of a common epidermoid or warty growth. The truer view, however, may be expressed by saying, that the part, whatever were its previous state, becomes the seat of epithe- lial cancer, the structures of which, as of a new disease, are inserted in and among the original or previously morbid textures of the part. This evidently happens when the cancer appears in parts previously healthy, or in the deep-seated tissues, or in the walls of ulcers, or in a pigmentary nasvus ; for, in these cases, no morbid structures like those of the epithe- lial cancer exist previous to its access. There is more appearance of similarity and continuity of disease between the epithelial cancers and the warty growths by which they are sometimes preceded : for here both the earlier and the later disease may have, in common, an accumu- lation of epidermoid cells and an enlargement of papillse. Yet the warts, whether incrusted, or others, in which the epidermoid structures are only superficial, should also, I think, be regarded as only predispos- ing conditions of epithelial cancer ; as diseased parts, not cancerous, though peculiarly apt to become the seats of this form of cancer. For the great majority of these remain stationary, or may disappear, or be ' It appears to me, in 1870, to have become of late years much rarer than it used to be. Cases are now very rare at St. Bartholomew's, where twenty or thirty years ago they were often seen. INFLUENCE OF INJURY AND PREVIOUS DISEASE. 735 cured, even in cancerous persons ; they are comparatively few in wHcli, after a certain duration as simple warts, the cancerous disease is mani- fested. And the time of the change in them is often well marked. Nearly all patients — even those who can assign no date to the beginning of the wart or hardness, or other previous disease — can refer exactly to some time of change in it, when it began to 'grow up,' or 'be sore,' or ' get bad,' discharge, or bleed. They thus mark the time when the cancer- ous mode of progress was commenced ; and from this time the history of all such cases is nearly uniform — even remarkably uniform, if it be compared with the variety of the histories of the previous states. Now, I believe that this change in the life of the warty or other dis- eased parts is always associated with a change in its structure : and that whatever were its previous state, its proper tissue, whether papillary or any other , now becomes the seat of the formation of epithelial cancer- cells. It is hardly possible to prove such a change of structure in any single case, but it is rendered highly probable by this — that in those warty structures which we remove because experience makes us believe that they are in progress as epithelial cancers, we find the tissues infil- trated with the specific cancer-cells : while in those which have been long stationary, without extension or outgrowth, without ulceration or ichorous discharge, no such infiltration is found. Certain cases must be excepted from this statement because of error in diagnosis. I have known rodent ulcers excised, in the belief that they were epithelial can- cers ; but I never saw any growth removed as an epithelial cancer, in which the epidermoid cells were placed only on the surface of the vas- cular tissues ; and, on the other hand, I have never seen such cells in the cutis or papillte of any incrusted or other wart, in which the cancer- ous mode of progress was not yet manifested. The opportunities of examining such warts as observation shows to be most apt to be precur- sors of epithelial cancer are rare ; but I have examined some on the scrotum, and one on a lower lip. The last may deserve description. A healthy-looking farmer, sixty-six years old, came to me with an induration, about two lines wide and half-a-line thick, at the middle of the flLOrid margin of his lower lip. The indurated part was slightly sunken, and covered with a thin yellow scab. This disease had existed two years, frequently scabbing thickly, then desquamating, never soundly healing ; yet it had made no progress. I removed it, chiefly be- cause the patient's father, when eighty-five years old, had had cancer of the lower lip ; and because, if not already cancerous, this could not but be 736 EPITHELIAL CANCEE. thonglit a place very likely to become so. I found, in the indurated tissue, inflammatory products infiltrated among the natural structures of the skin ; but no appearance of epithelial cancer-cells. The cutis was slightly thickened ; but there was no evidence of enlargement of papillae, or of accumulated epidermis : the scab seemed formed chiefly of dried secretion. I believe that such a description as this would apply to most of the warts that precede epithelial cancers of the lower lip, and that we may justly say of them that they are not cancerous, but are such parts as, in certain persons, are peculiarly apt to be the seats of cancer. Why only some among them should become cancerous we can no more ex- plain, than we can why, among so many injuries inflicted, so few should be followed by erysipelas or tetanus ; or why, among so many pig- mentary moles or nsevi as may be found, only few should become the seats of melanoid cancer ; or, in a yet nearer parallel, why, when a person has many such moles, the melanoid cancer should appear m only one. In these varieties of fate, there is nothing unusual in warts if we regard them as only predisposed to become cancerous ; but, if we re- gard them as the first stages of a cancroid or cancerous disease, such varieties of progress as they manifest would be without parallel. (e.) The general health of patients with epithelial cancer is usually good, till it is affected by the consequences of the local disease. Less than ten per cent, of them appear ill at their first observation of the disease. No primary cachexia can be observed preceding the appearance of the growth ; nor does a secondary cachexia ensue earlier than it pro- bably would in any disease of equal duration and severity. When the formation of an epithelial cancer has once commenced, its natural course is as regularly progressive to the destruction of life as that of either a scirrhous or a medullary cancer. Only, the rate, and some parts of the method, of progress are different. The average rate of increase of epithelial cancers is less than of either of the other kinds. It is not apt to be arrested altogether ; yet it is sometimes so slow that, ia a year, the cancer may gain only a line or two in any of its dimensions. In other cases, however, and especially when such a cancer has been violently injured, the progress is much more rapid. I have known three- fourths of the scrotum covered with ulcera- ting soot-cancer, and part of the urethra surrounded by it, in three months after a laceration received while in apparent health ; in another case, a spheroidal mass of soft ejithehal cancer, an inch in diameter. EPITHELIAL CANCER. 737 formed in the substance of the cheek in two months ; in another, a growth more than an inch in diameter formed in ten weeks ; in another, the whole depth of the lower lip, and two-thirds of its width, were occupied with epithelial cancer, in three months after a blow on a little cancer at its margin ; in another, within twelve months, the eyelids and a large part of the contents of the orbit were destroyed by ulceration, and tuberous masses, from one to three-quarters of an inch in diameter were formed under the integuments of the brow, the temple, and the other boundaries of the orbit. Cases such as these, and they are not rare, may prove the error of regarding epithelial cancer as a trivial or an inactive disease in com- parison with the other forms. Its rate of progress is, like that of scirrhous cancer, widely various in difierent cases ; it has its acute and its chronic instances. Of its modes of growth, and of ulceration, and of the usual coincidence of these processes, I have spoken fully in the former part of the lecture (p. 710) ; I will here only add that the ulceration, at whatever rate, seems constantly progressive. Some por- tions of the ulcer may appear, for a time, as if skinning over, or, portions of the disease may slough away and the surfaces they leave may partially heal ; but I do not remember to have seen any process of healing or wasting so nearly accomplished in an epithelial cancer, as I have described in some cases of both scirrhous and medullary cancer, in the former lectures (pp. 640, 685). The progress of the ulceration, and the coincident deepening of the growth, are usually attended with great pain — hot, scalding, and "widely diffusing pain ; or with pain hke that of neuralgia darting in the course of nerves. With this, and the constant ichorous discharge from the ulcer, and the occasional bleedings from ulcerated bloodvessels, the patient becomes cachectic ; yet probably not sooner than in other diseases of equal extent, nor in any very characteristic manner. Primary epithelial cancers are usually single. Two growths may sometimes appear at once in the same region, as, e.g., on the prepuce and glans, or on the scrotum : once, I found three on the same face : I have also seen instances of simultaneous growth in the eyelid and rectum : the finger and rectum : and the lip and scrotum ; but such events are so rare, that they may probably be called accidental. In the later progress of the disease, separate masses of epithelial cancer may be sometimes found in the tissues, or cancerous warty growths on the surface, around the primary growth or ulcer. Healthy tissue appears 3b 738 MULTIPLICITY AND EXTENSION. to intervene between tHese secondary cancers and the primary one : and they may be compared with the tubercles so often grouped around a scirrhous mammary gland. The lymphatic glands, sooner or later in the progress of the disease, usually become cancerous. I have already (p. 719) described the manner of their infection. I feel almost disposed to think that epithelial cancer is a much worst disease in this country than in France or Denmark, when I see how far my observations on the affection .of the lymphatics differ from those of Lebert and^ Hannover. Lebert' says that he has found the lymphatic glands affected with ' cancroid ' three times in 81 cases ; and of th-ese 81, 60 were certainly cases of epithelial cancer. Hannover^ has even less frequently seen them diseased. Now, in 42 cases of epithelial cancer collected in the ordinary course of hospital and private practice, and including many in the early as well as in the latest stages of the disease, 1 have observed the lymphatics cancerous twenty times. In the greater part of these cases the characteristic cancer-structures were found in the glands rem.oved during life or after death : in the rest their existence was concluded, with scarcely less certainty, from the enlargement, with induration, rapid growth, clustering, and destructive ulceration of the glands. It need not be suspected that in any of these cases the glands were enlarged merely through ' irritation ; ' such a state does, indeed, occur with epithelial as with scirrhous cancer ; but the diagnosis of this from the cancerous enlargement is seldom, in either case, difficult. I do not suppose that the proportion cited above expresses the greatest frequency of epithelial cancer in the lymphatic glands. I believe rather, that no cases reach their natural end without infection of the glands. Even after the primary disease has been wholly re- moved, and when the glands at the time of the operation appeared healthy, they are frequently, and often alone, the seats of recurrences of the disease. Sometimes also, as with scirrhous cancers (p. G21), we find the disease in the lymphatics greatly preponderating over that in the primary seat. My observations are scarcely less different from those of Lebert, in re- lation to the occurrence of secondary epithelial cancers in internal organs. In eighteen autopsies (some of which, however, were made in fatal cases of rodent ulcer) he has not once found ' cancroid growths ' in any internal part. In seven autopsies,' I have found epithelial cancer once ' TraiU Pratique, p. 619. ^ Das Ejn/Mioma, p. 24. ^ In two of these the disnase had not reached its natural end ; for the patients EPITHELIAL CANCER. 739 in tie heart, and once in the lungs (p. 721). Doubtless, the internal organs are more rarely infected than in any other form of cancer ; but they do not enjoy an absolute immunity ; the difference between the epithelial and the other cancers is, in this point again, one of degree not of kind. It is a peculiarity of epithelial cancers, that in nearly all the characteristics of mah'gnant disease — whether the propagation to the lymphatics or other organs, the extension to deep-seated parts, the recurrence after removal, or the rate of progress towards death — greater diffeiences are noted according to the seat of disease than among the medullary cancers of different parts. The anatomical characters of the disease are in all parts essentially the same, but their history, in all the particulars noted above, differs, so as to justify the expression that the disease is less malignant in some parts than in others. It is, generally, most malignant in the tongue, the interior of the mouth, and the penis ; least in the lower extremities and the scrotum ; in general, also, the epithelial cancers that are deep-seated are more malignant than the superficial, and mttch more so than the ex- uberant. These diversities make it very difiScult to assign the average duration of life in persons with epithelial cancer ; and the difficulty is greatly increased by the recorded cases being often mixed or confounded with those of other cancers and of rodent ulcers. Taking cases with clear diagnosis, without regard to the parts affected, the average duration of life in twenty-three cases which ran their natural course was 27'4 months ; and in thii-ty-five cases in which the disease was once or more removed by operation, 57'6 months. The following table will show the durations of life in the cases, and may be compared with those in p. 646, and p. 691, from which the fore- going statement was derived: — died in consequence of amputation. In another case I found epithelial cancer of the tongue, "with medullary cancer of the cervical glands, and of the lungs ; hut, as I have already said (p. 720, note), though no medullary cancer-structures were found in the primary disease, it was impossible to prove that they had never existed, for a large portion of the tongue had sloughed before death. Virchow's observations on the occurrence of secondary epithelial cancer in internal organs are very clear. 3 n 740 COURSE AND DUEATION OF LIFE. Duration of Life. Number of Cases. "With, Operation Without Less than 6 montlis . 1 Between 6 and 12 months . 1 6 „ 12 „ 18 „ . 5 6 „ 18 „ 24 „ . 4 1 .. 24 „ 36 „ . 3 4 JI 3 „ 4 years . 4 3 )> 4 „ 6 „ . 8 I) 6 „ 8 „ . 1 More than 8 years . 9 2 35 23 The chief point which this table shows, in contrast with those of other cancers, is in the larger proportion of patients living more than four years. Great differences, however, as to length of life, may be noted among the epithelial cancers of different organs. Those in the tongue rarely survive more than four years ; those in the trunk or Hmbs rarely destroy Life in less than three years : a majority of those in the lower lip snrvive that period. The age at which the disease commences has no great influence on its duration. The average duration among four- teen patients, in whom it commenced at or below 4-5 years of age, was 39 months ; that among seventeen, in whom it commenced later, was 45^ months ; and the general average duration was not exceeded in the first list more often than in the second. A considerable prolongation of life would appear, by the cases I have collected, to be obtaiued by the removal of epithelial cancers. The average advantage, as shown by the foregoing table, is 30 months, and although this great difference may be ascribed to a careful selection of cases, yet the average is sometimes greatly surpassed. I have seen a man whose leg was amputated twenty years previously for epithelial cancer, commencing in or beneath a scar, and he was still well. A sweep was some time back in St. Bartholomew's with a small scrotal cancer, from whom one of the same kind was excised thirty years previously. Of another, Mr. Curling ' gives a history extending over twenty-two years, and including five operations. A man from whom Sir ~SY. Lawrence removed a cancer of the lip remained well for nine years, and then the disease appeared in the lymphatic glands. Cases such as these must, however, be considered very rare. Too On Diseases of the Testis, p. 535. EESULTS OF OPEEATIONS. 741 mucli regard to them, and the confasion of the rodent ulcers with the epithelial cancers, have led to a common belief that recovery or long life may be promised as the consequence of operations. Such a pro- mise will not prove true ; and yet, as a general rule, the operation is to be advised, whenever the whole of the disease can be removed without great risk of life. For (1), though the instances of operations followed bylong immunity from the disease are very rare, yet, in certain cases, these results may be hoped for. This is especially the case, I think, with the epithelial cancers of the lower extremity, which follow injury, and for which am- putation is performed ; with the more superficial cancers of the lip ; and most of all, with the soot-cancers which are not making quick progress. On the other side, according to present experience, such lengthening of life can rarely be hoped for after operations for the epithelial cancers of the tongue, the gums, or other parts in the interior of the mouth. The best instance of these that I have yet known, is one of a removal of an epithelial cancer of the tongue, in which eight years elapsed before the recurrence. (2.) In the majority of cases, and even when very little increase of life can be hoped for, the removal of the disease may give great comfort for a time. In general, also, the greater part of the time that intervenes between the recovery from the operation and the recurrence of the disease may be reckoned as so much added to life ; for although we cannot deny a diathesis, or specific constitutional affection, in epithelial cancers, yet it is by the progress and consequences of the local disease that, in the majority of cases, the time of death is determined ; so that, while local disease is absent, life may be shortening at scarcely more than the ordinary rate. Of course, in applying such a rule as this may sugo-est in practice, we must except from it certain cases in which the general health is already very deeply affected, or in which the operation would be perilously extensive. (3.) The extension of the epithelial cancer to the lymphatic glands is not an insuperable objection to operations. The disease usually remains long limited to the glands which are nearest to its primary seat (p. 720) ; its complete removal can therefore be usually accomplished ; and although I can cite no instance of very long survival after opera- tion including cancerous glands, yet, on the other side, I can cite none which would prove that the recurrent disease is quicker or more severe after such operations, than it is after those of equal extent in which the glands are not yet diseased. 742 EESEMBLANCE TO SCIREHOUS AND MEDULLAEY CANCEES. (4.) The general rule concerning operations in cases of recurrent epithelial cancer may be the same, I think, as for the primary disease. A second operation is, in general, less hopeful than a first, yet nqt always so ; for although the epithelial, like other cancers, usually make progress at an accelerating rate, yet cases are not wanting in which the intervals between successive operations have progressively increased. (5.) The recurrence of epithelial cancer after operation is in some cases very rapid, in others greatly retarded. The number of cases in which recurrence ensues at a medium period appears comparatively small. I cannot explain the fact, if it be one, but I believe that if, after operation, a patient remain free for eighteen months, it is very probable that the immunity will continue for at least five years. Let me now collect from the facts of this lecture the grounds which seem to justify the inclusion of this disease under the name of cancer. It is not unimportant to do so ; for we may be certain that, in this case, the name of the disease will often guide the further study and the treatment of it. I have excluded from the group of epithelial cancers the rodent ulcers, which M. Lebert includes with them under the name of ' cancroid,' and which Mr. Moore names rodent cancer. The two diseases are so constantly unlike, in both structure and history (see p. 724), that their separation under different titles seems consistent with the most usual rules of nosology. I have also excluded those papillary and other affec- tions of the skin, in which epidermoid structures are accumulated only on the surface of the affected part. For, although these may sometimes appear like the first stages of certain epithelial cancers (see pp. 702 and 734), yet the distinction between the two is commonly well marked in the history of each case : and, in their respective anatomical relations, the distinction between a superficial and an interstitial epidermoid structure is very significant ; since the former has its nearest homologue in natural epithelia, the latter in cancerous infiltrations. Thus limiting the diseases to be included under it, the name of epithelial cancers seems justified by their conformity with the scirrhous and medullary cancers in these following respects : — (1.) The interstitial formation of structures like those of epithelium is not an imitation of any natural tissue ; it constitutes a heterologous structure ; for superficial position is more essential to the type of epithe- lial structures, than any shape of elemental cells or scales is. EESEMBLANCE TO SCIERHOUS AND MEDULLARY CANCERS. 743 (2.) Even that delusive appearance of homology, which exists when the structures like those of epithelium are formed in the dermal tissues, and therefore near the surface, is lost in nearly all the cases of deep- seated epithelial cancers, and in all the similar affections of the lym- phatic glands and internal organs. (3.) The interstitial formation of cells in epithelial cancer is con- formed with the characteristic plan of all cancerous infiltrations, and leads to a similar substitution of new structures in the place of the original tissues of the affected part. (4.) The interstitially-formed cells often deviate very widely from the type of any natural epithelial cell, in shape, in general aspect, in method of arrangement, and in endogenous formation (p. 715, et seq.) The difference between them and any natural elemental structures is, indeed, m.uch greater than that between many medullary and scirrhous caucer- cells, and the cells of the organ in which they grow e.g. it is sometimes difficult to distinguish the cells of a medullary cancer in the liver from those of the liver itself. (5.) The pathology of epithelial cancers is scarcely less conformed than is their anatomy to the type represented by the scirrhous and medullary cancers ; for, not only are they prone to incurable ulceration, and to repeated and often very rapid recurrence after removal, but (which is much more characteristic) they usually lead to the formation of structures like themselves in the lymphatic glands connected with their primary seat ; they lead sometimes to similar formations in more distant organs (p. 719, et seq.) ; and the average duration of life in patients affected with them, is, on the whole, not greater than that of those who have scirrhous cancer. (6.) In their growth, and in their recurrence, there is no tissue which the epithelial cancers do not invade and destroy (pp. 705 and 711). (7.) A peculiar liability to them exists in members of those families in which scirrhous or medullary cancer also occurs (p. 731). Such are the affinities between the epithelial and (as I would say) the other cancers. They are so numerous and so close, that I cannot but think we should be guided in the choice of a name by them, rather than by any other consideration. They are surely more significant of affinity with the other cancers than the contrast between the shapes of the elemental cells is indicative of such difference as should be expressed by a different generic name. 744 MELANOID AND OTHER CANCERS. LECTURE XXXIII. MELANOID, H.S;MAT0ID, OSTEOID, TILLOUS, COLLOID, AND FIBEOirS CANCERS. Of the tkree chief forms of cancer which I have now described, we may observe, I think, that thongh two of them may be mixed in one mass, or may occnr at different times in the same person, or in differ- ent members of the same family, and thongh there are forms intermedi- ate and transitional between them, yet a mass of one of them does not, by any transformation, assnme the characters of another. A scirrhous cancer, I think, never itself becomes medullary or epithelial ; neither does the converse happen ; nor do we see any indication that inter- ference with the development of a cancer of either of these forms wonld lead it into the assumption of the characters of another. Com- bination, coincidence, succession, or interchange of these three forms, maybe found; but, I believe, no transformation of a growth com- pleted or in progress. If this be true, it indicates that the degree of difference between each two of these three forms is greater than that which exists be- tween them and the cancers to which I shall devote this lecture. For there seems sufficient reason to believe that, by certain generally re- cognised processes of degeneration or disease, a medullary or epithelial cancer may become melanoid, or hsematoid ; that a scirrhous or firm medullary cancer may become osteoid ; that the colloid character may be, in some measure, assumed by either of the three chief forms ; and that either of them may observe the villous or dendritic mode of growth. It need not always be supposed that, in the transformations here implied, the cancer- structures already perfected change their characters. It is probable, indeed, that such changes do occur in some of the instances we have to consider ; but, in others, we may rather believe that the peculiarities of structure are due to something which induces degeneration or disease in the cancer-elements in their most rtsdimental state. MEXANOID CANCER. 745 The belief that tlie six forms of cancer, whose names head this lec- ture, are modifications or varieties of one or more of the three already- described, may justify my describing them more briefly, and, in many parts, by terms of comparison with the chief forms. Or, if this belief be not a good reason for such a course, it must be sufficient, that the examples of all these six forms are so rare, that complete and indepen- dent histories of them cannot, at present, be written. It is, I think, probable that other groups of cancers besides these might be conveniently described as varieties of the principal kinds ; ' but, at present, it seems better to defer the introduction of new names till we have attained more accurate knowledge. MELANOID CAHCER. The Melanotic or Melanoid Cancers are, with very rare exceptions, medullary cancers modified by the formation of black pigment in their elemental structures. On this long-disputed point, there can, I think, be no reasonable doubt. I have referred to a case of melanotic epi- thelial cancer (p. 718) ; but this is an exceptional case. Some patho- logists have recently described pigment-formation in one of the forms of sarcoma, to which, in consequence, the name ' pigment sar- coma ' has been given (note, p. 641). In the horse and dog, I believe, black tumours occur which have no cancerous character. The condi- tions, which some have classed under the name ' spurious melanosis,' are blaokenings of various structures, whose only common character is that they are not tumours. Melanotic cancers may have the general characters of any of the varieties of the medullary cancer ; but the primary growths are rarely either very firm or very soft. They may appear as infiltrations ; but are more often, I think, separable masses. Their characteristic pig- ment marks them with various shades of iron-grey or brown, deepening into deepest blackness. The pigment is variously arranged in them. Sometimes, we see, on the cut surface, a generally diffused brownish tint, derived from thickly sprinkled minute dots : sometimes, a whole ' This may he the case with -what Miiller named Carcinoma fasciculatum seu hyaliiram. But, judging from his description and Schuh's, I cannot tell trhcther it is a disease which I have not yet seen, or whether (as I am more inclined to helieve) the name has not heen applied to some specimens of the soft, flickering, mammary or parotid glandular tumours, or to the mammary proliferous cysts that are prone to recur (see pp. 432, 563). 746 STRUCTURE OF MELANOID CANCER. mass is uniformly black : sometimes, one or more deep black spots ap. pear m the midst of a pnre white brain-like mass : sometimes (as in the specimen here fignred) in half a tumour there are various shades of brown and black, in the other half the same texture nncoloured : sometimes a whole mass is, as it were, delicately painted or mapped as with Chinese ink. There are thus to be found, in melanoid cancers aU plans and all degrees of blackening ; and these diversities may be seen even in different parts of the same tumour, or in difiFerent tu- mours in the same person.' Nay, even in can- cers that look colourless to the naked eye, I have found, with the microscope, single cells or nuclei having the true melanotic characters. And both the general and the microscopic aspect of the disease may be yet further diversi- fied by the coincidence of degeneration or haemorrhages, producing, in the unblackened parts of the tumours, various shades of yeUowi or of blood-colour. In the dark turbid creamy or pasty fluid that may be pressed from melanotic cancers' the greater part of the microscopic structures are such as" might belong to an uncoloured medullary cancer. It is often remarkable by how small a proportion of pigment the deepest black colour may be given to the mass : a hundredth part of the consti- tuent structures may suffice. The pigment is generally in granules or molecules : but it is sometimes in nuclei or in corpuscles like them. The majority of the pigment- granules are minute particles, not much nnlike those of the pigment-cells of the choroid membrane. When out of focus, they appear black or deep brown ; but, when in focus, they have peUuoid centres, with broad black borders. They appear spherical ; and usually the majority of themarefree, i.e. notenclosedin cells, though they probably have escaped from them, and vibrate with molecular movement in the fluid that suspends them. The greater part of the Fig. 122. Section of a variously-sliaded melanoid cancer formed beneath a mole or pigmentary njevus. jMuseum of St. Bartholomew's, Series xxxv. No. 102. Natural • AJl these varieties are illustrated in the Museums of the College and St Bar- tholomew's, by specimens referred to in the Indices of the Catalogue, i. p. 133, and i. p. xiv. STRUCT UEE OF MELANOID CANCER. 747 colour depends on these free granules (Kg. 123) ; but others like them are enclosed in the cancer-colls, or, more rarely, in nuclei. Sometimes those in the cells are clustered round the nucleus ; sometimes they are irregularly scattered ; in either case they appear as if gradually in- creasmg till they fill the cell, and change it into a granule-mass, which, but for its colour, we might exactly compare with the granule-masses of fatty degeneration. "While the pigment-granules are thus collecting, the nucleus remains clear ; but at last, when the cell appears like a granule-mass, it is lost sight of. After this, moreover, the masses formed Fig. 123. of pigment-granules may break up, and add their granules to those which we may suppose to have been free from their first formation. The completely melanotic cells and their corpuscles seen singly in the microscope, look not black, but rusty brown or pale umber-brown : like blood-cells, it is only when amassed that they give the full tint of colour. With the melanotic granules, there is sometimes a much smaller number of particles of the same colour, and the same apparently simple structure, but of larger size : from ^^^-u to ^xyVtr oi an inch in diameter. These may be both free and in cells ; in the latter case, lying mingled with melanotic grannies in the contents of the cell. More rarely, corpuscles like the nuclei of cancer-cells, preserving their shape, size, and apparent texture, present the characteristic brown tint. Such corpuscles rnay be free ; but they may also occupy the place of nuclei in cells, whose other contents are either uncoloured or mixed with pigment-granules : and more rarely, a single corpuscle of the same kind may be seen in a cell containing an ordinary colourless nucleus. The colouring material is called Melanin. It is soluble in alkalies, from which it may again be precipitated by the stronger acids. A Fig. 123. Elemental structures of melanoid cancer, referred to in the text. Mag- nified 350 times. 748 PATHOLOGY OF MELANOID CAKCER. modification of tliis pigment material is said to occur in the urine of those affected with melanosis, which gives to the nrine when long ex- posed to the air a brownish or blacls. colour.' In all the main, facts of their pathological history, the melanotic cancers are in close conformity with the medullary : and this may be reckoned among the eyidences that there is much less difference be- tween these two forms than there is between the medullary cancers and either the scirrhous or the epithelial. In the tables of 365 cases of cancer from which those in the fore- going lectures were derived, there are 25 cases of melanoid cancer. Seventeen of the patients were females, 8 were males. In 14 cases, the primary seat of the disease was in the skin or subcutaneous tissue ; in 9, in the eye or orbit ; in 1, in the testicle ; in 1, in the vagina.^ In this limitation to a few primary seats, and in its proneness to affect certain abnormal parts of the skin, are the chief peculiarities of this variety of cancer ; but on the other points which may be settled by counting, I might have added the 25 cases to those of ordinary medullary cancer, without disturbing the results stated in Lecture XXXI. Thus, the ages of the patients at the access of the cancer were as foUow : — Under 10 years . . 2 Between 10 and 20 „ . . 1 7 4 5 4 2 The only notable difference in this table, when compared with that at page 679, is in the inferior proportion of cases before 20 years of age ; a difference mainly determined by the large number of cases of nncoloured medullary cancer of the eye in children.' > Dressier and A. Pritram. Frag. Vicrtcljahrschrift, 88, pp. 9, 16. ' I once saw primary melanotic cancer of the liver ; but I hare no complete record of the case. Eiselt found, in an anlysis of 104 cases, the primary seat of the disease 47 times in the eye, 40 times in the skin, 5 times in the liver, thrice in the lungs, twice in the peritoneum, uterus, lymphatic glands, intestinal canal, once in the brain. Ueber Pigment-Krebs in the Prager Vierteljahrsckrift, 70 and 76. ' This fact is corroborated by one of the tables in Mr. Pemberton's Olservatwni )» 20 J) 30 )) 30 3> 40 )) 40 » 50 » 50 >» 60 Above 60 PATHOLOGY OF MELANOID CANCEK, 749 Among 10 patients with melanoid canoer, one had had a relative "Vfho died with cancer of the breast ; another had many relatives with pigmentary naevi hke that in which her own cancer origuiated. In another group of 10 cases, 3 had had cancerous relatives. In 20 of the cases, the previous history of the affected part is re- corded. In 3 of those in which the eye was affected it had been mor- bidly changed by previous inflammatory disease ; in 2 it had appeared healthy. Among the 14 cases affecting the skin or subcutaneous tissue, one patient assigned no local cause ; 2 referred to injury, and were uncertain of the previous condition of the skia ; in 10 the disease commenced beneath a congenital pigmentary nrevus, or dark mole ; and in 1 in what the patient called a wart of several years' standing.' I shall presently revert to these facts. In regard to their rate and method of growth, their ulceration, and their multiplying in parts near and distant from their primary seat, I believe the general history of the melanotic cancers is parallel with that of the medullary given in a former lecture (p. 683, et seq.) But they present even a greater tendency to multiply in the subcutaneous tissue, growing here in vast numbers of small soft tubercles. Secon. dary growths occur also with great frequency in the internal organs. In like manner, the duration of life in melanotic nearly corresponds with that in medullary cancers. In 18 cases, in all of which the pri- mary disease was removed (but in two only partially), the durations of life from the first notice of the cancer were as follow (and the table may be compared with that in p. 693) : — Between 6 and 12 months in 3 cases 12 „ 18 „ 4 „ 24 „ 36 „ 5 „ 36 „ 48 „ 1 „ Above 48 „ 5 „ Among 18 oases, whose history is known for some time after the removal of the primary disease, one has survived for three years, ano- ther for ten months, without recurrence of the disease. In the rest the disease recurred at the following periods (compare p. 697). on Melanosis, 1857, p. 18 ; an essay containing the results of the records of 60 cases of melanosis. ' Of Mr. Pemberton's 34 cases of Melanosis of the skin, 1 5 commenced ' in or near a congenital mole, wart, or mark.' 750 PATHOLOGY OF MELANOID CANCER. Between 1 and 3 montlis in 7 cases » 3 „ 6 „ 4 „ 6 „ 12 „ 2 „ 12 „ 24 „ 2 „ I) 24 „ 36 „ 1. „ Seeing this close correspondence in their general pathology, the rules respeotiag operations for melanoid cancers must be the same as for the medullary. (See p. 694.) I have reserved for separate consideration some of the peculiarities of melanoid cancers. Three things in them especially deserve reflec- tion — namely (1) their colour ; (2) their proneness to take their first seat in or near cutaneous moles ; (3) their profuse multiplication. 1. The colour of the melanoid cancers is due to a pigment-forma- tion, corresponding with that which we iind, in the normal state, in the pigment-cells, of the choroid membrane, and in the rete mucosum of coloured skins. Their usual primary occurrence near these seats of natural pigments may, therefore, be regarded as an illustration of the tendency of cancers to conformity, at least sometimes and in some respects, with the characters of the adjacent natural textures. But another meaning of the pigment in melanotic cancers is sug- gested by its likeness to that which accumulates in the lungs and bron- chial glands in advancing years, and in the darkening cuticle of many old persons. The colouring particles are probably difierent in these cases ; they produce difierent shades or tinges of blackness, but their plans of formation and arrangement are in all similar. And the analogy of their formation in the aged, and in some other instances (p. 74), may warrant us in regarding melanosis as a pigmental degeneration of medullary cancer. The chief characters of its minute structures agree with this, especially the gathering of pigment-molecules about the nucleus, their gradually filling the ceU-cavity, till both the nucleus and the cell- wall disappearing, the nucleated cell is transformed into a dark- coloured granule- mass. In all these characters there is an esaot parallel between the transformations of the cells in melanoid cancers and the usual changes of the fatty degeneration. (Compare p. 615 and p. 713.) 2. The proneness of melanoid cancers to grow first in or beneath pigmentary moles is very evident ; and I am not aware that such moles are peculiarly apt to determine the locality of any other tumours ; for. CONNECTION OF MOLES WITH MELANOID CANCER. 751 except a case (p. 701) in which an epithelial cancer grew from, one, I have met with no instance of other than melanoid cancers connected with them.i The fact is, I suppose, quite inexplicable ; but it may be usefully suggestive. It seems a striking illustration of the weakness in resisting disease which belongs to parts congenitally abnormal. It seems, also, to be an evidence that a part may very long remain apt for the growth of cancer, and not become the seat of such a growth, till the cancerous diathesis, the constitutional element of the disease, is established. And this event may be very long delayed : as in a woman, eighty years old, whom I saw with a large melanotic tumour, which had lately grown rapidly under a mole that had been unchanging through her long previous life. But again, this peculiar affinity (if it may be so called) of moles for melanoid cancers, may make us suspect that there may be other, though invisible, defects of first formation in our organs, which may render them, or even small portions of them, peculiarly apt for the seats of malignant and other specific diseases. It is often only the colour that makes us aware of the peculiarity of that piece of a man's skin in which cancer, if it ever occur in him, will be most likely to grow ■- and yet colour is so unessential a condition of texture, that we may well believe that all the more real conditions of such liability to cancer may be present without peculiarity of colour, though being without it, the part in which they exist may not be discernible. I have spoken of the pigmentary moles as becoming the seats of melanotic cancers. It might seem as if the mole were, in some sort, the first stage of the cancer ; but it is not so : the structures and the life of the mole are those of natural skin and epidermis, abnormal in quantity and colour, but in no more essential properties : there are no structures in moles like those of cancer till, at a certain and usually notable time, cancer begins to be formed in them. And here let it be observed, how close is the correspondence in these respects be- tween the pigmentary moles, and the warts that are apt to become the seats of epithelial cancers (p. 733). The patient is usually aware of the time at which a mole, observed as an unchanging mark from birth or infancy, began to grow. In some instances the growth is superficial, and the dark spot acquires a larger area and appears slightly raised by • PivogoS (Klmische Chirurgie, H. i. p. 34) relates three cases of removal of njevi (angeiektasie), which was followed by growth of medullary cancers, at or near the seat of operation. They all appear to have been medullary, not melanotic, cancers ; but the third case may have been melanotic. 752 CONNECTION OF MOLES WITH MELANOID CANCER. some growth, beneath it : in other cases the mole rises and becomes very- prominent or nearly pendnlons. I believe that -when the mole becomes thus prominent, the chief seat of the cancerous formation is in the superficial layer of the cutis and in the place of the rete muoosum ; and that vyhen it only extends itself, the cancerous growth is chiefly in the skin and subcutaneous tissue. In the former case, the cancer- structures are usually infiltrated among the natural structures of the affected part ; in the latter, they generally form a distinct tumour, which may be dis- sected from, though it is closely connected with, the surrounding tissues and the thinned layer of cutis and dark cuticle that covers it. (Fig. 122, p. 746.) The general characters of the growths thus forming correspond, I believe, in every respect with the medullary cancers of the skin and subcutaneous tissue (p. 674) : colour alone distinguishes them ; they are equally prone to multiplicity. Often, in removing a deep-set mela- notic mass, smaller masses are found imbedded in the adjacent fat or other tissue, and sometimes the formation of one or more subcutaneous growths almost exactly coincides with the outgrowth of the mole and its occupation by the cancer-structures. 3. The multiplicity of secondary melanoid formation is often very striking. I have, indeed, seen one case in which, to the last, only the lymphatic glands connected with the primary growth were diseased ; and another in which only the liver and some lymphatics were affected ; l)ut the more frequent issue of the cases almost Hterally justifies the expression that the disease is everywhere. Are we to conclude from this that the multiplication of melanoid cancers is more abundant than that of the medullary cancers, which in other respects they so closely resemble ? I think not. We can easily see aU the secondary melanoid for- mations, even the smallest and least aggregated ; and it is often the colour alone that draws attention to many which, but for it, we should not have noticed. I suspect that equally numerous formations exist in many cases of medullary cancers, but are unseen, being un- coloured. Hjematoid Cancer. This name may perhaps be retained to express a form of cancer which Mr. Hey had chiefly in view when he proposed the name of Funwus Hsematodes.' It is most probable that all the cases to which he gave this name were soft medullary cancers ; and his attention ' Observations in Surgery, p. 239. H^MATOID CANCER. 753 was especially directed to the fact that when the morbid growth pro- trudes through the skin, the protruding portion may have such a shape as, in the conventional language of surgery, is called fungous, and often bleeds largely, and is so vascular, or so infiltrated with blood, that it looks like a clot. The identity of the fungus haematodes of Hey with the medullary cancers was fully recognised by Mr. Wardrop and others ; but unfor- tunately, certain foreign writers, regarding the htemorrhage as the dis- tinctive character of the disease, included under the same term nearly all severely bleeding tumours of whatever kind.' It was an unhappy misuse of Hey's name, by which he meant to express, not a bleeding growth, but one like a clot of blood : and it led to a confusion which is still prevalent. Leaving the term fungus hasmatodes, we may employ that of heematoid cancer, for such as are like clots of blood through the quan- tity of blood that they contain. The likeness is indeed, I believe, only au accidental one, due to htemorrhage into the substance of the cancer, from rupture of some of its thin- walled bloodvessels' It seldom exists in the whole mass of a cancer ; but usually, while some parts have the ordinary aspects of medullary or some other form of cancer, other parts are blood-like. The best illustration of the disease that I have seen is in a large tumour,^ of which one half might be taken as a good type of the brain-like medullary cancer, and the other half as an equally good type of the hffimatoid. This half had been deeply punc- tured during life ; it had bled very freely and the simultaneous bleed- ing into its own substance had, doubtless, changed it from brain-like to blood- like. Probably any cancer may thus be made heematoid ; but the change is peculiarly apt to happen in those which are of the softest texture and most rapid growth, and which are situated where they are least supported by adjacent parts. ' Among the cases thus confused are some strange ones of profuse bleedings from supposed grOTTt.hs, of which little or nothing could be found after death. Such a case is related by Mr. Abernethy ( On Tumotirs, p. 127, note) ; and a specimen from Mr. Liston's Museum is in the Museum of the College, 302 a. It is perhaps impossible at present to say what these diseases were; but I suspect they were medullary cancers with bloodvessels excessively developed, like those of an erectile tumour. ^ Mus. of St. Bartholomew's, Series xxxv. No. 28. 3o 754 STEUCTUBE OF Osteoid Cancer. Miiller assigned the name of osteoid tumour, or ossifying fungus growth,' to a form of disease of whicli, with admirable acumen, he col- lected several cases illustrating these as its distinctive characters ; — that the primary tumour consists chiefly of bone, but has, on its surface and in the interstices of its osseous parts, an unossified fibrous consti- tuent as firm, as fibrous cartilage ; and that, after a time, similar growths ensue in parts distant from the seat of the first-formed, and not on bones alone, but in the areolar tissue, serous membranes, lungs, lymphatics, etc. Mr. Stanley ^ has described the same disease under the name of Malignant Osseous Tumour ; and single examples of it may be found under the names of periosteal exostosis, fibrous osteo-sarcoma, foliated exostosis, etc. Miiller was disposed to caU it osteoid cancer ; and certainly this name is best suited to it, its intimate afl&nity with the other forms of cancer being evident in these things — (1) its correspond- ence, in nearly every particular of structure and of history, with the characters of cancerous disease, as exemplified in the scirrhous and me- dullary forms ; (2) its not unfrequent coexistence with medullary can- cer of the ordinary kind, either in a single mass of tumour, or in difie- rent tumours in the same person ; (3) the uninterrupted gradations between it and the scirrhous and medullary cancers ; (4) its mutations with the same, in hereditary transmission or in secondary productions. I cannot doubt the propriety of calling a disease cancer, in which these facts can be demonstrated ; and I believe that the most probable view of the nature of osteoid cancers would be expressed by calling them ossified fibrous or medullary cancers, and by regarding them as illustrating a calcareous or osseous degeneration. (See p. 629, and compare p. 73.) The primary seat of osteoid cancer is usually some bone ; but it is not limited to bones. In a case by Pott,^ quoted by Miiller, the primary tumour lay ' loose between the sartorius aad vastus internus muscles.' In the Museum of St. Thomas's Hospital there is a tunaour like an osteoid cancer, -which was removed from near a humerus, and ' Ueber oasificirende Schwamme, oder Osteoid-Geachwulste : (Miiller's Archiv, 1843, p. 396. ^ On Diseases of the Bones, p. 163. ' Works, by Earle, iii. 313. I think that No. 2429a in the College Museum may be regarded as an osteoid cancer of the testicle, though the bone-like substance has not the characters of perfect bone. OSTEOID CANCER. 755 another from a popliteal space. In all these cases, the removal of the tumour was followed by the growth of medullary cancers with little or no bone in them. Among the bones, the lower part of the femur is, with remarkable predominance, the most frequent seat of osteoid cancer. Among twenty- seven cases, of which I have seen histories or specimens, fifteen had this part for their seat : the skull, tibia, humerus, ilium, and fibula, were each affected in two cases, and the ulna and metacarpus each in one case. In most cases the osteoid growth occurs coincidently within and on the exterior of the bone, following herein the usual rule of medullary cancers ; but it may exist on the exterior alone : and I have twice seen its fibrous basis in the cancellous tissue of a bone, of which the exterior was surrounded with soft medullary cancer. In the best examples of osteoid cancer, i.e. in those in which its pe- culiar characters are most marked, it presents, if seated on a long bone, such as the femur, an elongated oval form ; if on a flat bone, a bicon- vex form. Its elongated shape on the femur, the swelling gradually rising as we trace down the shaft, and then rather less gradually sub- siding at the borders of the condyles, is almost enough for a diagnosis of the osteoid cancer from other hard tumours. It is like the enlarge- ment produced by simple thickening of the bone or periosteum ; a like- ness which is increased by the smoothness of surface, the nearly incom- pressible hardness, and the considerable pain, which, in general, all these swellings alike present. When we dissect down to an osteoid cancer (taking one on the femur for a type), we usually find the adjacent tissues healthy, except in being stretched round the swelling. Small masses of firm cancer may, however, be imbedded in them, distinct from, but clustered round, the chief mass. The periosteum is usually continued over the cancer, but scarcely separable from it. The surface is smooth, or very lowly and broadly tuberous. A section generally shows that the exterior of the growth is composed of a very firm, but not osseous, substance ; while its interior part, i.e. that which lies nearest to the shaft, and that which is in the place of the cancellous tissue, ia partially orwholly osseous. The two substances are closely interblended where they meet; and their relative proportions difier much in different specimens, according to the progress already made by ossification. The unossified part of the tumour is usually exceedingly dense, firm, and tough, and may be incompressibly hard ; its cut surface uprises 3 c 2 756 STRUCTURE OF like that of an intervertebral fibrons cartilage, or tbat of one of tie toughest fibrons tumonrs of tbe uterus. It is pale, greyisb, or with a slight yellow or pink tint, marked with irregular short bars of a clearer white ; rarely intersected as if lobed, but sometimes appearing banded with fibres set vertically on the bone. The bony part of the tumour, when cleared by maceration, has cha- racters altogether peculiar (Fig. 124). In the central parts it is (in the best-marked specimens) extremely compact, scarcely showing even any pores, white, and dry. To cut, it is nearly as hard as ivory, yet, like hard chalk, it may be rubbed or scraped into fine dry powder. At its periphery it is arranged in a knobbed and tuberous form, the knobs being often formed of close thin grey or white lamellae, whose presenting edges give them a fibrous look,- exactly like that of pumice- stone. In this part, also, the bone is very brittle, fiaky, and piilveralent. In some specimens the whole of the bone has this delicate lamellar and brittle texture ; but more generally, as I have said, the central part is very hard, and this, occupying the walls and cancellous tissue of the shaft, equally with the surrounding part of the tumour, makes of the whole such a compact white chalky mass as the sketch here i-epresents (Fig. 124). In the osteoid cancers of the lym- phatic glands (Fig. 125), and other soft parts, the bone is finely porous, spongy, or reticulated ; or it may be finely lamellar, and look fibrous on its sur- face. It is always soft and brittle, and, often, it has in these parts no regular ■^'S- l^'i- plan, but is placed in small close-set grains or spicules, which fall apart in maceration. In whatever plan or part the bone is found, it has no medulla ; its interstices are filled with cancer-substance. Fig. 124. Section of ths osseous part of an osteoid cancer of the femur. Museum of St. Bartholomew's, Series i. 109. OSTEOID CANCER. 757 Fig. 125. Wlien the salts of lime are removed from the bone with acid, an or- ganic basis-substance remains, which presents the same general aspect as the unossified part of the cancer, while re- taining the lamellar and fibrons arrangement of the bone.' This basis yields gelatine ; and the saline constit- nents are similar to those of ordinary bone, but with a disproportionate pre- ponderance of phosphate of lime (Miiller, loc. cit. p. 412). With the microscope, the unossified part of an osteoid cancer appears fasciculated or banded, and is always very difficult to dissect. In some specimens, or in some parts, it has only a fibrous appearance, due to markings and wrinkles of a nearly homogeneous substance, in which abundant nuclei appear when acetic acid is added. In others, it is dis- tinctly fibrous, but not in all parts with the same plan. The fibres are sometimes moderately broad, about -g-j^Vi!" °^ ^^ ^^^"^ wide, have uneven thorny edges, and, arranged in bundles, look like faggots (Fig. 126, a). Pig. 126. In other parts they are finer, like sharp-edged, crisp, and stiff filaments. Such as these may present a nearly regular reticular arrangement, with well-formed meshes (b) ; or they may be nearly parallel, and construct a more distinctly fibrous texture (o) ; or they may be closely matted and, except in their exceeding toughness, may be like the short, crooked filaments of a fibrine-clot (d). I never saw them presenting the undulating glistening aspect of the filaments of an ordinary fibrous tumour, or of natural fibrous tissue. Pig 125. Section of an inguinal lymphatic gland, with osteoid cancer, after maceration. Natural size. Museum of St. Bartholomew's Series i. No. 109. Pis 126 Pibruus tissue of osteoid cancer in different forms, as described in the text. Magnified 400 times. Mus. Coll. Surg. No. 809. 758 STRUCTURE OF OSTEOID CANCER. Fibrous tissue, in one or other of the forms just mentioned, makes up the main mass of the unossified part of the cancer. But other elemen- tary forms usually exist with it. Sometimes cancer-cells are mingled ■with it, as if imbedded in the interstices of the fibres. They aTe of ordinary form, not difiering from those of common sohirrous can- cers in anything, unless it be in that they are smaller and less plump. Sometimes granule-masses and minute oil-moleoules are scattered among the fibres. Both these and the cancer-cells appear foreign to the fibrous tissue, as mingled with it, not part of it ; but, if acetic acid be freely added, the fibrous tissue becomes clearer, and we find (what may before have been very obscurely seen) abundant nuclei imbedded in it. They are generally oval, smooth, well defined, from ^-^Ijjtj- to -^-^ of an inch in length ; but, I think, as the fibrous tissue becomes more perfect, they shrivel and become crooked, or like little stellate cracks in the basis-substance ; or else that, as it ossifies, they are imbedded in the accumulating lime-salts, and become the lacunae of the bone.' Structures such as these exist in the osteoid cancers of all parts ; and when a series of those occurring in the lymphatics and other organs can be compared with the primary disease on a bone (for example), I believe no other difierence will be found, than that the secondary cancers are less definitely fibrous, and have a larger proportion of can- cer-cells or granule-masses, than the primary disease. These, however, are no greater difierences than may be found in comparing the less with the more firm parts of a single primary mass of the disease. The microscopic characters of the ossified part of the cancer are those of true bone, but rarely of well-formed bone. In some parts — especially in the secondary cancers — there is only an amorphous granu- lar deposit of lime-salts, like those inordinary calcareous degenerations. In other parts the lacunae of true bone are distinct, but they are small, and their canalicules are few and short, and without order. Haversian canals also exist with these, but they have not a large series of concen- tric lamellffl like those in normal bone. In other instances, but these are rare, the lacunae are more nearly perfect ; their canalicules commu- nicate with one another, and with the cavities of the Haversian canals. The bone with distinct lacunee and canalicules is not found exclusively in the primary cancer, or near the natural bone on which it is seated ; here, indeed, the complete bone is most frequent ; but it may be found, also, in the secondary growths in the glands and elsewhere. These ' Gerlach also described this in hie Ecsay, Ber Zottenhnhs und das Osteoid, p. 62. PATHOLOGY. 759 differences between the bone of the primary and that of the secondary osteoid cancers, like the similar differences of their nnossified parts, are only differences of degree, such as may be found in separate parts of the same mass ; they are, probably, to be ascribed only to more recent or more rapid gro-wth. The foregoing description of the osteoid cancers may suf&ce to show that their nearest af&nities, judging by the structure of their unossified part, are to the fibrous cancers, of which I spoke at p. 628, and to the firmest of the medullary cancers (p. 661). When abundant cancer- cells are present, they most nearly resemble the latter form ; when they are almost wholly fibrous, the former.' Their peculiarity, as cancers, ia in their ossification. In this they may seem to approximate to the non- cancerous tumours ; but, really, they remain, even when ossified, very distinct from any of them. I have enumerated (p. 539) the characters by which they are distinguished from both the hard and the cancellous osseous tumours ; and the difference is as complete, and, I believe, as constant, as that of their fibrous basis is from the structure of any non- cancerous fibrous tumour. If we consider only their osseous part, the osteoid cancers most nearly resemble those soft medullary cancers which have the most abun- dant internal skeletons. There is, indeed, no absolute line of distinction to be drawn between the two. It may be very evident, in the typical specimens of each, that the skeleton of the soft medullary cancer is formed by ossification of the intersecting and overgrown infiltrated periosteum (p. 660) ; and that the bone of the osteoid cancer is formed by ossification of the proper cancerous substance ; but, between these extremes or types, there are numerous instances in which the two con- ditions are mingled, or through which the one condition merges into the other. And this is no more than we might expect, seeing the frequency with which the osteoid and the medullary disease appear together, or in succession. The materials for a general pathology of osteoid cancers are very scanty : yet one may be written ; for if we collect only well-marked examples of the disease, their histories will be found consistent with one another, and distinct from those of the other groups of cancers. ' A case of osteoid cancer is minutely related by Mr. Sedgwick {Br. and For. Med.-Ghir. Rev. July 1855), in which there were secondary formations in the claTicle, thorax, and head, but the tumours in the head assumed the characters of ordinary en- cephaloid, which, Mr. Sedgwick thinks, favours the opinion expressed in the text of the relation of these osteoid cancers to the medullary cancers. ^60 OSTEOID OANCEE. Among twenty cases, fifteen occurred in men, and five in women : a preponderance on the male side approximating that observed in epithelial cancers, and (if we may trust to a result from so few cases) contrasting, in a striking manner, with the distribution of medullary and scirrhous cancers. Among nineteen of these patients, five were between 10 and 20 years old ; nine between 20 and 30 ; four between 30 and 40 ; one between 40 and 50 : — proportions which again do not correspond with those in any other form of cancer. Among thirteen of the patients, five distinctly referred to injury as the origin of the cancer, and two to previous disease in the part ; the others assigned no cause. The growth of osteoid cancers is generally rapid, and accompanied with severe pain in and about their seat; their multiplication in the lymphatics and in distant parts takes place with proportionate rapidity ; and intense cachexia occurs early in their course. There are exceptions to these things; but in all these respects the majority of the osteoid cancers appear as malignant as the medullary, and are as quickly fatal. Among fourteen cases, of which the ends are recorded, three died in consequence of amputations. Of the other eleven, four underwent no operation, and aU died in or within six months from the first notice of the disease. Of the remaining seven, in all of whom the disease was once or more removed, and in all of whom it recurred before death, two died in the first year of its existence, one in the second, one in the third ; but one lived for seven and a half years, another for twenty- four, and another for twenty-five years. In all the instances of speedy death, secondary osteoid cancers existed, and the result was probably to be assigned to these and to the coincident cancerous cachexia ; for the primary growths have little tendency to ulcerate or protrude, and they seem to contribute directly to death by their pain alone. In the instances of life extended beyond twenty years, the disease appeared to recur only near its primary seat. The most frequent seats of the secondary, or recurrent, osteoid cancers are the lymphatic glands, in the line from the primary seat to the thoracic duct, the lungs, and the serous membranes : but it is not limited to these ; it may be found even in the bloodvessels, as in a case which I shall relate, and has been traced in the thoracic duct.' Its ' Cheston, in Philos. Trims. 1780, Ixx. PATHOLoay. 761 condition in these secondary seats need not be described : in stracture it resembles in them the primary disease, with only such differences as are already mentioned ; in plan it is like the growths or infiltrations of secondary mednllary cancers in the same parts. But it is to be observed that, sometimes, the secondary cancer is medullary, without osseous matter. I have mentioned three instances of this (p. 754), and Pro- fessor Langenbeok told me that he once removed an upper jaw with a bony growth, and the patient died soon after with well-marked medul- lary cancer in the lungs. The reverse may occur : for the same distinguished surgeon told me that he once removed a humerus with a medullary cancer, and the patient died with osseous tumours in the lungs.' The ordinary course of osteoid cancers may be known by the fore- going account of them, and by the cases recorded by MiiUer and Mr. Stanley.^ But deviations from this course are sometimes observed, which it may be well to illustrate by cases that displayed the disease in an unusually acute, and an equally unusual inactive, form. A girl, fifteen years old, was admitted into St. Bartholomew's Hospital, with general feebleness and pains in her limbs, which had existed for two or three weeks. They had been ascribed to delayed menstruation, till the pain, becoming more severe, seemed to be concentrated about the lower part of the back and the left hip. A hard deep-seated tumour was now felt, connected with the ala of the left ilium. This gradually increased, with constant and more wearing pain ; it extended towards the pelvic and abdominal cavities ; the patient became rapidly weaker and thinner; the left leg swelled; sloughing ensued over the right hip : and thus she died cachectic and exhausted, only three and a half months from her first notice of the swelling. A hard lobulated mass was found completely filling the cavity of the pelvis, and extending across the lower part of the abdominal cavity. It was firmly connected with the sacrum, both ischia, and the left ilium ; it held, as in one mass, all the pelvic organs ; and the uterus was so • A case is reported by Mr. Quain in Brit. Assoc. Med. Jour. Oct. 26, 1855, p. 70, of osteoid cancer, in which there were secondary formations both in the cavities of the thorax and abdomen. The microscopic appearances are related by Dr. Hillier and Sir W. Jenner, in Trans. Path. Soc. vi. p. 317. 2 Loc. cit. See also Gerlach's two cases (Joe. cit.), and that by Hunter, in the Catalogue of the College Museum, ii. p. 176. 762 PATHOLOGY OF OSTEOID CANCER. imbedded in it, and so infiltrated with a similar material, that it could scarcely be recognised. The general surface of this growth was uneqiial and nodnlar. It was composed of a pearly-white and exceedingly hard structure, in which points of yellow bony substance were imbedded, and which had the characters of osteoid cancer perfectly marked. The ihum, where the tumour was connected with it, had the same half-fibrous and half- bony structure as the tumour itself. The common iliac veins, their main divisions, and others leading into them, passed through the tumour, and were all distended with hard substance like the mass around them. From the common iliac veins a continuous growth of the same substance extended into the inferior cava, which, for nearly five inches, was distended and com- pletely obstructed by a cylindriform mass of similar fibrous and osseous substance, one and a quarter inch in diameter. At its upper part this mass tapering came to an end near the liver. The lower lobe of the right lung was hollowed out into a large sac, containing greenish pus and traversed by hard coral-like bands, which proved to be branches of the pulmonary artery plugged with firm white substance intermingled with softer cancerous matter, and resembling the great mass of disease in the pelvis. The rest of the lung was healthy, with the exception of some scattered greyish tubercles ; and so was the left lung, except in that there were a few small abscesses near its surface, with hard, bone-like masses in their centres, like those in the branches of the right pulmonary artery. The skull, brain, pericardium, heart, and all the abdominal organs, were healthy.' I suppose that few cases of osteoid cancer can be found equal with this in the acuteness of their progress. The opposite extreme is illustrated by a case communicated to me by Mr. Thomas Sympson, and exactly corresponding with one of which the specimens are in the Museum of the College.^ A swelling appeared in the upper arm of a woman thirty- two years old. After ten years' growth, when it had increased to seven pounds weight, it was removed by Mr. Hewson. It had the characters of osteoid cancer. The patient completely re- covered from the operation ; but, about a year after it, a new tumour appeared about the humerus, and at the end of four years had > The specimens from this case are in the Museum of St. Bartholomew's, Series siv. No. 60. 2xNo. 3244-5-5A. VILLOUS CANCER. 763 acquired a huge size, and a weiglit of fifteen and a half pounds. For this, which proved to be a similar osteoid growth, the arm was ampu- tated at the shoulder-joint. She recovered from this operation also ; but the disease returned in the scapula, and, in about ten years after the amputation, and twenty-four years from the beginning of the disease, she died. Villous Cancek. The name of Villous Cancer (Zottenkrebs of Rokitansky) has been applied to growths possessing a papillary or villous form, with inter- spersed cancerous elements, which occasionally project from mucous or other free surfaces. But it is probable that under this name have been included growths having the villous character, which in their structure were altogether innocent, such as have been already referred to on p. 592. It would appear that the dendritic growths of a medullary cancer may not unfrequently assume a villous or papillary character, so that the cell-elements of this form of cancer may be mingled with projecting villi' (p. 670). Even more readily, the finely warty or cauliflower- like cylindriform epithelial cancers may take on the villous form (p. 699).^ But though many new villous growths may thus be excluded from the group of villous cancers, yet there would still appear to be cases, which occur more especially in the urinary bladder, to which the term villous cancer may be applied with advantage, so that it may be well not altogether to discard it. For these cases, then, both for their own sake, and for the illustrations they afford of a remarkable mode of growth, which probably prevails throughout a wide range of morbid structure, a separate description may be given. The plan of their construction has been well described by Roki- tansky,^ from whose essay I make the following abstract : — ' Dr. Bristowe {Trans. Path. Soc. xi. p. 94) relates a case of cancer of the stomach, in which cancerous growths were mingled with villous and papillary projections. ^ In St. Bartholomew's Museum are specimens of such villous cancers in the gall- bladder (xix. 3) and on the peritoneum (xvi. 60). See also a case by Mr. H. Gray, (Trans. Fath. Soc. vi. p. 183) of villous and epithelial cancer of the pharynx and oeso- phagus, and one by Mr. Sibley {Ibid. viii. p. 18) of villous growth on the dura mater. * Ueber der Zottenkrebs in the Sitzungsberichte der Kais. AJcad. April 1852. In a case of villous cancer of the urinary bladder which Dr. Joseph Bell has described and figured {Edin. Med. Jour. May 1863), the appearances corresponded very closely with tie description given by Eokitansky of the ' dendritic vegetation ' quoted in the text. 7(54 DENDfilTIC VEGETATION. The villous growth consists, in its stem, of a fibroid membranotis structtire, on which villons flocculi are borne, as buddings or sproutings of the stem or its branches. The ' dendritic vegetation,' of which these sproutings are an example, has been already often referred to, especially in the account of the stroma of medullary cancers (p. 670). Other examples are in the en- dogenous growths of the cysts ; in the Lipoma arborescens of MiiUer — i.e. the tufted and villous growths on synovial membranes ; and in the intracystio growths of thyroid and other gland- substance illustrated in Lecture XXIII. The ' dendritic vegetation ' appears originally as a hoUow club- shaped or flask-shaped body, consisting of an hyaline structureless membrane. It is either clear and transparent or opaque — i.e. filled with granules, nuclei, and nucleated cells (^ig. 112, p. 670) : externally, ,<^-T^ Fig. 127. it is either bare or covered with epitheh'um. The vegetation does not usually develop itself into villous growths directly on the mucous or other surface on which it rests, but on the bars of some previously formed meshed-work, such as is described at p. 669. The further de- velopment of the vegetation is commonly in one of two chief plans. Either the mfimbranous flask grows uniformly into a sac, which contains a serous fluid, or is filled with a delicately fibrous meshed-work ; or else it grows and sprouts in various degrees and methods. Of this sprouting growth, which alone is illustrated in villous cancers, there are three types. They are represented in the adjoining copy of Roki- tansky's sketches. In the first (Fig. 127, A), the flask grows out in low, nearly hemi- spherical sprouts. These may contain serous fluid, as in the cystic disease of the choroid plexuses ; or they may be filled with gland-struc- tures, as in the thyroid and mammary intracystic growths ; or they may Fig. 127. Methods of growth of the 'dendritic vegetation,' from Eokitansky. j\I;(gDified 30 times : explained in the text. VILLOUS CANCER. 765 contain and be covered with cancerons structures, as in the instance of the small excrescences within a cyst in a cancerous kidney from which Fig. 127, A, was drawn. In the second type (Fig. 127, b) the flask grows lengthwise into a tube, and shoots out new ones, which grow to secondary tubes, and again shoot out others, which grow to tertiary tubes, and so on. On these outgrowths abundant broader sprouts and buds appear. Thus a multiform ramified dendritic structure is produced. Its sprouts may be filled with connective tissue, or fat (as in Lipoma arborescens), or with cartilage and bone (as iu the pendulous growths of these tissues within joints) ; or they may contain and be covered with the elements of the cancer, as in the villous cancer of the urinary bladder, of which part is sketched in Fig. 127, B. In the third type, illustrated by Fig. 127, C, from another villous cancer of the bladder, the flask grows with considerable dilatation into a stem, which gives off' branches that do not ram.ify further, but break up at once into a great number of flask-shaped sprouts. The usual arrangement of the bloodvessels of the dendritic vegeta- tions is that (as in the synovial fringes and the villi of the chorion) a vessel runs along the contour of the vegetation, forming frequent loops, and supplying to the stem, as well as to each of the sprouts and branches, an ascending and a descending vessel. There are, however, pouches in the vegetation in which only a single vessel exists, and ter- minates with a rounded end. The vessels are generally large examples of the so-called colossal capillaries, thin- walled, with longitudinal, and sometimes also transverse, oval nuclei in pellucid membrane.' In structure, the vegetation in villous cancers contains, together with its bloodvessels, a quantity of nuclei and cells, in some of which endogenous developments are taking place, and, especially at the ends of its sprouts, structureless simple and laminated vesicles. On the surface, epithelial cells, with cancer-elements, adhere to it ; the latter consisting of nucleated cells of various shapes, which form a soft, or a more consistent, deposit, and are often present in such quantity that they make up the greater part of the morbid mass into which then the vegetations seem to grow. In other cases, a fibrous texture develops itself in the interior of the veo'etation, and with it cancerous elements form. In this state the villous cancer, in consequence of the accumulation of the fibrous and 1 Gerlach's account of the bloodvessels nearly corresponds with this {Der ZoUen- Jerebs und das OMmid, Taf. i. Fig. 3) 766 COLLOID CANCEK. cancerous stmcturea, appears as a collection of excrescences whicli, in their stems as well as in their branches and sprouts, and especially towards their free ends, are swollen thick and big. They are here filled with a deHcately-fibrillated meshed- work ; and, as their swollen ends are often mutually compressed, the whole appears like foliage growiag on shorter or longer stems. When the villous cancer is cut through to its base, one finds a tolerably abundant, porous, fibrous stroma, which, on nearer examina- tion, presents a compressed meshed-work, traversed by fissure-like apertures. Its bars consist of a hyaline substance, beset with oblong corpuscles, and here and there dividing into filaments of connective tissue. The connective-tissue stroma is continuous with the submucous coat, or with the deeper layer of the mucous membrane, on which the growth takes place.' In this stroma new-formed cell- elements of the cancer are produced. In all the instances that have been fully examined, the cell-forms met with on the villi' and within the stroma have been like those of medullary or melanotic cancer. But I believe Rokitansky is right in the anticipation that certain epithehal cancers will be found to grow on the same plan as the villous. I have referred (p. 702) to instances of warty epithelial cancers growiag where they could not have had origin in natural papillse. Virchow also describes arborescent epithelial can- cers growing in cavities where no papillae could weU be ; and I have seen the same in cysts within what I believe to be an epithelial cancer of the clitoris.^ • The shapes of the most exuberant epithelial cancers so imitate those of the villous cancers, that it seems highly probable that some of them are produced by the dendritic mode of growth rather than by the enlargement and deformity of papillse. The correspondence of the stromal structures, and the exact simi- larity of the cancer- elements, found in the medullary and melanoid cancers on the one hand, and in the villous cancers on the other, are enough to warrant us in regarding these as varieties of the more general form. This view is confirmed by numerous oases in which the central and basal parts of the growth are like common medullary cancer, its surface being villous ; and by some in which villous cancers appear as secoodary growths with primary medullary cancers of the more common kind ; thus, e.g., the former occur on the peritoneum, with the latter in the ovaries. It may be anticipated that the histories of the villous can- ' A description, with illustrative dra-wings, of a case of villous cancer of the uterus, is given by Forster in his Atlas, pi. 24. ^ Museum of St. BartholomeVs, xxxii. 39. COLLOID CANCER. 767 cers will equally coincide with those of the medullary and melanotic ; but, as yet, the cases recorded are too few for the deduction of any general rules. Colloid Cancee. Many names have been given to this form of cancer — Colloid, Alveolar, Gelatiniform, Cystic, and Gum Cancer. I have adopted the first, because it seems to be now most frequently used, and expresses very well the most obvious peculiarity of the diseased structure, the greater part of which is, usually, a clear flickering or viscid substance, like soft gelatine. The most frequent primary seats of colloid cancer are the stomach, the intestinal canal, uterus, mammary gland, and peritoneum. As a secondary disease, it afl^ects most frequently the lymphatic glands and lungs, and may occur in many other parts. To the naked eye, a colloid cancer presents two chief constituents — ■ an opaque-white, tough, fibrous-looking tissue, which intersects, parti- tions, and encloses its mass ; and a clear, soft, or nearly hquid material, the proper ' colloid ' substance. According to the proportions in which these are combined, the general aspect of the disease varies. When the fibrous texture is predominant (as I have twice seen it in the central parts of colloid cancers of the breast), it forms a very tough, white, fasoia-like mass, in which are small separate cysts or cavities filled with the colloid substance. In the opposite extreme, large masses of the colloid substance appear only intersected by fibrous white cords or thin membranes, arranged as in areolar tissue, or in a wide-meshed net-work. These extremes often exist in diflerent parts of the same mass, and with them are various intermediate forms, in which, probably, the essential characters of the disease may be best learned. In these, the cancerous substance appears constructed of small thin- walled cysts, cells, or alveoli, arranged without apparent order, and filled with the transparent colloid substance. The cysts or alveoli are typically of round or oval form, but are changed from this, as if by mutual pressure ; some may appear closed, but the great majority communicate with those around them, through apertures like imperfections in their walls. They vary from an inch in diameter to a size as small as the naked eye can discern. The largest cysts, and the least abundant fibrous tissue, are usually at or near the surface of the mass ; and in these large cysts, when the colloid substance is emptied from them, we can generally see intersecting 768 MICEOSCOPIC STRUCTURE OF bands, or incomplete partitions, as if they were formed by the fusion of many cysts of smaller size. The walls of the cysts appear formed of delicate white fibrous tissue, but cannot be separated from the sur- rounding suhstance, and are continuous with the coarser bands or layers of fibrous tissue by which the cancerous mass is intersected. The colloid matter is, in different parts or in different instances, various in consistence ; resembling a thin m.uoilage, starch-paste, the vitreous humour, size gelatine, or a tenacious mucus. In its most nor- mal state, it is glistening, translucent, and pale yellowish ; but it may be colourless, or may have a light green, grey, pink, or sanguineous tint ; and may become opaque, whitish, or buff-coloured, by (apparently) a fatty or calcareous degeneration ; or, in the extreme of this degenera- tion, may look like tuberculous matter. In water, or in spirit, it oozes from the alveoli, and floats, in light cloudy flocculi ; and when the surface of the cancer is exposed by ulceration or by rupture, it is dis- charged from the opened alveoli and lies on them like a layer of mucus. The colloid cancers have, usually, in the first instance, the shape of the part that they affect ; for they are always, I believe, infiltrations of the affected part, whose tissues are gradually removed and super- seded by their growth. But the growth of the colloid cancer enlarges and surpasses the part in which it is seated, and produces, in such an organ as the breast or the lymphatic glands, a considerable rounded and tuberous firm swelling, or, in such an one as the stomach or the peritoneum, a flattened expanded mass with more or less of nodular or tuberous projection. The extent of growth is sometimes enormous, especially in the peri- toneum, in which, as in a case related by Dr. Ballard,' the greater part of the parietal and much of the visceral portion may be infiltrated with the morbid structure, either in a nearly uniform layer, or in nodulated swellings formed of groups of cysts, and sometimes projecting far into the peritoneal cavity. The cavity itself may, in these cases, contain free colloid matter, discharged, I suppose, from the open superficial alveoli, and the abdominal walls may be thus distended, with a fluctua- ting vibrating swelling like that of ascites.^ ' Med.-Chir. Trana. xxxi. 119. In Dr. Ballard's case, six quarts of free colloid matter were removed from the peritorial cavity after death. I remember an exactly similar case in which, I think, the quantity removed must have been greater, and in which it certainly appeared to be derived from the dehiscence and constant discharge of the alveoli. In the Museum of the College, No. 294, is a mass of peritoneal colloid cancer, from eight to ten inches in its diameters, which was removed from the lower surface of a liver. COLLOID CANCER. 769 It IS not unfrequent to find one or more large and thick-walled cysts near or attaclied to masses of colloid cancer, and imitating the characters of sach proliferons mnltilocular cysts as are found in the ovaries. They are usually filled with colloid matter, and their Hkeness to the ovarian cysts may confirm the belief that many of the latter are really colloid cancers of the ovaries. Moreover, colloid cancer is sometimes found mingled in the same mass with medullary cancer. This is, indeed, frequent in the digestive canal. Villous and melanotic cancers have been similarly combined with it ; and, more frequently, in different parts of the same person, the medullary and the colloid are found in distinct masses. Microscopic examination of fragments of colloid cancer brings into view an arrangement of delicately fibrous and lamellar structures— the stroma^imitating, in miniature, the larger appearances visible to the naked eye. Fine tough fibres, or fibred membranes, are ar- ranged in curved bundles and lamellffi, which, by their diver- gences and interlacements, en- circle or enclose oval or spherical spaces, containing the colloid substance.' The enclosed spaces are seldom complete cavities ; they communicate freely with one another ; and both in their plan, and in the general aspect of the tissue, remind one, as Lebert says, of the structure of a lung, with its communicating air-cells. The fibres are very fine, but appear stiff and tough, not undulating or easily parting ; they are but little and slowly changed by acetic acid. Elongated nuclei are often seated on these fibres, and sometimes, Lebert says, elastic fibres are mingled with them. The colloid substance fills all their interspaces, not merely the cavities which they circumscribe, but, as it were, mere crevices between the fibres, and spaces in the walls of the larger cavities. Fig. 128. Fibrous tissue of a colloid cancer of the breast. Magnified 70 times. ■ Mr. Sibley, in a paper in the Trans. Med.-Chir. Soc. ixxix. p. 261, states that the stroma of colloid in its most characteristic form- assumes the shape of a convoluted membrane, which in places is so thin and transparent, that its presence might be overlooked. But in other places well-defined fibres may be seen, which here and there expand so as to be continuous with, and evidently form a part of, the membrane ous stroma. 3d 770 MICROSCOPIC STEUCTURE OF The colloid substance generally appears, however magnified, clear and structureless ; it might be invisible but for the seeming filamentous texture produced, as it often is in spread-out masses, by its folds and creasings. Sometimes the colloid material is sprinkled with minute dots, like oUy or fatty molecules,' which to the naked eye may give it a pecaliarly milky or ochrey aspect ; and sometimes it is beset with clusters of such molecules, resulting apparently from the degene- ration of imbedded nuclei or imperfect cells. "With these, also, crystals of the triple phosphate, cholestearine, and some peculiar fatty matter,' may be mingled. Lebert ^ has published an exact analysis of this coUoid matter by Wurtz. The main results are, that it is quite unlike any variety of ge- latine, being insoluble in water, and containing only 7 per cent, of nitrogen, a peculiarity which distinguishes it as well from all protein- compounds, and from the materials of which (imperfectly and impurely as they have been examined), the essential structures of other cancers are composed. Imbedded in the colloid substance, but in very uncertain quantity, are corpuscles of peculiar form. According to Lebert (of whose description and sketches I again gladly avail myself), they are chiefly these : — (1.) Nucleated cells lie free in the colloid substance, or inclosed within large brood-cells, or grouped like an epithelium on the bounda- ries of the alveoli or cysts. These, the so-called colloid corpuscles, are small, granular, moderately transparent cells, of irregular shape, from -rJ^^ to tt^Vtt o^ ^^ inch in diameter, with small nuclei or none. These are, probably, cancer-cells hindered and modified in their development by the peculiar circumstances of their formation ; for, with such as th''se, more perfect cancer-cells are sometimes found. (2.) Large compound cells, mother-cells or brood-cells, which in typical specimens (Fig. 129, a) are from ^^ to -g^ of an inch in dia- meter, are in some instances very numerous. They are very pale, oval, round, or tubular, and lie in clusters : some of them display a lamellar surface, indicated by concentric boundary-lines ; and they inclose one large granular nucleus, or several of smaller size imbedded in their general granular contents, or, together with such nuclei, complete nu- cleated cells like cancer-cells. ' But the observations of Sir W. J enner (Proc. of Pathol. Soc. 1851-52, p. 323) makp it probable that these are granules of phosphate of lime. 2 Luschlia, in Virchow's Arckiv, iv. 412. ' In Virchow's Arrhiu, iv. 203. COLLOID CANCER. 7Y1 (3.) Large laminated spaces (Fig. 129, b) are also found of nearly ciystalline clearness, from jTj- to -j-J-j- of an inch in diameter. These are usually oval and grouped, so as to form a soft parenchyma. Between the lamellse of their walls elongated nuclei are scattered ; in the interspaces between them are clusters of small nucleated cells and nuclei ; and they inclose brood-cells in the cavities surrounded by their concentric lamellae. Fig. 129. Whether we consider the larger or the minuter characters of this colloid cancer, it seems difficult to believe that such a structure can have any close affinity with the cancers I have already described ; they appear, at first sight, to have scarcely anything in common. Hence, some have denied altogether the cancerous nature of this disease.' But if we look, not to its structure alone, but as well to its clinical history (so far as it is illustrated by the great majority of the recorded cases), we shall find in it all the distinctive features of the cancers. Thus (1), its seats of election are, remarkably, those in which the medullary can- cers are, at the same time of life, most apt to occur ; (2) like the typi- cal cancers, the colloid infiltrates, and at length supersedes and re- places, by substitution, the natural tissues of the affected part ; (3) like them also, it is prone to extend and repeat itself in lymphatic glands, the lungs, and other parts near to or distant from its primary seat ; ^ (4) Fig. 129. Structures of colloid cancer described in the text. From Lebert (Virehow's Archiv, iv. Taf. v.) and Eokitansky [Ueber die Cyste, Taf. vi.) ' Mr. Sibley especially, from an examination of nine cases, 'which have fallen under his own observation, has concluded that colloid is a disease perfectly sui generis, and is neither of a cancerous nature, nor frequently associated with cancer. 2 CoUoid cancer was thus multiplied in ten out of eleven cases recorded by Lebert. In a case by Dr. Warren {Med.-Chir. 7¥ans. xxvii), the multiplication was to an amount scarcely surpassed by any medullary cancers. It is true that it is not un- frequently limited to the stomach, or rectum and the adjacent lymphatic glands ; but this is equally observable in the cases of villous and other medullary cancers, and I suspect is only an example of a general rule, that cancers (of whatever kind) on exposed surfaces are, on the whole, more apt to remain single than those growing in other p.nrts. 3 d2 772 CYSTS COMBINED WITH CANCERS. the colloid is often associated with, other forms of cancer in the samo mass, or in different tomonrs in the same person ; (5) it appears as apt as any other form to recur after removal ; (6) it may be derived, hereditarily, from a parent having scirrhous cancer, or a parent vfith colloid may have offspring with medullary cancer. These facts seem enongh to prove the right of including the colloid with the generally received forms of cancer ; certainly they are enough, if we can explain the peculiarities of the colloid cancer as the result of any known morbid process in snch elemental strnctm-es as, in other condi- tions, might have been conformed to the ordinary types of cancer. And such an explanation is not impossible, for, as Rokitansky shows, the colloid cancer has a near parallel in many cyst-formations in the normal structures, and especially in those forms of bronchocele in which abun- dant cysts, full of viscid fluid, are formed in the growing thyroid gland. It seems, therefore, a reasonable hypothesis that the peculiarities of the colloid or alveolar cancer are to be ascribed to cystic disease occurring in elemental caoicer-structnres. Such a cystic disease may ensue in a medullary or other cancer already formed ; but in the well-marked and uniformly constructed colloid cancer, it is probable that the deviation to the cystic form ensues in the very earliest period of the cancer- structures, while each element is yet in the nascent or rudimental state. Such may be the explanation of the structures of those cancers in which the formation of cysts is carried to its maximum ; and I have reserved for this place an account of the various combinations of cysts with cancers of all kinds — combinations giving rise to many singulari- ties of appearance, of which I omitted the description in earlier Lec- tures, that I might once for all endeavour to explain them. And first, we may divide these cases into those in which the cysts are formed independently of the cancer-structures, and those in which they are, or appear to be, derived from them. In the first class vfe may enumerate many cases in which cysts and cancers are in only accidental proximity. For example, a scirrhous cancer may occupy part of a mammary gland, in the rest of which are many cysts that are in no sense cancerous, or of which the chief lacti- ferous tubes are dilated into pouches or cysts (see p. 606). And such a cancer, in its progress, may enclose these cysts, and they may, I be- lieve, remain for a time imbedded in it. In like manner, the ovary, or any other organ, being already the seat of common cysts, may become CYSTS IN CANCERS. 773 the seat of cancer ; and the two morbid structures may become connec- ted, though not related. In this class, also, may be reckoned the cases in which cancers grow from, the walls of common cysts ; i.e. of cysts which did not originate in cancer-structures. Thus medullary cancers may grow, especially in • the villous form, from the walla of ovarian cysts, which have themselves no cancerous appearance.' There- may be other methods in which, as by a sort of accident, cysts and cancers may thus become connected ; but these are the chief exam- ples. In the second class, including those in which the cysts appear to be derived from cancer-structures, we find numerous varieties, which may be studied as a series parallel with those of the simple and the proliferous cyst-formations in the natural structures, or in innocent tumours. (Compare Lectures XXII. and XXIII., and p. 433.) (a) Cysts filled with fluid, like serum variously tinted, and in their general aspect resembling the common serous cysts (p. 399), are often connected with cancers, especially with those of the medullary form that grow quickly or to a great size. There may be one or many of such cysts, lying at the surface, or imbedded in the substance, of the cancer. Sometimes, a single cyst of the kind enlarges so as to surpass the bulk of the cancer, exceedingly confusing the diagnosis.'' In other cases so many cysts are formed, that the tumour appears almost wholly com- posed of them, the cancerous structure only filling the interstices be- tween their close-packed walls.' Such cases might justly be grouped as a ' cystic variety ' of medullary cancer. Cb) Sanguineous cysts are found, as often as the serous, in connec- tion with the medullary and other cancers ; and the changes which the blood undergoes in them add not a little to the multiformity of ap- pearances that the cancerous masses may present. (c) The colloid cysts here find their type (p. 412) ; not only as constructing the peculiar variety of cancer just described ; but as being- mingled with ordinary cancerous growths ; for it is common to find with such growths, especially in the abdomen and pelvis, cysts filled with thickly- viscid material, like mucus, or half-liquid jelly, in all the varieties of tint that we see in the cystic disease of the kidney or of the thyroid gland. ' Museum of St. Bartholomew's, Series xxxi. No. 20. 2 Bruch {Die Diagnose der losartigcu Geschwiilste, p. 1) ; Mus. Coll. Surg. 281. ' Mus. Coll. Surg., 277, 279, 280, etc. ; Mus. St. Bartholomew's, xxxy. H, and others. 774 EELATIONS OF COLLOID TO OTHER CANCERS. (d) Wliile thus the principal varieties o£ simple or barren cysts are found in ca,ncerous growths, as in the original tissues, or in simple tumours, so m.ay we also trace in them the production of prolifei'ous cysts; i.e. of cysts from whose inner surfaces cancerous growths arise, corresponding with the glandular growths that may fill the cysts in the mammary or thyroid gland (p. 424). I have already often referred to this (pp. 434, 657, etc.) ; and now need only add that such endogenous growths are often to be found in the alveoli of the colloid cancer. Clus- ters of clavate, or flask-shaped villous processes, Hke those formed in the early stages of the dendritic vegetation of villous cancer (p. 764), spring from the wall of the alveolus. With laminated walls, and can- cer-structures, or new cysts in their cavities, such villous growths crowded together probably constitute the structures which I have des- cribed after Lebert (p. 777, Pig. 129, c).' To less perfect endoge- nous growth we must, I suppose, ascribe the cancer-structures which are found disorderly mingled with the colloid contents of the alveoh. Respecting the history of colloid cancer, the number of well-record- ed cases, especially of those in which external parts were its primary seat, is too small to authorize many general statements. Lebert has shown, by his collection of cases, that it generally corres- ponds with the history of scirrhous and medullary cancers ; that the cases are about equal in the two sexes ; that the greatest absolute fre- quency is at the middle period of life ; that the disease is very rare in childhood ; ^ that it is probably of somewhat slower average progress than the medullary cancers ; that it more slowly affects the lymphatics and the organs distant from its primary seat ; that, in general, its symptoms in each part correspond with those of other cancers affecting the same part and this summary, I believe, includes all that can be pru- dently said upon the matter. FiBEOus Cancee. Anaong the Cancers it may, perhaps, be as well to arrange those tumours which, in the first edition, I classed, by the name of Mahgnant Fibrous Tumours, with the Fibrous Tumours. For although in their ' Compare Lebert's figures with those of Eokitansky ( Ueber die Cyste, pi. i v. fig. 16) ^ He adduces two cases of children, in which one was two, the other one and a half, years old. Mr. Edward Bikersteth has observed two cases of colloid cancer of the kidney in children, one of whom was three and a half the other eleven, years old. FIBEOUS CANCERS. 775 structure they do not contain ttose ce]l-forins whict we are in the habit or regarding as especially cancerous or malignant, yet in their tendency to recur, and to produce secondary formations of a similar structure in internal organs, and in the influence which they evidently exercise in shortening the lives of those in whom they occur, they present so many malignant features, that they seem to fall more naturally into this rather than the innocent or the recurrent class of tumours. For although in the very large majority of cases the structures of cancers are unlike those of the normal textures of the body, yet there are in- stances in which tumours, eminently cancerous or malignant in history and habits, approach, or even attain to, close similarity to the natural tissues. And here I might repeat what has already been stated in the lecture on recurrent tumours, that in studying the histories of tumours it is not sufi&cient to content one's self with a mere determination of their structure. The ' life ' of tumours is, in some respects, at least for the present, a better basis for classification even than their structure. One of the best marked cases in which a tumour, presenting the usual characters of a fibrous tumour, not only recurred after removal, but even formed secondary tumours of a like nature in internal organs, occurred in a poor widow who was under my care several years ago. She was forty-seven years old, and had been crippled with acute rheu- matism for ten years before she found a small movable tumour in her right breast. This had increased slowly till seven weeks before I saw her, when, having been struck, it began to grow very rapidly, aud be- came the seat and centre of severe pain. It increased to between two and three inches in diameter, was nearly spherical, very firm, tense, and painful — even extremely painful. I supposed it to be a large hard can- cer, and removed the whole breast. I found the tumour completely separable from the mammary gland, which was pushed aside by it, but was healthy : the cut surface could not, I think, have been distinguished from that of an ordinary fibrous tumour of the uterus, with undulated white bands, excepting that part of it had a sufiused purplish tinge.' The whole substance of the tumour had the same characters; and in microscojiic examination, often and lately repeated, I could find nothing but tough, compact, well- formed fibrous tissue, with imbedded elon- gated nuclei. On boiling, gelatine was freely yielded. In short, I be- lieve it would be impossible to distinguish, by any means but the ' One section of it is in the Muspum of St. Eartholomew's, Series xxxiv. No. 24 ; another in the College Museum, No. 223. 776 FIBROUS CANCEES. history, tHs tnmonr from a common tmmixed fibrous tumour of the jaw or subcutaneous tissue. Three months after the operation a tumour appeared under the scar. It grew very quickly, and felt just like the former tumour. After two months the thin scar began to ulcerate, and the integuments around sloughed ; and shortly the whole of this tumour was separated by sloughing, and was removed entire. This also had, and, in the Museum of St. Bartholomew's, stUl retains, every character of the common fibrous tumour. After the separation of this second tumour, a huge cavity remained, with sloughing walls ; then, as the sloughs cleared away, hard knots, like those of a cancerous ulcer, grew up from the walls, and the disease assumed all the characters of a vast and deep hard cancerous sore. In two months she died. I found the ulcer nearly a foot in diameter ; its walls were formed of a thick nodulated layer of hard, whitish, vascular substance, like the firmest kinds of medullary cancer. Both lungs contained between twenty and thirty small masses of similar substance imbedded or infiltrated in their tissue;' and this substance I have recently again examined, and found to be complete fibrous tissue, hke that of the first tumour removed. I found no similar disease else- where, AH the characteristic features of malignant disease were thus super- added to the growth of a tumour which appeared to he, in every struc- tural character, identical with the common innocent fibrous tumour. Nearly the same events were observed in the following case : — In 1836, a man was in St. Bartholomew's Hospital, under the care of Mr. Earle, with a large spheroidal tumour, lying by the base of his scapula, and extending beneath it. It was removed; and I remember that it was easily enucleated from the adjacent parts, and was called ' albuminous sarcoma ; ' but it was not preserved. About a year afterwards the man returned with a yet larger tumour in the same situation. Mr. Skey removed this, together with a large portion of the scapula, to both surfaces of which it was closely united. The wound was scarcely healed, when another tumour appeared, and increased rapidly. With this the patient died, and growths of similar substance, white, very firm, and nodulated, were found beneath that part of the pleura which corresponded with the growth on the exterior of the chest. I state these particulars from memory ; but I have found, from repeated 1 Mus. St. Bartholomew's, Series xW. No. 43 ; illus. Coll. Surg. 224. FIBEOUS CANCERS. 777 recent examinations, that the tumour removed by Mr. Sbey is of fibrous texture, resembling the common fibrous tumours both in ge- neral and in microscopic characters, and, like them, yielding gelatine when boiled.' It is lobed, -with partitions of connective tissue, and its several lobes are intersected with obscure opaque white fibres : it is tough, compact, and heavy, and tears with an obscure fibrous grain. It is easily dissected for the m.icroscope, tearing into fasciculi, and appears com- posed wholly of closely-placed and nearly parallel undulating filaments. A few shrivelled nuclei appear among the fi.bres, but no cells are distinguishable. Its structure is represented in Pig. 130. To these cases I may add, though it be an im- perfect one, that of a woman from whose back Sir W. Lawrence removed a large well-marked fibrous tumour, which had grown nine months after one of the same appearance had been removed from the same part.^ Before removal, this was judged by all who saw it to be malignant ; but it presented a genuine fibrous structure, and could not, I think, be distin- guished from an ordinary fibrous tumour. Such are the cases which make me beheve that tumours occur, re- sembling in all respects of structure and chemical composition the fibrous tumours of the uterus (excepting their muscular fibres) or of the bones or subcutaneous tissue, yet differing from these in that they pur- sue a course like that of cancers, recurring after removal, growing at the same time in internal organs, tending to sloughing or ulceration, and in the latter process involving adjacent structures. I have related only cases in which the fibrous structure was proved by microscopic examination ; but I have little doubt that others might be added from Fig. 130. Tissue of a malignant fibrous tumour of the scapula ; described above. Magnified about 400 times. Fig. 130. ' It is in the Museum of St. Bartholomew's, Series xxxt. No. 51. A similar- case by Mr. J. Z. Lawrence, Diagnosis of Surgical Cancer, p. 73. This case is also described by Mr. Sibley, along with several others {Path. Trans, viii. p. 340), as a multiple fibrous tumour. He fully recognises the relations, both as regards structure and progress, to the tumours described in the text, but he pronounces against their cancer- ous nature, and thinks that they have close analogies to the recurring fibroid tumours. Virchow includes them in his group Sarcoma. 2 Mus. St. Bartholomew's, Series xxxv. 52. 778 FIBEOUS CANCERS. cases of tumours of the jaws and otLer bones, whicli have been beUeved, from their general appearance, to be fibrous, yet have pursued a malig. nant course. I will only add that these are not such growths as those which Miiller and others have named Carcinoma fibrosum, and of which I beKeve that they are always infiltrations in the substance of the affected organs, and they generally include cancer-cells with their fibrous tissue, and that they have in this tissue such hardness, stiffness, and other peculiarities of structure, as make it easily distinguishable from the normal fibrous tissue and its imitation in the fibrous tumours. CONDITIONS PEECEDING THE CANCEROUS GEOWTH. 779 LECTURE XXXIV, GENERAL PATHOLOGY OF CANCEK. PAET I, CONDITIONS PEECEDING THE CANCEROUS GROTTTH. I PBOPOSB, in this and the next Lecture, to consider the general patho- logy of all the forms of cancer which have now been particularly do- scribed ; to gather a general history of them from the statements made concerning each ; and to trace how the laws observed by them corres- pond with the more comprehensive laws of all specific diseases!. I have stated on page 386 the hypothesis which 1 think we mttst hold concerning cancers : namely, that they are local manifestations of certain specific morbid states of the blood ; and that in them are incor- porated peculiar morbid materials which accumulate in the blood, and which their growth may tend to increase.' In the terms which are more usual in discussions respecting the nature of cancers, T would say that a cancer is, from the first, both a constitutional and a specific disease. I believe it to be constitutional in the sense of having its origin and chief support in the blood, by which the constitution of the whole body is maintained ; and I believe it to be specific, 1st, in the sense of its being dependent on some specific material, which is different from all the natural constituents of the body, and different from all the materials formed in other processes of disease ; and 2ndly, in the sense of its presenting, in the large majority of cases, structures which are specific or peculiar, both in their form and in their mode of life. ' I have not retained this hypothesis without repeated reconsideration, or without due regard to the weight of the opinions from which mine differs. I am still satisfied that the belief in the constitutional origin of cancer offers the best explanation of all its various phenomena, and is necessary to the consistency of the pathology of cancer, with that of other diseases. "780 GENERAL PATHOLOGY OF .CANCER. Tlie evidences for this hypotliesis appear in the conformity of can- cer to the other specific diseases, for which a similar hypothesis is nearly proved (Lectnre XX.), and in .the fitness of the terms which it supplies for the general pathology of cancer. I will speak in this lecture of the conditions that precede the formation of a cancerous growth, and in the next of the growth itself. The general history of cancers, and their analogy with other diseases that are, in the same senses, specific and constitutional, imply that before the formation of a cancerous growth, two things at least must co-exist : namely, a certain morbid material in the blood, and some part appropriate to be the seat of a growth incorporatiug that material some place in which the morbid material may assume, or enter into organic structure. The existence of the morbid material in the blood, whether in the rudimental or iu the effective state, constitutes the general predisposi- tion to cancer ; it is that which is by some called the predisposing cause of cancer. The morbid material is the essential constituent of the ' cancerous diathesis or constitution : ' and when its existence produces some manifest impairment of the general health, independently of the cancerous growth, it makes the primary cancerous cachexia (see p. 643). That which evidently makes some part of the body appropriate for the growth of a cancerous tumour is a so-called exciting cause of can- cer ; but it is a cause of cancer only in so far as it fits some part for the local manifestation of a disease which already, in its essential mate- rial, exists in the blood. It seems very important to keep constantly in view that these two conditions must coincide before the appearance of a cancerous growth ; important not only to recognise their existence, but, if we can, to measure the several degrees in "which, in each case, they are present; because, upon our recognition of the shares in which they respectively contribute to the production of the cancerous tumour, must depend the chief principles of practice in relation to the removal of such tumours. The larger the share taken by the constitutional element of the disease — that is, by the cancerous condition of the blood — in the production of a cancerous growth, the less, on the whole, is the proba- bility of advantage to be derived from the removal of that growth ; while, on the other hand, the more largely the local state enters into the conditions upon which the cancerous growth is founded, the more bene- CONDITIONS PRECEDING- THE CANCEROUS GROWTH. 781 fit may we anticipate from tlie removal of the cancer and of the locality with it. So, too, in onr considerations of the mere pathology of cancerous diseases, it seems essential to have a just regard of both these previous conditions. If we look at only a certain class of oases, we may easily find enough to persuade ourselves that cancers are, from the first, and throughout their course, wholly constitutional diseases ; or, if we look exclusively at another class, which are as truly cancerous as the first (according to any natural definition of the term), we may find equal evidence for believing that they are, at least in the first instance, en- tirely local diseases, 8,nd that the constitutional affection which may attend them is only something consequent upon their growth. When, for example, we see that certain organs are much more liable than others to the growth of cancer, and that, in those organs, the growth sometimes follows the infliction of a local injury or some pre- vious disease ; and much more when we see, as in the case of the scro- tal epithelial cancers, that the repeated application of a stimulus, such as soot, to a part of the body, will lead to the formation of cancer in even a large number of persons, we might assume that the growth has its origin wholly in the local state, and that whatever may follow of diseases in other parts is only the consequence of the growth. On the other hand, when we consider the numerous analogies between cancers and the admitted specific blood-diseases ; when we see the rapidity of outbreak with which cancerous disease sometimes manifests itself in multiple growths, apparently irrespective of the locality in which they are produced, and how, sometimes, a distinct affection of the general health, intense and destructive, exists even while the cancerous struc- ture is yet trivial or unobserved ; and when we see the insufficiency of all local causes to excite the growth of cancer in some persons, we might suppose that the cancerous disease is one wholly constitutional, wholly - dependent upon some morbid condition of the blood, and that the for- mation of the tumour is but as an accident of the disease, and is inde- pendent of the state of the part in which it occurs. It is in correspondence with these classes of cases, too partially examined, that two distinct opinions are commonly entertained respect- ing the nature of cancer : some holding that it is from the beginning, and throughout, a constitutional disease ; and others, that it is, in the first instance, if not through its whole course, a local one. The reconci- liation not only of the two conflicting opinions, but of the seemingly conflicting facts upon which they chiefly rest, is to be found in this — 782 GENERAL PATHOLOGY OF CANCEE. that the complete manifestation of cancer, the formation of a cancerous growth, is suspended till such a time as finds both the constitutional and the local conditions co-existent, — ^till the blood and the part are at once appropriate. I might show how consistent the belief of tlie necessity of this coin- cidence is with what is known of other specific diseases. But let me illustrate it by two cases, such as may frequently be met with. Bruch ' records tbe following : — A woman had a child at eighteen years of age. The child died when it was a month old, and her breasts were left to the disturbance which usually ensues in prematurely arrested lactation. At the age of thirty-four she received a blow on the right breast. This was followed by no manifest change of structure, but, for some days, by severe pains, and then, for a much longer time, by feelings of swel- ling and tension at the menstrual periods. At thirty-nine she received another blow upon the same breast which was followed by an increase of pain. Soon afterwards she was exposed to cold, and then there ensued erysipelatous inflammation of the breast, followed by induration of the part of the mammary gland. This, however, contiaued without change for four years : but then, after menorrhagia, a tumour appeared in the breast. When this was removed, or partially removed, it was found to be not a cancerous, but a cystic tumour, with growths from the interior surfaces of the cysts. She remained well after this, the wound having perfectly healed, for twelve years more, and in this interval she ceased to menstruate ; but now, when she was fifty-five years old, after having a whitlow and inflamed lymphatics of the right arm, another tumour formed in the breast, which had every appear- ance of being cancerous. It was removed ; but it recurred, and ended fatally. Now, surely, in such a case as this, we may say that all the local conditions necessary for the production of a cancer of the breast had been amply provided. They had existed, or had been reproduced from time to time, for a period of upwards of twenty years ; yet being alone, they had been insufficient ; and no cancer appeared till the time when, at a more favourable condition of age, the cancerous condition of the blood was manifested, and filled up the measure of the necessary prece- dents of the disease. Contrast with the cases of this kind those to which I had occasion to refer in a former lecture (p. 681), and of which I may here repeat ' Die Diagnose der hSsartigen Geschwiilste, p. 94. LOCAL AND CONSTITUTIONAL TREDISPOSITIONS. 783 one : — A boy received a cut in his eye, wMch had been previously sound. Within three weeks of the injury a fungus protruded from the eye. It ■was removed with the whole eyeball and the contents of the orbit. The wound had scarcely healed before a fresh growth appeared ; and shortly afterwards the boy died with medullary cancerous disease extending from the orbit to the brain. We can scarcely express such cases as this in any other terms than that the cancerous condition of the blood existed at the time of the injury, but was insufi&cient for the production of a cancerous growth, and remained latent, for want of an appropriate locality for the growth, till the injury, disturbing or causing the suspen- sion of the natural course of nutrition in the part, supplied the appro- priate local condition. These cases, I repeat, are but examples of classes. In the one class we seem to meet with all the constitutional or blood conditions of cancerous disease complete, waiting only for the existence of some part in which the cancerous growth may be manifested ; in the other class, the local conditions are abundantly present, but the disease does not appear till the cancerous condition of the blood is complete (compare p. 366). It may, further, be deduced from these cases, in which the extremes illustrate the ordinary mean, that if either of the two conditions be present in an extreme degree, its intensity may compensate for a com- parative defect of the other. Among the cases to which I have been referring, we find certain in which the cancerous disease makes its appearance in such a multiplicity of growths and of parts, that it seems indifferent to local conditions ; and these are the very cases in which all the other constitutional characters of cancer are most strongly marked : in which cachexia often precedes the growth, and in which the removal of the cancer interferes in no way with the progress of the constitu- tional disease, unless it be to accelerate it. On the other side w^meet with cases in which long-continued irritations, or frequent injuries of certain parts of the body, seem almost sure to be followed by cancer ; and these are the cases in which the constitutional characteristics of the disease are least marked, and in which, as in epithelial cancer of the scrotum and of scars, we may hope that the recurrence of the disease mav be long deferred, if that which has first appeared be removed with its seat. In this class of cases, it may be said, the cancerous blood- condition is so lowly developed, that the cancerous growth can ensue in none but one peculiarly appropriate part, which part being removed, the o-rowth is for a time, or for life, impossible ; while, in the former 784 THE STATE OF THE BLOOD. class the blood-condition is so tigUy developed, or so intense, that almost any part suffices for the seat of growth. Let me now proceed to consider what each of these conditions, ne- cessary as precedents of the growth of a cancer, consists in. What is the cancerous condition of the blood ? and what is the state of a locality apt for the formation of a cancerous growth. I. Concerning the state of the blood, onr positive knowledge is very trivial and obscure ; pei'haps it would be safest to say that we have at present none. We may be sure, on grounds to which I have already referred, that there is a peculiar material in the blood which is separa- ted from it, and constantly renewed, in the formation of a cancer ; but we can say what this material is not rather than what it is. We may reasonably hold that, in cancerous persons, the .whole con- stitution of the blood is not perverted : for we see that all the tissues may for a long time be perfectly nourished, even while the cancer is making progress ; that injtiries may be repaired with the ordinary quickness and perfection ; that the products of iuflammation may be like those in non-cancerous persons, and may pass through their ordi- nary developments ; and that some other specific diseases may have their usual course. It would therefore be unreasonable to regard the whole of the blood of a cancerous person as perverted from its normal condition. The cancerous state is not a total change of the blood, but depends, probably, on some definite material mingled with the natural constituents ; and this material, we may beheve, is derived from a morbid transformation of one or more of the natural constituents of the blood, and is maintained, as morbid structures are, by the per- sistence of the same method of transformation, or by its own assimilat- ing force. But now, as to what this material is ; or, again, is not. I believe, it is not anything visible to the sight. There is not, so far as 1 know, anything in the blood of a cancerous person which we can recognise as a cancer-structure. There are no cancer-cells, nor, ia any form, visible germs of cancer, existing in the blood, and only needing to be separated from it to make up or grow into the cancerous structure. In advanced cases of cancer, and especially in those in which the cancer- ous substance is very softened and broken, we may meet with portions of it in the blood, which appear as if they had been detached or ab-. sorbed from some growth, and carried on with the stream. In similar eases we may find cancerous formations in the blood itself. Such seem THE STATE OF THE BLOOD. 785 to bo somo of tlio cancerous growtlis in the veins and the right side of the heart. For, although among the former there are many in which the growth has only extended into the veins, through their walls in- volved in cancerous tumours, yet there are others in which, as in the endocardial cancers, the internal growth takes place far from any other tumour. In these we may believe that cancerous structures have been conveyed in the blood to the part of the vein, or of the right side of the heart, at which they have been arrested, and to which adhering (either alone or with blood-clot), they have subsisted and grown on materials derived from the passing blood. But not one of these cases affords any support to a belief that, previous to the existence of a cancerous tumour, any visible germs of cancer exist in the blood. Other means for investigating the very nature of the cancerous material in the blood seem as impotent as the sight. Minute chemistry has, up to this time, done nothing ; neither can we accept, I think, that which is in part a chemical theory, and has been especially held by the pathologists of the Vienna school — namely, that particular diatheses or dyscrases of the blood appropriate to such diseases as cancer and tuber- cle, may be recognised by a superabundance of albumen or of fibrine. The facts adduced as bearing directly on these doctrines are, at present, few and incomplete ; and I think they are not sufficient either to estab- lish the theories based on them, or to outweigh the general improbabi- lity that diseases so complex as cancer and tubercle should depend chiefly on quantitative variations in any of the larger constituents of the blood. Neither can it, I think, in the present state of organic chemistry, and with so few analyses as we yet possess of the blood of cancerous and other diseased persons, be more than a guess, that either cancer or any other such specific disease, depends, in any sense, on qual- itative modifications of the albumen, or the fibrine, or any other single constituent of the blood. At present, I believe, the best part of the facts established, or made probable, by these investigations, relate to the antagonism or incompa- tibility of cancer and certain other specific diseases. I think we can- not doubt that, as a general rule, cancerous and tuberculous diseases do not make active progress at the same time ; and that, in this sense, they exclude one another, and are incompatible. I mentioned in a former lecture (p. 640) a striking case bearing on this point, in which, as it seemed, the rare event of arrest and almost complete recovery from scir- rhous cancer was connected with the evolution of tuberculous disease. I believe also, that I have seen at least one instance in which active tu- 8b 786 INHERITANCE OF CANCER. berculous disease of the lungs was arrested immediately before the appearance of a scirrhous cancer in the breast : and we find, ia so many of those who die with cancer, the remnants of tuberculous disease from which they have suffered in earlier life, that we may believe that the recovery from the one has been in some manner connected with the supervention of the other. So, on the other side, the rarity of progres- sive tuberculous disease in those that are cancerous may be because, except in such extremely rare cases as that to which I have referred, the cancerous diathesis excludes that condition of the blood in which the tuberculous disease has its rise. To the same class of facts, as illustrating the exclusion of one mor- bid condition of the blood (or, as Hunter would have said, of one mor- bid action), by another, we may perhaps refer the occasional withering of a cancer under the influence of some fever, and the more rarely oc- curring complete death of one, so that during an attack of acute fever the whole mass may slough off ; and this whether the feverish condi- tion of the blood be produced by some miasma, or by medicinal means. Such, I fear, is all that can be at present safely regarded as matter of fact in relation to the nature of the peculiarity of cancerous blood ; and it must be admitted that these facts are scarcely more than indications of the direction in which inquiry should be made. Let us next see if we can in any measure trace the method of its production ; — whence the specific material is derived from without, and the conditions most fa- vourable to its generation within, the body. First, it is evident that a disposition to cancer may be derived by inheritance ; that something may be transmitted from the parent to the offspring, which shall ultimately produce both the cancerous con- dition of the blood, and in some instances the locality apt for the cancer- ous growth. In 322 cancerous patients, there were 78, or very nearly one-fourth who were aware of cancer in other members of their families. The pro- portion is much larger than could be due to chance ; and its import is corroborated by the fact of many members of the same family being in some instances affected.' ' Medico- Chir. Trans, xlv. op. cit. But the influence of inheritance in the produc- tion of cancer must be much greater than it will appear in any tables. Many cases of cancer of internal organs are overlooked ; many are forgotten after a generation ; many persons in whom cancer would be manifested late in life die before its appear- ance, but not before transmitting the tendency to their offspring (pp. 787, 788). Every year's experience in practice among persons whose famiLy histories are known makes me more sure that inheritance is the great power in the production of all diseases that are not of distinctly external origin, and, among these, of cancer. INHEEITANCE OF CANCER. 787 That wMcli is transmitted from parent to offspring is not, strictly speaking, cancer or cancerous material, but a tendency to the production of those conditions, which will, finally, manifest themselves in a cancer- ous growth. There are here some facts worth dwelling upon, both for their own sake, and because they are clear instances of the manner m which the hereditary transmission of the properties of the parent- body takes place. I repeat, that which is transmitted from parent to offspring is not cancer itself, but a tendency to the production of cancer at some time far future from the birth. We have no reason to believe that a cancer- ous material passes with the germ or the semen : none is furnished by any frequency of congenital cancer. But while, on the one hand, we cannot assume that a cancerous material passes with the germ or with the impregnating fluid ; on the other, we cannot understand' the transmission of a tendency or disposi- tion to any event, independently of all material conditions. The germ or the semen from the cancerous parent must be already, in some con- dition, different from that from a parent who is not cancerous, if, in the course of any number of years, cancers are to be formed out of the substance which the germ, in its development, or subsequent changes, will appropriate. Our expression, then, may be, that, in the impregna- ted germ from a cancerous parent, one or more of the materials, normal as they may seem, are already so far from the perfectly normal state, that after the lapse of years, by their development or degeneration, they will engender or constitute the cancerous material in the blood, and, it may be, the locality apt for a cancerous growth. But now let it be observed, this tendency to cancerous disease is most commonly derived from a parent who is not yet manifestly can- cerous ; for, most commonly, the children are born, and sometimes even become cancerous and die before cancer is evident in the parent ; so that, as we may say, that which is still future to the parent is transmit, ted potentially to the offspring. Nay, more ; the tendency which exists in the parent may never become in him or her effective, although it may become effective in the offspring : for there are cases in which a grandparent has been cancerous, and although his or her children have not been so, the grandchildren have been. How admirable a discovery it would be if we could find the means by which the tendency, conveyed from the grandparent to the child, was yet diverted from its course, even after it had been transmitted to the germ of the grandchild ! Let me repeat, the cases of hereditary cancer only illustrate the com- 3 E 2 788 INHERITANCE OF CANCEE. mou rule of the transmission of hereditary properties, whether natural or morbid. Just as the parent, in the perfection of maturity, transmits to the offspring those conditions, in germ and rudimental substance, which shall be changed into the exact imitation of the parent's self, not only in the fulness of health, but in all the infirmities of yet future age ; so, also, even in seeming health, the same parent may communi- cate to the materials of the offspring the rudiments of diseases yet future to himself ; and these rudiments must, in the case before us, be such modifications of natural compositions as, in the course of many years, shall be developed or degenerate into materials that will manifest themselves in the production of cancer. There is, surely, in all science, no fact so strange as this : and it need not be a barren fact, fit merely for wonder and vain speculation ; for we may deduce from it that the cancerous substance in the blood, whatever it may be, and whencesoever derived, is a result of long-con- tinued elaboration ; needing, as the normal materials of the body do, to pass through a life of continual change before it attains its complete efficiency. The period required for this completion of the cancer- material, is the time, often of long delay, during which the disease, according to various expressions, is ' latent,' or only ' in predisposition.' But such expressions are deceptive. As with other specific blood-dis- eases, so with cancer, the predlspositioa to it is a substantial thing ; and we should hold that, in all the time of latency, there is that thing in the blood which will become, or generate by combination, the effec- tive cancer-material, unless (as in the healthy generation between the cancerous grandparent and the cancerous grandchild) it be destroyed or retained in the course of natural nutrition. Inherited cancer appears at an earlier age in the offspring than in the parent ; a rule subject to very few exceptions, and useful even in diagnosis. In some instances it is observed in many successive genera- tions. I saw a young lady of twenty-four,^ who had epithelial cancer of the pharynx, and quickly died with it. Her mother, grandfather, and great-aunt, and great-grandmother (all in one Kne) died with cancers of different organs. The great-grandmother died at eighty or older ; the grandfather between sixty and seventy ; the great-aunt (I think) about forty ; the mother between forty and fifty. It is within the same rule that not rarely the son or daughter dies with cancer before the parent from whom it was inherited. In hereditary transmission, the cancer-material may be modified, so ' Entered as 34 in Mr. Baker's table. INHEEITANCE Of CANCEE. 789 tliat tlie form of the disease in the offspring may be different from that in the parent. The change from scirrhous to medullary cancer, and vice versa, is not rare. I have mentioned cases of alternation between these and the epithelial cancers (p. 730) ; and a case of melanoid can- cer m a patient descended from one with a scirrhous breast (p. 749). Mr. Simon has told me that he removed a colloid cancer from the cheek of a woman whose child, seven years old, was dying with medullary cancer of the eye ; and M. Lebert, with two cases like these, relates that the celebrated Broussais died with medullary cancer of the rectum, and his son Casimir, with colloid cancer of the same part. With so many oases supporting it, this kind of transmutation during transmission of cancer, can hardly be doubted. But I believe we may trace further changes in the transmission ; and that the material may be so altered that, as we may say, the cancerons disposition may gradually cease, or fade out in the production of recurrent and other tumours, whose characters are intermediate or transitional between cancerous and- simple growths. I have referred (p. 563) to cases illustrating this opinion ; and I feel sure that many more will be found ; for we may ob- serve corresponding changes in both form and degree, in the hereditary transmission of many other diseases. Thus the syphilis of the infant is seldom exactly like that of the mother ; the same family may include oases of insanity, epilepsy, palsy, chorea, stammering, and other diseases allied to these, in that all are affections of the nervous centres, but differing in form and degree.' When the tendency to cancer is inherited, the disease may affect the same part in the child as in the parent ; but in at least an equal number of cases it affects a different part. This fact is of great or even decisive force in reference to the question as to the local or the con- stitutional origin of cancer generally. If it were local, the inheritance, should fall on the same or similar parts, as does that of scalp-cysts or of cartilaginous tumours ; if constitutional, the general character of the- disease should be preserved, but the part affected might be inconstant, as in gout and scrofula. Among 61 cases taken without selection from my note books, Mr. Baker^ found that in 27 the cancer in the offspring was in the same part as in that of the parent or grandparent ; in 34 it ' Hureditary malformritions display similar mutntions in transitu ; as in instances in the Museum of St. Tijirtholomew's, Casts A 21 to 27. The whole of this subject of the chnnge of diathesis in hereditary transmissions -will repay, I believe, the deep- est study. 2 St. Bartholomew's Hospital Reports, ii. pp. 132-136. 790 INHEEITANCE OF CAKCEE. was in a different part. Among other relatives there were 42 instances of cancer affecting the same organ ; 32 of it affecting different organs. And the same principle is sometimes illustrated with great force in single famiHes. Some cases are referred to at p. 730. In one well known to me, a lady died with cancer of the stomach. She had seven children and abont thirty grandchildren, who grew np. Some of them are still living, but of those who are dead, one danghter died with can- cer of the stomach ; and of the granddaughters, two with cancer of the uterus and one with cancer of the breast ; and of the grandsons, one with cancer in the bladder, one with cancer in the rectum, and one with cancer in the axillary lymph-glands. It seems unreasonable to call a disease local, which can pass, by inheritance, with so complete a disre- gard of localities. What local condition or disposition can we suppose to have been transmitted in this series of cases, or in that mentioned at p. 788, in which cancer occurred in different organs in four succes- sive generations ?' For the cases of cancer that owe absolutely nothing to iaheritance — I suspect them to be few — can we trace any external source of the morbid condition of the blood ? Inoculation and contagion are the only probable sources of the kind ; but concerning these the presumed facts are, at present, very few and uncertain. There are cases in which, by the inoculation of cancerous material into the bodies, or by the injection of such naaterial into the blood of dogs, cancer has seemed to be pro- duced. I think that, in a large number of experiments, that result has been three times obtained ; but it is quite possible that the dogs used for these three experiments were cancerous before the human cancerous matter was injected into them ; for cancer is indeed a frequent disease among dogs. The instances are certainly too few for proof of inocu- lation. There are, also, certain cases in which it seems possible that cancer may have been transmitted from the wife to the husband during the ' M. Paul Broca also relates (Traiie des Tv/meurs) an important case of family transmission. A woman, -who di ed of cancer of the breast, had four married daughters ; two died with cancer of the liver, two with cancer of the breast. One of these daughters had seven children, of whom one son died with cancer of the stomach, three daughters with cancer of the breast, and one with cancer of the liver. Another of the daughters had also seven children, three of whom died with cancer of the breast, one of the liver, one of the uterus ; and of these daughters one had a daughter who died with cancer of the breast. Dr. Newman tells me of a family where a grand- mother, three daughter.s, and two granddaughters died with cancer — the uterus, breast, oesophagus, and rectum, being the organs alFectcd in one or other of these persons. INOCULATION OF CANCEE. 791 act of copulation. Such cases are recorded by Dr. Watson and Dr. Copland : ' wives having cancer of the uterus had husbands with can- cer of the penis. Of course it must be questionable whether there were m these cases more than the accidental coiaoidence of persons having married, in both of whom an ordinary and independent generation of cancer ensued ; and we cannot conclude that inoculation of cancer may thus occur, unless it should appear that persons thus related become cancerous in larger proportions than they do who, being otherwise in similar conditions, are not thus exposed to the possibility of inocula- tion. Again, I have heard that cancerous matter having been inoculated under the skin of frogs, cancerous growths have been produced in them. I have repeated this experiment, but without effect ; for all the frogs in whom I inserted the cancerous matter died soon after.^ But the facts, so far as I have yet heard them, have not much meaning in relation to the general pathology of cancer ; for I beUeve it is not yet proved that the local growths of cancer, which are the consequence of the inocula- tion, are followed by general cancerous disease, or by the production of cancer in distant parts, as well as in that in which the matter was de- posited. Unless this occurs, the experiments only prove the fact (and a very strange one it is) that materials of disease from human bodies, being inserted in the bodies of cold-blooded animals, will live and grow even upon the materials of the cold-blooded creature. In like manner, if any one could establish the supposed cases of husbands inoculated by their wives he might only prove that cancerous elements may subsist and increase upon other materials than those of the body in which themselves were generated. Unless the cancers thus generated, in the first instance locally, are found to multiply themselves in distant organs, these cases of inoculation will prove no more than that cancer, like a parasitic growth, may be transplanted, and grow on common or in- different nutritive material ; they will have no bearing on the questions concerning the nature and origin of cancerous blood. ' Hict. of Fract. Med. ; Art. Scirrhous and other Tumours. * The question of the inoculability of cancer from man to animals, or from one animal to another, is still an open one. For though von Langenbeclc, 0. Weber, and Gouion, consider that they have obtained positive results, the number of experiments which they have performed is not sufficient to settle the question in the affirmative, as it is possible that the cancer may have arisen spontaneously in the animals operated on and not have been due to the inoculation. On tlie other hand, Billroth, Lebert and Wyss, and Doutrelepont, hare obtained purely negative results from their experi- ments. The subject is discussed by the last-named author, and ample references given, in Virchow's Archiv, xlv. p. 501. — 1860. "rS^ INFLUENCE OF SEX AND AGE. At the most, then, we may assume that a transference of cancer by inoculation is possible. But such an assumption will not materially diminish the number of cases in which we look in vain for any external source for the disease, and in which all thac we can study are the con- ditions most favourable for its production within the body. Of these conditions I have already spoken, in relation to each of the principal forms of cancer. I need, therefore, do little more than sum up the ge- neral conclusions concerning them. First, respecting the influence of sexual peculiarities. Women are on the whole, more liable to cancer than men are : but in what propor- tion they are so cannot be exactly stated. Lebert assigns about 37 per cent, as the proportion of cancers in males : Dr. Walshe finds it scarcely more than 26 per cent. This is just one of the points on which the truth will not be known till statistics are collected by practitioners under whoso charge the two sexes, and all the organs of each, fall in just proportions, and by whom the existence of internal cancers is as constantly ascertained by autopsy as that of external cancers. The frequency of cancer of the breast and uterus gives an apparently large preponderance of cases in women ; but, on the other side, the cancers of the skin, bones, and digestive organs, greatly predominate in men. The liability of the breast makes scirrhous cancer by far most frequent in women ; but this, in a general estimate, may be nearly balanced by the preponderance of epithelial, osteoid, and villous cancers in men.' The influence of age may be more definitely stated. Dr. Walshe has clearly shown that ' the mortality from cancer ' [i.e. the number of deaths in proportion to the number of persons living] ' goes on steadily increasing with each succeeding decade until the eigbtieth year.' His result is obtained from records of deaths ; but it is almost exactly con- firmed by the tables I have collected, showing the ages at which the cancers were first observed by the patients, or ascertained by their at- tendants. In 772 cases, including cancers of all kinds, the ages at which they appeared were as follows :— Under 10 years . . 27 Between 10 and 20 „ . . 30 „ 20 „ 30 „ . . 78 ' The particular influences of sexual dilFerence maybe cclleoted from pp. 632, 633, 678, 7:37, 748, 760. On these and all the questions capable of being solved by statistics, the largest information is collected by Dr. Walshe, and in the tables of llr Sibley and Mr. Baker, Med.-Chir. Trans, xlii. xlv. INFLUENCE OF AGE. 793 20 » 30 80 ]} 40 40 )) 60 60 5J 60 60 J) 70 70 )J 80 Between 30 and 40 years . . 130 40 „ 50 „ . . 200 60 „ 60 „ . . 152 „ 60 „ 70 „ . . 98 „ 70 „ 80 „ . . 67 The proportions between these numbers and the numberm of persons living at the corresponding ages (calculated in the same manner as in the previous Lectures, pp. 632, 679, 729), will show the proportionate frequency of cancer at each period of life, and may be represented by the following numbers : — Under 10 years . . 5 Between 10 and 20 „ . . 6-9 21 48-5 100 113 107 126 Thus, the liability to cancer seems always increasing from childhood to 80 years of age. A single exception to the rule (between 60 and 70) appears to exist ; but this would very probably not appear in estimates from a larger number of cases. The general fact, and that of the immense increase of cancer after 40 years of age, are of exceeding value in proving that it is a disease of degeneracy ; even though it is observ- able that cancer very often affects those who are most robust, and in the full bloom of health ; and even, as Mr. Moore has shown, though it is most frequent in the healthiest districts of England. Within this larger rule, others may be collected from the foregoing Lectures. Of the three chief forms of cancer, the medullary alone ex- emplifies the rule of frequency constantly increasing from earliest to latest life ; but the rate of increase is, of course, different from that shown in the general table (pp. 679,680). The epithelial cancers ex- emplify the rule after the age of 20 ; before that age they are scarcely found (p. 729). The scirrhous have their maximum proportionate frequency between 40 and 50 • (p. 632). The melanoid cancers are nearly conformed to the rule of the medullary. The osteoid and ' It is probably due to this great frequency of scirrhous cancer in the female breast that (as Dr. Walshe found) the increase of mortality from cancer between 40 to 50 is so much greatpr in women than in men. 794 INFLUENCE OF CLIMATE. colloid probably have rules of frequency peculiar to themselves, and depending upon local conditions ; but we need more cases to calculate them. The increase in frequency of cancer with increasing years, its great prevalence after middle age, and the conformity to this rule shown by medullary cancers which are least of all dependent on locality for their development, — these facts may prove, as a rule, that cancer is a disease of general or constitutional degeneracy. But, as in every other part of the pathology of cancer, so in estimating the influence of age in its pro- duction, we must consider the effect of time in making certain parts apt to be the seat of cancer. Such an effect is shown in the different liabilities which each organ manifests at different periods of life. These cannot be exactly stated ; but, beyond doubt, the eye and orbit are earliest apt to become cancerous ; then the bones, testicles, and the areolar tissue of the limbs and trunk. These are its chief seats before 30 years of age ; from 80 to 50 it predominates in the penis, uterus, external sexual organs, and the breasts ; after SO, in the integuments and digestive organs.' I fear nothing can be said of the real nature of the changes ensuing in each organ, which thus make it, at different times of life, more or less appropriate for the seat of cancer. In some parts, as the testicles and limbs, the chief liability seems to coincide with the first attainment or with the time of failing in the attainment or maintenance of full functional power ; in others, it falls- in with the beginning of the loss of power, as in the uterus and breast. Two other conditions seem to have influence in producing or promo- ting the cancerous constitution — namely, climate and mental distress. Dr. Walshe has collected evidence that ' the maximum amount of can- cerous disease occurs in Europe,' and that it is very rare among the patients of the Hospitals at Hobart Town and Calcutta and among the natives of Egypt, Algiers, Senegal, Arabia, and the tropical parts of America. We cannot, indeed, be sure that this difference depends on climate ; it may be due to the national differences in habits of life : possibly, as Dr. Walshe suggests (p. 161), the greater prevalence of cancer may be due to the more wasting influence of the higher state of civilisation. More records are necessary to decide such questions ; and it may be well if they include accounts of the apparent variations of ' More rules of this kind may perhaps he gathered from iho stali.stics of Walshe and Lebert ; hut with caution, for want of such records as I have said are necessary to estimate the lifibilities of the sexes. INFLUENCE OF MENTAL DISTRESS. 795 cancer among nations whose climate and habits of Hfe are not materially different (see pp. 380, 470). It is only on a general impression, not by counted facts, that we can reckon deep mental distress among the conditions favourable to the production of cancer. I do not at all suppose that it could of itself ge- nerate a cancerous condition of the blood ; or that a joyous temper and prosperity are a safeguard against cancer ; but the cases are so frequent in which deep anxiety, deferred hope, and disappointment, are quickly followed by the growth or increase of cancer, that we can hardly doubt that mental depression is a weighty addition to the other influences that favour the development of the cancerous constitution. Nor is it strange that it should be so ; it is consistent with the many other facts showing the aflSnity between cancer and depressed nutrition. But, after all, when we have assigned to these conditions their full weight in producing the cancerous constitution or state of the blood, that which may strike us most of all is the comparatively small in- fluence which any known internal or external conditions possess. We are, as yet, wholly unaware of any great difference in the frequency of cancer, among those of our own nation who are most widely apart from each other in all the ordinary conditions of life. The richest and the poorest alike seem to be subject to it ; so do the worst and the best fed ; those that are living in the best conditions of atmosphere, and those that are immured in the worst ; those that are cleanly and those that are foul ; those of all temperaments, and of all occupations (except such as have peculiar local influences) ; those that appear healthy and those that are diseased, except those with some few specific diseases. We can hardly lay oar hand upon any one of the various circumstances of life, in the various orders of society in this country, to which we can refer as rendering one more or less liable than another to the acquire- ment of the cancerous constitution. Dr. Walshe's evidence amply shows the want of foundation of all the general impressions opposed to this conclusion. Prom this confession of ignorance respecting the production of the cancerous constitution, or, as I would say, of the cancer-material in the blood, when it is generated within the body, I will proceed to speak of some of the changes which, being once generated, it may undergo. In all ordinary events, the normal course of cancerous disease is that of steady progress towards death. The increase is indicated by two different, but usually commensurate, series of phenomena ; those, 796 IKCEEASJ; OF DIATHESIS. namely, of increasing formation of cancer-structures, and of increasing cachexia. We may commonly observe, that, from the beginning of a cancer- ous formation, there is a constant increase in its mass, and in the rate at which it is added to. Even the cancers that are, in part, ulcerating, are usually growing, at a greater rate, at the border or surface opposite to that in which ulceration is destroying them ; or else, while ulceration is going on in one cancer, there is a greater rate of increase in others . or, the number of growing masses is constantly increasing. In one or more of these methods most cases exemplify the general rule, that the quantity of cancer which is formed within any given length of time, regularly increases from the beginning to the end of the case. In most cases the increasing formation of cancer is accompanied by manifest indications of increasing cachexia, and, in doubtful cases, constant decrease of weight is among the most significant aids to diag- uosis. But it is not always thus ; in a large number of cases, especially of cancers of external organs, no cachexia appears till the local disease hfls made great progress ; and, on the other hand, we find cases, espe- cially of internal cancers, in which the cachexia increases without pro- portionately increasing cancerous formations : cases in which we may say that the cancerous condition of the blood manifests itself less plainly in the production of growths, than in its interference with the ordinary phenomena of life. Such cases are not unfrequent among those of cancer of the rectum : we see the patient intensely ill, and dying with cachexia, to which the extent or rate of growth of the can- cerous tumour bears no proportion. So, sometimes, with cancer of the liver ; the cachexia is quite disproportionate to the amount of cancer- ous formation, and to the degree in which it interferes with the func- tions of the organ. In these cases the cancerous disease, exemplifies a frequent event in the history of specific diseases : namely, that when the morbid material is most intense and acute in its action, when it most manifestly affects the constitution, it may produce the least indi- cations of local morbid influence. In both these sets of cases, the increase of cancerous disease, and its accelerating rate, are illustrated as the rule of its career. The phe- nomena, in the first set of cases, may be explained by assuming that the quantity of cancer-material in the blood regularly increases ; those in the second, that, with its increase, it undergoes some transformation, rendering it less appropriate for growths, but more injurious to the other offices of the blood. INCREASE OF DIATHESIS. 797 (a.) The cancerous constitution may apparently cease ; a growth already formed may maintain itself, subsisting, probably, on the normal constituents of the blood,i but its progressive increase may be for a time suspended. I have exemplified this by cases of medullary cancer (p. 683), of which the general history was, that, after a certain period of increase, the tumours ceased to enlarge, were for a time stationary (tlie general health also remaining the same), and then resumed the cancerous mode of progress. (6.) The cancerous constitution may be in some measure changed or modified. It may manifest itself for a time in a certain form of cancer, and then in some other form. Thus scirrhous cancer may be succeeded, in secondary growths, by medullary cancer ; osteoid by medullary, and vice versa, ; and, I think, epithelial by medullary. We must, I beheve, in these cases assume a transformation of the specific cancerous material in the blood — a change corresponding with that which may be more regularly traced in the materials of other specific diseases (e.g. of syphilis) in their successive stages or periods of life (pp. 360, 368). Lastly, the cancerous diathesis, even after it has been manifested by growths, may be superseded. Thus we may express the cessation, or re- trocession of cancer, when tuberculous disease ensues in its course. In the last three events the rule of progress in cancer is departed from. But if we could reckon all the cases in which any of these events happen, they would make but a few exceptions to the general rule, that the cauoerous constitution regularly increases at an accelerating rate, and with little change in its methods of manifesting itself. I pass now to the consideration of the second necessary precedent of a cancerous growth — namely, the existence of some part fitted to be its seat — some apt locality. Such fitness may be natural or acquired ; and in parts in which it is in sonae measure natural, it may be increased by accident or disease. Certain parts of the body are evidently, and independently of ex- ternal influences, far more liable than others are to become the seats of cancer. They are, thus, naturally apt localities ; not equally so throughout life, but usually becoming so at certain periods. For ex- planation of this natural aptness, we may, in some cases, look to in- ' I shall revert to this point in the next lecture. The maintenance, or even the increase, of a cancerous growth, does not necessarily imply that a cancerous condition of tho blood is maintained : once formed, a cancer, like any other tumour, may live and grow by its assimilative power over common materials. 798 LIABILITY 01<' CERTAIN PAETS. heritance — the local aptness being transmitted together with the con- stitntional tendency. This, as Mr. Baker's tables show, is especially frequent with cancers of the breast,' and is sometimes very marked, as in a case in which a mother and five out of her six daughters had can- cer of the breast.^ One of Mr. Baker's tables^ shows the proportions in which, in 600 cases of cancer, separate organs were primarily affected, as follows : — Males Females Total Intermuscular and other connective tissue 10 3 13 Bones 16 7 23 Lymphatic glands . 10 6 16 Eye . . . 2 2 4 Lips and cheeks 25 4 29 Gums and palate . 6 3 9 Tonsil 1 1 2 Parotid 1 2 3 Tongue 19 11 30 CEsophagus . 2 5 7 Larynx 2 1 3 Eectum . 8 3 11 Urinary bladder 4 1 5 Integuments of limbs and trunk 13 5 18 „ scalp 1 1 2 „ nose and face . 8 1 9 „ external ear 1 — 1 „ scrotum 7 — 7 Scars 3 1 4 Cutaneous moles and naevi 1 5 6 Testicle 14 — 14 Penis 6 — 6 Labia — 2 2 Breast, right and left in equal proportion 7 269 276 167 333 600 But this table, constructed almost entirely from cases in my surgical practice, leaves out cancers of internal organs, and has far too few of the uterus, and of other parts that are usually ' specially ' treated. But even among those organs which are enumerated in it, we can gain no insight into the reasons of the various liabilities of parts. As Dr. Walshe observes, all that has been said to explain the liability of the breast and uterus, may be equally well said of the ovaries, which are comparatively rarely cancerous. So, too, what might be said about the brain and stomach, and testicle, would bo as applicable to the spinal cord, the duodenum, and the epididymis; yet these parts of similar systems are. St. Bartholomew's Hospital Reports, ii. * Lancet, May 3, 1856. = Trans. Med.-Chir. Soc. xlv. p. 890. LIABILITY OF CERTAIN PAETS. 799 severally, in complete contrast in their aptness to be tb.e seat of cancer. And, still more, the fact seems inexplicable that the organs in which primary cancer is most frequent are most rarely the seat of the second- ary disease. It seems impossible, at present, to discover what it is that makes one part more than another naturally fit to be the seat of cancerous growth ; or any part more fit at one time of life than at another. We are, of course, disposed to look for explanation to peculiarities of tissue, and to their changes with age : and we can hardly doubt that these are chiefly influential : and yet, as the medullary cancers of the eyeball and orbit show (p. 672), we must ascribe something to locality as well as to tissue. The allooatimi of cancers is certainly not wholly determined by aptness of structures. An osteoid cancer, for example, affects at once cancellous and compact osseous tissue, medulla, periosteum, and surrounding muscles ; a medullary cancer may occupy, from the first, many tissues both within and around the eye-ball ; when a cancerous breast is cut away, the recurrent growths appear very commonly ia the scar — i.e. in the same locality, though all the tissues affected by the primary growth are gone. Very numerous cases such as these might be cited ; they cannot, I presume, be explained, but they suggest the need of con- sidering always that morbid products may be determined to certain places as well as to certain structures. As each natural organ has its appropriate place as well as structure, so morbid growths may have laws of allocation not wholly determined by tissue. A question of much interest is connected with the liability of other tumours to become cancerous ; it is of interest not only as a subject of pathological inquiry, but in relation to an opinion which is often made a reason for operations — namely, that if a tumour of any kind is left to its own course, it is not unlikely to become cancerous. I have -looked carefully into this question, and I believe there are no facts sufficient to iustify the opinion that an innocent tumour is more likely to become the seat of cancer than many other parts of the body in which it is growing. The only case supporting such an opinion is that of cystic disease of the ovary. I think there is no doubt that it is not unfre- quent for cysts of the ovary to exist for a time as an innocent disease, and then become the seat of cancerous growths. But then the case of cystic disease of the ovary is so peculiar in all respects, that we cannot deduce from it any rule to be applied to instances of other tumours. With regard to the supposed transformation of any other tumours into cancers, the. facts are very few. 800 CANCEROUS AFFECTION OF SIMPLE TTJMOTJES. M. Lebert states that he has twice met with tumours whicli were at first of an innocent kind, but afterwards becarae cancerous ; but lie does not state whether they were in persons who had cancer in some other part : i.e. whether the cancer in the tumour were secondary or primary. Sir Benjamin Brodie mentions a case in which he removed a tumoTir, the general mass of which appeared to be fatty substance, somewhat more condensed than usual, but ' here and there was another kind of morbid growth, apparently belonging to the class of medullary or fungoid disease. ' ' A few other cases of the same kind are related ; and some would assume that in all the cases of mixed cartUaginons and cancerous tumours (mentioned at p. 623) the cartilaginous growth was being transformed into, or superseded by, the cancerous one. I see no good evidence for such an assumption : the contrary might very well be maintained in argument ; or the two growths might be regar- ded as simultaneous in their origin. It need not be denied that cancerous growths may occur in tumours that were previonsly of an innocent kind, but I feel quite snre that these may be regarded as events of the greatest rarity. My own experience has (perhaps by chance) been such as would indicate that innocent tumours are less liable to cancer than the struc- tures they resemble ; for, as I have elsewhere mentioned (p. 563), I have seen three cases in which cancer affected the natural structure of the mammary gland, while, close by, mammary glandular tumours re- mained unaffected ; and once several such tumours, after existing with scarcely any change for many years, disappeared on the occnrrence of chronic scirrhous cancer in one of the mammary glands. It may be asked, whence is derived the impression that so com- monly exists, that a tnmour of an innocent kind is peculiarly apt to become cancerous ? I believe it has arisen from several different kinds of deceptive cases. First, there are the cases of what I have refeired to as the suspen- sion, for a time, of cancerous progress ; in these the cancer seems for a time to be an innocent tumour ; it is judged to be so becanse it remains 60 long qniet ; and when it assumes the ordinary progress of cancer, it is said to be a tumour once innocent but now become cancerous. This might have happened in the first and fourth of the cases mentioned at p. 683 ; yet, without doubt, in these cases, the tumours that made little or no progress had all along the cancerous structure. ' Lectures on Vathohgy and Surgery, p. 282. CANCEROUS AFFECTION OF SIMPLE TUMOURS. 801 Anottier class of deceptive cases tave a history of tliis kind: — A tumour is removed wliicli is apparently of an innocent sort ; but, some time after, a cancer appears at tbe same part. The explanation of some of these cases is (as I suggested in p. 563), that a simple tumour has grown in a person having an hereditary or other constitutional tendency to cancer ; and that, in the rem^oval of this tumour the sur- geon has unwittingly supplied, by the local injury, what was needed for the production of a cancerous growth ; he has made some locality apt for the manifestation of a constitutional disease already existing. In a third class of cases, we may find in the same person a succes- sion of tumours, of which the first may have few or no characters of cancer, and the last, as if by gradual change, niay be evidently cancer- ous. I have referred to this in connection with recurrent tumours (p. 592) ; but the facts have little bearing on the; question whether an in- nocent tumour can become cancerous ; for here the transition is effected, not in one tumour, but in a succession of tumours. By cases such as these, we may, I believe, explain away the grounds for the assumption that simple or innocent tumours are parts peculiarly apt to become cancerous. Cancers may grow in such tumours, but the event is so rare, that it cannot, in any given case, be reasonably antici- pated. It remains to consider how parts may acquire an aptness for can- cerous growth in them, or, in most instances, how that aptness which they naturally possess may be increased ; for it is very observable that the ' exciting causes ' of cancer act with far greatest effect on the parts which are, without their help, most liable to it. Three chief conditions may be here enumerated — namely, the re- sults of certain diseases in intra-uterine life, indicated by congenital defect ; the results of certain diseases after birth ; the consequences of injury. The aptness for cancer due to congenital defect is exemplified in the peculiar liabiUty of moles or pigmentary nssvi to become the pri- mary seats of melanosis. I have already enlarged on this (p. 761), and have suggested that these defects, which we can easily see, may be only examples of a larger group which, though invisible, are not less efficient in rendering certain parts peculiarly liable to cancer. The aptness due to diseases after birth may be illustrated by the liability of the incrusted warts and scars, and other morbidly changed parts, to become the primary seats of epithelial cancers. For other than epithelial cancers the effect of disease in disposing parts to cancel is 3f 802 EFFECTS OF INJURY AND DISEASE. slight. We find no remarkable liability in parts that have been changed by inilammation, whether of common or specific kind. Few theories, I think, have been less fonnded than those which have regarded scir- rhous or mednllary cancer as, in any sense, the resnlt or sequence of inflammation. Parts that have been the seats of inflammation may become the seats of cancer ; but I doubt whether the proportion in ■which they do so be much greater than that in which they become cancerous when apparently healthy. The influence of injuries is more evident, About a fifth of those who have cancer ascribe it to injury ; and although, doubtless, some of these are wrong in their belief, yet, among the rest, there are some in whom the consequence of injury is too evident to admit of doubt. But here a distinction must be made as to the manner in which injury pro- motes the production of cancers. In certain cases the cancerous growth appears immediately after the common efiects of the injury. A person receives (suppose) a blow, and when its direct effects are passing away, a cancer appears in the injured part. I have cited cases of this kind in the history of medullary cancers (p. 681) ; among which, indeed, the event seems more frequent than among those of other forms. In other and more usual cases, a much longer interval passes be- tween the injury and the appearance of the cancer. The injured part seems to recover without change of structure. In most cases, indeed, such as those of ordinary blows on the breast, the direct effects of the injury are not such as we might expect to be followed by structural change, yet, doubtless, the part remains different from what it was. In a third class of cases, which are most frequently exemplified in the epithelial cancers, the injuries appear to be ineffective unless they are repeated time after time, so as to produce, we may suppose, a real change of structure in the part that at length becomes the seat of can- cer (p. 732). It is important to remember these different relations between in- juries and the growth of cancers, not only for pathology's sake, but for practice. It is often stated, as a rule, that those cancers are least likely to re- turn (it should be said, to return quickly, after removal, which have formed at the seat of injury, or some previous disease in the part. Now, this is only partially true ; it is probably often true of the epithelial can- cers that have grown in the seats of repeated injury, of scars, of frequent ulceration, and the like ; but I know no facts relating to scirrhous and EEI.ATIOX BETWEEN INJXJEY AND GEOWTH OF CANCERS. 803 medallary cancers that will support it ; and I believe that the cases in which cancers follow quickly after accidental injpry are just those in w hich a speedy return may be anticipated after operations. The growth ot a cancer immediately after an ipjury implies th^ existence of an in- tense cancerous diathesis, which no removal of the cancer is likely to attect ; but when a part has been repeatedly injured, and only at length becomes the seat of cancer, it implies such a }ow degree or state of can- cerous diathesis, as we may expect to remain long ' latent ' if the slowly- prepared locality, with all that has grown in it, be cleanly removed ; or when an old scar has become the seat of cancer, it may be that it is the only part of the body in which the formation of cancer is possible, and that its removal may remove all present liability to recurrence. Of the intermediate cases, in which some clegir time intervenes between the injury and the growth of the cancer, we must hold, I think, that the abiding effects of the injury keep the part, in a state peculiarly apt for the growth, till the constitutional condition is established. This being complete, the removal of the growth cannot change it ; and the injury done by the operation would be enoijgh to prepare a place, if none else were appropriate, for a recurrent cancer. S t2 804 GENERAL PATHOLOGY OF CANCEE- LECTURE XXXV. GENERAL PATHOLOftY OF CANCER. PART II. DEYELOrilENT, STRUCTURE, AND LIFE OF CANCEROUS GROWTHS. I ENDEAVOUEED to illustrate, in the last lecture, those two conditions which, judging from the general history of cancers, and the analogy of other specific diseases, we must assume as necessary precedents of a cancerous growth : namely, the cancerous diathesis, constitution, or morbid condition of the blood, and the condition of some part appro- priate for the growth. Now, according to the same analogy, the assumed cancer-material in the blood, if it cannot be removed by any natural excretory organ, will determine the formation of some abnor- mal organism in which itself may be incorporated ; and this organism will have a specific structure and mode of life significant of its origin. It is of these — the development, general structure, composition, and life of cancerous growths — that I shall now speak. It may be generally held that the characteristic structures of a can- cer are altogether of new formation. And the question may now be asked, in what textures are these characteristic new-formed structures developed, or by what process are they produced ? Some years ao-o Virchow directed attention to the changes in the corpuscles of the con- nectlve tissue of a part which precede the production not only of can- cer-structures, but of other new formations. These changes, he held, are not confined to those parts which are largely or almost entirely composed of connective tissue, but are observed in organs where the connective tissue occurs merely as an interstitial texture. The for- mation of new growths is preceded and accompanied by the multipli- cation of the nuclei of the corpuscles of the connective tissue ; the cor- puscles then divide and form groups or masses o^ young cells. In the DEVELOPMENT OF CANCER. 805 early stages of their production, these young cells present such ill- defined characters, that it cannot be said with any certainty whether they will become pus-cells, cancer-cells, or the corpuscles of some other new growth. To these young cells Virchow applied the term ' indif- ferent cells.' As the cause of irritation, however, becomes more mani- fest, the new-formed corpuscles acquire their characteristic form, and in a case in which the cancerous diathesis is manifested, they become cancer-structures. By other observers, also, the development of cancer-cells through proliferation of the corpuscles of the connective tissue has been described. But the connective tissue is not the only texture in which prolifera- tion of pre-existing corpuscles has been observed in connection with the production of cancer in a part. In the muscular tissue, also, changes in the corpuscles proper to the muscular fibre have been pointed out in connection with the production and extension of cancer in the sub- stance of a muscle. Professor C. 0. Weber has given ' some illus- trations of this process in cases of scirrhous and epithelial cancer of the tongue and lips, and Dr. Neumann has observed ^ similar changes in the pectoralis major in a case of scirrhous of the breast. By Professor Turner, also, changes have been described within the muscular fibre in a case of cancer affecting the scapula and its muscles.' At a in Figure 131, a muscular fibre is shown, in which mul- tiplication of the nuclei of the muscle-corpuscles has taken place, and the new-formed structures are arranged either in linear series or in little masses within the saroolemma. At 6, the multiplication is much further advanced, the proper sarcous substance has entirely disappeared, and the saroo- lemma is filled with a young brood of corpuscles. In other localities a more advanced stage was observed. The fibres were jagged and broken, and the corpuscles developed in their interior being set free, formed collections of small new cells within the substance of the Fig. 131. ' Vii-uliow's Archiv, xv. pi. si. ^ Bid. xx. p. 1.52. « Edinb. Monthly Jour. April 1863. 806 DEVELOPMENT OF CANCER. mascle. By the extension of this process in differeilt parts of the muscle, the fibres were in a gi'eat measure disintegrated — the increase in the size of the cancer being obviously due to the multiplication of the oorptisoles within the muscular fibre, and to their subsequent liber- ation. Pathologists have long recognised that the cells met with in cancer are formed on the type of gland^cells and of epithelial cells, and that the cancer-cells are imbedded in alveoli or spaces within the con- nective tissue. This similarity in formation, and to some extent in arrangement, to epithelial structures, has led to the introduction of an hypothesis that not merely epithelial cancer, but cancer generally, takes it rise from increase and multiplication of pre-existing epithelial cells, and not from proliferation of the corpuscles of the connective tissue. Attempts have been made to connect this hypothesis with the results of embryological inquiry ; and the recent observations of Profes- sor His have been more especially referred to as hearing out this view of the structural afiinities of cancer. Of the three germinal layers into which an. early embryo is subdivided, two only give origin to true epithelium. The outer, to the epidermis, the glands of the skin, the sexual glands, the crystalline Jensj aid the central organs of the nervous system. The inner, to the intestinal epithelium, and the secretiiig cells of the pancreas, liver, kidney, etc. Whilst from the middle layer of the embryo, the connective substances, bones, muscles, blood and lymph vessels, and distributory nerves, proceed. It is further contended that a texture, which is derived from one of these germinal layers, can never be produced by any other; but that the differentiation of struc- tures takes place from the beginning. Hence, it is said, there can be no ' indifierent ' cells, in the full sense of the term as used by Virchow. But a new formation of any given texture can only arise in connection with one or other of the parts or organs which are descended from the layer of the embryo in which that particular texture was originally produced. According to this view, therefore, epithelial and gland cells cannot be derived from the connective substances, and true epithe- lium cannot give origin to connective tissue.' If it be true, then, that ' This hypothesis is fully discussed in the following works : — Thiersch: Der Epithelial Krebs, Liepzig, 1865. Waldeyer: Die Entviicklunff dtr Cardnome, Virchow's ArcUv, xli. Billroth: Die Allgenmne Ckirurgische Pathologie und Thurapie, 3d edit., 1868. Liicke ; Billroth und von Pitha's Handhuch, ii. part i. p. 205. It should be stated, however, that the relation of the 'materies morbi' to histological structure and embryological development, more especially in connection with gout^ and rheumatism, was advocated some yeai-s ago by Professor Laycock DEVELOPMENT OF CANCER. 807 tbe cancer in its stracture is conformable to the type of epithelium, and if epithelium can only be produced from its like, then the conclusion follows that cancer, as a primary growth, can only be developed in con- nection with parts in which epithelium occurs as a normal constituent of the texture. Any change which may take place in the adjacent con- nective tissue would be of a secondary nature, due either to the irrita- tion of the canoer-juice, or to the wandering into this texture of the young cell-elements of the cancer. In conformity with this view, some ©f the most recent writers on the pathology of cancer recognise only two primary subdivisions of this disease — the Epithelial Cancer, or cancer of the skin, and the Glandular Cancer, or proper Carcinoma, such as affects the mammary gland and the glands and mucous mem- brane of the alimentary canal. But it is impossible to reconcile such a doctrine as this with the facts observed in a clinical study of cancer. For if it were true that cancer could only arise as a primary growth in epithelial structures descended from the outer and inner layers of the embryo, then the pri- mary formation of cancer in organs which are derived from the middle embryonic layer ought never to take place. There ought to be no such thing as a primary cancer of bone or muscle, of inter'inuscular tissue or of lymph-glands,— and, accordingly, it is denied that primary cancer does occur in any of these parts, and all the growths in them which are commonly regarded as primary cancers are transported into the ill- defined collection of sarcomata. Now, there is no principal fact in the life of a cancer of the breast (for instance) which is not equally observed in what is commonly called a cancer of bone. The primary cancer of a lymph- glaud is not distinguishable, except in its apparent origin, from a secondary one : structure, and life, and relations, are alike in both. Equally alike are the primary and secondary cancers in inter- muscular spaces. In all these cases— (and primary cancers of bone, muscles, lymph-glands, and other middle-layer-organs are far from rare) iji all these cases the evidence of identity of nature is too strong to be set aside by the supposed necessity of believing that there can be no primary cancers except in the birthplaces of epithelia. tn general construction, cancers may be either infiltrations or separate masses : i.e. their elementary structures may be either com- (Lectures on the Principles and Methods of Medical Observation and Besearch, Edin- burgh, 1856), wlio, not only in this, tut in other writings, holds that a particular irritant affect's structures having something in common as totheir structure or nature. 808 STRUCTURE OF CANCERS. mingled, and form one mass, with those of a certain portion of a natural part, or they may be collected' unmixed in a mass ronnd which the natural tissues are extended. In any case, the mass they form is a growing part ; and herein is the ground for classing them with tumours, and for separating them from those results of disease, such as inflammatory products and tubercle, which may be increased, but prob- ably not by their own power of growth. (See p. 373, etc.) In both their likeness and their unlikeness to other tumours, cancers exemplify what is common among specific diseases — namely, that they take certain general characters of common diseases, and as it were, stamp them with some specific mark. Syphilitic emptions are known by some specific character, added to those which are common to other eruptions of the same group : each specific form of ulcer has its own together with common, characters ; so, cancers have many characters in common with other tumours, but specific characters are superadded. (See p. 354). When, as in infiltrations, the cancer-structures are mingled with those of a natural part, the most frequent event is, that the growth of the cancer preponderates, and at length excludes that of the natural structures ; so that, finally, the latter disappear and a substitution (to use M. Lebert's term) of cancer in the place of the natural tissues, is effected. But the reverse of this sometimes happens ; instead of atro- phy, hypertrophy ensues in the natural structures of the affected part ; and within the same area both normal and abnormal structures grow excessively. Thus it is with the growths of bone that form skeletons of the medullary cancers, and with those of connective tissue that extend into the exuberant epithelial cancers. The developed cancer-structures, if we except the few cases in which they are fibrous or osseous (pp. 628, 758), may be generally described as formed of nucleated cells, or of such corpuscles as are rudimental of, or degenerate from, the nucleated cell. Herein, and in the fact that the corpuscles are neither imbedded in formed inter- cellular substance, nor orderly arranged, lies one of the chai-acters by which cancers are distinguished from other tumours, and from all na- tural parts. Their chief heterology, in respect of construction, is in this disorderly crowding of their elements ; and I believe it is constant, unless when they imitate the plan of some adjacent natural gland-struc- ture (pp. 665, 674). The question is often asked, What are the characters of the true cancer-uell ? or — Has the microscope discovered any strnctnre which STRUCTURE OF CANCERS. 809 IS decisive of cancer, wherever it is found ? The answers may be— (1.) Where cells, such as are described at pp. 613 and 715, are fonnd alone, or chiefly composing a tumour, we may be certain that the tumour is a cancer: we may, therefore, regard these as especially cancer-cells. (2.) When a tumour is composed, chiefly or alone, of corpuscles, such as the nuclei described at p. 665, or any others which we can trace as rudiments or degenerations of the cancer-cells, the diagnosis of can- cer is not less certain : structures such as these are found composing none but cancerous tumours. But if the question be changed to— Are there any cancers which are not formed of structures such as these ? the answer must be afiirmative : for there are rare tumours which pre- sent the whole clinical history of cancers, and which should therefore be called by the same name, though they have not these peculiar cancer- structures, or have them in very subordinate quantity. I do not refer here to cancers of which all the structures are imperfect, or degenerate, or diseased ; but to such as the fibrous cancers (p. 628), the osteoid (p. 754), and certain varieties of the medullary (pp. 666, 667).' These aU deviate from the assumed specific cancer-structures ; and two of these, the fibrous and osteoid, approximate to the characters of natural tissues. Together with the disorderly construction, and the peculiar eoll- forms, we may often observe, as characteristic of cancers, the multifor- mity of the structures composing their mass. It is not equalled, I think, by any tumours, unless they be the cartilaginous or the mixed glandular and cartilaginous (pp. 497, 517). The variety of forms appears due, in part, to the mingling of the perfect structures with such as are in various stages of development and degeneration ; and, in part, to what seems like a disorderly overgrowth and endogenous increase in cells and their contents. All these forms have been already described ; but thoy may be thus enumerated and arranged : — (1.) The chief of those to be referred to incomplete development are the free nuclei, and abun- dant undeveloped liquid or cancer-juice (pp. 614, 665, 713). (2.) The chief forms due to degeneration are the transitions from cancer- cells or nuclei to granule-masses (pp. 61 5, 713) ; the withering corpus- ' Some pathologists would exclude from the name of cancer all these tumours, and all which are not composed of the ' specific' cancer- strxictures ; hut I feel sure that we shall do right if (when a choice must be made) we choose modes of life, rather than structures, for determining the affinities of morbid products, and for arranging them under generic names. As of all tumours, so, especially of cancers, the true nature is to be apprehended only by studying them as living things. (Compare pp. 37.9, 691, 77S.) 810 STEUCTUEE OF CANCERS. cles with fatty degeneration found in the material like tubercle in can- cers (p. 615, et seq.) ; the calcareous deposits (p. 686) ; the abundant granular matter ; and the occasionally mingled melanoid cells (p. 747). (3.) Overgrown or abnormally-developed corpuscles are seen in the various extensions of cell- walls into angles and processes (pp. 613, 666, 714) ; and in the enlargement of free nuclei and their assumption of .the characters of nucleated cells (pp. 614, 665, 713). (4.) The endo- genous increase in cells is exemplified in all that is described of the brood-cells and laminated corpuscles of the medullary, epithehal, and colloid cancers (pp. 676^ 714, 771). It would be too tedious eyen to enumerate more forms than these of the component cancer-structures, and I need not again describe them. It is not their multiformity, so much as the existence of many of them in a single mass, that is generally characteristic of cancer. Various as are these corpuscles of cancers, it is yet to be observed that none so entirely differ from those of normal structures, that we cannot point out among them a type or parallel. No observation since Miiller's time has invalidated his demonstration of this principle! The experienced microscopist will, indeed, very rarely fail in the diagnosis of a cancer by its minute structures ; but he only discriminates them as specific modifications of the nucleus, nucleated cell, endogenous cells, and other forms, of which the types are in natural parts ; he finds among them no new type-forms. In like manner, the elemental cancer-structures show no method of growth or development which is without parallel in natural struc- tures ; they are formed and increased according to the same general laws as are observed in the normal rudimental structures ; their peculiarities) in this regard, are chiefly in the seeming disorder that often prevails among them — in the absence of an apparent singleness of design. The abundance of cell-structures in cancers has suggested that they are lowly organised, and many consequences have been hence deduced. The terms ' high ' and ' low,' in relation to structures, are derived from very arbitrary estimates, and are too fallacious for any important de- duction in pathology ; still, it may be observed, that among morbid products, canciers should stand high rather than low ; for their elemen- tal forms are on a level with those of natural excretory organs, and more developed than any but the best inflammatory lymph. If there were any correspondence, such as has been assumed, between lowness of organisation and malignancy, the ordinary croupous or corpuscular STRUCTUHE OF CANCEES. 811 lymph, should be a much worse material than cancer; but malignant properties, like malignant spirits, are not confined to the vilest forms. The proper structures of cancers are supported and held together by fibronsj membranous, or other connective tissue, forming their ' stroma,' which forms an alveolar structure, in the meshes of which the cancer-cells lie. This stroma, as I have elsewhere described, is formed in the case of cancerous infiltrationSj by the natural fi.brous or other tissues of the infiltrated part, which, in different cases, are either gra- dually reduced in quantity or increased. In these cases the stroma is no proper cancer-structure) and varies with the nature of the aifected part (pp. 617, 660, 703). But in distinct, isolable, cancerous tumours, a stroma is formed appropriate to the cancer, and, in many cases, with a definite mode of growth — the dendritic mode (pp. 669, 764). Gene- rally, however, it is only in its plan or construction that the stroma is peculiar ; its tissues are simply membranous, or nucleated, or filamen- tous, or, it may be, osseous : they are not cancerous.' We see, there- fore, in cancers thus formed, as well as in the cancerous infiltrations • with overgrowth of the natural structures, the coincident growth of morbid and of normal tissues within the same area, and out of the same mixed materials i With the stroma of cancers are their bloodvessels, among which v?e -mast again distinguish, as in the preceding paragraph, that some are the vessels of the affected part now involved in the cancerous infiltra- tion, others are new formed. Concerning the changes which the first- named may undergo in the growth of the cancer, we have, I believe, at present no knowledge. They are not, as in tuberculous infiltrations, gradually destroyed or removed rather they seem to be increased ; so that an injected scirrhous cancer of the breast (for example) often appears more vascular than the adjacent substance of the mammary gland, though, in the first instance, it had only the bloodvessels of the part of the gland which it occupies. No direct observations, however, have shown the method of this increase. ' Exceptions to this statement must be made foi? certain fibrous and osteoid cancers, in which the fibrous and osseous tissue, if regarded as a stroma for the mingled cancer- cells, must be admitted as a proper cancer-structure ; and ior some cases of medullary cancer, in which a kind of stroma is described as formed of series of elongated cancer- eellsi It must be observed, also, that the line between infiltrations and isoluble tumours is here, as elsewhere, somewhat artificially drawn. It is not to be denied that the latter may involve small portions of natural tissues, which may remain intersecting or partitioning their masses, and supplying a framework upon which their peculiar stroma may be constructed. 812 CHEMISTRY OF CANCEES. The new-formed bloodvessels of the insolable cancers and the can- cerous outgrowths extend from those of the adjacent parts. It is by some thought that they are formed as an isolated system of tubes in the cancer : I know no satisfactory evidence of this ; and the associated theory of blood being formed in the substance of a cancer, and out of cancer-materials, seems to me wholly untenable. The descriptions already given of them (pp. 659 and 765) will show that the bloodvessels of cancers do not differ from those of other abnormal growths, except in that generally their calibre is more than proportionate to the thick- ness or complexity of structure of their walls. Hence the term ' colossal capillaries ; ' and hence, when the bloodvesels are abundant, the hke- ness to the simple vascular erectile tumours ; but in neither of these respects are the vessels of cancer without parallel in those of natural parts ; those of the placenta and of the cavernous erectile tissue might be their types. Such are the component structures of cancers. We might hope that chemistry, carrying its analysis far beyond the reach of sight, would find in them something as different from natural compositions, as their mode of life is from that of any natural member of the body. But it has failed to do this : and the numerous analyses made since those of Miiller have not materially added to his results.' In a general com- parison, the cancers are distinguished by the predominance or exclusive existence of albuminous compounds, while in the non-cancerous tumours gelatinous compounds (or in the adipose tumours, the fatty) are the chief constituents. But there are large exceptions on both sides. The fibrous and osteoid cancers yield abundant gelatine ; the albuminous sarcomata of Miiller (including probably, many of the least developed proliferous cystic tumours and the recurring fibroid tumours) are as albuminous as the typical cancers. It is probable, moreover, that the broad general difference between albuminous and gelatinous growths is not directly related to their respective properties, as malignant and innocent, but to their retaining or passing beyond the cell-form. The want of a more definite result from chemical analysis is not to be ascribed to the absence of difference between cancerous and normal materials — we may be nearly sure that they are chemically essentially distinct — but, rather, to the fact, that an exact analysis of cancer- structures is nearly impossible. That which would be given to a ' The test of these analyses may be found in Lebert's TraiU Pratiqtie, p. 44, et sc^. LIFE OF CANCER. 813 chemist for examination is not a pure cancer- material, but a mixture of it with the materials of blood, blood-vessels, connective tissue, and, in many cases of the natural or degenerate structures of the part in which the cancer has been growing. Add to this, that, in every sample, the cancer-structures themselves are probably, in all stages of development and degeneration ; and the search for the essential chemical properties of cancer will surely seem as difficult as it would be to find those of muscle, or of bone, in the analysis of the whole of a foetal, or of a paralytic, limb.' In studying the liffe of a cancerous growth, we have always to con- sider it as adding to the conditions of disease which already existed, and which usually still continue ; it is a new factor in an already com- plex morbid process. The formation of cancerous material in the blood does not cease because some is incorporated in a growth ; the transfor- mations of parts, making them apt for the allocation of cancer, do not cease because one part is occupied. In all the history of cancers, therefore, we have to study the continuation of those processes which I have described in the last Lecture, as preceding the growth of the can- cer, and which now (with rare exceptions) are concurrent with it, and increase with it. Before the formation of a cancerous growth, we trace two distinct though usually concurrent, processes ; namely, that which leads to the cancerous condition of the blood, and that which makes certain parts fit to be seats of cancerous growths. When once a growth is formed, it introduces a third element of disease, without necessarily removing or diminishing either of those that preceded it. As a living part, the cancer, like any other tumour, has the power of self -maintenance and of growth, which power, though favoured by the continued or increasing cancerous condition of the blood, is, probably, not dependent thereon. Also, in the results of its nutrition, the cancer reacts upon the blood, and through it influences the whole economy ; and these influences are added to the cancerous diathesis or cachexia which is usually, at the same time and of itself, increasing. The manifestations of life in a cancer may be divided (but it is too artificial a division to be followed far) into those which are pro- gressive and those which are retrogressive. The latter are traced in ' The case of the colloid material may not seem open to this objection ; but the colloid is, probably, njt a true cancer-substance, but the product of disease in cancer. 814 GROWTH OF CA>XER. the various degenerations and diseases of its structures ; the former in its growth, extension, and multiplication. The chief characteristics of the growth of cancers are seen, in those that are infiltrated, in their invasion of all tissues, as if indifferently. Thus the scirrhous cancer of the breast, though limited for a time to the mammary gland, at length extends beyond it, and gradually occu- pies every surrounding part alike : thus the epithelial cancer extends from the integument of the lip to its muscles, glands, and aU deeper tissues, and thence to the gum and jaw ; and thus the medullary cancer grows into and through the walls of bloodvessels and other canals, and extends, among their contents, along their cavities. Such reckless growth (if it may be so called) is scarcely known except in cancers. They supply, also, the iastances of most rapid increase ; but although they do this frequently enough to make rapid growth one of the diag- nostic signs of cancers, yet the cases are far from rare in which the growth is very slow. Pew diseases are more variable than cancers are in this respect. (Compare pp. 618, 682, 736.) Two things administer to the growth of a cancer ; namely (1) the continued formation of the specific material in the blood ; and (2) the inherent power in the cancer, as a living part, to assimilate to itself the common or indiiferent materials of the blood. The first of these maintains and augments, as it originated, the growth ; the second efiPects an independent increase, like that of a non-cancerous tumour. In ordinary cases, both these conditions are engaged in the growth of cancer ; but, if the first fail, the second may suffice. The canceroua diathesis may cease, or be exhausted for a time, or sometimes even permanently ; cancer-material, we may suppose, is no lopger formed in the blood ; yet the cancer may subsist and increase by its own power. It may do so like any other tumour ; especially like those which I men- tioned (p. 386) as beginning during or after some general disease, but continuing to grew when that disease has ceased. Now, in this state, the cancer might be essentially a local disease living upon the materials of blood restored to health, though capable, probably, of infecting that blood, and inducing secondary phenomena of extension and multiplication. It would illustrate in this state a prin- ciple which we are too apt to forget — namely, that diseases of constitu- tional origin may become wholly local. The origin of local diseases in constitutional conditions has been well studied, and the necessity of constitutional treatment, in chronic as well as in acute diseases, has been rightly referred to the local aflFections beiijg maintained by tbp EXTENSION OF CANCER. 815 continued morbid condition of the blood : but it has been less considered that, after the constitutional disease has ceased, the local one may of itself continue, and need local treatment. Such cases are revy frequent. One often sees syphilitic ulcers, which doubtless had a constitutional origin, and were maintained by specific material in the blood, and would have needed specific treatment of the blood for their cure ; but now, while retaining their specific forms, they are curable by local treatment alone. Just so it may be, though very rarely, with cancers. While the cancerous diathesis is suspended, they may subsist by their own powers of assimilation ; and I believe the very few credible cases of recovery after operation are to be referred to the chances which have led to the occasional removal of such as were thus localised, or else to the removal of the only part fit to be the seat of cancer. The extension of cancers (so far as it may be distinguished from their growth) is that which takes place through lymphatic vessels to their glands. The number of cases in which lymphatics, filled with cancer, have been traced from the primary growth to the nearest glands, is suflicient to make it probable that the disease often thus is propagated by embolic extension from the one to the other. But, even when such tracts of cancer cannot be traced from the primary disease to that in the lymphatic glands, I think Mr. Simon's suggestion is very probably true — that the disease is one of the lymph, not of the parenchyma or vessels of the glands. We do not, indeed, yet know exactly the derivation of the lymph, nor what is its relation to the materials of the part from which it comes ; but what we do know of it is consistent with the belief, that lymph, from the seat of specific disease, is likely to contain such of the materials of the disease as may either be carried to the blood, or may be organised in the lymph after the same plan as in their primary seat. The characters of the secondary cancers thus formed in lymphatic glands, arB already described (pp. 620, 675, 719, etc.) ; and these general principles may be gathered concerning them : — (1). The disease in the lymphatic glands usually repeats exactly that in the primary seat; the apparent differences between them de- pend only on the structures among which the cancerous elements are placed. Bnt this rule is not without exceptions (p. 622, etc., as cited above). (2.) The cancer in the glands seldom appears before that in the primary seat has made considerable progress. At a general rough estimate, it appears about midway in the course of the disease 81fi SECONDARY CANCKE. towards death. The delay is, perhaps, not to be explained, seeing that lymph is carried from the primary disease as well in its earlier as in its later stages. (3.) While the disease in the glands makes progress, the priioary disease usually keeps the lead which its earlier origin gives it. Occa- sionally, however, that in the glands so far surpasses it that we are in danger of overlooking the primary disease (p. 622, etc.). I do not know how the fact can be explained ; but it has its parallel in the occurrence of primary cancer in the glands that are usually secondarily diseased, and in the recurrence of cancers after operations in the glands, rather than in or near its primary seat. (4.) The lymphatic glands usually become cancerous in direct succession from the primary disease to the thoracic duct. The ex- tension is, generally, made slowly ; in scirrhous and epithelial cancers, the disease often remains long limited to the glands nearest to its primary seat ; in nearly all cases, also, it is prone to increase in these proximate glands much more than in those more distant. Barely, the secondary cancer appears in distant, rather than in proximate glands ; but in these cases it illustrates the multiplication, not the extension, of disease. The multiplication or discontinuous increase of cancers may take place in the following ways : — (1.) The cancer-growth may multiply itself, from its primary seat, to a part not directly continuous, but in contact, therewith. Thus Dr. Hodgkin and Dr. Budd relate cases of cancer in abdominal and pelvic viscera, with corresponding formations on the portion of parietal peritoneum or other parts in contact with them ; and thus there may be correspondence and contact of cancers on the two layers of pleura, or on the glans and prepuce. (2.) The multiplication may take place on a surface not in contact, but continuous, with the primary seat ; as in cases by Mi- , Simon (loc. cit.), in which cancerous gp"owths were found scattered along the tract of mucous membrane leading from primaiy cancers in the kidney and lung. In both these cases, the multiplication of the cancers seems to be the result of simple transference of the materials from the primary to the secondary seat of growth : it is effected by a kind of inoculation. The materials of a cancer pass from its mass, and develop themselves, and grow, where they rest. (3.) Cancers are multiplied in parts neither directly continuous, nor MULTIPLICATION OF CANCER. 817 m contact, with the primary seat. In some instances the parts are near, in others remote from, the primary disease. When cancers are thus multipUed near their primary seat by ' irra- diation,' we find them, as it were, springing up in an area which gradually widens, and of which the primary cancer is the centre. Thus it is with the tubercles in the skin and muscles near a scirrhous breast (p. 623) ; and with the secondary medullary, osteoid, and melanoid growths scattered round the main disease, but separated from it by intervals of healthy tissue (pp. 752, 760). It is possible that the protoplasm of the young cancer-cells niay, like that of the lymph or white blood corpuscles, possess the property of contractility, so that a ' wandering ' of the cells may take place. In this manner, by migrating from their original habitat, they may act as centres for the production of secondary cancers in the neighbourhood of, or at some distance from, the primary growth. This mode of increase of cancers may be due to the seeming tendency of specific diseases to be allocated, not only in certain tissues or organs, but in certain places or regions (pp. Q7'S, 799). Certainly, peculiarities of tissue have little to do with this grouping of the cancers around the primary formation ; for they may be found, promiscuously, in all the surrounding tissues within a certain area. Neither does the course of lymphatic or other vessels seem to determine their places. In the increase of cancers by multiplications distant from the primary growth, there is scarcely an organ that may not be afieoted. We see this most easily in the cases of melanoid cancers ; yet their multiplicity is, probably, not greater than that of other medullary cancers (see p. 682). The cancers that thus least frequently multiply are the epithelial and colloid, and those, of whatever kind, in the rectum, urinary organs, uterus, and brain. The organs in which the secondary cancers formed by multiplications are most frequently found are the liver and lungs. After these organs, the most frequent seats of such secondary cancers are, I believe, the pleura, bones, lymphatic glands, and subcutaneous tissue : after these, no rule or proportion can be stated, except that many of the organs in which primary cancers are most frequent are very rarely the seat of secondary cancer, e.g. the breast, uterus, testicle, and stomach. ^ At present, probably, none but a very general explanation of this ' Lebert gives the best statistics on all these points (p. 81). 3g 818 MULTIPLICATION OF CAXCEE. multiplication of cancers can be given : we can scarcely venture to guess what determines the above-mentioned peculiarities. The general explanation may refer the multiplication to two sources, which are in- dependent, though concurrent and mutually influential — namely, the increasing cancerous diathesis or morbid condition of the blood, and the conveyance and transplantation of cancerous matter by the circulating blood or lymph. The constant increase of the morbid condition of the blood was shown, in the last Lecture, to be a general fact ia the history of cancers. And, though it may sometimes be represented only by the accelerating growth of the primary tumour, yet we might well expect that it would often produce a numerical increase of cancers. The common indication of the most intensely constitutional cancerous disease is the simultaneous or rapid formation of numerous primary growths in different parts. This is sometimes witnessed at the very onset of the disease (p. 675, 682) ; and it is, probably, also exemplified in the later periods of ordinary cases. Certain cases scarcely admit of explanation, on the supposition that the first-formed cancer is, in any sense, the source of all that grow after it : such, for example, as those in which a sudden rapid multiph- cation of cancers takes place (p. 683), and those in which they appear some long time after the removal of the first-formed growth. The second method of remote mnltiplication of cancers, that of con- veyance by the blood, or embolic extension, is sometimes visibly demon- strated, and may almost always be assumed. I have spoken of cases (p. 785) in which cancers so grow into veins, that we cannot doubt fragments may be washed from them by the blood, and may grow wherever they come to rest ; and I related one instance of osteoid can- cer in which this almost certainly occurred (p. 762).' But, even when no such intra-vascular growths appear, similar events may occur. In a case of primary cancer of the liver, in which the growths were all tinted with bright yellow by the bile, I found numerous small cancer- ous masses of the same colour infiltrated in the Inngs ; and the small branches of the pulmonary arteries leading to these were filled with bright yellow substance, as if they had been minutely injected with chromate of lead. The accidental colour of the cancer-materials, in this case, made their transference from the liver to the lungs very evident ; but the same event is often, though less plainly, traceable. ' It is probably only by tbis means that tumours, other than cancers, can be gen- erated in parts distant from their primary seats. See the Tery rare case of cartilagin- ous tumour related at p. 522 ; and the Lecture on Eecurrent Tumours. MULTIPLICATION OF CANCEB. 819 The transference of cancer-materials, with the blood from a cancer abeady formed, need not always be seen to be believed. Its frequent occarrenoe is made very probable by the many points of correspondence which Dr. Walshe ' has shown, between the dissemination of cancers, and that of secondary abscesses after the entry of pus or other degene- rate inflammatory prodncts into the veins. The peculiar liability of the liver and the lungs to be the seats of both these secondary diseases, and the evidence that they are the organs in which foreign matters, introduced into the circulation, are most commonly arrested, may nearly prove that they are, in all these cases alike, affected by materials brought to them in the blood. We need not assume that entire corpuscles of pus or cancer must be thus carried for the multiplication or dissemination of disease. Cancer- juice or minute fragments of the protoplasm of the cancer-cells, mingled with the blood, may be as effectual as entire corpuscles ; and must almost necessarily be assumed, in the explanation of cases in which the dissemination takes place, not in the lungs, but in organs be- yond them in the course of the circulation, as, e.g., in the very frequent affection of the liver in cases of cancer of the breast.^ The materials conveyed with the blood from the primary cancer must be such as are capable of development, in order to the multiplica- tion of the disease. In the ordinary absorptions occurring in the pro- cess of natural nutrition, and probably, also, in those that take place in the nutrition of cancers, the venous blood carries away only degene- rate or refuse materials, such as we may assume would be incapable of development. I have mentioned cases (pp. 675, 688), in which masses of cancer, probably thus degenerate, were absorbed, without any ap- pearance of consequent dissemination or other damage. We do not know what leads to the removal of such cancerous matter as can be de- veloped ; but the necessity of some change in the ordinary process of absorption is evident, and is the more worth studying because there are corresponding similar differences in the effects of the absorption of pus and other morbid products. Such are the various means of numerical increase of cancers — by local inoculation of parts continuous, or in contact, with the primary disease ; by extension, through a transportation of particles, or through continuity of lymph to the lymphatic glands ; by transportation of potent cancer-materials with the venous blood ; by the cancerous con- ' Nature and Treatment of Cancer, p. 106. ^ Sibley, Med.-Chir. Trans, slii. 3 G 2 820 DEGENERATIONS OF CANCEE. dition of the blood becoming, of itself, more intense. In certain cases the increase may be accomplished by all these means at once ; the secondary cancers, also, as soon as formed, become like centres, from which a tertiary formation may be derived, as they were themselves derived from the primary ; and to all this it may be added, that, with lapse of time and failing general health, all parts of the body are con- stantly becoming less resistent of disease, and more appropriate for the residence of morbid growths. By all these means, it is evident that the multiplication or general- isation of cancers might be explained withont reference to a primary cancerous condition of the blood. Doubtless it might be that, if a cancer were entirely local in its origin, it would thus extend and mul- tiply, and infect the lymph and blood, and become a constitutional disease. But the choice between the rival hypotheses of the local or the constitutional origin of cancer must be determined by other facts than these, which, like many more, may be fitted with either of the two.' I have now to trace a general history of the retrogressive life of cancers ; of that which, as I said (p. 814), is signified in their various degenerations and diseases. The degenerations of cancer- structures are like those of natural parts, and of other products of disease. Examples may be cited of every form corresponding with those enumerated on pages 72 and 277. (1) The withering, or wasting and drying, of the structures is exem- plified in many scirrhous and epithelial cancers (pp. 619, 714) ; (2) The fatty degeneration is so common that it might be hard to find a cancer in some of whose corpuscles it does not exist. The granule- masses (' the mulberry-cells ') of cancers are hence derived, as they are from many more morbid products. Hence, too, the ' saponification ' of ' But the assumption that the generalisation of cancer is entirely due to diffusion from a local primary disease is apt to lead to disappointment in practice, when it is assumed that the infection of blood, or other manner of diffusion, does not begin till the primary cancer has attained a -risible or tangible size, and that, if now it be re- moved, recurrence will not ensue. The analogy of all inoculable and blood-infecting diseases would tell that, as soon as ever a cancer is formed, and even while it may be stiU microscopic, or only a few days old, its influence on the blood may begin, and be effective for mischief. So far as concerns the question of operating for cancer it really matters little whether we hold it to be from the first a constitutional disease or at first local, for we can never have a chance of excising a cancer which has not already infected the blood, or become in some way constitutional. DISEASES OF CANCER. 821 cancers (p. 686) ; -while to the fatty degeneration, ccnihined with more or less of ■withering, we may ascribe the masses of substance, like tubercle, so often imbedded in medullary cancers (p. 658), and the minuter spots and lines of soft ochre or yellow substance traversing scirrhous and medullary cancers, like a 'reticulum' (pp. 615,667). (3) A calcareous degeneration is observed in medullary cancers, and in osteoid (pp. 686, 758) ; and, probably, exists in many instances mingled with the fatty degeneration. (4) Pigmental degeneration is probably the essential character of melanoid cancers (p. 745). (5) Thickening of primary membrane is, perhaps, indicated in some of the cancer-cells whose walls appear simply laminated (p. 716, Fig. 120, d). A liquefactive degeneration may occur in some of the softenings of cancers ; but, so far as I know, it ensues only in connection with disease. (Compare p. 305.) In the interpretation of degeneracy in cancers, we must again refer to the two conditions of their life ; namely, the maintenance of the morbid condition of the blood, and their inherent power of self-mainte- nance. The supervention of another diathesis may lead to the degen- eration or death of a cancer (pp. 640, 688) ; but this is extremely rare. A transformation of diathesis may, I am. disposed to believe, lead to the degeneration of one cancer while it promotes the growth of one or more others ; for there are cases of apparent metastasis of cancer, in which the primary disease has withered, while secondary growths appear to have increased.' But these cases, again, are too rare to be reasoned from ; and the usual course of events indicates that degeneration of cancer is, in the great majority of cases, an essentially local thing. For, commonly, part of a cancer, or one mass in a group, degenerates, while growth continues in the rest ; and extensive degene- ration is often found, in cases in which the rapid progress of the disease has testified to the full maintenance of the morbid blood. Hence the unhappy rarity of the recovery from cancer. One that is degenerate or absorbed may be as inaffective for harm as one that has been cut away ; but the constitutional element and progress of the disease are as little affected by the natural as by the surgical process of removal. We cannot tell what are the local events that lead to this de- generation ; but I suspect that the chief of them is the local obstruction of bloodvessels by growths of cancer into them. The diseases of cancers, like the degenerations, are essentially local ' Cases cited by Walshe, pp. 110, 134. 822 DISE.iSES OF CANCER. processes ; they are most apt, iadeed, to occur in the enfeebled general health, but they do not certainly indicate a decreased diathesis. It may suffice to refer, for examples of most of the diseases, to those already cited (pp. 640, 686, etc.) ; but two require more consideration ; namely, softening and ulceration. Some have believed that softening is almost a natural event in can- cers, a change parallel with that in tuberculous deposits, and a necessary precedent of ulceration ; while others, recoiling from the error of this belief, have written of the softening of cancers as a rare and unim. portant accident. The truth is about midway between these extremes. There is no probability that (as some have supposed) the hard scirrhous cancers ever become medullary by any process of softening ; a softened cancer is very different from a soft one. There is no natural tendency in cancers to become soft in their later stages ; those of the oldest date commonly retain, if they do not increase, their original consistence. Neither is softening a necessary precursor of the ulceration of cancers. But any scirrhous or other cancer may be softened by degeneration, or, more effectually and extensively, by inflammation of its substance. The fatty degenerations of which I have just been speaking are usually at- tended with a softening ; but the altered substance becomes drier and more greasy than before ; it does not appear, in any degree, liquefied (p. 615). That which is generally understood as softening of cancer is, so far as I have seen, a more acute process, and the result of iuflam- mation of its substance. One may see it very well in the exposed pro- truding growths of medullary cancers (p. 686) ; or in those parts of them which lie just beneath inflamed portions of the integuments. Sometimes, also, within scirrhous cancers that have rapidly enlarged, with heat and pain, and redness of the superjacent skin, one finds large portions liquid, or else very soft, as it were rotten, shreddy, and infiltrated with pale, yellow, serous, or puriform fluid. Sometimes such softening has distinct appearance of suppuration in the centre of the cancer ; but these cases (which have suggested the terms cancerous suppuration or abscess) are, I think, naost frequent in the secondary epithelial and medullary cancerous afiecfcions of lymphatic glands. If, as I believe, these softenings of cancer are the results of inflam- mation, they correspond with the softenings produced by the same disease in natural parts (p 296) ; they are the results of such defective nutrition as always ensues in the proper textures of an inflamed part ; and when pus is diffused in the softened cancer-substance, the process may be compared with ordinary purulent infiltration, which is always DISEASES OF CANCER. 823 attended -with, loss of consistence in the affected part. "With this view the microscopic characters of the softened cancers agree. Sach softening as this, taking place within a cancer, generally leads to ulceration, and to the discharge of the liquefied and degenerate materials, with whatever xDf serum, or pus, or blood, may have been mingled with them. This discharge is essentially similar to the open- ing of an abscess ; but it is less regular, and the ulceration is quickly more destructive, and exposes widely the cancerous walls of the evacu- ated cavity. I have already described both this and the other forms of ulceration that may ensue in cancers (pp. 637, 684, 710). They are all, like the degenerations, essentially local processes, and not indicative of any pe- culiar advance or transformation of the cancerous diathesis. Ulcera- tion is, indeed, a feature of the later progress of cancer, and it is most likely to occur in those whose health is most enfeebled ; it is, there- fore, often coincident with an exceeding intensity, of constitutional disease ; but it is not the consequence of such intensity, and is not rare even while the general health seems good. The amount of constitu- tional disease is indicated by the growth, or by the multiplication, of cancers, rather than by anything which, like ulceration, implies imper- fect maintenance of their structures ; and so we commonly see one part of a cahcer growing rapidly, while another is being destroyed by ul- ceration, or many growing while one is ulcerating. Now the growth is, generally, the measure of the force of the constitutional disease ; the ulceration is the measure of the local defect of nutrition ; and in these instances we may watch, at once, both the progressive and the retro- gressive phenomena of the life of the cancer. While dwelling on the constitutional origin of cancerous growths, I must not forget their constitutional effects — the changes in the blood and other parts which are their consequences. I said that a cancer adds a new element of disease to those that were already in progress. And this may be said of it in consideration both of its own life, and of the influence which its growth and changes have upon the whole economy. If we assume a constant process of nutrition in cancers, it cannot but be that the blood will be affected both by what tliey take from it, and by what it derives from them in the process of nutritive absorption. This latter source of change of the blood has been too little considered, — the former, perhaps, too much ; for the quantity of good nutrient material abstracted from the blood, in the growth of a cancer, is probably very trivial, whereas what returns to the blood is 824 CANCEROUS CACHEXIA. almost necessarily a morbid substance. It may be incapable of deve- lopment into cancer, but, unless it can be at once eliminated, it must injuriously affect the blood. What change it works we cannot tell ; nor can we tell more of the later ehanges produced when complete cancerous ma- terial is absorbed into the blood, or when secondary cancers multiply in important organs, hindering their functions ; or when ulceration ensues with pain, hsemorrhage, discharge, and hectic, and all the various signs of mined health. When these things are added to the still increasing cancerous condition of the blood, and when all, with mutual influence are in progress, they make a state so complex that analysis seems im- possible, and so various that no single or genercl description can be true. The general result is what is commonly called the cancerous cachexia ; but (as I have said before) it should be called the secondary cachexia, to distinguish it from the primary, which may, though it rarely does, precede the formation of a cancerous growth, or, in its in- dependent increase, may far exceed the probable consequences of the local disease (pp. 643, 691).' The constituents of the secondary cancerous cachexia, I say. are too numerous and complicated for analysis ; stiU we must always re- cognise, in the later stages of the disease, the double source of the mor- bid phenomena — namely, the progressive constitutional disease, and the effects, direct or indirect, of the local disease. How nearly inde- pendent the former is of the latter is proved by the results of removing the local disease. The secondary cachexia and many of its components may be for a time decreased ; pain and discharge, and all the local ac- cidents of the disease, may cease : but the average lengthening of life is not great (pp. 648, 691, 740). The fact proves not only that the progress of the peculiar constitutional part of the disease is nearly in- dependent of the local part, but also, that the constitutional part gene- rally contributes most to the fatal issue. However, in this, as well as in the times and manners of dying, and the times of recurrence after removal of the first growths, the differences in the several forms of can- cer are such as should not be put out of sight by a general or summary description ; death is the common, and almost constant end of all, but its circumstances should be studied separately in each. ' The induction of this secondary cachexia by the presence of a cancerous tumour is well illustrated by such eases as sometimes occur, in which, after the removal of the tumour, the general health remarkably improves, to fail again when recurrence ensues, and again to mend after the second removal. See a case by Mr. Jonathan Hutch- inson. Med. Trans, and Gaz., July 16, 1833. NOSOLOGY OF CANCER. 825 In conclusion, let me add a , few words respecting the nosological relations of the several forms of cancer to one another and to other Here, as everywhere in pathology, it is difficult to keep the just mean of classification; to avoid, on the one side, confusion; on the other, too rigid circumscription. The many features of resemblance in all the forms of cancer, and the large general history which may be truly "written of them, might lead us to merge all minor distinctions, and speak as of a single and uniform disease ; but it would be easy to show that, if in this view we write of the general symptoms, progress, and diagnosis of cancer, or of the history of cancers in any single organ, ■we write vaguely, and are obliged to omit many points of importance, for fear of contradictions. If, on the other hand, we look at contrasts rather than likenesses, we might be induced to separate some forms, as the epithelial and colloid, from the name of cancer, and to believe that the remaining forms have no affinity with any other disease. I suspect that the errors of such extremes as these (in all nosology, as well as in that of cancers) come from our attaching too much mean- ing to the terms that imply specific distinctions among diseases ; from our proneness to think of them as if they meant the same as they do in zoology. Now, there is no real correspondence between the two sets of terms. A specific name, in zoology, usually implies that all to whom it is given have origin from a common stock ; certain characters fixed, and not changeable, beyond certain narrow limits, by variety of external circumstances ; and circumscription, i.e. intervals of difference between them and other species, which intervals are not filled up by varieties or intermediate forms. Now in all pathology there are, pro- bably, no such species as these ; and the terms implying the existence of genera, species, and varieties of disease, mean only that the products of diseases may be arranged, and the diseases themselves considered, in larger and smaller groups, according to the number and importance of the characters which they have in common. Such terms do not mean that the borders of each group of diseases are naturally circumscribed ; they allow that the borders of each are confused with those of every adjacent group. With this meaning, I have adopted the terms used in the foregoing Lectures. The whole group of diseases included under the name (used like a generic name) of Cancer or Carcinoma are sufficiently distin- guished by the concurrence in them of all the characters of malignant tumours enumerated on pages 380-385. But this group is not cir- 826 NOSOLOGY OE CANCER. cumscribed ; its borders are everywhere overlapped by those of diseases to which other names are given : there are no one or two characters pathognomonic of cancer and found in it exclusively. The foregoing Lectures have repeatedly illustrated this, especially in the accounts of the recurring proliferous cysts (p. 432), certain cartilaginous tumours (pp. 503, 522), some of the myeloid (pp. 552, 592, note) and mammary glandular (p. 663), the recurring fibroid and fibro-nucleated (pp. 594, 602), and the rodent ulcers (p. 724). At the same time, this want of definition in the assumed genus of Cancers has been exemplified, it will be observed, chiefly by rare and exceptional cases ; all the general facts collected in the Lectures have illustrated the sufficiency of the con- current signs of cancer for a ground of general classification (see p. 886). Among the different forms of cancer, I have already said (p. 74-5), that there appear to be unequal degrees of difference, which may be ex- pressed by speaking of three forms — namely, the scirrhous, medullary, and epithelial — as species, and of the remainder as varieties, of cancer. All that has just been said of the want of circumscription for the so- called genus will, I need hardly say, be applicable to these smaller groups. But here is the chief point, at which, while avoiding too much precisioa, we must also guard against indiiference ; for, as it has been wisely said, truth is more likely to emerge from error than from con- fusion. The species and varieties of cancer, as of other diseases, do not correspond with those of living creatures ; yet the differences of the groups thus named are inconsistent with the theory of a single unchang- ing disease ; and I believe the future study of the grounds of these dif- ferences will prove very fruitful both in knowledge and in practical titility. As yet we can only speculate upon them in questions. Do they imply so many essentially and originally different morbid materials ? or is there one material for cancer, one carcinogen, which, like an organic radical, may form different yet closely allied compounds, in its combinations with the various substances provided by different bloods, or difi'erent parts ? Is not this hypothesis more appropriate than the first for the less usual phenomena of transformation, such as I have described as occurring in the progress, succession, and hereditary transmission of the cancerous constitution ? Is it incon- sistent with the gradual fusion of the characters of typical cancer in those of other diseases ? INDEX. ABB ABEENETHY, Mr., on classification of tumours, 390 ; on pancreatic tu- mours, 656 Abscess, contents of chronic, 292; for- mation of, 284-290; opening of, 30i; in bone, 300 ; residual, 295 Absorption ; preceded by transformation, 42; of bone, 190; of degenerate parts, 42 ; of blood, 136 ; of bloodvessels, 302; of cancer, 819; of dead tissues, 352; of inflamed parts, 304, 311 ; of inflammatory lymph, 280, 283 Actinia, experiments on, 122 Acupressure, 205 Addison, Dr. W"., theory of inflammation, 232, 7iote Adenoid tissue, 570 ; tumour, 655 Adhesion, primary, 147 ; secondary, 149 Adhesions, formation of, 264 ; absorption of, 280, 293 ; degenerations of, 293 Adhesive inflammation, 147, 263 Adipocere, 81 Adipose tumour : see Fatty tumour Age, as affecting repair, 117; general relation to cancer, 792 : and see Cancer Air, cysts containing, 399 Albuminous sarcoma, 599 Allocation of cancers, etc., 672, 799 Alveolar cancer : see Colloid Amoeboid movements, 172, 233, 260 Amputation, healing after, 149, 175 ; changes in nerves after, 112 Amyloid degeneration, 78, note Anchylosis, followed by atrophy, 101 Aneurism; of bone, 583, note; by anasto- mosis, 673 ; eflfects of pressure by, 67 ; Hunter's operation for, 26 Angeioma, 573 Annandale, Mr,, on fatty tumours, 460 ; on vascular recurrent tumours, 585 Animation, suspended, 339 Anstie, Dr., nervous system in nutrition, 32 Antlers, growth of, after castration, 22 BAT Antrum, osseous growtlis of the, 537 ; polypi in the, 463 ; teeth in the, 443 Aplastic lymph, 240, 278 Apoplexy, with degenerate cerebral and pulmonary vessels, 100 Arachnoid, organisation of blood-clots in the, 133 Arcus senilis, 113 Arrests of development, 2 Arterial vascular tumour, 677 Arteries, contraction of, 204 ; degenera- tion of, 106; healing of injured, 203; obstruction of, inducing mortification, 26, 341 ; inducing degeneration in can- cers, 822 : and see Bloodvessels Artery, femoral, traversing tumours, 618, 656, 688 Ascites, fibrine exuded in, 326 Assimilation, 3; of blood, 11 ; in diseased parts, 3 Assimilative force, 46 Asteridse, repair in, 120 Atheroma, 437 Atheromatous aifection of arteries, 106 Atrophy, 69, et seq, ; from pressure, 66 ; modes of, 72 : see Degeneration ; dis- tinguished from inflammation, 323 Auditory passages, polypi in, 453 ; exos- tosis in, 530 Auricle, cysts fasciculated like an, 411 Autogenous cysts, 393 BAKER, Mr., liquefaction of blood- clots, 279 ; statistics of cancer, 633, et seq. Baly, Dr., on ulceration, 313 Barky warts, 732 Barlow, Mr. W. F., on paralysed tnuscleo, 92 ; on fatty degeneration, 82, note Bastian, Dr., on atrophy of central nerve- organs, 93, note; on migration of blood-corpuscles, 233, note Bats, circulation in the wings of, 223 ; their temperature, 223 ; rhythmical contraction of veins, 224 828 INDEX. BAU Baum, Piof.. on teeth in tlie antnrni, 443 ; on aural jolxpi, 453 Beale, Dr., on geiminal matter, 139 ; on amoeboid tnoTements, ] 72, note Bell, John, on aneurism by anafrtcmosis, 673 Bell, Dr. Joseph, case of myxoma, 458 ; on pulsating tumour of orbit, o83, note ; case of Tillous cancer, 763 Bell, Sir C, on cancerous cachexia, 643 Bennett, Dr. J. H., on fibro-nucleated tumours, 602 ; on cancroid disease, 697, note; on blood in inflamed parts, 234 Bernard, Claude, nervous system in nutri- tion, 30, 326, note. Bickersteth, Mr. E., ease of cartilaginous tumour, 508 ; on colloid cancer, 774, note. Billroth, Dr., on development of blood- Tessels, 159; on cylindroma, 470, 5?o^e ; on mucous polypi, 453 ; on salivary glandular tumours, 520, note Birkett, Mr., on mammary cysts, 428 ; on mammary glandular tumours, 556 Bites, etc., venomous, 358, 366 Blastema, nucleated, its development, 1 42 : see also Nucleated blastema Bleeding : see Hsemorrhage Blisters, different fluids in, 251 Blood, abeorption of extra va sated, 135; accumulation inducing growth, 62; as- similation by, 11 ; in cancerous persons, 784; initiating inflammation, 327; death of, in dead parts, 347 ; defect and disease of, inducing mortification, 341, 345; effusion in inflammation, 243; effused, supposed origin of tumours, 387 ; extravasated, in wounds, its dis- posal, 133; in inflammations, 225; influence on inflammatory products, 250 ; in vessels of inflamed parts , 228 ; life of, 12 ; maintenance of morbid state of, 39 ; materials of, determining for- mation, 19; morbid materials in, 14; organisation of, 133 ; in tied arteries, 207 ; regular supply for nutrition, 24 ; right state of, for nutrition, 11, et seq. ; clots, softening of, 279 ; stagnant after injuries, 152; transference of cancer, etc., by, 818 Blood-cells, length, etc., of life, 9 ; deve- lopment of, 44 ; in inflammation, 234 ; white, in wounds, 151 ; in a clot, 135 ; migration of, 233, 248, 308 Blood-scabs, 168 Bloodvessels, absorption of, 302 ; adapta- tion to atrophy, 89 ; atrophy of, 1U5; initiating inflammation, 326; of can- cers, 659 ; enclosed by cancers, 656, 688 ; cancerous ulceration of, 712 ; con- traction on stimulus, 224 ; in granula- BEO tions, 163 ; enlarged in growing parts, 61 ; in inflamed parts, 219; formation of new, 159, et seq., 248, 272; obsfruc- ticn of: see Arteries; ofBce of, in nutrition, 26 ; relation to organisation, 164; growth of, in tumours, 581; 681; supplying tumours, 446; in erec- tile tumours, 674 Boils, sloughs in, 345 Bone, abscess in, 300; absorption of, 190, 300, 353 ; aneurism of, 583, note; atrophy of, 99, et seq. ; cancers of, 625, 660, 764 ; cancerous ulceration of, 712; cartilaginous tumours on or in, 510, 496 ; degenerations of, 100, et seq., 301 ; flbrous tumours on or in, 484 ; granu- lations on, 152, 163 ; hypertrophy of, 58 ; inflammation of, 297 ; lengthening of, 64 ; myeloid tumours on or in, 543; in necrosis, 352 ; nutrition of, 27 ; seats of osteoid cancer, 764 ; pus from, 313 ; serous cysts in, ?99, note; softening and expansion of, 297 ; ulceration of, 313 ; under cancerous and other ulcers, 384; formation of, in cartilaginous tumours, 602 ; in fatty tumours, 450 ; in fibro- ccllular tumours, 459 ; in fibrous tu- mours, 475 ; in inflammatory lymph, 268 ; in labial glandular tumours, 666; in myeloid tumours, 644 ; in osseous tumours, 627, 639 ; in osteoid and medullary cancers, 539 Bowman, Mr., on healing of wounds in the cornea, 334, note Brain, adaptation of skull to, 60, et seq. ; atrophy of, 110; bloodvessels of, in red softening, 221 ; cysts in, with fat, hair, etc., 437 ; degeneration of minute vessels of, 107 ; effects of its diseases on the cord. 111; effects of exercise, etc., 5 ; penetration by ulcer, 386 ; sloughing of, 26; softening of, 108 Brain-like epithelial cancers, 703 Breast : cancer not affecting glandular tumours in the, 562 ; cancer of the, following the excision of glandular tumours, 663 ; hard cancer of the : see Scirrhous cancer ; healing after Removal of, 144 ; induration of, in- fluenced by the mind, 36 ; irritable tumour of the, 493 ; malignant fibrous tumour in the, 774, et seq. ; medullary cancer of, 673; myeloid tumour in the, 562 : see also Mammary Gland Broca, M., on hereditary cancer, 790, note Brodie, Sir B. C, on fatty outgrowths, 444, and tumours, 446, note ; on morti- fication, 343, note, etc. ; on serpent- poison, 365, note; on cancerous tubercle, 724 Brood-cells in cancer, 667, 714 INDEX. 829 BBO Brow, cysts upar the, 436 Brown-Sequard, M., on repair of spinal cord, 213; on nervous system in nutri- tion, 30, 34 Brucli, Dr., case of cancer, 782 ; on mul- til'ormity of cancer-structures, 498 Budd, Dr. W., on symmetrical diseases, 14 Buffy coat on blood in inflammation, 235 Bursse, 392 ; with endogenous growths, 418 ; under corns, 61, 66 CACHEXIA in cancer, 824 Calcareous deposits in fibrous tu- mours, 478 Calcareous degeneration, 73 ; of blood- vessels, 105 ; of lymph, 280, 283 ; of cancer, 821 Callus, 180 Cancellous osseous tumours, 528 Cancer: general pathology [for special pathology, see the specific names, Scirrhous, etc.]. Origin of cancer-cells from connective tissue, 804 ; from epithelium, 806 ; constitutional and specific disease, 781 ; preceding condi- tions, 782 ; morbid material in the blood, 782 ; appropriate part, 783 ; necessity of their coincidence, 783 ; and of considering it, 783 ; nature of the cancerous blood, 783 ; cancerous particles in it, 784 ; chemistry, 785 ; glandu- lar, 807 ; incompatibility, 785 ; me- thod of its production, 786 ; by in- heritance, 787 ; modification therein, 789 ; inoculation, 791 ; favourable condition of sex, 792; age, 792; constitutional degeneracy, 793 ; cli- mate, 794 ; mental distress, 795 ; increase of cancerous diathesis, 796 ; suspension, 797 ; modification, 797 ; supersession, 797. Apt locality, 797 ; most and least frequent seats, 797; allo- cation, 799 ; liability of innocent tu- mours, 799 ; whence supposed, 799 ; acquired aptness, 801 ; congenital de- fect, 801 ; disease, 801 ; injury, 802 ; rule thence derived, 802 Cancer structures, development of, 804; construction, 807 ; infiltration, 808 ; changes in affected parts, 808 ; primary cell-forms, 808 ; diagnosis, 808 ; multi- formity, 809 ; conformity with normal types, 810; stroma, 811; bloodves- sels, 812; chemistry, 812; life, 813; growth, 814; two ministrant conditions, 814; localised cancer, 815 ; extension, 815; in lymphatics, 8 15; multiplication, 816; by contact, 816; on continuous surfaces, 8 16; in groups, 817; to distant parts, 817 ; by increasing diathesis, 818 ; by transference in blood, 818; degene- CHI rations, 820 ; diseases, "822 ; softening 822 ; ulceration, 823 ; constitutional effects, 823; primary and secondary cachexia, 824 ; effects of removal, 824 ; nosology, 824 Cancerous growths in cysts, 434 ; disease in erectile tumours, 586 ; and cartilagi- nous tumours mixed, 623 ; following the excision pf mammary glandular tumours, 563 Cancerous parents : tumours in the child- ren of, 564 Cancroid, 697 ulcer, 724 ; of the face, 623 Canton, Mr., on the arcus senilis, 113 Capillary vascular tumours, 575 Capsules, laminated, 715 ; investing tu- mours, 445 Carcinoma, 807, 815; fibrosum, 628; reticulare, 606 : see Cancer Carpenter, Dr., on combination of morbid poisons, 370 ; on morbid material in blood, 368 ; on the individual life of parts, 5, note ; on vital and pliysical forces, 46, note Cartilage, repair of, 194; inflammation of, 307 ; increase in inflammation, 271 ; ulceration of, 307 ; in fibro-cellular tu- mours, 459 Cartilaginous tumours : general seats, 495 ; on or in bones, 496 ; construction, 496; texture, 497 ; microscopical structure, 498 ; of basis, 498 ; of cells, 499 ; of nuclei, 500 ; growth, 503 ; size, 503 ; ossiflcation, 505; degeneration or defect, 507; softening, 507; cysts, 508 ; case of extreme softness, 508 ; sloughing and suppuration, 510. Of the long bones, 510 ; of the jaws, 512 ; of the skull and vertebrae, 513 ; of the hands, 514; by the parotid and sub-maxillary glands, 617. General nature, 620; recurrence, 521 ; extension along lymphatics, 522; hareditary, 523 ; conjunction with can- cer, 523 ; and with other tumours, 525 Castration, effects of, on antlers, etc., 22 Catalytic action of discharges, 316 Cauliflower appearance of papillary tu- mours, 688 ; excrescences of uterus, 722 Cavernous tumours, 573, 580, 587 Centres of ossification, hypertrophy at, 60 Cerebriform cancer: see Medullary Cancer Chancre, lymph in, 267 Cliannelling of bloodvessels, 162 Cheesy metamorpliosis, 569 Chemical composition: relation to vital activity, 158 Chemical changes in granulations, 158 Chimney-sweep's cancer, 733 : and see Epitlielial Cancer 830 INDEX. CHO Cholestearine in cysts, 403, 440 Cholesteatoma. 439 Chondroma, 495, note Chorda dorsalis cells in a cartilaginous tumonr, 505 Chorion, cystic disease of, 469 Chronic mammary tumour, 556 Church, Dr., on lymphoid mediastinal tumours, 572 Cicatrices : see Scars. Cancer of, 726 Cib'ated epithelium in cysts, 395 Clarke Lockhart, Mr., on connective tissue in spinal cord, 112; on atrophy of cen- tral organs of nervous system, 93, note Cleland, Prof., on absorption of dead bone, 353, note \ on tumours of dura mater, 589 Climate; relation to cancer, 794 Clitoris, cancerous cysts in the, 435 ; out- growth of, 455 Clot : see Blood- Clot Coagulable lymph, 244 : see Lymph Cohnheim, Dr., theory of inflammation, 233, note, 249, iwte, 308, note Cold, producing mortification, 344 Colloid cancer ; primary seats of, 767 ; general characters, 768 ; manner and extent of growth, 768 ; mingled, 769 ; minute structure, 769 ; analysis, 770 ; relations to other cancers, 772 ; general relations of cysts to cancers, 773 ; ge- neral history of, 774 ; likeness to carti- laginous tumours, 508 Colloid cysts, 412 Collonema, 452 Colossal cells, 546 ; capillaries, 724 Common disease, 354 Complemental nutrition, 17, et scq.; in disease, 19 Compound cysts, 417 Concurrent development of organs, 23 Conditions of nutrition : see Nutrition Condyloma, 589 Congenital defects; liability to disease, 751, 801 Congenital excesses; contrast with tu- mours, 377, note Congenital hypertrophy, 33 ; cysts in neck, 402 Congestion, active, 225, ei seg.; mechani- cal, relation to inflammation, 326 Conglomerate tumour, 517, note Conical clot, 205 Conjunctiva, inflamed after stimulus of retina, 331 Connective tissue corpuscles ; their pro- bable use in nutrition, 28 ; develop- ment in newly-formed skin, 214 ; proli- feration of, in inflammation, 247 ; in cancer, 804 Connective tissue ; development of, 140 ; | CTS mucous form of, 458; structure of, 140; tumour of, 451 Constitutional disease, 359, et seq.: see Specific Diseases ; become local, 814 ; in cancer, 780, et seg. Contraction of organised inflammatory products, 267 Cooke, Dr., case of recurring mammary proliferous cysts, 433 Cooper, Sir A. P., on chronic mammary tumours, 427, 556 ; on irritable tumours of the breast, 493 Coote, Mr., on vascular tumours, 402, 580 Cord, spinal, consequences of injury, 34 ; atrophy of, 112 Cornea, fatty degeneration of, 113; in- flammation of, 308 ; ulceration of, 32 Corns, 66 ; bursa under, 51 Corps fibreux, 471, note Innomine, 414 Corpuscular lymph, 245 : see Lymph Corrosive properties of discharges, 315 Cowperian cysts, 407 Cranium: see Skull Croupous lymph, 250, note Crystals, repair of, 118 Curling, Mr., on atrophy of bone, 87 ; on fibro-cystic disease of the testicle, 476; on scrotal cancer, 701, 740 Cutaneous outgrowths, 454 proliferous cysts, 435 ; with perfect skin, 435 ; in the ovaries, 436 ; in the subcutaneous tissue, 436 ; in various parts, 437 Cuticle, life of, 8 ; thickening of, 66 ; de- velopment of new, 214; formed on granulations, 155 ; separating over ab- scesses, 305 Cuticular cysts, 437 Cylindroma, 469 CylindrLform epithelial cancer, 718 C^sts or cystic tumours, 392 ; primary and secondary, 393; mode of origin, 394; general structure of, 395 ; modes of de- velopment, 396 ; their various contents, 397 ; endogenous formation of, 419; with endogenous cancerous growths, 434 ; with cholestearine, 403 ; colloid, 412; complex ovarian, 418 ; compound or proliferous, 417; connected with Cowper's glands, 408 ; with organ of Giraldes, ,414 ; with organ of Kosen- miiller, 416 ; cutaneous proliferous, 435; dilatation, 413; gaseous, 399; glan- dular proliferous, 418 ; mammary pro- liferous, 424 ; Meibomian, 436, note ; mucous, 407; near orin Fallopian tube, 415 ; containing oily or fatty matter, 412 ; proliferous in the thigh and other parts, 430; proliferous recurring, 432; sanguineous, 40 9 ; s. baceous, epidermal, INDEX. 831 CTS or cuticuliir, 437 ; containing semen or other secreted fluids, 413; serous, 399 simple or barren, enumeration of, 392 synovial, 406 ; containing teeth, 442 , with cancer in the hroast, 405 ; with cancers of glands, 676 ; with epithelial cancers, 714 ; general relation to can- cers, 773 ; in cartilaginous tumours, 508 ; in fatty tumours, 450 ; in fibrous tumours, 476; in myeloid tumours, 544 ; in vascular tumours or naevi, 685 Cystic cancer : see Colloid Cystoid growths, 417 Cysto-sarcoma, 417, note, 65B, note DAXYELL, Sir J. &., experiments on Hydra, Tubularia, etc , 122, ct seq. Darwin, Mr., 23, 119, note Dead parts, separation of, 42 Death, and degeneration, distinguished, 42, 338 ; natural, of parts, 4 Decay, natural, of parts, 4 : see Degenera- tion, 69 Degeneration ; general meaning of, 70 ; natural occurrence in old age, 70; natural issue of life, 70 ; design of de- generations, 71 ; their importance in pathology, 72 ; methods of, 72 ; amy- loid, 78, note ; withering, 72 ; fatty, 73 ; calcareous, 73 ; pigmental, 74 ; thickening of primary membranes, 74 ; combinations, 75 ; their occurrence be- fore old age, 75 ; distinction from dis- eases, 76 ; general diagnosis, 76 ; re- lations with development, 76 ; and with diseases, 78 ; liquefactive, 78 ; conditions of, 86 ; spontaneous atrophy or degeneration, 88 ; contrast with hypertrophy, 86 Degeneration and death distinguished, 42, 338 ; mixed with morbid processes, 10 ; of the fangs of teeth, 8 ; in inflamed parts, 296, et seq. ; of inflammatory products, 277 ; of cancer-cells, 615, 685, 713, 750; of cancers, 820 Dendritic vegetation, 669, 764 Dentigerous cysts, 442 Deterioration of parts, sources of, 4 Determination of blood, 226 Development, meaning of, 2, 261 ; sepa- rate from growth, 2 ; arrests of, 2 ; determination of the order of, 22 ; as part of the formative process, 43 ; in hypertrophy, 48 ; consumption of force in, 116 ; arrest or error of, in granula- tions, 156 ; congenital excess of, con- trast with tumours, 377, note Developments of inflammatory products, 260 Dickinson, Dr., on atrophy of nerves after amputation, 111 BPI Dilatation tumours, 413 Diseased parts, assimilation in, 37 Diseases occurring only once, 38 Diseases of cancers, 822 ; of granulations, 157 ; of organised lymph, 'fdQ Dittrich, Prof., on pulmonary apoplexy, 109 Dropsies, fibrinous, 240 Duncan, Dr. M., on haemorrhage from uterine tumours, 480, note Duration of life in parts, 9 Dysentery, ulcers in, 313 EAE, vascular tumour of the, 577 ; fibrous tumours in the lobules of the, 486 Eburnation of bone, 301 Ecchondrosis, 495 Elastic tissue in adhesions, 268; in fibrous tumours, 475 Election, seats of, 15 Elective affinity in nutrition, 45-47 Elephantiasis scroti, 455 Embolic extension of cancer, 8 1 5 Encephaloid : see Medullary Cancer Enchondroma, 405, et seq. ; see Cartila- ginous Tumour Enchondroma mucosum, 507 Endogenous cells, in cancer, 667, 715 cysts, 418 : see Cysts Energy, conservation and transformation of, 46 ; potential, 47 Epidermal cysts, 437 Epidermis, growth of, 49 Epithelial cancer; primary seats, 696; secondary, 696 ; superficial form, 698 ; warty and other external characters, 699 ; distinction from common warty growths, 701, 734; interior structure, 703; peculiar soft material, 703; papillary and deep-set portions, 704 ; infiltrated cancer-structures, 705 ; stroma, 706; deep-scatid form, 707; cases, 707; uleeratjon, 710; micro- scopic structures, 712; their arrange- ment, 712; varieties, 713; melanotic, 718; cylindriform, 718; intermediate, 718. In lymphatic glands, 719 ; primary, 720 ; lungs, 721 ; heart, 721 ; uterus and vagina, 722 ; diagnosis from other cancers and from rodent ulcers, 723 ; cancer of cicatrices, 726. Pa- thology : influence of sex, 728 ; age, 729 ; hereditary disposition, 730 ; in- jury or disease, 732 ; warts, 733 ; can- cer-structures new formed in them, 734 ; general health, 736 ; growth, 736 ; ulceration, 737 ; pain and ca- chexia, 737; multiplication, 738 ; varia- tions according to seat, 739 ; duration of life, 740; rules for operations, 741; 832 INDEX. in cases of rfcurrence, 742 ; relations to otlier cancers, 742 Epithelioma, 696, note Epithelium, on adhesions, etc, 268 Epulis, 485 Erectile tumours, 573 Ejsipelas, suppuration in, 290 Ethmoid bone, -with cartilaginous growth, 513 Excoriation in inflammation, 314 Excretion office of each part, 1 7 Excretions, mutual, betiTeen organs, 23 Exercise, effects of, in tissues, 4 ; inducing growth, 51 ; atrophy in defective, 86 Exostosis, 528 ; foliated or periosteal, 754 ; spongy or fungous, 661 Exudation, inflammatory, 244 Eye, acute cancer of the, 681 ; medullary cancer of, 672, 686 ; melanoid cancer of, 748 Eyelash, life of an, 6 FACE, growths on thebonesof the, 613, 536 Ealse membranes, 265, et seq. Fat, formed in adhesions, 268 ; in the place of atrophied muscles, 90 ; in nerves. 111 Fatty degeneration, 73, 79 ; general characters of, 79; wasting of nuclei, 80 ; source of the fatty matter, 81 ; imitative chemical changes, 81 ; adi- pocere, 81 ; relation to defective nutri- tion, 82 ; as in old age, 82 ; two modes of atrophy in old persons, 82 ; causes of fatty degeneration, 83 ; correspond- ence with those of wasting, 83 ; relation to general obesity, 84 ; of voluntary muscles, 89 ; of the heart, 94 ; of the uterus and the smooth-flbred muscles, 99; of bones, 99; of bloodvessels, 105; nervous tissues, 109; cornea, 113; lymph, 278, 282, 293; of inflamed parts, 308 Fatty matter in degenerate parts, 43 ; in the uterus after delivery, 99 Eatty tumours : outgrowths, 444 ; in the heart, 444 ; tumours, tissiie of, 445 its arrangement, 445 ; capsule, 445 bloodvessels, 446 ; multiplicity, 446 seats, 447 ; shifting, 447 ; deep-seated, 449; growth, 449; diseases, 450 causes, 451 ; in emaciated persons, 376 Femur, lengthening of, 63 ; absorption of neck, 301 ; tumour detached from the, 529 ; frequent seat of osteoid cancer, 755 Fever, cancer withering in, 786 Fibrine in effused fluids, 240; delayed coagulation, 241 ; degenerations ' of, 277 FOE Fibrinous form of inflammatory lymph, 249 Fibrinogen, 240 Fibriuoplastic substances, 241 Fibro-calcareous tumours, 477 cellular tissue, development of, 139, et seq. Fibro-cellular tumours. Previous descrip- tions, 451 ; Polypi, 462-454. Cutaneous outgrowths, 454; elephantiasis, 455; fibro-cellular tumours, general form, etc., 456 ; texture, 457 ; microscopic structure, 458 ; myxomatous variety, 458; chemical character, 469 ; contain- ing cartilage or bone, 459 ; degenerate, 459 ; seats, 460 ; in the scrotum, 461 ; by the vagina, 462 ; in the limbs, 464 ; in the testicle, etc., 466 ; general history, growth, etc., 466 Fibro-cystic tumours, 476 ; with cartilage, 508 Fibroid tumours, recurring, 594, et seq. Fibro-nucleated tumours: general char- acters and cases, 602 Fibro-plastic tumours, 542 Fibrous cancer, 774 tissue, ossification of, in bony tumours, 534 ; fibrous tumours in or near, 482; in cancer, 611 Fibrous tumours. Polypi: of the uterus, 472 ; of the pharynx, 472 ; rectum, 472. Tumours : general shape, 473 ; capsule, 473 ; texture, 473 ; plan of fibres, 474 ; vascularity, 474 ; micro- scopic structure, 475 ; muscular form or myoma, 475 ; cysts, 476 ; calcareous deposits, 477; fatty degeneration of 478 ; seats, 478; uterus, 478 ; nerves, 480. Subcutaneous, 481 ; protruding, 481 ; near fibrous tissues, 482; of the jaws, 484 ; in the lobules of the ears, 486 ; multiplicity, 486 ; growth, 487 ; general nature, 487 ; malignant, 775 Fibula, acute cancer of the, 681; cartila- ginous tumour in the, 512 First intention, union by, 143, 148 Food, effects of, in the formation of tis- sues, 20 Foot, atrophy of, 68 ; cartilaginous tumour, 514 ; fibro-cellular tumour in the, 465 ; fibrous tumour in the, 482 Forces, actuating the formative process, 46 ; conservation of force, 46 Form, organic, dependent on composition, 47 Formative force, 46; its method, 45; hypothesis concerning, 47 ; illustrated in repair, 116 Formative process ; its modes, 1 ; its pr.-- cision, 17-47; disposal of old particles, 42 ; degener.ition and denth, 42 ; in- stanced in teeth, etc. 42 ; development INDEX. FOX of new particles, 43 ; influence of nuclei, a ; repetitiou of parts, 44 ; likeness to older structures, 44; nature of formative forces, 45 ; theory of assimilation, 45 ; Its inapplicability, 45 ; formative force, 45 ; as in development, 46 ; its method, 46 ; dependence of form on composition, 47 ; hypothesis, 47 : see also Nutrition Fox, Dr. W., on ovarian cysts, 421 ; on inoculation of tubercle, 671 Fractures, share of the blood in repairing, 135 ; followed by partial atrophy, 87 ; ununited, 192 ; spontaneous, in atrophy, 99 ; in moUities ossium, 103 ; in can- cerous patients, 626 : see Repair of Fractures Frogley, Mr., cases of cartilaginous tu- mours, 503 Frog's web, experimental injuries of, 151, 223, etc. Frontal sinuses, osseous tumours in the, 532 Fungus haematodes, 059, 687, 753 GANG-LIONS, 407 Gangrene : see Mortification ; re- lation to ulceration, 315 Graseous cysts, 399 G-elatiniform cancer : see Colloid Gelatinous polypi, 452 sarcoma, 452, 617 Generalisation of cancer, 820 Genital organs, relations of development of, 22 Gerlach, Dr., on osteoid cancer, 758, note ; on villous cancer, 765, note Giraldes, organ of, 414 Glands, products of inflamed, 255 Gland-cells, length of life, 10 ducts involved in cancer, 611 growths, intra-cystic, 378, 418, et seg. ; outlying, 378 Glandular cancer, 807 tumours : general relations, 655 ; mammary, 656 ; usual seats, 667 ; shape, etc., 567 ; construction, 557 ; structure, 558 ; microscopic structure, 559 ; growth, 560 ; pain, 660 ; disappearance, 661 ; large size, 661; in the male, 662; relation to cancer, 662; in cancerous families, 563 ; Labial, 664 ; Prostatic, 565 ; Thyroid, 665 ; Lymphatic, 668 ; Mixed, on the parotid and submaxil- lary glands, 517 Glioma, 467 Globes ^pidermiques, 715 Glossy fingers, 32, 332 Gluge, Prof, on albuminous sarcoma, 599 ; inflammatory globules of, 282 Goodsir, Prof., on absorption and ulcera- 3 tion, 313, note; on ulceration of car- tilage, 307 ; on erectile tumours, 574 ; on nuclei in bone corpuscles, 27 ; on multiplication of nuclei, 249, note Graafian vesicles forming cysts, 418 Granulations, process of, 149; and see Eepair by granulation ; ossification of, 182 ; effects of infliimmation and con- gestion on, 263 ; of cancer, 638 Granulation-cells, 140 Granule cells and masses, 283, etc. Growth, meaning of, 3 ; separate from development, 2, 120 ; its nature, 48 ; various duration, 48 ; adapted to need, 48 ; hypertrophy, 49 ; its rule, 49 ; in- stanced in cuticle and muscle, 49 ; with development, 50 ; in the uterus, etc., 60 ; conditions necessary, 51 ; conditions in- ducing hypertrophy, 51 ; increased exercise, 62 ; increased materials for nutrition, 52; increased blood, 53; mor- bid and inflammatory hypertrophies, 54; simple and numerical hypertrophy, 57 ; consumption of force in, 116: see also Hypertrophy Gulliver, Mr., ou absorption of bone, 301 ; on degeneration of arteries, 106 ; on softening of clots, 278, note Gum-cancer: see Colloid Gums, cysts connected with the, 403, 442 ; fibrous tumours of, 485 H.I;MAT0ID Cancer, 752 Hair, life and death of, 6 ; change of colour under nervous influence, 31 ; ex- cretion by, 18 ; increased growth in afflux of blood, 52 ; in cysts, 436, etse^. Hair-foUieles ; growth into cysts, 438 Hancock, Mr., on fatty degeneration of the bladder, 99, note Hands, cartilaginous tumours in the, 514 Hannover, Prof., on epithelioma, 697, 719, etc. Harelip, healing after operations, 149 Harting, Prof., on growth of muscles, 57 Hawkins, Mr., on cancerous ulcers, etc., 724, 726, note ; on epulis, 485 ; on cystic tumours, 586 Healing: see Eepair; in paralysed limbs, 33; of ulcers, 316 Heart, atrophy and degeneration of, 86, et seq., 94; cancer in, 722; fatty de- generation of inflamed, 94, 306 ; fatty growths in, 444 ; growth of, 48 ; mal- formed, 2 Heat in inflammation, 317 Helmholtz, Prof, ou changes in muscles, 4 Hemiplegia, state of muscles in, 92 Haemorrhage, arrest of, 205 ; from cancers, 687 ; from fibrous tumours, 480 Henle, Prof, theory of inflammation, 332 834 INDEX. HER Hereditary disposition to cancer, 786 ; disease, transformation in, 361 ; car- tilaginous tumours, 522 ; cysts, 438 ; osseous tumours, 539 Hernia, lymph in the sac and intestine, 254 ; with sloughing, 350 Herpes, lymph of, 245, 284 Hewett, Mr. Preseott, on membranes formed from blood-clots, 133 Hodgkin, Dr., his account of cysts, 419 Home, Sir E., on vessels in lymph, 275 Homologous parts, similar diseases of, 16 Homologous and heterologous tumours, 375 Horns, 588 ; epithelial cancers like, 701 Humeras, cartilaginous tumours on the, 511 ; osteoid cancer of, 754 Humphry, Professor, on hypertrophy of muscles, 56 ; on softening of fibrous tumonre, 478, note; on removal of tumom'S, 440 ; on torsion of arteries, 205 Hunter, John, on effects of pressure, 66 ; on hypertrophy of muscles, 55, 57 ; on incompatible diseases, 786 ; on increased action in inflammation, 320 ; on moUi- ties ossium, 103 ; operation for aneu- rism, 26 ; on subcutaneous injuries, 131; on union by first intention, 143 ; on nnion by adhesion, 147; on union of granulations, 154 ; remoral of large tumour, 618 Hutchinson, Mr., on rodent ulcers, 726 Hurley, Jlr., case by, 370 Hyaline cylinders, 469 Hydatid disease of testicle, 387 Hydatid mole, 468 Hydra, repair in, 121 Hydrocele-fluid. 241 ; encysted, of the cord, 413 ; with spermatozoa, 413 Hydrocephalus, hypertrophy of skull in, 58 Hydrops fibrinosns, 240 Hygroma, 399 ; colli cysticum congeni- tum, 400 Hyperostoses, 527 Hyperplasia, 57 Hj'pertrophy : for general history, see Growth. Of urinary bladder, 55; other iuToluntary muscular parts, 56 ; induced by obstacles to their action, 56 ; growth of fibres, 57. Of bone : in the skull, 68; in hydrocephalus, 58; with shrinking of the brain, 60 ; especially at the original centres of ossification. 60. Lengthening of bones, 62 ; with curvature of the tibia, 63 ; inequality of limbs, 64. Of cuticle, 66 ; effects of pressure, 66 ; from within and from without, 66 ; oc- casional and constant, 68. Of thyroid and other glands. 378 ; or mammary INF gland, 556 ; of cancerous parts, 808 ; contristed with tumours, 373 ; distin- guished from inflammation, 323: inflam- matory, 256 ; discontinuous and con- tinuous, 388 ICHOR, 315 Imbibition, by parts of nutrition, 27 Immediate union, healing by, 143 Impairment of parts, sources of, 4 Inaction, or incubation, after injury, 161, 361 Incompatibility of cancer and other dis- eases, 786 Incorporation of materials of the blood, 19, 362 Incrusted warts, 733 Incubation of disease, 361 Infiltrations, general characters of, 381, 389 Inflammation, phenomena of, 218 ; altered supply of blood, 219; enlargement of vessels, 219 ; method of, 219 ; gorging with blood, 220 ; increased redness, 220 ; appearance of newvessels, 221; changed shape of vessels 222 ; changed move- ment of the blood, 223 ; observed in bats' wings, 223 ; contraction of stimu- "lated vessels, 224 ; subsequentdilatation 224; adapted movement of the blood, 225 ; effects of various stimuli, 225 producing determination of blood, 225 retardation of blood, 226 ; stagnation 227 ; observations in bats' wings, 228 summary of changes in the blood and vessels, 229 ; non-coagulation of the stagnant blood, 230 ; causes of the changed movement of the blood, 230. Changed composition of the blood, 231 ; change in its corpuscles, 232 ; bu% coat, 235. — Products of infiammation, 237; Strwm, 240; containing fibrinogen, 240 ; delayed coagulation, 241 ; fluid of mechanical dropsies, 242. Blood, 242 ; frequency in pneumonia, 243 ; blood-stained lymph, 243. Inflamma- tory Lymph, 244 ; fibrinous, 244 ; cor- puscular, 244 ; corpuscles, 245 ; their developments, etc., 246 ; mixed lymph, 249; plastic and aplastic varieties, 250. Influence of the blood on inflam- matory lymph, 250 ; observed in the effects of blisters, 291. Influence of the tissue inflamed, 253 ; examples and exceptions, 253. Influence of the degree of inflammation, 255. Sum- mary of influences determining adhesive or suppurative infiammation, 256. Mucus, 257 ; mixed lymph. 258 ; pig- mental cells, 259. — Developments of inflammatory products, 260 ; inde- INDEX. 835 INF renilent lif,-, 261 ; and meaning, 261 ; aiidnocrssavyeiniclitions, 262; eessiition of inflammatory process, 263 ; and of passive congestion, 263 ; wliat deter- mines the direction, 264 ; formation of adhesions, etc., 265 ; of fibrous or con- nective tissue, 266 ; its contraction, 267 ; of adipose tissue, 268 ; of elastic tissue, 268 ; epithelium, 268 ; bone, 268 ; car- tilage, 271; muscular fibre, 271; blood- vessels, 272 ; lymphatics, 273 ; nerve- fibres, 274 ; times for development, 274. — Degenerations of inflammatory products, 278; conditions favouring, 277; infibrine, -withering, 277 ; fatty, 279 ; liquefaotive, 279 ; resolution, 279 ; calcareous, 280 ; pigmental, 280 ; in the corpuscles, withering, 281 ; fatty, 282 ; absorption of granular matter, 283 ; calcareous, 283 ; pig- mental, 283. — Pus ; inflammatory suppuration ; origin of, from pre-exist- ii!gti.ssu6elemenfs, 283 ; from migration of white blood-corpuscles, 248 ; transfor- mation of lymph into pus, 284 ; relations of inflammatory and reparative suppu- ration, 285 ; abscess, 286 ; its form- ation, etc., 286 ; opening, 304 ; chronic abscess, 289 ; diffhse siippvration, 289 ; superficial sup^mration, 290 ; relation of pus to mncus, 291 ; relation to abrasion and ■ ulceration, 291; degenerations of pus-cells, 292 ; various contents of chronic and recurrent abscesses, 292. Degenerations of organised lymph, 293 ; wasting, 293 ; fatty and calcareous, 293 ; pigmental, 294 ; diseases, 294 ; hsemor- rhajres, inflammations, etc., 294 ;residual abscesses, 296. Changes in the tissues inflamed ; all injuries, 296 ; their dou- ble source, 296 ; softening. 296 ; expan- sion, 298 ; absorption, 300 ; in open- ing of abscesses, 303 ; fatty and other degenerations, 305, et seq. — Ulceration, 310 ; dependent on inflammation, 311 ; ejection of particles, 311 ; solution of them, 313 ; coi-rosion, 314 ; ichor, 315; healing, 316. — Signs, nature, and causes of inflammation; redness, 317; heat, 317; swelling, ?18; pain, 319; quantity of nutrition in inflammation, 320 ; ' in- crea.sedaction,' 320 ; diminished forma- tive force, 320 ; method of nutrition in inflamed parts 323. Causes, 324 ; in changes of bloodvessels, 326 ; in the blood. 326 ; its localisation. 328 ; in dis- turbed nervous force, 331 ; in the state of parts, 333 Inflammation, leading to mortification, 340 ; specific, 353, et seq. ; relation to repair, 216 ; interfering with union, 146 ; in cancers, 823 KID Inflammatory hypertrophy, 53 products ; contrasted with tumours, 374; developments of, 260; degenerations of, 278 Inheritance of specific disease, 360 ; of cancer, 786 Injury, inaction after, 151 ; engendering inflammation, 334 ; killing parts, 338 ; making apt for constitutional disease, 330-335; as cause of tumours, 387, 801 Innocent and malignant tumours, contrast between, 380 ; fusion of, 825 Innocent tumours, general characters of, 385; occasional constitutional origin of, 386 ; development of, 398 ; becoming cancerous, 676, 799 ; in members of cancerous families, 730 ; cancerous dis- position fading in, 790 Inoculable disease, 19, 329, 359, 364 Inoculation of cancer. 792 Insects, repair in, 125 Integuments, cancer of: see Epithelial Cancer Intermuscular tissue, fibro-cellular tu- mours in the, 461 ; cancer in, 624, 656 Intestines, with gaseous cysts, 399 Intestinal canal, hypertrophy of, 56 ; hard cancer of, 626 ; medullary cancer of, 676 Intra-cystic glandular growths, 418, et seq. Ivory-like osseous tumours, 530 JAW, atrophy with anchylosis, 101, cartilaginous tumoiirs on the, 613 ; cysts in front of the, 403 ; denti- gerous cysts in the, 442 ; fibrous tu- mours on or in the, 484 ; ivory-like tumour of the, 633 ; myeloid tumours on or in the, 648 ; osseous tumours of the, in animals, 633 Jenner, Sir "W., on degeneration, 1 06, notf ; on calcareous molecules in colloid can- cer, 770 note Joints, cartilaginous growths in, 495 ; effects of inflammation about, 267 ; effects of chronic inflammation, 271 ; false, 192 ; loose bodies in, 496; loose bone in, 67; softening ot ligaments, 299 Jones, Dr. Bence, on changes of materials of the brain, 5, 322 Jones, Wharton, Mr., on the circulation in the bat's wing, 224 ; on the blood in inflammation, 234 ; experiments on in- flammation, 226, et seq. Juice of cancer, 612, 658, 668 KEL'^ID, 456, note, 724 Kidney, inflammation in, 309 ; cystic 3 H 2 836 INDEX. KIE disease of, 395 ; effect of destruction of one, 19 Kirkes, Dr., on adhesions of tlie pericar- dium, 280 ; on obstruction of cerebral arteries, 110 Kolliker, Prof., on dilated small blood- vessels, 221 ; on the change of hairs, 7 ; on degeneration in the uterus, 99 Kiiss, E., on pus-corpuscles and inflam- mation, 285, note, 352, note Kreatine, in transformed muscles, 43 IABIAXi glandular tumours, 564 J Labium, fatty tumour in the, 447, note; fibro-cellular tumours in the, 464; outgrowths of, 455 ; proliferous cysts in the, 429 Lactiferous ducts, dilated into cysts, 404; involved in cancer, 611 Laminated, capsules, 715 ; cells in mye- loid tumours, 551 ; epidermal scales in eholestfiatoma, 440 Lanugo, purpose of, 18 Lardaceous tumour, 446 Larynx, cysts in front of the, 401 ; epi- thelial cancer of, 708 Latency of disease, 361 ; of cancer, 788 Lawrence, Sir W,, on determination of blood, 230 ; on fibro-cellular tumours, 451 ; on glandular tumours, 556, et seq. Laycocb, Prof., on degeneration, 74, note ; on relation of disease to structure and embryological development, 806, note Lebert, M., on inflammation, 220, note, 222, note, etc. ; on lipoma, 444, note ; on mammary glandular tumours, 556 ; on fibro-plastic tumours, 541 ; on vessels of cancers, 658 ; on cancer and cancroid, 697. note, 728, 770, etc. Lepoides, 732, note Leucocythaemia, 234, note, 568 L-ebiff, Dr. G., on transformation in mus- cles, 4 Life of blood, 9 individual, of parts, 5 ; length of, in each part, 8 ; independent in morbid products, 261 Ligaments, softening of inflamed, 299 Ligature of arteries, effects of, 205 Limbs, unequal length of, 62, et seq. Line of demarcation, 351 Lions' bones, symmetrically diseased, 13 Lip, arterial tumour on the, 580 ; cancer of, 735: and see Epithelial Cancer; glandular tumours in the, d65 ; glandu- lar and bony tumour in the, 626 ; pro- liferous cysts in the, 429 Lipoma, 446 : see Fatty Tnmour ; arbor- escens, 446, 765 ; mixtum, 446 Liquefection of fibrine, etc., 279 Liquefactive degeneration, 78 ; in cartila- ginous tumours, 508 ; in cancer, 822 Lister, Prof, germ theory, 132 ; antiseptic ligature, 43, note, 207, note; antiseptic mode of treatment, 147, 169, Tiote; influence of nerves in nutrition, 30 ; on exostosis, 528 ; on inflammation, 226, et seq. Listen, Jlr., on spermatozoa in cysts, 413 Liver, cancer of the, 818 Lloyd, Mr., on spermatozoa in cysts, 413 Local disease in cancer, 783 Local production of pus or inflammatory lymph-corpuscles, 248 Loose bodies in ganglions, 407 Ltmg, cartilaginous tumours in, 496, 522 ; cancer in, 819 ; epithelial cancer of, 721 ; osteoid cancer of, 762 Lymph, for repair, 138; in primary adhe- sion, 147; inflammatory, 244; absorp- tion of, 280, 283 ; varieties of, in blis- ters, 251; supposed origin of tumours, 387 Lymphatic cavernous vascular tumours, 587 Lymphatic glands, chronic inflammation, 281 ; hypertrophy of, 668; tubercle in, 669 ; enlargement before cancer, 621 ; epithelial cancer of, 719 ; medullary cancer of, 675 ; osteoid cancer of, 757 ; scirrhous cancer of, 621 Lymphatics, in adhesions, 274 ; ? in granu- lations, 165 ; cancer in, 816 ; in cancer, 659 ; extension of cartilaginous growths in, 622 Lympho-sarcoma, 541, 671 Lymphoid corpuscles, 570 ; tumours, 568 MACAETNEY, Dr., on immediate union, 143 Maclagan, Dr., case of recurring fibroid tumour, 600 Maintenance, 3 ; of diseased blood, 39 Malignant and innocent tumours, fusion of, 825 Malignant tumours: general characters of, 380 ; fibrous tumours, 774 ; myeloid tumours, 552 Malum senile, 100 Mammary gland : contracted and indu- rated, with cysts, 406 ; serous cysts in the, 404 Mammary glandular tumours, 424, 556 ; neuralgic, 493 ; proliferous cysts, 424 ; recurring, 432 Many-nucleated corpuscles in myeloid tumours, 645 ; in medullary cancer, 667 ; in epithelial cancer, 716 INDEX. 837 MAX Maxillary bones : see Jaws Median nerve, consequences of injury of, oo Mediastinal lymphoid tumours, 572 Mediastinum, tumour in, containing teeth, etc., 442, note Medicines incorporated in tissues, 20 Medullary caucer : varieties, 654 ; general relations, 655 ; usual seats, 655 ; soft kind; shape, etc.. 656; relation and attachments of lobes, 656 ; capsule, 657 ; material, 657 ; cancer-juice, 658 ; varieties, 658 ; bloodvessels, 658 ; erec- tile and pulsating, 659 ; lymphatics, 660 ; nerves, 660 ; infiltrations, 660 ; in bones, 660 ; with osteoid cancer, 661 ; firm kind, 661 — Microscopic cha- racters, 663 ; cells, 663 ; varieties of nuclei, 664; of cells, 665; of stroma or intercellular substance, 668 — In the testicle, 671; aje, 672; breast, 673; SKbciitaneotis tissue, 674; multiplicity, 675 ; absorption, 675; lymyliatic glands, 675 ; rectum, 676; Pathology: influence of sex, 678 ; age, 679 ; hereditary dis- position, 681 ; injury and disease, 681 ; temperament, 682 ; multiplicity and growth, 682 ; arrest, 683 ; ulceration, 684 ; degenerations, 685 ; wasting and absorption, 685; bleeding, 687; in- flammation, 687 ; sloughing, 687 ; pain, 691 ; cachexia, 691 ; duration of life, 691 ; effect of removal, 694 ; recurrence, 694 ; rules for operation, 694 Melanin, 747 Melanoid cancer : general characters, 745; microscopic, 747 ; general pathology, 748 ; colour, 760 ; connection with moles, 761 ; multiplicity, 752 Meliceris, 407 Membranes, products of inflamed, 247, 257, 266 Memory, connection with nutrition, 41 Menstruation, relation to cancer, 632 Meryon, Dr., on atrophy of muscles, 93 Metamorphosis in disease, 360 Mettenheimer, Dr., on intra-cysticgrowths, 429 Migration of white blood-corpuscles, 233, 248, 308 ; of lymph-corpuscles, 572 ; of cancer corpuscles, 817 Milk, cysts containing, 404 Miller, Prof., on painful subcutaneous tumour, 489 ; on cartilaginous tumours on hands, 616, note Miller, Dr., A. G., polypus of rectum, 472, note Mind, effects of its exercise, 5 ; its influ- ence on nutrition, 31 ; connection with a changing brain, 41 ; depression of, in relation to cancer, 795 Mixed tumours, 390; fibro-cellular and cartilaginous, 488 ; cartilaginous and myeloid, 525 ; cartilaginous and fibro- cystic, 526; cartilaginous andglandular, 617 ; cartilaginous and cancerous, 624 Modelling process, 176 of united bones, 190 Moles : liability to cancer, 751 Mollities ossium, 102 MoUuscum simplex, 455, note Moore, Mr., on a mucous enchondroma, 614 ; on liability to cancer, 793 Morbid materials in blood, identity of, 15 : see Specific Diseases Morbid poisons, 357, et seq. : see Specific Diseases Morbid structures, maintenance in, 37 Morgagni, hydatid of, 414 Mortar-like degeneration of abscesses, 292 Mortification : distinction from degenera- tion, 338; causes, 340; direct, 340; relation to inflammation, 340 ; indirect, 341 ; senile gangrene, 342 ; various causes, 342 ; appearances of dying and dead parts, 346 ; separation of them, 350 ; phenomena of necrosis in hone, 352 ; after loss of blood, 25 ; after obliteration of vessels, 25 ; after injury of the spine, 33 Motor nerves, influence on nutrition, 35 Mucous cancroids, 469, note cysts, 407; Nabothian, 407; Cow- perian, 407 ; their various contents, 408 Mucous membranes, cancer of: see Epi.. thelial Cancer ; villous cancer in, 763 Mucous polypi, 462 tissue, 452, 458, 507 Mucus, 257 ; relations to pus, 291 Miiller, Prof., on cholesteatoma, 439 ; on enchondroma, 495 ; on osteoid cancer, 754 ; on cysto-sarcoma, 417, note Multilocular cysts, 418 Multiple tumours, 383 ; cartilaginoufc tumours, 522 ; fatty tumours, 446 ; fibrous tumours, 487 ; osseous growths, 538 Multiplication of cancers : see Cancer, general pathology Muscles, growth of, 49 ; hypertrophy of, 56, et seq. ; effects of action, 4 ; atrophy and degeneration of, 89 ; voluntary, 89; the heart, 94 ; smooth-fibred, 98 ; materials derived from their transfor- mations, 43 ; healing of divided, 201 ; inflammation of, 306 ; hard cancer in, 624 Muscular tissue in fibrous tumours of the uterus, 476 ; developed in infiammatory lymph, 271 Myeloid tumours: relation to the fibro- plastic, 641 ; and to sarcoma, 641 . 838 INDEX. MTO aiBnitj to uatural bone-textuves, 542 ; situations, o43 ; general shape, 543 ; texture, 544 ; cysts, 544 ; microscopic structure, 545 ; general history, 546; cases, 547 ; recurrence and multiplicity, 553 ; with cartilage, 525 Myoma, 475 Myxoma, 458 NABOTHIAJSI cysts, 407 Naevi, 675, 584 ; pigmentary, liable to cancer, 751 Neck, serous cysts in the, 400; blood- cysts in the, 402, 410 ; proliferous cysts in the, 431 ; myeloid tumour in the, 553 Necrsemia : see Mortification Necrosis, 352 : and see Mortification ; of osseous growths, 537 ; preceding cancer, 732 Nerves, adaptation to atrophy, 89 ; healing of divided, 209 ; atrophy after dirision, 109; in granulations, 165; in adhe- sions, 274 ; fibrous tumours in, 480 ; relation of painful tumours to, 491 Nerve-centres, atrophy of, 93, 109 force, defect of, inducing mortifica- tion, 34, 346 ; disturbance of, initiating inflammation, 331 Nervous system, effects of exercise, 4 ; influence on nutrition, 28, et seq. ; on secretion, 36 Nervous tissues, degeneration of, 109 Neuralgia, with cancer, 643 ; with tumours, 493 Neuroglia, 112 Neuroma, 480, 491 Neua'o-pathological theory, 332 Newman, Dr., cases of hereditary trans- mission of cancer, 789, note Newport, Mr., on repair in insects, 125 Nipple, hard cancer of the, 619 Noll me tangere, 724 Non-vascular parts, nutrition of, 27 Nose, cutaneous outgrowth of, 455 ; epi- thelial cancer on, 708 ; sloughing after bleeding, 25 Nosology of cancers, 824 Nucleated blastema, 142 ; in blood-dot, 134; ossiflcation of, 182 Nuclei : capacity for development, 667, 715 ; in parts actively nourished, 44 ; proliferation of, 247, 804 ; stellate or branched, in cartilage, 500 ; erring as origins of cysts, and tumours, 397 Nutrition : nutritive process, modes of, 2; conditions of, 11 ; right state of the blood, 11; assimilation of the blood, 11; life of blood, 12; diseases of blood, 12; sj-m uetrical diseases, 13; seats of election of diseases, 15 ; identitv of OST specific morbid materials, 15. — Excre- tory office of each part, 17 ; office of ru'.limental organs, 18. — Incorporation of materials of the blood, 19 ; deter- mining the formation of certain struc- tui'es, 19 ; favouring the order of deve- lopment, 21. — Complemental nutrition, 21 ; simultaneous changes in nutrition, 23; commensurate development, 23; constitutional disttirbanoe, 24. — Supply of blood, 24 ; consequences of defect, 25 ; imbibition by tissues, 27 ; office of bloodvessels, 27. — Influence of the nervous system, 28 ; of the mind, 31 ; injuries of nerves, 32. — Healthy state of the part to be nourished, 37 ; assimi- lation in diseased -parts, 37 ; and in blood after diseases, 39 ; its precision, 40 ; and in the brain, 40 : see also. Formative Process Nutrition, altered conditions of, in inflam- mation, 2] 8 ; contrast of normal and inflammatory, 320 Nutritive repetition, 44 Nymphse, outgrowths of, 455 O'FEREALL, Dr., ease of fibro- cellular tumour, 462 Ogle, Dr. John, on an intracranial cuta- neous cyst, 437 Oily or fatty cysts, 412 Open wounds, repair of, 131 Orbit, cy^ts in or near the, 436 ; fibro- cellular tumour in the, 466 ; medullary cancer in, 672 ; osseous tumours grow- ing into the, 632 Organic affinity, 47 form dt-pendent on composition, 47 Organisation of blood-clot, 133 Ormerod, Dr., on fatty hearts, 81 ; ou in- flammatory products, 330 Osseous tumours : in soft parts, 526 ; of bones, 527 ; chief kinds, 527 ; homo- logy, 527 ; modes of ossification, 528 ; cancellous, 528 ; ivory-like, 530 ; of the skull, 531 ; sloughing, 533 ; of the lower jaw, 533 ; of the toes, 534. — Osseous growths of the superior maxil- lary and other bones, 53.5 ; of the skull bones, 537. — Multiple osseous growths, 538 ; symmetrical and hereditary, 539. — Distinctions of the bone in osseous and other tumours, 539 ; malignant, 754 Ossific diathesis, 639 inflammation, 270 Ossiflcation, in repair of fractures, 181 ; of cartilaginous tumours, 505 ; of mye- loid tumours, 548 Osteoid cancer : general nature, 754 ; INDEX. 839 OST seats, 754 ; general characters, 756 ; in lymphatic glands, 757 ; microscopic characters, 757 ; fibrous, 758 ; osseous 759 ; affinities to osseous tumours, 759 ; and medullary cancers, 661, 760 ; gene- ral pathology, 760 ; secondary disease, 760; cases, 761; characters of bone in, 539 Osteo-chondroma, 495 Osteoma, 526 Osteomalacia, 104 Osteophyte, 269 Osteoporosis, 103 Osteo-sarcoma, 495, note : 639 Outgrowths: general characters of, 389; cutaneous, 454 ; fatty, 444 ; fibrous, 472 ; osseous, 529 ; multiple osseous, 538 ; of bloodvessels, 161 Ova, length of life, 10 Ovary, cysts in, 417 ; their affinities vrith cancer, 435, 769 ; containing skin and its products, 436 ; with teeth, 442 ; hard cancer of, 628 Overgrowth : see Hypertrophy Owen, Prof., on ossification, 77 ; on den- tine tubes, 27 PACCHIONIAN bodies, 689 Pachydermatocele, 466, note Pain in mammary glandular tumours, 561 ; with cancer, 642 ; nature of, in tumours, 490 Painful subcutaneous tumours : general seats and relations, 487 ; microscopic structure, 488 ; pain, 490 ; growth, 490 ; distinctions from neuromata, 491 ; neuralgic pain, 493 ; pain in other tu- mours, 493 Palate, absorption of, under pressure, 67 Pancreas, cystiform dilatation of, 413 Pancreatic tumour, 556 Papillae, reproduction of, 214 ; cancerous, 702 : and see Epithelial Cancer Papillary growths, destructive, 727 Papillary tumours, 688 ; skin, 688 ; mu- cous membranes, 588 ; synovial mem- branes, 690 Paralysed parts, nutrition in, 33 ; treat- ment of, 92 Parenchymatous inflammation, 309 Parotid, blool-cysts on or in the, 41 ; cartilaginous tumours on or in the, 517 ; cysts over the, 400 ; cancer in, 686 Pearly tumour, 440 Pedunculated intracystic and other growths, 426 Perforating ulcers, 341 Pericardium, absorption of lymph from, 280 ; corpuscular lymph from, ininflam- mation, 246 Periodicity, in disease, 361, 366, 369 PHO Periosteum : its injury in fractures, 179; importance of, in formation of new bone, 180, Tiote ; cancer rising from, 726 ; in medullary cancers, 660 Peritoneum, colloid cancer of, 768 Peritonitis, lymph in, 248, 266 Personal modifications of disease, 370 Phalanx of the toe, osseous tumour on the, 534 Pharynx, fibrous polypi in the, 472 ' Phillips, Mr., on vascular tumours, 587 Phletolithes, in venous tumours, 585 Phymatoid substance, 686 Phymosis, effect on the bladder, 57 ; pre- ceding cancer, 732 Pigment in melanoid cancer, 746 Pigmental degeneration, 74 ; of small arteries, 106, note; degeneration of lymph, 283, 294, 259 Pigmentary naevi, liability to cancer, 751 Places, morbid products in certain, 799 Plasticand aplastic lymph, 260, note, 278 Pleurisy, lymph in, 246, 266 Pleuro-pneumonia, mixed lymph in, 254 Pneumonia, effusion of blood in, 243 ; lymph in, 264 Pointing of abscesses, 304 Poisoned wounds, 329 Poisons, morbid, 368, et seq. : see Specific Diseases Polypi, 462 ; fibrous, 472 Porcellaneous change in bone, 301 Potential energy, 47 Predecessors, formation after plan of, 116 Predisposition, meaning of, 788 Pressure, effects of, on nutrition, 66 ; pro- ducing sloughs, 342 Primary adhesion, 147 Products, inflammatory, development of, 260 ; degeneration of, 277 Progenitors imitated in offspring, 44 Proliferous cysts, 407 ; in the ovaries, 418 ; with broad-based endogenouscysts, 419 ; with pedunculated cysts, 420 ; intermediate forms, 420 ; probable mode of formation, 421 ; with glandular and papillary endogenous growths, 421 ; separation of ovarian cysts, 423 ; in the mammary gland, 424 ; method of intracystic growth, 426 ; consolidation ajd protrusion of the growths, 426 ; general structure of the growths, 426 ; their minute glandular structure, 426 ; their structure not evidently glandular, 429.— In the lip, 429; in the labium, 430 ; in various parts, 430. — Eecurring proliferous cysts in the breast, 432 ; in cancers, 434 Prostate gland, intracystic and detached growths of, 378 Prostatic glandular tumour, 666 Protoplasm nucleated, 142 840 INDEX. Purpose, in relation to accidents, 115 Pus, 170, 284 : see Inflammation and Suppuration ; transference in blood, 819 Putty-like degeneration of abscesses, 292 Pyogenic membrane, 288 Q UAIN, Dr., on fatty hearts, 81, et seq. Quekett, Mr., on formation of new vessels, 160 ; on ossification in cartila- ginous tumours, 502 ; on osseous tumours, 531 EABBIT'S-EAES, inflamed, 220 Eanke, on nutritive changes in muscles and nerves, 4 Eanula, probable varieties of, 393 Recovery from inflammation, process of, 237 Eectum, hard cancer of, 608 ; polypus of the, 472 Eecurrent tumours, 385, 591 Eecurring cartilaginous tumours, 524 ; fl.bToid tumours, 594, et seq. \ myeloid tumour, 553, 692 ; proliferous cysts, 432 Recurring fibroid tumours : cases, 594 Rodfern, Dr., on repair of cartilage, 194 ; on inflammation of cartilage, 307 Reid, Dr. John, on paralysed muscles, 92 Relaxing process over an abscess, 304 Eemoval of cancer, effects of, 825 ; partial, 685 Eepair and reproduction after injuries, 115; adaptation of parts for future events, 115; illustrations of formative force, 116. Repair of crystals, 118; its degrees in animals, 118; at different ages, 119; according to amount of development, 120. Repair in asteridse, actiniae, and hydrse, 12J. ; in tubularia, 123; gradual recovery of perfection, 124. Eepair in insects, 125, and lizards, 126 ; in man and other mam- malia, 127 ; general deductions, 127. Materials for repair, 130; distinction between subcutaneous and open injuries, 131. Methods of repair, 132. Organ- isation of blood, 133; its share in repair, 134. Lymph, 138; development of con- nective tissue, 139 ; granulation-cells, 139 ; nucleated blastema, 142 Eepa,ir, of open wounds, 143 ; by immediate union, 143. Dr. Macartney's account, 143 ; description of cases, 144 ; and experiments, 145; the best healing, 146; conditions necessary for it, 146 ; by primary adhesion, 147. Hunter's ac- count, 147 ; examples of the process, 148 ; its quickness, 148 ; by granulation, EEP 149 ; glazing of an open wound, 150 ; inaction after injury, 161 ; granulations forming, 153 ; afflux of blood, 163 ; comparison with inflammation, 153 ; production of reparative material, 154; its vascularisation, 154 ; minute struc- ture, 156; without suppuration, 165; development, 165 ; arrester error, 166 ; and diseases, 156 ; contraction, 176 ; chemical changes, 158 ; formation of new vessels, 159 ; three modes, 159, — that by outgrowth, 161 ; by channel- ling, 162; general arrangement of vessels, 163 ; structure, 164 ; relations to organisation, 164; development of nerves and lymphatics, 165; by secondary adhesion, 165 ; its plan, 166 ; examples, 167 ; conditions necessary, 167 ; by scabbing, 167 ; its process with blood, 168 ; with pus, 168 ; Suppuration and Scars [see these words] Eepair — fractures, 178; nature and extent of injury, 178 ; extravasation, 179 ; inflammation,. 179 ; period of calm, 179 ; commencement of repair, 180 ; immediate union, 180 ; reparative material or callus, 180 ; its rudimental state, 180; ossification through fibrous tissue, 181 ; through cartilage, 182 ; charactersof thenewbone, 183 ; position of the reparative material, 184; provi- sional or ensheathing callus, 184 ; inte- rior callus, 185; intermediate callus, 186 ; differences of repair in man and animals, 189 ; modellingafter the repair, 190; repair of compound fractures, 191 ; times of the stages of the repair, 192; false joints, etc., 192 Eepair of cartilage, 194; of tendons, 196 ; disadvantages of open wounds, 196; effect of dividing the sheath of connective tissue, 197 ; repair after sub- cutanenus division, 197 ; retraction of upper portion, 197 ; extravasation, 198 ; reparative material, 199 ; its develop- ment, 199 ; imperfection, 200 ; strength of the union, 201. Of muscles, 201. Of arteries and veins, 203 ; with small wounds, 203 ; with partial division, 203 ; with complete division, 203 ; con- traction and retraction, 204 ; acupres- sure, 206 ; after ligature, 206 ; inflam- mation of the tied end, 206 ; contraction of the part above it, 207 ; changes in the stagnant blood, 207. Of nerves, 209 ; cases of primary union, 210 ; se- condary union, 212 ; formation of new fibres, 212 ; repair of nerve-centres, 213. Of skin, 214; new formation of papillae and cuticle, 215; relation to inflammation, 216 INDEX. 841 EEP Repetition, nutritive, 44 Eeptiles, repair in, 126 Residual abscess, 295 Resolution of inflammation, 279 Retention tumours, 419 Reticulum of cancer, 616, 821 Retro-tracheal cysts, 409 Rheumatism, localisation of, 330 Rickets, 105 ; effect of, on tibiae, 64 Right state of blood, 11 Ringing, effects of, 20 Robin, M., on marrow cells, 642 ; on vessels in erectile tumours, 577 ; on epithelioma of kidney, 696 Rodent ulcer, 724 Rokitansky, Prof., on the formation of cysts, 395 ; on dendritic vegetation in villous cancer, 764 ; on erectile cavern- ous tumours, 574 ; on endogenous cells in cancer, 717; on inflammatory pro- ducts, 250 ; on stroma of cancer, etc., 669 RoUeston, Prof., on complementary nutri- tion, 23, note; on appendicular struc- tures to the testis, 415; on relation of reproductive power to respiratory process, 127 Rosenmiiller, organ of, 416 Rudimental organs, purpose of, 1 8 Rutherford, Dr., on influence of vagus on vascular system, 35, note SALIVARY glandular tumours, 517 Sanders, Professor, on pus corpuscles, 284, note Sanderson, Dr., on inoculation of tubercle, 571 Sanguineous cysts, 409 ; their various contents, 410 ; in the neck, 410 ; in the parotid gland, 410 ; internally fascicu- lated, 411 ; formed from dilated veins, 411 Sap, effects of accumulation, 20 Saponification of cancer, 820 Sarcoma, 641 ; albuminous, 599 ; colos- sal-celled sarcoma, 641, 546; gelatinous, 452, 517; myxo-sarcoma, 541; round- celled, 541 ; pigment, 841 ; spindle- celled, 641, 594, 602; sero-cystic, 417 Savory, Mr., on absorption of dead bone, 43, 353 ; on cyst in neck, 401 Scabbing, healing by, 167 ; and see under Repair Scars, maintenance and growth of, 37 ; their contraction, 176; improvement and gradual perfection, 176; loosening, 177; warty and cancerous growths on, 707 Schroeder van der Kolk, Prof., on lym- phatics in adhesions, 274 ; in cancers, 660 Scirrhous cancer, 605 ; usual form in the SEB breast, 606 ; usual state of the gland, 606 ; hardness, 607 ; size and shape, 607 ; adhesion and retraction of tissues, 608 ; cut surface, 609 ; mixture of can- cerous and natural structures, 610; wasting of natural tissues, 611; cancer- juice and stroma, 612; infiltration of cancer-structurea, 613; cells, etc., 614; degenerate structures, 615; degenerate normal structures, 615 ; reticulum, 616 ; fibrous tissue, 617. Varieties: acute and clironio, 618; of the nipple and skin, 618. In the lymphatic glands, 620; in the skin, 622; muscles, 624; bones, 625 ; intestinal canal, 626 ; mingled forms, 627 ; fibrous cancer, 628 ; in ovaries, etc., 629. Pathology : influence of sex, 630; age, 631; of menstruation, 633 ; hereditary disposi- tion, 634 ; injury, 634 ; general health, 634 ; first appearance, 636 ; growth, 636; multiple growths, 636; ulceration, 637 ; superficial, 637 ; fungous growths, 638; arrest and healing, 641 ; in con- neclion with phthisis, 641 ; shrivelling, 641 ; pain, 642 ; cachexia, 643 ; primary and secondary, 644 ; multiplication, 644; duration, 645; effects of age, 646; effect of removal, 648 ; recurrence, 650; rules concerning operations, 662 Scrofula, relation to tuberculous disease, 569 Scrofulous matter, 279 Scrotum, cancer of: see Epithelial Cancer; fatty tumour in the, 448 ; fibro-cellular tumours in the, 461 ; hypertrophy of, 466 Sebaceous and epidermal cysts, 438; here- ditary origin, 438 ; twofold formation, 438 ; various characters, 438 ; of the walls and of the contents, 438 ; ulcera- tion, 440 ; fatal case, 441 ; protruded contents becoming vascular, 441 ; con- nected with epithelial cancer, 709 Secondary adhesion, 149 cysts, 393, et seq. Secretion, influence of nervous force on, 36 Semi-malignant tumours, 554, 602 Seminal cysts, 413; their spermatozoa, 414 ; probable position, 414 Senile, gangrene, 342; atrophy of skull, 100 Separation of ovary, 423; of fibrous tu- mours, 480 Sequelae of diseases, 369 Sero-cystic sarcoma, 417 Serous cysts : their contents, 399 : seats, 399 ; in the neck, 400 ; connected with the thyroid gland, 401 ; transformations of vascular tumours, 402; with viscid contents and cholestearine, 403 ; near the gums, 403 ; in the mammary gland 842 INDEX. SEE 404 ; dilated ducts, 404 ; autogenous cysts, 393 ; large single cysts, 404 Serpent-venom, 364 Sex, influence of, in cancers. See Cancer, genpral pathology Sexual characters, related development of, 22 Shifting of tumours, 448 Shortening of bones, 66 Sibley, Mr., on colloid cancer, 771 ; on villous cancer, 763 ; on multiple fibrous tumours, 777 Signs of inflammation, 317 Simon, Mr., his observations on cysts, 395 ; on extension of cancer, 815; on morbid poisons, 368, et se