it Private Library OF D. E. SALMON. Book No. Case Ho. CORNELL UNIVERSITY. C dht^ THE THE GIFT OF ROSWELL p. FLOWER FOR THE USE OF THE N. Y. STATE VETERINARY COLLEGE 1897 8394-1 Cornell Unlveralty Library RB 25.C81m 1882 V.1 Manual of pathological histology, 3 1924 000 291 108 I Cornell University J 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/cu31924000291108 PATHOLOGICAL HISTOLOGY VOL. I. MANUAL OF PATHOLOGICAL HISTOLOGY BY COKNIL AND RANVIER SECOND EDITION, RE-EDITED AND ENLARGED Sranslateb fait^ t^t ^pprottal of tfej ^«tfeors By a. M. HAKT Vol. I. GEJSERAL PATHOLOGICAL HISTOLOGY LESIONS OK TiiK ELEMENTS and TISSUES WITH 2SI FIGURES lyXEItSPERs^ED IN THE TEXT LONDON SMITH, ELDEE, & CO., 15 WATEKLOO PLACE 1882 {All lights rtterved] AUTHOES' PEEFACE TO THE SECOND EDITION. The first edition of this manual was published in three parts ; the first in 1869, the second in 1873, and the third in 1876. It has been very favourably received by the French medical pubhe, and the successive issues demanded have afforded us the satisfaction of seeing that we have succeeded in making the most important data of pathological histology part of the ordinary knowledge of students. The first edition is now out of date and no longer abreast of science, so that we have been obliged almost entirely to recast the work. The general account of normal histology placed at the beginning of the first volume has been remodelled and brought up to the level of the progress made in the last ten years. In this decennial period normal histology has made relatively greater pro- gress than pathological histology, but the latter, which is based on the former, and which borrows from it not only its discoveries but its methods, has also undergone great changes. Thus in some chapters we have preserved nothing but the heading, and we have added many chapters which were not in the first edition. Many new illustrations have been added, and in every detail we have striven to make the second edition worthy of the success which attended the first. The entire work forms two volumes : the first contains the general pathological anatomy of the tissues ; the second will include the pathological histology of the organs, Pakis : October 25, 1880. TEANSLATOE'S PEEFACE. In translating this standard treatise from French into English I have accomplished a task, the usefulness of which will, I believe, be generally acknowledged by students and others in England. In its simplicity of arrangement, its comprehensiveness and originality, the Pathological Histology of Comil and Eanvier is acknowledged to have no rival. Only the first volume of the second edition is now presented. The second volume will follow in due course, and will be translated as soon as it is published in France. The translation closely follows the original ; but, mindful of the needs, and to serve the convenience, of students, I have re-paragraphed the book, grouping under one heading all that is said on one subject, and for facility of reference I have headed the paragraphs with letters in Egyptian type. I have also compiled and added a com- plete index and a few notes. The translation was undertaken with the conciurence of my master. Professor Eanvier, and of M. C«mil, they being the more desirous of an authorised English translation, as a translation of the first edition had appeared in America without their authority. The figures are from the same blocks as those used in the French edition. I wish gratefully to acknowledge the kindness of Dr. Klein in reading and correcting the proofs for me as the book passed through the press. London : March 14, 1882. CONTENTS. PART I. GENERAL PATHOLOGICAL ANATOMY. CHAPTER I. A 8T7MMAEY OF NOBMAI. HtSIOLOaT— CELLS AND NORMAL TISSUES. L'AGE I. The cell theory and the structure of cells ... 1 II. Normal tissues ....... 10 III. Lymph, blood, plasma . . . .41 CHAPTER 11, GENEEAI CONSIBEKATIONS ON PATHOLOGICAL HISTOLOGY — MORBID CHANGES IN THE CELLS AND TISSUES. I. Lesions of nutrition of elements and tissues . . . . 58 II. Formative lesions ; new formation of cells . . . .82 CHAPTER in. INFLAMMATION. I. Definition of inflammation . . . .86 n. Artificial inflammation of non-vascular tissues . . . 88 ni. Experimental inflammation of vascular tissues . .92 IV. Analytical study of inflammation . . . . . 100 V. Synthetical study of inflammation and its clinical form . .118 CHAPTER IV. TUMOURS. I. Tumours formed of embryonic tissue — sarcoma . . . . 126 II. Tumours the type of which is found in the different varieties of con- nective tissue : — Myxoma ....... 15i Fibroma . . . . 161 Lipoma ........ 168 Carcinoma . . 172 Syphilitic gummata ...... 187 Tubercle . ■ • • . . 199 Glanders . . • ■ 211 a CONTENTS. in. Tumours having their type in cartilaginous tissue— chondroma . 214 IV. Tumours formed of osseous tissue — osteoma .... 225 V. Tumours formed of muscular tissue — myoma . . . . 231 VI. Tumours formed of nervous tissue— neuroma .... 235 Vn. Tumours formed of blood-vessels— angioma . . . . . 239 VTII. Tumours formed of lymphatic vessels — lymphangioma . . 243* IX. Tumours formed of the tissue of the lymphatic glands — lympha- denoma . . . . . . . . . 245 X. Tumours of the type of epithelial tissues — .... 255 1. Epithelioma . . . . . . . 257 2. Papilloma ....... 277 3. Adenoma . . . . . . 283 4. Cysts . . . . . . . .292 XI. Mixed tumours . . . . . . . . 302 Analytical table of tumours ..... 306 Appendix to tumours . . . . . 315 Melanotic masses in the form of tumours . .315 Hydatid cysts . , . . . . 318 PART II. LESIOKS OF THE TISSUES. OHA.PTER I. LESIONS OP THE BONES. I. Congestion and hsemorrhage of bones II. Ostitis ..... HI. Necrosis . . IV. Caries ..... V. Callus ...... VI. Tumours of the bones . . . . VII. Osteomalacia ..... Vm. Eachitis ...... IX. Syphilitic lesions of bones in the new-born . .326 327 338 343 348 3.53 365 367 374 CHAPTER IT. LESIONS OE CARTHiSINOUS TISSUE. . CHAPTER in. PATHOLOGICAL ANATOMY OF THE AETICTOATIONf I. Normal histology of the articulations II. Acute arthritis III. Chronic arthritis . . " ' IV. Scrofulous arthritis or white swelling V. Gouty arthritis . . VI. Tumours of the articulations 379 381 387 396 401 405 CONTENTS. xi CHAPTER IV. ALTERATIONS OP CONNBCITVB TI8STIB. lAUK I. Congestion and hsemorrhage of connective tissue . 408 n. (Edema . . . . . . . +10 ni. Inflammation of connective tissue . . . . .113 rv. Purulent inflammation of connective tissue or acute phlegmon 41.5 V. Chronic phlegmon . . . . . .418 VI. Tumours of the connective tissue . . . 420 CHAPTER V. LESIONS OP THE 8BEO08 MUMBBINB . I. Haemorrhage of the serous membranes ..... 422 II. Inflammation of the serous membranes . 423 III. Tumours of the serous membranes .... 4.S1 CHAPTER VI. THE ALTEEATI0K8 OF MUSCULAR IISSUK. I. Normal histology of the striated muscles . . 43i; II. Lesions of nutrition of the primitive muscular fasciculi 4;i7 III. Tumours of the muscles . . . . . ioi IV. Parasites of the muscles ....... 456 CHAPTER VH. PATHOLOGICAL HISTOLOGY OF THE BLOOD. CHAPTER VIII. MORBID CHANGES IN THE BE.VRT. I. Lesions of the pericardium . 4i;;i II. Lesions of the myocardium . .472 III. Lesions of the endocardicm . . . . . 481 CHAPTER IX. LESIONS OP THE ARTERIES. I. Normal histology of the arteries ..... 490 II. Pathological histology of the arteries 491 CHAPTER X. LESIONS OF THE CAPILLAET VESSELS. I. Normal histology of the capillaries ..... .520 U. Pathological histology of the capillaries 5i'l xii CONTENTS. CHAPTER XI. tESIONS OF IHB VEINS. FAGS I. Normal histology of the veins . ■ • • • • 526 II. Pathological histology of the veins . . • • • • 527 CHAPTER Xn. LESIONS OF THE LYMPHATIC VESSELS. I. Normal histology of the lymphatic vessels . . . .537 II. Pathological histology of the lymphatic vessels . . . . 538 CHAPTER Xin. LESIONS OF THE LYMPHATIC 6LANDS. I. Normal histology of the lymphatic glands .... 542 II. Pathological histology of the lymphatic glands . . . . 546 CHAPTER XIV. LESIONS OF THE NERVES. I. Normal histology of the nerves ...... 560 II. Pathological histology of the nerves . . . . 561 CHAPTER XV. LESIONS OF THE CEREBRUM AND CEREBELLUM. I. Normal histology of the central nervous system . . . 569 II. Lesions of the meninges . . . . . 578 III. Lesions of the cerebrum and cerebellum .... 587 CHAPTER XVI. LESIONS OF THE SPINAL CORD. I. Normal histology of the spinal cord .... 601 II. Histological lesions of the spinal meninges ■ . . , 604 III. Pathological histology of the spinal cord . . . , gOS INDEX 641 MANUAL OF PATHOLOGICAL HISTOLOGY. PART I. GENERAL PATHOLOGICAL ANATOMY, CHAPTER I. A SUMMARY OF NORMAL HLSTOLOGY— CELLS; AND NORMAL TISSUES. I. — The Cell Theory and the Structure of Cells. Before entering on the study of pathological histology, we pro- pose in a few pages to give a summary of our present knowledge of normal histology, so that the reader may understand the prin- ciples which have guided us in our exposition of pathologica. facts. Histology, founded by Bichat under the name of General Anatomy, took a fresh departvire from the moment that Schwann, extending to animal tissues the discoveries Schleiden had made in the vegetable world, founded the cell theory (1839). From the researches of Schwann it was established that the cell, in the animal as in the vegetable world, is essentially the organic unit, the most simple body in which life is individualised, in such a manner that certain living individuals, vegetable or animal, possessing the functions of nutrition, motion, and reproduction, are composed of a single cell. In beings of a more complex structure, cells are either sur- rounded by an intercellular substance which differs according to the 2 SUMMARY OF NORMAL HISTOLOGY. nature of the tissues and organs, the cells being the essential part ; or they are so greatly modified that they can scarcely be recognised unless the metamorphosis has been watched; here, again, cells play the principal part. According to Schwann, the cell is composed of: 1, an enveloping membrane; 2, contents more or less liquid; 3, a nucleus ; 4, one or more nucleoli contained within the nucleus. This conception and definition of a cell were accepted by the successors of Schwann, of whom the most illustrious were Remak, Eeichert, Virchow, KoUiker, Donders, &c. These teachers, how- ever, have completely modified Schwann's theories regarding cell-formation. Schwann, in fact, admitted a free forTnation (spontaneous generation) in a primordial generative fluid, which is found alone, or situated between pre-existing cells (blastema or cytoblastema). In this fluid a granule appears ; this is the rudiment of the nucleolus. '■'n^'-M-K^''''®'' «*'•»• • Q ^ - * « FlQ. 1. — DiAQKAM OF THE DEVELOPMENT OF CELLS (after Schwann). Around it new granules group themselves : these are inclosed by a membrane, and thus the nucleus is formed. The nucleus acts on the surrounding blastema, fresh granules appear, and soon become enclosed in a cellular membrane ; from this moment is formed the complete element, called a cell. Eemak, whilst engaged in studying the phenomena of embry- onic development, entirely reversed this theory, preserving, how- ever, all that was fundamental in Schwann's conception of a cell. Starting from the idea that the ovule is a true cell, of which the vitelline membrane is the cell-wall, the vitellus the contents, the germinal vesicle the nucleus, and the germinal spot the nucleolus, he observed that all the cells of the embryo were derived from this cell, according to the following process : After fecundation the vitellus is divided by cleavage into two parts, by a second cleavage into four parts, and so on until a great number of spherical bodies are formed. These segmented balls, or new cells, apply themselves to the internal surface of the vitelline mem- THE CELL THEORY. 3 brane so as to form a layer (the blastoderm), which soon divides into three laminae composed entirely of cells. It is from these cells, by a process of which segmentation is always the essential characteristic, that all cells, according to him, are produced. After investigations into the origin of all tissues from these embryonic cells, Remak concluded that every cell was produced from a pre- existing ceU by one of three different methods : by segmentation or scissiparity, by germination or budding, or by endogenous formation. At the present time, according to the conception of the cell we shall presently unfold, these three methods cannot be looked upon as essentially different. Virchow applied to pathological anatomy the data furnished by Remak concerning physiological development. He considered that every new formation of cells, or every neoplasm, is the result of a continuous development from pre-existing cells ; and he thus tightened the bonds uniting pathology and physiology. Like I'lG. '1. — Skumkntation ok the Ovui.k in Asi aris NlGROVKSOSA. (Figure borrowed from Kblliker.) Remak, he adopted Schwann's definition of a cell, recognising in it a cell-wall, contents, a nucleus^ and nucleolus. Subsequently, owing to the labours of Max Schultze, Reckling- hausen, Kiihne, L. Beale, &c., the definition of a cell was con- siderably modified. It is long since Dujardin first observed that the lowest order of beings composed of a single cell were not always enveloped by a membrane, and composed of a substance insusceptible of chang- ing shape, inasmuch as very extensive processes could be sent out from it. Dujardin called this substance sarcode, and its move- ments aarcodic movements. Max Schultze, investigating the same phenomena more completely, observed these movements not only in the unicellular animals called amoebae, but also in the cellular elements of more complex animals. He compared the animal cellular masses, susceptible of movement, to the vegetable cellular masses long known under the name of protoplasm, and called the fundamental substance of animal cells also by the name B 2 4 SUMMARY OF NORMAL HISTOLOGY. oi protoplasm, and the movements of which it is capable amoeboid m,ovements. A very large number of the cells in the higher animals and in man, white blood-corpuscles and embryonic cells for ex- ample, are composed of protoplasm, have no cell-wall, and show amceboid movements. In order that the truly characteristic movements of protoplasm may be observed, cells should be placed in the same medium and under the same conditions of humidity and temperature in which they exist in the normal state. In cold-blooded animals the phenomenon is observed very easily, as conditions of temperature may be disrega.rded. All that is necessary is to take the blood of a frog or triton, and to examine it, taking care to prevent evaporation. Protoplasmic processes are seen to be pushed out from the periphery of the white blood- corpuscles, and to ramify in such a manner that expansions arising from the same cell, and coming in contact with others, they are Fig. 3. — Pus Cells. a, seen in a neutral fluid ; 6, seen after the action of water or acetic acid ; c, living cells showing amceboid moTements. often fused together ; little by little the entire mass of protoplasm may pass into a process, thus causing the body of the cell to become displaced : the process may also sometimes be seen to be withdrawn and to melt away into the common mass. If coloured particles are in the neighbourhood of the cells showing these movements, they are absorbed into the amceboid process, and may thus penetrate into the interior of the cell. Fusion of the amceboid processes, and penetration of coloured particles into the interior of the cell, prove that the cell possesses no membrane. These facts alone suffice to destroy the definition of a cell given by Schwann and accepted by Eemak and Virchow. Nevertheless it is not contended that every cell is destitute of a cell-wall ; but that, when this exists, it constitutes only an accessory part of the ceU. The definition of a ceU is thus reduced to a mass of protoplasm enclosvng a nucleus. The nucleus of the cell seems to be a vesicle, the enveloping CELLS. 5 membrane of which is often made evident by a double contour. The contents are sometimes clear, sometimes slightly granular. The high refraction of nucleoli has given rise to the idea that they may be composed of fat ; but the facility with which they are coloured with carmine, and their solubility in liquor potassse, show that we have not here to do with fat, which is not coloured with carmine, and does not dissolve in cold liquor potassaj. Further, the researches of Balbiani on the ovule demonstrate that the germinal spot, of a size large enough to be studied, is a vesicle capable of change of shape and size under the eye of the observer. We shall also see, later on, that, with regard to the epithelial cells of the skin, nucleoli are capable of becoming vesicular under even slight irritation. Originally every cell is simply composed of a mass of protoplasm surrounding a nucleus. Among all the cells possessing this initial structure no differences have been ob- served indicating that a given cell will undergo certain ulterior changes. In the adult animal, cells of this simple structure are only found in the blood (white corpuscles or lymph cells), or in tissues subject to constant renovation ; but they constitute the entire embryo, and thus deserve the name of evibryonic cells. Cells which have no cell-wall, and which are composed of a proto- plasm capable of amoeboid movements, are — 1, embryonic cells before they have taken any determined form ; 2, the cells in the de- veloping layer of the medulla of bone ; 3, the mother-cells found in the same spot ; 4, the white corpuscles of the blood. Embry- onic cells of a mean diameter of 10 yu. to 15 /i' are composed of an irregular mass of granular protoplasm, and are generally of a spherical form. The protoplasm swells on the applica- tion of water or acetic acid, and is coloured dark brown with a solution of iodine, and feebly with carmine, which latter renders its granular condition more apparent. This mass encloses an ovoid or spherical nucleus, which is often not visible till after death, or till acted upon by water or acetic acid. The nucleus generally shows a double contour, and contains one or more nucleoli. In the place of one nucleus, if the element be losing its vitality, there are often seen several little angular nuclei resembling small fragments, Buch as are formed in pus cells undergoing caseous degeneration. If the cells are growing, the nuclei are spherical and well de- veloped. In the developing layer of bone from cartUage, cells are met ' We take as the unit of microscopic measurement the thousandth of a milli- loitin and represent it by the letter /i. 6 SUMMARY OF NORMAL HISTOLOGY. with presenting such close analogies to embryonic cells, that we know of no characteristics sufficient to distinguish them. These cells subsequently undergo modifications which slightly differentiate them from the primitive type. The multi-nucleated cells which are met side by side with them possess the same general properties, with the exception of the multiplicity of their nuclei, the great irregularity of their shape, and the buds which they throw out ; the protoplasmic material of which they are composed shows identical reactions. Later on these elements become flattened, more consistent, and diverge from the original type. Embryonic cells, as well as lymph cells of the blood and lymph, which are of like structure, habitually contain glycogenic Fig. 4. — Cells of the Medulla of Bonk undergoimg Development. o, Mother-cell with multiple nuclei and processes ; 6, the same elements showing buds about to separate ; c, young cells with a single nucleus identical with embryonic cells ; d, a mother-cell seen sideways • e, a fusi- form cell with a single nucleus. ' matter in a notable quantity. In fact, when acted on by iodine in a solution of iodide of potassium, these elements are stained a diffiise violet colour, or they present in their interior little drops of the same colour. We are justified in the present condition of science in considering this reaction as characteristic of glycogenic matter. The researches of Claude Bernard have, moreover, taught us that most of the embryonic tissues, when in a state of great activity of development, contain glycogenic matter in their cells. The most remarkable example of this presence of glycogenic matter is afforded us in the striated muscular tissue of the embryo. The primitive bundles are composed of cylinders of which the MULTIPLICATION OF CELLS. 7 periphery alone is striated, whilst the central formative protoplasm is not. The glycogenic matter is stored up only in this proto- plasm. In coryza also, at its commencement, the lymph cells which escape with the serous effusion contain glycogenic matter, whilst the ciliated cylindrical cells, even those which are broken up into fragments still provided with cilia, do not contain glyco- genic matter. If we leave aside the early phenomena of the development of embryonic cells investigated by Biitschli, Auerbach, Balbiani, Fol, &c., to occupy ourselves especially with the growth and multipli- cation of cells after their production, we shall find in the lymph cells of the axolotl and proteus, examined in their living state, remarkable examples of multiplication of cells by division. . If the •:f:S^ Flo. 5. — Lymph Cell of thk Blood of Axolotl examined IN THE Living State. k, cell at the beginning of the observation; c, protoplasm with ita amoeboid processes; fl, the nncleus constricted at e ; n', nucleoli. B, the same cell observed at the end of twenty minutes ; the nucleus is enlarged at the middle and is sending out two buds, 6, l/ c, the corpuscle treated with a 33 per cent, solution of alcohol ; p, nucleus with its buds n, n'. lymph cells of the blood of these animals be observed in their own plasma, and without the addition of any reagent, the nuclei which they contain may be seen quite distinctly, whilst in the frog and in mammals no nucleus can be distinguished in similar cells when alive and in a state of physiological activity. A drop of blood of the axolotl, obtained by an incision either in the membranous expansion of the skin or in the gills, should be placed in the centre of a moist-chamber slide, evaporation being prevented by a border of paraffin round the edge of the cover- glass. Among the red corpuscles, the white blood-corpuscles, 8 SUMMARY OF NORMAL HISTOLOGY. recognised by their rounded form, their smaller diameter, and by the absence of haemoglobin, are soon seen to send forth little amoeboid processes, the form and size of which vary incessantly. In the midst of the protoplasm the sharp outline of the nucleus is perceived. It is round, irregular, or elongated in shape, or often folded on itself. The form of the nucleus varies according to the amoeboid activity of the protoplasm which surrounds it. Whilst engaged in following one of these cells in its changes of form, and in its migrations, it may chance to divide under the eye of the observer. The nucleus, at first distorted in a thousand different ways by the pressiure of the moving protoplasm, finally divides into two distinct nuclei contained within the same cell. The cell, itself participating in turn in the process of division, is either divided by a line of segmentation, or retracts centrally till separation is completed. Nuclei of the lymph cells of the blood and of the lymph are often elongated, and folded on themselves, affecting a serpen- tine form. If fixed by the action of dilute alcohol or by the vapour of osmic acid, and then coloured with picro-carmine or with aniline red, their true shape can be accurately ascertained. It is then easy to understand how that cells containing one elongated nucleus folded on itself have often been described as multi- nucleated cells. In the process of multiplication of lymph cells the amoe- boid activity of protoplasm plays an important part. In the multiplication of the cells of tumomrs, the multiplication of the nuclei which precedes that of the cells seems to depend principally on a process of change which takes place in the nucleus itself. All embryonic cells have the property of producing elements similar to themselves by the following process: the nucleus enlarges, the nucleolus becomes constricted and divides ; the nucleus soon also divides, either by cleavage, which cuts it in \fno, or by a kind of constriction which gives it the shape of an hour- glass. The protoplasmic mass surrounding the two new nuclei then divides, and two cells are the result. The segmentation of the protoplasm does not always follow that of the nucleus, so that a large number of nuclei may be contained in the same cell (a, 6, fig. 4). A portion of protoplasm may not unfrequently be seen to become detached enclosing a nucleus (6, fig, 4). Embryonic cells are either destroyed, or undergo a series of changes which give them the characteristic appearances found in the different tissues. The simplest example of modification of THE CELL-WALL. 9 embryonic elements is that in which there is an elaboration, within the protoplasm, of substances which did not exist there before ; for example, in the first stage of the formation of fat cells, minute drops of fat may be seen in the protoplasm. In other cases pig- ment granules are found, for example in the cases of cells con- tiguous to red blood-corpuscles which have been extravasated into a tissue. The most important modification which embryonic cells undergo is in the formation of a membrane enclosing the proto- plasm. This membrane is comparable to the secondary mem- brane of vegetable cells where it is composed of cellulose, whilst in animals it is composed of an albuminoid substance : such are fat cells, cartilage cells, &c. In every kind of cell there are strik- ing differences with regard to this membrane. It is still disputed whether it is produced by thickening of the superficial layers of Fig. 6. — Vakious Phases in the Division of tub Nucleolus and Nucleus in Cells from Sakcoma in a Horse. a, DQCleuB already constricted and having two nucleoli ; 6, division more ad- vanced ; c, nucleolus about to undergo division ; d, «, various forms of seg- mentation of the nucleus. Magnified 460 diameters. the protoplasm, or by secretion of the latter. Whichever it may be, it is entirely distinct from the protoplasm, and capable of being isolated from it. This can be well observed in fat cells, cartilage cells, and the epithelial cells of the buccal mucous membrane. To demonstrate this fact in the latter a 40 per cent, solution of potash should be employed. From the moment that a cell is surroimded by a secondary membrane, or that a substance, more often elabo- rated by itself, is formed at its periphery, it is fixed in a permanent form. It then assists in the construction of a tissue, so that it is impossible to study cells without considering the tissues which contain them. Hence we shall study cells in considering the tissues. SUMMARY OF NORMAL HISTOLOGY. II. — Normal Tissues. Normal tissues may be divided into three groups, GrROUP I. Those in which the substance uniting and separat- ing the cells is characterised by its form, its physical and chemical properties (connective, cartilaginous, and osseous tissues). In these tissues, though the cells have special physiological pro- perties relating to the formation and preservation of the tissues, their form is not characteristic when considered separately. GrEOUP II. The second group comprises those tissues in which the cell has undergone such modifications that it has generally become unrecognisable as a cell, but has assumed certain fixed physical, chemical, and physiological characters. These are the muscular and nervous tissues. Group III. This includes tissues composed of cells having a regular and constant evolution. They are closely bound together by a cementing substance very slight in quantity. Of such are glandular and investing epithelium. Their cells have often a characteristic form, and they elaborate certain fixed sub- stances ; thus, the epidermal cells elaborate horny matter ; cer- tain mucous cells, mucin ; certain glandular cells of the stomach, pepsin, &c. GrEOUP I. Connective, Cartilaginous, and Osseous Tissues. Connective Tissues. — ^The connective tissues are the mucous, areolar, fibrous, adipose, retiform, and elastic tissues. The formation of mucous tissue from embryonic tissue is very simple. In the simplest variety of this tissue, that met with in the vitreous humour, a hyaline substance containing a large quantity of mucin is thrown out between the cells, these remaining quite independent of one another. In another variety, that of the umbi- lical cord, the cells become fusiform or stellate and anastomose, a gelatinous substance being formed between them. In the midst of this gelatinous material little bundles of connective tissue, re- cognised by their fibrous structure and their wavy form, are grad- ually developed. These bimdles increase in diameter progressively as they develop. As to the cells, they are always formed of a mass of protoplasm containing one or more nuclei. Eoimded CONNECTIVE TISSUES. n cells, composed also of a mass of protoplasm, are frequently seen beside the stellate cells. The cells which form the constituent elements of areolar tissue are also derived from embryonic cells. Between them are bundles of connective tissue, which, but slightly developed in mucous tissue, are here greatly increased. They are very numerous, and the larger number of them are of a considerable diameter. The bundles are made up of fibrils held together by a soft cementing substance which permits them to glide one over the other. It is this which gives them their undulating appearance, resembling ^■*'^c,. Fio. 7. — Mucous Tissue of the Umbilical Cord of tuk Embryo of the Sheep. c, ramifying cells ; n, embryonio or lymph cells ; F, bundles of connective tissue ; B, amorphous material. Magnified 600 diameters. hair. Connective-tissue cells are never seen in the interior of a bundle, but always on its surface. They are flat, branching, and often have equally flat processes which unite them with one another, as in mucous tissue. On their surfaces ridges are often seen, caused by the impression of neighbouring bundles — ridges which, recently described by Waldeyer, are analogous, but not simi- lar, to those one of us described in tendons. These cells have one nucleus, which is also flat. In the first edition of this manual we adopted Virchow's view, modified by Recklinghausen, as to the structure of connective 12 SUMMARY OF NORMAL HISTOLOGY. tissue. We thought then that this tissue was formed of a funda- mental fibrillar substance, in the midst of which canals were hollowed out (plasmatic canals, serous channels) and that the plas- matic or connective-tissue cells were included within these canals. This false interpretation arose from the fact that connective tissue was generally examined in transverse sections after desiccation or hardening in chromic acid or alcohol, and after the action of acetic acid. But Henle, who, in studying connective tissue, continued to have recourse to dissociation, always declared himself against the teaching of Virchow and his pupils. His description of con- nective-tissue bundles is perfect. He recognised their fibrillar structure, and described the annular and spiral fibres which are twisted round the fasciculi, lacing them together and consolidating them. Henle, however, was not aware of the existence of active cells, so that, according to him, connective tissue only contained Fig. 8. — Connective Tissue. o, connective-tissae bundles cut "transrersely or obliquely to their direction ; 6, connective-tissue cells. Magnified 20O diameters. Section obtained after desiccation, stained with carmine and treated with acetic acid. elements derived from primitive cells, and which he called fibres of nuclei (annular, spiral, and elastic fibres). Annular and spiral fibres are stained red with carmine, and retain their colour after the addition of acetic or formic acid, whilst elastic fibres remain colourless. The nuclei of connective-tissue cells, and the surface of the bundles, are stained with carmine exactly as the spiral fibres. Virchow, who recognised the existence of the nuclei, considered that they were contained within cells analogous to osseous corpuscles, in that they are necessarily limited by the surface of the fasciculi, which are also distinguished by theii- colour. Although Virchow was mistaken in the form, the relations, and the signification of the connective-tissue cells, yet to him never- theless is due the merit of having affirmed their existence. To understand the structure of connective tissue, that is to AREOLAR TISSUE. '3 say, the form of its cells and the relatiori of these cell« tp the bundles of fibres, simple dissociation in water, as was formedj 'done, and as Henle practised, is not sufficient. In fact,-; if a; sufell' portion of subcutaneous tissue, taken from the human, subject oj? a 'mammal, be dissociated in water with needles, the bundles are, Qoafusedly mixed together, so that it is difficult to distinguish one from the other, and to see what occupies the spaces between them, ^is tissue can only be studied by means of interstitial injections. The iie%od of procedure is as follows : With a hypodermic swinge provided with a pointed cannula, a fluid such as serunlj simple or feebly ^ Fig, 9.— Subcutaneous Cellular Tissue from the Inguinal Region of the Dog. o, oonneotive-tissue bandlea swollen by the action of formic acid and sliowlnK annular fibres ; h, elastic fibres ; c, flat oonneotive-tissue cells seen full lace ; c', the same seen sideways ; n, lymph cells. iodised, or a solution which has the property of fixing the delicate elements (nitrate of silver j-jVoj osmic acid y^, alcohol ^, water f ) is injected. A bulla of artificial oedema is produced, which in- creases in size as more fluid is injected, without its shape being notably modified. From this bulla thin sections of cedematous tissue are cut by very sharp scissors, and deposited at once on a slide and covered by a cover-glass. In preparations thus made, large, membranou.^^, branching connective-tissue cells can be recog- / 14 SUMMARY OF NORMAL HISTOLOGY. nised, and alongside them connective-tissue bundles, elastic fibres, and lymph cells. These latter do not occupy a fixed position in the tissue. They belong to the plasma which fills up the meshes between the fibrous bundles. Lymph cells are capable, like aU similar cells, of amoeboid movements. When alive, and under favourable conditions, they give origin to protoplasmic processes, which implant themselves on neighbouring surfaces, are then withdrawn, whilst other amoeboid or pseudopodic processes are formed, grow, and attach themselves like the first. It is by this mechanism that lymph cells move and travel. Thus they are essentially migratory ele- ments, even though they are not carried along by any current of fluid. The migration of cells from the very centre of the tissues was discovered by Eecklinghausen, and it has become a fact of considerable pathological importance. Areolar tissue may be looked upon as mucous tissue in a more advanced stage of development. Thus, in the embryo where eventually connective tissue is formed, mucous tissue exists. At birth the umbilical cord and the vitreous humour are the only parts which remain as mucous tissue. Into fibrous connective tissue (ligaments, aponeuroses, and ten- dons) the same constituent elements enter as into areolar tissue, that is to say, connective-tissue bundles, elastic fibres, and flat cells, only that the fasciculi, instead of lying, as in the areolar tissue, in every direction, and being up to a certain point inde- pendent of one another, are here parallel, or crossed in a simple manner in planes which are either perpendicular or more or less oblique. If parallel, the flat cells situated on their surface are arranged in rectilinear series, and bear impressions, more or less numerous and parallel, of other connective-tissue bundles pressed against their surface. When the fasciculi are perpendicu- lar to one another, as in certain aponeuroses of the frog, for ex- ample, in that of the triceps cruralis, between the two layers of fibres flattened cells are noticed, having ridges formed by pressure corresponding to the interstices of the bxmdles, which are per- pendicular to one another, some corresponding to the superficial plane of fibres and others to the deeper. In tendons, ligaments, and aponeuroses, lymph cells are not met with, and the plasma which bathes the constituent elements does not contain formed elements. Adipose tissue results from an accumulation of fat within the cells of mucous or areolar tissue. The fat forms distinct granules ADIPOSE TISSUE. '5 in tbe midst of the protoplasm of the cell. Little by little these granules become larger, and they melt into one another. The nucleus is displaced towards the periphery. A secondary mem- brane is formed which completely envelops the element, so that a fat cell fully developed is formed of three distinct parts, ex- ternally an enveloping membrane, beneath it a layer of protoplasm containing the nucleus of the cell, and within a large drop of fat. In man, fat is fluid at the ordinary temperature of the body ; after death, needles of margarin are developed in it. Connective-tissue Fii;. 10. — Section of the Medullary Substance of a Lymphatic Gland OF THE Ox. a, follicular sabetonce ; 6, flbrons trabeonlBO ; c, lymph cbiuinelB ; d, blood-vessels. Magnified 300 diameters. Figure taken from Recklingbansen. cells which have become adipose cells are not arranged in a chance manner in connective tissue ; they form groups, lobules of variable size possessing a distinct and very characteristic capillary network, each vascular mesh containing one or more fat vesicles. In retifonn tissue the fibres of connective tissue are extremely fine. They adhere together, then separate to unite with other fibrils, forming by their union a delicate reticulum, the trabeculse of which pa.'is in every direction, and are covered by flat delicate i6 SUMMARY OF NORMAL HISTOLOGY. cells spread out on their surface and moulded on them like a varnish. The meshes of retiform connective tissue are traversed by vessels, and are filled with a plasma charged with lymph cells. Retiform connective tissue is found in the lymphatic glands, in the spleen, in Peyer's patches, &c. Elastic fibres are found more or less in areolar tissue, atid in fibrous tissue, but they only form an accessory part of these. The yellow ligaments found between the vertebral laminae are, on the contrary, entirely formed of elastic tissue. Elastic fibres, of which the diameter varies, produce by anastomosing with one another a » ^ \x Fig. 11. — Longitudinal Section of the Human Aobta. a, elastic layer ; h and c, muscular fibres. reticulum of different-sized meshes. In the yellow elastic tissue the fibres are voluminous, cylindrical, and frequently anastomose. In the large arteries elastic tissue forms the fenestrated membrane (the internal elastic layer and the middle coat of the aorta and carotid), the openings of which are of variable size, whilst in areolar tissue the meshes of the elastic tissue are so large that it is difficult to trace the network which they form. Elastic fibres, like connective-tissue bundles, are developed in the inter- cellular substance between the embryonic cells and connective- CARTILAGINOUS TISSUE. 17 tissue cells already formed ; if the cells take any part in their development it is simply an indirect one. In all the various kinds of connective tissue which have been described, the cellular elements are at the commencement more or less globular ; their protoplasm is succulent and their nuclei are well defined, but in the course of development these elements become thinner, dry up, so to speak, and it is then only that they take the form of laminae. It will be shown hereafter how that irritation is sufficient, by increasing their nutrition, to bring the connective-tissue cells back to their primitive form. Cartilaginous Tissue. — Cartilaginous tissue, like connective tissue, is found in the organism imder dififerent forms ; but we always find in it one essential characteristic, that it is composed of cells completely surrounded by cartilaginous substance, that is to say, by a transparent substance which yields chondrin on boiling. The true cartilage cell is a mass of protoplasm con- taining a nucleus ; its volume and form are very variable, even in the same kind of cartilage. Its diameter varies between 6 /* and 30 /t. In living cartilage the form of the cell is spherical, ovoid, or lenticular, but, when observed under the conditions in which an examination of cartilage is generally made, that is to say, after the addition of water, acetic acid, and other reagents, the cartilage cell assumes the most varied forms. Frequently fat granules or droplets of fat accumulate in the protoplasm of cartilage cells, but, even when fat is in such abundance that the cell might be called a fat cell, the nucleus persists, is well developed, and is always to be found alongside the drop of fat. It is spherical or slightly oval in form, and is bounded by a double line; the nucleoli are well defined. This slight description of the cartilage cell is based on numerous examinations made by means of a saturated solution of picric acid, a reagent which at the beginning of its action does not cause retraction of the protoplasm of the cartilage cell, and enables the nucleus to become apparent. A 1 per 200 solution of alum makes a still better reagent, in that it de- finitely fixes the cartilarge cell in its natural shape. The nucleus can be afterwards stained with a solution of purpurin. The cartilage cell has no peculiarity sufficient to distinguish it when isolated, and it is only because it is found in the cartilaginous tissue that the name cartilage cell has been given it. This cell cannot there- fore be defined by its physical characters ; it is solely distinguished by the property which it possesses of secreting cartilaginous material around itself. C 1 8 SUMMARY OF NORMAL HISTOLOGY. In embryonic development, when cartilaginous tissue is about to appear, the embryonic cells are separated from one another by a substance, soft at first, which afterwards becomes more con- sistent and has all the characters of cartilaginous substance. At first, this substance exists in small quantity, but it soon increases and condenses in the form of a capsule round the cell. The cap- sule may also be produced by a new elaboration of the cell itself. Such is the embryonic variety of cartilage in which the cells and capsules are small and spherical. Soon the cells begin to multiply, and this is also one of the methods of the growth of cartilage. At this period it is not rare to observe two nuclei in one cell, and sometimes even the division of the nuclei may be observed. The nucleus enlarges and elongates, becomes constricted in the centre, and separates completely into two distinct elements. The division of the protoplasm is always consecutive to that of the nucleus, so that cells may be seen with two nuclei. Each of the Fig. 12.— Cartilage Cells about to Proliferate. e, protoplasm of the cell ; a, nucleolus ; h, nucleus ; d, primitive and secondary cartilaginous capsule ; e, matrix. In one of the cartilage cells are two nuclei. new cellular masses has the property of elaborating around itself cartilaginous substance. Thus two secondary capsules may be produced within the primitive cell. In multiplying thus the cells are pressed one against the other, and become elongated and pris- matic in shape. Foetal cartilage is of this kind. When the nutritive process is very active, the cells become larger and take a globular form, as is seen in cartilage under- going ossification. Owing to the large size of these cells, aU the phases of their development can be easily studied (fig. 12). Permanent cartilage of the adult is composed of medium-sized cells which often contain secondary capsules. At the surface of the articulations and under the perichondrium they become changed in shape ; the capsules are here lenticular and flattened in the direction of the surface, and contain no secondary .capsules. CARTILAGINOUS TISSUE. ,9 In the adult, whenever cartilage is in contact with bone, cal- careous infiltration is observed in its deeper parts. This incrusta- tion forms a perfectly regular layer in which cartilage cells are preserved. Calcareous infiltration causes such a change in car- tilaginous substance that even after complete decalcification by means of an acid (hydrochloric or chromic) this layer remains condensed and perfectly distinct. This is calcified cartilage. In individuals advanced in age the cells of the costal and thyroid cartilages show fatty infiltration, and the matrix mucoid degeneration. Owing to these changes irregularly shaped cavities are formed filled with mucus and fat granules. Sometimes cal- careous infiltration is present at the same spot. Finally Virchow, after treating these parts with a solution of iodine alone, or followed by the action of sulphuric acid, observed that the cells give a red mahogany colour, and has hence described this change under the name of amyloid degeneration, Eapidly proliferating cells in cartilage undergoing ossification give a violet colour with a solu- tion of iodine in iodide of potassium. This colour is owing to the presence of glycogenic matter in the protoplasm of the car- tilage cells, the same as is met with in every cell that is in an active state of growth or proliferation (see p. 6). In the centre of the intervertebral discs, and other sym- physeal ligaments, a mucous substance is found in which either isolated cartilage capsules, or systems of capsules nested one within the other, exist. The protoplasm and the nucleus of a cartilage cell are found in the isolated capsules, or in the most internal of the nested capsules. This kind is called mucous cartilage. The matrix which separates the cartilage capsules shows in certain places, as in the fibrous portion of the symphyseal liga- ments, all the characters of fibrous tissue. Here the capsules are quite distinct from the matrix, and often contain secondary capsules. This is fihro-cartilage. In the cartilages of the ear, in the arytenoid and the epiglottis, there is a cartilaginous tissue with well-defined capsules separated from one another by a reticulrmi of elastic fibres resembling felt. This is called elastic cartilage. OsBCons Tissue. — Osseous tissue comprises the osseous firame- work, the medulla, and the periosteum. The framework, which has everywhere the same composition, is made up of parallel lamellae and bone corpuscles. In a section of dry bone the bone corpuscles appear as ovoid bodies c 2 20 SUMMARY OF NORMAL HISTOLOGY. when seen edgewise, but rounder if seen flatwise. From every side of them spring numerous canals which ramify and anastomose with those arising from neighbouring corpuscles. Virchow has shown that these corpuscles correspond to cellular bodies. If a fragment of bone be decalcified by the action of hydrochloric acid and boiled, the masses showing these incomplete ramifications, and which he looked .upon as cells, can be isolated. In some of them he was able to perceive nuclei. These nuclei are extremely distinct, and axe always present in every osseous corpuscle. They can be perceived in all, if, after having decalcified a bone by chromic or picric acid, fine sections are made and stained with aniline red dissolved in acetic acid, or with an ammoniacal solution Fig. 13. — Section of Osseous Tissue with its Cokpuscles ramifying AND anastomosing. of carmine, or better stUl with a solution of purpurin. The stellate body which Virchow succeeded in isolating by means of hydro- chloric acid is not a cell but a species of capsule. The true osseous cell is contained within it. It has the appearance of a protoplasmic mass surrounding a nucleus, and in the adult bone looks flat. The cellular nature of the bone corpuscle is thus perfectly demonstrated. The numerous canaHculi proceeding from it are intended to carry nutritive fluids to different parts of the osseous substance, which does not itself possess the property of imbibition, and very probably is not capable of giving rise OSSEOUS TISSUE. 21 to any of the phenomena of endosmosis necessary to nutritive changes. Bone corpuscles are situated in the middle of the bony lamellae, and are parallel to their planes of separation. The osseous lamellae form systems by their imion; it is thus that systems of lamellae parallel to each other are arranged on the surface of bone, and that every medullary cavity is regularly surrounded by them, in the compact, as well as in the spongy, tissue. The medullary cavities contain the medulla and blood-vessels ; in the long bones they are generally cylindrical, and run in a direction parallel to the axis of the bone. These are called the Haversian canals, and are united by transverse or oblique canals. The cancellous tissue does not differ from the compact except by the larger size and the less regular form of its canals. The medulla is always traversed by blood-vessels. Between them and the walls of the medullary spaces there are : 1, small round Fio. 11. — Bonk Corpuscles observed in a Fragment of Decalcified Bonk and stained with Carmine. granular cells measuring 10 /* to 15 /t, with a large and well- defined nucleus (the medullocelles of Eobin); 2, large cells of irregular shape and with many nuclei interspersed in their sub- stance (the myUoflaxes of Eobin) (fig. 4, a, b) ; 3, round cells having many nuclei in their centre, or one nucleus folded on itself and throwing off buds (the cells with budding nucleus of Bizzozero) ; 4, adipose cells ; 5, connective-tissue cells accompany- ing the blood-vessels. These different elements exist in varying proportions in different bones, and according to the phase of development of the osseous tissue. In the bones of the Hmbs, the adipose cells predominate ; in the bodies of the vertebrae and in the sterniun the non-fatty elements are the most numerous ; hence the redness of the medulla. The medulla is the seat of the most important nutritive and pathological phenomena which take place in the bones. The periosteum is a fibro-elastic membrane analogous to an 22 SUMMARY OF NORMAL HISTOLOGY. aponeurosis, a fact which struck Bichat. The periosteum sur- rounds all parts of the bone, and stops at the commencement of the articular cartilages. It is composed of fibrous and elastic tissue, which in its deepest layer, that which is in contact with the bone, is formed of very fine and close fibrils. The vessels of the periosteum are very numerous, and detach themselves from its deeper layer to penetrate directly into the bony canals. The osteo-periosteal vessels play an important part in pathological subperiosteal phenomena. The development •of osseous tissue is extremely interesting, in that osseous tissue is not formed directly from embryonic cells, but from fibrous and cartilaginous masses which have already taken the form of the bone ; and as in pathological conditions transformations of tissue are often observed, that which takes place in bone has served as a basis and objective point for all anatomo-pathologists. They have, in fact, based upon osteo- genesis their general comprehension of pathological histogenesis. The formation of pathological tissue at the expense of healthy tissue differing from it has been called heteroplasia by Virchow. The development of osseous tissue from fibrous and cartilaginous tissue is the physiological type of heteroplasia. Virchow did not look upon it from this point of view, for he considered osseous and cartilaginous tissues to be histological equivalents, and that osseous tissue is developed in consequence of nutritive changes in fibrous and cartilaginous tissues, consisting especially in incrustation of the fundamental substance with calcareous salts. Virchow applied what takes place in rachitic bone to the normal develop- ment of bone. But on studying more thoroughly the phenomena of normal ossification, Henry Miiller constructed an entirely new theory. Continuing these researches, we have ourselves verified the fact that bone always develops according to the same general law, whether from cartilage, or under the periosteum, or from fibrous tissue. A. Intra-cartilaginous ossification takes place in the following manner : the cartilage cells increase by the process we have already described; the new cells are surrounded by secondary capsules (fig. 12, a) ; the mother cells, being fall of them, enlarge and become elongated by reciprocal pressure, so as to converge towards the point of ossification. The matrix of the cartilage is spHt up so as to appear fibrillated; it is soon infiltrated with calcareous salts. At this moment, in consequence of the influence exercised by the blood-vessels, which have spread fi-om the perios- INTRA-CARTILAGJNOUS OSSIFICA TION. 23 teiim or from the already formed medullary cavities, the secondary capsules are dissolved and the cartilage cells are set free and proliferate (a, e, fig. 15); they then take on the characters of embryonic cells described above — at this stage they may show amoeboid processes. The cartilaginous tissue is destroyed, but the osseous tissue does not yet exist. This new tissue, which has not yet received a name, and which we propose to call ossiform, consists of trabeculse incrusted with calcareous salts, and represents the matrix of the old cartilage Fig. 16. — Intka-cartilaginois Ossification. o, primitive capsule filled with seoondaiy capsules ; rf, cartilage cell of whidi tbe capsule is about to disappear ; e, proliferation of cells resulting in the formation of embryonic medullary tissue ; g, channels filled with new medullary tissue, and bounded by the calcified matrix, /. At the lower part of this figure stellate bone corpuscles begin to appear. Magmfled 300 diameters, (fig. 15,/). In these trabeculce there are no cellular elements. They are the bovmdaries of the cavities or alveoli which, commu- nicating with one another, form cavernous spaces (:fig. 15, g) filled with a vascular medullary tissue. The ossiform tissue in no way 24 SUMMARY OF NORMAL HISTOLOGY. corresponds to the description of Virchow's osteoid tissue, nor to the spongeoid tissue of Guerin and Broca. These authors based their descriptions on observations of rachitic bone. Now, as we shall see when studying rickets, the usually calcified trabeculse of the osteoid or spongeoid tissue of these authors contain cellular elements. In ossiform tissue, vessels from the bone penetrate into the alveoli and form loops. Then begins true ossification. The cells of the embryonic medulla arrange themselves along the calcified trabeculse ; they are often pressed one against the other, and form along the osseous trabeculse, undergoing development, a contin- uous layer simulating an epithelium. Gegenbauer has given the name of osteoblasts to these cells. Around some of those which have already sent out processes a new intercellular substance is deposited ; this is the osseous material. Cells may be seen but half enclosed in the osseous deposit, the rest of their surface — ^that turned towards the medulla — being free. Soon, however, they are completely surrounded by the bony material, and become veritable bone corpuscles. To this first layer new ones are added, always by the same mode of formation, and at the expense of the medulla. It is thus that a medullary space, primitively irregular, is transformed into a Haversian canal, containing medulla and vessels. After the above description, we do not consider it neces- sary to enter into more circumstantial details as to the forma- tion of the various bones and the various kinds of osseous tissue. B. Sub-periosteal ossification. — Hitherto we have only con- sidered the formation of bone from primitive cartilage; but, once formed, the bone can continue to grow and to increase in thickness by the deposition of new layers beneath the periosteum. This growth takes place in the following manner. Beneath the periosteum there is, at this period, a layer of round or polygonal cells containing one or more nuclei, differing in no way from cells of embryonic medulla. In the midst of this layer, examined in transverse sections of bone, straight or cm-ved osseous needles advance. Their bases are continuous with the old bone, their free extremities being directed towards the periosteum. The medulla cells pressed against the surface of these needles of bone are then seen to be successively surrounded by osseous substance. Here again cells may be seen half within the osseous and half within the medullary tissue, so that the process of sub-periosteal ossification is identical with that observed in the second phase of ossification from cartilage. These needles, in the centre of INTRA-MEMBRANOUS OSSIFICATION. 25 which connective tissue fibres are always present, correspond to vertical sections of laminaB ; they gradually increase in size, curve over, and unite together, and end by bounding a round space corresponding to a Haversian canal. The connective- tissue fasciculi, which are found in the centre of the sub-periosteal osseous needles, persist in the bone when com- pletely formed ; they occupy a position in the parts intermediate to the Haversian systems. They were first discovered by Sharpey, and they are known imder the name of Shxt/rpey's fibres. I'W,. 16. — SUB-l'EEIOSTEAL OSSIFICATION. A, tranavcrso Bection of the periosteum showing connective-tissue cells ; B, medullary tissue ; 0, osseous trabeculee containing stellate osseous cor- puscles. All along the osseous trabeculee there is a close layer of medul- lary cells flattened by reciprocal pressure. Many of these cells may be t^cen undergoing transformation into bone corpuscles. Magnified 120 diameters. V. Intra-membranons ossification. — In the bones of the skull osseous tissue is developed from a fibrous membrane, and from trabeculse which gradually increase in thickness, curve over, and limit the medullary spaces. In the human embryo two to three months old, osseous plates are found corresponding to each of the bones of the skull. These bones terminate in the fibrous tissue by needles. Along these needles are seen one or two layers of embryonic cells, polygonal by reciprocal pressure, altogether similar to the osteoblasts observed beneath the periosteum and in the medullary cavities. These cells become bone corpuscles by an analogous process. The osseous needles terminate in the fibrous tissue by a long filament formed of a refractive and vaguely fibrillar substance containing no cells. These fibres are in every way comparable to the trabecula3 of the matrix of cartilage which we have studied in the first mode of ossification, and constitute Sharpey's fibres in the adult bone. They seem to be the result of a special conden- 26 SUMMARY OF NORMAL HISTOLOGY. sation of certain bundles of connective tissue, and serve to direct the process of ossification. The embryonic cells which line the osseous trabeculse are evidently derived from the surrounding connective tissue, the cells of which proliferate. The same general law is therefore seen to regulate every- where the formation of osseous tissue, and may be formulated thus : — The ground substance of the tissue {cartilage-capsules and cells or fibrous substance) is partially dissolved ; the cells proliferate, become free, give rise to an embryonic tissue the elements of which are surrounded by a new ground substance, and become bone corpuscles. This process of bone-formation by a veritable physiological heteroplasia will be found to have numerous appUcations in pathology. Group II. Muscular and Nervous Tissues. Muscular tissue. —In man there are three distinct varieties of this tissue to be considered : 1, the muscles of organic life, formed of fusiform cells, which contract slowly and involuntarily ; 2, the muscular tissue of the heart, the fascicuU of which are striated, anastomose together, and contract in a brusque and involuntary manner ; 3, the muscular tissue of the trunk and limbs, composed of non-anastomosing striated fasciculi, and characterised physio- logically by brusque and voluntary contractions. Fig. 17. — Isolated Smooth Muscular Fibres. The elements of the muscles of organic life are fusiform cells varying from 40 /* to 200 /i in length, and in which the existence of a cell wall has never yet been definitely ascertained. They appear to be formed throughout of a transparent refractive and amorphous substance, but which is in reality composed of con- tinuous fibrils. In the centre of the cell there is an elongated rod-shaped nucleus, which becomes apparent after staining with carmine and treating with acetic acid, the latter causing it to MUSCULAR TISSUE. 27 assume a serpentine form. The nuclei of the smooth muscular fibres possess one or many nucleoli, described by Frankenhauser. The nuclei are separated from the contractile material by a granular protoplasmic mass, particularly abundant at each ex- tremity. The cells of involuntary muscular tissue are rarely found in an isolated state in the midst of the tissues (the middle wall of the large arteries). They are more often united, sometimes to form bundles, sometimes to form membranes as in the arterioles. They are then bound together by a cementing substance, so that it becomes difficult, if not impossible, to separate them. Their com- plete dissociation may be, however, obtained by means of certain reagents, such as a 20 per cent, solution of nitric acid (KoDiker), or a 40 per cent, solution of potash (Weismann). According to most histologists, KolUker among others, these muscle-cells are derived directly from embryonic cells, the protoplasm of which, after undergoing successive changes, is transformed into muscular substance, the nucleus elongating and becoming rod-shaped. Fig. 18. — Muscular Fibres of the Heart, scporatc'd by transverse lines which indicate the limit of the component cells. The muscular fasciculi of the heart are also derived from embryonic cells ; their ground substance is always striated, and oval nuclei occupy the centre of the bundles. The cells forming part of a cardiac fibre never melt into one another, and even in the cardia of adults their boundaries can be determined. Weis- mann, by treating fragments of myo-cardium with a 40 per cent. solution of potash, was enabled to isolate the component cells, whilst 28 summaiIy of normal histology. Eberth, by means of nitrate of silver, has outlined the limits of each cell in the muscular fibres of the heart (fig. 18). Vbluntary striated muscular fibres are developed from embryonic cells which elongate, the nucleus becomes ovoid and multiplies, the protoplasm also undergoes certain nutritive changes which transform it into striated material, whilst at the same time an amorphous resisting membrane, destined to become the sar- colemma, is developed around the cell. At the commencement of these changes only the peripheral part of the protoplasm undergoes the changes which result in muscular tissue ; there always remains around the nuclei, which in the mammiferse are finally conveyed to the periphery of the muscular substance, a certain amount of unchanged protoplasm. The nuclei are found under the sarcolemma surrounded by a small fusiform mass of protoplasm. This protoplasmic substance extends, moreover, in the form of extremely fine laminae throughout the thickness of the fasciculus, dividing it into longitudinal columns (primitive Fig. 19. — Steiated Muscular Fibkes. cylinders of Leydig) ; these columns are again separated by proto- plasm into cylinders of a diameter scarcely exceeding 1 /j, {jpri/mi- tive fibrillce). Such is the origin of the longitudinal striation of muscular fibre. The transverse striation, which is so distinct as to strike the observer at once, and which has given muscular bundles the name of striated fibres, must be looked upon as a kind of geometric arrangement of the contractile parts of muscular substance. These, to which Bowman was the first to draw attention, have been described under the name of sarcous elements. According to Bowman, the contractile substance is essentially composed of little prisms placed regularly end to end one against the other and bound together by a cement. This view of the composition of striated muscular fibres is corroborated by the action of certain reagents, of which some (alcohol, chromic acid, bichromate) favour the longitudinal division of the primitive fasciculus into fibrils, whilst others (gastric juice, dilute organic acids, caustic alkalies) cause the separation of the same fasciculus into discs superposed like coins in a pile of money. NERVOUS TISSUE. 29 According to Bowman's theory, there are in the muscular fibre neither longitudinal fibrils nor transverse discs, but sarcous elements united by a longitudinal cement soluble in alcohol, chromic acid, &c., and by a transverse cement soluble in gastric juice, the dilute organic acids, and caustic alkalies. This view of Bowman's has held sway for ten years, though it ought to have been destroyed by the observations, no longer recent, of Amici, — observations which have been confirmed and extended by Krause, Hensen, and ourselves. In the transverse lines which separate the sarcous elements a fine striation is present which has the same optical characters as the sarcous elements themselves. The sarcous elements are, moreover, divided transversely into two equal parts by a clear line. It results from these observations that the structure of the striated fasciculi is not so simple as Bowman supposed, in fact, they have a very complex structure. If we examine an isolated fibril, which can be easily obtained by dissociating the muscles of insects' wings, we see after staining with picrocarminate of ammonia or with haematoxylin that there are in successive order: 1, a thick disc, divided into two equal parts by a clear stria ; 2, a clear space ; 3, a thin disc ; 4, another clear space ; then a thick disc and so on. This arrangement, which is that of all striated muscles, is related to their mode of contracting, in which two factors come into play : 1, contractility appertaining to the thick discs ; 2, elasticity, which seems to depend on the thin discs and the intermediate portions between the thin and thick discs. Nervous tissue. — The elements of nervous tissue are cells and fibres. Nerve-cells are very variable in form and in size ; they vary between 10^ and 100/*; they are always furnished with simple or branching processes, which connect them with one another and with nerve-fibres. Among these processes there is one, discovered by Deiters and bearing his name, which arises from every motor nerve-ceU of the spinal cord and of the brain. It is homogeneous, vitreous, does not branch, and is evidently the origin of the axis- cylinder process of the medullated nerve-fibre. It is therefore called by the name of the axis-cylinder process (a, fig. 20). Nerve- cells of the centres have manifestly no ceU wall ; their funda- mental substance is finely granular, often containing pigment granules, and is striated towards the periphery. All nerve-cells have a nucleus showing a double contour and containing one or Fig. 20.-MULTIPOLAR Nkkve-cei,i, from the Anterior Horns of the Spinal Cord of the Ox. After Deiters. a, axis-cylinder process ; b, t, processes, called protoplasmic. Magnified 300 diameters. NERVOUS TISSUE. 31 two nucleoli. Such are the cells of the grey matter of the brain, of the cerebellum, and of the spinal cord. In all the spinal ganglia the nerve-cells are round. They have only one process ; they are enclosed in a delicate capsule composed of a supple, homogeneous, and elastic substance ; the inner surface of this capsule is lined with endothelial cells. According to Remak, KolUker, and Lockhart Clarke, nerve- cells are developed from primitive embryonic cells. Nerve-tubes or fibres are of two kinds ; those having a sheath of myelin (medullated nerve-fibres or dark-bordered fibres), and those having no medullary sheath. In the embryo the latter only exist. In the course of development the medullary sheath is added. Fig. 21. — ^Nekve-fibres. a, n, axis-cylinder partly sarrounded by the mednilsry sheath. Medullated nerve-fibres may be divided into two classes — those of the peripheral nerves, and those of the nervous centres. The former are limited by a resisting structureless membrane, called the membrane of Schwann. At regular distances the fibres are constricted, and appear as if they had been included in a ligature (a, fig. 22), hence segments of equal length (inter-annular segments) are formed. These segments vary in length with their diameter ; in the largest they are more than a millimetre. The myelin is not continuous from one segment to another; there is a solution of continuity at each constriction. The membrane of Schwann appears as if it passed over all the segments of the same nerve-fibre, but actually it is composed of as many fragments as there are segments, for nitrate of silver reveals a line of 32 SUMMARY OF NORMAL HISTOLOGY. junction always situated where the break occurs.' Every me- dullary tube is traversed in the direction of its axis by a cylinder, homogeneous and vitreous in appearance, and of which the diameter is in accordance with that of the medullary sheath. This cylinder (the axis-cylinder, axial fibre, primitive riband) is continuous — that is to say, it passes through the medullary tube from, its origin to its termination without undergoing any inter- ruption or junction at the annular constrictions. Near the centre of an inter-annular segment a flattened oval nucleus is perceived, under the membrane of Schwann, and lodged in a depression of the myelin. It is surrounded by a granular protoplasmic layer, Fig. 22. — Nekve-tubes SHOwraG Annular Constrictions. a, annular constrictions ; cy, axis-cylinder ; nt, myelin. Magnified 300 to 600 diameters. which, extending beneath the membrane of Schwann, lines it in its entire extent from one constriction to the other. At the constriction this layer folds on itself and is reflected on to the axis-cylinder, constituting a special sheath to it — a sheath of which Mauthner long ago observed the existence without recog- nising its significance. We have, however, designated it the sheath of Mauthner. The result of this arrangement is that the myelin of each inter-annular segment is contained within a proto- plasmic sac, formed of an extremely fine layer, and containing one • These constrictions are known as the Nodes of B,* » 9 ® ® 9 * 9 o e e • 9° 9 *' ee 9 '«7 © / \ o e • e 9 9 9 oet O So 9 9 99 ** ( 9 9 9 9® ® / \ 9 ® ©^ nt A n 9 o _ ^ «■ 9 ' (f ^ e > •:-i ® e @ .9 e » 9 « e > ,»9e 9 9 9 y ^ <; © 9 9 9 ( »« •y r _ e e,e ^ ^""^ •^'o- 1-— Appearance of the Corpuscles in the Ruled Space of Malassez's New Cokpuscle-counter. the most fallacious conclusions, and are not at all trustworthy, whether for scien- tific or clinical data. 'In Malassez's new Covvpte-Qhhules he has adopted the great improvement in- troduced by Gowers, of drawing the squares on the surface of the slide. He has moreover succeeded, by many ingenious contrivances, in carefully avoiding all the sources of error in Hayem's and Gowers's instruments above enumerated, to several ot which I had occasion to call his attention. This new micrometric graduated corpuscle-counter with wet chamber (^Compte-Glolmlm a ehaml,-e hmnide graduie NUMERATION OF THE ULOOD-CORPVSCLES. 55 viicromctriqxie*) consists of a thick nickel slide, in ttie centre of which is a circular groove enclosing a glass cylinder about a centimeter in diameter. Outside this groove are three pointed metal screws, equidistant from each other. The eleva- tion of these points above the surface of the metal slide is exactly i mm. In the centre of the glass surface, limited by the groove, are drawn the squares, in which the corpuscles are counted. These have a side of ^^ mm., and they are arranged in groups of 20, each group having a length of ^ = 1 mm., and a width of J^j = | mm., and an area, therefore, of lxi = i square mm. Each group of 20 squares is separated from adjoining groups by a double line (fig. 1). The peripheral parts of the ruled space are simply divided into rectangles, \ mm. long and \ mm. wide. The cover-glass, which is gTound accurately flat, is attached, by moistening the edges slightly with saliva, to a frame lixed to the sides of the slide. By an inge- nious and delicate rack movement of this frame the cover-glass is lowered without delay, and in a linrizniitul pmition down upon the drop. The slide carrying the frame is represented in fig. 2. ' To make a numeration, the solution is made in Potain's Mixer at the strengtii of 1 per 100, 200, 300, 400, or 500, as desired ; and, whilst being rapidly agitated. Fig. 2. — Malassez's Micrometric Graduated CoRri'scLE-coi'NTEr. a drop is placed in the centre of the ruled space, and the cover-glass, having been previously attached to the frame, is lowered and clipijcd, so as to rest firmly on the points of the screws. To prevent evaporation, if desired to keep the prepara- tion any length of time, a drop of water should be placed at the edge of the cover-glass, and allowed to run under and fill the vacant space between its edge and the groove. The red corpuscles that are lying within a group of 20 squares are then counted. These 20 squares, it wdll be remembered, have an area of j\i mm.', and, the depth of the fluid being i mm., the quantity of the solution under review will be i x 1 = jij of a mm.' The number of corpuscles seen, there- fore, has to bo multiplied by 100, and then again by the number representing the strength of the solution, and the product will be as before, the number of corpus- cles in a cubic millimeter of blood. ' Thus, for example, let the solution be 1 per 200, and let 250 corpuscles be found on an area of 775 mm.'; then — 250 X 100 X 200 = 5,000,000. * ' Sur les rcrfectionncments les plus recents apportt'S aux Methodes et aux Apparcils dc Numeration dcs Globules Sanguins, et sur un nouveau Compte- G lobules.' Par L. Malasscz. Air/i. go Fig. 55.— Pus Cells. A. a, b, Id water; c, d, e, after tlie addition of acetic acid. £, division of the nucleus. Figure borrowed from Yirchow. is their normal diameter, to 1 1 or 12 fi; they become spherical and show easily, especially after staining with carmine, 2, 3, 4, or 5 nuclei of 2 to 3 ytt in diameter. The nuclei resist the action of iicetic acid, though under its influence the cell becomes spherical and paler, still bordered however by a very delicate line which finally disappeai's. Pus corpuscles do not differ, as we have already [lointed out, from certain white blood-corpuscles. The theory of pus formation. — According to an old opinion of Zimmermann, and the experiment just cited of Waller, it was believed that pus escaped direct from the blood-vessels. Cohnheim asserted the same, and lent this opinion the support of the experi- ments already described. But is pus always found thus ? We are in the position to assert the contrary. The epithelial cells of all serous and mucous membranes swell and hypertrophy when irritated and their protoplasm becomes more abundant ; they show all the different phases of multiplication by division ; each one of io8 INFLAMMA TION. the new cells may divide in turn, and when, in the smallest cells the nucleus divides without the cell participating in the division, pus cells are produced. Large mother-cells may contain a certain number of embryonic cells which very little will convert into pus cells. This is what is observed in pustules of the skin, in pem- phigus, and catarrhal inflammation of the mucous membranes. Thus we admit two modes of pus formation : 1, by proliferation of cellular elements ; 2, by diapedesis of white blood-corpuscles. In very rapid suppuration diapedesis is the most important factor. Pus undergoes change very easily ; according to its age and the influence of the substances with which it is in contact it undergoes the following modifications : — Fatty degeneration of pus cells occurs whenever pus becomes old. Inside the cells fine refractile fatty granules are formed, and are seen without the addition of water. Acetic acid does not act upon them. The presence of fat granules in the interior of pus cells is owing to two causes : the death of the cell and the active absorption of fat granules situated in its neighbourhood.' When pus cells are filled with fat granules they increase in size and reach 15 to 20 jj.. They have been long known under the name of inflammation corpuscles, or the corpuscles of Gluge. These corpuscles seem to be peculiarly formed lymph cells which have absorbed fat granules near them. They generally have one, rather large, oval nucleus. They are more particularly found in the lymph spaces and in the lymphatic vessels leading from organs rich in fatty matter and which are undergoing a process of degene- ration, the brain for example. Thus, the perivascular sheaths of the brain or spinal cord contain a large number of these cor- puscles in the neighbourhood of a hsemorrhagic focus or a centre of softening. A fact which proves that it is by penetration that the fat finds its way into the cells, is that red blood-corpuscles or fragments of them, or blood pigments, are found in the same elements. As to the fatty degeneration of pus cells connected with the death of the cells, this is chiefly met with in large puru- lent collections. The corpuscles which are the seat of this degene-.. ration contain only a limited number of small fat granules. Caseous degeneration of pus cells is also observed when pus has remained a long time in an abscess or natural cavity. The serous part of the inflammatory product is absorbed, and the cellular elements pressed together, become angular and atrophied, and some present very fine fat granules, not modified by water or ' See p. 91 , note 1 . A'Ell- FORMATION OF VESSELS L\ INFLAMMATION. "109 acetic acid. They form, by their conglomeration, a white or yellow caseous mass more or less dry. Such is one of the modes of origin of the angular corpuscles which Lebert looked upon as character- istic of tubercle. Pigmentary infiltration occurs in pus cells when- ever a notable transudation of red blood-corpuscles accompanies suppuration. Calcareous transformation is produced in very old purulent foci. In gouty abscesses formed in the neighbourhood of small joints, acicular crystals of urate of soda are often found. Watery and acid transformation of pus is observed in bone abscesses. The pus in fact then contains lactic acid, under the influence of which the pus cells swell, their protoplasm dissolves, and their nuclei are set free. It is this serous appearance, well known to surgeons, by which they recognise chronic bone abscess at first sight. Pus cells are in time dissolved in the same way if the fluid con- tains a large proportion of water. B. New formation of vessels in inflammation. — Whenever in- flammation occurs in a vascular tissue, tho blood-vessels undergo changes which often result in the formation of new vascular branches. This inflammatory new formation of vessels is analo- gous to that which takes place in tumours and is the more inter- esting to study as its mode of production is more common. The capillaries are, as we know, formed of nucleated endothelial cells cemented together at their edges. When irritated, these cells swell and soften, and if the inflammation continues, their nuclei mul- tiply by division. These phenomena are identical with those already described in the endothelial cells of the great omentum in artificially produced peritonitis. The blood-vessels of the in- flamed tissues return to the embryonic condition, that is to say, they are formed of embryonic cells arranged in rows, and having in their centre a canal through which the blood circulates (fig. 50 V. p. ^5). This modified wall of the vessel is soft and is easily distended or ruptured by the blood pressure. It is clearly under- stood how, under such conditions, the passage of red and white blood-corpuscles through the walls of the vessel is rendered easy. This inflammatory change in the walls of blood-vessels, which we indicated in the first edition of this manual, has been re-studied by many histologists. We wish to notice among these the thesis of our much-regretted friend Chalvet, in which the view that diapedesis in inflammation is allied to a change in the vascular walls was first expounded. This view has been recently developed by Cohnheim. The capillaries and small blood-vessels thus modi- fied become the point of departure for new vessels in various no INFLAMMATION. ways; sometimes a capillary loop enlarges and makes a long parabolic curve, sometimes prolongations spring from the convex portion of a capillary loop and become hollowed in proportion as the blood penetrates. According to Eindfleisch the cells con- tained in the exudations of serous membranes become elongated and disposed in parallel rows, between which the blood penetrates from a neighbouring capillary; but it is very improbable that the new formation of vessels occurs in this manner. Finally, as Meyer and Plattner have shown, in embryonic tissue the capillaries may be seen to start from plasmatic cells according to the process described by KoUiker in the membranous expan- sion of the tail of the tadpole. These cells have anastomosing canalicular processes which put them in relation with the old vessels, after which they enlarge so as to receive the blood- corpuscles. It is well known that inflammatory new membranes which rapidly develop on the surface of serous membranes, notably on the pleura in acute pleurisy, are soon provided with blood-vessels, the abundance of which is not exceeded by any other vascular organ. This exuberant development of capillaries, which takes place in a few days' time, can hardly be explained by simple expansion of the few vessels belonging properly to the normal pleura. An inde-. pendent new formation must therefore be admitted. Some authors had formerly expressed the opinion that it must be so, but no direct proof had been adduced in support of this view, which was for a long time abandoned. No micrographic anatomist had ever supported it. It wanted a basis borrowed from normal histology, for vaso-formative cells were yet unknown. Vaso-formative cells. — ^These cells can be easily observed in the omentum of young rabbits.' They appear in certain milky spots which are not yet connected with the blood-vessels of the omentum. These spots are characterised by a group of lymph cells in the midst of which the vaso-formative cells are situated ; originally they do not differ much from lymph cells, but they soon increase in size, and in the midst of their protoplasm red blood-corpuscles are formed just as in the midst of vegetable cells starch granules appear. They then send out processes which ramify and anasto- mose with one another, whilst the formation of red corpuscles goes on within them with increasing activity. They soon cover with their ramifications the whole extent of the milky spot, forming a network, at the nodal points of which red corpuscles are found • For fuller information consult Banvier's TraiU techniqiw d'histologie, p. 625. BLOOD-VESSELS FROM VASO-FORMATIVE CELLS. Ill accumulated, while at others anastomatie branches are given off. It IS only later that the small arteries and veins, springing from the principal vessels of the membrane, become connected with the vaso-formative network and a circulation is established, by means of which the red corpuscles, formed in situ, are carried into the general current. It may sometimes happen that by a freak of nature no veins are connected with the capillary network of a milky spot, the connection being only with the arterial system. A network may then be produced along the course of a small artery. It is from the arteries and veins of the great omentum that the capillary arteries and veins spring and are pushed forward till united with the newly formed capillary network of a milky spot. The method of growth of these vessels is according to a tyi^e well described by Grolubew in his ' Study of the Formation of Blood- vessels in the Membranous Expansion of the Tail of the Tadpole.' He observed that in this membranous expansion the formation of blood-vessels takes place solely by the extension of old vessels, and not by connective-tissue cells, as Kolliker had affirmed. It was moreover already known that these cells are not hollow and cannot therefore form vessels by simple distension of their cavity. Vessels in the act of growing terminate by buds from which proto- plasmic filaments spring, these thicken, elongate and anastomose with similar filaments springing from neighbouring vessels. They eventually become tubular. Arterioles directed towards the milky spots also terminate like the blood-vessels of the tail of the tad- pole in protoplasmic filaments, and on reaching and joining the vaso-formative network they become tubular and establish a com- munication with the general circulatory system. Although a sufficient number of observations on the formation of blood-vessels in inflammatory false membranes has not yet been made, it is probable that they develop in a manner similar to that described above, and that perfect capillary networks are formed independently in the exudations, so rich in lymph cells, of which at the beginning these membranes are composed. The old blood- vessels of the serous membrane finally communicate with the newly formed vascular network. The large multinucleated mother- cells, observed by Langhans a long time ago in serous exudations, were' probably only vaso-formative cells. C Granulations (granulation tissue), which by then- fusion form membranes called pyogenic, are only developed on the surface of wounds, or inflamed surfaces communicating with the external air. 1 1 2 IN FLA MM A TIOA'. It is a general physiological law that in all higher animals the external, and part of the internal covering, especially at orifices where skin and mucous membrane meet, present papillae ; these are nothing else than permanent granulations. In the same way every new pathological formation on a surface takes this papillary or granulating form ; for example, almost all tumours of whatever nature situated on the skin, or at one of the external orifices, assume this character. The granulation tissue of inflammation consists of embryonic tissue ; it forms slowly in induced irritation, because, for its production, a large quantity of embryonic tissue and new blood-vessels are necessary. It gives the key to the process of cicatrisation of wounds, and histology teaches the cause of the different appearances of granulation tissue, differences well knoTvn to the surgeon, such as healthy and unhealthy granulations. Granulations differ greatly in size ; sometimes they can only be Fig. 56. — Vessels of Grajsulation Tissde injected. After Billroth. Magnified 40 diameteis. seen with a magnifpng glass, at others if exposed long to some irritation, a seton or drainage tube for example, they may become very large. They are simple or compound ; the latter of larger size have secondary buds and are generally simple. At the beginning they consist simply of spherical or angular embryonic cells, uni- or multinucleated, in the midst of which are capillaries composed of embryonic ceUs. This initial stage lasts but a short time, soon a certain number of the embryonic cells change shape, become angular, their processes unite, and they form a network of embryonic connective-tissue cells. The meshes formed by this network are filled with an amorphous substance in the midst of which round cells are imprisoned. The cells contained in the ground substance are especially lymph cells or pus cells. In the granulations of bone there are also multinucleated mother-cells. On scraping the surface of a section of granulation tissue and GRANULATION TISSUE. "3 examining the product in a neutral fluid spherical or angular cells are found, also cells with processes and pus corpuscles. All these are capable of amoeboid movements. The quantity of pus cells imprisoned varies according to the age of the granulations and the varying general and local patho- logical condition of the subject. At the beginning, pus cells are abundant ; later if the granulations are red and healthy, there are fewer. When cicatrisation is slow and uncertain and the general condition of the patient bad, the granulations become grey and are said by the surgeon to be unhealthy ; they then contain many pus cells. When the granulations contain many pus cells, they, to employ an old expression but one which well expresses the appearance, secrete them from their surface. How do pus cells reach the surface of granulation tissue? Are they produced on I,-|0. 57. InFI.AMMATOKY KMIlKYUNir TlBSUK. Figure borTOwe.1 from Billrotli. Magniflod 300 diamc>tor». the surface, or do they travel there from the deeper parts? Hitherto there has been no direct proof of migration in the interior of granulations, but there is on the other hand proof of the migration of cells in inflamed tissues, and the secretion of pus is sometimes so abundant in a short time as to lead one to suppose that the cellular elements travel, either by means of amceboid movements, or under the influence of a current of fluid which is estabUshed from the capillaries towards the surface. This fluid transudes through the vessels, and sweeps along in its passage the free elements it meets with. The following experiment seems to us to demonstrate this fact ; if after having well cleansed a wound, it be irritated by chloride of sodium or by the approach of the actual cautery, the surface is covered with a dew of Uttle drops ; in this fluid will be found pus cells which have evidently been carried 1 1 4 IN FLA MM A TION. along with it. As cicatrisation advances the pus dries up and is no longer produced in the interior of the granulations. The cementing substance of the latter condenses, fibrils of connective tissue are developed, and become organised into iibrous tissue which contracts, the granulations consequently shrinking. The adjacent granulations unite, and their blood-vessels conimunicating, a continuous memljrane is formed. D. Cicatrisation of wounds. — A wound may imite by first, second, or even third intention. In every case cicatrisation con- sists essentially of the formation, between the edges of the wound, of embryonic tissue which gradually passes to the state of adult tissue. After a traumatic solution of continuity, there is haemor- rhage from the divided blood-vessels. This however soon stops, and the blood coagulates in the divided vessels as far as the first collateral capillaries ; it however continues to circulate in the network which remains patent. The edges of the wound undergo formative irritation which results in filling up the loss of substance with embryonic tissue. The permeable capillaries present the changes already described, namely proliferation of their cells and softening of their walls ; new capillary loops spring from the old modified vessels, advance towards the wound and present a convex surface to other convex loops proceeding from the opposite side, and if the edges of the wound be kept in contact, a vascular communication is established. The cells of the embryonic tissue filling up the solution of continuity then become organised and take the form of true connective-tissue cells, the ground substance becomes fibrillar, and as resistant as that of the old tissue. Such is union hy first vntention. Although a wound of this kind may unite rapidly, there is not simple adhesion as some authors have believed ; in fact, the simplest wounds, healed by first intention, leave indelible cicatrices though they may be Httle apparent. In union by second i/ntemtion, the granulations spring up on the surface of a wound, the edges of which cannot be kept united. These granulations, which are well formed towards the sixth or eighth day, constitute a tissue or membrane, the vessels of which anastomose from one granulation to another. When all the granulations are well united together, cicatrisation takes place by the transformation of embryonic tissue into connective tissue, as in the preceding case. The intimate mechanism is absolutely the same in both cases ; in the second, cicatrisation is slower, for the granulations must have time to grow to compensate for the loss of substance. They may become grey and infiltrated with pus, or so CICATRISATION OF WOUNDS. 115 exuberant that they have to be suppressed. The patient, in fact, undergoes all the various risks incidental to suppurating wounds. Union by third intention differs from the preceding only by the slowness of the process, which is owing to the depth of the tissues divided, or more often to a considerable loss of substance ; but the same process is at work, namely the formation of granu- lations. Thus there are two modes of cicatrisation of wounds ; in the first, the cicatrix is formed of embryonic tissue which is organised into connective tissue as soon as the divided vessels are united, the two edges of the wound being kept in contact : in the second, a large quantity of embryonic tissue is developed and forms granulations. Cicatricial inflammatory tissues have very various sequelte. In the skin, a cicatrix is formed of fibrous tissue in the deep layers of which fat vesicles soon show themselves, but are never as abundant as in normal skin; the fibrous tissue is very dense. The fibrous and elastic tissue of the corium is reproduced, but the sudoriparous glands and hair folHcles are never regenerated. The normal papillae of the skin, which first hypertrophied and transformed into granulations have assisted in the formation of cicatricial tissue, return to their primitive condition as the granu- lations melt away and their tissue is changed from embryonic to connective tissue. This is what specially takes place in callous ulcers of the leg, the cicatrix of which, covered by a normal epidermis, shows a layer of generally hypertrophied papilla;. But if the granulations spring from deep parts and the papillae are destroyed to a notable extent, they are not reconstituted in a complete manner and a flat or depressed cicatrix results, or on the contrary a projecting cicatrix, if the exuberant granulations have not been suppressed. Depressed cicatrices are observed after variolous pustules, syphilitic ulcers, in fact, wherever papilLc have been destroyed by suppuration. When, as often occurs in children, granulation tissues grow in an exuberant manner, projecting or cheloid cicatrices are observed. The epidermis is reproduced on the surface of shrunken granulations at the level of the skin. Does the new epithelium spring from neighbouring epidermic cells or is it formed on the surface of the granulations ? Either one or the other of these views as to the reproduction of epidermis may be supported, for though in a wound undergoing repair the new epithelium is more often developed from the peripheiy towards the centre, startmg from the existing epithelium, islets of epithelium may also be I 2 ii6 INFLAMMATION. found having no connection with the external surface. This fact may however be susceptible of another interpretation. Of late years M. Eeverdin has in the case of extensive flesh wounds fixed, with slips of diachylon plaster, little flakes of epidermis lined with the rete Malpighii, on the centre of a granulating surface. In a few days a new formation of epidermis, in the form of isolated islets, is developed around the grafted epithelium. This new epithelium is developed round the graft in the same way as it is formed at the edge of a wound in continuity with normal epithe- lium. M. Reverdjn made experiments on animals with the object of following step by step what takes place in a wound undergoing the process of epidermic grafting. He thought he observed that the transplanted epidermis acted by causing the transformation of the embryonic cells of the wound into epithelial cells. We are quite inclined to admit his explanation, recognising however that we are dealing here with a very difficult subject which may require fresh researches. We are of the opinion that, generally, epidermic cells result from the transformation of the embryonic cells of the superficial layer of the granulation tissue. Cicatricial epidermis is always very thin and is more subject than the adjacent epidermis to desquamation. Bone granulations quickly give origin to bone tissue. The osseous cicatrix or callus will be studied when considering bone ; and the cicatrisation of nerves when studying the diseases of the peripheral nervous system. We shall be content here to formulate the general law which governs the ulterior transformation of in- flamed tissues. Whenever artificial or pathological irritation causes an exuberant development of embryonic elements, and the irritation be removed, the new embryonic tissue tends to return to the frimitive form, of the tissue which served as a Tnatrix. Thus cicatrices of the skin reproduce dermal tissue, bone cicatrices bone, nerve cicatrices nerve tubes. Another still more important consideration is the seat of the new embryonic tissue at the moment that it constitutes a permanent tissue. Whatever may be the origin of the embryonic tissue it has a tendency to re- produce the tissue of the region in which it is situated. Thus, when a bone is extirpated in a young subject, the embryonic tissue, by which it is replaced, aids in the structure of new bone similar to that removed. As a counter fact we may cite cases where a fragment of cartilage or bone introduced under the skin disappears at the end of a few months : it is changed first into embryonic tissue, then into fibrous tissue. It might be thought a priori DEGENERATIONS CONSECUTIVE TO INFLAMMATION. ,17 that there is here pure and simple absorption of the parts necrosed ; but It IS nothing of the kind. Instead of mortification, there is on the contrary an excessive formative activity of the elements which determine, first the metamorphosis of the bone into em- bryonic, then into fibrous tissue. Formation of a special cicatricial tissue is again under a third law: a mass of embryonic tissue, formed in the immediate neighbourhood of a tissue of the organism, has a tendency to become organised according to the latter tissue. This influence of propinquity is particularly well marked in osseous tissue, hyperostoses and exostoses called epi- physial are remarkable examples of it. 4. — DEGENERATIONS CONSEQUENT ON INFLAMMATION. a. Fatty degeneration. — We have already seen that the dis- appearance of fat in the fat vesicles is a result of inflammation ; on the other hand, fat granules appear in cells developed in consequence of irritation, whenever these elements are more numerous than the reconstitution of the tissue requires, or when the nutritive supply is insufficient. Thus, in the first hours of coryza, the pus cells do not contain any apparent fat ; but later, when the muco-pus becomes opaque, numerous fat granules are found in the cells. In irritation of the special cellular elements of organs, for example in nephritis, hepatitis, &c., the elements, after showing some of the phenomena of hyper-nutrition or even proliferation, become infiltrated with fat granules. The proliferat- ing elements of connective tissue may undergo analogous changes ; thus, newly formed cells of the internal coat of arteries in chronic endo-arteritis are filled with fat granules, which, by the absorption of the ground substance, become free and constitute the semi-fluid contents of atheromatous foci. b. Gangrene. — Gangrene consequent on inflammation is seen under two essential forms. In the fitrst the mortified parts are eliminated entire and form so-called eschars. This occurs whenever there is stasis in the inflamed parts followed by coagulation of Ijlood in the vessels, or inflammation of the arterial coats causing endo-arteritis and the formation of a clot, or when pus cells and exudation accumulating round the vessel compress it and stop the circulation. The latter condition is frequently observed in acutely inflamed osseous tissue. In subacute ostitis, necrosis is to be feared, and it occurs when an arrest of the circulation is brought 1 1 8 IN FLAM MA TION. about by the blocking of the Haversian canals by an exaggerated production of osseous tissue. In all such cases of gangrene, the mortified part acts on the neighbouring .living tissues like a foreign body; these being irritated, embryonic tissue, pus, and granulations are produced and the necrosed part is thus isolated and eliminated. The second form is that oi progressive molecular gangrene. It is met with in the ulceration of phagedaenic ulcers, in hospital gangrene, &c. ; and in the diphtheritic inflammation of German authors. It is considered to result from the infiltration of the tissues with fibrin and pus, which by compressing the blood- vessels impede the afiflux of blood to the affected parts. As these lesions are localised on diseased surfaces, the superficial layer is alone deprived of life, and a molecular elimination is the consequence. Beneath the eliminated part granulations are developed, which may in turn be destroyed by an analogous process. This form of gangrene is also met with in variola. In the pustules, the papillae may simply show a superficial formative irrita- tion which does not prevent them being reconstituted ; but when the inflammation is violent the papillse suppurate, the infiltrated cutis is itself destroyed, and indelible cicatrix results. Grenerally this progressive molecular gangrene is the result of a local affection which appears to be associated with the presence of microphytes or microzoa, of which the species vary according to the nature of the disease, and are as yet insufficiently determined. Investigations on the subject are still in progress. V. — Synthetical Study of Inflammation and its Clinical Forms. Having analysed the various phenomena of inflammation, we may now proceed to the synthetical study of these different states and their natural grouping in inflammatory diseases. All authors have agreed in dividing inflammation into acute and chronic. Abscess is the type of the first, cirrhosis of the liver of the second ; but between these two extremes all intermediate forms may be observed, it being often difficult to define the exact limit between chronic and acute inflammation. For example, the histological phenomena of chronic catarrh of a mucous membrane approach very near to those of the same disease in the acute state, and only differ by the greater thickness and pigmentation of the membranes. A more useful and anatomical division is based on FORMS OF INFLAMMATION. ng the forms of the lesions themselves, on their situation, degree of intensity and cause ; and thus the following grouping may be accepted : — I. Congestive inflammation. — Such are inflammatory hyperaemia, cutaneous erythema, erysipelas, acute catarrhal inflammation of the mucous membranes, rheumatic inflammation of the joints, &c. In these lesions ^^besides congestion, proliferation and mucoid exu- dations containing pus cells are foimd ; but congestion is always the predominant fact. II. Exudative inflammation. — For the general study of this subject we refer the reader to what has been said regarding exu- dations. There should be as many dififerent forms of inflammation as there are distinct varieties of exudation ; but in reality almost all these varieties are mixed, and contain flbrin, albumen, mucus and pus cells, and may almost all be included under that form, called by the Germans, croupous exudation ; such are the exuda- tions of acute pneumonia, pleurisy, pericarditis, peritonitis, &c. III. Purulent inflammation. — Purulent and puerperal infections belong to this variety. To produce this form of inflammation there must be a suppurating wound, either traiunatic, or physio- logical like the sanious idcers of the uterine mucous membrane at the point where the placenta is attached. In this form of infec- tion, pus is produced in most organs with extraordinary facility and abundance, and 'per contra the congestive phenomena are but little marked. Thus, a joint may be full of pus with the synovial membrane hardly injected. The hypothesis of Cohnheim does much to explain this facile suppiuration, although it is difficult to understand how such an enormous mass, often many pints of pus, can pre-exist in the blood and pass from it in the course of a few days. According to the researches of Pasteur, purulent infection is produced by a vibrio which lives in common water, and which is at the same time aerobic and anaerobic, that is to say, capable of living in air or without air. By inoculation with these microbia, pus is produced in a few hours, and a veritable abscess is formed a few days after. If the generating microbium finds a suitable medium of culture in the economy, it produces centres of suppu- ration in various organs and death. (Communication made to the Acad, des Sc. and to the Acad, de Med. April 1878.) IV. Infection, suppuration and septicaemia. — According to M. Pasteur, septicaemia is due to another septic vibrio or microbium which he has succeeded in cultivating and reproducing by suc- cessive cultures, as he had also done with the microbium of puru- I20 INFLAMMATION. lent infection. This microbium is killed by oxygen ; it is anaerobic. A distinction must, however, be made between the adult vibrio and the germinal corpuscles. The latter can in fact preserve their properties in spite of contact with air. The bacteria which are constantly met with in the blood of animals affected with malig- nant pustule (Toussaint, Davaine, &c.) are aerobic according to Pasteur, and cannot exist without oxygen. According to Pasteur, Coze and Feltz, Hallier, Cohn, Klebs, Tiegel, Tigri, &c., there are microbia possessing special characters and properties in the ma- jority of contagious and infectious diseases. But these researches have given rise to so many denials and contradictory discussions that their conclusions cannot yet be regarded as proved. V. Hyperplastic or interstitial inflammation. — This springs suddenly into existence either in the acute or chronic state by a development of embryonic tissue which gradually passes to the state of adult connective or bone tissue. Such are cirrhosis of the liver and kidney, interstitial pneumonia, sclerosis, periostoses, exostoses, &c. VI. Gangrenous inflammation. — See above, page 117. VII. Caseous inflammation (Forster). — In this the products of inflammation are not "eliminated. They become atrophied, broken up and filled with fine fatty granules, destruction of the part affected being the result. The lungs and the lymphatic glands are the usual seat of this form of inflammation, but it may occur in all the other organs. The essential condition of its pro- duction is that the infiltrated pus should remain long in such abundance in an organ, that the vessels are compressed by the inflammatory elements. The same result occurs when inflamed vessels are themselves the seat of endo-arteritis. VIII. Pseudo-membranous inflammation. — Such are the lesions of croupous laryngitis or true croup. They have been studied above (page 104). BIBLIOGRAPHICAL REFERENCES. Bkoussaib, Traite des pAlegmasies. Hunter, Treatise on InflcmnmaUon. Kaltbnbeunnbe, Repertoire d'anatorms et de physiologie de Bresehet, vol. iv. Whabton Jones, Gwy's Hasp. BepoHs, 1850 ; Med. Clwr. Trans. 1853. Hasse and KOLLIKEE, Zeitsohr. f. rad. Med. iv. 1845. ViKCHOW, Cellular Pathology. Recklinghausen, Mter wnd BindegenelsMrperchen, in Vvrohom's ArcMm., vol. xxxviii. 1863, p. 157. Estoe and Saint-Pibeee, Jov/rnal de I'amM. vol. i. 1864, p. 403. OOHNHBIM, Mntziliidung und Mterwng, in Virohow's ArcMm., vol. xl. 1867, p. 1. Vorlesvngen alter die allgemeine Pathologie, 1878, vol. i. — For the bibliography concerning the r61e of microphytes in inflammation see Thesis on Bacteria, byTM. A. Magnin, Paris 1878. 121 CHAPTER IV TUMOURS. Tumours differ from inflammatory new formations by their ten- dency to persist and grow, while new inflammatory formations tend always to disappear or to reproduce the tissue which served them as a matrix. DEFINITION OF TUMOUR. The word tumour (tumor, ojkos) has been applied in medicine from all antiquity to the most various productions. At first every swelling, every tumefaction of whatever kind, was called a tumour. Thus displacements of an organ, hernias for example, were placed among tumours, and so they are still called clinically in the path- ology of the crural and inguinal regions, &c. The word was afterwards limited to abnormal tumefactions, demonstrable after death ; but lesions becoming better known by means of micro- scopic analysis, the group of tumours became more circumscribed, as histological structure became the basis of definition. We call a tumour any mass composed of a tissue of new for- Tnation (neoplasm.) which has the tendency to persist or to increase in size. This definition comprehends two terms which we will analyse ; the neoplasm ' and its persistence or growth. In a general way, neoplasms are subject to two laws : the first, which results from the labours of J. Miiller may be thus stated : The tissue of which a tumour is formed has its type in the tissue of the organism in the embryonic state or in that of complete development. The second is from Virchow: The cellular ele- ments of a tumour are derived froTU pre-existing elements of the organism ; to which Virchow adds that they are derived from the cells of connective tissue. ' By neoplasm is understood a tissue of new formation, whatever be its nature or origin. 122 TUMOURS. Histologists of every school are now inclined to admit J. Miil- ler's law, a law which was misunderstood at first, and still badly interpreted, even by his most immediate pupils. The first pro- position of Virchow's law is true. Hazardous and hypothetical at the time that it was put forth, the assertion, that the elements of every tumour are derived from pre-existing cells of the organism, seems to us to be now perfectly demonstrated. But the second proposition of Virchow, that connective-tissue cells are the starting- point of every tumour, is not true, for they may be developed from epithelial cells and other cellular elements. The word neoplasm, which we make use of to define tumours, distinguishes them from effusions, retention of secretions, &c., wrongly considered, we think, by Virchow as tumours. Thus a collection of blood should no more be considered a tumour than a hernia. The retention of the secretion of a serous bursa, as in - hygroma, is also, in our opinion, not a tumour. For a long time infarcts were included among tumours, and Virchow does not hesi- tate to include among them the necrobiotic changes of the tissues consequent on obliteration of blood-vessels. The second term of our definition, persistence and growth, dis- tinguishes tumours from infiammatory neoplasms. In the latter case the new growths become organised by reproducing the tissue from which they are generated, or they disappear little by little by suppuration or caseation, &c. This is too important a fact to be passed over. Tumours obey, in a general way, the laws which regulate living tissues, but they live to a certain degree an independent life, and possess a special circulation. They in- crease and grow at the expense of the individual in whom they are implanted, so as to constitute a new organism grafted on a more complete organism. For example, a patient affected with lipoma emaciates without seeing the tumour diminish. In the same way patients affected with carcinoma emaciate and fall into a condition of incurable cachexia, whilst the tumour grows rapidly. This development and autonomy of tumours suggest the idea of parasitism. Laennec looked upon them as parasitic masses having their own individuality and developing as distinct beings.' This idea of Laennec is now completely abandoned, as we have already indicated by the statement of Miiller's law, and if the word para- ' The words heteromorphia, heteroplasia contrasted with homoeomorphia, ho- mcBoplasia, &o., representing the idea of parasitism or tissues without analogues in the economy, seem to us useless after what we have said above regarding J. Miiller's law. CLASSIFICATION OF TUMOURS. 123 sitic tumour is employed clinically, it is to specify a particular case m which parasites form a distinct mass. CLASSIFICATION OF TUMOURS. JMiiller's law, that the tissue of every tumour is the analogue of a physiological tissue in the embryonic or adult state, leads us to a classification of tumours, in which to each kind of tumour a name is given, the Greek root of which is borrowed from the analogous normal tissue, the termination oma, omata, being added.' But it must not be thought that J. Miiller or his immediate successors or pupils have always made use of this law in the classification of tumours ; often the contrary. Thus, in speaking of certain tumours, J. Miiller employs the words cholesteatoma and steatoma, the radicles of which are the words cholesterin and stearin ; but we may remark that sometimes the tvmiour called cholesteatoma does not contain either one or the other of these substances. The pupils of J. Miiller have also devised and employed words which in no way recall the names of tissues, as we shall see in proceeding with oin- description. Virchow, the author of the most recent and extensive treatise on this subject, divides tumours into four groups, which are : — 1 . Tumours formed from the elements of the blood ; for example, hsematoma or blood tumomr. 2. Tumours formed by the retention of secretions, as glandular cysts, hygroma. 3. Tumours resulting from the proliferation of the ceUular elements of pre-existing tissues of the organism. This class is divided into histioid tumours, composed of a single tissue ; organ- oid tumours, reproducing the configuration of an organ ; teratoid tuTThours, resembling by the union of different organs an incom- plete being. Each of these three large groups is divided and sub- divided. 4. Mixed tumours resulting from the union of many of the preceding. The third group of Virchow's classification includes almost all tumours. "We cannot admit his first group, nor the majority of those contained in the second, as being tumours at all. In a remarkable work, called the Pathology of Tumours, he has included almost all general pathology. We, on the contrary, wish to treat simply from the histological point of view, and ' Certain well-defined tumours being designated from long use by certain names, we adoPt them, not being willing to introduce new words. 124 TUMOURS. have therefore included under the head of inflammation and haemorrhage what seemed to us to rightly belong to them, blood tumours, hygromata, for example. We also think we have a right to reproach Virchow vnth having invented new words, drawn from gross physical characters, whereby to designate certain tumours, instead of employing words representative of the tissues. Thus he uses the word psammoma to signify a tumour of the meninges, because it contains calcareous granules similar to fine sand, and the word glioma is applied to tumours of the brain because they are of a consistency analogous to glue. He thus departs from the classification which Miiller's law suggests, and which we intend to follow absolutely. The classification made by Forster comprises : — 1. Tumours formed of a simple tissue, and sometimes even of a single element of this tissue, for example, fibroma, osteoma, &c. 2. Txmiours having a complex arrangement, the analogue of which can be formed in the economy ; for example, papilloma, cysts. 3. Tumours formed of cells having their analogues in the economy, but arranged in a manner other than physiological. This group includes sarcoma, carcinoma, epithelioma, lymphatic tu- mours, under which may be classed the organic lesions of typhoid fever, tubercle, syphilitic gummata, and true lymphoma. Forster's classification, more particularly the third group, does not seem to us to be good, in that it does not take sufficient account of the embryonic state of the tissues, nor of their ulterior metamorphoses. Moreover, in the last group he depends on a different basis to that on which he founds the first two classes, and neglects the consideration of the tissue, taking note only of cha- racters drawn from cells. Our classification is based solely on the analogy of tumours with normal tissues. Thus, we recognise those analogous to em- bryonic, fibrous, cartilaginous, osseous tissue, &c. ; and employ, as far as possible, words formed by the radicle of the normal tissues to which the terminations OTna, omata, are added. GrEOUP I. — Comprises tumours formed of a tissue analogous to embryonic tissue. We might employ a new word to indicate this analogy, but we prefer to make use of the old word sarcoma, though it has been employed in very different senses by difi'erent authors. This group only contains one genus, sarcoma, of which there are a great number of species and varieties. Group II. — Contains tumours formed of a tissue, the type of which is found in connective tissue. This tissue is sometimes CLASSIFICATION OF TUMOURS. 125 mucous and the tumour is called myxoma, sometimes fibrous and called fihroma (Vemeuil), or inoma, from Ivh,, fibre (Paget), sometimes adipose, when called li-poma. In some cases the tissue undergoes hypertrophic aberration affecting the size of the cells ; this IS the case in carcinoma, which would be better called alveolar Jibroma; m others, the cells atrophy, as in tubercle, glanders, and 8yph%ht%c gummata. This second group therefore contains the varieties myxoma, fibroma, lipomxi, carcinoma, tubercle, glan- ders and syphilitic gummata. Group III.— Contains tumours formed of cartilaginous tissue, of which there is but one genus, chondroma. G-ROUP IV. — Is composed of tumours formed of osseous tissue, 08teom,a. Group V. — Tumours, formed of muscular tissue or myoma, are divided into two kinds, according as the fibres of new formations are striated or non-striated : myoma of striated fibres, myoma of non-striated fibres. Group VI. — Tumours formed of nervous tissue are of two varieties : the meddollary neuroma containing nerve cells, and the fasiculated neuroTua containing nerve tubes. Group VII. — In this are tumours formed of blood-vessels or angioma. Group VIII. — Contains tumours formed of lymphatic vessels, lymphangioma, and those which reproduce the structure of lymphatic glands, lymphadenoma. Group IX. — Contains tumours composed of epithelium of new formation. They are divided into four varieties according as the cells are arranged in irregular masses, epithelioma, or in papillae, papilloma, or in culs-de-sac, adenoTna, or in cavities of new for- mation, cysts. Group X. — Contains mixed tumours, containing a great number of tissues ; they are formed specially during intra-uterine life. The classification of tumours which we propose differs, it will be seen, notably from those hitherto published. It is an anatomical classification. It cannot consequently serve to determine the degree of gravity of a tumour. No anatomical classification can at present answer this legitimate desire of the physician. To determine the degree of gravity of a tumour, knowledge of the order, species, and variety to which it belongs can alone be depended upon. The sole general consideration, which may be advanced on the subject of the benignity or malignity of tumours. 125 ' TUMOURS. is that the most serious are those which determine the formation of a large quantity of embryonic elements, at the expense of which they grow rapidly. Our classification has the advantage of being purely histological and of being based on one law and on one con- sideration which seems to us to be supreme, that is, the general arrangement of the morbid tissue and the distribution of the elements composing it. I. — TUMOUES FORMED OF EMBRYONIC TiSSUE. Sarcoma. We will first study the generic character of tumours analagous in structure to embryonic tissue, and then discuss the characters belonging specially to each species and variety. Synonyms. — There are no tumours which have received a greater number of names than the sarcomata. J Miiller partly described them under the name of fibro-albiomwioid tuTnours. Lebert, having remarked that many of these tumours contained an abundance of fusiform cells, called them fibro-plastic hcmmtrs. Charles Kobin thought that fibro-plastic tumours should be separated from certain tumours having numerous analogies with them but differing from them in the round form of their cells, and ' he called them embryo-plastic tumours. Paget gave to fibro- plastic tumours the name of recurring fibroid, and grouped them with certain tumours having a structure analogous to that of the medulla of bone, which he called myeloid tumoicrs. These latter were called by Charles Eobin tumours of medulla^cells, and tumours of myeloplates. Finally, Virchow separated from sar- coma certain tumours which had always been classified with them and gave them the names of glioma and psammom^a. Definition. — We define sarcoma as a tumour formed of em- bryonic tissue either pure or undergovng one of the first modifi- cations it shows previous to becomAng adult tissue. Thus, when embryonic tissue is changed into fibrous tissue, from the spherical form its cells become elongated and fusiform, and an amorphous ground substance is thrown out between them. This is an embry- onic state of connective tissue, and tumours showing an analogous structure are called sarcomata. Though sarcomatous tissue has its type in the physiological condition, its analogue can also be found in the pathological condition during inflammation. Thus, in SARCOMA. J 27 graniilation tissue all the embryonic phases of connective tissue are met with ; certain sarcomata have a similar structure. Further, if inflammatory tissue arises in the medulla of bone, it shows when granulatmg, cells identical with those of the medulla of bone and often osseous trabeculae in the process of development ; identical forms are met with in certain sarcomatous tumours. The difference between sarcoma and inflamed tissue consists essentiaUy in the origin and termination of the two morbid processes. \\Tien inflamed tissue originates in a wound, or chronic disease of the bones or joints, the end will be elimination or reconstitution of A 00 1 Fig. 58. — Inflamed Tissue. a, c, embryonic cells occupying the place of adipose cells, one of which shows at 6 — a drop of fat ; (/, ?, embryonic tissue ; v, vessel, the wall of which is formed of cells which are themeslves embryonic. the permanent normal tissue, in one word recovery; while sarcoma will continue to grow indefinitely. As to the histological elements of these two neoplasms, they are, we repeat, generally identical, but often larger in sarcoma than in the inflammatory neoplasm. If, however, the latter develops slowly, the cellular elements may be as large. Further, the form of the cells in sarcoma is not entirely subordinate to the seat of the tumour ; thus, in sar- coma developed in the skin or a gland large mother-cells, similar to those found in inflamed medulla of bone, may be observed. Almost the whole mass of a sarcoma is composed of ceUular ele- ments, hence Forster classifies these tumours among those solely composed of cells. 128 TUMOURS. General description of the genns sarcoma. — Sarcoma cells assume the most varied forms. Sometimes they are spherical, especially if examined in water — the same element which is an- gular in a neutral fluid may swell and become round in water ; at other times the cells are irregular, containing one or many ovoid nuclei, and furnished with processes which often anasto- FiG. 69. — Sakcoma Cells with Ramifying and Anastomosing Peocesses. Magnified 26 diameters. mose (figs. 59 and 62); many of the cells are fusiform with ovoid nuclei (a, fig. 60) ; in certain cranial tumours they are flat, extremely thin, variable in size, and have one central lenti- cular nucleus ; seen full face they appear plaited and folded over like a handkerchief taken up by one comer ; observed sideways they look like a fibre with a central elongated nucleus (vide, fig. 73, p. 146). It is thus seen that the form of the cells of the genus Fig. 60.— Cells and Tissue op Melanotic Sarcoma. a, fuslEorm cells ; 6, round and deeply tinted cell. sarcoma is very compHcated ; in size they may vary from 5 /i to 50 /A, or even more. The structure of the cells is simple. They have one or many nuclei which are spherical or oval and of a size varying between 5 /* and 9 /* ; the nucleoli are generally small and brilliant, but they may exceptionally be as large as 5 fL. The number of nuclei in one cell varies from one to fifty; they are SARCOMA CELLS. 129 found in these large numbers in ceUs, flat or otherwise, called giant cells, described by J. Miiller in sarcoma by the name of mother- cells, and called myeloplates by Eobin, in consequence of an erroneous interpretation which led him to look upon them as plates and not as cells ; around the nucleus is a granular substance ; FiQ. 61. — Mother-cells, Round and Fusifokm Cells, fkom a Myleo- SAKCOMA OF BoNE. Figure borrowed from Ordonez. examined in a neutral fluid the nuclei are often indistinct, but on the addition of water or acetic acid they become clearly visible. The cells have no membrane and on the addition of acetic acid they swell and become extremely transparent and very indistinct. In some cases the albuminoid granules of the cell are arranged in such a way that a kind of striation is produced coarsely resembhng that of a muscular fibre, but it disappears on the addition of acetic K 13° TUMOURS. acid. Sarcoma cells Uke embryonic cells are very sensitive to tHe action of reagents ; their friability is such that on scraping, the cells are ruptured and the nuclei set at liberty. Observations made in this way have led certain micrographers to admit the existence of free nuclei, which were in fact artificial products or the result of cell destruction. If a small portion of a tumour be put in a few cubic centimetres of a 33 per cent, solution of alcohol, and dissociated twenty-four hours afterwards^ free nuclei are not found, but the cells are isolated and show exactly the same forms they have in the tumour itself. They can then be stained with picrocarminate of ammonia and preserved for an indefinite period, provided that the glycerine has been allowed to penetrate slowly. Sarcoma cells are thus seen to be of such various forms and sizes that they are little characteristic when examined alone, so that Fig. 62.— Sarcoma Cells Isolated in a 33 pee cent. Solution op Alcohol AND Stained with Piobo-cakminate of Ammonia. They show very long and miatiple processes. One of them has three nuclei. Magnified 300 diameters. the anatomical diagnosis of sarcoma cannot be made from elements obtained by scraping. Sarcoma is defined and characterised by the arrangement of the elements and their mutual relations to one another. The ceUs are placed one beside the other, either touching or separated by an amorphous substance, which is soft and small in quantity. Of all tumours, sarcoma is the only one with so simple a structure a veritable embryonic organisation. The blood-vessels are numerous and are in direct relation with the cells ; some of them how- ever, and particularly the large vessels, are surrounded by fasci- culated connective tissue ; they have no regular arrangement ■ STRUCTURE OF SARCOMA. 131 and their structure is simHar to that of blood-vessels in inflamed tissues, their ceUs being embryonic. In soft sarcoma, in spite of the softness of the tissue, it is impossible to isolate the vessels. This IS owing to the fact that the ceUs of their walls are embryonic Fig. 63. — Section op a Fasciculated Sakcihia. Magnified 200 diameterB. Figure borrowed from RlndfieiBch. and not distinct irom those composing the mass of the timiour ; if an attempt be made to separate them by dissociation, they have no resistance and their elements are dissociated together with those of the tumour. Blood-vessels may be isolated in a fresh state Fig. 64. — Vascular Nbtwork injected, from Sarcoma of Boxe. After Billl-oth. from a sarcomatous tumour which is tending towards a higher stage of organisation. After hardening ' such a tumour, and ' The hardening of sarcomata, like that of other tumours, may be obtained by different methods. The simplest consists in placing portions of the tumour in strong alcohol at 90° ; twenty-four hours afterwards they are sufficiently hard to allow of sections being made, which may be stained with ammoniated carmine, or with a 1 per cent, solution of picrocarmine. With the latter reagent staining is K 2 132 TUMOURS. examimng fine sections witH a power magnifying 150 or 200 diameters, the lumen of the divided vessels is seen to be bounded by round or fusiform cells, but the walls properly belonging to these canals can rarely be made out. This is an essential point, and, together with the general arrangement of the elements, is characteristic of sarcoma, and explains the facility with which vascular ruptures and effusions occur, as well as the formation of blood cysts so frequently observed in these tumours. Species and varieties of sarcoma. — The form of the cells, the cementing substance, the blood-vessels and the scheme of organi- sation of the morbid tissue, form the bases for the classification of the species and varieties of sarcoma. A sarcoma is not always composed of a single kind of cell ; every form described above may be met with, and there is perhaps hardly a sarcomatous tumour in which some of those cells, known in France under the name of myelo'plates, may not be ultimately discovered. If, therefore, in classifying tumours use is to be made of the form of the cellular elements present, the presence of such or such cells should not alone be considered, but the proportion in which they are found. The intercellular substance is sometimes semi-fluid, so that the molecules may be displaced, and in this case pressiu-e being equal in every direction, the cells are round. At other times there is no ground substance or it is more or less solid, and the cells may then be pressed one against the other and take various forms. If they are compressed laterally in both directions they elongate and become fusiform with two plane surfaces; if compressed almost instantaneous, it being sufficient to put a drop of the solution on a thin section placed on a slide, to cover it, and add glycerine. With a little dexterity very beautiful preparations are obtained by this method, but preparations simply hardened in alcohol are never hard enough to resist much pressure, so that if it is necessary to use a microtome recourse must be had to the following method : let the pieces remain twenty- four hours in alcohol, after which put them in a saturated solution of picric acid, and then into a weak solution of gum arable where they should remain twenty-four hours ; then let them be put again into alcohol for another twenty-four hours ; the alcohol, coagulating the gum which has penetrated into the interstices of the tissues, completes the hardening process. Perfect hardening may also be obtained by leaving the tumour in a -2 per cent, solution of chromic acid for one or two weeks. A solution of bichromate of potash or ammonia also hardens tumours, whilst preserving the form of the elements • only they must be immersed for many months, at the end of which time, if the hardening be not sufficient, recourse must be had to the successive action of gum and alcohol. The elements of sarcomata and other tumours, subjected to the process of hardening by chromic acid or the bichromates, stain badly with car- mine, but staining of the cells and nuclei can be obtained by means of hsemat- oxylin and purpuriu. It should be added that before attempting to stain the sections made after hardening in gum, they must be soaked for some time in water. SPECIES OF SARCOMA. 133 only in one direction, they are flattened. These facts, noted in the first edition, have since been confirmed and verified by Neu- mann. We must also consider as an important element in the classification of sarcoma the scheme of organisation of the em- bryonic tissue composing it. This scheme of organisation may be after the type of fasciculated connective tissue, neuroglia, medulla of bone, or osseous tissue. Account must also be taken of changes in the vascular walls ; the blood-vessels are sometimes embryonic, dilated in a pouch-Kke or fusiform manner (erectile sarcoma), or sometimes ruptured producing blood cysts ; at other times, on the contrary, the walls are resistant and even infiltrated with calcareous salts (angiolithic sarcoma). These elements in the classification of the species of sarcoma being recognised, the following is what we propose : — 1st Species, Encephaloid sarcoma. — When sarcoma is solely formed of embryonic tissue, its ground substance soft and small in quantity, and its cellular elements globular and small, it is said to be encephaloid, for the tumour resembles softened cerebral sub- stance (the embryoplastic tumour of Eobin). 2nd Species. Fasciculated sarcoma. — If the ground substance is thicker and more solid, and the elements fusiform presenting the first stage of the transformation of embryonic into connective- tissue cells (connective-tissue fibres may even be formed), it is fasciculated sarcoma (the tumour of fibro-plastic cells of Lebert). 3rd Species. Myeloid sarcoma. — Especially in bone but also sometimes in other organs, the morbid mass is composed of a tissue similar to embryonic bone marrow ; this is myeloid sarcoma. 4tli Species. Ossifying sarcoma. — In a certain number of sarcomata the embryonic tissue shows a tendency to become organised into a more or less perfect bony tissue; such are ossifying sarcomata. 5tli Species. Neurogliac sarcoma.— In sarcoma of the nervous centres, and occasionally in other organs, the embryonic tissue has a tendency to take the form of neuroglia; this is neurogUac sarcoma {glioma of Virchow). eth Species. Angiolithic sarcoma. — In the meninges, sarcoma tends to take the vascular arrangement of the choroid plexus, and shows the peculiar buddings and calcareous granules which are physiological in the choroid plexus ; we call this form angioUthic sarcoma (psammoma of Virchow). Such are the species based on histological forms properly so called ; but the three following species of sarcoma may also be 134 TUMOURS. considered as distinct, though they present but purely nutritive modifications of their elements. They are : — 7tli Species. Myxo-sarcoma, in which the cells have under- gone mucoid degeneration. 8tli Species. Lipomatous sarcoma. — This is a sarcoma in which the cells are filled with droplets of fat which distend with- out destroying them, as in the subcutaneous cellulo-adipose tissue ; such is the lipo-sarcoma of Virchow or lipomatous sar- coma. 9tli Species. Melanotic sarcoma. — The cells have undergone a very important change, which consists in their impregnation with pigment granules. What justifies the distinction of the various species given above is the fact that all possess the property of producing secondary growths vn situ or far from their point of origin, having the same characters. Independently of these principal species, in each, varieties may be distinguished, based on nutritive changes in the cells. These disorders of nutrition are as follows : — a. Fatty degeneration. — This is general at the centre of most large and old tumours ; the cells are then infiltrated with fine proteid and fatty granules which bring about their destruction. The sarcomata which show this change must not be confounded with those described under the name of Lipomatous sarcomata. 6. Infarction. — In certain large sarcomata, white opaque caseous masses are observed, often of very irregular form ; the blood- vessels are also seen to be fiUed with a fatty granular pigmented detritus, while at the same time the cells are compressed and contain fat granules. This state, which is consecutive to oblitera- tion of the blood-vessels of the altered part, may be considered as a kind of infarct. c. Calcareous degeneration. — In sarcoma developed at the expense of osseous tissue and periosteum, or sometimes far from bony tissue, a more or less considerable calcareous transformation of parts of the tumour may be observed. This metamorphosis is often shown in the form of calcareous radiating needles, or irregu- larly arranged stalactites. This impregnation with calcareous salts begins, as in every similar case, in the ground substance ; the cells, preserved at first in the midst of little soUd frameworks, ultimately also become implicated. These are retrograde phenomena ending in the cessation of nutritive functions in part of the tumour ; they must not be confounded with ossification, that is to say the ENCEPHALOID SARCOMA. 135 formation of true osseous tissue, whicli takes place in ossifying sarcoma. d. Formation of blood cysts.— The transformation of a part of the tumour into blood cysts is brought about when the blood- vessels, having no proper resisting wall, are ruptured and extra- vasation of blood follows ; a haemorrhagic focus is thus produced, and the cells that have undergone mucoid degeneration mis with the elements of the blood. This compHcation is very frequent in the soft varieties of sarcoma. e. Inflammation.— When a sarcoma is irritated, all the phe- nomena of inflammation are observed. In virtue of its embryonic structure it is more than any other tissue disposed to inflammation and suppuration. Sarcoma has a great tendency to exuberant growth and to give rise to volmninous granulations ; this is the villous variety of sarcoma. Every sarcomatous tumour situated on a surface tends to become villous. It is a curious fact that osseous tissue, already existing in a schematic manner it is true in sarcoma, may under the influence of irritation disappear by absorption of its ground substance, and return to the embryonic state. Another equally interesting fact is that when a sarcoma has rendered a bone friable and fracture occurs, a new production of cartilaginous tissue is often seen to take place at the expense of the tumour, just as if an ordinary fracture had occurred. "We will now study in detail each one of the species sketched above. Encephaloid sarcoma. — This was formerly confounded with carcinoma under the name of encephaloid cancer. It is often called in France by the name of embryo-plastic tumour. The encephaloid appearance of these tumours and their pulpy con- sistence are often well marked ; they are of a grey or greyish-white colour and often more or less translucent. The primary tumour very qtuckly acquires an enormous size, and may become generalised and give origin to secondary masses, particularly in the lung. The blood-vessels are large and the walls embryonic ; they are often dilated, varicose or aneurismal, when they appear to the naked eye as little red points ; they may finally be ruptured and give rise to small cysts filled with fluid or coagulated blood mixed with mucus, and holding retrograde elements in suspension ; the vascular walls often give way and ecchymoses or diflfuse haemor- rhages are produced. In most of these haemorrhagic foci the red blood corpuscles are preserved, and there is no pigmentation of the neighboiu-ing elements ; it seems as if circulation still takes 136 TUMOURS. place in these irregular lacunse. If the surface of a section be scraped directly after separation of the tumour from the living subject, the fluid obtained is quite transparent — but twenty-four or forty-eight hours after removal scraping yields an abundant white fluid similar to cancer juice ; this milkiness is due to the fact that the embryonic cells of the tumour have been set free, in consequence of a cadaveric liquefactioii of the ground substance. It is thus seen that this character, formerly given as peculiar to cancer, may be met with in certain sarcomata, examined some hours after death. The cells of eneephaloid sarcoma are generally small, round or more or less irregular, and may have a diameter of 30 /i ; their nuclei, which sometimes measure more than 10 /i, contain one or more nuclei ; they never have the same variety of form as carcinoma cells ; they consist of a mass of protoplasm sur- rounding one or more nuclei, a vesicular condition of which, or of the cellular substance, may sometimes be observed. In eneephaloid sarcoma there is often found a certain amount of old connective tissue which was pre-existent at the spot where the tumour was developed. Besides the nutritive changes indicated above, in the earliest- formed parts of these tumours the cells are often found infiltrated with fine fat granules, and larger granules of the same kind are found united in the form of granular bodies. Parts of the tumour may undergo mucoid or calcareous degeneration, or become in- filtrated with red or black pigment. In tumomrs where these changes are very limited, and which cannot consequently be clas- sified among primary mucous or melanotic tumours, to the name eneephaloid sarcoma, signifying the species, should be added a term describing the partial degeneration observed ; thus, for example, eneephaloid sarcoma with partial mucoid degeneration. The seat of eneephaloid sarcoma is very variable ; it may be observed in the skin, the subcutaneous cellular tissue, the bones, muscles, glands, and especially in the breast and testicle. The most serious form of sarcoma is that which relapses most frequently, and is generalised in a great number of organs. Fasciculated or spindle-celled sarcoma. — In this species the embryonic tissue has already undergone an attempt at organisation and evolution in the direction of connective tissue : this is the fihro-plastic turrvour of Lebert. As this species is very common, it is usually regarded as the type of sarcoma. Some surgeons have made embryo-plastic tumours a sub-variety of fibro-plastic tumours, which is a senseless classification when looked at either SPINDLE-CELLED SARCOMA. 137 from Lebert's or our own point of view. From the translucence ot these tmnom-s and their fasciculated appearance they have been compared with flesh, and hence the name sarcoma, a name after- wards appHed to the whole genus ; the word is bad from an ety- mological point of view, though defended by use. The cells of fasciculated sarcoma are fusiform, terminating in two long, sometimes ramifying, extremities. Their dimensions are variable ; they have a mean length of 15 /a to 30 yit, but they ^ i Fig. 66. — Section of a Fasciculated Sarcoma. a, sarcoma cells arranged in bundles and seen sideways ; &, cells belonging to bundles lying perpendicular to the first and seen full face ; t; blood-Tessel showing in its wall a series of flattened cells. Magnified 200 diameters. may attain the enormous size of 100 /*. Perhaps it would be convenient, as Rindfleisch has done, to classify these tumours according as they have small or large fusiform cells. The tissue of fasciculated sarcoma is very simple. The cellular elements are so arranged that they are in contact, the extremities of one cell being in relation with the dilated portion of neigh- bouring cells. Cells unite so as to form veritable fasciculi, which are sometimes parallel to one another and sometimes crossed. The genreal direction of the blood-vessels is the same as that of the 138 TUMOURS. cells. When seen in section, vortices or pellets are observed, separated and surrounded by longitudinal tracts. The vortices represent the transverse section of fasciculi, the interposed tracts their longitudinal section {vide fig. 65 ). The centre of the vortices often makes a conical projection after section, an appearance which we shall see more marked in fibrous tumours. The periphery of these tumours is sometimes well defined as in fibroma, sometimes diffused, the morbid mass being continuous without interruption with the neighbouring normal tissues. They grow from the periphery, sometimes irregularly, sometimes by Fig. G6. — Fasciculated Sarcoma. Figure borrowed from Virchow. distinct spherical lobules. Their size varies, but they are generally smaller than encephaloid sarcoma ; in the limbs, however, fasci- culated sarcoma, springing from the periosteum, is often found to reach the size of the head of an adult. In the fresh state they have no juice, but a day or two after operation, or in the cadaver, a little juice is observed, less abundant than in encephaloid sarcoma, and also less abundant and less thick than in carcin- oma, where it may be squeezed out by pressure like a milky exudation. FASCICULATED SARCOMA OF THE BREAST. ,39 FMciculated sarcoma is often seated under the periosteum ; It IS also found in bone, connective tissue, muscles, the breast, tesucie, <&c., and may become subsequently generalised in all tne organs. In the breast this, and also the preceding form of sarcoma, is accompanied with proHferation of the cells of the glan- dular culs-de-sac. Hence BiUroth made a distinct variety- odrnw-sarcoTm. In France when situated in the breast it is often wrongly called adenoma of the breast, a confusion constantly made by Velpeau. A great number of different tumours of the Fio. 67. — Fasciculated Sarcoma of the Periosteum. breast have been confounded, under the name of adenoma, or adenoid tumour. Two forms of sarcoma of the breast are recognisable. The tumour may form a mass through which the culs-de-sac are disseminated, massive sarcoma of the breast, or the sarcomatous tissue buds, and pushes back the walls of the canals and the glandular culs-de-sac, bulging into their cavities. Budding protruding masses are thus formed, and the galactophorous ducts and acini being increased in size, they are transformed by these into lacunar cavities, into which the buds of the sarcoma 140 TUMOURS. project, bwddAng sarcoma of the breast. These buds and cavities are covered by pavement or cylindrical epithelial cells. The lacunar cavities are of variable size, and appear in section like stellate or semilunar fissures, or they may appear as large spaces separating the tumour into lobes. Their walls are thin, smooth, and always lined with epithelial cells, which we have succeeded in staining with nitrate of silver. Twenty-four hours after death, on scraping the surface of a section of tumour, an abundant milky fluid is obtained; it is well to know of this character, if the juice of a tumour be considered of importance in determining its malignity. Tumours of the same character may be developed in the testicle and give rise to the same phenomena. Fig. 68. — Bddding Fibroma of the Beeast. d, bud projecting into a galactoplioroas canal ; a, epithelial investment of this &, connective tissue. canal; The adeno-sarcoma of Billroth ought not to be looked upon as a distinct species. In fact when sarcoma of the breast containing glandular culs-de-sac is removed surgically, and recurs, the new tumour will no longer contain glandular elements, or a very small number. If the tumour becomes generalised in other organs, the secondary growths never have glandular culs-de-sac. In sarcoma of the breast or other organs, adipose tissue is never found iu the midst of the morbid mass. We shall see later that this character is important, differentiating sarcoma, by the naked eye, from carcinoma, where, on the contrary, adipose islets are often observed in the midst of the morbid tissue. Myeloid sarcoma {myeloid tumoxir of Paget, the tumour _ MYELOID SARCOMA. 141 of medulla^cella cmd myeloplates of Robin). — Myeloid sax- coma is a soft tumour, the cells of which are in contact, without the interposition of intercellular substance, or of a very slight amount : the cells are similar to those of the preceding species {vide figs. 59, 60, and 62). Some are small and spherical like cells of embryonic medulla or of every embryonic tissue, particularly encephaloid sarcoma ; these are the medulla-cells of Eobin : others axe fusiform, and sometimes, large, irregular, flat cells may be seen with oval nuclei, myeloplates {vide figs. 61 and 66). It is essential to notice, however, that these latter elements are not peculiar to myeloid sarcoma ; they are found, in small numbers it is true, in encephaloid and fasciculated sarcoma of various organs ; in the breast and testicle, for example. Finally, some cells of myeloid sarcoma resemble^elements which^ have been Fio. 69. — Myeloid Sarcoma of the Maxilla. Figure borrowed from ttie * Surgical Pathology * of N61flton. rendered angular by reciprocal pressure, called osteoblasts by Gegenbauer. The seat of myeloid sarcoma is always in the bones. It is generally limited to a single bone, which it may destroy com- pletely, and transform into a red soft mass, its course being only arrested by the deep calcified layer of the articular cartilage. Tumours, formerly called aneurisms of the bone, are often myeloid sarcomata, the blood-vessels of which have dilated and ruptured, so that the blood circulates in a cavernous system. Ossifying sarcoma. —This species is very similar to the pre- ceding. It differs from it in the tendency the tumour has to ossify. The ossification is never complete ; some osseous trabeculse only are produced limiting alveoli filled with the tissue of myeloid sarcoma. 142 TUMOURS. The little tumoiirs of the alveolar processes called epnles are sometimes myeloid, sometimes ossifying sarcomata. These tumours, covered by buccal mucous membrane, present in the midst of their mass, or at the periphery, more or less complete osseous trabeculsB, in the form of radii irregularly arranged, or diverging from their base of implantation. These trabeculse are surrounded on all sides by an embryonic tissue similar to young medulla; in their interior true bone corpuscles are seen with well-marked anastomotic processes, more numerous and broader than those of physiological osseous tissue. At the periphery of these osseous trabeculse, it is not unusual to see young cells situated half within the medullary tissue and half within the bone Fig. 70. — Teaksvebsb Section of the Ossified Pakt of ah Epulis Decalcified in Chkomic Acid. A, medullary aad fibro-plastic cells. B, layer of embryonic cells ranged and pressed against the new osseous trabeculse. o, bone corpuscles. which has overtaken them in the process of development. Finally the osseous trabeculse, in process of development, are always im- planted on the old bone and spring from rigid fibres. These fibres, the arciform fibres of the ossifying shell, Sharpey's fibres when present in bone, exist in such great numbers in epulis that they form the largest part of the tumour. It may be asked if epulis is an osteoma or sarcoma. It belongs to the genus osteoma by the property which it possesses of generating bone, but bone transformation is never perfect in these tumours ; there is simply an attempt at ossification. Hence we include it among sarcoma. The little tumours known as sub-nngueal exostoses have a structure analogous to that of epules. They, however, habitually SUB-UNGUEAL EXOSTOSIS. contain cartUaginous islets, at the 143 expense of which, or in part "" -^ ,'iifetr''®*'^ -^^>^i< ^^1' , -\^ Nt' ■^-£. St// Fig. 71.— Section op a Sub-unqueal Exostosis of the Bio Toe. 0, naU; e, epia«™is and malpighlan layer; p, hypertrophied papilla, of tho cntis-' n „ osseous trabeoulai; », embryonic tissue. Ma^fled 26 dlSneLrs. " "' "' at least, are produced the osseous trabeculEs of new formation. Fio. 72. — Ossifying Part of the Tumour eepkesented at n IN THE PKECEDINO FlGUKE, 1. Osseous trabeculse and bone ooi^usdes. 2. Medulla cells arranged along the osseous trabecule ; it is SQen that many of these cells are about to become bone corpuscles. 8, 4. Connectire-tissne elements. These tumours, which sometimes relapse, never form perfect bone; ' Vide jVott! sii?' exogtofcs soug-wigvialei in Jour, de I'Anat., Eobin, 1867. 144 TUMOURS. they only show a tendency to ossification. Ossifying sarcoma selects the spongy tissue of bone as its favourite seat ; the big toe, the fingers, the maxilla, and the long bones, are attacked by it, especially their epiphysial extremities. The osseous trabeculse it contains must not be confounded with growths simply en- crusted with calcareous salts, though differentiation is not always possible with the naked eye. On isolating the needles incrusted with calcareous salts, found in certain encephaloid or fasciculated sarcomata, they may be seen under the microscope to be com- posed of a substance impregnated with calcareous granules, and hollowed iuto little ovoid or spherical cavities without prolongations ; these little cavities, which are not bone corpuscles, for they have no anastomotic canals, serve to lodge the sarcoma cells. Neurogliac sarcoma or glioma. — Virchow gave the name of glioma to this variety of tumour on account of its glue-hke con- sistence, and, as he found its tissue similar to that of the neuro- gUa, he classified it apart from sarcoma. He, however, implicitly recognised its analogy with the latter when he created the varieties glio-sarcoma and sarco-gliom,a. This tumour is composed of cells, measuring from 6 ^tt to 12 /i, consisting of a nucleus and a very small amount of protoplasm. Eound the cells delicate filaments can be distinguished, which are connected together so as to form a reticulum. This reticulum is never seen in fresh preparations, but only after hardening with alcohol or chromic acid ; it is, in part at least, artificial, for in two preparations made by us from the same tumour, one after harden- ing in picric acid, and the other in chromic acid, it was only visible in the latter. We may add that in other specimens of sarcomata, which have been well hardened, an analogous reticulum may be recognised in certain parts. It is therefore not characteristic. Small free cells, recalling by their characters and reciprocal relations those of encephaloid sarcoma, are present in the meshes of the reticulum. It is, however, rare that the entire mass of one of these tumours is formed of tissue thus reticulated ; frequently isolated regions are found having the structure of encephaloid or fasciculated sarcoma. We are therefore only able to recognise in glioma a sarcoma, the tissue of which shows a tendency to organisation similar to that of neurogha. The centre of these tumoiu-s has generally undergone fatty degeneration, so that in the brain we might at first sight hesitate between masses of tuber- cle and sarcoma. But fatty degeneration in the latter does not cause atrophy and dryness similar to what it does in tubercle ; in ANGIOLITHIC SARCOMA. ^^^aTC: If r''"^? ^'' accumulated in large granular bodies, and the blood-vessels are not generally obHterated, while this 18 always the case in tubercle. The blood-vessels of neiu-offUac sarcoma often have lymphatic sheaths, which are easily seen tksue ''^'''^' ^'^ ''''^^'''* ""'^^ ^^^^^^^ ^'''°' ^^^ surrounding NeurogHac sarcoma is found in the brain and spinal cord, both m the white and grey matter ; it may also be developed along the course of the cranial nerves and in the retina ; and it often pro- jects into the cavities of the cerebral and spinal ependyma. Virchow reports a case of glioma, observed by him, in the cortical substance of the kidney. Like all other sarcomata, the neurogHac vanety often shows mucoid degeneration causing the formation of pseudo-cysts. Angiolithic sarcoma.— This very curious species, which dififers by the form of its cells from all those hitherto studied, is only observed in the cranium, vertebral canal, the parietal and visceral arachnoid, and in the pia-mater and dura-mater. The tumours contain cerebral sand similar to that met with in the choroid plexus. In the physiological condition, the blood-vessels of the choroid plexus have on their walls buddings or ampullar dilata- tions lined by the pavement epithelium of the ependyma ; they are formed of flat cells encrusted, in the adult, with calcareous salts, so as to form true phleboliths. It is the presence of analogous buds or concretions in the blood-vessels of sarcomata which justifies the name of angiolithic, which we propose to give them. During development these tumours are soft, and easily crushed, although they contain no juice. They are grey in colour, more or less opaque, and, particularly when seated on the dura-mater, are often enclosed in a fibrous capsule. Their cells are flat and thin, of colossal si^e and irregular form ; they resemble a sail, and are often crumbled or folded over at the comer (A, fig. 73) ; viewed full face the border of the ceD is so delicate that it is difficult to trace it ; the centre is occupied by a lenticular nucleus ; seen sideways it may be taken for a fibre, or an extremely long fusiform cell, the centre of which is fiUed with a nucleus. These elements so resemble the endothelial cells of the veins, that Eobin looked upon angiolithic sarcoma as an epithe- lioma ; as, however, the cells are not imited together, they are deficient in the characteristic which we consider essential to the definition of epithelioma. These neoplasms are also sharply dis- tinguished from all epithelial tumours by the fact that their T 146 TUMOURS. blood-vessels are in direct relation with the cells, a condition which never exists in epithelial elements either in the physiological or pathological state. The blood-vessels are numerous and easily isolated by disso- ciation; their walls, whatever be their thickness, are entirely composed of cells similar to those which constitute the whole morbid mass. The cells feebly adherent to one another are easily pushed aside by the blood current so as to form vessels. Fig. 73. — Angiolithic Sarcoma. A, isolated cells seen full face at m, and sideways at n. Magnified 400 diameters. B, vascular bud containing a calcareous ball, o ; c, blood- TCBsel Infiltrated mtli calcareous salts, and showing at a lateral bnd infiltrated with calcareous salts. Magnified 150 diameters. Hollow buds are often seen communicating with the vascular channel ; these buds in growing become pedimculated, while the cellular elements which form the waU of the bnd get flattened, arranged in concentric layers, and encrusted with calcareous salts. This process of infiltration is in every point similar to that which occurs in the choroid plexus. If these calcified buds MYXOSARCOMA. i^y have not lost their connection with the blood-vessel from which they spring, their pedicle and a part of the vascular branch, with which they are in connection, are often encrusted with calcareous salts to form a single mass (fig. 73); but if the pedicle be accidentally broken or be not infiltrated with calcareous salts, it may pass unperceived, the little round bud looking Uke one of the bird's-nest bodies of epithelioma. Virchow, who neither re- cognised the pedicle nor observed the process just described, looks upon these little buds as simple masses of cells, similar to bird's- nest bodies, and infiltrated towards the centre vnth calcareous salts. The fact, often easy of demonstration, that these balls are connected with blood-vessels alone dififerentiates them from epi- thelioma nests. They are not necessarily calcified though there is a strong tendency to calcareous infiltration ; this property is again sufficient to distinguish them from epithelioma nests. In other parts of the body, particularly in the thymus, nests com- posed of concentric layers, calcified or not, are very frequently met with ; these are also connected with vascular walls and have the same origin. To recapitulate, although angiolithic sarcoma differs from the species already described by the form of its cells and the special modification of its blood-vessels, we think it allowable to treat it as a variety of sarcoma, inasmuch as it presents the same general arrangement of elements. Myxo-sarooma. — Mucoid degeneration of sarcoma cells, accom- panied or not by fatty degeneration, ends in the destruction of the cells and the formation of cavities filled with a transparent gelatin- ous matter. These cavities vary greatly in size ; they are often so large that they can hold an egg or a fist. The whole tumour may be riddled with them, in which case some authors call it cysto-sarcoma. The blood-vessels of mucous sarcomata generally show more or less considerable dilatations, and inter- stitial hsemorrhages may be concurrent ; the extravasated blood, combining with the mucus, assists in forming the contents of a pseudo-cyst, and gives origin, according to the quantity present, to various tints, from red to chocolate brown, in proportion as the hsemoglobin is more or less abundant, or has undergone more or less complete change. The fibrin of the blood coagulates and also concurs in varying the appeai-ance of the tumour. The cyst wall is not HnedbyepitheUum ; it is generally irregular and is not dis- tinguishable by the naked eye, or by the microscope, from the rest of the tumour ; it is sometimes covered by fibrinous lamellae. L 2 148 TUMOURS. Very small parts of a sarcoma may be in a state of mucoid degeneration without it being permissible to call it a myxo- sarcoma. We only look upon sarcoma as mucous when the mucoid degeneration is very marked, almost general, and when it has attacked the most recently formed parts. Tumours of this kind may give origin to secondary tumours having the same degenera- tion. It is this fact which justifies the distinction of this variety of sarcoma. Lipomatous sarcoma. — In this variety the sarcoma cells are infiltrated with fat without being destroyed or ceasing to hve, a capital distinction which differentiates lipomatous sarcoma from that in which the cells are destroyed or are undergoing destruc- tion from granular fatty degeneration. The cells of lipomatous sarcoma are large and fusiform ; those containing one or more fat droplets are naturally dilated, and the nucleus is pushed towards the periphery. The cells are close together and the ground sub- stance is very slight in quantity. Owing to the presence of fat granules and the small quantity of ground substance, the tumour is sometimes so soft that surgeons are apt, at first sight, to call it encephaloid cancer, a mistake which would be impossible if the microscope were used. These tumours are generally very volu- minous and may cause secondary growths. Melanotic sarcoma. — Melanotic sarcoma has its usual point of origin in the eye or in the skin, but it may also appear primarily in the lymphatic glands. In a tumour in process of development not all the cells are pigmented nor equally so : zones may be observed of various colours which may be white, grey, often semi-transparent in the young parts, or black in the older parts and sepia or slate-coloured in the intermediate ones. Such is, in fact, the usual rule, but there are sarcomata which are entirely black from the beginning and throughout their entire mass. The cells are round or fusiform ; their arrangement and that of the inter- mediate substance vary, but in their form and grouping they recall that of fascictdated sarcoma (see fig. 74). The specific cha- racter of this variety of tumour is the presence of black granules in the interior of its cells. These granules are never yellow or reddish when they first appear, a fact which establishes a funda^ mental distinction between melanotic black pigment and the black pigment present after extravasation of blood. When blood is in- fused into cellular tissue, the colouring matter of the blood infil- trates the cells — the epithelial cells of the lung in pulmonary haemorrhage for example— and the colouring matter is deposited in MELANOTIC SARCOMA. ,49 the form of yellowish-red pigment, which tmns first red then black : the whole series of these changes may be followed as Virchow has shown. In melanotic sarcoma, however, the granules are colourless, grey or black from the beginning, and are round and highly refractive ; at first they might be confounded with very fine fat granules, but when angular they are more easily recog- nised ; they are often aggregated together into small round blocks surrounded by a clear zone corresponding to a deposit of albu- minoid material around them. If the black juice obtained by scraping be examined, a great number of these granules are seen floating free in the fluid and agitated by Brownian movements. Melanotic granules are first deposited in the protoplasm surround- ing the nucleus, subsequently in the whole cell. The ground Fig. 74. — Various Forms of Cells from a Melanotic Sarcoma. substance is also soon pigmented and often more strongly so than the cells, while the nuclei themselves may be infiltrated with melanin, in which case they are more or less strongly tinted. On adding acetic acid they contract and become darker, almost black. This form of sarcoma is well marked and distinct from the other forms by the tendency its elements show to become com- pletely black, and by the same tendency in secondary products originating far from the primary tumour. Secondary growths, in the form of nuclei and black masses, are formed in great rapidity and may be found in all the organs and tissues of the economy. Melanotic sarcoma must not be confounded with simple melanosis, which may also take the form of tumours (see the description of simple melanosis, given elsewhere). It is not always easy to I50 TUMOURS. distinguish melanotic sarcoma from melanotic carcinoma. Me- lanotic tumburs of the skin and of the suhcutaneous cellular tissue are often of such a structure that hesitation must be felt before deciding whether the case be one of sarcoma or carcinoma. Clinically, this is not of much importance, since the prognosis of all tumours of the kind, whether sarcoma or carcinoma, is extremely grave. The name of melanotic sarcoma must not be given to those tumoTu-s in which extravasation of blood has occurred, pro- ducing little brown or slate-coloured masses. This is an accident which may be observed in different varieties of sarcoma, and which does not constitute a distinct species. Melanotic sarcoma is very common in white horses, in which animals it is rapidly pro- pagated in all the organs. Papillary sarcoma. — The different species of sarcoma described above take the papillary form when seated in a mucous mem- brane or the skin. We have already indicated that sarcoma of the breast has a tendency to bud into the interior of the acini and galactophorous ducts. Sarcoma of the skin sometimes shows on its surface rugse, and irregular projections bounded by depressions, at others it is decidedly of the papillary and budding variety. In consequence of the proliferation of their cells, the papillae of the corium undergo considerable hypertrophy and lateral buds may even be given off. They are covered by epidermic layers, the cells of which are more pigmented than normally. In certain cases, even the cells of sarcomatous papillae are also slightly pigmented ; it is possible that here may be the beginning of a melanotic sarcoma, but in the majority of cases the pigmentation seems to be due to ecchymoses. The cells of these papillary buds are often voluminous and pressed one against the other, so that if but little ground substance be present they may become polygonal in form. Large mother-cells {vny^loplaxes) are also found here. The very numerous blood-vessels are in immediate relation with the cellular elements of the new tissue. These tumours grow rather slowly, but they may, however, at a given moment increase rapidly and cause secondary groAvths. Development, extension, and generalisation of sarcoma. — The development of sarcoma, Hke that of most tumours, has three stages : 1, the development of the primary tumour ; 2, the growth of the primary tumour ; 3, the formation of secondary tumom-s. I. The development of the primary tumour is very siihple. It were well if it were possible to examine the neoplasm from its first appearance, but this is not absolutely necessary. DEVELOPMENT OF SARCOMA. 151 for the process of growth may be studied in the peripheral parts of the tumour, hence it is only necessary that the tumour should show parts in course of formation, a condition which is however not always present. Development should also be studied by preference in tissues of which the structure differs greatly from that of the sarcoma, in order to mark and follow the series of striking changes. In bone, the development of sarcoma is exactly similar to that of inflamed tissue ; the proUferation of the medulla-cells, the disappearance of the fat vesicles, and the consecutive absorption of the osseous tissue, are identical, and we shall therefore not redescribe them (see page 92). In tendons, the connective-tissue cells, atrophied in the adult condition, swell, their nuclei divide, are separately surrounded by distinct masses Fig. 75. — Various Phases dt the Division of the Nucleolus and Nucleus of Cells taken from Sarcoma of a Hokse. o, nucleus restricted and showing two nucleoli ; 6, division more advanced ; c, nucleolus undergoing division ; d, c, various forma of segmentation of the nucleus. Magnified 460 diameters. of protoplasm, and the new embryonic cells are arranged in long lines whilst the fibrillar substance disappears. Hence results an embryonic tissue similar to that of encephaloid sarcoma, but which may become, by changes in its cells and ground substance, a fasciculated sarcoma, an osteoid, &c. This type of development is found in areolar connective tissue, in cellulo-adipose tissue, &c ; it is not necessary to insist here more upon it. It is only necessary to recall the fact, that in every case of sarcoma, the adipose tissue disappears, the cellulo-adipose subcutaneous tissue as well as that in the breast. II. The growth of the primary tumour takes place — (a) By •proliferation of its own cellular elements. The cells multiply by division, which begins with the nucleus, and is soon followed 152 TUMOURS. by that of the cell. In sarcoma all the phases of cell multipli- cation by division may be followed ; a nucleus in the form of an hour-glass or presenting more or less deep notches, two or a great number of nuclei in the same cell, two cells united by a thin pro- cess,— these all may be observed. The prognosis of tumours which develop by proliferation of their ovm cells, is less serious than by the two following modes : (&) By continuous invasion of neigh- bouring tissues. If the excised morbid mass be smooth and uniform at its periphery, it signifies that it has not invaded the neighbouring tissues. If not sharply bounded, but melting gradually into the surrounding parts, it shows that the neoplasm is invading the neighbouring tissues. This may be proved by microscopic examination of the peripheral regions, where masses of embryonic tissue may be found in course of formation at the ex- pense of the normal elements of the tissues, (c) By interrupted or discontimtoivs invasion. The preceding mode gives ground for a serious prognosis, but less serious than when morbid masses, isolated from the principal tumour, are met with in the sur- rounding regions ; this is called discontinuous invasion, and when found it may be suspected that similar growths exist near the primary tumour in parts not excised by the surgeon. In this case secondary growths in situ, and in distant organs may be feared. III. "When new tumours of the same nature as the primary growths are developed in distant organs there is said to be generalisation ; this is also called metastasis, from a pathogenic idea not yet proved. "We have based our classification of sarcoma on the property which the various species admitted by us possess of reproducing themselves with their specific characters in secondary tumours. Thus, secondary masses arising from the generalisation of encephaloid, melanotic, and mucous sarcoma, &c., possess a structure essentially similar to that of the primary tumour. Prognosis of sarcoma. — The gravity or malignity of sarcoma depends particularly on the energy of its progressive development, continuous or discontinuous, and on its generahsation. Every voluminous tumour is serious, but besides the gravity due to its volume, sarcoma often extends to neighbouring parts and fre- quently relapses locally after ablation ; sarcomata moreover, with the exception of the angiolithic and neurogliac varieties, have a tendency to generalisation. The gravity of sarcoma, however, is rela,tive and varies according to the species. It may be said that a sarcoma is more serious the lower is its organisation, or in other PROGNOSIS OF SARCOMA. 153 terms that sarcoma, formed solely or for the most part of embry- omc elements, is much more serious than that in which these same elements show a tendency to become organised into connective tissue, bone, &c. Thus, in order of gravity, the classification of sarcomata should be: encephaloid, melanotic, colloid, lipomatous, and then fasciculated and ossifying sarcoma. The sarcoma which shows veritable osseous trabeculse is less to be feared than that which has simply undergone calcification. The more marked the tendency of the sarcoma to produce perfect tissue and the more advanced the organisation, the less serious is the sarcoma. Thus amongst myeloid sarcomata, those which most resemble the medulla of bone are more benign than those in which parts are found representing the tissue of encephaloid or fascicu- lated sarcoma. It is essential to take note of these complications, they are of great prognostic value, and explain why tumours which some authors still call ' tumours of myeloplates ' cannot always be regarded as benign. Virchow, who has made no distinction between ossifying and calcifying sarcoma, says that in a general manner they are both serious ; but by differentiating one from the other, we are enabled, on the contrary, to say that ossifying tumours, such as epules or subungueal tumours, are, as everybody knows, benign, while fasciculated sarcoma encrusted with cal- careous salts is grave, the gravity resulting, not from calcification, but from its species as a fasciculated sarcoma. Neurogliac sarcoma is grave, by reason of its situation and the extension of the primary tumour, but it never becomes generalised. The same may be said of angiolithic sarcoma, which has no tendency to generalisation, and less than the preceding to extend and become volimainous ; it very rarely causes symptoms by which it may be recognised during life, and is found by chance in persons dead of another disease. To recapitulate what we have stated with regard to the diagnosis and prognosis of sarcoma, we may say — I. That it is essential first to determine to which genus, species, and variety of sarcoma the tumour examined belongs. II. That the prognosis of sarcoma must be deduced, first from its classification in respect to its species, secondly from its mode of development, continuous or discontinuous, and finally from the presence, in more or less con- siderable quantity, of new embryonic elements in its neighbour- hood. From what precedes it is evident that, at the present day, the mode of investigating tumours is more precise than at the time when it was thought sufficient to scrape the surface of the 154 TUMOURS. section of a tumour and to look for specific cells. All the pre- ceding ideas of genus, species, variety, and mode of development, are essential to enable the surgeon to establish the diagnosis and prognosis of the tumour he is about to remove. II. — Tumours the Type of which is found in the different Varieties of Connective Tissue. Class I. — Myxoma. Definition. — Myxoma is a tumour composed of mucous tissue. Its definition is given by that of the mucous tissue itself. This tissue forms the umbihcal cord ; in the adult it is only persistent in the vitreous humour of the eye, but in the embryo is found in various parts of the body. In the embryo, mucous tissue is observed as one of the earliest phases in the development of connective and adipose tissue, so that tumours formed of it have consequently their place indicated for them between the sarcomata, formed of embryonic connective tissue, and tumours composed of perfect connective tissue. Physiologically, mucous tissue presents two varieties : 1, isolated round cells in the midst of a mucous ground substance ; 2, stellate and anastomosing cells arranged in the midst of the same substance. It is rare for myxoma to be composed solely of one or the other of these varieties, while we have never observed a tumour composed only of the first variety. Description of myxoma. — Myxoma is a gelatinous, mucous tumour, traversed by blood-vessels which are easily recognised and isolated. On scraping, a fluid is obtained resembling a solution of gum arable — milky juice is never found. In this fluid red corpuscles are found, owing to the contents of a number of divided blood-vessels having been squeezed out, and also cells of various shape, round, angular, or fusiform, many with processes. They contain one or many nuclei, and are aU pale with iU- defined borders, since they are seen in a substance almost as refractive as themselves. Hence the old opinion that myxoma bad no cellular elements. The tissue inay be studied in the fresh state. After section of the tumour, the divided surface swells in a ridge-like manner ; this may be sliced off by a second section and the raised part, though thick in the centre, is sufficiently fine at the borders to be examined microscopically. In a preparation thus made, a large meshed network of capillary vessels containing red corpuscles is SPECIES AND VARIETIES OF MYXOMA. 155 first perceived ; the nuclei of the walls and even the endothelial cells of the internal coat can be easily made out; between the vascular meshes is seen the mucous tissue, containing large, pale cells, fusiform or anastomosing by numerous processes. Besides this cellular network there are always small, round cells, un- connected with neighbouring cells, suspended in the mucous fluid. This network of cells is rendered more apparent by the addition of a solution of iodine, or of picro-carminate of ammonia. Besides these elements, elastic fibres and fat cells are often met with. Such are the general characteristics of tumours of this class. Species and varieties of myxoma. — I. Pure myxoma is composed of blood-vessels and of a mucous material, in which are distributed round or stellate cells more or less large. Fig. 76.— Section of Myxoma containing Elastic Fibres. o, stellate and anastomosing cells ; b, elastic fibres. II. Myxoma containing a considerable quantity of elastic fibres (fig. 76). III. Lipomatous Myxoma.— In the midst of the mucous tissue fat cells, isolated or massed together, axe often so abundant that it is frequently embarrassing to decide whether we have to do with a myxoma or a lipoma. The distinction is however ahnost useless for myxomatous lipoma and pure lipoma closely resemble each otheXm the histological point of view and are equally benign ^^^Bllides these three species which define themselves and require no more detailed description, myxoma often undergoes the following nutritive changes :— 156 TUMOURS. a. The blood-vessels, ill supported by an almost fluid tissue,, may become distended and ruptured — an accident less frequent than in sarcoma, for the capillary walls are comparatively more solid. This accident characterises telangiectasic and hcemorrhagic myxoma. b. The cellular elements of the tumour often undergo mucoid or colloid degeneration, which may at first sight seem surprising, seeing that myxoma is essentially mucoid. But it must not be forgotten, that in true myxoma the intercellular substance alone is mucous and that the cells suspended in it are ordinary connective- tissue cells. They are not flat, for being immersed in a fluid mass they have equal pressure on all sides ; they are composed of a mass of active protoplasm, contain one or more nuclei, and are A Fig. 77. — Section of Lipomatous Myxoma. Cells of the mucous tissue fiUed with fat ; a, uormaJ cell ; &, cell con- taining a drop of fat ; c, cell quite f uU. Magnified 250 diameters. subject to mucoid or colloid degeneration, Like many other cellular elements; when undergoing mucoid degeneration, they break down, forming a detritus, and in their place is left a mucous mass contained in a pseudo-cyst. Vascular ruptures frequently occur, and to the substance contained in the cysts is added blood which undergoes the usual retrogressive changes. Colloid degeneration of myxoma cells is generally accompanied with fatty degeneration, which aids in bringing about their death. When pseudo-cysts are formed in myxomata in consequence of degeneration or haemorrhage, the colour and consistency of the morbid mass vary so greatly, that the diagnosis cannot be made without the aid of the microscope. This variety of myxoma may be called cystic myxoma. c. Myxomata of the mucous membrane are often papillary, pedunculated, or polypoid. Such is myxoma of the nasal fossse, SPECIES AND VARIETIES OF MYXOMA. ,57 known under the name of mucous polypus. This form of polypus, developed from the cellular-tissue of the pituitaiy mucous membrane, is covered by the cylindrical, ciliated ceUs of this mem- brane. \\ hen projecting externally, it often presents at certain pomts more or less hypertrophied glandular tubes. The mucous tissue of nasal polypus is very subject to fatty degeneration and to interstitial haemorrhage. A most singular variety of papillary Fig. 78. — Hydatiform Myxoma of the Placenta. Figure borrowed from Virchow'B ' Pathology of Tumours,' and enlarged. myxoma is seen in the hydatid mole or hydatiform myxoma of the placenta. These moles are formed of round or pyriform masses of mucous tissue (fig. 78), varying in size, and bound together in great numbers by portions of the placental villi which have not undergone myxomatous change. When these moles have attained a certain size they usually vmdergo fatty degeneration and become opaque. Interstitial haemorrhage is sometimes observed in them. d. When myxoma is superficial, especially if of the polypoid IS8 TUMOURS. variety, it may inflame and ulcerate. Embryonic and pus cells are then developed in large numbers in the same way as in all inflamed tissue. e. Myxoma may also become gangrenous in its entirety or in part. The seat of myxoma is variable. It sometimes develops, as we have just seen, in the placemta, forming the hydatiform mole of that organ. In the umbilical cord of the embryo or new-born infant, small iU-defined myxomatous growths are met with, form- ing slight projections on the surface of the cord. The name of ,— It Fig. 79. — Much Atrophied Muscular Fasciculi obtained by dissociation of a myxoma de- VELOPED IN THE MASSETER MuSCLE. A, A, primitive bundles containing nuclei, « ; e, a f ascicnlus in the last stage of atrophy. myxoma should, however, hardly be applied to these, though nevertheless they must be so called, for they are sometimes found the size of a pigeon's egg. Myxoma is rather frequent in the subcutaneous cellular tissue. It alsoi invades the Tnuscles, where it is developed from the connective tissue situated between the muscular fasciculi ; the latter, separated from one another by the morbid neoplasm, become slowly atrophied, a change which is in- deed generally observed in cases of invasion of striated muscle by tumours. The primitive bundles show a multiplication of their nuclei and undergo fatty degeneration ; they become thinner at various points and may be separated into little fusiform blocks SEAT OF MYXOMA. ,5^ fsoktfd Vt '"° ^1'^ ^^' '^' '^- ''>^ ^^^'^^ -« --t-es present'th/ ^^."""^^^ ^'^^'"^ by delicate filaments which re- mroma^ ^T^ '^'^ '""^P^"** *^^^^ °f sarcolemma. In nerve. rXTto ^'^^^.^^^',it i« then generally called ,ze.™r««, owing to a confusion which it is important to avoid, for to be consisten m our classification we gfve the name o'f ne^oml only to tumours formed of nervous tissue of new formation. In Fio. 80. — Myxoma of Xerves. myxoma of the nerves, the nervous fasciculi are generally dissociated and spread out on the surface of the tumour (B, fig. 80), which therefore occupies the centre of the nerve ; but it is not always so, for the nerve tubes may be found in the centre of the morbid mass. The power of resistance which the peripheral nerve tubes offer to the compression and invasion of these tumours is truly remarkable. They do not generally undergo any appreciable jgg TUMOURS. nutritive change. This peculiarity is, however, in agreement with what we know of the resisting power of nerves to all neoplasms. In the hrain myxoma forms a greenish-coloured tumour (collo- nema of J. Miiller). The glands may. also be the seat of myxoma. It has been observed in the papillse of the kidney. In the maTrima myxoma is rather common ; like sarcoma of the mamma, it is seen under various forms. It may consist of a more or less defined mass in the midst of which a number of acini are generally found, the epithelial cells of which are hypertrophied and proliferating. It may, like sarcoma, take the papillary and budding form; the myxomatous tissue then projects into the interior of the galaetophorous ducts and acini and spreads by budding. The buds are variable in number, may be of a consider- able size, and, by distending the glandular cavity in which they are contained, may transform it into a lacunar cavity, often of great size. These lacunar cavities are lined with pavement or cylindrical epithelium. Care must be taken not tq, confound such a tumour of the breast with adenoma. This is an error all the more easy to fall into, inasmuch as the proliferation of the epithelial cells of the glandular ducts and the different changes of the papillae and buds, indicated above, may at first sight give rise to the opinion that the tumour is a cystic adenoma. The anatomical diagnosis depends upon the tissue situated between the glandular elements. "We have often witnessed singular mistakes made in the diagnosis of papillary and cystic myxoma of the breast; numerous and compHcated growths projecting into dilated glandular ducts have been taken in our presence, even by well-trained histologists, for glandular acini. By superficial observation, however, it may be ascertained that the growths are lined by epithelial and not by glandular cells. Myxoma may be seated under the periosteum, forming a lobular tumour; it is also met with in bone, particularly in the short bones, when it is generally well defined and springs from the periosteum; it has, however, been seen to develop in the interior of spongy tissue. In the sJdn myxoma often takes a papillary form. Anatomical diagnosis of myxoma. — Differential anatomical diagnosis only leads to confusion if an attempt be made to deter- mine whether a tumour be sarcoma with mucoid degeneration, or myxoma with spots of embryonic tissue. But this source of error is und^.r° by remembering that at the spots where sarcomar SS;rST.>.''r"^^^'^°"' *^^ -«« -- destroyed, whUe remamder of the tumour the proper structm-e of T sarcoma is FIBRO.irA. ,6j Eime'.itt.l '^^^ '""^'^"''^ °^ elastic fibres or true adipose ceUs immedidtely suggests myxoma. com JeSr" °' "'J^on^a.-Myxoma is not usually veiy serious. If Is mav t ''""'' '' '''''^ '''''''• If -completely exti^.ated, as may happen, particularly in soft polypus situated high up in the nasal fossae it redevelops with new vigour Hke every other tumour irntated by surgical interference which has not been suc- cessluJ. ihe contmuous growth of myxoma takes place at the expense of the neighbouring connective tissue which becomes em- bryonic, or at the expense of its own mass. In fact, nests of embryomc tissue are sometimes found in the centre of the tumour, and It IS possible that this new formation takes place by hyper- plasia of the cells of the mucous tissue. Virchow has often seen myxoma become generalised, and it is probable that the tumour is the more serious the more embryonic tissue it contains, and the more benign the more elastic and adipose tissue. Class II. Fibroma. Synonyms. — This tumour has also received the name ot fibroid or desmoid. If very hard J. Miiller called it steatoma, a vague name applied to many different species. It has also been called a fibroid body, but this expression has been chiefly applied to tumours formed of unstriped muscular fibres, which consequently are myomata. Verneuil proposed the name of fibroma, which is that generally employed and which defines the tissue, though the the word inoma, used by Paget and formed from the Greek radicle (ivos, fibre), may be preferable in the opinion of a purist. Definition. — The definition of fibroma is suppUed by that of fibrous tissue, composed, as is well known, of bundles of connec- tive tissue separated by flattened connective-tissue cells, ramify- ing and anastomosing with one another. There is also another special form of connective tissue composed of fibrillar lamellae, between which are flat connective-tissue ceUs ; this form is met with in the internal coat of large arteries and in the cornea. Both these varieties of connective tissue may be seen in fibroma. For a tumour to be called fibroma it is not enough that it should con- tain connective tissue, it must also contain no other tissue. Nearly all tumours have a fibrous framework. Carcinoma, for example, has a fibrous stroma often dense and i^redominating in certain ])arts of the tumour, but it always limits alveoli filled with cells • tumours consisting of cellulo-adipose tissue also often 1 62 TUMOURS. contain much fibrous tissue surrounding islets of fat cells ; in most sarcomata and myxomata, there are near the tumour and some- times within it fibrous tracts which generally accompany the large vessels. But in these various tumours the fibrous tissue only con- stitutes the framework supporting the most characteristic parts of the neoplasm. Fibroma on the contrary is composed solely of connective tissue. Description of fibroma. — Fibroma is a dry, resisting, pearly, rose-coloured or whitish tumour. If after division the surface be scraped with a razor no juice is obtained, but small portions are detached, which, if examined in water, seem to be entirely formed of rectilinear or undulating connective-tissue bundles ; if acetic acid be added they are changed into a homogeneous mass, in the midst of which nuclei are apparent ; but the cells, to which these nuclei belong, are somewhat difiicult to isolate. They are connective-tissue cells differing little from those of myxoma. Fig. 81. — Section of Fibroma, stained with Carmine AND treated with Acetio Acid. a, bundles of fibres cut across ; h, anastomosing connective-tissue cells. Magnified 200 diameters. Connective-tissue fibres being met with in all tumours, dissociation does not give sufficient data on which to make the diagnosis ; in fact, with regard to the differential diagnosis between carcinoma and fibroma (see later), dissociation may lead to error, as portions of hard or scirrhous carcinoma are solely formed of fibrous tissue. Sections should therefore be made of the morbid mass after hardening with alcohol, chromic acid, picric acid, gum and alcohol, or after simple dessication. Examination will then easily permit the observer to ascertain if, in the midst of the fibrous tissue, the alveoli of carcinoma, epithelial islets or unstriped muscle fibres, &c. are present. In a fine section of a fibrous tumour, bundles of fibres are seen crossing one another in various directions, as in the skin, some in a longitudinal, others in a transverse direction. LAMELLAR FIBROMA. 163 The arrangement of these bundles can be well seen if the prepara- tions are examined in water, not so well if they are preserved in glycerine, and is hardly perceptible at all if acetic acid be added. The last reagent makes the nuclei apparent and of a red culi mr, if care be taken to previously stain the section with carmine ; the nuclei and the cellular bodies surrounding them are then clearly seen to be arranged around the longitudinal or trans- verse bundles (see fig. 81). There are generally no elastic fibres in fibroma, the tissue appearing to be the purest form of fibrous tissue. This is an important point. The vessels are not abundant, and are even wanting in the species called lamellar fibroma. There are two species of fibroma : 1 . Lamellar fibroma ; 2. Fasciculated fibroma. I. Lamellar fibroma. — On serous membranes such as the pleura, pericardium, and peritoneum — particularly that fold of the peri- toneum which covers the liver and more especially tlie .sjilccn — ]•,,; S-_>._TiiANsVKiisi, Si;( rioN m- A Lamki.i.ai: Kiiikoma. hard tumours are often seen arranged in plates, villositics, or little globular masses. They are included by certain authors in the description of chronic peri-hepatitis and peri-spknitis. These tumours ai-e more or less thick and are sometimes flattened on the convex surface of the organ, so that on being divided per- pendiculariy they appear crescentic in shape ; at other times they are projecting and form one or many lobules united by fasciculated connective tissue. These bodies have a coarse analogy to cartilage. They are translucid, slightly yellow, hard and difficult to cut, resisting under the scalpel, but do not creak like cartilage when cut. The arrangement of the concentric or parallel layers of which they are composed is easily seen^^ith the naked eye ; it is this arrange- ment in flattened lamelhr which gives them the feel of extreme hardness when subjected to pressiu-e perpendicular to then- surface, ^vhile on pressing them laterally they are found to be relatively M 2 1 64 TUMOURS. soft. They are hard enough to admit of delicate sections being made in the fresh state. These when examined under water, with- out the addition of any reagent, show parallel lamellae separated by openings, resembling the layers of fibrin lining an aneurismal sac. After staining with carmine and being submitted to the action of a mixture of glycerine and formic acid, well-defined cells with flat nuclei and united together by ramifying processes are seen to occupy the openings. These preparations so closely resemble those of sections of the cornea perpendicular to its surface and stained in the same manner, that Eindfleisch has called this tumour corneal fibroTna. It contains no blood-vessels. Calcareous infil- tration is frequent ; fine calcareous granules are deposited in the ground substance, where they are at first isolated, then united into groups ; the tissue now becomes opaque, yellow, and solid, while the granules increase in size, join together, and bring about a true petrifaction. Hard and transparent plates of variable size are thus produced ; the whole fibroma may undergo similar trans- formation, but more frequently many superimposed calcareous lamellae can be distinguished, separated from one another by non- calcified fibrous tissue, while at the periphery of the indurated plate distinct calcareous granules are almost constantly met with. Such are the petrified growths which the old writers on pathological anatomy called by the name of osseous plates of the pleura, peri- toneum, &c. Calcareous degeneration in these tumours almost always begins in the centre of each lobule. II. Fasciculated fibroma. — To the naked eye this fibroma has a characteristic appearance ; it is formed of a conglomeration of lobules, each composed of a ball of fibres. On section of the tumour the centre of each lobule projects. Many similar lobules are united together by loose connective tissue traversed by blood- vessels which penetrate sometimes, but not always, into the interior of the lobules. This fibroma is formed of bundles of con- nective tissue intersecting in every direction and leaving inter- fascicular spaces in which cells similar to those of young or adult connective tissue are found (see fig. 81). The varieties of fasciculated fibroma depend upon some modifications of nutrition ; they are as follows : — a. Mulluscoid fibroma or Molluscum simplex. — In this variety there is serous infiltration as in oedema; the connective-tissue bundles remain perfectly distinct, but are infiltrated with serous fluid. h. Mucoid fibroma. — Here mucoid degeneration of the fibres MODIFICATIONS OF FIBROMA. 165 and cells has taken place leading to partial destruction of the tumour and the formation of a pseudo-cyst. c. Fatty degeneration is rare in fibroma with the exception of those of syphilitic origin. In conjunction with mucoid degenera- tion it attacks the centre of syphilitic fibromata ; it may disappear in the natural progress of the disease or as the result of tieat- ment. d. Calcareous degeneration is so frequent in fibroma that few cases of fibroma are free from it, if they have existed a long time. It begins at the centre of the lobules, that is at the points furthest removed from the blood-vessels. Yirchow admits varieties of fibroma according as it enters into combination with lipoma, myxoma, and carcinoma. It is clear that fibrous tissue is always met with in these tumoiars as an accessory eli'inent, and there is nothing essentially novel in their constitution when this tissue Fig. 8:1.— JIoLi-uscuiu Fiuikima ok JIcii.ia-sci'm Simpi.kx. Figure borrowed from Virchow's ' Putliulnp-y j£ Tumours.' exists in greater or less abundance. They are none the less lipoma, myxoma, or carcinoma. e. Inflammation occurs when fibroma takes the form of a projecting polypus. When irritated by contact with neighbom-ing solid or fluid parts it may inflame, ulcerate, and granulate, Uke other suppurating wounds. New embryonic elements are developed in the parent mass from the older ceUs, while the dissociated fibres are destroyed ; in a word, the same phenomena of inflammation occur as in normal connective tissue. The development of fascicTilated fibroma is not well understood, for these tumours are generally removed when growth is stationary or c.mpleted. We have not studied the subject from personal observation, but Forster has noted islets of embryonic tissue in growing fibroma, from which it would seem that each constituent lobule has a distinct, autogenic development. 1 66 TUMOURS. The seat of fibromata is variable. In the skkti they are generally projecting in the form of hard moles or polypi. True 'molluscum is also met with in the skin (we do not mean molluacum contagiosuTTi formed by the sebaceous glands and called by Bazin varioliform acne), and is included by some writers among fibromata. A series of lobules are found here, less defined than in other fibromata, for the whole tissue is soft. The tumours are some- times sohtary and small, and sometimes of such an enormous size that they have been known to weigh fifteen to twenty pounds. Undulating bundles of connective tissue are found in islets, saturated with serum (fig. 83), while a large quantity of fluid is present between them. 'Surrounding the bundles, cells are observed, and if the development of the tumour is active, embryonic or migratory cells are found. Molluscum is vascular throughout. Fig. 84.— Calcified Fibroma of the Maxillary Sinus. Fignie borrowed from Virohow's ' Pathology of Tumours.' In the subcutaneous cellulo-adipose tissue, particularly on the internal surface of the tibia, very dense and small fibromata are met with, varying in size from that of a millet seed to that of a pea. In the same subject, they may be found at different periods of evolution and calcareous infiltration, petrified only at their centre or throughout the whole mass. They are generally encysted and siurounded by a true serous bursa, and though often attached to the cyst-waU by a more or less lengthened pedicle they are mobile under the skin. Fibroma of the mucous membranes is rare; less frequent in this position than myxomata or tumours formed of unstriped muscular fibres. In the breast fibroma shows itself under two forms. It may be a homogeneous mass and correspond to the description given of fasciculated fibroma (the fibroid body of the breast of Cruveilhier), or it may be complex and accompanied by proliferation of the epithelium lining the acini and ducts of PROGiXOSIS AND DIAGNOSIS OF FIBROMA. 167 the glands. The galactophorous ducts increase in size and are transformed into true lacunar cavities, into which fibrous and generally vascular growths project (6, fig. 85), these growths being lined with epithelium (see c, fig. 86). In the 'periosteum, fibroma is frequent. With regard to the differential anatomical diagnosis between fibroma and sarcoma of the periosteum, Virchow insists that fibroma does not invade bone like sarcoma. Fibroma is, in fact, always distinct from neighboming tissues, while sar- coma is surrounded by an invading peripheral layer of embryonic tissue. Eetro-pharyngeal polypus is generally a fibroma developed in the periosteum of the bones at the base of the skull. Virchow describes small fibromata of the Jcidney situated at the union of the cortical and medullary substance, but as interstitial nephritis is always present in such cases these are no more fibromata than those collections of fibrous tissue which are always found in cirrhosis of the liver. Prognosis of fibroma. — Fibroma is benign and generally Fig. 85.— Lacunar Fibroma of the Breast. Figaro boiTOwod from Virohow's ' Pathology of Tumours.' solitary. It does not relapse after removal, though retro-pharyngeal fibroma seems to be an exception to the rule ; this form of fibroma certainly relapses frequently, but to establish the gravity of the species we must be sure that the whole tumom- has been removed, and that the anatomical diagnosis has been con-ect. ISIolluscum is sometimes serious by reason of its extension to a great number of spots on the skin, or of its great size. We may say, however, that all things being equal, fibroma is less serious than myxoma ; this is comprehensible as mucous tissue is more neai-ly allied to the embryonic tyiie than fibrous tissue. The anatomical diagnosis of fibroma is easy. The cystic variety of sarcoma and myxoma is the sole form of tumour which mavbe confounded with certain mucous fibromata ; but data tor solution of the problem are always to be found in the periphery of the cys-ts. 1 68 TUMOURS. Class III. Lipoma. Synonyms.— Cruveilhier proposed the name of adipoma for this tumour, but it is not so good as that of lipoma, for the radicle is latin. When a lipoma was firm it was formerly called steatoma. Cruveilhier also called it adipo-fibroma. Definition.— The definition of lipoma is given by that of the cellulo-adipose tissue of which it is composed. Normally cellulo-adipose tissue is formed of vesicles which are spherical, or polygonal from reciprocal pressure, the vesicles resulting from the accumulation of fat in embryonic or connective-tissue cells, the nuclei of which are pushed towards the periphery. The adipose vesicles are contained in a network of capillaries, and form Fig. 86.- -Papillaey Fibroma of the Bkeast. Fibrous vegetations projecting into the galactophorous ducts which have become cystic ; they are liied by epithelium at c, and denuded of it at rt ; 6, connective-tissue cells. Magnified 300 diameters. little groups separated from one another by fibres of connective tissue. Every circumscribed collection of adipose tissue is not necessarily a lipoma. The mass of adipose tissue which replaces an atrophied organ, or the presence of a large quantity of adipose tissue in the great omentum or other parts of corpulent subjects, does not constitute lipoma. This name must be reserved for cir- cumscribed masses of adipose tissue having, up to a certain point, a vitality independent of that of the rest of the organism. This independent vitality is demonstrated by the fact that an individual affected with lipoma may emaciate without the tumour diminishing in size, which is not the case with other adipose deposits. Description of lipoma. — Physiologically, adipose cells are SEAT OF LIPOMA. 169 grouped together to form lobules of fat. These lobules are also met with in lipoma. The adipose vesicles are large and sur- rounded by a cell wall which is easily seen ; the nucleus is also distinct. The lobules are larger than normal, and to this pecu- liarity of structure is due the feeling of softness and false fluctua- tion which is characteristic. The appearance of lipoma and its complete resemblance to subcutaneous cellular tissue renders the employment of the microscope for its recognition^ rarely necessary. Microscopical examination is only useful to ascertain certain forms or varieties of lipoma, and certain modifications of nutrition, which it sometimes undergoes. Lipoma varies in size from that of a cherry to those colossal dimensions which make this tumour the heaviest which afflicts the human species. Lipoma may be lobu- lated, diffuse, or distinctly defined ; it may be found in the form of polypus, solitai-y or multiple. Weber has counted 200 on the I'll;. IS7. — Ai>ii'iisr'; Vi:sici,i;s khoji a Lirnir.v. (I, cill wall ; &, Tat drop. ^lagnifleJ 3U0 diameters. same subject, and there are similar observations which suggest tlie idea of a lipomatous diathesis. With regard to the seat of lipoma it is frequently observed in the areolar tissue of the skin, where it is often pedunculated. In the subcutaneous cellular tissue it is capable, in certain regions, of becoming displaced by its own weight ; a lipoma is said to have been seen to descend, under the skin, from the umbilicu.s to the perineum, its form being preserved. In the stomach and intestines pedunculated lipomata have been seen to project into the cavity of these viscera. As cellulo-adipose tissue does not exist normally in the sub- mucous tissue of these cavities, lipomata must here be regarded as heteroplastic -an example of the inanity of the idea that heteroplastic tumours are synonymous with malignant tumours. Certain serous membranes normally possess villous gr.iwths composed of adipose tissue, such as the appen- dices epiploic,'' of the large intestine, which iumv hyijertrophy, become detached and fall iuto the peritoneal cavity, where as we 170 TUMOURS. have said above they undergo fatty or calcareous degeneration ; such are also the synovial frmges which may likewise become lipomatous (the arborescent lipoma of 0. Weber). In muscles, fat cells are grouped parallel to the muscular fasciculi, and may become the seat of lipoma. The muscular fasciculi remain normal, which is not generally the case when neoplasms invade muscular tissue. Lipoma of the hones is rare. "We have seen one example of it in the body of the femur. The compact tissue of the bone was here transformed into a spongy tissue with thin trabeculse and large aveoli filled with adipose tissue ; the stroma of the tumour, instead of being formed as in lipoma generally of fibrous tissue, was composed of osseous trabeculse. Lipoma of the glands, particularly that of the breast, may acquire a con- siderable size. In the breast, the adipose tissue of new formation is disposed around the galactophorous ducts and acini; the organ preserves its form, but acquires an enormous size and weight. When the cellulo-adipose tissue surrounding the hid/ney or lymphatic glands greatly hypertrophies a capsular lipoma is said to be formed ; atrophy of the organ thus enveloped is not a necessary consequence. Varieties of Lipoma. 1st. Pure lipoma, composed simply of pure cellulo-adipose tissue and a small quantity of connective tissue surrounding the lobules. The latter are large and well defined and distinctly give the characteristic sensation of false fluctuation. 2nd. Myxomatous lipoma is that in which mucous tissue is found between the adipose vesicles ; it does not differ from lipo- matous myxoma (see fig. 77). 3rd. Fibrous lipoma is that in which connective tissue is very abundant. This is the adipo-fibrous tumour of Cruveilhier, and the steatoma of the older writers. To diagnose this variety of tumour histological examination is necessary, as otherwise it might be confounded with pure fibroma or carcinoma. 4th. Osseous lipoma is represented by the solitary case we have given above, in which the tumour was traversed by osseous trabeculse. 5th. Erectile lipoma. The blood-vessels are very nuraerous and distended, particularly when the tumour projects on a serous or mucous membrane. DEVELOPMENT OF LIPOMA. 171 The nutritive changes to be studied in lipoma are : — a. Fatty degeneration which seems a mere pleonasm. The fat vesicles break down into fine granules, and in the place of large cells or vesicles filled with a single drop of oil, there are granular bodies. To the naked eye the tissue is then opaque, grey in colour and of a peculiar consistence, resembling that of a sarcoma or carcinoma undergoing fatty degeneration. b. Pedunculated lipomata may become necrosed by their pedicle being ruptured and falling into a natiu-al cavity. This occurs especially in the peritoneum where, by the hypertrophy of the appendices epiploicse, they become in fact small, fatty polypi ; on becoming detached and falling into the peritoneal cavity they break up, their fat is decomposed, fatty acids are set free and cholesterin separates, while the capsule which surrounds the little tumour grows in density and constitutes a cystic envelop. c. Calcareous degeneration may take place and stony masses be produced. d. Projecting and voluminous lipomata are often affected by infiammation and ulceration. Embryonic tissue is developed, the fat vesicles are partly absorbed, while the tumour becomes harder. Development of lipoma. — The development of lipoma is little understood. Forster considered that lipoma was developed from a mass of embryonic tissue, the cells of which were afterwards infiltrated with fat. He adduced this opinion from the fact that islets of embryonic tissue are sometimes found in the centre of lipoma. Virchow thinks that the adipose tissue of lipoma pro- ceeds from mucous tissue. There is, it is true, a close relationship between mucous and adipose tissue ; mucous tissue represents in fact a stage in the development of connective tissue, and tumours in which mucous and adipose tissues are mixed in different pro- portions are not rare (mucous lipoma or lipomatous myxoma, see fig. 77 ). Forster explains the growth of lipoma by another theory ; he mentions having seen the adipose cells elongate, become restricted at a point, and divide. This would be a true proli- feration of fat vesicles. ^Ve think that there is here an error of interpretation. Adipose cells are indeed so easily deformed by pressure, that in preparations of them they may be observed elongated and bean-shaped, without their being necessarily m process of division. Although embryonic cells or mucous tissue cells mark the first step in the neoplasm, it is m these cells, which are but slightly differentiated from one another, that 172 TUMOURS the fat is deposited. This is the ordinary mode of development and the one best understood. Prognosis of lipoma. — Lipoma is serious only when from its volume it prevents the performance of some function, or when it gives rise to inflammatory accidents, for example, inflammation of a serous membrane. The anatomical diagnosis is so easy even with the naked eye that there is no necessity to insist upon it. Class IV. Carcinoma. The class Carcinoma comprehends those tumours, which by their aspect and gravity seem removed from the other classes of tumours, the type of which is found in the connective tissues. They never- theless belong to them by reason of their origin, their mode of development, their constitution, and particularly their stroma, the essential element in their definition. Synonyms. — Carcinoma is also called alveolar, scirrhous, and encephaloid cancer. The word ' cancer ' is vulgarly given to any malignant tumour which spreads rapidly and causes secondary growths ; but though thus employed by most medical men the term has no histological signification and defines no tissue. The words encephaloid and scirrhous correspond to varieties of carcinoma and have a meaning based on gross appearances. A tumour which resembles softened cerebral substance is called encephaloid, while a hard tumour is scirrhous. Carcinoma was formerly considered by pathological anatomists to be characterised by a so-called cancer juice, discovered by Cruveilhier, but, as we have already shown, this juice may be obtained from sarcomata, which also often have the appearance of encephaloid and scirrhous tumours. The words 'scirrhous' and 'encephaloid' as understood by the old writers no longer describe a definite tissue. Definition. — The word carcinoma, first employed in Germany in the same vague sense as cancer, has lately received a more precise definition based on histological study. It is, however, not yet sufficiently rigorously defined, since Forster, for example, speaks of ' carcinoma properly so called ' and ' epithelial carcinoma,' the latter being cancroid or epithehoma, quite distinct from carcinoma, as we shall see further on. This confusion is due to the fact that the true characters of carcinoma and epithelioma have not been recognised. The latter has the structure and mode of develop- ment of epithehal tissue, while carcinoma belongs to the con- DEFINITION OF CARCINOMA. 173 nective-tissue type. The word ' carcinoma ' is not of more value than that of cancer, both having the common root cancer, crab, from a gross resemblance certain tumours, traversed by superficial veins, have with this animal. To be logical and to give each tumour the radicle of the tissue it apjiroaches nearest, carcinoma should be called alveolar fibroma ; nevertheless, not to change a name received and adopted by all, we will continue to employ the word carcinoma defining it in the following manner: Car- cinoma is a tumour coTnposed of a fibrous stroma limiting Fig. 88.— Cells from Carcinuma Juice. n tailed ceUs : b, round ceUs ; c, prismatic cells ; rf, toiform 'oeUs- c an hour-glass-shaiiid ceU ; /, A, ceUs midergomg mu^id degeneration (the pLysaUphorous cells of Virchow). alveoli, which by communicating xvith one another form a cavernous system; these alveoli are filled wUh free cells separated from each other only by a more or le3s abundant •^"'Leral description of carcinoma.-The contents of t^he alveoli and the stroma are the parts to be studied. The contents of the dveoli form the milky juice of cancer. It is easily squeezed from ?he cavernous tissue in which it is contained by scraping or by pressTe! When this juice is examined under the rnier,. scope, a ?arge number of carcixioma cells of every conceivable vanety of 174 TUMOURS. shape and size are observed. Some are round, small, and measure 9 /A or 10 /i, others also spherical, but larger, and may reach 20 /I., 40 fi, or even more ; some are polygonal, with rounded or extremely sharp angles — such are the tailed or racket-shaped cells, one extremity being elongated while the other is enlarged. Nothing can be more varied and unexpected than the forms ; some carcinoma cells appear flat when their surface is seen, and narrow viewed in profile, which may be well observed as they roll over and over under the eye of the observer; they may be elongated in a fusiform manner, like the cells of fasciculated sarcoma. A similar variety of form, though less pronounced, may be, as we have seen, met with in sarcoma. All the cells have one or many nuclei ; there are sometimes as many as fifteen or twenty in one cell ; they are spherical or oval, and contain one or many nucleoli, generally well developed. The nuclei are large and from 9 /a to 20 /x. or 30 ^L, the nucleoli themselves sometimes measuring 5 /* to 9 ^. When large they appear vesicular ; the nuclei are surrounded by a double line as if they possessed an enveloping membrane. Similar forms of nuclei and nucleoli are met with in sarcoma, sometimes even in purely inflammatory neoplasms ; they therefore, no more than the cells, can assist in defining carcinoma ; neither can the polymorphous state of the cells be depended upon to characterise carcinoma, for in some tumours all the cells may be similar, either round or polygonal. Carcinoma cells are polygonal by reciprocal pressmre when contained in a cavity where the intercellular sub- stance is slight. The anatomical reason of this form of the cells is the same which determines the tesselated form of epithelial cells, and from this resemblance some authors have concluded a natural analogy, and the terms epithelial or epithelioid have been used to designate carcinoma cells. These cells seem to have no enveloping membrane and are not cemented together, which fact diiferentiates them sharply from epithelial cells. They are subject to various nutritive changes. Sometimes they swell and become spherical as if infiltrated with serum. Often the nucleolus enlarges so as to fill the nucleus ; hypertrophy of the nucleolus may be so great as to make the nucleus vesicular — such are the physaliphorous cells of Virchow (A, fig. 88). Similar vesicles are produced, not by the dilatation of nucleus or nucleolus but in the midst of the protoplasm itself, by a mechanism similar to that described by Dujardin when little cavities are hollowed in sarcode by the action of water. In these sarcodic vesicles, better called vacuoles, free granules are often present. Carcinoma cells under- THE STROMA OF CARCINOMA. 175 go Other changes of nutrition which we shall consider when treating of the varieties of carcinoma. The stroma, the second essential constituent part of carcinoma, may be studied in dissociated fragments of tumours, or in sections Irom Iresh or hardened specimens. It is composed of fibrous trabeculae united so as to form a continuous system, each fibrous trabecula representing one or more bundles of connective tissue, between which are scattered ordinary connective-tissue cells, or cells slightly differentiated from them (fig. 91). These cells are indistinct if examined in the fresh state, but if acetic acid be stroma of carcinoma, from which the cells have been brushed away. Magnified 300 diameters. added, the nuclei become distinct, the fibres swell, and the tra- beculae become transparent and homogeneous. It is still an open question if carcinoma contain lymphatics ; Schroeder van de Kolk has injected them, and Kindfleisch thinks they form perivascular sheaths similar to those of the nerve cells. We will return to this point. When a very delicate section of carcinoma is examined, the cells being still in situ, it may be thought that each alveolus is closed, but, if the section be a little thicker and the cells be removed by brushing them away with a camel's-hair brush, it is easily seen that the tissue is cavernous, the cavities communicating with one another. For example, two cavities may be seen com- municating with a third situated beneath them (see fig. 89). 176 TUMOURS. Development of carcinoma. — The study of the development of carcinoma throws much light on its nature. To take first the development of carcinoma in bone, as an example, we observe that, at the beginning, the same phenomena occur as in inflammation. In the case of a short bone, the fat vesicles disappear and give place by proliferation to embryonic cells, the osseous trabeculse are partially absorbed, and medullary spaces limited by festooned lamellae are seen filled with embryonic medulla, as in rarefying ostitis (see fig. 185). This irritative process may end in a new formation of osseous tissue, when sclerosis of bone or condensing ostitis is produced. These phe- nomena of rarefying or condensing ostitis are the first phase, or the uncertain stage, in the development of primary carcinoma of Fig. 90. — Development or Caeoihoma in the Bkeast. Section made after hardening in chromic acid. A. Plasmatic spaces wliich enlarge by tlie mnWplioation of their cells ; at c they haTe preserved their angular form • at D they have become globular and form the alveoli of carcinoma. MaKnified 160 diameters. the bone. Soon, however, the embryonic tissue is transformed into fibrous tissue, which is the second or fibrous phase. The cells contained in the fibrous trabeculse give origin to a more or less con- siderable number of small cells, which are in close contact and packed together in a small space; by multiplying, these cells enlarge the spaces containing them and assist in the formation of the first alveoli of carcinoma. In the mamma, a similar develop- ment is observed. The trabeculse of fibrous connective tissue, which enter into the structure of the gland and spread out thence into the neighbouring adipose tissue, thicken and become infil- trated with fluid. If a section be made after hardening and staining DEVELOPMENT OF CARCINOMA. 177 with carmine, it can be seen that the qiaces included between the connective-tissue fibres contain globular cells isolated or united into groups, and that the formation of the alveoli of carcinoma is by the progressive growth of these groups of cells (see figs. 90 and 91) contained within the fibrous trabeculae. These by their growth cause the absorption of the surrounding fibrous tissue which, on the other hand, becomes denser under the pressure exercised by the newly formed cells ; this pressure exercised equally in every direc- - tf^ ^j^;«;j* ^^^|f:■-•'J_^ '/ ^ J T Fig 91 -Development of C.MiCiNnMA in a Small RECENr Nodule mtdated IN A Fibrous Tract, nicak a Frimauy Tum.hu of the Breast. . hnnrilM nf flbroiia tlssuo sliowliiK connootivo-tissue colls between them ; o, carctDomtt celU kS^fdto^onXi^in^veiu between the fibrous bundles. Magnified 2U0 dmmet^rs. tion, is also probably the cause of the tendency the alveoli show to take the spherical form. In carcinoma of the mamma the cellulo-adipose tissue is pre- served ; the tumour increases, in fact, at the expense of the con- nective tissue of the trabeculae which separate the lobules of adipose vesicles, the latter, however, remaining for a very long Uinr intact in the midst of the morbid mass. The preser^-ation of these adipose angular masses, seen on section of a tumour to be irregularly disseminated, has many times aided us m ascertammg with the naked eye the cai-cinomatous nature of a tumour; a 178 TUMOURS. diagnosis always verified by microscopical examination. The integrity of the adipose cells is explained by the fact, that in the breast, carcinoma develops chiefly in pre-existing fibrous tracts, and not firom previously formed embryonic connective tissue. In the glandular tissue, in the acini and ducts, very interesting phenomena are at the same time taking place. The epithelium of the acini and ducts proliferates in consequence of the irritation in their neighbourhood; the acini become filled with cells and hypertrophy, so that it might be thought, there was a direct relation between proliferation of the epithelial cells and development of carcinoma ; it has even been maintained that a carcinoma is a new gland destined to eliminate poisonous products from the organism, in the same way that the kidney eliminates urea. This view of the humoralists is, however, invali- dated by the fact that removal of the tumour does not cause poisoning, but is on the contrary the only remedy. On the exist- ence of new epithelial tissue in the acini and ducts of the mammary gland affected with carcinoma, is founded the idea of the analogy between the latter and a gland, an idea, which the development of the tumour as described above, is sufficient to destroy. In epithelioma, on the contrary, new epithelial tissue is never seen to be developed in isolated centres between adjoining bundles of connective tissue, but from masses of embryonic tissue, and in the form of buds springing from pre-existing epithelial tissue. Sympathetic irritation of the glandular acini and ducts gives rise nevertheless to rather important phenomena, to which attention is drawn. The epithelial cells of the galactophorous ducts multiply and fill up the lumen of the ducts, so that they appear like solid cylinders. On transverse section, the ducts are seen to be filled with epithelial cells cemented together and adherent to the walls, whilst the centre is occupied by round, opaque cells, undergoing fatty degeneration, free or united to- gether so as to form a kind of plug, in which case the ducts are distended and filled with a grey or yellowish caseous mass. Their direction may be easily followed by a section of the breast passing through the nipple and the morbid mass. There is often during life an ichorous discharge fi-bm the nipple. At their fur- ther extremity the degenerated ducts terminate in irregular sinuous spaces corresponding to the destroyed acini, in the place of which there are often true cysts. These cysts are round or cavernous, sometimes large, and filled with a mucous or serous fluid, or with a detritus in which cellular elements, free fatty GROWTH AND VARIETIES OF CARCIXOMA. 179 granules, and even blood pigment may be recognised. In all tumours of the breast, the galactophorous canals are the seat of changes and cysts similar to those described above ; ichorous discharge from the nipple is, however, only observed in carcinoma. The growth of caroinoma is at the expense of its own mass, or by invasion of neighbouring tissues. The proof that the tumour grows at the expense of its own tissue is, that in hardened sec- tions spaces filled with cells are found in the trabeculse of the fibrous stroma ; these are in process of development into carcino- matous alveoli. Growth by invasion of neighbouring tissues may be continuous or disccmtinuoua, both modes being common in carcinoma. In continuous development the tracts of fibrous tissue which spread out from the breast into the adjacent parts undergo carcinoma- tous metamor]:)hosis. Secondary growths in organs far removed are preceded by induration and increase in the size of the glands communicating with the lymphatics of the tumour. How is it that carcinomii is the pathological tissue which most easily and almost invariably determines lesions of the lymphatic glands? It is because the alveoli of carcinoma are in direct communication with the lymphatic vessels. This communication may be easily demon- strated by injections. If with a Pravaz syringe, provided with a finely pointed canula, Prussian blue be injected into the alveoli of carcinoma, the injected fluid first fills the alveoli, mai'king out a more or less extensive cavernous system, and then penetrates into the lymphatic vessels issuing at the wound made in the opei-ation. For the injection to be successful the tumour should be intact. Indurated glands in carcinoma do not always show, at the com- mencement, the structure of the primary tumour ; sometimes they simply undergo fibrous change ; but in the newly formed fibrous tissue alveoli are soon developed. These facts, which are often very marked, have nevertheless escaped the observation of writers preceding us ; they, however, appear to us to be of great importance, for they lend support to our views as regards the morphological signification of carcinoma. Varieties of carcinoma. — It is not possible to classify carcinoma according to the dimension or form of its cells, for they are often extremely variable even in the same tumoiu. Generally the softer the carcinoma the larger the cells, the harder it is tJie smaller they are. This is however not an absolute rule. The round or polygonal form of (he cells is solely due to the larger >>r i8o TUMOURS. smaller quantity of intercellular substance present. We classify carcinoma according to the state of the stroma and the nutritive modifications of the cells. I. Fibrous or scirrhous carcinoma. — When the trabeculse are thick and resistant the carcinoma is called hard or scirrhous. In fine sections the fibrous trabeculse appear attenuated, homo- geneous and highly refractive ; granular degeneration of the cells contained in the alveoli is often observed, or the cells may be destroyed and the resulting detritus is carried away by the lymphatics ; the morbid tissue then shrinks, so that the alveoH, in which a little fluid and some fatty granules still remain, are IiG. 92. — Aneuiiismai, Dilatations ok Capillary Vessels in Encephaloid Carcinoma. Magnified 50 diameters. almost effaced ; the tumour is then called atrophic scirrhus. This atrophy does not take place in all parts of the tumour at the same time ; it generally invades the centre. This part then yields no juice on section, but juice is obtained from the periphery where alveoli filled with cells are still to be seen. In the parts most profoundly atrophied, and where more or less ulcera- tion is also frequently present, the shrunken stroma sometimes contains a great number of large elastic fibres in masses or arranged in parallel lines, or tangled together in a most irregular and intricate manner. Infiltration of the glands is soon observed in scirrhous cancer, but secondary growths are formed but slowly in most of the organs and tissues, while the primary tumour ENCEPHALOID CARCINOMA. iSi increases slowly, or may remain stationary, or indeed almost entirely disappear. II. Encephaloid or medullary carcinoma. — The trabecule? are more delicate and the alveoli larger in this species than in the preceding; they may even be so large a? to be visible to the naked eye. The stroma is weak and interstitial haemorrhages are frequent, so that in section the tissue is variously tinted, white, grey, rose-coloured, red, yellowish and even brown, owing to the changes of the extravasated blood. The primary tumour grows much more rapidly than scirrhus, but secondary gi-owths are generally less extensive. Two varieties of encephaloid carcinoma may be distin- guished : — l'"i(^ 93. — lii.iniii-vi:.-..-Ki.s 111 jiDiNu (IN iiiK Walls ok an j\L\Ki1H'S. Magniflod ISO diameters. The pultaceous form, in which the tissue is extremely soft, and out of the alveoli, which are very large, may be pressed a thick and abundant juice. Erectile or hcematode carcinoma. — In this variety, often associated with the preceding, the blood-vessels, which are numerous and well developed, present moniliform dilatations (see fig. 92) as well as little aneurismal tumours, visible to the naked eye as minute red points. The blood-vessels project into the interior of the alveoli and bud on their walls (see fig. 93) ; they often rupture and cause extravasations of blood. The softness of encephaloid carcinoma maybe solely due to the fact that the alveoli though small, ai-e separated by di\isions of extreme delicacy. 82 TUMOURS. The following three species of carcinoma are produced by nutritive changes in their cellular elements. III. Lipomatous carcinoma. — The cells in the alveoli may become filled with fat droplets and resemble adipose vesicles ; but they are not grouped together by bands of connective tissue, nor by capillary blood-vessels like the adipose globules of subcutaneous cellular tissue. We have twice observed this form of carcinoma, notably in the bones. It so closely resembles lipoma that it may, at first sight, be confounded with it, if all the elements of the problem be not considered. The cells are not destroyed by the Fig. 94. — Colloid Cakcino.ma. m, thick fibrous trabeculse ; m, thinner trabeoulse containing cells in a state of mucoid degeneration, and limiting alveoli filled with cells, which have also undergi.ne mucoid degeneration. Magnified 300 diameters. adipose infiltration. We have seen one example of generalisation of lipomatous carcinoma, in which all the secondary growths pre- sented the same characters ; this fact justifies our describing it as a distinct species. IV. Blucoid or colloid carcinona.— Colloid degeneration of car- cinoma cells gives them a characteristic, gelatiniform appearance, which is reproduced in the secondary growths. Thus it is a distinct species. The alveoli of coUoid carcinoma do not difier from every other form of carcinoma ; the trabeculse are only easier to see being filled with a mucoid fliiid. The cells, infiltrated with droplets of muciu, become spherical aud vesicjalar, and are finally destroyed. MUCOID AND MELANOTIC CARCINOMA. ■83 Those which persist sometimes attain an enormous size ; but there are only a few in each alveolus suspended in a fluid equally mucoid. The alveoli distended by the fluid become regularly spherical. As is always the case in mucoid degeneration, there is also some fatty degeneration of the cells. The stroma of the tumour may be un- modified, sometimes the trabeculae are cedematous and the fibrils separated by a fluid substance, or they may also undergo mucoid degeneration and become much thinner or be destroyed. The morbid mass may then contain portions, more or less extensive, in which colloid change is so marked that they seem simply formed of an amorphous substance containing scattered groups of cells. To the naked eye these groups of cells appear as so many small Fui. ll."l. — CkLT.S .11- CoI.T.Cilli Cahcinoma. II liiiK'' Lvll oii.'losins anothrrceU: rf, mother-coll ; f, cells liiHltiatpil «ilh c.iUoid nintvrlal ; 6, cell fllli'd with a colloid .^r.ip; f, i-ills uducud to a ttlm uudei'eoing destruction. Jlngnifled 3S0 diamet-TS. opaque spots. Generally some connectivi-tissue fibres, ares of circles limiting spaces, remnants of the old trabeculae, remain around these groups of cells (fig. 94). The tumour is not homogeneous, and the alveoli, which have undergone such advanced colloid degeneration, form groups separated from others by ordinary fibrous tissue. It is this arrangement which to the naked eye gives the tumour an a'veolar appearance. The blood-vessels of colloid carcinoma are often dilated, and sometimes rupture and cause extravasations of blood. V Melanotic carcinoma.— .Alelanotic carcinoma is rarer than melanotic sarcoma. In this species the cells in the alveoli show melanotic granules in their interior. The trabeculse may also 1 84 TUMOURS. become infiltrated with the same granules, which are then deposited in the connective-tissue cells proper to the trabeculse. Independently of the preceding species, each of which possesses the property of producing secondary growths having its specific characters, the following changes may be observed in every carcinomatous tumour : — a. Fatty degeneration. — In every old carcinoma, parts varying in extent, those at the centre in particular, present traces of fatty degeneration. In an alveolus, for example, some cells are found filled with fine, fatty granules, looking with a low power like opaque blocks, and not differing from granular bodies except by their larger size due to the dimensions of the carcinoma cells. When fatty degeneration is very marked, the parts affected are yellow and more or less opaque. The capillary walls and the protoplasm of the connective-tissue cells of the stroma may also be affected with the same degeneration. The intra-alveolar cells being destroyed and the degenerated trabeculse broken down into Fig. 96. — Granular Bodies and Free Fatty Granules OBSERVED IN CARCINOMA, ALSO IN CeREERAL SOFTEN- ING AND IN Fatty Degeneration generally. Magnified 300 diameters. a detritus which is taken up by the lymphatics, a shrinking or partial atrophy of the timaour results. In secondary deposits in the serous membrane or liver, this atrophy is characterised by a falling in of the centre which originally projected. In the skin, and particularly in the mammary gland, atrophy is shown by a depression in the form of a hard or callous cicatrix. h. Caseous degeneration. — In all rapidly growing tumours, car- cinoma in particular, obliteration of the vessels may occur, caused either by fibrin, or by excrescences or buds forming on the veins. These buds, generally supplied with blood-vessels and composed of carcinomatous tissue, may be developed at a distance from the primary tumour ; they thus form true cancerous emboli. They are more often observed in the portal vein, and in the iliac and axillary veins, when the latter traverse the centre of a primary tumour, or are surrounded by degenerate lymphatic glands. The parts of the morbid mass deprived of the circulation of the blood are slowly destroyed, ulceration resulting if the tumour INFLAMMATION OF CARCINOMA. 185 projects upon a cutaneous or mucous surface, or infarcts if seated within a viscus. These infarcts undergo caseous melting; the softened parts are taken up by the circulation, and a depression is produced. Infarction is recognised when the small vessels are found filled with a granular mass. WTiether consequent on initial fatty degeneration, or on arrest of the circulation, whether slow or rapid, this atrophy characterises a distinct clinical variety, atrophic scirrhus, scirrhus in cuirass, the fibrous carcinoma of Billroth. If fine sections be examined, parts of the tumour seem formed of a fibrous tissue, in the meshes of which only a few fatty granules are found ; the alveoli, the cells of which have been destroyed, are collapsed, in proof of which they may be compared with other parts, where the carcinomatous tissue is in a less senile condition. Calcareous transformation is rare in carcinoma. Near to bones, however, the stroma may sometimes undergo this change, producing what has been incorrectly called ossifying carcinoma. (Paulicki). c. Inflammation of carcinoma. — Carcinoma may become in- flamed and ulcerated, either as the result of traumatism or by progress of the tumour. What occurs is very interesting and aids, together with development, in explaining the true nature of car- cinoma. An active proliferation of the cellular elements con- tained within the alveoli is observed near the ulcerating point, the cells divide and give origin to elements having all the charac- ters of embryonic cells ; they measure 8 fito 10 /x, but the granular and refractive protoplasm of which they are composed mask their nuclei. The alveoli break down and are lost in a mass of em- bryonic tissue, in the midst of which are still found a few fibrous trabeculae of the stroma. The embryonic tissue, which constitutes the base of the ulcer, takes on the surface the form of highly vas- cular granulations. The newly formed vessels, the walls of which ai-e composed of young cells, resemble those of granulation tissue. Thus the cells contained in the alveoli take the embryonic form as a consequence of the irritative influence of inflammation. A simi- lar change is never observed in the cells of epithelioma. d. Villous carcinoma. — Whatever may be the variety of carci- noma, if it attacks a cutaneous or mucous surface, granulations spring up on the sm-face inmiediately after ulceration. These villous granulations are sometimes much longer than simple granulations, and are also numerous and pressed together. It is these which gi\'e the tumour the name of villous carcinoma. The blood-vessels, not being sustained by a solid framework, pre- 1 86 TUMOURS. sent small aneurismal dilatations, and are often the point of departure of repeated and considerable hsemorrliages. Anatomical diagnosis of carcinoma. — The anatomical diagnosis of carcinoma is very difficult to make with the naked eye. Patho- logists have indeed in the past confounded carcinoma with every malignant tumour, and even with infarcts, till recourse was had to microscopical examination. The presence of the so-called cancer juice is not sufficient. We have seen that a similar fluid may be obtained from sarcoma a short time after removal, and always from tumours on the cadaver twenty-four hours after death ; we shall find that a similar fluid can be obtained from soft epithelioma and from lymphadenoma whatever may be its seat ; the same with infarcts and tissues aff'ected with diffuse suppuration. The cells of carcinoma have in themselves nothing characteristic ; to be certain of the presence of carcinoma it is necessary to recognise the alveolar nature of the stroma and the form of the contained cells. Sections, delicate enough to submit to microscopical examination, can be made in the fresh state, if care he taken to moisten the surface well and not to press hard with the razor ; no error is possible if the preparation be previously hardened in a •2 or -4 per cent, solution of chromic acid, or in alcohol, picric acid, or in gum and alcohol. The peculiar cavernous arrange- ment of the stroma of carcinoma always differentiates it from sar- coma, in which fibrous trabeculse parallel to the vessels may be met with, but never regular alveoli. Colloid carcinoma, which with the naked eye may be confounded with myxoma, differs from it by its alveolar stroma ; in myxoma not only is there no stroma, but a perfectly characteristic network of anastomosing connective- tissue cells may be observed. Atrophic carcinoma may be con- founded with fibroma, if the collapsed alveoli of the atrophied parts are only examined ; but the unmistakable characters of the peri- phery of the tumour will remove all hesitation. On the other hand, in fibroma there are never free cells comparable to those contained in the alveoli of carcinoma. The anatomical diagnosis of carcinoma and epithelioma will be made when treating of the latter. Prognosis of carcinoma. — Whatever may be the seat, the species, or the variety of carcinoma it is always fatal ; but the dura- tion of the disease and consequently its gravity varies according to the species. The encephaloid form is that in which the primary tumour most rapidly acquires a great size by invading neighbour- ing tissues; the scirrhous, particularly the atrophic variety, is remarkable for the slight tendency the primary tumour has to SYPHILITIC GUM M ATA. 187 extend, and for the slowness of its growth. In infirmaries this form of tumour may be seen dating ten or fifteen years back ; but nevertheless it always terminates by the production of secondary growths extending to the greater number of organs the longer the disease has been established. It is diflficult to decide if generalisation is due to the particular species of tumour or to its long duration ; indeed, encephaloid carcinoma may become very rapidly generalised. We must draw attention to the fact that the development and generalisation to many organs of little secondary nodes of scirrhus does not always cause death rapidly, though such is constantly the end. Carcinoma is developed primarily in all the organs, but viscera lined by mucous membrane and glands, especially the stomach, uterus, and breast, are more frequently attacked by it. The primary tumour constantly infects the corresponding lymphatic glands. We have now completed the description of those tumours composed of connective tissue which are characterised by hy- pertrophic aberration of the cellular elements, and we shall now proceed to study those tumours in which, on the contrary, the cells atrophy ; of such are syphilitic gummata, tubercle, and glanders. These three species of tumours have this in common, that they are each in relation with a general constitutional disease. Class V. Syphilitic Gummata. FVom the anatomical point of view the most characteristic lesions of syphilis are gummata ; but every syphilitic neoplasm is not a gumma, and in many of these neoplasms no anatomical difference can be found between them and those caused by simple inflammation. We will rapidly pass in review the various syphi- litic accidents, for studied alone, gummata would not be suffi- ciently understood, and it is desirable moreover to indicate their place in the history of syphilis. The lesions determined in connective tissue by hard chancre, or the primary accident of syphilis, do not differ essentially from those produced by inflammation in the same tissue. At the base of indurated chancre, cells are met with resembling those of granula- tion tissue, they are round or fusiform embryonic cells, and are situated in the midst of an amorphous or fibrillar, and resistant ground substance, to which the chancre owes its induration. If characters distinguishing indurated chancre from simple influm- 1 88 TUMOURS. mation are ever found, they will be discovered, we think, in this ground substance. The blood-vessels contained in the indurated tissue of chancre are well preserved, but their walls are extremely thick and the lumen very narrow. This thickening is the result of an inflammatory process causing lesions absolutely similar to those of chronic arteritis. Bserensprung thought that the indurated tissue at the base of chancre was impregnated with an amyloid substance, capable of being coloured blue-violet by iodine and sulphuric acid ; this opinion, however, has not been verified by other observers, and we have tried in vain to obtain the reaction indicated by him. When indurated chancre heals, the newly formed embryonic tissue tends to develop into adult connective tissue. (For fuller details see the article ' Skin.') All the neoplasms of constitutional syphilis, both primary and secondary, tend on recovery to reproduce the previously existing tissue. Thus a papulo-squamous syphilide leaves no trace at the end of a certain period ; the same with lesions, of the same period, of deeper parts, of the periosteum, bones and parenchymatous organs. Affections of the bones and liver may be cured without leaving traces, or only a simple or hypertrophied cicatrix such as a hyperostosis. Syphilis is usually divided into pramctr^/, secondary and tertiary periods, the term secondary being applied particularly to superficial mucous or cutaneous syphilide s, the word tertiary to lesions of the bones and parenchymatous organs. This division does not seem to us to be accurate. It would be truer, from the pathological point of view, as Virchow has indicated, if the purely inflammatory lesions of syphilis were called secondary, and the later lesions, which manifest themselves under the form of tumours, were called tertiary. To thoroughly comprehend the phenomena of syphilis the lesions should be studied separately in each tissue and in each organ. In the 6on.es, contemporary with secondary accidents, pains, called rheumatoid by Eicord, but which are not due to permanent lesions, are observed ; later, chronic inflammation shows itself on the surface of the bone, or under the periosteum (periostitis or perios- toses), or is more profoundly seated causing ostitis, which is, at first, of the rarefying variety with thinning and destruction of the bony lamellae, ending later in the production and condensation of bone tissue. This condensation, by obliterating the Haversian canals, may cause necrosis. At a later period true gummata may form. Thus in the bones, syphilis may give rise to ostitis, hyperostoses. THE LESIONS OF SYPHILIS. 189 necrosis and gummata. In the liver, there is at first interstitial hepatitis either diffuse, generalised, or circumscribed, but always characterised by fibrous tissue of new formation ; later, veritable gummata appear. In the testicle, there are also fibrous neoplasms, interstitial at first, then gummata. In the lung, there is also Fig. 97. — DiI'TUse Syphilitic Intkhstitial Hepatitis. A, c, liver cells undergoing fatty degeneration ; B, isolated hepatic cell ; G, new connective tisdue. Magnified 300 diameters. interstitial pneumonia, which may be diffuse or limited. The lesions of circumscribed pneumonia have often been regarded as gummata of the lung ; Virchow described them under the name of white hepatisation. They are observed in new-born infants and B Kid. ii.'i. — LiMi ciK A Ni;\v BOHN Infant (ri.:ih-(i;d one Tniiin). H, apex ; D, base ; li, hilus ; a, nucleus of syphilitic interstitial pneumonia. in very young children, in the form of nodules, the seat, extent, and number of which are very variable. Theii- structure is analogous to that of foetal lung. In this, as is well known, the alvcnli ai'e separated from one another by an embryonic connective tis.>^"^=?SiS»^;cS>-^ FlG. 109. — TUBEEOPLAB GRANULATION. From Virchow's ' Cellular Pathology.' number of nuclei, — the giant-cells of Grerman authors ; often also fusiform and embryonic cells, but the elements which pre- dominate are small cells, measuring 4 yu. to 9 yu, in diameter, the nuclei of which are surrounded by a very small amount of proto- plasm. These are embryonic cells undergoing atrophy. The reciprocal arrangement of these cells is important. In a section of a granulation, a peripheral zone of proliferation may be recognised Fig, 110, — Section op a Tubercle of the Brain. A, tubercular tissue ; B, white blood-corpuscles and endothelial cells ; 0, blood-vessel filled with granular fibrin. Magnified 400 dia- meters. containing large mother-cells and fibroplastic elements. This zone is sometimes much more extensive than might, at first sight, be supposed ; in the centre the elements are closely packed together, they atrophy as they grow older and finally break down into a granular detritus (fig. 109). Around all these elements a DESCRIPTION OF TUBERCLE. 203 granular or fibrillar ground substance is produced which agglo- merates and binds them close together. As the result of atrophy and molecular destruction, the centre of the little nodule becomes fnable and opaque. The blood-vessels are never permeable at the centre of a granulation ; examination shows that this obUteration is brought about slowly. If studied in a delicate section of tubercle (fig. 110) the outline of the vessels can be made out and they are seen to be filled with a coagulum of granular fibrin. In the midst, and particularly on the border of the granular contents, white blood- corpuscles (6, fig. 110) are found, distinguishable from adjacent cells belonging to the tubercular granulation by their larger size Fio. 111. — Isolated Vessel of the Pia Mater passing through a TunERCULAR Granulatiow, the Limits of -which are indicated by the Dotted Line. A, lymphatic sheath ; B, vascular wall ; r, proliferating elements of the adventitious coat of the vessel ; c, coagulated fibrin in the interior. Magnified 100 diameters. and regular arrangement in a circular manner within the walls of the vessel. Now there is an accumulation of leucocytes along the vascular walls every time that the blood-current slows. This pro- position results from experiments made on the web of a frog's foot, in which, if an incision be made, the vessels obliterated at the point of incision form culs-de-sac, where the circulation passes slowly ; these diverticula in which the blood-current slows become filled with leucocytes, for the impulse of the current is not sufficient to overcome the adhesive property of the white corpuscles. As, on the other hand, white corpuscles are not more numerous in tuberculosis than normally, we are obliged to admit that slackening of the blood-current, shown by the accumulation of the 204 TUMOURS. leucocytes along the walls of the vessels, has preceded coagulation, and arrest of the circulation. In sections of tubercle obtained after hardening in alcohol, round or irregular granular masses are generally found in the granulations or at various points ; at the periphery of these masses are oval nuclei stained red with picro-carminate of ammonia, rVl IT 1 '^^ Ifc ' \ *^^".«J^ ■':'•...' Fig. 112. — Section of Livek containing TnBEEOLB. H, H, central veins of the hepatic lobules ; M, M, interlobular connective tissue thickened and embryonic ; a tubercle, t, is seen in the midst of this tissue ; T, section of a branch of the portal vein. Magnified 20 diameters. while the granular substance is stained orange-yellow. This staining allows, even with a low power, of the recognition of these masses ; they are the giant cells of the Grermans. The frequency of giant cells in tubercle induced Schiippel to look upon them as the characteristic element of tubercle, but they are nothing of the Fig. 113. — Giant-oell obtained by dissociating a Fkagment of TuBEKOLE IN Alcohol. e, granular centre ; c, processes of the protoplasmic substance which forms the cell; b, nuclei. Magnified 250 diameters. kind, as they are met with in other pathological products, notably in all caseous masses of whatever source, provided that the patho- logical evolution has been slow. These large cells can be isolated by macerating a portion of tubercle in a 33 per cent, solution of alcohol. They are of irregular shape, granular at the centre, and send out branching processes; they may be compared to the DESCRIPTION OF TUBERCLE. 205 mother-cells of the medulla of bone. Owing to their position and shape it has been thought that these cells are developed in the interior of vessels or at all events in their walls ; it may even be possible that they are a variety of vaso-formative cells. Such is the interpretation given by MM.. Malassez and Monod after a research which they made on these elements in sarcoma. The question re- quires fresh investigation. In the first edition of this book we did not regard them as cells, but as fibrinous plugs formed in the interior of the vessels. The obliteration of vessels is constant in tubercle, and the fibrinous coagulum including cellvilar elements closely resembles a giant cell. According to some observers, Cohnheim in particular, giant cells are lymph cells placed under exceptional conditions of nutrition ; indeed, in chronic inflamma- FiG. 114. Section op the Thyroid affected with Tubercle. a alvGoU of the thyroid ; (, fibroos trabeoulffl ; v, vOBBels ; 5, b, tnberoles. Magnified 20 u, ttiTcw -.» diameters. tion lymph cells may acquire a considerable size and form true giant cells, like those observed in tubercle. Sometimes though not attaining the size of large giant cells, they may be called small giant cells. The constant and essential fact is that tubercles have no permeable blood-vessels. Development of tubercle.— Tubercle is developed in the midst of embryonic tissue, so that tubercular granulations are always sur- rounded by a zone of proHferating cells. They are often developed from the connective tissue of organs ; in the liver, the granulations develop from the interlobular tissue and are always preceded by interstitial hepatitis (fig. 112) ; in the bones, tubercle is preceded by ostitis, that is to say, by the formation of embryonic tissue in the medullary spaces. It may be asked if it is not possible for tubercle to develop equaUy well from connective tissue, the •2o6 TUMOURS. medulla of bone, or epithelial cells ? Colberg and Eindfleisch have decided this question in the affirmative as regards the pleura and peritoneum ; and in, the thyroid body we have observed the epithelial cells contained in the alveoli proliferate and most un- questionably take part in the formation of a tuberculous nodule. In the adult the thyroid gland is composed of alveoli, lined with pavement epithelium, and containing colloid material. In the development of tubercle of the thyroid body, the epithelial cells are seen to multiply (fig. 115) and press on the central colloid mass {d, fig. 115) until it is finally entirely absorbed. The alveoli ^ ■.-':■ 1 » 1 * - , ri ■ * 3 4 "'V-'' , JU/lfil/yl/- Fig. 115.— Periphery of a Tubercle of the Thyroid. D, thyroid alTeoli with the epithelinm normal, and with colloid masses in the centre • !■; alveolns, the cells of which have proliferated, the coUoid mass having almost entlrelv disappeaied; at h the alveolus is no longer rcoogmsable except by the arrangement of the fihronp tissue at its periphery; it is fflled like the adjacent connective tissue with new cells, b, which are atrophied m proportion as the centre of the granulation is of the gland are then filled with new and small cellular elements (f, fig, 115), at the same time the interalveolar connective tissue proliferates, and the whole constitutes a mass of embryonic tissue in which the nodule of tubercle is developed. In the lung, tubercle may be developed from the interlobular, peri-bronchial and inter- alveolar connective tissue, but more frequently the tubercular granulations are seen to occupy the centre of many alveoli, the elastic septa of which have been preserved. The embryonic tissue springs from the inner wall of the alveolus, the Uning epithe- lium of which taking an important part in the production of the new tissue; it is certain also that in the alveoli there is an VARIETIES OF TUBERCLE. 207 accumulation of white blood-corpuscles which reach them by diapedesis ; so that tubercle seems to be formed from very different elements ; from connective-tissue cells, lymph cells and epithelial cells. Tubercle develops in an analogous manner in the thyroid body, the lungs and the medulla of bones. On the structure of tnbercle a great variety of opinions has been put forward. Forster classifies tubercle among tumours of lymph cells, that is to say that the cells of tubercle resemble those of the lymphatic glands, which is equal to saying that they are small and round ; other observers have adopted this view, though since Donders, KoUiker, His, and Frey asserted that reticulated stroma was the chief characteristic of lymphatic tissue, it is more difficult to regard tubercle as composed of new lymphatic tissue. Rind- fleisch, it is true, has described a reticulated stroma in tubercle, but after the description given by himself and after our own observations made to verify its exactness, we affirm that there is in tubercle no true reticulated stroma similar to that of the lym- phatic glands, and that the appearance of a reticulum is due to the action of hardening reagents on the intercellular substance. Virchow considers tubercle to be a lymphoid product, while gummata are formed of a tissue similar to granulation tissue. But in fact gummata and tubercle have essentially the same histological constitution, and the same mode of development ; both are formed of small cells surrounded by fibrous tissue, and in our opinion they are both species of fibroma composed of nodules of cells of which those at the centre undergo atrophic degeneration. Varieties of tubercle. — Tubercular granulations are either dis- crete or form by their imion distinct masses the size of a pea, hazel-nut, or walnut ; if developed on a surface, such as a serous membrane, they form more or less extensive plaques. Discrete tubercle is surrounded by a zone of proUferation in which blood- vessels, often dilated, are present ; this red vascular zone renders the tubercle, which is anaemic, semi-transparent, or opaque, much more apparent. Confluent tubercles are often massed in great numbers ; they are held together by a framework of embryonic tissue. The centre of each tubercle is atrophied in the same way as that of gummatous nodules, but in the former the blood-vessels are soon obliterated, those of the neighbouring embryonic tissue becoming so later ; from which it results that the granulations, no longer separated from one another by vascular tissue, are blended together and form an anoemic mass, in which it is impossible, with the- naked eye, to recognise separate centres, and the whole mass 2o8 TUMOURS. soon softens and becomes uniformly opaque. In the lung, similar caseous centres are often spoken of, even by distinguished observers, as caseous pneumonia (the infiltrating tubercle of Laennec) ; but the lung is not the only organ in which these masses of tubercle may be observed ; they may be studied in bone, where they have often been confounded with the caries called by the Grermans atonic caries ; further, every osseous lesion with a caseous appearance has, in the absence of microscopic study, been called tubercular. Hence, a confusion of opinion regarding tubercle of the bone, some obser- vers denying its existence, others seeing it everywhere, which con- FiQ. 116. — ^Transverse Section of the Body of a Lumbar Vektebka AFFECTED WITH CONFLUENT TUBERCULAR GRANULATIONS. o, osseous trabeculse; e, embryonic medullary tissue; 5, tubercular granulations. Magnified 20 diameters. fusion we shall hope to remove when studying osseous lesions. Eound, irregular or flattened masses of confluent tubercle may also be observed in the kidney, supra-renal capsules, lymphatic glands, intestinal mucous membrane, and serous membranes, &c. , Modifloations and secondary lesions of tubercle. — Tubercle does not seem to be capable of absorption like softened syphi- litic gumma. The cicatrisation which follows is always the result of mortification, and elimination by ulceration. However, isolated foci are often found in the apices of the lungs, filled with a caseous or almost solid calcareous substance, and surrounded by indurated tissue ; but it is often impossible to determine the origin SECONDARY LESIONS OF TUBERCLE. 209 of such foci which might as well be the remains of infarcts, abscesses, or dilatated bronchi separated from the rest of the air-passages, as cicatrised tubercular cavities. Tubercle frequently undergoes fibroid degeneration. At the apex of the lung, in the midst of interstitial pneumonia, little hard nodules may, for example, be found composed of homogeneous fibrous tissue and containing a small number of round atrophied cells ; these nodules do not generally contain blood-vessels, and their form, arrangement, and the Intermediate states observed between them and typical tubercles leave no doubt as to their nature. They seem to be tubercles arrested in their evolution. Gaseous degeneration is usual in old tubercular granulations. This character is so essential that no hesitation need be felt as to the tubercular natiue of a small nodule, the centre of which is opaque and yellow and in a state of caseous degeneration. Granulations which are semi-transparent throughout their entire mass may, on the contrary, be confounded with other neoplasms of inflammatory origin, or with carcinoma, fibroma, sarcoma, &c. Caseous degeneration is generally attributed to obliteration of the blood-vessels ; this explanation is natural, but as caseous degeneration occurs in gummata in which the blood-vessels are permeable (see p. 193 ), it is one that is open to doubt. The caseous degeneration of tubercle causes their death and softening. The progress of the process of elimination by inflammation is <'xtremely variable ; it is generally very slow and irregular, and varies according to the seat of the tubercle, the organs aff"ected, and the constitution of the subject. Thus, in the bones, tubercle causes suppurative ostitis, and in the lung, cavities are the most common results; in the liver, on the contrary, tubercle never causes suppurative inflammation ; in the lymphatic glands, tuber- cular granulations sometimes determine, as in the bones and lungs, foci of suppuration, but generally, as in the liver, the adjacent tissues tolerate the new growth, which ultimatelyundergoes complete caseous degeneration ending in petrifaction. As regards the personal conditions of the patient, though knowledge is incom- plete on the subject, it is known that bad hygienic conditions, insufficient food, unhealthy dwellings and excessive labour favour suppurative inflammation. From what precedes it is evident that the progress of inflamma- tion around tubercle causes very varying lesions in the surrounding tissues ; in the bones, if tubercle is confluent, there is necrosis, and besides the suppurative inflammation which is the local con- p 210 TUMOURS. sequence, there are, at variable distances from the focus of suppura- tion, rarefying or condensing ostitis in the bone or under the periosteum, or hyperostosis. In the lung, the lesions accompanying tubercle are catarrhal, fibrinous and interstitial pneumonia ; these different forms of pneumonia are present alone or united in the same subject in both lungs or even in the same lung, side by side with discrete or confluent, granulations in various states of evolution. These tubercular masses act on the surrounding living tissues like foreign bodies, often producing ulcerative inflammation around themselves, and the formation of a focus which may open into a mucous canal, such as a bronchus, the intestine, or epidydimis. By softening, the same result is brought about and cavities are pro- duced. If the tubercular mass remains enclosed in parenchy- matous tissue it dries and undergoes calcareous degeneration. The fat is decomposed into fatty acids, crystallised stearic acid for example, and into cholesterin in the form of rhomboidal plates ; the calcareous granules, at first indistinct, become welded together so as to form hard concretions which may remain in the economy for an indefinite period. But the same series of phenomena is common to infarcts and tumours, so that seeing a calcareous nodule in the midst of some organ it is impossible to say, as is however often done, if it is a degenerated tubercle or not. Anatomical diagnosis of tubercle. — The diagnosis of solitary tubercle is easily made with the naked eye, but if the tubercles are confluent and form a caseous mass they can only be recognised by means of the microscope, unless there is a zone surrounding the mass in which granulations are distinctly recognisable ; in fact, in tubercle as in all tumours, the centre presents the lesions of the periphery in a more advanced stage ; the proof of which is given on microscopical examination, for tubercular granulations are then. recognised in the midst of a caseous mass composed of them. We have often seen the name of caseous pneumonia given to such caseous masses, when an attentive examination left no doubt as to the presence of tubercular granulations. With the naked eye it is sometimes difficult to distinguish between confluent tubercle and syphilitic gummata in process of evolution. In fine sections, however, made after hardening in alcohol or chromic acid, it may be observed that in tubercle all the vessels are obliterated by a granular mass, while in gummata they are empty or contain red blood-corpuscles. When gummata are old and their blood-vessels are also obliterated, they form well-defined, hard, lardaceous, caseous masses, surrounded by a thick, firmly adherent fibrous PROGNOSIS OF TUBERCLE. 211 layer (see p, 1 97), while the caseous masses resulting from confluent tubercle have not the same solidity, they break down, and are incapable of isolation from the surrounding tissues which have simply the appearances of inflammation. Prognosis of tubercle. — The grave nature of tubercle is so well knovm that there is no occasion to insist upon it. It is still a question if tubercle is capable of cure, or if it acts Uke certain malignant tumours in causing at a distance growths similar to itself. The cHnical study of patients followed for a long period of time, considered together with post-mortem examinations, show that solitary tubercular granulations often remain small, undergoing but slight caseous degeneration, for an almost indefinite period in the midst of indurated masses resulting from interstitial pneumonia. At the autopsy of old subjects, isolated, small, rather hard tubercular nodules are also found probably dating back a great number of years, and of which the centre is in a state of caseous degeneration. The curability of this form of tubercle, as well as that which has undergone fibroid change, is manifest. The conditions necessary to bring about this happy termination seem to be that the tubercles should be solitary, or few in number. Confluent tubercle may remain at the same spot for a long time without setting up reaction, but more often it acts as a foreign body producing eUminative inflammation around itself, which may sometimes terminate by cicatrisation and cure. The most serious manifestation of tuberculosis consists in the generalisation and dissemination of tubercular granulations in many organs at once, notably in the serous membranes. The peritoneum and pleura are very often invaded at the same time. Class VII. Qlanders. In glanders, as in syphilis and tuberculosis, there are two orders of lesions, those purely inflammatory and those in the form of nodules. In glanders the nodules are similar to tubercular granulations. Spontaneous in the horse, in man glanders is always the result of equine infection. In man, as in the horse, the disease commences by a tumour, or by a primary ulcer, the farcinmts chancre, soon followed by lymphangitis and accom- panied by abscess, acute or chronic suppuration with discharge of serous pus. \M\eu the disease is locaUsed in the skin, blood- vessels, and lymphatic glands, it generally receives the name of acute o'r chronic farcy. If the disease begins in the air passages. p 2 212 TUMOURS. the nasal foss^, the larynx, trachea, bronchi, or lung it is called acute or chronic glanders. Glanders, properly so called, and &cy are two manifestations of the same general disease also called glanders, a disease essentially contagious and moculable. In the horse, in which we will first study the histological changes of glanders, the disease is characterised by two kinds of lesions, granulations and inflammation, which show a great tendency to be-^ come caseous and produce ulcers. In the horse the granulations of glanders — the glanders tubercle of veterinary surgeons — whether studied in the submucous tissue of the air passages, in the lungs, serous membranes, or connective tissue of the skin, always present the same constant characters, which greatly resemble those of tubercular granulations in man. When, either solitary or con- fluent, the granulations are situated in the nostrils and project on the surface of the mucous membrane, they soon cause desquama- tion of the epithelium, and slight superficial ulceration and catarrh. On microscopical examination these granulations are found to consist of an accumulation of embryonic or lymph cells, those at the centre being atrophied and in a state of granular degeneration, while those at the periphery are in a state of active development. In the lungs, if situated in the connective tissue adjacent to a small bronchus, they often eiicircle it hke a complete ring (fig, 117); intense catarrh and ulceration of the bronchus are the con- sequence of this peri-bronchitis ; at the periphery of a similar glandular nodule there is pulmonary congestion and pneumonia, and the pulmonary alveoli are foimd filled with lymph cells and red blood-corpuscles. But the granulations are not always situated around a bronchus, more often thej occupy an entire infundibulum; the alveoli of the infundibulum are then fiUed with embryonic cells held together by a granular substance, while the epithelial cells have disappeared (see Kenaut, art. Morve, in the Bict. mcydo. des sc. mSd.). The nodule is surrounded by a more or less extensive zone of lung tissue in which the alveoli are filled with blood. The nodule soon undergoes caseous degeneration and suppurative inflammation, from which cavities result, similar in the horse to those produced by pulmonary tuberculosis in man. The granulation of glanders is formed of small cells contained in a partially fibrillar substance ; the elements which are at the centre atrophy and soften from granular fatty degeneration. It is difficult to distinguish these growths, produced by glanders in the horse, from tubercle in man. In man, glanders may show itself by acute symptoms by catarrh,. special inflammation of the air passages, cutaneous pustules GLANDERS. 213 and multiple abscesses situated in the subcutaneous connective tissue and in the muscles ; accidents rapidly terminated by death, or succeeded by the more localised symptoms of acute or chronic farcy. The small foci in various organs are similar to those observed in purulent infection. In a case under the care of M. Herard' we ascertained that the little nodules of the lung, trachea, and larynx, instead of being similar to the glanders granulations of the horse, did not differ from the abscesses of purulent infection. The larynx and trachea simply showed small submucous abscesses, and the lung areas of metastatic, lobular pneumonia. The pustules of the skin did not differ notably from those of variola, the diffuse suppuration of the sub- cutaneous cellular tissue was identical with celluUtis, and the abscesses of the muscles presented nothing special. M. Kelsch has since published a histological examination of Fio. 117. — Section of a Glandkks Nodile from the Ling of A Horse. Tho tissue of the growth forms a regular ring rouud a small bronchus. Magnified 40 diameters. the lesions observed in a subject who died from glanders, and like ourselves, he saw in the lung small centres of suppurative pneu- monia, and in the mucous membranes and skin, small miliary abscesses. In an autopsy recently made on a patient of M. Hayem, at the Hospital of St. Antoine, it was the same. The preparations of cutaneous pustules which we made in this last case showed us that, compared with the pustules of variola, the difference consisted in the suppuration commencing in the corium and subcutaneous connective tissue, instead of in the Malpighian layer as in variola. (For fuller details see the ' Pathological Histology of the Skin.') Prognosis. — Death is the rapid and invariable termination of ' For fuller details see the case published by M. Caxville in the Gazetie des /iiijiitaux, August 25, 1868. 214 TUMOURS. acute glanders; this is in consequence of dissemination and generalisation of the granulations ; but chronic farcy and even acute farcy may be cured if the lesions are superficial and are energetically treated from the beginning. III. Tdmoues having theik Type in Cartilaginous Tissue. Chondroma. Definition,— Formerly all tumours which presented the physical characteristics of cartilage were called chondromata ; but we have eliminated certain tumours which resemble cartilage with the naked eye, but which are nothing of the kind, such as the lamellar fibroma described above (p. 164). On the other hand, true chondroma does not in the least resemble with the naked eye typical, that is to say, hyaline cartilage. Chondromata being composed of cartilage, their definition is subordinate to that of the cartilaginous tissue. Certain carti- laginous growths, called ecchondroses and developed only from pre-existing cartilage, should from the beginning be distinguished from chondromata. They are found on the articular cartilages and are generally multiple and developed in consequence of in- flammation (see chronic rheumatism and white swellings) : also on the costal cartilages at their union with the bones cartila- ginous nodules are sometimes observed, the result of rachitis, to which the name of ecchondroses has also been given. Virchow describes as ecchondroses the little cartilaginous masses found on the thyroid cartilage and tracheal rings. Description. — Chondroma, properly so called, is never developed from pre-existing cartilage. Every variety of cartilage, previously described (p. 17), is met with in chondromata, and also a variety which does not exist physiologically in man, but which is found in the cephalic cartilages of the cephalopods. In these animals, the cartilage cells are not enclosed in a capsule, but they have processes by which they anastomose together {vide fig, 119), The ground substance surrounding them is of a cartilaginous nature. On observing the mode of development of this variety of cartilage, it is seen that the capsules which, primitively, envelop the cells, are pierced by anastomotic processes sent out to adjacent ceUs, The facility with which the capsules and ground substance are pierced is truly remarkable. Later, the capsules become indistinct DESCRIPTION OF CHONDROMA. 215 and disappear. This variety of cartilage of the cephalopods has its exact analogue in certain chondromata ; hence the necessity of describing it. In the adult, cartilaginous tissue is deprived of blood-vessels, and it is the same in most chondromata ; but a cartilaginous tumour may become vascular for a limited extent as far as the centre, while new layers of cartilage are deposited at the periphery. The part of the cartilaginous lobe which has been pierced by blood- vessels accompaiued by connective tissue, is transformed into an embryonic tissue similar to the medulla of bone ; the tumour is finally reduced to a cartilaginous shell containing medulla and blood-vessels. It is rare for a chondroma to be formed of one lobe, par- ticularly if of large size, there is generally an union of many distinct cartilaginous masses, separated by connective tissue. These masses are usually spherical, though sometimes of irregular form and variable in size ; in the same tumom-, some being uo larger than a pin's head and others as large as a pigeon's ^gg. It may happen also that all the lobes of a tumour have not the same structure, some may be formed of hyaline cartilage, others of mucoid cartilage, some of fibro-cartilage and others again of cartilage with ramifying cells. These various lobes are generally covered by a fibrous membrane which acts as a perichondrium and in which the vessels ramify ; beneath it there is a layer of len- ticular capsules flattened horizontally, more deeply, the capsules are globular, and in the centre there are large capsules containing many generations of secondary capsules. It is in chrondroma that the largest capsules are found. Varieties of chondroma. — The differences between chondromata are not very marked, but the tissues of which they are composed and the modifications these tissues undergo furnish bases for a classification of varieties of chondroma : — (a) Unilobular, hyaline chondroma is formed simply of a single lobe of hyaline cartilage covered by a fibrous membrane ; on the surface are lenticular capsules and at the centre capsules similar to those of permanent cartilage in the adult. (6) Multilobular, hyaline chondroma consists of a certain number of lobules similar to the preceding and separated by con- nective tissue. (c) Sometimes the lobules of the latter variety are separated by vascular fibro-cartilage. {anl, one third of the children bom at the Clinic of the Faculty of Medicine at Paris, come into the world with congenital nrevi, 240 TUMOURS. which in most cases disappear spontaneously during the first months of life. 2. Cavernous angioma {Ncevus cavernosus, erectile tumour, hematode fungus) is iormed oi an erectile tissue, the cavities of which are filled with blood. The tissue is hollowed by alveoli which communicate with one another in a very irregular manner, much in the same way as the alveoli of carcinoma intercommuni- cate. The blood circulates in this cavernous system which takes the place of capillaries, situated as it is between the arteries and veins. The circulation is active, as is proved by chnical obser- vations of the sudden variations of the volume of these tumours ; and as we shall see histology confirms this opinion. In angioma ~ may be studied — 1. The septa limiting the alveoli. They are formed of dense fibrous tissue in which, in sections made after hardening in alcohol, no cellular elements can at first be distin- guished; but on treating the preparation with acetic acid and staining with carmine, they become apparent. These trabeculsB may also contain smooth muscle cells or even striated muscle fibres, if the tumour be developed in one of the muscles of the ex- tremities. In the septa, adipose vesicles are also sometimes met with and blood-vessels proper to them, a kind of vasa vasorum, and in one case Esmarch discovered nerve filaments. 2. The endothelvum which lines these cavernous cavities. It consists of flattened endothelial cells of fusiform shape, if seen isolated and sideways ; they are similar to the endothehum of the veins. 3. The blood contained in the cavernous spaces is quite normal, and similar to that which circulates in the rest of the vascular system. If after removal of such a tumour it be cut into, all the blood escapes and nothing remains but a kind of sponge which collapses. If such a tumour, situated on the surface of the liver, be opened, though it may have been hard and prominent, it becomes soft and flaccid and converted into an irregular, wide- meshed network. If, on the contrary, the blood coagulates en masse, which occurs if the tumour be placed entire in absolute alcohol, a magnificent natural injection of cavernous angioma is produced. In sections of a tumour thus prepared and hardened, the blood can be examined in the same condition as it existed at the moment of death, and the state of the circulation ascertained. With a power magnifying 200 diameters the trabeculse, alveoli, and their contents consisting of red corpuscles may be seen, the red corpuscles, as frequently occurs after hardening in alcohol, taking a regular polygonal form ; a few white corpuscles are present and by staining CAVERXOUS AAGIOMA. 241 with carmine, they may be counted, and it is then seen that they are few in number and are not adherent to the septa. These two facts, the small number of the white coqiuscles and their non- adherence to the vascular walls, indicate the activity of the cir- culation in the tumour ; for owing to the adhesive property of white corpuscles, a strong impulse of the blood current is necessary to prevent them stagnating along the vascular walls. The facility of circulation in cavernous angioma is proved, moreo\'er, by clinical observation during life. Angiomata are, in fact, erectile, and distension by afflux of blood is produced by emotion, exercise, Ac. When the tumour is inflated with blood, pulsation may be Fio. 136. /t. - -CAVicnxous Anoiihia ok the Livek. (Section a'ter hardening in alcohol.) a, cavernous spaces filled with blood ; b fibrous trabecules bounding the cavernous slices. distinctly jierceived, a phenomenon met with in erectile tissues. The name of erectile tumour, given to angioma by Dupuytren, is apparently therefore well chosen ; but all cavernous angiomata are not erectile, and moreover a tumour which has been erectile for a certain time may cease to be so ; thus, the name cavernous angioma expresses a constant anatomical condition, and defines the tumour better than a name which expresses a passing and incon- stant physiological state. With regard to the development of angioma, Eokitansky ad- mitted that the areolar tissue is developed first, outside the vasculnr system, and only communicates with the blood-vessels at a later stage. He compared the initial alveolar tissue of angioma to that 242 TUMOURS. of carcinoma, and considered that their development was analogous. Luschkaj having at the same time observed that blood cysts are found along the course of the cerebral blood-vessels without com- munication with the latter, used these facts in support of Eoki- tansky's opinion as to the origin of angioma ; but we know, at the present time, that the blood cysts, described by Luschka, are nothing else than dilatations of the perivascular sheaths. In the active development of angioma, embryonic tissue is first produced, and new capillaries, which at first show simple dilatations ; but the dilated capillaries being in contact, wide openings are estabHshed between them, resulting in the formation of a capillary system with large cavernous dilatations. Cavernous angiomata are subject to various changes of nutri- tion. Their vascular walls may be the seat of calcareous concretions similar to those present in the choroid plexus and angiolitliic sarcoma. Cysts filled with serum have been observed by Holmes Coote in angioma ; they are caused by the isolation of a vascular bud and subsequent metamorphoses of the contained blood. Can angioma develop into carcinoma or sarcoma ? J. Miiller reports cases of malignant cavernous angioma with a tendency to increase and produce secondary growths. These must certainly have been sarcomata or carcinomata with dilated blood-vessels. Pulsatile tumours, often regarded by surgeons as erectile tumours, aneurisms of the bone, &c., are nothing else, in fact, but sarcomata or carcinomata with much dilated blood-vessels. Angioma is sometimes diffuse, not separated from the surrounding tissues by an exact boundary, sometimes circmnscribed and it may even be surrounded by a true capsule; it is then called encapsuled angioma. Seat of angioma. — According to its seat cavernous angioma is divided into external and internal. External angioma of the shin is situated in the corium or • subcutaneous cellular tissue. Virchow calls it Upogenous if developed in adipose tissue and phlebogenoua if developed at the expense of the vasa vasorum of the veins. It may extend into the cellular tissue around or within the muscles and even into the bones. Angioma of the mucous orifices, the lips, for example, is called fissural by Virchow. Internal cavernous angioma is observed in the liver, kidneys, a,nd spleen ; it is most common in the liver. Angioma of the liver varies in size from that of a nut to the half of the hepatic organ ; but though it projects on the surface of the liver, it does SEAT OF ANGIOMA. 243 not generally increase the size of the organ, for it develops at the expense of the hepatic substance. If encapsuled the capsule is pierced by vascular openings. Surrounding the tumour the hepatic parenchyma is normal, but separated from it by a zone of proliferating connective tissue. It is here, when the tumour is ex- tending, that the embryonic walls of the blood-vessels dilate, open into one another, and form, in fact, a new mass of cavernous tissue which communicates and joins with the first. Such a tumoiur has been known to rupture into the peritoneum and cause peritonitis. Sometimes angiomata shrink after spontaneous coagulation of the blood which they contain, and undergo cicatrisation. Rayer states having observed tumours of this kind in the kidney ; they have also been seen in the spleen. Schuh has published a single but incomplete case of angioma of the lung. Prognosis of angioma. — These tumours have no other gravity than that which results from their situation and extent ; they may very well pass unpereeived. The anatomical diagnosis of angioma is easy when the vessels and alveoli remain filled with blood ; but if the tumour has been divided before being submitted to examination, and the blood has escaped, nothing is left but a collapsed, spongy mass. On draw- ing the tissue apart with forceps, a system of resisting and elastic septa is seen, which to an exjoerienced observer is sufificiently characteristic of angioma. It might be a question for discussion if such a tumour were not an erectile carcinoma or sarcoma ; in such a doubtful case the tissues in the periphery of the tumour should be examined for the characteristic elements of carcinoma or sarcoma. Around and within angioma, only the normal tissues of the invaded part, or embryonic tissue, are found. It might be sometimes difficult to differentiate angioma from myoma of smooth fibres traversed by dilated blood-vessels ; but here again the presence of a large number of muscle cells would establish the diagnosis. VIII. — Tumours formed of Lymphatic Vessels. Lymphangioma. Tumours formed of newly formed lymphatic vessels may be confounded with simple dilati;xrA. a, nuclei ; », reticulated stroma ; r , capillary blood-vessel ; n, nucleus of the cai illary. nifled 600 diameters. Mag. blood-corpuscles and blood pigment in different stages of decolor- isation, such as are found in the spleen. Cells apparently fusiform, but actually flattened and containing oval nuclei, are also found in the juice, they are derived from the endothelium of the vessels or the cells of the reticulate stroma ; there are also red coi-puscles and free nuclei of various sizes resulting from the rupture of the cells containing them. These various elements, obtained by scraji- ing, give very insufficient notions of the nature of the tumour, and do not differentiate it from encephaloid sarcoma, or carcinoma, from which it is also difficult to distinguish with the naked eve. To recognise lymphadenoma, delicate sections should be cut after 248 TUMOURS. hardening in alcohol, and removing the free cell elements with a camel's-hair brush. The reticulate stroma, the true character- istic of lymphadenoma, then becomes evident,' and is distinctly seen to spring from the capillaries (fig. 138). In adenia, if the preparations have been hardened only with alcohol, the blood- vessels appear empty or filled with red corpuscles, which do not stain with carmine. In leueoeythemia, on the contrary, the dilated capillaries contain a large number of white corpuscles which stain readily. Capillaries full of white corpuscles are also found in all the organs; so that by this single character leueoey- themia, which may have passed unnoticed during Kfe, can be recognised after death. Seat of lymphadenoma. — When lymphadenoma is developed in the lymphatic glands it causes a great increase in the size of the follicles, which are then compressed and modified in form. The connective tissue of the medullary portion of the glands seems to disappear and give place to a hypertrophied cortical substance. On section, the gland has an encephaloid or splenic appearance, and connective tissue can only be recognised at the slits which corre- spond to the lymph sinuses enveloping the follicles. If after slightly hardening such glands in alcohol or chromic acid a delicate section be cut, and the lymph cells brushed away with a paint- brush, the reticulum is seen united to the capillary vessels. The latter are filled with leucocytes in leueoeythemia and with red cor- puscles in adenia. The fibrils of the network are two or three times thicker than in the normal condition, their diameter being 2 yii to 3 ytt. The gland has everywhere the same structure and is entirely formed of modified cortical substance. The thymus glcmd after having undergone almost complete atrophy may, under the influence of leueoeythemia or adenia, recover its original form and acquire a considerable size. In many cases, which we have examined microscopically, we have found adenoid tissue, and we have been convinced that there was here a new formation in the thymus, and not simply hypertrophy of the peri-tracheal glands, for the corpuscles peculiar to the thymus were found. The spleen may become modified in the same way as the lymphatic ' The process of removing all the free cells contained in the reticulate stroma with a camel's-hair brush, is, after hardening in alcohol, both difficult and tedious ; the following proceeding will render it easier. A morsel of the tumour suspected to be lymphadenoma is first placed for twenty-four hours in a 33 per cent, solution of alcohol, then into a slightly syrupy solution of gum for twenty- four hours, and then into strong alcohol to complete the process of hardening. After this it is easy to brush away the cells from out of the stroma. SEAT OF LYMPHADENOMA. 249 glands. The Malpighian bodies, which in this organ represent the follicles of the lymphatic glands, become hypertrophied out of all proportion, they have been known, indeed, to attain the size of a filbert or walnut. The reticulated tissue shows almost every- where thickening of the trabeculse. The capillaries are filled and distended with white corpuscles, if the case be one of leucocy- themia. In the livetr there are many distinct changes. One, which is peculiar to leucocythemia, consists in diffuse extravasation of the white corpuscles. (This was demonstrated by a research carried out by one of us and Ollivier, 80c. de Biol. 1866.) The white spots, which in the liver, have been looked upon by all observers as caused by hyperplasia of the connective tissue, is in leucocythemia caused by accumulation of white coqiuscles. The hepatic capillaries allow of the escape, with or without rupture of their walls, of a large number of white coqjuscles, £. Fig. 139. — Thaxsveusk Skc tkin of ax Enlakgkd Livek is Adenia. r, V, veasols filled with corpuscles ; e, hepatic cells. which are collected in a small limited space or ai-e diffused between the hepatic cells. These undergo fatty degeneration and are soon destroyed. Here, therefore, there is not only development of adenoid tissue but an extravasation of white corpuscles. Besides these foci, there is in the liver a veritable new formation of retiform adenoid tissue. Perhaps the extravasated white cor- puscles are the starting-point of this new tissue. In adenia it is almost certain that this is not so, and that the origin of lympha- (lenoma of the liver must be attributed to hyperplasia of the eciniu'ctive tissue. In adenia we have also constantly noticed a marked enlargement of the liver due to congestion and dilatation of the blof section of the seminal tube, the wall of which is very much thickened and transformed into adenoid tissue ; to the very narrow channel, a few free cells are seen ; e, fibres of the reticulated tissue ; n, lymph cells. Magnified 300 diameters. (After a preparation by M. Malassez.) some of which may, at a given moment, be undergoing retro- gressive changes, whilst others are stationary or in process of development. They are composed of a new formation of perfect adenoid tissue located in the corium. The new tissue is developed between previously existing bundles of connective tissue which it separates so as to insinuate itself (fig. 143). It is hence easy to CUTANEOUS LYMPHADENIA. 253 understand how if the neoplasm disappears, the elements of the corium simply return to their primitive relations without a cicatrix being produced. A solitary tumour of cutaneous lymphadenia Fici. 143. — SEcnoN- of Skin affected with Ci taneois Ltmphaden'ia. /. m, epidermal Iflyorfl, below which are seen the tumefied papiUse. In the tissue of the corium, and in the ceUulo-adipose tissue, adenoid tissue is set'n, in which the elements of the sldn, the sudoriparous glands, *. and the lilood-vesfols, r, can be recognised. The thicliness of the corium Is considerable. Magnified 20 diameters. has then no positive tendency to persist and to extend. Hence it may appear that after the definitions we have formulated it ought not to be included among tumours ; but the exception is .254 TUMOURS. only apparent, for the neoplasm, considered as a whole, persists and has even a marked tendency to extend. The development of lymphadenoma can only be well followed in organs where adenoid tissue does not physiologically exist, as in the liver, kidneys, testicles, .skin, and bones. The iirst phase Fig. 144. — Adenoid Tissue developed in the Os Innominatum. a, flat cells applied against the trabeculse ; &, fibrils of the developing stroma ; c, a few ceUs contained in the meshes of the reticulum. Magnified 500 dia- meters, of development is the production of a mass of embryonic tissue from the interstitial connective tissue of the organ, and perhaps also from white blood-corpuscles extravasated from the vessels. Soon, however, trabeculse of lymphoid tissue are formed, in the meshes of which cells are imprisoned. Such is at least the most natural interpretation of facts observed in tissues of simple structure, as in the marrow of bones for example (fig. 144). Lymphadenomata are subject to various modifications of their Fig. 145. — Adenoid Tissue oe Lymphadenoma of Bone UNDEKGOING CASEOUS DEGENERATION. a, filament of atrophied stroma ; 6, lymph corpuscles in a state of caseous degeneration (the tubercle corpuscles of Lebert). Magnified 500 dia- meters, tissue. Diffuse hsemprrhages are often observed, either in the lymphadenomata alone, or at the same time in them and in the organs in which they are located. This occurs particularly in leucocythemia ; in which case the extravasations are explained by rupture of the capillaries, consequent on the accumulation of EPITHELIAL TUMOURS. 255 white corpuscles within them. The white corpuscles being adhesive and their number considerable, in some cases exceeding that of the red corpuscles, it is easily understood how the circula- tion may be impeded, and the blood pressure become so great as to cause rupture of the vessels ; the effused blood then undergoes the usual retrogressive changes. Sometimes the stagnation of blood in the vessels causes coagulation, and infarcts are then formed (see changes in the vascular system). These infarcts are common in leucocythemia ; we do not know if they exist in lymphadenoma. They are characterised by whitish, opaque, caseous s])ots, in which adenoid tissue is still met with, but both the stroma and lymph cells are atrophied (fig. 145). The blood- \essels are transformed into granular fatty tracts, opaque to trans- mitted light. The diagnosis of lymphadenoma can only be made in micro- scopic sections, cut after hardening and from which the cells have been brushed away ; the presence of a reticulated stroma is the true characteristic. The prognosis is always very serious. Leukaemia, adenia, and cutaneous lymphadenia are fatal, and the progress of the disease is generally rapid. IX. TUMOUKS OF THE TyPE OF EPITHELIAL TISSUE. The most essential characters of physiological epithelial tissue are that the component cells are joined together by an ill-defined substance or cement, and that the tissue is spread out in investing layers containing no blood-vessels. The existence of a substance ci'menting the cells together, the absence of blood-vessels, and the arrangement of the cells in layers of investment, are the three terms of the definition of epithelial tissues. The tissue may consist of a single layer of cells, or these may be stratified. Stratified epithelium is the most important form to study as regards epithelioma, for here indeed there is an evolution of the cells identical to that met with in epithelial tumours. For example, on the surface of the skin from the papillse to the superficial epidermis, a series of layers are found, in which the form of the cells varies according to their evolution, and accord- ing to the pressure put upon each layer. The cells implanted on the papillir are cylindrical, and perpendicular to the surface of 2S6 TUMOURS. implantation ; their nuclei are large and ovoid, their protoplasm slight in quantity, and they are intimately united to adjacent cells ; on their surface they show dentations which are not however so easily seen as in the cells above them. These are larger than the preceding ; and polygona,l, well-marked filaments hold them together, leaving clear interspaces, in which is found a substance less refractive than the filaments themselves. These polygonal cells form a layer, the thickness of which varies according to the region. The next layer is formed of cells slightly flattened towards the surface, and filled with granules, of variable size, which stain with carmine. The nuclei of these cells already look atrophied. This layer of granular cells is called the stratum grannlosum. To this succeeds the stratum lucidum of the epidermis, composed of flattened homogeneous cells of ill-defined limits, and of which the nuclei have already undergone more or less complete atrophy. Above the stratum lucidum is the homy or keratic layer in which the cells, reduced to simple dried laminse, form a collection of strata. Thus the deeply placed cells of the Malpighian layer become by gradual evolution the polygonal cells of the rete mucosum, the granular ceUs of the stratum granulosum, the flattened cells of the stratum lucidum and the epidermic scales of the keratic layer. This example shows what variations the same epithelial cell may undergo, and it would be easy to cite numerous other examples. Thus, a polypus developed in the cervix of the uterus, and covered in the first instance by cylindrical cells, shows in its vaginal portion, at the end of a certain time, pavement epithelial cells. If, in a later stage, this polypus were to project at the vulva, all that part of the epithelium in contact with the air would be covered by a layer of dried scales or keratic cells. This transformation of soft into horny epithelium may be traced in a great number of other instances. Thus in certain cases of long-estabhshed ectropion, the mucous membrane of the conjunctiva is partially covered by a horny layer similar to that of epidermis. The origin of epithelium in the embryo has already been described (p. 35), and we have seen that the distinctions made by His between epithelium and endothelium cannot be accepted with absolute confidence. The opinion of Thiersch that all epithelium is produced from previously existing epithelial cells seems to us to be contradicted by the formation of epi- thelium on the surface of granulations and in fistulas, it being very probable that there the epithelial elements spring from embryonic tissue. The history of cancroid shows very positively that EPITHELIOMA. 257 epithelial cells are developed in parts normally deprived of them, for example, in the marrow of the bones, the lymphatic glands, and the muscles. These facts cannot be explained by the continuity of the tumour with an epitheUal tissue, for nodules of cancroid may be produced by a process of discontinuous development. Thus, while recognising that the development of epithelial from embryonic tissue is difficult to observe, and can only be followed in very limited spaces, we do not admit Thiersch's theory as absolute. In epithelial tumours the arrangement of the tissue varies greatly and constitutes many distinct kinds or classes of tumours. I. Epithelioma properly so called in which the new epithelial tissue is arranged in small or large masses without presenting any definite form, such as that of glands or the covering of papillae. II. Papilloma, in which the epithelial tissue covers papillae. III. Adenoma, in which the epithelium affects the arrange- ment observed in glands. Y^. Cysts, in which the epithelium lines a cystic cavity. I. Epithelioma. Definition and classification of epithelioma. — Epithelioma is also designated by the name of cancroid, epithelial cancer, or even epithelial carcinoma, by German authors, a name introduc- ing a regrettable confusion. The polyadenoma and heteradenic tumour of many French authors is nothing more than certain varieties of epithelioma. Sometimes the cells of epithelioma are arranged in stratified layers, as in the buccal mucous membrane or the skin, sometimes they are cylindrical and only form a single layer. In the first case the epithelioma is pavement, and in the second it is epithelioma of cylindrical cells. A. Pavement epithelioma itself contains many species. 1. lobulated epithelioma. — In this species the epithelial masses form irregular lobules, in which from the periphery to the centre, stratified layers of epithelium are recognised under- going an evolution similar to that of cutaneous epithelium ; that is to say, that the cells, cylindrical and small at the edge of the lobules, become tesselated, then horny or colloid as they approach the centre of the lobule. 2. Pearly epithelioma. — The epidermic evolution is less marked, and all the cells of the lobule may become horny. 3. Tubular epithelioma. — The fibrous tissue forming the 258 TUMOURS. stroma of the tumour is grooved by cavities in the form of tubes filled with pavement cells showing no epidermal evolution. B. Cylindrical-celled epithelioma contains but one species. We will proceed now to describe the four kinds of epithelioma properly so called. 1. Lohulated pavement epithelioma. — This species has served as the type for the classic description of cancroid. It is generally observed in the skin and those mucous membranes presenting pavement epithelium. With the naked eye it has a granular appearance. On section the surface shows a grey or rose-tinted tissue, in which opaque, or translucent spots and fibrous tracts are distinctly seen. The tumour is of unequal consistence, very friable at certain points, dense at others. Grenerally it can be easily broken up, which fact led Cruveilhier to give it the name oi friable cancer. On scraping the divided surface with a scalpel, an opaque substance is obtained not miscible with water, while carcinoma Fig. 146. — Destate Epitheli.vl Cells of Cancroid. Magnified 450 diameters. juice is miscible with water and gives it a milky appearance. In these scrapings cells of various form are found, some resembhng the epithelial scales of the mouth, others showing one or more pro- cesses, fusiform when seen sideways and flat when their superficies is presented. Sometimes spherical cells are found distended by a colloid vesicle, which contracts on the addition of acetic acid (Forster). The dentate cells of the mucous layer are rarely isolated by scraping, which is easily explained by the adhesion of these cells together. By scraping, balls are however often found composed of epidermic cells arranged in concentric layers hke the leaves of an onion (c, b, fig. 147) ; these are epidermic spheres or bird's-nest bodies. In the centre of these bodies there are sometimes colloid cells ; cells may a,lso here be found contain- ing a more or less considerable number of nuclei, indicating that there is great formative activity. Thus we see that scrapings LOBULATED PAVEMENT EPITHELIOMA. 259 from the surface of a divided tumour may fumish some indications of the tissue composing it, but are useless for complete definition. To obtain more precise information the tissue of the tumour must be studied in sections cut in different planes. If the section is made perpendicular to the surface of the tumour, lobules are seen formed of epithelium and united together by epithelial tracts. In Fki. 147. — Elements op Lobulated Pavement Epithelioma of the Lip. a, ifiolatod cellR showiiig a multiplication of their nuclei ; 6, epithelial bud with epidermic bird'B-nest bodies ; c, crushed bird's-nest body. Magnified 400 diameters. sections cut parallel to the surface of the tumour, isolated lobule.s are seen divided transversely. The lobules are formed of epithelium similar to that of the epidermis. At the periphery, the cells are cylindrical and im- planted perpendicularly on the wall of the cavity; from the periphery towards the centre an epidermic evolution is observed 8 2 26o TUMOURS. similar to that of the epithelium of the skin ; that is to say there is first a layer of dentate cells, then of flat and horny cells which become dessicated and nested in one another filling up the centre of the cavity and forming what is called a bird's-nest body. The mode of formation of these epidermic bird's nests is easy to under- stand, on the datum of epidermic evolution from the periphery to the centre of a spherical cavity. The lobules are separated from one another by stroma, generally formed of connective tissue, which supports the arteries, veins, and capillaries. These vessels never penetrate into the substance of the epithelial masses. The varieties of lobulated pavement epithelioma are in relation Fig. 148. — Section of Lobux-ateu Pavement Epithelioma. Magnified 2d0 diameters. with histological modifications of the stroma and nutritive changes in the cells. The stroma may be composed of (a) embryonic tissue with numerous blood-vessels; (6) mucoid connective tissue ; (c) adult or fasciculated connective tissue ; (cZ) all these varieties of tissue united. The stroma is more or less dense, and sometimes in the same tumour all the varieties inter- mediate between embryonic and fibrous tissue may be observed. In epithelioma in a state of active growth the embryonic stroma may vegetate on the free surface of the tumour in the form of villi. The epithelioma is then said to be villous. The varieties of epithelioma related to nutritive modifica- tions of the epithelial cells are two in number, the colloid and COLLOID AND KERA TIC CHANGES IN EPITHELIOMA. 261 keratic. In the colloid variety the epithelial cells undergo changes similar to those observed in the epidermis, when the epidermal cells, instead of drying, become coUoid as the result of irritation. At the commencement of the morbid change the nucleoli of the dentate cells, in consequence of excessive supply of nutritive fluids, become vesicular. The nucleus is itself finally distended by the vesicular nucleolus. This change is observed in the cells of lobulated epithelioma as well as in the epidermal layer of the skin. Soon the cells themselves become vesicular and filled with colloid matter ; they may then com- municate with one another and form an areolar system, the trabeculae of which are formed of flat epithelial cells. These elementary lesions, observed in vesicles and pustules of the skin, are often also seen in epithelioma, but here the change more commonly consists in the formation of a droplet of colloid 1-i * Fio. 149. — KiMDiJ'MAL Dkntate C-Ki.i.s, THE Xuri,i;i OF ■\V1IKII HAVK, 1) lil I I.M K VeSICL1.au IIY REASON OF DILATATION OF TIIK Xim:1,K<)LIS. 1. Normal niiolous and nucleolus. 2. IJilatod nucleolus. 3 and 4. The same change at a more advanced stage. matter. This may be developed in the nucleus replacing it, or may appear round the nucleus ; often also it is seen in the proto- pla.sm of the cell, the nucleus being pushed towards the periphery. Colloid and horny change in the cells of epithelioma may some- times exist in the same tumour, but they more often exist singly, the epithelioma being decidedly colloid or horny. Lobulated epithelioma is subject to ulceration, which is caused by disintegration of the epithelial cells or by gangrene consequent on obliteration of the blood-vessels. In the first case, the consti- tuent cells of the lobules become detached from one another by softening of their ci'inenting substance, and form a soft mass, which can be squeezed out from the tumour by lateral pressure. At the same time the connective tissue, which separates the epithelial islets, is the seat of an abundant new formation of cells, in which process diapedesis of white corpuscles probably plays an important part. This new formation is accompanied, on the 262 TUMOURS. surface of the epithelioma, by a growth of connective tissue which may be so active as to produce granulations. These graniilations are generally lined by a layer of pavement epithelial cells, and the surface of the morbid mass then becomes papillary. A partial or total gangrene of the tumour is caused when the epithelial lobules mm ■PW^^ Fie. 150. — Surface of an Epithelioma which has become PapILI/AKY. epithelium ; h, papillae ; section made according to their longitudinal diameter. become enlarged, and press upon and obliterate the neighbouring blood-vessels. Sometimes the arterioles and veins contained in a tumour are obliterated by the inflammatory swelling of their internal membrane, from which result more or -less extensive Fig. 151. — Trahsveese Section of the Papillary Surface OF AN Epithelioma. a, epithelium ; 6, papiUse out across. modifications of the tumour. The surface of epithelioma at the neck of the uterus is often ulcerated and gangrenous ; for to the above-mentioned causes of gangrene is added the irritating action of vaginal mucus. Development of lobulated epithelioma. — Lobulated epithelioma DEVELOPMENT OF LOBULATED EPITHELIOMA. 263 develops at the expense of the investing epithelium of the skin and mucous membrane, or from newly formed embryonic tissue in its neighbourhood. Kindfleisch maintains that new epithelial tissue is not developed by proliferation of pre-existing epithelial cells, but by the apposition of such cells. We recognise the cor- rectness of this view in many cases, and think it can be explained by a kind of ' catalytic action.' We see in it a fact analogous to that observed when embryonic tissue, of whatever source, is converted into bone in the neighbourhood of bone. Lobulated epithelioma is however most usually developed by an extension of the rete mucosum situated in the inter-papillary spaces of the skin. The cul-de-sac between the papillae enlarges, and the epithelium extends by throwing out buds composed of newly formed embryonic tissue, which penetrate deep into the corium. These buds are constricted from place to place, which gives them a lobulated appearance. Epitheloid buds often spring laterally from older buds, and they may even become separated from one another. Epithelial masses may also spring from the hair follicles. The epithelial cells of the external sheath of the hair follicle pro- liferate, the hair falls out, the limiting membrane of the follicle disappears, the neighbouring dermo-papillary tissue penetrates by epithelial buds, and the rest of the process is as in the preceding case. In the sebaceous glands, which normally possess only one or two peripheral layers of pavement epithelium, the centre of the saccule being filled with fat cells, the pavement cells of the periphery are seen, at the commencement of epithelioma, to increase in number and to push the fat cells to the centre whence they are soon extruded (tig. 152). The limiting membrane of the gland disappears. In this way sebaceous glands are transformed into lobules of epithelioma. The peripheral connective tissue is soon also transformed into embryonic tissue. The phenomena which take place in the sudoriparous glands are still more interest- ing. These tubular glands, convoluted at their deep extremity in the form of glomeruli, are lined with a simple layer of pavement epithelial cells within the limiting membrane. In epithelioma an accumulation of epithelial cells is first observed in the interior of the gland, so as to fill up and distend the primitively hollow tube. These solid cylinders of epithelium send out epitheUal buds into the adjacent embryonic tissue which unite together to form a network ; they are all formed of small pavement cells. It is by the ulterior mi-tamorphoses of these epithehal cylinders that islets of lobulated epithelioma are produced. In fact, a certain 264 TUMOURS. number of these cylinders enlarge, the cells at the periphery re- maining small and implanted on the wall, but as the centre of the enlarged tube is approached the cells become larger, undergo Fig. 152. — Pboliferation ov the Epithelial Cells of Sebaceous Glands m A Case op Epithelioma. A, epithelial cells in a state of growth ; B, sebaceous cells filled with fat ; c, neighbonring connective tissue. Magnified 150 diameters. horny or mucoid change, and concur in' the formation of bird's- nest bodies. All the phases of this evolution may be followed in Fig. 153.- -Prolifeeation of the Cells op Sudoripakous Glands is LoBULATED Epithelioma. a, &, sudoriparous excretory glands cut across ; c, rf, secretory tubes filled with epithelial cells. Magnified 150 diameters. the same tumour. The lobules become finally isolated as in the previous examples. Growth and extension of epithelioma. — Whatever may be its mode of origin lobulated epithelioma continues to extend by pro- GROWTH AND EXTENSION OF EPITHELIOMA. 265 liferation of its own proper mass, the lobules becoming larger ; or else new centres of epithelioma similar to the primitive tumour are formed in the neighbourhood. The papillae, hair follicles, and glands, adjacent to cutaneous epithelioma, show the same phe- nomena as those described in the primary development of the tumour. If in the immediate neighbourhood of epithelioma there is striated muscular tissue, as in the lip or tongue, changes similar to inflammation first take place. The muscular fasciculi are separated by connective tissue rich in cells, or by embryonic tissue, and the nuclei of the sarcolemma enlarge and multiply. Fig. 154. — Section ok a Lonui.E of Epithelioma located in the midst oi- Bone. Somo of tbo epithelial cells of the lobule have fallen out in making the preparation, leaving the empty npace, B, At a, they have remained, c, osseous lamella. Magnified 20 dior- nieters. In these cases the presence of large nuclei with voluminous and brilliant nucleoli having been observed under the sarcolemma, some authors have supposed that the muscular tissue was infiltrated with epithelial nuclei ; but this opinion, based on the form of the nuclei and nucleoli which was erroneously considered to be characteristic of epithelioma, must be rejected. The muscular fasciculi atrophy, in consequence of the pressure of the inflamed connective tissue or of the lobules of epithelioma developed in it. They still, however, preserve their cylindrical form, or, constricted at certain points they become moniliform, a change observed in other tumours of the muscles (fig. 79, a ). The fasciculi containecl 266 TUMOURS. in the morbid mass almost always show fatty infiltration or vitreous degeneration. In muscle, epithelioma extends by means of the 'em- bryonic mass which has taken the place of the muscular fasciculi and insinuated itself often for a long distance between them. In extending an epithelioma may approach superficially situated bone, such as the maxillae, the bones of the nose, the os Fig. 155. — A part of the peecedisg Figure magnified 300 Diametees. P, epithelial cells of the islet of epithelioma represented at a in the preceding figure ; o, tissue composed of fibrous medulla ; M, osseous laniellse notched ; N, bone corpuscles. frontis, the sternum, &c. ; in which case the osseous tissue near the neoplasm shows lesions analogous to those of inflammation. Embryonic medulla is produced, the osseous lamellae are destroyed, the medullary cavities enlarged, and here again, it is in the midst of embryonic tissue that the epithelial buds are pushed out. A lobule of epithelioma located in an enlarged medullary cavity is PEARL Y PA VEMENT EPITHELIOMA. 267 surrounded by embryonic tissue, which is in contact with irre- gularly festooned osseous lamellae (see figs. 154 and 155). Generalisation of epithelioma. — Epithelioma is frequently generalised in the form of nodules which originate far from the primary tumour, either in the nearest lymphatic glands or in the internal viscera, the lungs, liver, kidneys, and even the heart. It should be stated however that secondary growths in the viscera are rare, and that their histological development has not been hitherto well studied. The prognosis of lobulated epithelioma differs greatly according to the structure of the tumour and its seat. The most serious cases are those in which the stroma is entirely embryonic, and the connective tissue at the periphery of the tumour in an em- bryonic state ; for this signifies that the epithelial mass is spread- ing rapidly. Epithelioma develops most rapidly in those parts of the body most plentifully supplied with lymphatic vessels, and where the circulation of the blood is active, and also in parts exposed to causes of irritation. For example, the moist mucous orifices, subject to movements or contusions, the lips, tongue, eyeUds, cervix of the uterus, &c., are the seat of epitheliomata as rapid in growth and as surely fatal as the most malignant car- cinomata ; and yet in structure such tumours are identical with epitheliomata of the skin, nose, and cheek, which may remain quiescent for ten, fifteen, or twenty years without increasing in size or causing serious accidents. The epitheliomata which extend slowly are generally superficial and they often show a cicatrix at the centre while the tumour is spreading at the periphery. After being long stationary they may however rapidly increase and invade the deeper structures. This shows that the malignity of a tumour is often less related to its histological type than to its seat and mode of development. II. Pearly pavement epithelioma. — This tumour was called eholmteatoma by J. MUller, who confounded many different tumours under the same name. It has a certain analogy to lobulated epithelioma, as it is itself lobulated and often encysted. Its surface on section is dry, opaque, whitish, slightly luminous Uke cholesterin ; but this is only a coarse resemblance, there are in fact but few cholesterin crystals present in these tumours, not more than are met with in the softened parts of lobulated can- croid, and the shining appearance is due to dessicated epidermic lamels. On scraping, small beads are obtained visible to the naked eye, regularly round and formed of many lobes united by 268 TUMOURS. enveloping concentric layers. On microscopical examination, these little granules are seen to resemble the spherules of the choroid plexus or of angiolithic sarcoma; but they contain no calcareous salts. When stained with carmine, attached epidermic lamels containing atrophied nuclei become apparent in their external layer. Beside these epidermic pearls, isolated homy cells may be observed. Sometimes also spangles of cholesterin are obtained by scraping. In delicate sections cut from a fresh specimen, or one which has been preserved in a '2 per 100 solution of chromic acid, the tissue is seen to be characterised by lobules resembling those of lobulated epithelioma; but on attentively examining these lobules it is seen that their epi- dermic evolution is stationary. Instead of the stratified layers of cylindrical and pavement epithelium, which are found at the periphery of the lobules of ordinary lobulated epithelioma, there is here but a single layer of flat cells the nuclei of which are atrophied. The pearls are sometimes completely separated from one another, sometimes united by delicate pedicles, themselves formed of epidermic cells. Between the lobules there is a dense connective tissue containing no blood-vessels (Forster). These tumours are very rare.^ They are quite benign, and remain in an almost mummified condition as foreign bodies, causing no accidents. As they are fully developed and have been long in a stationary condition at the time of their removal, their histological develop- ment is unknown. But their resemblance in seat and structure to lobulated epithelioma allows of the hypothesis of a similar development. The cause of their benign nature and of their mummification is likewise unknown. III. Tubular epithelioma.— This tumour has been called cylin- cbroma by Billroth, polyadenoma by Broca, and under the name of heteradenic tumour Eobin has described both lobulated and tubular carcinonia and epithelioma, and many other ill-defined tumours. Epithelioma developed from the sudoriparous glands, po well described by Virchow, partly belongs to these species. Definition. — Tubular epithelioma may be defined as a tumour composed of tracts or cylinders of pavement epithelium under- going no epidermic evolution, which anastomose together and are located in a stroma formed of embryonic, mucous, or fibrous tissue. The first stage in the development of lobulated epithe- ' Though for many years we have collected and examined a great number of tumours for the hospitals of Paris and the Anatomical Society, we have met with but three examples of these tumours. DEFINITION OF TUBULAR EPITHELIOMA. 269 lioma from the sudoriparous glands (see p. 263) — when the tubes filled with pavement cells are converted into solid cylinders anastomosing together — is the final stage in the development of tubular epithelioma. But still all tubular epitheliomata are not cancroids which have commenced in the sudoriparous glands and been arrested in the first stage of development ; for tubular epithelioma maybe present in organs which have no sweat glands, as in the uterus, and even where there are no epithelial glands at all as in the lymphatic ganglia. FiQ. 156. A, Section of tubular epithelioma, a, solid cylinders composed of pavement epithelium ; ft. stroma hollowed by tubes which lodge the cylinders. Magnified 20 diameters. B. Epi- thelial colls of the same tumour isolated and showing the dentations by which they are nnlted. Uagnified 400 diameters. Description of tubular epithelioma. — The tumour is regular, spherical, or ovoid in form; on section it shows a greyish tissue resembling that of a gland or sarcoma. The diagnosis is im- possible with the naked eye. No juice is yielded on pressure. On examining scraprngs under the microscope some notions may be obtained as regards the structure of the tumour under examina- tion. Segments of cylinders composed of pavement epithelium are found; they are sometimes branching, their edges are regular, generally parallel, and their extremities are limited by sinuou.'i, irregular borders, the result of fracture. The cells com- 270 TUMOURS. posing them are small, equal in size, -with ill-defined dentate borders, so that with a low magnifying power their edges are not clearly distinguished, but well-marked nuclei are seen in the midst of a granular substance. It is owing to the dentate borders and the intimate union of the cells that they cannot be isolated in the fresh state. The dentate cells can, however, be isolated twenty-four or thirty-six hours after the removal of the tumour, owing to cadaveric decomposition whick softens the cement- ing substance (6, fig. 156). Besides these cells fusiform eeUs, free nuclei, cells and even flakes of connective tissue may be found. But the various elements obtained by scraping are not truly characteristic of this species of epithelioma ; for at the commencement of carcinoma of a gland, we may find in the scrap- ings fragments of epithelium in the form of solid cylinders, pro- duced by a new formation of epithelium in the glandular ducts of the invaded region. In delicate sections made after hardening in alcohol or in a "2 per 100 solution of chromic acid, cylinders composed of pavement epithelium are seen anastomosing together, and ar- ranged in a stroma of variable composition. The epithelial cells are dentate, their borders ill defined unless the section is extremely delicate. The stroma is generally fibrous and very dense, but sometimes it is mucoid. In such a mucoid tissue surrounded on all sides by epithelial tracts, the connective-tissue cells are generally degenerated and destroyed, and from them are formed little cavities filled with mucus. It might be thought that these cystic cavities were caused by degeneration of the epithe- lium, while they on the contrary result from alteration of the stroma, Rindfleisch has given to tumours containing them the name of cystic epithelioma. The pavement cells of all tubular epithelioma may undergo colloid degeneration ; when colloid spherules having a diameter of 20 /* to 50 /i may be seen here and there, in the epithelial tracts. Sometimes also at certain spots these tumours may show an epidermic evolution. Lobules are then seen with horny cells at the centre, an arrangement which con- nects tubular epithelioma with lobulated epithelioma proper. . Seat and development of tubular epithelioma. — When located in the skin, it develops from the sudoriparous glands. This mode of origin was long ago observed by Verneuil ; it is here developed in exactly the same manner as lobulated epithelioma, (p. 263). Being seated in the deep layers of the skin tubular epithelioma ulcerates more slowly than lobulated epitheHoma. It SEAT OF TUBULAR EPITHELIOMA. 271 is also produced by modifications of tubular glands in the cervix uteri, and the maxillary sinus, and even from acinous glands, as may be observed in the velum palati. Among the numerous tumours of the mamma described formerly under the name of carcinoma, some may be observed corresponding in every detail to the description of tubular epithelioma. Tubular epithelioma is distinguished from carcinoma of the mamma by the fact, that in carcinoma the cells are not firmly united together so as to form masses or cylinders which can be detached by scraping. Exception must, however, be made in carcinoma of the breast, for the epi- thelial cyUnders which are developed in the galactophorous ducts of large and medium calibre, and which result from the prolifera- Fio. 157. — ^Transverse Section of a Tubular Epithelioma. A, epitholial cylinders divided obliquely ; b, fibrous stroma. tion and accumulation of epithelial cells in their lumen. Such epithelial cylinders may be met with in all tumours of the breast, whatever may be their nature ; they result from secondary irri- tation of the glactophorous ducts caused by the development of the tumour. By obliterating the glandular ducts the formation of cysts is frequently brought about ; the wall of these cysts is sometimes regular, sometimes covered by growths formed of the morbid tissue. Hence every tumour of the breast has the property of producing certain morbid forms which are common to all. An exhaustive histological examination is always necessary to deter- mine t he nature of a tumour of this organ. Many tubular epithe- 472 TUMOURS liomata, having readied a certain stage of development, remain sta,tionary. Sometimes they continue to extend, in which case the epithelial cylinders terminate in culs-de-sac in the midst of an embryonic tissue. Growth then takes place by simple exten- sion, or by successive metamorphoses of neighbouring embryonic cells. Prognosis of tubular epithelioma. — When located in the skin {partial sebaceous acne) it is less ^serious than lobulated epithe- lioma, a fact on which Verneuil has rightly insisted. But this benignity must not be understood in too absolute a sense, for tubular epithelioma often relapses after removal. It is often pro- FiQ. 158. — Section oif an Epithelioma containing Ovoid Bodies. This drawing represents a section of the skin and tbe snbjaoent tissue magnified 20 diameters. e, epidermic layers ; m, c, epittelial tracts and islets located in the midst of a subcutaneous fibrous tissue. This drawing and the following one are from a tumour examined by M. Molassez. pagated, as we have been able to verify, to the lymphatic glands in which a tissue is formed similar to that of the primary tumour. It is also sometimes transformed into lobulated epithelioma. Among tumours formerly regarded as cancerous, they are the slowest in development. Sometimes after destroying all the glandular elements of a part of a skin, the centre of the morbid mass may cicatrise whilst the periphery continues to extend — in a word, they extend in a similar manner to certain ulcerating chancres. When situated in the neck of the uterus, the prognosis is quite as serious as that of carcinomatous and other epithelial tumours in tbe same region. Tubular epithelioma primarily developed in the PROGNOSIS OF TUBULAR EPITHELIOMA. 273 maxillary sinus, a rather common situation, spreads rapidly and is extremely serious. With tubular epithelioma we must include certain tumours described by Robin, Forster, &c., which present a peculiar arrange- ment. They are formed of epithelial cylinders and lobules seated in the midst of fibrous tissue (figs. 158 and 159), in the centre of which are found here and there refiractive bodies (c, fig. 159) united together by anhistic processes. In the interior of these Fio. 159. — Suction^ OP the sajie Epithelial Tumour with the Ovoid Bodies as_jThe preceding, but magnified 250 diameters. n, wction of an epithelial tube in the midst of which is a little ovoid body ; e, a larger epi- thelial lobule, in the centre of which is a mucous ovoid body, c. bodies stellate cells are often observed. According to Forster these tumours are epitheliomata ; Kobin looks upon them as heteradenic tumoiu-s. They are very rare, and are, in fact, tubular epithelio- mata with mucous connective-tissue growths in the midst of the epithelial mass. The ovoid bodies correspond to buds of mucous connective tissue, and in the pedicle, which unites them to the stroma of the tumour, blood-vessels are often found. IV. Cylindrical-celled epithelioma. — This peculiar species of T 274 TUMOURS. epithelioma, discovered by Bidder, has been well described by Forster and Virchow, and we have ourselves examined and pub- lished a great number of cases. It was formerly confounded with encephaloid and colloid carcinoma. It is characterised by tubular or irregularly formed cavities, lined with one or more layers of cylindrical epithelial cells, located in a fibrous, embryonic, or mucous stroma. The cylindrical cells are similar to those which line certain mucous or glandular cavities, and are always inserted perpendicularly on the wall they cover. The naked eye appear- ances of these tumours vary. In the stomach and intestine they are like nummular prominences, varying both in number and size, generally ulcerated at the centre. When, as is frequently the case, they are propagated to the liver and other organs, they Fig. .160. — Tkaksverse Section of an Epithelioma with Cylxndeical . Cells. , o, tube divided transversely, lined %vith epithelium, c; in- the centre are a few free and isolated cylindrical cells; 6, tube divided longitudinally. show the same arrangement, dissemination, and naked eye ap- pearances as encephaloid carcinoma. In some cases whitish tracts are seen in section. These tumours have generally an abundance of milky juice, so that this character, taken in connection with their usual softness, might cause them at first sight to be mistaken for encephaloid carcinomata. The softness and juice are, probably in a great measure, due to cadaveric softening. In fact, these tumours, always seated in the internal organs, are never discovered till twenty-four hoiu-s after death. Cadaveric softening occurring less rapidly in the winter than in the summer, tumours examined during the cold season yield much less juice. The fluid obtained by scraping is, as in all other epitheliomata, distinctly grumous. The elements contained in the juice are C YLINDRICAI^CELLED EPITHELIOMA, 275 cylindrical cells. On their free surface they often show a double border. Some seen sideways appear like the fusiform elements of sarcoma, others show on their free border a vesicular or caliciform dilatation. They are generally elongated and rod-shaped, measuring 20 /A to 30 /i and even longer ; but some are polygonal or more or less irregular. They possess one or more oval nuclei, measuring lO^to 15/iin length, and contain one or more brilliant nucleoli. It is thus seen that there is a certain polymorphia in the cells. Sometimes cylindrical cells may be tmited by their lateral borders, and show along their free edge a limiting double line. This appearance is so characteristic that it is enough of itself to establish the diagnosis of cylindrical epithelioma. Fio. ]fil. — Skciiox of a Cvlindrical EpiriiELioMA OF THE Large Intestine. 9i 7( layer of hypertrophied glands of Liebcrklihn ; these glands are destroyed to the right of the drawing, which corresponds to the ulcerated part ; A, A, cavities lined with cylin- drical epitheliam. Magnified 40 diameters. The histological structure of the tumour is ascertained by the examination of hardened preparations : (if the tumour has softened it is as well to immediately use absolute alcohol). In a delicate section it is then seen that the tubidar cavities or irregular spaces are lined with cylindrical epithelium. These tubes and spaces, which are sometimes sinuous and have papillae on their surface, axe often distinctly seen to be continuous with neighbouring glands ; the latter, hypertrophied, may form a distinct layer on the surface of the tumour if it is situated in the stomach or intestine (see fig. 161 ). The cells, generally simply arranged, form a regulax layer, and are inserted directly into the stroma, without the interposition of any basement membrane (fig. 161). Besides the tubes and T 2 276 TUMOURS, irregular cavities thus lined, the surface of the tumour is often covered with papillae lined with cylindrical epithelium. When development is complete, the stroma is fibrous, but it is often embryonic in tumours of recent date ; occasionally it is mucous as in myxoma and composed of round or anastomosing connective- tissue cells. It always contains blood-vessels, which are numerous and similar in structure to those of sarcoma, if the stroma is embryonic. Though usually slight in amount the stroma may predominate and constitute the largest part of the tumour. Varieties of cylindrical epithelioma may be distinguished ac- cording as the stroma predominates or as it is fibrous, embryonic, or mucous. The blood-vessels often dilate, ending in hsemorrhagic ruptm:es, which is a rather frequent accident in the mucous form. An important and common variety consists in the colloid change of the epithelial cells. They are changed into transparent vesicles, which are successively detached from the wall of the tube and faU into the lumen, A border of cylindrical cells may then be found limiting a cavity filled with colloid substance and the debris of cells. At other times the parietal cells are themselves completely degenerated, in which case the little cavity containing them has no longer any of the characteristics of cylindrical epithelioma. Fatty degeneration is generally associated with colloid change. This form of epithelioma always eventually ulcerates when seated in the mucous membranes. Its superficial destruction is not solely in consequence of the evolution of the morbid tissue, but is also due to the irritating and even destructive action of the fluids with which it is in contact. For example, the gastric juice has a manifest corrosive action on living tissues developed in the stomach, if they are not protected by the physiological epithe- Uum of that organ. On the surface of tumours of the stomach coagula of black blood are often found, broken up in the blood^ vessels ; this coagulation is due to the action of the gastric juice, The development of cylindrical epithelioma takes ^place at the expense of the glands, by a process analogous to that described in pavement epithelioma. Seat of cylindrical epithelioma. — With the exception of the ovary, this tumour is always found on mucous membranes lined noTTnally with cylindrical epithelium,, that is to say the mucous membranes of the stomach, small and large intestine, rectum, bile ducts and uterus. Certain soft, polypoid tumours developed in the fundus or cervix of the uterus, and extending into the vagina, and which are difficult to remove on account of their softness, are. DIAGNOSIS OF CYLINDRICAL EPITHELIOMA. 277 in spite of their analogy with certain benign tumours of the uterus, cylindrical epitheliomata and really malignant growths.^ In the ovary, we have seen non-cystic tumours resembling carci- noma to the naked eye, and which had undergone partly fatty and partly mucoid changes, which were, however, cylindrical epithe- liomata. Certain polypi of the nasal fossae, which with the naked eye cannot be differentiated from other varieties of mucous polypus, correspond histologically to cylindrical epithelioma. Prognosis. — Secondary growths, the structure of which is iden- tical with that of the primary tumour, are met with particularly in the liver, in consequence of the venous relations of this organ with the intestine. There are also certain well-authenticated observations of the generalisation of cylindrical epithelioma, in the form of nodosities, in the lungs and bones. As they are located in the deep organs it is impossible to differentiate them during life from carcinoma, they have however the same gravity and the same fatal termination. The anatomical diagnosis is generally easy if attention is paid to the facts unfolded above. Tubular epithelioma must be care- fully differentiated from medullary or colloid carcinoma when soft. In secondary and rapidly growing formations of the liver, the centre is softened, and the epithelial cells dissociated and filled with fat granules. The tumour loses its characteristic appear- ance and becomes riddled with alveoli ; so that on brushing away the cells an alveolar stroma is discovered exactly similar to that of carcinoma. The similarity is so great that if the younger peripheral parts were not there to guide the observer, it would be impossible to make the diagnosis. To distinguish cylindrical epithelioma which has undergone colloid change from colloid carcinoma, the most recently formed parts not yet touched by colloid degeneration must be studied with the greatest care. II. Papilloma. Papillomata are not regarded by all pathologists as forming a distinct group of tumours. All tumours become papillary under certain conditions ; if located on a surface, for example. Thus certain pathologists, Eokitansky among others, describe papilloma as fibroma which has taken on a papillary appearance, and Forster has remarked that papillomata may be described with angiomata, as they nearly always possess as an essential part newly formed ' Thesis of M'liithmai, 1867 278 TUMOURS. blood-vessels. "We consider that the definition of papillomata is given by that of the papillae themselves. Now, it is well known, that papillae are composed of connective tissue serving to support blood-vessels which terminate in a capillary network or in vascular loops, and that they are covered by an epithelial lining. These normal excrescences, which limit the skin and certain mucous membranes, are sometimes covered by stratified layers of pavement and horny epithelium, sometimes lined by a mucous epithehum. These two normal types serve as the basis for two Fig. 162. — Hoknt Papilloma of the Loweb Lip. o, horny covering ; 5, granular layer ; «, rete mucosum ; d, blooi-vessels of the papillie ; e, connective tissue. Magnified 100 diameters. species of papilloma — horny papilloma, and mucous papilloma. For a tumour to be called papilloma the body of the papillae should be composed of connective tissue, and the layers of invest- ing epithelium arranged as upon normal papillae. The tissue at the base of the papillae should moreover not be constituted by that of one of the special tumours described in the preceding pages. It is essential in fact that sarcoma, fibroma, carcinoma, and epithelioma, presenting on their surfaces papillary buds, HORNY AND MUCOUS PAPILLOMA. 279 should not be confounded with papilloma. In these cases the tumour should simply take the name of papillary. I. Homy papilloma. — This class contains a number of tumours. Most authors include in it corns, warts, and horns. Corns seated upon the toes are caused by a constant pressure or irritation. They commence by hypertrophy of the papillae. The homy layers of the epidermis soon exercise pressure on the papillae, so as to flatten and drive them down like a nail in the cutis. The latter atrophies, the adipose tissue disappears at the point of pressure, and sometimes a mucous bursa is formed beneath. The papillae, at first hypertrophied at the base of the com, soon become depressed instead of projecting in a tumefied manner. Warts. — In these the papillae hypertrophy and give origin to secondary papillae. The covering composed of cells, similar to those of the rete mucosum and epidermis, envelops the entire new papillary mass with a smooth layer ; or a certain number of the papillae are isolated by an epidermic covering proper to each group; from which arrangement the tumour has an unequal, cracked appearance. The connective tissue which siurounds the blood-vessels is found to be less abundant as we pass from the base of the tumour to the superficial secondary papillae. In a transverse section, each one of the papillae on the surface of the tumour shows one or more central disks which correspond to the divided vessels. Around these disks there is a slight quantity of connective tissue bounded by layers of epidermis. Horns may be looked upon as warts the epidermic cells of which are welded together as in the nails. They are observed in different parts of the skin, but particularlly on the face. They are also met with in dermoid cysts. The epidermic cells of which these horns are composed are not desquamated, but are super- imposed indefinitely, from which result hard appendages of various length, and formed of imbricated layers of epidermal cells. Certain nsevi are also horny papillomata. They are formed of simple or composite papillae. Viewed full-face the tips of a great number of papillae are seen, all covered with layers of dried epidermis ; on separating the papillfe, between them at their bases, smaller papillfe are seen covered like the larger ones. These congenital tumours are sometimes deeply pigmented. II. Mucous papilloma. — In this form the papillae are simple or composite. Villous papillomata are also observed, in which the papillae by their length and tenuity resemble the villi of the 28o TUMOURS. mucous membranes. In papillse there are two parts to study, the papillary body and the epithelial covering. The papillary body has the form of a more or less voluminous bud which gives origin to a varying number of secondary and tertiary buds. Its variable shape depends upon the new formation of vascular loops. It is composed of connective tissue giving support to blood-vessels which terminate in loops at the extremity of the papillse. The connec- tive tissue is sometimes so slight in quantity that the epithelial covering seems to rest directly on the blood-vessels. In recent and rapidly growing papilloma, for example in certain cauUflower excrescences of the genital organs, the body of the papUla is formed of embryonic connective tissue. The blood-vessels of papilloma are arteries, capillaries, and veins of normal structure. The capillaries are often dilated in a regular or ampullar manner, fio. 163. — ViLioTis Papilla of new Fokmation on THE Mucous Membrane of the Stomach. Magnified 60 diameters. haemorrhages being caused by their rupture ; the blood escapes or remains imprisoned in the body of the papilla, where it undergoes pigmentary change. The vessels of the papilla may throw out buds, and undergo calcareous degeneration. Villous papillse are generally simple ; they sometimes become very long, particularly when compressed laterally against one another. The epithelial covering of papillae differs according to the pavement or cylindrical form of the cells. In the first case a large number of layers of cells imdergo an evolution identical with that of the rete muco- sum, or the epithelial lining of the buccal mucous membrane. The cells are plainly seen to be dentate, those at the surface being flattened. Papillomata often have a covering of pavement cells, DEVELOPMENT OF MUCOUS PAPILLOMA. 281 while the mucous membrane whence they spring may be lined with cylindrical cells. When the papillary body is covered with cylindrical epithelium, there is but one layer. The investing cells of papilloma are often vesicular and in a state of colloid degeneration. The development of mucous papilloma is generally at the expense of the vilU or papillae from which they spring, but they may develop in parts which have no papillsc, as for example in the ventricles of the larynx, or in the stomach. The precise pheno- mena of these hypertrophies and neoplasms have not been closely followed in papilloma, but the analogy of their structure with that of inflammatory granulations leads to the supposition that their Fig. 164. — Papilloma of the Larynx. A, base of composite papilto ; e, epitheUal covering of the papiUffl; jr, normal glands of the muoons membrane ; / a gland partly atrophied at the base of the papilloma. Magnified 20 diameters. mode of formation is the same. Chronic inflammation is often a cause of the development ol papilloma, as may be observed, for example, at the periphery of callous ulcers of the skin and in elephantiasis. Papilloma cannot, however, be considered as identical with inflammatory granulations, for the tendency of the latter is to heal, by the organisation of their elements into cica- tricial connective tissue, whilst papilloma tends to persist inde- finitely as a tumour. Their termination is thus dififerent, though in their origin they have numerous points of contact. There are nevertheless papiUomata, such as the cauliflower excrescences of the genital organs, which may disappear spontaneously or m conse- 282 TUMOURS. quence of local treatment. These may be considered as transitory between timiours properly so called and inflammatory products. Seat of papilloma. — Mucous papillomata are rather frequently found on the edge of the tongue, the uvula, and on the mucous membrane of the larynx, sometimes on the ventricles of the larynx and on the vocal cords. These are generally simple papil- lomata not complicated with adenoma. They are also rather common in the gastro-intestinal mucous membrane (for further details see article on stomach and intestine), where they are often combined with hypertrophy of the glands. On the mucous membrane of the bladder and the urethra papillomata are deve- Fig. 165. — Papilloma at the Ukethral Orifice. a, horny layer ; &, rete mucosum ; c, connective tissue in which ramify a great number of arterial vessels, u, or capillaries, d ; these vessels are all extremely sinuous in the papillss and at their bases. Kagnified 60 diameters. loped, composed of long, delicate, villous, and highly vascular papillae, which bud at the base of the bladder and at the urethral orifice. On both the male and female external genital organs, papillomata commonly called cauliflower growths, spring up from the most varied causes, sometimes they are very small, at others they attain a considerable size. Extirpation is generally necessary, but the irritation consequent on operation may cause recurrence of the growths. Papilloma may be observed in serous Tnembra/nes, particularly in those articular serous cavities which normally possess villi; these may hypertrophy so as to form veritable THE DIAGNOSIS AND PROGNOSIS OF PAPILLOMA. 283 tumours. The modifications of these villi will be studied when analysing the lesions of chronic arthritis, the most frequent cause of these changes. In the cerebral ventricles we have seen cases of papillary neoplasms ; these take their point of departure irom the walls of the ventricles, and are formed of enormous composite papillae completely covered with stratified and dentate pavement cells. Many of the papillae show calcareous globes and fatty in- filtration. The pavement cells covering the buds, partly disinte- grated by cadaveric softening, form a whitish juice, so that a tumour of this kind might be mistaken for encephaloid carcinoma. The type of this singular pathological product may be found phy- siologically in the choroid plexus, composed of blood-vessels and vascular buds infiltrated with calcareous salts ; the buds in the choroid plexus are also covered with pavement epithelium. The diagnosis of papilloma is easily made in the majority of cases ; but at times it is very difl&cult and can only be established after minute examination. To be certain that the tumour is a papilloma, neither the alveoli of carcinoma, nor glandular tracts, nor islets of epithelium should be found at the base of the papillae. Now, a section, cut perpendicularly to the surface of a hardened papilloma, shows spaces between the papillae at very dififerent levels, the epithelial cells of which must not be mistaken for lobules of epithelioma ; it is easy to make the distinction ; for the latter penetrate far into the corium or submucous tissue, while the deepest of the interpapillary spaces of papilloma are almost on the same level as normal papillae. On the other hand, if a trans- verse section of papilloma be cut rather obliquely, the interpapil- lary spaces, divided obliquely at their bases, resemble and may be mistaken for lobules of epithelioma. To be warned of the possibility of such an error is to avoid it, by making good prepara- tions. The diagnosis is only possible under this condition. The prognosis of papilloma is generally not serious, but by their seat they impede the performance of important functions — papillomata at the neck of the bladder for instance. In some cases, happily very rare, they become the point of departure of epithelioma. III. Adenoma. Adenomata correspond exactly to the glandular hypertrophies described by Lebert ; they have been confounded with a great 284 TUMOURS. many other tumours under the name of adenoid tumours, poly- adenomata, heteradenomuta, &c. We consider adenomata to be tumours having the same structure as glands. Glands are divided into — 1, racemose glands; 2, tubular glands, which latter may be again divided into those lined with a pavement and those with a cylindrical epithelium. In the same way adenomata may be divided into — 1. Acinous adenoma; 2. Tubular adenoma con- taining cylindrical epithelium. Many French authors have also described an adenoma composed of glands containing pavement epithelium. But the existence of this species does not seem to us sufficiently established to be admitted in a definite manner without new facts being adduced to establish it beyond doubt. 1. Acinous adenoma. — Cruveilhier remarked that all tumours of the breast were not scirrhous, encephaloid, or colloid cancers, and he recognised a group of tumours which were hard or soft, yielding no juice and often encysted. These he called fibroid bodies of the m,amma. Velpeau supposing that these tumours were caused by blows on the breast, a customary etiology to which all patients refer tumours, thought that they were caused by extravasations of blood which underwent ulterior modifications, and he gave them the name oi fibrinous tuTuours. It was only later, when Lebert had discovered the glandular acini of these tumours, that Velpeau called them adenoid tumours, a name which does not distinctly signify that these tumours are formed of glands, but simply of a tissue having a glandular appearance. Lebert described them in his great work under the name of hypertrophies of the mamma. According to Broca (Art. ' Adenoma ' in the Diet. Encyclo.) all that Cruveilhier called fibroid bodies of the breast and Velpeau adenoid tumours, are adenomata. The truth is, however, not as simple. We have in fact often examined tumours which had been diagnosed as adenoid by Velpeau, and have found them to be some- times massive or papillary fibroma of the breast (p. 166) or sar- coma (p. 140j or myxoma, and sometimes, but very rarely, true adenoma. In describing fibroma, myxoma and sarcoma of the breast, we drew attention to the peculiarities they present when located in the breast, the growths they cause in the galacto- phorous ducts and acini, and the round or lacunar cysts with which they are riddled. Adenomata of the breast are small and generally blended with the glandular tissue, while well-defined tumours quite distinct from the gland are generally fibromata, myxomata or sarcomata. They vary in size from that of a hazel nut to a walnut and are DIAGNOSIS OF ACINOUS ADENOMA. 285 rarely larger. They contain no lacunar cysts, so that if these are pre- sent, far from characterising adenoma they eliminate it altogether. They are composed of acini arranged side by side, and separated by a small quantity of fibrous tissue. These acini are bounded by a well-defined membrane, which is lined with a regular epithelium. The development of these tumours is very slow and they never cause secondary growths. It has been suggested that they may become converted into carcinomata. This hypothesis is not based on well- authenticated facts. Lesions analogous to those of the breast may occur in other acinous glands, such are certain tumours of the parotid gland, hypertrophy of the lacrymal gland of which Lebert reports a case. The velum palati and the pharynx may also be the seat of tumours caused by considerable hypertrophy of the acinous glands they contain. These tumours are sometimes solitary and prominent, at others diffused and cause a general uniform thickening of the mucous membrane.' Diagnosis of acinous adenoma. — In making the diagnosis of acinous adenomata they must be distinguished from all new growths, which by developing in the neighbourhood of glands cause a proliferation of the epithelium of their acini. Thus in acute or chronic laryngitis, at the same time that proliferation of the connective tissue of the mucous membrane takes place there is an increase in the size of the glandular acini, so that many attain double or triple their normal volume. They are also filled with epithelial cells, some arranged regularly against the wall, others free in the lumen of the gland, and in a state of fatty or colloid degeneration. Similar changes are met with in other mucous membranes. The glands of Lieberkiihn of the intestine are, for example, always much hypertrophied adjacent to the Peyer's jiatches which are not yet ulcerated in typhoid fever. It is evident then that these appearances are the consequences of inflammatory irritation of glands, and not of adenomata. In tumours hitherto described, we have seen that every neoplasm affecting the stroma of a gland is accompanied, at a certain moment, with proliferation of the epithelial cells of the acini and excretory ducts, followed by dilatation of these cavities, and by various ulterior modifications ' In a case of this kind examined by ourselves the velum palati measured no less than one centimetre in thickness, and the glands, perfectly distinct and alone (he cause of the thickening, showed their acini normally opening by the aid of ducts on to the surface of the mucous membrane, as in the physiological state. In this case the epithelial cells of the saccules presented physiological characteristics. 286 TUMOURS. of their contents. For example, every chondroma of the parotid causes proliferation of the glandular epithelium, and yet no one dreams of including these tumours among adenomata or epithe- liomata. In tumours when the glands hypertrophy at the com- mencement and in the adult condition of the neoplasm, they soon undergo various changes, such as fatty or colloid degeneration of their epithelial cells, changes which often end in the formation of cysts or in atrophy of the acini. But when a tumour containing many hypertrophied glandular acini, a sarcoma of the breast for example, recurs after removal, the new growth generally contains no glands ; an evident proof that the tumour was not adenoma, and that the hypertrophy of the glands in the primary tumour was an accessory fact. If the primary tumour had been an adenoma, the new growth on relapse in situ would have had the structure of adenoma. Such cases are common. Another example may be found in tumours of the testicle, called cysto- sarcoma or cystic tumour. When these tumours become general- ised, the secondary growths in the lymphatic glands, peritoneum, lungs, &c., are found to have simply the structure of sarcoma. It is only by exact knowledge, and by an attentive examination of each case, that true adenoma can be recognised. The diagnosis may be established by the complete resemblance in structure and arrangement of the culs-de-sac with those of the gland attacked, by the outhne of the acini, and finally by the nature of the inter- acinous tissue. We may add moreover that no tumour is more rare than true acinous adenoma. II. Tubular adenoma with cylindrical cells. — These tumours are very common in mucous membranes containing tubular glands. They result from general hypertrophy and budding of these glands, which hypertrophy causes a thickening of the mucous membrane and often even polypoid projections. The tumour is soft, generally but slightly vascular, and rather translucid. Superficially it has the same colour as the mucous membrane. On section it yields no milky juice, but a mucous fluid in which, under the microscope, cylindrical cells are seen isolated or united into flakes, also round and chalice cells. After hardening the specimens in alcohol or chromic acid, the sections obtained have a very different appearance according as the tubes are divided longitudinally or transversely. The longitudinal sections show the tubes lengthwise, often presenting lateral buds or true bifur- cations, and either opening on to the surface of the mucous mem- brane or terminating in culs de-sac situated at different levels TUBULAR ADENOMA. 287 These tubes are generally situated so close together that there seems to be no fibrous stroma. In other cases the latter is rather Fig. 166. — Tkansvekse Section ot' a Small Polypoid Adenoma OF THE Sm/Vll Intestine. Magnified 20 diameters. thick. The tubes are very often dilated in places. The epithe- lium which lines them is distinctly cylindrical. Its component cells are two or three times longer than is normally the case in Fio. 167.— Section uk a Micois Tolypus of the Intestine. _ O free surfncc ot the polypus ; m, oyUndrical epitheUnm which lines the surface of the 'graS^ t™bS and Wties c; d. flbroos tmbeculBssep«ut,ng the glandular tubes; r, blood-vessels ; a, thickened connective tissi;o. Magnified 20 diameters. the same glands; they have generally the same characters as chalice cells, that is to say, they are filled with mucus. It is 288 TUMOURS. particularly at the dilated points of the glands that chalice cells are observed. The tubes cut across transversely appear Mke circles with a regular border of chalice or cylindrical cells round a central lumen. The dilatation of the glandular tubes constitutes the first phase in the formation of cysts filled with colloid sub- stance, and which are common in these tumours. The ovules of Naboth (fig. 168), which result from modifications of the tubular glands of the mucous membrane of the uterus, are almost the physiological type of these cysts. Fig. 168. — Ovula Nabothi from the Vaginal poetion op the Cervix Uteri. o, spherical dilatation at a gland the orifloe of which opeus at p ; a, tubular gland. Magnified 20 diameters. Seat of cylindrical-celled adenoma. — Hypertrophied glands of the gastro-intestmal m,ucous membra/ne are found rather fre- quently ; in the stomach, the hypertrophied glands may be changed, by the plugging of their orifice with mucus and the retention of their secretion, into small cysts resembling the ovules of Naboth. Scattered through the mucous membrane irregularly, or in well-defined spots, various sized vesicles, which have taken the place of tubular glands or parts of them, may be met with (fig. 169). These hypertrophied glands and cystic vessels may form small tumours which often become pedunculated and form polypi. In the uterus, these mucous polypi may project into the vagina as far as the vulva, and as in the stomach (vide mucous polypi of these organs) hypertrophied glands may often combine with papillary neoplasms (vide fig. 170) to form composite tumours, villous on their surface, cystic and glandular throughout the rest of their mass. Similar tumours are developed in the rectum and small vntestine. In these the glandular buds springing from the terminal extremities of simple glands may be seen to give origin to new acini, so that glands originally tubular are changed into composite CYLINDRICAL-CELLED ADENOMA. 289 glands. It is seen, however, that these glands do not devinfe -Si*^ 1 1 -' ■HIM RICH -(. I 1 I) Al fc,\ lA 111 br HACII. Figure borrowed from Viroliow. from their primitive function, and that they continue to open on h\\ ^ .' Fifi. 170. — Cvi.iNPnirAi.-( Ki.TEii Adenomata ok tmk Sr<^^IA( ii wnh A Vii.i.ois loM.iiHPN oi' Till'. ^^i-iiiviK (ir Till: Tr.Miiri;. iJiitriilictl 20 diamcttTS. V 290 TUMOURS. to the surface of the mucous membrane and pour out the products of secretion. They may nevertheless, as in the preceding cases,' give origin to small cysts. The stroma of the tumour is fibrous in the parts completely developed, and embryonic in the parts where the gland is budding. If the tumour developed in the rectum projects after pedieulisation at the anus, the investing layers of epithelium change their character, the cylindrical cells being changed into pavement cells, which may even on the sur- face undergo horny degeneration. In the projecting parts in contact with the air, the glandular depressions are filled with stratified pavement cells, and the inter-glandular projections present thenceforth the appearance of papillse, so that a layer of tubular glands may be seen to be transformed into a layer of papillse covered with squamous epithelium. In the uterus, besides the vesicular changes of the glands we have indicated, glandular growths are seen characterised principally by' hyper- trophy of the glands of the cervix. These tumours are small, enclosed in the cavity of the cervix, or they may project through the OS uteri into the vagina. Described by Huguier under the name of Tnucoid cr utero-vesicular polypi, they appear as red, soft masses, over which transparent vesicles are scattered, varying in size from that of a millet seed to that of a grape stone, or as fleshy, sometimes flattened appendages ; the latter have superficial projections and depressions like the arbor vitse. In structure, they greatly resemble the mucous membrane of the cervix, only that the parts are considerably hypertrophied. The folds lined with cylindrical epithelium are deeper and more numerous, the cylindrical cells are longer, and the glands dilated and branching. Sometimes the glands are not distended into cysts, in which case the name of utero-vesicular polypus is not applicable. Most frequently, however, the glands have numerous cystic dilatations throughout the thickness of the morbid mass. The stroma of these tumours is habitually formed of succulent fibrous tissue, permeated by numerous and dilated blood-vessels. Sometimes smooth muscle cells are also met with. These uterine polypi are covered with cylindrical epithelium in the cervix, with pave- ment cells in the vagina, and when projecting externally, which is very rare, with horny epithelium. But these changes of form of the superficial epithelium do not extend to cells lining ducts of the tubular glands, nor even to the depressions similar to the folds of the arbor vitse which these polypi sometimes show. Polypi of the nasal fossae are also met with, formed of arbores- C YLINDRICAL-CELLED ADEXO.MA. 291 cent papillae, covered and surrounded with pavement epithe- lium. Diagnosis of cylindrical-celled adenoma. — Among nasal polypi there are some so similar to cj-stic adenomata of the uterus that it is impossible to distinguish between them, even after micro- scopic examination. We have seen cases of this kind, in which the glands lined with cylindrical epithelium, and the cystic dilata- tions perfectly resembled uterine tumours previously described. The most frequent form of nasal polypus is, as we have already Fill. 171. — Patillaky Polypus or the Nasal Foss.e. n, pavement epithelial cells of which tlio most deeply placed, , blood-vessel ; m, cj lindrioal epithelium. layer, small cysts are observed varying in size from a pin's head to that of a nut, exactly similar to the parent cyst. Ovarian cysts contain a serous or colloid fluid, sometimes colourless, but often stained red or a more or less dark brown. In it are found regular or deformed epithelial cells, in a state of colloid or granular fatty degeneration and undergoing destruction, free fat granules, and often cholesterin crystals, which may be present in such numbers that they may be seen to glitter in the fluid. When the fluid is coloured, red blood-corpuscles variously altered, granules, and crystals of hematoidin are found. The development of the secondary cysts has been studied by Forster and Wilson Fox with very different results. Forster found in the thickness of the wall of the primary cysts, islets of indifferent cells the most internal of which undergo colloid de- 302 TUMOURS. generation and are destroyed, while those at the periphery persist and constitute the epithelial lining of the cystic cavity. Accord- ing to Wilson Fox, secondary cysts are formed by the free ends of the papillae and villi becoming welded together, leaving at their bases cystic cavities lined by a continuation of the same, epithelium. Such is the mode of development represented at fig. 175. We do not deny the possibility of the mode of production indicated by Forster, but we are bound to say that we have been unable to follow it in a satisfactory manner. Thus, we have ob- served round islets of embryonic tissue in the walls of cysts, but we have been unable to trace the transformation of these into true cysts. We are aware that MM. Malassez and de Sinety think that secondary cysts are developed by epithehal buds and glove-like depressions, passing from the internal surface into the connective tissue of the wall, and it is reasonable to think that secondary cysts spring from the surface of a cyst already formed in the same manner as primary cysts are developed from the epithelium which covers the ovary. These tumours greatly resemble adenoma and papilloma, both as regards structure and character. In fact if a good pre- paration from the wall of an ovarian cyst be submitted for exami- nation, without the observer being previously informed whence it was taken, hesitation would be felt in deciding if it were a pro- liferous cyst, an adenoma of the cervix uteri or of the nasal fossae, a papilloma, or even a cylindrical-celled epithelioma. These tumours are also very similar to sarcoma developed in a gland, the mamma or testicle for example. But on examining the whole morbid mass doubt is no longer possible. Proliferous cysts may attain an enormous size and cause death, but they do not generally produce secondary growths like sarcoma or carcinoma. True cysts are included among mixed tumours. XI. Mixed Tumoues. In the foetus or new-bom infant, large tumours are sometimes found formed of an embryonic tissue, which has undergone such an evolution that most of the tissues are represented.' These tumours in form, colour, and consistency resemble encephaloid carcinomata. In the midst of the embryonic tissue, which is ' We have bad occasion to examine two voluminous tumours of this kind ; one was presented to the Soe. de Chir., with a histological note by Charles Robin, who considered it to be a heterotopia of the ovary. {Soc. de Ckw. 1867.) MIXED TUMOURS. 303 permeated by blood-vessels with embryonic walls, are found, firstly, striated muscular fibres in the process of development ; secondly, embryonic cartilage ; thirdly, bone in the act of developing from cartilage : the cartilaginous and osseous masses are covered re- spectively with perichondrium and periosteum; fourthly, cysts with a well-defined membrane and internal epithelial lining formed of tesselated or cylindrical ciliated cells ; fifthly, long tracts or tubes of cylindrical epithelium, or lobules of pavement epithelium. These tumours cannot be looked upon as foetal inclusions, for there is nothing in them resembling the form of a foetus. The name of teratoma which Virchow proposes to give them does not seem to us to be suitable, for though they are formed of various tissues in process of development as in the embryo, they have as a whole no fixed form recalling that of an added being. They have, on the contrary, the form of an enormous embryonic bud springing from the surface of a being undergoing development, and participating in the property, which at this age all embryonic tissue possesses, of forming every kind of organic tissue. These various tissues, muscular, osseous, &c,, have a much less advanced degree of development than those in the subject bearing the tumour ; so that supposing that the elements develop regularly, the date of their origin can be calculated. As new-born infants affected with these tumours soon die, it is not known what they might become later. These complex embryonic tumom-s may be strictly regarded as sarcomata developed in embryo ; but owing to the multiplicity of the normal tissues met with in them, par- ticularly by the presence of epithelial, cartilaginous, and muscular masses, they are distinguished from all sarcomata hitherto di scribed. Bibliographical References. Apart from the treatises of pathological histology indicated on p. 56, the following monographs on tumours should be consulted : — MOllkh (J.), Vohei- den feincrcii Ban ,afon,ir pathdoyiqve, with atlas. PAGET, Leetnees on Surgical Path., London, 304 TUMOURS. 1853, vol. ii. pp. 151, 155, 212. Robin, Comptes Rendm de la SoHete de Biohgie, 1849, p. 119. Nblaton (Eugtee), Twmetirs a myeloplaxes, thfese, Paris, 1860. ViRCHOW, Psammomata and gUomata (^Pathologie des twmeurs), lecture 18, t. ii. ; Sarcomata, Lecture 19, same volume. Coenil et Tkasbot, De la Milanese, in 4to, Paris, 1868. L. Malassbz et Ch. Monod, Sur les Twmewn b, myiloplaxen {Ar- oMves de Physiologie, 1878). Myxoma. — Muller (J.), Mutter's Arcltw. 1836. Virchow, Pathology of Tuttwurs, lecture 15, vol. i. Fibroma. — Vbenbuil, Quelgnes Propositions siw les Fibromes ou Twmews formees pa/r du tissu cellnlaAre (^Gaa. mid. de Pam, 1856, No. 5, p. 69; No. 7, p. 95). Cruvbilhieb, Traite d'Anat.path. gin., t. iii. pp. 63, 715. Virchow, Pathology of Twtmurs, Lecture 13, v. 1. Lipoma. — Cettveilhibr, Traite d'Anat. path, gen., t. iii. p. 302. Mullbe (J.), Ueier fei/neren Bail, Sec, p. 50. Ybenbuil, 6az. mid. de Paris, 1854, No. 16, p. 242. GoDAED (E.), Meoherches swr la subsftitution graAsneuse du rein, Paris, 1859. VlECHOW, Pathology of Twmowrs, t. i. lecture 14. Beoca, Traite des Twmewrs, t. ii. p. 375. Caecinoma. — Ceuvbilhibe, Anat. path., t. v. Lbbbet, Phys. path., t. ii. ViECHOW, Vvrehom's Archim. t. i. 1847. Beoca, Mem. de VA ead. de Mid., t. xvi., 1852. Wagnee (B.), ArcMv. fur phys. ffeilkunde, p. 153, 1857 ; p. 306, 1858. BiLLEOTH, Pathol, chi/rur. gin., 1868, p. 757. Coenil, Du Cancer, in Mem. de I'Acad. de Mid., t. xxvii. Foestee, Mamdhuch, t. i., 2nd edit., 1865, p. 388. Syphilis. — CHnigue ieonographAgue de I'Sopital des Viniriens, Paris, 1851. Babebnspeung, Deutsche Klinih, 1858, No. 17 ; Annalen der Gharite, Berlin, 1860, t. ix. p. 139. LOEAIN et EoBiN, Gax. med. de Paris, 1855, No. 12. Vir- chow, Constitutional Syphilis ; Pathol, of Tumows, t. ii. lecture 20. Van Ooedt, Des tvmewrsgommsuses, th^se, Paris, 1859. Wagnee (Ebnst), Ueler das SypM- lom (Archiv. fur Heilhunde, t. iv. pp. 1, 161, 356, 430). Lancbebaux, Traiti historique et pratique de la Syphilis, Paris, 1866. Coenil, Leqons swr la sypMlis foAtes d, I'hopital de Zov/rcvne, 1 879. TuBEECLB. — Lebbet, Comptos rendus Ac. Sc, March 4, 1844. Ebinhaedt, Anmalen der Cha/riti, Berlin, 1850. Virchow, Path, oellu., Twmews, lecture 20. ViLLBMiN, Du Tubercule, Paris, 1862 ; Atudes swr la tuierculose, Paris, 1868, 8vo. Heeaed et Coenil, De la phthisic puhnonaire, 8vo, Paris, 1867. EINDPLBISCH, LehrMich der Cremebeleh/re. Nibmbybe, Leqons clmiques sur la phthisic puhrummre, recueillies pwr Ic dooteur OU, Paris, 1867. Lbbekt et WySS (Oscar), Ueier Cawernenbild/img in den Lung en nach Impfumg, etc. (Virchow's Archiv. t. xli. p. 540). Wilson Fox, Oh the Artificial Production of Tuiej-cle (^British Med. Journal, 1868). Eanvibe, Tubercnles des os (^ArcA. de physiologie, 1868). ThAON, Thhc su/r I'a/natomie pathologigue dc la tuierculose, 1873. Gran- chee, Swr I'wnite de la phthisic, 1873, tuierculose pulmonaAre {Archives de physio- logic, 1878). Lbpinb, De la pneumonic easieu^e, 1872. Easmussbn, Continued Ohservations on Sernoptysis. Schtjppbl (Oscar), Uhtersuchungen ilber Lymph- driisen^Tubereulose. Martin (H.), Recherches a/natomopathologiques et expirimen- tales swr le tuiercuU, Paris, 1879. Lebeet, Traiti clinigue et pratique de la tuberoulose, 1879, Paris, Delataye. Hanot, art. Phthisic du Nouvean djction- naire, 1879. Chaecot, Leqons reswmees by Hanot, in the Revue mensuelle, 1879. Glandbes. — Viechow, Path, of Twmou/rs, lecture 20, art. Moevb du Diation- nai/re eneyclop., par Bouley et Eenaut. Chondroma. — MOllbe (J.), Rede zur Peier des iiten Stiftumgstages des K. Med. Chir. Fried. Wilhelms-Institutes, Berlin, 1836. Dolbbaij, Gaa. liebd., 1858, No. 42, p. 720 ; No. 44, p. 752 ; Bull, de la Soc. anat, 1859, pp. 296-336 ; mSme recueil, 1860. Virchow, Tumours, lecture 16. Eanvibe, Contribution a BIOGRAPHICAL REFERENCES. 305 I'Hude de la etruature et du developpement det tvmevrt cartilagineuies {Bull, de la Soo. anat., 1 86/;). Osteoma. — MtJLLEB (Henry), Beitrdge tnr Kenmtnus der Entmickel. d. Knochengewebes, in Zeitschr. f. miss. Zool., ix. 3. Eokitanskt, Leh/rb-uch, t. i. p. 179 ; t. ii. p. 96. SouLiutl, Du pa/ramiisme pa/rfalt, etc., thfese, Paris, 1864. ViRCHOW, Tumours, t. ii. lecture 20, 1864 ; Odontomata, same lecture, 51. Beoca, Recherches »u/r un nowveau groupe de tumours (_Aead. des so., December 30, 1867) ; Trmt6 des Tvmewrs, t. ii. 1869. Myoma. — Zenker, Ueher die Verlimderumgen der willlt. Muslt^ln m Typhus, etc., Leipzig, 1864. Fohstee, Handhuoh, 1. 1. p. 339. Virchow, Die liramhhaft. Oesohm., t. iii. p. 98. Neiteoma. — Odier, Manuel de mSdeaine pratique, Geneva, 1803, p. 278. DUPUYTBEN, Leqons de elmique cMru/rgicale, t. i. Descot, Sur les affections des nerfs, 8vo, Paris, 1825. Valentin, Lehrbuoh der Physiologie, t. i. p. 772. Lbbebt, TraAU d!anat. path., t. i. p. 160, pi. xxii. figs. 4, 5. Virchow, Gesam- melte Abhandl., p. 999 ; Tumours, t. iii. Sanoalli, Delia ipertrofia parziale del cervello, Milan, 1858. Veenbuil, Archives ginirales de Medicine, 5me s6rie, t. xviii. p. 540. Axmann, Beitritge zur mihr. Anat. des Qanglion-Nervengystems, Berlin, 1853. Angioma.— Plenck, Doctrina de morbis outoMeis, Wien, 1776. Dupuytren, Clitdque ohirurgioale, t. ii. Alibbbt, Nosographie naturelle, Paris, 1838. Brbs- CHBT, Ripertoi/re gtntral d'anat. et phys., Paris, 1826, t. ii. Eaybr, Maladies des reins, t. iii. 1871, p. 612. ScHtJH, Pathologie undTherapie der Pseudoplasvien , Wien, 1854. Lttschkb, VvroTwm's Archiv., t. vi. Esmaech, Virchow's Archiv., t. vi. Broca, Tumeurs, t. ii. chap. vii. Virchow, Tumours, t. iii. lecture 25. MoNOD, Etude sur I'a/ngiome simple, 1873. Lymphangioma.— Dbmabquay, Mim. Soa. ohiru/rgie, t. iii. p. 139. Fetzer, Arehiv. f. physiol. Heilkunde, 1849, t. viii. p. 128. Michel, 6az. mid. de Stras- bourg, 1853. TiLBZBN, Canstatfs Jah/resb., 1856, t. iii. p. 271. Anger (Th.), Time, Paris, 1867. Virchow, Tiimou/rs, t. iii. lecture 25. Lymphadbnoma. — His, Zeitsohrift f. miss. Zool., xi. p. 65 ; xii. p. 223 ; xiii. p. 445 ; XV. p. 127. HODOKIN, Medic. Ckir. Trams., t. xvii. p. 68, 1832. ViRCHOW, Proriepi Natizen, 1846. Bennett, Edinb. Med. and Swrg. Journ., 1846. Bonpils, Sociiti Mid. d'Obs., t. i. p. 157, 1857-58. Troussbau, Clinique de VHdtel-Dieu, Paris, 1862, t. ii., first edit. CORNIL, ArcMves de Medeoine, 1865, t. ii. Waldbybb, UroJum's AroMv., t. xxxv., 1865. Bottchbr, Virohom's Arohiv., t. xxxvii. p. 163, 1866. Ollivier et Banvier, Obs. pow servir a I'Sist. de la LeucooytMmie {Soo. de Biol., 1866). Eanvier, Note sur un cas de Twmeur Zymphatique des oa {Jowmal de VAnat. et de la Physiol., 1867). Dbmansb, Mude sur la lymphadinie, 1874. Humbert, Nioplaimes des ganglions lymphatiques, thfese d'agrfigation, 1878. Epithelioma.— Schultze (Max), Virohom's Archiv., xxx. His, Die Haute wnd Hohlen des mensoM. KSrpers, Bas., 1865. Robin, Sob. Biol., 1855, p. 210 ; id. p. 283 ; Oaz. Mid., 1856. Ordonez, SociHS de Biologie, 1866. Verneuil, Etudes sur les tumeurs de la peau (Archiv. de Mid., fifth series, t. iii. p. 555 j t. iv. pp. 447, 693). Thiersch, Das Epithelialkrebs, 8vo and atlas ; Leipzig, 1865. COBNIL et Ranvibb, Diveloppcment Hist. {Jowmal de VamM., vol. ii. pp. 266, 476). BIDDBB, Mailer's Archiv., 1852. Gauwbiloff, Wiiitzb. med. Zeitung, t. iv. 1863. Dbmonchy, Epithelioma Panmenteuse, thfese, Paris, 1866. Mont- FUMAT, Polypes de Vutirus, tlifese, Paris, 1867. Rindpleisch, Zehrbuoh der Path. Gemebelehre, 1867. Billboth, Pathx)l. chirwrg . ginirale. Adenoma.— Cbuvbilhiek, Bulletiu Aoad. Boy. de Mid., t. ix. p. 360, 1844. Vf.lpbau, Dictionnaire, en 30 vol., t. xix. p. 59. Lebebt, Phys. Path., 184b. X 3o6 TUMOURS. Beoca, art. Adbnome du Diet. EncyeUp., t. i. Kblsh et Kibner, Adenoma du foie (^Arch. de Phyg., 1876). Cysts. — Kohleatjsch, Eygtes dermo'ides (MuUer's ArcTvim., 1843, p. 365). Lbbebt, Anat. Path. Demoulin, Sv/r quelques Produolions Seterotopiques, etc., tMse, 1866. Wilson Fox, Ort the Origin and Structwe of Ova/riwn, Cysts (Jowr- nal of Anatomy, 1865, p. 323). Malassbt, Sw la Maladie kystique dM Testicule {Archiv. de Physiologie, 1876). De Sinbty et Malasset, &»• la 8tru(yture, I'Origiae et le Developpement des Kystes de VOvaire {Archives de Physiologie, 1878). ANATOMICAL DIAGNOSIS OF TUMOUES. ANALYTICAL TABLE. To determine tlie histological composition of a certain given tumour a hypothetical diagnosis is first made from naked-eye appearances. When made by an expert, this diagnosis is often verified by microscopical examination, or it is abandoned or modified according to the results of this examination. In the following table the two kinds of appearances are set out, those seen with and those without the aid of the microscope. CHARACTERS BISTINGUISHED BY NAKED-ETE EXAMINATION. The tumour may be : — A. Ossiform. B. Cartilaginiform. 0. Soft, with a milky juice. D. Soft, with a grumous juice. E. Fleshy. F. Adipose. G. Gelatiniform. H. Fibrous. 1. Black or melanotic. J. Formed of granulations. K. Caseous. L. Papillary. M. Cystic. N. Erectile. 0. Complex; presenting at diiferent points many of the preceding characters. CHARACTERS BRAWN FROM MICROSCOPICAL EXAMINATION. A. OssiFOEM Ttjmoties. Method of Examimation. — On scraping an ossiform tumour it generally yields only a few angular fragments, which give on testing the reaction of carbonate of lime, but offer no precise histological characters. To ascertain the constitu- tion of ossiform tissue sections should be cut by means of a saw, and ground down between two pieces of fine pumice-stone cut in the direction of their fibres and saturated with water. To demonstrate the vascular canals, which is useful in a great number of cases, the preparation must, after having been ground, be placed in an anmioniacal solution of carmine, allowed to dry, and then ground afresh, the pumice-stone being wetted with alcohol. In this way the walls of the Haversian canals alone remain coloured. Sections thus obtained should be examined in Canada balsam. To see the cells and nuclei contained in the acunEe the bone should be decalcified in chromic or picric acid, and sections ANALYTICAL TABLE OF TUMOURS. 307 cut and afterwards stained with picro-carminate or purpurin. When the tumour has ossiform trabeoulse or delicate needles they can be separated, withdrawn, and submitted at once to ezamination. Microscopical examination enables us to ascertain the following pecu- liarities : — a. Bone corpuscles situated in a laminated ground substance. h. Granular, or very transparent, and non- ^ laminated ground substance, in the midst of ■which are seen striae or irregular lacunae of unequal size, but which have a coarse resemblance to bone corpuscles. c. The same ground substance limiting small cavities which lodge globular elements, i.e. the cells of sarcoma or chondroma. Osteoma (p. 226). Ossifying sarcoma (p. 141). Ossifying chondroma (pp. 217 and 222). Calcified fibroma (p. 165). Calcified sarcoma (p. 134). Calcified myoma (p. 234). Calcified sarcoma (p. 134). Calcified chondroma (p. 221). In sarcoma, fibroma, myoma, and chondroma it is rare for calcareous infiltra- tion to be present throughout the entire mass of the tumour so as not to find parts in which the constituent tissue can be studied. Maceration of small frag- ments of these tumours in chromic or picric acid removes the calcareous salts, and allows of sections being cut in which the true histological structure can be studied. B. Caetilaginiporm Tumotjrs. Method of Exwmmatwn. — These tumours may be studied by moavis of sections made in the fresh state ; alcohol, chromic and picric acid are only employed as preserving or fixing agents. Solutions of iodine and picric acid are useful. a. Cartilage cells and capsules ; the different varieties of cartilaginous tissue (see p. 17) .... h. TrabeculsB formed of a ground substance, which may be homogeneous or infiltrated with calcareous salts, containing angular corpuscles. These trabeculee limit spaces filled with vascular connective tissue ; they sometimes contain islets of hyalin or calci- fied cartilage c Homogeneous ground substance arranged in lamellse, between which are found elongated, flat, or fusi- form ceUs, the flat and ovoid nuclei of which take the stain of carmine and become clearly apparent after being acted upon by acetic acid . Chondroma (p. 214). Osteoid tumours (p. 222). Lamellar fibroma (p. 163). C. Soft Tumottrs tielbinq a Milky Juice. Method of Examination. — To ascertain the presence of juice the tumour is divided, and the divided surface scraped, or else the juice is squeezed out by- lateral pre8.sure. This juice always contains cells and nuclei, which are how- over, never sufficiently characteristic to define the species of tumour under X 2 3o8 TUMOURS. examination. Every tumour containing juice should be hardened in alcohol, picric, or chromic acid, or in Miiller's fluid, and afterwards by the successive action of gum and alcohol. Sections can then be cut, from which, if it is wished to make a careful examination of the stroma, the cells can be brushed away with a camel's-hair brush. Carmine, purpurin, and haematoxylin are used for staining. a. Small round cells and reticulated stroma (p. 16) , 6. OeUs round or irregular, small or large; stroma alveolar and fibrous While these two dasses of tumours are found to contain juice immediately after removal, the follow- ing do not yield juice immediately after removal from the living subject, but it is present twenty-four hours afterwards, or when the tumour is removed from a cadaver. c. Round or fusiform cells which are in contact, or separated by a slight quantity of a soft substance ; the blood-vessels, the walls of which are embry- onic, permeate the tissue in every direction . d. Stroma limiting alveoli lined with cylindrical epithe- lium Lymphadenoma (p. 247). Carcinoma (p. 172). e. Stroma limiting ramifying tubes filled with pavement epithelium showing no epidermic evolution . /. Stroma limiting lobules of various forms, composed of pavement epithelium, showing epidermic evo- lution g. Tumours of the mamma, testicle, and cervix uteri, which determine budding growths into the ducts. These growths and the tissue of the tumour itself >re formed of fibrous tissue mucous tissue embryonic tissue Sarcoma (v. E, a'). Cylindrical-celled epithelioma (p. 273). luliular epithelium (see D, a). Lobulated epithelioma (see D, 6). Fibroma (p. 161). myxoma (p. 154). Sarcoma (p. 139). I). SOPT TtTMOTJKS WITH GrTJMOTTS CoiHENIS. Method of Esoamivnation. — These tumours yield a grumous substance on scraping the divided surface. On this surface whitish spots or tracts are seen. The- grumous substance is found under the microscope to be composed of epithelial ■ In this table we make use of two kinds of references, some to pages in the text and others to other parts of the table. For the latter we use two letters : a capital letter when referring to naked-eye appearances, and small letters to microscopic characters. ANALYTICAL TABLE OF TUMOURS. 309 cells joined together. To study these elements in an isolated state the tvunour should be examined in the fresh state, or in sections cut after hardening, as described at C. Stroma limiting ramifying tubes filled with pavement epithelium showing no signs of epidermic evolu- tion Stroma limiting lobules of various forms, and which are composed of pavement epithelium showing epidermic evolution Tubular pavement epithelioma (p. 268). Lobulated pavement epithelioma (p. 258). 0. Combination of the two preceding forms. d. Fibrous stroma usually containing no blood-vessels, closely surrounding lobules which show no epi- dermic evolution, but in the centre of which are epidermic pearls e. Tumours of the breast, containing whitish tracts radiating from the nipple ; these tracts, formed of epithelial cylinders, are located in the galacto- phorous ducts, and may be obtained by scraping. The rest of the tumour shows the characters of carcinoma Oaroinoma (p. 177). Pearly epithelioma (p. 267). E. Fleshy or Saecomatotts Txjmoubs. Metlwd of Examination. — These tumours, of the consistence of flesh, are grey or rose-coloured, homogeneous or fibrillar, semi-transparent and soft. They are examined in the same way as the preceding. a. Cells round, irregular, or fusiform, small or large, con- taining one, many, or a great number of nuclei. Cells are arranged without order or are gathered into bundles ; the capillaries are irregular, often without proper walls, and sometimes form a true lacunar system Sarcoma (p. 126). b. Smooth musole-ceUs arranged in bundles, and sepa- rated by vascular loose connective tissue. It is difficult to separate the cells by scraping or by dis- sociation with needles ; to eflFect this, maceration in nitric acid must be resorted to (vide Mttsctjlab Tissue, p. 26) Myoma (p. 232). c. Tumour composed of acini and glandular tubes, exactly like those of normal tissues .... Adenoma (p. 283). F. Adipose Tttmours. Method of Examination. — The tumours, in appearance like adipose tissue, arc semi-transparent, yellowish in colour, and contain brilliant oil globules. 310 TUMOURS. The microscopical examination is made by means of sections cut from fresh or hardened specimens. a. Typical adipose tissue : lobular arrangement ; tracts of connective tissue and capillaries round adipose cells Lipoma (p. 168). h. In the midst of the adipose tissue are found more or less extensive islets of a gelatinous tissue, show- ing, under the microscope, all the characters of mucous tissue Tumours -without stroma; generally very large. All the cells are in contact, and contain distinct fat droplets without there being any tendency to cellu- lar destruction Stroma alveolar ; cells free in the alveoli, and contain fat droplets without there being any tendency to cellular destruction Lipomatons myxoma (p. 155). Lipomatous sarcoma (p. 148). Lipomatous carcinoma (p. 182). G. Gelahnifoem Tttmoites. Method of Examination. — These tumours, transparent in appearance, and of a remulous consistence like gelatine, yield on scraping a gummy juice, in which, on microscopical examination, are seen cells of various forms, debris of elements, a few granules, and fat drops. Their structure may be studied in sections cut from fresh or hardened specimens ; as they are not hardened by chromic acid, recourse may be had to simple dessication. To make the isolated elements apparent it is well to stain them with a weak solution of iodine, or with car- . mine. a. Tissue regularly formed of fusiform or stellate ceUa, anastomosing together and separated by an amor- phous ground substance, permeated with blood- vessels. In some tumours there are in addition elastic fibres and fat vesicles Myxoma (p. 154). h. Tumours corresponding to the description of sarcoma (vide E, a). In some spots, where the morbid mass is destroyed it is replaced by a mucous, structureless substance, more or less fluid, and often containing the debris of cells, fat, and pig- ment granules e. Tissue fibrous, with mucous cavities and masses similar to the preceding • , d. Stroma distinctly alveolar ; the alveoli filled with a mucous mass generally containing cells in a state of colloid degeneration Myxo-sarcoma (p. 147). Mucoid fibroma (p. 164). Mucoid carcinoma (p. 182). ANALYTICAL TABLE OF TUMOURS. Cartilaginous tissue with generally anfractuous cavi- ties filled with a mucoid suhstance ; or else formed of a mucoid groxmd substance in which ramifying cartilage cells are found, or well-pre- served capsules, as in the intervertebral discs 311 f. Alveoli irregular, often elongated, some filled with a mucoid substance in which round cells in a state of mucoid degeneration are suspended, as well as cellular debris and fat granules ; others lined with cylindrical-celled epithelium and contain mucus. Alveoli are also found simply lined with cylindrical-celled epithelium .... g. Tubular epithelioma (vide D, a) with a mucous stroma h. Lobulated epithelioma (vide D, 6), in which the cells undergoing epidermic evolution are in a state of colloid degeneration In the supra-renal capsules and lymphatic glands lacunar spaces are found filled with colloid masses having festooned borders. This arrangement, normal in the thyroid body of the adult, may be exaggerated so as to constitute a tumour Mucoid chondroma (p. 217). Cylindrical-celled epithelioma in a state of mucoid degeneration (p. 276). mucoid tubular epi- thelioma (p. 270). Colloid lobulated epi- thelioma (p. 261). Colloid cysts (p. 296). H. Ftbeoid Tumoubs. A certain quantity of connective tissue enters into the composition of almost every tumour. If this tissue becomes very abundant, and the specific tissue of the tumour ceases to produce disseminated islets, the total mass takes a fibroid appearance, without it for all that being a fibroma. Thus every fibroid tumour requires a most attentive examination. Method of Examination. — Sections cut from a fresh or a dried specimen, or one hardened by the reagents already mentioned. Staining with carmine, alone or after the action of acetic acid, is very useful in order to demonstrate the existence of connective-tissue cells. n. Oonnective-tissue bundles intersecting in various di- rections, with or without blood-vessels. Lobulated arrangement Fibroma (p. 161). b. Tissue carcinomatous and alveolar ; the cells con- tained in the alveoli are undergoing destruction, and may be even entirely absorbed . Atrophic carcinoma (p. 180). 312 TUMOURS. a. Stroma fibrous and very abundant ; in it are found epithelial tracts arranged as in lobulated, tubular, or cylindrical- celled epithelioma (vide D, a, b; C,b) Epithelioma (p. 257). d. Intersecting bundles of smooth muscle-cells, separated by fibrous tissue, and united in the form of lobules ; always located in non-striated muscular tissue . . . Loliulated myoma of smooth fibres (p. 233). e. Tissue which on dissection is found to consist of me- duUated nerve-tubes and drops of myelin. The tumour is always developed on the course of a nerve . . myelinic neuroma (p. 237). /. Tumours composed of non-meduUated fibres . . Amyelinic neuroma • (p. 237). g. Whitish, caseous, and lardaceous masses, formed of elements undergoing atrophy and retrograde changes, surrounded by a thick fibrous zone, in which are irregular lacunae filled with fat granules ........ Syphilitic retrogres- sive gummata (p. 187). I. Black or Mblanoiic Ttjmodes. Method of Exammation. — In appearance the tumour is either completely black, or slate-coloured, or a mixture of grey and black. It always yields a blackish or sepia-coloured fluid. On scraping only black granules are often obtained. The black spots of the tumour should be particularly examined. Delicate sections cut from fresh or hardened specimens are indispensable in order to make the diagnosis. a. Pigmentary infiltration into the elements of the various physiological tissues (very rare in man) . Simple melanosis (see appendix to tumours). h. Sarcomatous tissue (vide C, c) Melanotic sarcoma (p. 148). c. Carcinomatous tissue (vide 0, c) . , . . Melanotic carcinoma (p. 183). Care must be taken not to confound melanotic granules, which are black from the beginning, with blood pigment, which takes different tints before turning black, or with fragments of carbon, which are angular, while melanotic granules are spherical. J. TUMOTJES I'OBMED 01' GeANULATIONS. Methods of Examinatwn. — Small spherical masses the size of a millet seed, isolated only by dissection or by dilaceration. Their structure is studied in sec- tions made after hardening, as previously described. ANALYTICAL TABLE OF TUMOURS. Tissue composed of small cells, immersed in a fibrillar and resisting sulbstance. The centre of the granu- lation is atrophied, and has generally broken down into a caseous detritus. The periphery of the granulation is formed of embryonic tissue . 313 All tumours which are capable of generalisation may determine the growth of small spherical masses, which are composed of tissue identical to that of the parent tumour. The diagnosis of the primary tumour will aid in making that of these growths . K. Caseous Tttmottrs. Tubercular granula- tions (p. 202). Carcinoma, epitheli- oma, sarcoma, lym- phadenoma, &c. Under this denomination are included all tumours in which the entire mass, or a part only, is composed of an opaque, whitish, or yellowish substance which recalls by its appearance and its consistence that of rotten cheese. They are either friable or have a firm, lardaceous feel. The nature of the degenerated tissue cannot be deduced from the microscopical examination of the altered parts. a. Isolated granulations in a state of caseous degenera- tion h. More voluminous masses, on the borders of which, and sometimes throughout their entire extent, tubercular granulations are found c. Sarcomatous tissue (vide E,a); or carcinomatous (vide C, h, &c.), round the caseous mass d, Dense caseous masses surrounded by a fibrous zone (vide H, ^) Tubercular granula- tions (vide J, a). Confluent tubercular granalations (p. 208). Sarcoma, carcinoma, &c., in a state of caseous degenera- tion. Syphilitic gnmmats. L. Papili-aey TtTMoirRa. Method! of Eseamination. — Sections made for the study of papillary tumours must be cut quite parallel to the direction of the papillae, else the inter-papillary spaces, filled with epithelium, appear like islets of epithelioma. a. Fibrous tissue provided with blood-vessels consti- tuting the body of the papilla, the base of which is formed of the normal tissue of the region . 6. The body of the papilla, or the tissue which forms its base, is composed of sarcomatous tissue Papilloma (p. 277). Papillary sarcoma (p. 160). 314 TUMOURS. c. Or of carcinomatous tissue . . . . d. Or of mucous tissue e. Or of lobules of epithelioma .... M. Ctstic Ttjmotjes. Villous carcinoma (p. 185). Papillary myxoma (p. 166). Papillary epithelioma (p. 261). True cysts, lined with an epithelium and possessing a proper membrane, must be distinguished from lacunae filled with serous, mucous, or colloid matter, hollowed simply in the tissue of sarcomata, carciuomata, fibromata, ohondromata, etc. The lacunae Uned with epithelium developed in tumours of the mamma, testicle, and many other glands we regard only as simple complications, and not as cysts. To make the diagnosis certain, the tissue surrounding the cystic cavity should be carefully examined. Serous cysts (p. 296). Colloid cysts (p. 297). Sebaceous cysts (p. 293). Dermoid cysts (p. 296). a. Containing serous fluid b. Containing colloid substance c. Containing epidermic cells and fat . d. Cysts the membrane of which is similar to the skin, and may even contain bones, teeth, muscular and nervous tissue N. Ekectiie TtrMOUEs. All erectile tumours are not angiomata, this term only applying to tumours formed entirely of blood-vessels and of a stroma of connective tissue. Method of Moeammation. — When these tumours are gorged with blood they should be hardened in absolute alcohol, concentrated solution of picric acid, Miiller's fluid, or in gum and alcohol ; sections are then cut, stained with carmine, and examined in glycerine rendered slightly acid with formic acid. The red blood corpuscles which fill the vascular spaces are not stained with the carmine, while the other cellular elements are rendered distinct by the colour. a. Irregular lacunse without proper walls and filled with blood, hollowed in sarcomatous tissue . b. Dilated capillaries in a tissue showing the structure of carcinoma c. Dilated capillaries in a tissue showing the structure of smooth-celled myoma d. Numerous and dilated vessels, separated by connec- tive tissue, or by the tissue of the part in which the tumour is developed ..... e. Cavernous spaces filled with blood, and separated by incomplete septa of fibrous tissue. If the blood has escaped the tumour has a spongy appearance . Erectile sarcoma (p. 145). Erectile carcinoma (p. 181). Erectile myoma (p. 234). Simple angioma (p. 239). Cavernous angioma (p. 240). APPENDIX TO TUMOURS. 315 O. Complex Tumotjks. In various parts of its mass the tumour has different naked-eye appearances. Each of these parts has characters corresponding to one of the preceding divisions, and may be studied separately by proper methods. The examination of the tumour requires the greatest attention. APPENDIX TO TUMOUES. By a strict adherence to our definition of tumours we have been unable to include any description of circumscribed collections of pigment, nor of hydatid cysts. We have therefore added an appendix in which these may be briefly described. Simple ciicumscribed melanotic masses in the form of tumours. Synonyms. — These simple melanotic masses have often been confounded with melanotic carcinomata or sarcomata, under the name of melanosis or Tnelanomata. Anxious to avoid a similar confusion we do not, to designate these masses, make use of the name svmple melanoma, for the radicle is not representative of a tissue. Definition. — The melanotic masses now under consideration are distinct from melanotic sarcoma or carcinoma, inasmuch as the melanotic granules do not accumulate, as in those tumours, in cells of new formation, but in the normal pre-existing elements. When melanotic pigment granules accumulate in the cells of a normal tissue (p. 75) the cells are destroyed, and, on the process of infiltration continuing, the tissue itself is destroyed, and replaced by a nodule or tumour softened at the centre. We give the name of melanotic masses to those collections of pigment which occur simultaneously in a great number of spots in the body. They are distinguished from infiltrations of pigment in the skin (ncevi matemi), and also from the pigmentation sometimes found round the blood-vessels of the nervous centres, in that in the case of melanotic masses the tissues are destroyed, and secondary growths occur in all the organs, like the most malignant tumours. Description. — In the records of science we have found but one reliable report of a case of this kind, published by ]MM. Dubrueil 3i6 TUMOURS. and Lancereaux. We have investigated a similar case, submitted to us by M. Landrieux. Contrary to the generally slow progress of simple melanosis in the horse, in which animal the disease is very common, in man products of this kind generalise with ex- treme rapidity, and cause death. The progress of the disease is so rapid that it is often difficult to decide if a primary mass has caused secondary infection of the organism, or if the numerous masses result from some general cause. These melanotic masses vary greatly in size from that of a microscopic granule to that of an egg or fist. They are well defined, and at their edges no intermediate Fig. 177. — Section of Kidney. 1, pigment deposited in the stroma of the organ ; 2, uriniferous tube ; 3, glomerulns. Magnified 100 diameters. zones of tint are found between them and the normal tissues. When they have obtained the size of an almond they are soft at the centre, while the periphery is as firm as the tissue in which they are developed. Nothiag is discovered under the microscope in the central softened fluid mass except melanotic granules, the smallest of which are agitated by Brownian movements. The microscopical examination of the parts which are still firm is made from sections cut after hardening in alcohol. The constituent elements of the parent tissue are then found to be infiltrated with melanotic granules, without there being any evident new formation of cells. Thus, in the subcutaneous cellular tissue, the connective- MELANOTIC MASSES. 317 tissue cells are seen to be infiltrated with pigment, recalling the pigmented stellate cells of the choroid (vide fig. 40). In the peritoneum, the melanotic granules are primarily deposited in the connective-tissue cells, exactly as in the corium. A similar pig- mentation of cells is observed in the trabeculae of the great omen- tum, which is non-vascular. Soon, however, the cells are entirely hidden by the accumulation of pigment which is then deposited in the fibrous tissue. The large nodosities are formed by the union of masses originally solitary. In the kidney, the deposit of pigment is seen either in the form of spots or of small black granules. Sections examined under the microscope show that the Fio. 178.— Epithelial Cells of the Galactophorous AciNt INFILTRATED WITH BLACK PIGMENT. I, galactophorous colls and acini ; 2, interetitial connective tissue. Magnified 260 diameters. pigment is localised in the cellulo-vascular framework and in the glomeruli ; the epithelium of the tubuli remaining intact for a long time (vide fig. 177). In the case which we examined there were spots, visible to the naked eye, in the nipple; the melanin was deposited in the glandular ducts and acini, but not in the connective tissue. In rather thick sections treated by tartaric acid, the acini of the gland were well seen, some of them were normal and others stained black. With a high power, and in sections made after hardening in alcohol, it could be clearly seen that the melanotic 3i8 TUMOURS. granules were deposited round the nuclei in the protoplasm of the cell (fig. 178). In our own case, and in that reported by MM. Lancereaux and Dubrueil, pigment was found deposited in the muscular fasciculi of the heart. These facts prove beyond doubt that pigment is deposited simultaneously in the connective-tissue cells and epithelial cells, and even in the muscular fasciculi, and that it does not come directly from the colouring matter of the blood. We believe, in fact, that melanotic change is not produced by simple penetration of pigment, but that it is the result of pathological activity of the cells themselves. This morbid species can only be mistaken for melanotic car- cinoma or sarcoma ; but from naked-eye appearances alone, simple melanosis may be suspected, if between the black and the healthy tissue no zone is found showing intermediate tints ; this is hardly ever wanting in melanotic carcinoma and sarcoma. To be certain that the diagnosis is correct, it is not sufficient to scrape the tumour, nor to examine the elements obtained by dilaceration, but, as we have already said, delicate sections must be cut. The generalisation of melanotic masses is always very rapid, and death occurs at the end of a few months. Hydatid Cysts. Hydatids are described in the part of this work which treats of general pathology, for they are met with in all organs and tissues. The other human parasites which have a special habitat will be described when treating of the tissues and organs in which they are found. Thus trichinae will be described in connection with striated muscles, and the trichophyton and microsporon with the skin, etc. Definition. — Hydatid cysts, which owe their name to the transparent fluid they contain, are essentially caused by the vesicular worms which represent a phase in the development of taenia. In man only two kinds of hydatids are found, the cystic cercus and the echinococcus. The cysticerci are solitary in their cysts, while the echinococei are produced in more or less con- siderable numbers in a primitive cyst. They proceed from various species of taenia, but most frequently the Cysticercus cellulosce (Eudolphi) belongs to the Tcenia solium. To understand their place in the zoological series and their mode of production it is necessary first to give a clear description of the taenia. The Taenia Solium, which lives in the small intestine of man, T^NIA SOLIUM. 319 IS a nband-shaped, white worm, many yards in length ; it is com- posed of rings the smallest of which are near the head, while the ^gest are found at the opposite extremity. The head is about the size of a pin's head ; on it are four suckers and a smaU tuber- cle or proboscis, the base of which is surrounded by twenty-four to twenty-eight hooks, arranged in two series. The entire head is Fig. 179. — T^nia Solium. a, head or scolex ; b, rings or proglottides. called by the name of scolex. The rings situated immediately after the head gradually increase in size as the other extremity is approached. These rings, which may have a diameter of 12 mm., are flat, and each represents a hermaphrodite individual. The orifices of the male and female genital organs are united at a slight eminence, situated at one of the borders of each ring ; 320 TUMOURS. these organs are composed of sinuous ducts which represent the uterus and ovaries ; the latter being filled with ovules ; the male organ consists of a falciform penis and a seminiferous duct. The fecundated &g^, in the ripe rings, contains an embryo already pro- vided with six booklets. The ultimate rings become detached ; they are called proglottides or cucurbitini. They are filled with fecundated eggs, and if swallowed by certain animals, pigs for example, the eggs lose their enveloping membranes on reaching the intestine, and the liberated embryo passes through the in- testinal walls, to be located in various parts of the organism, where Fig. 180. — Head and Neck of the T^nia Solium. «r, proboscis ; &, crown of booklets ; c, c, suckers ; 2, an isolated booklet ; a, hinge-like projection by whicb it is attacbed to the bead of the tsenia. it becomes the cysticercus cellulosse. The presence of cysticerci in pork constitutes pig measles (ladrerie). The Cysticercus cellulosse, which is seen very rarely in man, is found in the muscles, piaf-mater, and brain, beneath the con- junctiva, in the chambers of the eye, in the pleura, and perito- neum, etc. It is generally encysted. The cyst wall is formed of a membrane of connective tissue supplied with blood-ves- sels. This membrane is deficient when the cysticercus is located in a natural cavity. On incising the membrane, the cysticercus is found in the form of a round vesicle, from eight to twenty mm. in diameter, filled with a transparent fluid. On its surface is seen a slight depression. On pressing the vesicle, the body, neck, and head of the animal protrude from out of its caudal receptacle (fig. 181). The head is exactly like that of the Taenia ; on the neck and body of the animal are folds or rugae, without any distinct rings, and there are no genital organs. For the cysticercus to attain the perfect development of the taenia it is uecessary for it to THE T^EXIA ECHI.VOCOCCUS. 321 pass into the intestinal tube of another animal. The tsenia solium of man is most frequently derived from the cjsticercus contained in pork. The cysticercus cellulosas is not the only variety found in man, some isolated cases have been reported of the cysticercus of the Tcenia acanthotriaa and of the Tajiiu eerrata, etc. If the forementioned cysticerci are rare in man, Fig. 181. — Ladric Cysticercus, a, adventitious cyst ; 6, sac in which the animal becomes invaginateil ; c, body ,■ d, head with proboscis, sudters, and double row of booklets. echinococci are, on the contrary, very common. They bear the same relation to the taenia echinococcus as the cysticercus cellulosse does to the taenia solium. The Taenia ecMnocoocus, the existence of which is doubtful in man, lives in colonies in the intestine of the dog. It differs from the Taenia solium chiefly by the small number of its rings, of which the third or fourth from the head contain eggs and become detached. On reaching the human intestine, the eggs of this taenia lose their enveloping membrane, and the embryos locate themselves in the serous cavities and in the parenchymatous tissues. They are the point of departure of cysts, which, when fully deve- loped, are composed of an adventitious fibrous membrane, belong- ing to the organ affected, and of one or more vesicles, which are free or contained one within the other. These transparent, tremu- lous vesicles, which give to the hand the characteristic sensation known as the hydatid thrill, are spherical, and vary from the size of a nut to that of an orange. They contain a transparent Y 322 TUMOURS. fluid which is not coagulated by heat nor by acids. The mem- brane of the cyst is gelatinous, transparent, and formed of delicate superimposed leaflets, which may be separated by dissection, and roll up in the same way that elastic membranes do. On microscopical examination, the leaflets appear to be formed of amorphous and still more delicate lamellae, separated from one another by beautifully distinct parallel lines. The most internal, called the germinal membrane, has attached to its free surface echi- nococci, which appear to the naked eye as small whitish granules. Some of them become detached and float in the fluid. Within the large vesicles much smaller vesicles of identical structure are often found. The echinoeoccus is formed of a caudal vesicle, adherent to the germinal membrane, in which is found the head and body of the invaginated animal, just as in the cysticercus. \ Fig. 182. — Delicate Section of a Portion of the Membrane of A Hydatid Cyst. MaguiSed SOO diameters. Echinococci vary in diameter from •! to -2 mm. On the head is a proboscis, a double row of booklets, and four suckers. Scattered over the body of the animal are calcareous plates. Hydatid vesicles do not always contain echinococci. The germinal membrane may be deficient, or the echinococci may have ceased to live ; in the latter case booklets are found free in the hydatid fluid. This variety of sterile hydatid cyst has been called acephalo-cyst. In certain cases, the wall of the vesicles is very thick, and composed of a large number of superimposed lamellae, the central cavity being small. A variety of hydatid cysts, called multilocular hydatid tumour, has been recently described by Friedreich, Virchow, Ost, etc. It is characterised by the presence of a large number of very small HYDATID CYSTS. 323 miliary cysts in a fibrous stroma.' Each of these cysts contain one or more hydatid vesicles, inclosing echinococci or hooklets ; but even if the latter are not present, the cysts are always charac- terised by the membrane peculiar to hydatids. There is at first sight a great resemblance between these tumours and colloid carcinoma, with which they are easily confounded; but after microscopic examination, hesitation ceases. If hydatid cysts remain long in the organism after reaching perfect development, their different constituent parts undergo great modifications. The fluid is absorbed, the echinococci become detached and decomposed, the hydatid membranes collapse and break down into flakes suspended in a thick soup-like fluid which is rich in calcareous salts, and in cysts of the liver, stained of an ochrous or reddish hue from the presence of the colouring Via. 183. — Invaoinated Echinococcis, detached from the MOTUER-HYDATIP, matter of the bile. The adventitious membrane — that is to say, the fibrous membrane belonging to the organ in which the hydatid is developed, and which forms its external envelop — becomes thicker, retracts, and often undergoes fatty or calcareous infiltra- tion. In the adventitious fibrous membrane of an old cyst of the liver we have observed spots of osseous tissue containing veritable osseous trabeculsB, medulla, and blood-vessels. We are, however, only aware of this solitary example, for generally in very old hydatid cysts the adventitious membrane undergoes simple petri- faction, a carapace being formed composed of superimposed cal- careous lamellae united by fibrous tissue. ' These tumours are extremely rare in France ; we have had but one opportu- nity of studjring them in specimens brought us by M. Carrifere, and which he made the subject of his inaugural thesis in 1868. 324 TUMOURS. The relation of vesicular forms with taenia was estabHshed by the experiments of Van Beneden, Kiichenmeister, Leuckart, etc. In the last edition of the excellent treatise on entozoa by C. Davaine, 1877, will be found an examination of all the known facts regarding the parasites of man and animals, ■> t'l" PART II. DISEASES OF THE TISSUES. CHAPTER I. LESIONS OF THE BONES. Lesions of the bones are important, not only on account of their number and variety, but because the ease with which they are produced, their precise development, and their easily compre- hended evolution guide pathologists in their researches on other tissues, and suggest to them general ideas regarding pathological histology. These considerations have induced us to commence the study of lesions of the various tissues of the organism by those of osseous tissue. The development of osseous tissue is typical, and enables us to understand most of the pathological phenomena which occur in bone. As we have already seen, osseous tissue does not result from the direct transformation of cartilaginous tissue, for in its formation the cellular elements of the cartilage become free and give origin to embryonic medulla, the cells of which are subse- quently changed into bone cells. Those embryonic cells which do not become bone corpuscles undergo changes which differentiate them from the original type ; some preserve their primitive characters, while others diverge widely ; thus some become fat cells ; some aid in the formation of a true connective tissue, which may be observed round the blood-vessels of a certain caHbre, and between the fat cells of the meduUary spaces or the canals of the long bones ; others again do not divide while their nuclei multiply, thus forming the giant-cells of bone medulla; later, these become dry and flattened in the form of lamellae ia which nuclei are included (my^loplaxes). Almost all the pathological phenomena observed in bones have .326 LESIONS OF THE BONES. their starting-point in the cells of the embryonic medulla, or in those cells which have undergone some one of the modifications indicated above. The bones of young persons, or those which in the adult contain foetal medulla, as the sternum or vertebrae, are particularly exposed to both nutritive and formative pathological changes. Different parts of the same bone are however not equally subject to the same disease ; the most recently formed, that is to say, the superficial or subperiosteal parts, or the bony extremities, particularly when stiU growing, are those which are most easily affected. Diseases of the osseous system are much more varied and much more frequent than the classical descriptions would lead one to infer ; this is owing to the fact that surgeons only investigate bone lesions when they possess some great clinical interest, and also that the skeleton is very rarely examined in post-mortem examinations, I. Congestion and HsBmorrhage of Bones. Congestion of bone is recognised by the red appearance of the marrow. To appreciate this change the normal colour of marrow in various bones, and at different ages, must be known. The medulla is red in the sternum, and in the bodies of the verte- brae, and also in those parts of the bone which are undergoing development. In young subjects the epiphyses, adjacent to the cartilage of ossification, show a condition of physiological conges- tion, while in parts long formed the medulla is fatty and has the yeUow tint and translucent appearance of adipose tissue. In more advanced age, the medulla of the vertebrae and sternum loses its colour and becomes paler. The red colour of marrow is not always related to congestion. To ascertain its cause, however, histological examination is necessary. Sections should be cut after maceration in a '5 per 100 solution of chromic acid, or in a saturated solution of picric acid.' In such preparations, preserved in glycerine, it will be seen that bones, containing red-coloured marrow in the fresh state, do not owe this appearance solely to the fact of the capillaries being dilated and full of red blood corpus- cles, for congestion is frequently accompanied by rapid proHfera- ' To obtain good preparations the piece to be examined should be small and immersed in a large quantity of the solution ; otherwise the amount of acid is insufiScient to dissolve out the calcareous salts and to give the bone the con- sistency required. Picric acid is preferable to chromic aoid, for it never crystal- lises, and preserves the blood corpuscles better ; also preparations so obtained stain well with carmine. Chromic acid may, however, be used, provided that purpurin be employed as the staining agent. OSTITIS. 327 tion of the medulla cells, and more or less complete absorption of the fat. Diffuse haemorrhages may sometimes occur, and red blood corpuscles are then found mixed with the medulla cells. The extravasated red corpuscles slowly undergo considerable changes ; their colouring matter is set free and infiltrates the elements which were hitherto colourless, or they themselves may be ab- sorbed by the young medulla cells in which they may be found intact ; in other cases, the medulla cells only show granules of hsematoidin or a slight yellow tint. Thus it is seen that in bones the redness of the medulla may be due to congestion, to haemor- rhage, or to staining of the medullary elements with haemoglobin. It may also be due to newly formed blood-vessels, in which case it is no longer one of simple congestion. Simple or complicated congestion of the medulla is met with in a great number of conditions, such as ostitis, caries, various tumoiu-s, rachitis, and osteomalacia ; it is easily produced, for the medullary blood-vessels are not supported by a solid framework. It is seen also in purely physiological conditions related to a for- mative movement, such as ossification, and it often accompanies the development of new blood-vessels, at the same time that it causes extravasations of the red blood corpuscles into the medullary parenchyma. Hsemorrhage into bone is frequent in the spongy tissue and under the periosteum, owing to the fact that in these parts the blood-vessels are not solidly supported ; it may be observed not only as a consequence of traumatism, contusions, wounds, and fractm-es, but whenever there are marked changes in the walls of the capillaries, such as are observed in inflammation, and active new formations (vide p. 92). The walls of the capillaries, composed at such times of embryonic cells, become so soft that the blood corpuscles easily pass through them, and are extravasated into the medullary parenchyma. In a third category of facts, osseous apoplexy is related to one of those general diseases which cause haemorrhages, such as cachexia, purpm^, leucocythaemia, etc. Whenever haemorrhagic foci are found in the viscera, similar foci may almost always be found in the epiphyses of the bones, or under the periosteum. II. Ostitis. When a bone is submitted to some simple cause of irritation, such as denudation, a wound, the presence of a foreign body, etc., it undergoes certain modifications which serve to establish the 328 LESIONS OF THE BONES. anatomical definition of ostitis. The irritation causes excessive functional activity of the osseous cellular elements, and the lesions which follow are directly consequent. These lesions do not differ essentially from those produced in other tissues by similar causej, being, in fact, those of inflammation. Experimental production of ostitis. — If in an animal the surface of a bone be denuded and the wound kept open, an enlargement of the Haversian canals by absorption of the osseous substance is observed at the end of a few days, while under the periosteum, at the periphery of the denuded surface, a layer of newly formed bone is already perceived. This simple experiment shows that irritation simultaneously causes both absorption and exuberant production of osseous tissue. How is it that the same cause pro- duces results so different ? This is our first subject of study, for here may be found almost the whole histological history of ostitis. The first phenomenon observed in a bone submitted to arti- ficial irritation is the formation of embryonic cells in the me- dullary spaces, the Haversian canals, and under the periosteum. These cells resemble those which fill the primitive medullary spaces during the development of bone from cartilage, or those found under the periosteum when bone increases rapidly in thick- ness. They are derived from the various cells composing the medulla (wcZe p. 21). Hence we see that irritation brings bone back to an embryonic condition, and here we find an application of the general law governing the iiritation of all tissues. The phenomena resulting from the production of embryonic tissue in the medullary spaces and under the periosteiun are the following. A. The enlarge-ment of the Haversian canals and the TneduUary spaces by absorption of the osseous tissue which limits them. B. The formation of new osseous traheculce. It is advisable to study each of these phenomena separately, and then to ascertain what relation there is between them. A. The enlargement of the Haversian canals may be easily seen in preparations made as described on page 326 (see footnote). The osseous lamellae axe then observed to be eroded so as to form notches fiUed with embryonic cells (Howship's lacunae, fig. 185 b, c). On the edge of these notches the bone corpuscles open and permit the cells they contain to escape, and mixing with those filling the medullary spaces they become indistinguishable fi^om them. Little by little the osseous lamellae disappear in places, and the Haversian canals communicating, form large irregular spaces filled with embryonic medulla. ABSORPTION OF THE OSSEOUS TISSUE. 329 The cause of the absorption of the osseous substance is still veiled in obscurity, though many hypotheses have been put forth in explanation. Billroth, having remarked that the serous pus of chronic bone abscesses contains lactic acid or acid phosphates, was led to think that the solution of the bone depended on the presence of these substances. To reverse this opinion, it is enough to show that, as may be seen in necrosis, pus has only a feeble action on the fragments of dead bone which form sequestra. Eindfleisch thought that absorption of bone was preceded by its mucoid degeneration. It is true that in some preparations a zone clearer than the adjacent osseous tissue may be observed at the edges of trabeculae which are undergoing absorption ; but it seems Fio. 184. — Rarefying Ostitis of the Phalanx of thk Big Toe in a Case ok Peufokatino Ui.cer of the Foot. Bc'Ction cut after maceration in a '5 per 100 solution of chromic acid. A clear Z' ine is observed at the i dges of the lacunaj ; but in the upper part of the preparation, where the section has been cut perpendicularly to the sur- face undergoijig absorption, this zone docs not exist. to us that this zone is due to the fact that the section has been cut obliquely. Virchow is of opinion that the bone corpuscles enlarge, undergo change, and bring about solution of all the osseous substance which corresponds to the cartilarge capsule from which the bone corpuscle and the tissue surrounding it were originally developed, and on this interpretation he founds his theory of cellular territory. This interpretation cannot be ac- cepted, for it is now known that bone corpuscles do not proceed directly from cartilage capsules. 0. Weber and Yolkmann con- sider that absorption of the osseous substance depends upon fatty degeneration of the bone corpuscles ; this error arose from their confounding caries witli rarefying ostitis. It will be shown later that true caries is the only disease in which granulo-fatty de- 33° LESIONS OF THE BONES. generation of the bone corpuscles is observed, and that in this disease the osseous trabeculse, in which the change has taken place, die without being necessarily absorbed. The bone cor- puscles found at the edges of the trabeculse, which are notched by the progress of ostitis, are often in a condition of perfect integrity. Sometimes the cell within is slightly larger and more defined than usual, but signs of proliferation are rarely present, and the cells never contain fatty granules. It is thus seen that it is very difficult to form a positive opinion as to the cause of the absorption of bone in ostitis. Though, in acute ostitis, osseous cavities are sometimes found containing one large cell or many cells resulting from multiplica- tion of the primitive cell, so that the enlarged cavity may open into a medullary space, yet this is, nevertheless, not the usual mode of the absorption of osseous trabeculse; more often the lacunse produced by loss of substance are seen in sections to have a rounded notched appearance (fig. 185), and seem to be formed by cellulo-vascular buds which spring from the growing medulla. Kolliker, who has seen the same notches produced in plates of ivory inserted in bone, maintains that absorption is due to the activity of certain cells of the medulla, the mother-cells or myeloplaxes, to which he has given the name of osteophagi or ostoclasts. The role attributed to these cells seems to us to be hypothetical, for they are found at the edges of osseous trabeculse in process of growth, as well as near those which are undergoing absorption in inflamed bone. The absorption of the osseous sub- stance in ostitis seems to us to be more closely related to the action of the vascular buds of the medulla, which act upon the osseous trabeculse in the same way as medullary buds do in phy- siological ossification, or as aneurisms of the aorta on the sternum. The absorption of the osseous trabeculse cannot be attributed to the action of pus ; we have ourselves examined necrosed bones which had lain for a number of years in purulent foci, the pus of which was caseous, without finding any erosion of the superficial osseous lamellse (vide Necrosis). The formation of new osseous trabeculse takes place by tb'' agency of the embryonic cells which have been produced in the first stage of inflammation. Irritation first prepares the materials of ossification, but these are not utilised in the development of new osseous trabeculse till the irritation has lost its original intensity. Thus new osseous tissue is not produced at the spots where inflammation is acute, but in the parts adja,cent to the NEW BONE-FORMATION IN OSTITIS. 331 inflammatory focus. The subperiosteal medulla possesses in the highest degree the property of producing bone, as has been well demonstrated by OUier's experiments. The rapidity with which osseous tissue when irritated is formed beneath the perios- teum is truly prodigious. The mode does not differ from the physiological type {vide p. 24). For new osseous tissue to be rapidly developed on the surface of a denuded bone, it is not necessary that it should be covered with periosteum, though the preservation of the periosteum, and particularly of the blood- vessels which pass from its under surface into the Haversian canals, greatly favours the formative process. It is not only, moreover, on the surface of inflamed bones that osseous tissue is produced ; in fact, when inflammation ceases, the anfractuous cavities which have been hollowed in the bone are soon filled up by new osseous layers which are developed in exactly the same way as on the surface of the bone. The medullary canal itself may become the seat of new osseous growths, if the central medulla has been irritated. These facts show clearly what is the rela- tion, in ostitis, between rarefaction and formation of osseous tissue, that is to say between rarefying and formative ostitis. In the inflammatory rarefaction of bones, the materials of re-edifica^ tion are prepared ready to be used by the organism the moment that the irritation ceases : an application of the laws formulated on page 116. If the irritation persists with all its original intensity, granulations and pus are produced on the surface of the bone. The granulations spring directly from the medulla contained in the enlarged medullary cavities, and show, as Troj a observed, that the osseous tissue comprised between several canals has been absorbed. This absorption continuing, all the denuded surface may be covered by a soft, granular, and highly vascular layer. From this general description of ostitis we pass on to the study of its several varieties. We shall consider acute and chronic ostitis together, for the distinction between them is more inter- esting clinically than pathologically ; neither can we distinguish between periostitis and osteomyelitis, for periostitis is, in fact, simply superficial ostitis, and histologically considered ostitis is essentially characterised by phenomena which occur in the medulla ; so that every ostitis is, in fact, an osteomyelitis. We shall treat separately, simple ostitis, raref3ring ostitis, formative ostitis, and diffuse phlegmonous ostitis. Caseous ostitis, being almost always related to caries, tubercle, or gummata of the bone, we shall not treat separately. 332 LESIONS OF THE BONES. I. Simple ostitis. — The phenomena of simple ostitis may be seen as the result of severe traumatism, contusions, compound fracture, etc., if necrosis does not take place. The most perfect example of it is seen in the extremity of a bone six or eight days after amputation. The medulla under the periosteum, in the Haversian canals, and a portion of that in the central canal, becomes embryonic ; the periosteum is congested, slightly tume- fied, infiltrated with serum, and easily detached from the bone, from which it is separated by a layer of round or angular cells resembling those of embryonic medulla; the Haversian canals enlarge and are filled with similar elements, and opening into one another form an anfractuous lacunar system. The canals, which are divided in sections of the bone, are seen with the unaided eye as red points, or as openings from which small fleshy granula- tions project. At the same time new osseous trabeculse are seen to be formed under the periosteum, from the embryonic medulla which has been produced by the irritative process. The new formation of bone never begins at the point where the irritation is most intense, that is to say, on the surface of the divided bone, nor in the midst of the parts which are suppurating, but at a certain distance beyond. If the stump is conical and the bone projects, traces of new ossification are found, not at the level of the wound, but a little higher up, and new osseous trabeculse are produced on the surface of the bone. This subperiosteal osseous formation, coincident with absorption of the old bone, must not be attributed to any osteogenic property of the peri- osteum, for it is, in fact, the medulla-elements, developed by an irritative process under the periosteum and in the Haversian canals, which, as the irritation subsides, concur in the formation of new bone. When cicatrisation of the wound is complete, osseous tissue of new formation is produced in the formerly enlarged Haversian canals and in the meduUary canal, and when cure is obtained, the medullary canal is obliterated by an osseous plug, and the extremity of the stump is formed of a round mass of compact osseous tissue, covered with a new periosteum. Similar phenomena occur in every case of simple ostitis, provided necrosis does not take place. It is thus seen that simple ostitis, taking a natural course towards resolution, is rarefying at the beginning and condensing at the end ; we have therefore no more reason to call inflammation of the bone of a suppurating stump rarefying ostitis, than to give it the name of condensing ostitis, when the stump has cicatrised. Hence RAREFYING OSTITIS. 333 it is seen how necessary is the study of the pathological evolution of lesions, in order to arrive at a rational nomenclature. n. Earefying^ ostitis. — When in inflammation of the bone absorption of the osseous substance is the dominant phenomenon, and the Haversian canals by continually enlarging eventually bring about the entire disappearance of the bone, we call the ostitis rarefying. This variety of ostitis is remarkable by the absence of any attempt at new ossification. The focus of inflamma- tion, lined with large granulations, is generally in communication with the external air and secretes pus. Thus defined, rarefying ostitis is an uncommon disease. It may be observed in the small bones of the upper and lower extre- Fig. 185.— Accte or Fungoid Kaeefying Ostitis. a, cmbryonio mednUary tissue ; the osseous lamellse, 6, are notched in an uregnlax and festooned maimer (Howshlp's lacnnio) by the formation of meduUary cells, as at c. Section made from a bone decalcified by the action of chromic aoid. Magnified 100 diameters. mities, or as the result of traumatism, or of a continuous irritation, such as perforating ulcer of the foot. In the latter disease par- ticularly, one or more phalanges may entirely disappear without necrosis, though necrosis is sometimes met with in perforating 334 LESIONS OF THE BONES. ulcer. The diseased bone forms the base of a suppurating and more or less sinuous wound, Hned with granulations. These granulations, which are large, succulent, red or greyish in colour, are continuous, at the level of the bone, with an inflammatory tissue which extends into the enlarged osseous cavities. This inflammatory tissue has all the characters of bone granulations (p. 93 and p. II 1 ), and resembles that of certain sarcomata of bone, but is distinguished from them by the fact that in ostitis sup- piuration is an initial phenomenon, and is continuous during the whole time absorption of the bone is proceeding ; ostitis is, more- over, capable of undergoing spontaneous cure. The inflammatory tissue at the base of the granulations may, sometimes by spreading into the substance of the bone, isolate portions of osseous tissue, which thus form living sequestra possessed of blood-vessels and embryonic medulla, and which consequently are capable of being absorbed equally as well as the osseous tissue left in situ. Fig. 185 is drawn from a preparation of one of these sequestra. Living sequestra must be distinguished from the dead sequestra found in necrosis, and which are destitute of blood-vessels. The absorption of osseous tissue in rarefying ostitis occurs in exactly the same way as in simple ostitis ; the process is only more intense and continuous. Starting from the focus of sup- puration, it extends towards the two extremities of the diseased bone. When an entire bone — a phalanx, for example — is entirely absorbed, acute arthritis is produced at the same time. Not a trace is then left of the old bone, nor of the cartilage, excepting sometimes a thin, opaque, friable lamella, formed by the calcified layer of the diarthrodal cartilage, which is easily recog- nised under the microscope. On examining this lamella in gly- cerine with a power magnifying 150 diameters, a granular ground substance is noticed containing large, round, granular, and dark corpuscles, which are the representatives of the cartilage capsules infiltrated with calcareous salts, III. Formative ostitis. — Whenever ostitis ends in recovery it determines a new formation of bone. This new formation is some- times effected before the cessation of the ostitis. Sometimes ossification does not exceed the limits of the old bone, in which case the ostitis does not then merit the name of formative ; in other cases, on the contrary, the new formation is exuberant, and either exceeds the original limits of the bone, or causes the osseous :lssue to become more dense. The disease is then called hyper- OSTEOPHYTES. 335 ostosis, exostosis, enostosis, or condensing ostitis. All these varieties are included among formative ostitis ; nevertheless it must not be concluded that all osseous growths are related to ostitis (on this subject see Osteoma, p. 225). The subacute form of the inflammatoiy process and the length of time it lasts are the usual causes of formative ostitis. Thus it is particularly observed in deeply seated and chronic bone abscesses, in necrosis, and in syphilis of the bones. These diseases are, as is well known, cha- racterised by the slowness of their progress. We do not propose to include callus in our description of formative ostitis, for owing to the importance of the subject it wiU be considered separately. New bony growths may be developed on the surface of the bone under the periosteum, or in the sub- stance of the bone itself, or in the central medulla. a. Osteophytes. — In subacute ostitis of long duration, irregular osseous masses, called osteophytes, are found on the surface of the Fid. 186.— Pabenciiymatous Exostosis of the Tibia out across perpendicularly TO THE Axis of the Bone. fl, Hftversian canals of the parent bone cut across in a transverse direction ; 4, Haversian canals of the exostosis, the general direction of which is seen to bo perpendicular to those of the old bone. Magnified 10 diameters. bone. The trabeculae and blood-vessels of these new growths have a direction at right angles to those of the parent bone, so that it is extremely easy to distinguish one from the other. On examining the section of a long bone covered with osteophytes, the Haversian canals of the bone are seen to be divided transversely, while most of the canals of the osteophytes are divided longitudinally. The direction of the Haversian canals is subordinate to that of the blood-vessels, and the latter are derived either from the osteo- periosteal vessels, or from buds springing from the Haversian canals on the surface of the parent bone ; the new osseous layers are as in the physiological process of ossification, formed from the embryonic elements of these buds and deposited round the blood- 336 LESIONS OF THE BONES. vessels, whence it results that in the new growth the Haversian canals and systems are perpendicular to the surface of the bone on which they are developed. h. Eburnation. — In the body of the bone formative ostitis causes condensation or thickening (condensing ostitis, bony sclerosis, eburnation.) This is generally preceded by inflammatory rarefaction, traces of which may be easily discovered with the microscope. If the embryonic cells contained in the notched and anfractuous cavities which are produced by ostitis cease to be sub- mitted to intense irritation, they aid in the formation of new osseous layers which fill up the irregular festooned spaces. Thus the characteristic border of rarefying ostitis is seen distinctly in bones which have undergone subsequent ebmiiation. If the inflammatory action continues for several years in the same bone, as, for example, in necrosis or deeply seated abscesses, there are from time to time accesses of acute inflammation, and the bone attains a great size, double or triple that of the normal. The tissue is then extremely irregular, and appears to have been reconstructed many times. The lamellar systems are arranged in the most unexpected manner, and the accidental forms of such a pathological process can be better imagined than described. Eburnation of the osseous tissue produces, not only narrowing of the Haversian canals, but sometimes their complete obliteration (fig. 191) ; necrosis then occurs from the arrest of capillary circulation in the bone. c. Ossification of the central medulla. — Formative ostitis is rare in the medullary canal. Troja, Tenon, Broca, Oilier, etc., have reported cases of ossification of the central medulla in consequence of ostitis, and we om'selves communicated to the Societe de Biologic a case in which a new piece of bone was formed in the interior of the medullary canal of a necrosed bone ; as we have already shovm in amputations followed by recovery, the extremity j3f the medullary canal is always closed by a plug of compact bone of varying thickness. IV. Diffuse phlegmonous ostitis. — This disease is called osteo- myelitis (Chassaignac), 'phlegmonous periostitis (Giraldes), epi- physial ostitis, according to the views of the author as to the seat of the lesion. "We are of opinion that it consists essentially in diffuse suppurative inflammation which may be seated in every part of the bone, namely under the periosteum, in the superficial layers, in the substance of the bone itself, or in the central DIFFUSE PHLEGMONOUS OSTITIS. 337 medulla. As it occurs particularly in young children, and as growth of the bone takes place under the periosteum and near the epiphyses, the physiological activity of these parts is favour- able to more intense inflammation than the rest of the bone. The primary and dominant phenomenon of the disease consists in the rapid formation of pus, so that on incising the periosteum after the lapse of twenty-four to forty-eight hours a purulent focus is opened (Louvet). In these cases of rapid and extensive suppura- tion the entire bone may become necrosed, detached from its epi- physes and periosteum, and be contained in an enormous abscess. Purulent infiltration of the cancellous tissue of the extremities B A. Fig. IS, . — Syphilitic Solehosis of the Os Fhostis. A A, modullary spaces of tho diploo ; c c, the same spaces considorably retracted ; B, osseous substance. and of the medullary tissue may then be observed ; and it is easily understood how pus, accumulating within the rigid bony walls of the Haversian canals, may compress the blood-vessels, completely arrest the circulation, and cause necrosis. It is essentially a sup- purative inflanmiation, that is to say, inflammation in which pus is the principal product. There is generally in these cases no rare- faction of the osseous tissue, and the necrosed bone presents the same appearance as it does after maceration in water. It is rare for the suppurative inflammation to be so intense and extensive ; it may be limited to the neighboiurhood of an epiphysis, in which case an abscess is formed on the surface of the bone, on opening which a series of anatomical phenomena are observed, varying according to circumstances. In the least severe cases, the inflam- mation being superficial, the same lesions occur as in sijnple ostitis z 338 LESIONS OF THE BONES. after denudation of the bone, that is to say, rarefaction of the osseous tissue followed by condensation. But the superficial layers of the bone are often infiltrated with pus, in which case partial necrosis may occur. In another series of cases the sup- purative inflammation having invaded the medullary canal, or the areolae of the cancellous tissue, holes are very slowly, and by a pro- cess still hidden in obscurity, drilled, as it were, in the substance of the diaphysis or near the epiphyses, by means of which the abscess is drained. In these cases the inflammation is acute at the centre of the bone and almost nil at the periphery, though it persists in a subacute form on the surface as long as there is acute inflamma- tion at the centre. In consequence of this superficial inflamma- tion layers of new bone are, by a process of formative ostitis, deposited under the periosteum, and these being superimposed greatly increase the diameter of the bone. Even when suppurative ostitis is limited, partial necrosis is a very cpmmon consequence. III. Necrosis. With the majority of authors, we give the name of necrosis to mortification of bone resulting from traumatism or ostitis. Necrosis is caused by an arrest of circulation, generally related to compression of the blood-vessels in the Haversian canals, either by pus or by new osseous growths. When ready for elimination the necrosed bone is called a sequestrum. French surgeons dis- tinguish the sequestra of necrosis from those of caries ; when treating of caries it will be observed that we consider the distinc- tion legitimate, not only on account of naked- eye appearances, but chiefly by reason of the mode of formation of the sequestrum, as revealed by the microscope. At present, necrosis properly so called will only be considered. In compound comminuted frac- ture the detached fragments of bone are called splinters. They are either removed by the surgeon or eliminated by suppuration, and are unimportant; not so however the secondary mortification of the bone consequent on inflammation. These cases of necrosis are similar to those which are sometimes seen in a stump after amputation, if there is acute inflammation at the end of the bone or if it projects externally. It is difiicult in fact to understand, a priori, why after division a thin layer of bone is not always necrosed. After the bone has been sawn through, haemorrhage is arrested as soon as the blood coagulates in the small divided, blood-vessels; the bone cells being deprived of their ordinary EBURNATION OF SEQUESTRA. 339 means of nutrition, it must be supposed, if they live till cir- culation is re-established, either that they can for a time exist without nutrition, or that nutritive fluids reach them by another route, for instance, by the surface of the bone being bathed in the plasma of the wound. If the stiunp is conical, and the surface of the bone in contact with the dressings or the external air, a small part of the bone is generally necrosed. When necrosis results from acute inflammation of the stump, it is caused in a different way. Pus is i)roduced, not only in the soft parts, but in the bone itself, under the periosteum and in the Haversian canals ; the blood-vessels contained in these canals are therefore compressed, circulation is arrested, and necrosis results. In the case of wounds with denudation of the bone the conditions are the same as those in a divided bone. Separation and elimination of the sequestrum. — Whether necrosis results from traumatism, sujipurative ostitis, or formative ostitis in which the Haversian canals have undergone obliteration (p. 337), the phenomena of the separation and elimination of the sequestrum are as follows. The necrosed bone, acting as an irritating foreign body, occasions rarefying ostitis around itself, and is soon surrounded with granulations. The adjacent Haver- sian canals enlarge by proliferation of their medulla, and by absorption of tlieir osseous lamellee ; this process of absorption continuing, the living osseous trabeculse and those in which the blood-vessels are obliterated are both destroyed, and the canals cormnunicate. The disappearance of the trabeculse completely isolates the sequestrum in the midst of a granulating medulla. Owing to this process the sm'face of the sequestrum is not smooth, but furrowed by tortuous depressions, corresponding to the medul- lary buds of new formation. The method of ehmination differs according to the situation of the sequestrum. If located at the periphery of the bone, or under the periosteum, or at the ex- tremity of a divided bone, it is soon isolated in the midst of pus ; if it is on the surface of a large bone, or is the result of amputation Or denudation of bone, the necrosed part is also eliminated without difficulty ; if there is no wound opening externally, a deeply seated abscess is formed, and if this be opened spontaneously or with the knife, the sequestrum which is completely detached may be dis- charged with the pus ; but if the abscess communicates with the external surface by a fistulous opening, the surgeon is able to ex- plore the position of the sequestrum and to perform any operation necessary for its extraction. But if an entire bone, or a large poi+iou z 2 340 LESIONS OF THE BONES. of the diaphysis of a long bone, be necrosed, the subperiosteal medulla proliferates, becomes embryonic, and produces new osseous tissue under the periosteum and even beyond it. The new layers of bone slowly become thicker, so that the old necrosed bone is surrounded by new osseous tissue. In this case the extraction of the sequestrum is difficult, and it may remain included for years ; the sequestrum is then said to be invaginated. An invaginated sequestrum is never in direct contact with the bone which sur- rounds it ; the latter is lined internally with a layer of granula- FiQ. 188. — Invaginated Sequestkum of the Femuk with oonsidbkablb Sdepekiosteal Bony Growth. From the ' Pathological Surgery ' of Nflaton. tions, which constantly secrete pus and separate the dead from the living bone. When th^pus is not easily drained away by means of fistulous fenestras, it remains in situ, dries, and undergoes caseous degeneration. Action of pus on sequestra. — It is admitted by some that a sequestrum may be absorbed and slowly disappear by the action STRUCTURE OF SEQUESTRA. 341 of pus. This opinion is based upon the fact that inequalities and depressions are seen on the surface of necrosed bone. We are unable, however, to adopt this view, for if sequestra which have remained long in the midst of pus be examined with care, in some of them the surface will certainly be found to be smooth. On microscopically examining a section of such a bone, with a low power, the peripheral osseous lamellae which normally en- circle long bones will be recognised. We have frequently ascer- tained this to be the case in many old sequestra, one of which had remained thirty years in the midst of pus, and in which, at certain points, we still found the peripheral layers of the old bone. From this we conclude that the solvent power of pus is very limited, if it exists at all. The researches of Billroth and Kolliker have, however, proved that necrosed bone, and even Fio. 189. — Transverse Section of the Sequestrum of a Humerus which had BEEN FOR Thirty Years in the midst of Pus. The flguro only shows a portion of the surface of the bone where the peripheral lamellie, a, are prciicrved ; b. Haversian canalB ; c, Haversian systems. Magnified 20 diameters. wedges of ivory, may be partially absorbed; but the absorption should not be attributed to the action of pus, for, as we have already pointed out vrith regard to rarefying ostitis, it is the result of the action of the cellulo-vascular buds of the inflamed medulla.' Microscopic appearances of sequestra. — Sequestra and the living bone which contains them have very different appearances according to the progress and cause of the necrosis. Thus in acute suppurative ostitis, sequestra are found presenting the nor- mal structure of bone or the lesions of rarefying ostitis; in chronic ostitis, such as that caused by syphilis or phosphorus-poisoning, the necrosed bone shows special lesions. In syphilitic necrosis, ' Very beautiful preparations of osseous tissue may be made from sequestra, for the fatty substances and cellular elements have been completely destroyed by the prnloiiguil maceration in pua. 342 LESIONS OF THE BONES. SO common in the bones of the skull, the sequestrum corresponds exactly to a certain portion of the bone ; it has the same thickness and the same surfaces. The latter, however, have generally a rough- ened appearance from small losses of substance, so that it might be thought, at first sight, there -was some rarefaction of the bone ; but on making a section through the sequestrum, it will be seen that, on the contrary, the diploe is transformed into compact tissue. Such a sequestrum is not invaginated as in the long bones, but around it new bone is thrown out which overlaps the edges and holds it, in the same way that a watch-glass is held. In most cases of syphilis, formative ostitis extends over a large \^\<^ijN^\>s;^ Fig. 190. — Syphilitic Neckosis of the Os Fkontis with Pkoductive Ostitis. A, OS frontis ; a, sequestrum ; &, circinate and eburnated bony growths developed under the peri- cranium ; B, longitudinal section through the sequestrum a, and the part of the living bone 6, in which it is lodged. area and forms small, flat, often circinate hyperostoses (vide 6, fig. 1 90). Examined under the microscope the medullary cavities of the diploe are seen to be replaced by very narrow channels, and in good preparations this change is seen to have been caused by a formation of osseous tissue, which, deposited layer by layer on the internal surface of the canals, has narrowed them. These osseous layers are often so arranged that the lumen of the canal is not in the centre of the primitive cavity. By con- tinuation of the process the canal may be entirely obliterated, so that, instead of a canal in the centre of concentric layers, there is osseous substance containing one or more bone cor- puscles (fig. 191). Near the sequestrum there is often more or less extensive sclerosis of the diploe of the living bone, which may sometimes even be general. In a section cut at right angles to CARIES. 343 the surface, the whole process of condensation may be followed at certain points (wde fig. 187), just as we described it when con- sidering formative ostitis. In necrosis of the maxilla, found in workers in phosphorus, the sequestra are heavy, ebumated, and Fio. 191. — Section of a Sequestrum in Syphilitic Necrosis. Part of THE Preceding Figure Enlarged. ThiB figure representB a Havereian canal obliterated by succes- stTe layers of bone corpuscles, and ground substance arranged in regular lamella}. 1. Bone corpuscles ; 2. Centre o£ the Ha- Tersian canal. Magnified 300 diameters. often have superficial spongy osteophytes, which are easily detached. In that part of the sequestrum which belongs to the old bone, the lesions of condensing ostitis may be recognised. This condensation of the osseous tissue and the production of osteophytes show in a distinct manner that necrosis was preceded by slow formative ostitis. IV. Caries. The disease of the bones called caries is defined in a very vague manner by pathologists. Surgeons call caries every suppuration of osseous tissue accompanied with great friability. Their diagnosis is made by introducing a probe by a fistula into the substance of the bone, and breaking down a certain number of the osseous lamellae, in doing which a crackling noise is produced and the hand given a peculiar sensation. Pathologists, however, do not agree regarding the anatomical characters of the disease. German pathologists use the word caries to signify rarefaction of bone; according to Virchow, the changes in a bone after amputation, and the cavities which lodge syphilitic gummata of the skull, are both equally diic to caries. Billroth considers the name caries as absolutely synonymous with chronic ostitis, with 'melting of the bone,' and he describes many forms of caries, according as it 344 LESIONS OF THE BONES. is located in the superficial or deep layers of bone, and according to the appearance of the diseased parts, which may be sometimes vascular — fungoid caries — at others quite bloodless — atonic, torpid, or caseous caries ; he also admits a necrotic caries. Thus considered, caries includes a large part of the diseases of bones. We consider that the various lesions described by different authors in caries are all the result of one initial lesion, which consists in fatty chamge destructive of the cells contained in the lacunce. Our researches have also led us to recognise two distinct periods in caries : in the first, the bone cells undergo fatty degeneration with- out there being previously the least sign of inftammation.; in the second, the osseous trabeculce, killed by the death of their cellullar elements, form so m,any small foreign bodies which determine suppurative inflammation around themselves. This second period, in which ostitis takes on special characters according to the cause which produced it, is that which has alone been described by other observers. The initial lesions and first period of caries. — Caries generally occurs in short bones and in the extremities of long bones; among short bones the bones of the feet are most frequently affected. It is almost always accompanied, preceded, or followed by chronic disease of the joints^ — white swelling. The epiphysis of a joint, recently affected with white swelling, is formed of extremely fine trabeculse in the midst of a fatty medulla. To separate the tra- , beculas and distinctly see the delicate reticulum they form, a current of water should be directed on the spongy tissue ; they may then be removed with the forceps, and examined under the micros- cope. It is then seen that they are perfectly regular, have under- gone no loss of substance, and are not eroded and notched as in ostitis. Their thinness must be explained by the regular absorption of the surface, or by an arrest of development, an hypothesis which can only be considered in the case of young subjects in whom the bones are still growing. In these trabeculss granulo-fatty degeneration of the bone corpuscles is noticed, with atrophy of their nuclei. To recognise this lesion the calcareous salts should be removed by macerating the trabeculae for a few minutes in dilute hydrochloric acid, then washing with distilled water, and examining them after the addition of acetic acid; granules and droplets of fat are then seen to be present in the bone corpuscles, but the state of their nuclei cannot be clearly made out. To ascertain this, the trabeculae should be placed for twenty- four hours in a -2 per-cent. solution of chromic acid; after which they THE FIRST AND SECOND PERIODS OF CARIES. 345 are supple, showing that their calcareous salts have been dissolved out ; they are then washed, placed on a slide, and stained with a solution of anilin in acetic acid ; at the end of a minute they are again washed with distilled water and examined in water. With a lens magnifying 300 diameters it will be seen that in some corpuscles the nuclei have been preserved, but are irre- gular in form and surrounded with granules of fat ; generally the corpuscles simply contain fat ; some trabecule are found in which not a single corpuscle contains a nucleus. To observe these phenomena pieces of bone which have been dried in the open air .N^^" '9 c. & -^ J^-- ^ '^■siai Fid. 192. — OssKOUS Tbabecula of a Sicquesthum ok Caries iij the SiJi'KRioK Extremity OF THE Tibia i.v a Child. It has been De- f.vLciiir.ii BY Weak Ciiudmic Acid and Stained with Anilin Red. A, ground substance of the bono transparent and without fatty granules ; b, osHet^us corpusoles filled with fatty granules and coutabiing no nuclei. Mugnl&ed 260 dlameteis. must not be used, for as the bone dries the water evaporates, and the fiit contained in the medullary spaces takes its place and forms granules and droplets of fat in the bone corpuscles. Fatty degen- eration of the bone cells is only present in airies ; it may be looked for in vain in dry arthritis, in rhemnatism nodosum, in an- kylosis, etc., in which diseases, nevertheless, the osseous extremities are friable and contain adipose medulla. Second period. — Fatty degeneration, characteristic of the first period of caries, is present also in the second. Newlesions|then occiu-, which are visible to the naked eye, and correspond exactly to the anatomical description of cai-ies given by the older surgeons. These lesions are of an inflammatory nature, and seem to be caused by the presence of a large number of dead trabeculae, irregularly scattered through the osseous tissue. The medulla becomes very vascular. 346 LESIONS OF THE BONES. the adipose cells disappear and are replaced by embryonic cells, and suppuration is established. The bone cells, which have escaped fatty degeneration, become active, the osseous substance surround- ing them is dissolved, the necrosed trabeculse become free, and granulations are formed from embryonic medulla. These granu- lations, which are very vascular, may attain a great size when located in an open space, such as a fistulous tract, or better still the cavity of an articulation. The dilated blood-vessels they contain often rupture, and cause both external and interstitial haemorrhages. .These large granulations form what are called fungosities. Similar but much smaller granulations are found welded together in the enlarged areolar spaces of the epiphyses, and osseous trabeculas with cells infiltrated with fat are sometimes found imprisoned in their tissue. Sequestra of caries. — In some cases, islets of osseous tissue become necrosed, and are surrounded with granulations which may penetrate even the substance of the trabeculse composing the frag- ment. These carious sequestra are quite distinct from those caused by simple ostitis, for they are formed of trabeculse which are undergoing fatty degeneration and which are thin but not notched ; while the sequestra of ostitis always show, on the con- trary, the characters of inflammatory rarefaction or condensation, and their corpuscles never contain fat granules. The sequestra of caries, in the form of delicate trabeculse or larger fragments, may be dislodged by granulations and carried away by suppuration, if the fistulse open externally; and in their place are left irregular cavities, lined with granulations which slowly undergo fibroid organisation ; thus a kind of cyst is formed containing granular or caseous pus, and which may be often mistaken for old tubercle. In long-estab- lished and suppurating white swelling, islets, some centimetres in diameter, may sometimes be observed, formed of an ill-organised fibrous tissue, a iirm and slightly fibrillated ground substance similar to that observed in old fistulse leading to diseased bone. But at other times, there being no external outlet for the pus, carious sequestra may be found imprisoned, surrounded with granulations and infiltrated with caseous pus, the morbid mass having been isolated. Such foci closely resemble centres of puri- form tubercular infiltration in process of elimination (to be de- scribed later) ; and it is probable that the two are often con- founded ; the distinction between them may be made by certain signs which will be indicated when treating of tubercle of the bones. In caries, the embryonic medulla and voluminous granulations THE COURSE OF CARIES. 347 may undergo caseous degeneration for a more or less considerable extent. This change, probably due to vascular obstruction, was formerly considered to be of a tubercular nature. Inflammation occurring in a bone afifected with fatty degen- eration is reparative when, by a process already indicated, it has succeeded in eliminating all the necrosed fragments ; it then becomes less intense, and the regeneration of the tissue com- mences. But long previous to this, there have been exuberant formations of bone at points near to the centre of the inflammatory focus, under the periosteum and particularly round the fistulous tracks. The new subperiosteal layers, which are then thick, are formed of delicate separate osseous lamellae. The morbid process of caries being, however, very irregular, some parts of the bone have been long ago eliminated by the suppurative inflammation, while others only show some slight inflammatory lesion : in the former, eburnation is often met with, and in the latter rarefaction. This eburnation may lead to true necrosis by obliteration of the Haversian canals ; in which case, however, it is clear that irritation has been excessive. In a bone affected with caries the course of the phenomena, such as we have described, is not identical in different parts of the bone ; only during the first period does an entire epiphysis have the same appearances throughout : in the second period, the osseous tissue varies in consistency and colour, which variations have been rightly considered characteristic of caries ; some portions are yellowish, semi-transparent, and slightly vascular, with delicate osseous trabeculse (first period) ; others are vascular and purplish in colour ; some are whitish and opaque (caseous change, torpid or caseous caries of Billroth) ; here and there are spongy sequestra, partly detached, and surrounded with highly vascular fungosities (necrotic caries of Billroth) ; elsewhere there are islets of ebur- nated osseous substance ; finally there are upon the surface of the bone newly formed osseous layers, which are more or less extensive, thick, and stratified. After this description of caries, based on accurately observed facts, it is no longer possible to regard it as the same disease as simple ostitis, and, if inflamma- tion pl:iys an important part, it does not play the principal part, for the true though slightly apparent cause of caries is the primary fatty degeneration of the bone corpuscles. 348 LESIONS OF THE BONES. V. Callus. The name callus is given not only to the definite cicatrix which is formed between the two fragments of a fractured bone, but also to the new growth which precedes it. The anatomical phe- nomena in the evolution of callus are of a complicated character, and serve to connect inflammatory neoplasms and those consti- tuting tumours. Fractures may be divided into three classes : — 1. GoTnpound, i.e. those which communicate with the ex- ternal air and are complicated with wounds ; 2, simjple, i.e. those not complicated with wounds ; 3, resulting from a friable and diseased condition of the bone, as in cancer, rickets, etc. The two first only will be considered here. I. Compound fractures, or those complicated with external wounds, are the most simple from the histological point of view, and are those in which bone is reproduced most rapidly. The pheno- mena are identical with those observed in ostitis. At all the irri- tated points on the surface of the solution of continuity, the medulla becomes embryonic, as in simple ostitis; under the periosteum the embryonic medulla throws out new osseous trabeculae, which may be found there five or six days after the accident, whether the fracture be in man or experimentally produced in an animal ; the Haversian canals, laid open by the fracture, enlarge by absorp- tion of the osseous substance limiting them, and the medulla and blood-vessels which they contain concur in the formation of granulations ; and the central medulla more slowly undergoes similar changes. Thus, over the whole surface of the solution of continuity, granulations spring up and, uniting together, constitute an embryonic or inflammatory tissue. In this embryonic tissue, which is also present at the base of the granulations, and which forms a mass varying in depth and extent, osseous trabeculae are developed by the physiological process of ossification. Osseous needles spring from the old bone, which always seems to serve as the basis of the new growth, advance in every direction, and uniting with others near, and with those which spring from the opposite fragment, they limit spaces filled with embryonic tissue. These spaces are gradually lessened as fresh layers of osseous tissue are added, and thus consolidation is brought about by the solid adhesion of the two fragments of bone. In experi- ments made on small mammals, it is frequently found that sup- SIMPLE FRACTURES. 349 piirative inflammation is limited to the part in connection with the external wound, while cartilaginous masses are found in the deep part of the fracture which is not in contact with the external air. We shall show that cartilage is always produced in simple fractures imcomplicated with wounds. Suppuration continued for a variable time does not always prevent ossification. The process in its entirety does not differ essentially from condensing ostitis as seen in necrosis. 2. Simple fractures uncomplicated with wounds give rise, both in men and animals, to the production of a cartilaginous callus which subsequently undergoes ossification. Cruveilhier taught that ' the callus was formed by the ossification of all the soft parts which surround the fragments,' adding, however, that it was the connective tissue, whether in muscle or periosteum, which con- tributed to its formation. Opportunities are rarely found in practice of examining cases of simple fracture during the period of repair ; but in old subjects affected with senile osteomalacia the occasion not unfrequently presents itself, and in these cases it is always found that consolidation of fracture is by means of a cartilaginous callus. The structure of callus in simple fracture can best be studied experimentally in animals. The first phenomenon following fracture is haemorrhage, which goes through all the phases of ecchymosis, and is generally so extensive as to gradually spread towards the skin. Soon phe- nomena due to irritation occur in the subperiosteal medulla and in the Haversian canals. This irritation, reaching the periosteum and the neighbouring connective tissues, causes proliferation of the cells, so that on the fifth or sixth day after the fracture all these tissues, rich in plasma and cells, concur in forming a single, firm, and consistent mass, which is, however, not yet cartilaginous. I'nder the periosteum and between the two fragments appears a tliin, pulpy layer, in which, on microscopical examination, are seen cells of the varied forms of embryonic medulla, that is, small round cells similar to white blood corpuscles, round or irregularly shaped cells, 15 /I in diameter and containing one or more oval nuclei, and cells with peripheral buds (vide. fig. 4). Among them red blood corpuscles and blood pigment are also found. This pulpy layer completely seiKirates the mass of the peripheral embryonic callus from the bone ; it is limited by the smooth internal pearly surface of the periosteum, ^^'llen this pulpy layer is raised, the surface of the bone is complet«ly denuded, and the Haversian canals are seen 350 LESIONS OF THE BONES. as red points or lines, just as in the commencement of ostitis. In a case of fracture of the clavicle with tearing of the periosteum, the pulpy layer of subperiosteal embryonic medulla was found at some spots to be more than a millimetre in thickness. In animals, when the periosteum has been torn, this layer is not so thick ; it has even often escaped observation. If the irritation is not intense, the periosteum adheres to the bone as in the normal condition. At a later period, towards the eighth day, the cellular elements of the peripheral callus have multiplied to such an extent that the connective-tissue bundles and elastic fibres have almost Fia. 193. — Superior Fragment of a Fractured Tibia from an Adult White Eabbit, at the End op Twelve Days. The inferior fragment which was displaced is not included in the figure ; in it the same layers were observed as in the part here represented. 0, old bone ; m, central medulla of the o'd bone; a, new bone in which embryonic medulla is abundant and causes the opacity observed in the . draw- ing ; the blood-vessels of this tissue are generally at right angles to the surface of the bone ; b, cartilage ; tk, embry- onic connective tissue intermediate between the two frag- ments, and penetrating into the medullary cavity ; p, peripheral tissue blending with the periosteum. Magnified 20 diajneters. entirely disappeared, while the blood-vessels, particularly on the border of the callus, have greatly developed. It is then, that is, from the eighth to the tenth day, that the cells of the peripheral callus are observed to become surrounded with cartilaginous sub- stance, while the cells of the peripheral medulla still remain free. The peripheral callus is now cartilaginous, of the variety known as embryonic cartilage (p. 18), and is quite independent of the bone. CALLUS IN SIMPLE FRACTURE. 35" From the tenth to the fifteenth day the callus is infiltrated with calcareous salts, which appear in disseminated points near the bone ; but calcareous infiltration is preceded by proliferation simi- lar to that seen in the physiological ossification of a short bone.' Large cartilage capsules are observed filled with secondary cap- sules and opening into one another as the cartilaginous substance separating them becomes encrusted with calcareous salts ; areolar spaces are thus formed, communicating with the periosteal medulla, and into which vascular branches from the blood-vessels of the old bone are pushed. Osseous trabeculae are soon developed the bases Fio. 194. — Callus aftku Simi'lk Khactuuk of the Tibia in ON THE IWliNTY-SKVEXTH DaY. Rabbit, of which are implanted on the old bone. In the majority of cases which we have examined, the first trace of ossification is not seen near the ends of the two fragments, but near the upper or lower borders of the callus. While bone begins to show at the margins of the callus, the formative cartilage increases between the two fragments, and undergoes calcareous infiltration, which infiltration invadt-s parts of the cartilage where there has been no prolifera- tion. At this period — that is to say, from the fifteenth to the twen- • These preparations are obtained from specimens of callus decalcified in a -5 per 100 siihition of chromic acid, or in a concentrated solution of picric acid. 352 LESIONS OF THE BONES. tieth day— the callus is firm and resistant, but, ttough now solid throughout its entire mass, the whole of it does not undergo ossification. The peripheral parts, though infiltrated with cal- careous salts, are not ossified ; it being probable that they are absorbed without undergoing ossification. The part of the callus near the bone between the two fragments slowly ossifies and becomes finally converted into a sohd mass, dividing the medullary canal into two portions ; subsequently, and by a mechanism very imperfectly understood, this solid mass is perforated in the centre to re-estabhsh the primary medullary canal. By the time that this final process has been effected, the peripheral callus has dis- appeared, so that in some cases it is difficult to believe that there has been a fracture. Hence Dupuytren had some reason in calling the peripheral callus the provisional callus. We have already said that all the soft parts surrounding a broken bone aid in the for- FiG. 195. — Transverse Section of the Tibia of an Adult White Eat j Cut AFTER Decalcification in a '5 pee 100 Solution of Chromic Acid. The bone -was denuded in the living animal, and a wedge-shaped piece, a, about a centimetre in length, was removed with a scalpel. The gap has been filled up by new osseous tissue, and it is to be noticed that it has been deposited so as to give the bone its original shape twelve days after the operation ; jp, periosteum ; o, old bone ; a, new bone compensating for the loss of substance produced by the operation ; d, new bone developed under the periosteum ; 6, medullary cavity diminished in size by the new osseous growth. Magnified 20 diameters. mation of callus ; the muscles are no exception to this rule, as Cruveilhier pointed out; but it is not the muscular fasciculi themselves, but the inter-fascicular connective tissue, which is the active element. The muscular fasciculi undergo fatty degene- ration, atrophy, and slowly disappear, and all those which are implicated in the formation of callus are lost to the organism. Thus two methods of formation of callus are observed, ac- cording as the fracture is simple or compound; in compound fractures ossification takes place directly from embryonic and granulation tissue, while in simple fracture bone is formed from TUMOURS OF THE BONES. 353 cartilage by the physiological method. In the present state of science it is impossible to explain what is the cause of this difiference ; the influence of the presence of bone in inflamed tissues cannot be adduced as the cause, as this occiu's equally in both cases ; neither can it be due to different degrees of irritation, for in condensing ostitis, whether acute or chronic, cartilage is not produced. If in a small mammal the bone is scraped so that the medullary canal is opened, the loss of substance is filled up by new osseous tissue, which is not preceded by cartilage, even if the wound unites by first intention, a result easily obtained in rats {vide fig. 195). These facts, which were discovered by one of us, have not met with attention ; hence it is that Forster is unable to explain how, in man, he has never found cartilage in the callus, while in the rabbit fracture always cicatrises by means of carti- lage. This arises from the fact that Forster, as well as most patho- logists, have only had the opportunity of examining subjects who have died from serious compound fractures, while in experiments made on animals with the object of studying fractures, simple fractures only are produced. VI. Tumours of the Bones. Almost every kind of tumour previously described is met with in bones ; but those most frequently seen are the principal varieties' of sarcoma. In studying the seat of tumours of the bones an important distinction should be drawn between primary and secondary tumours. In the first case, it is generally the bones wliich are exposed to external injuries which are most frequently affected — the tibia and maxilla, for example. The bones most frequently attacked by secondary growths are, on the contrary, the vertebrae, sternum, and ribs — that is to say, those in which red medulla is present. Soft primary and rapidly extending tumours invade and destroy the osseous tissue as they progress. The bone is absorbed by a process similar to that of destructive ostitis. The morbid tissue of the tumour is not generally in contact with the osseous trabeculae, being separated from them by a layer of em- bryonic tissue, from which the tumour develops. Sometimes the morbid process is continued to the extremity of the bone, but there, as in ostitis, it is arrested by a calcified layer of cartilage, which barrier is rarely passed, though in such cases subacute arthritis is generally present. Secondary tumours affect the bones much more frequently than is generally supposed; they A A 354 LESIONS OF THE BONES. can only be discovered by carefully made autopsies. The prog- nosis varies according to the nature of each tumour. We have nothing to add to what we have said regarding tumours in general, only that in tumours of the bone it must be noted that, the medullary system being continuous throughout the entire bone, tumours may find here a convenient nidus ; and if in an operation the apparent tumour is alone removed, the adjacent part of the bone being left intact, a recurrence of the growth almost always follows. Species and varieties of tumours of bone. — Encephaloid sarcoma is common in bone (p. 135), where it may attain a large size and spread rapidly ; it not unfrequently assumes the erectile form, and in bone may give rise to symptoms which have been clinically ascribed to aneurism of the bone. The vascular dila- tations, caused by the return of the walls of the capillaries to the embryonic state, may be so large, and the communications esta- blished between them sometimes so extensive, that one large sac may be formed. Inside this sac delicate, soft, and floating septa may often be found, the structure of which is the same as that of the tumour. On a superficial, naked-eye examination, such a growth might easily be mistaken for aneurism of the bone. Hsemorrhagic foci and cysts due to mucoid degeneration may also be observed {vide p. 147) in encephaloid sarcoma of bone. Fasciculated sarcoma is much more common in bone than the preceding. The arrangement of the tissue in fasciculi is more or less complete, to which is due the firmness of these tumours, varying from that of encephaloid to that of fibroma, so that it is often difficult to distinguish between encephaloid and fasciculated sarcoma, particularly in those rather common cases in which the two morbid varieties are united in the same tumour. Soft fascicu- lated sarcoma is often observed in the substance of the bone, while hard fasciculated sarcoma is more frequently subperiosteal. In fasciculated sarcoma of the bones, large giant cells — the largest found anywhere — are frequently observed; but the presence simply of these cells is not sufficient to characterise any particular species of tumour, and to indicate, as Nekton thought, that the growth was consequently benign. These cells are, in fact, met with in every kind of sarcoma both of the bones and of other organs. Both encephaloid and fasciculated sarcoma very often become incrusted with calcareous salts ; this lesion has no influ- ence on the prognosis. The change generally occurs in the form SARCOMA OF BONE. 355 of needles or friable trabecule, in whicb the cells of the morbid growth are found inclosed in small lacunae without processes. Bones, affected with sarcoma, are very easily fractured at the diseased spots, and from the sarcomatous tissue islets of cartilage are formed which do not, however, succeed in producing a solid callus. This fact seems to indicate that fracture acts on morbid tissue in the same way that simple fracture acts on the normal tissues surrounding it. Fio. 196. — Section of a Fasciculated Sarcojia. a, sarooma cells arranged in foaciculi and seen sideways ; b, cells of the fasciculi placed at right angles to the former ; v, blood-vessel showing a row of flat cells in its wall. Magnlflod 20 diameters. In myeloid sarcoma the tissue is soft., like that of the foetal medulla of bones, and has moreover the same histological charac- ters. It is composed chiefly of round transparent cells, larger than normal ; mother-cells are sometimes numerous ; the walls of the blood-vessels are normal, and do not become embryonic. We lia\ e seen a tumour of this kind almost entirely destroy the tibia. Ossifying sarcoma is a very common species ; it is that which forms almost all the epules, subungueal tumours, and many of those tumours known in France under the name of tumours of myelo- plates (tumeurs a myeloplaxes). All the latter are, however, not A A 2 356 LESIONS OF THE BONES. ossifying sarcomata, so that the terms are not synonymous, for fesoiculated sarcomata may contain a great number of giant cells, but they must not be confounded with ossifying sarcomata, which are relatively benign, while fasciculated sarcoma is extremely malignant. Lipomatous and melanotic sarcomata are also met with in bone, the latter are secondary growths {vide fig. 199). myxoma is found in bone in the form of a globular, clearly defined tumour. It is generally developed under the periosteum, and causes an absorption of the bone which supports it ; we have Fig. 197. — Secosdakt Melanotic Tumouks of the Femur, and Melaitotic Infiltkation of the Bone Medulla. After Benjamin Anger and WortMngton. never seen it infiltrate the osseous tissue in a dififuse manner. With myxoma must not be confounded a nutritive lesion of the marrow of the bone, which is seen when cachetic conditions have existed for a long time, and which is characterised by a gelatinous appear- ance, due to the more or less complete absorption of the fat of the adipose cells, and its substitution by serum or plasma. Lipoma. — "We have seen but one case of lipoma of bone ; the tumour was very large, and had developed in the body of the tibia ; the lobules of adipose tissue, instead of being bounded by fibrous septa, were separated by osseous trabecule. CARCINOMA AND TUBERCLE OF BONE. 357 Carcmoma. — In bone is found every species and variety of carcinoma; we have seen well-authenticated cases of primajry carcinoma in bone, but secondary growths are much more frequent ; thus, scirrhous carcinoma of the breast of long duration is almost always accompanied by secondary nodules in the vertebral column, which rarely develop into large tumours, the morbid tissue being more often substituted for the osseous tissue, so that a bone, a ver- tebra, for example, may be almost entirely composed of carcinoma- tous tissue, without its showing any marked change in form. There may even be considerable atrophy of bone without ulceration or erosion. If one or more vertebrae are affected with carcinoma and they break down, being in a friable state, such a loss of substance may be occasioned that curvature of the vertebral column may result, as in Pott's disease. When developed in the body or ex- tremities of the long bones, spontaneous fractures may occur, followed by extravasation of blood ; but we have never seen the least attempt at repair by ossification, the irritation only resulting in the transformation of the neighbouring tissues into carcinomatous tissue. The development of carcinoma in bone has been de- scribed at page 176. Tubercles are generally observed in the cancellous tissue of long or short bones, but their seat of predilection is the bodies of the vertebrae, the sternum, and the ribs. It is in these places that general miliary tuberculosis is most frequently met with, ;md where the interesting evolution of tubercle can be most easily followed. In the adult, the medulla of the sternum, ribs, and bodies of the vertebrae is red, inclining to violet, and sHghtly trans- lucent. It is composed of the usual medulla cells, a few scattered fat cells, and blood-vessels, around which there is a delicate layer of ordinary connective tissue. An isolated tubercle in such a tissue is so distinctly characteristic that it is impossible to mistake it ; it forms a cfrcular spot, one to two mm. in diameter, quite bloodless, semi-transparent, and often with a slightly iiTegular border ; in the centre it is frequently opaque, while at its peri- phery the medulla is of a deep red colour. The tubercular nodule cannot be felt with the finger, owing to the presence of osseous trabeculae. The semi-transparent, grey granulation of osseous tissue can thu.s be distinctly recognised with the naked eye ; but to make a thorough examination, the method of preparing the bone is not a matter of indifference. After dividing the bone with a saw, the surfaces should be scraped with a strong scalpel. The bone may be equally well divided by means of a blunt wedge and 3S8 LESIONS OF THE BONES. a hammer, for even the finest saw produces a great deal of debris on the surface of the bone, and completely changes its appearance. In bone thus prepared discrete tubercular granulations can be distinctly seen, for they show plainly in the midst of a highly coloured tissue ; but if the granulations are grouped together in the same medullary space, their recognition becomes impossible without recourse to the microscope. Confluent granulations form irregular m.asses varying in diameter from three to four mm. to many centimetres. At the beginning of the process it can be easily seen that large masses are formed by the union of a certain number of smaller masses ; in form these are generally very irre- gular, and there is nothing in their appearance to lead any one, who had not already examined similar growths under the micros- cope, to guess what was their true nature, and even such a one might be deceived. They are bloodless, granular, grey, and semi- transparent, at some places they form very small opaque spots, which in the older growths, by extending and blending together, give a decidedly caseous appearance to the morbid mass. The osseous trabeculae which are contained in the midst of this caseous mass are most frequently intact. At the border of the entirely caseous parts there are two zones, the most internal of which is narrow, anaemic, and semi-transparent with opaque spots; the external is a deep red, not transparent, and melts gradually into the violet medulla. In some cases when the formation of tubercle has been rapid and has occurred simultaneously at a great number of spots, the medulla of the entire bone (sternum, bodies of the vertebrae) is of a very dark red. In such cases also the osseous framework is seen to have undergone rarefaction. There are therefore two varieties of tubercle in bone : dis- crete tubercular granulations, and confluent tubercular gra/nvr lotions. Discrete tubercular granulations in bone. — If a tubercle in bone be removed with a cataract needle, it looks like a small, round, or slightly angular mass. Placed on a sHde in a drop of water and examined without being covered with a cover-glass, with a power magnifying 150 diameters, the mass appears to be composed solely of medulla cells movable on one another ; but this appearance is an illusion caused by the mass being completely enveloped by meduUa cells ; in fact, if the granulation be washed with a camel's-hair brush, it is found that it cannot be disintegrated, and, on examining it again after covering it with a cover-glass, very small cellular elements (5 /i to 7 /*) are perceived, immersed in a granular, or DISCRETE TUBERCLE IN BONE. 3S9 slightly fibrillar substance ; if the centre of the granulation is already caseous, this part appears opaque. But this process is very imperfect, and, to study tubercle well, delicate sections should be cut after maceration in -5 per 100 solution of chromic acid. To decalcify the specimen so as to cut sections of the osseous tissue with a razor, time, varying according to the size and density of the fragment, is required. To complete the hardening process, and to retain the cellular elements vn, situ, it is well to afterwards em- ploy gum and alcohol. A granulation seen in a section has, under Fio. 198. — DiscBETE Tubercle of the Sternum, from a Case OF Acute Tuderculosis. Py periosteum of the anterior surface of the sternum witli thick embryonic subperiosteal layers as in ostitis ; o, first osseous layer in which the lameUro are irregularly notched by the inflanunatory process ; m, em- bryonic medulla in the midst of which a tubercle is seen surrounded by a dark aone produced by vascular dilatations and hsemorrhages. Mag- nified 20 diameters. the microscope, the following characters : at its periphery the medulla is observed to contain no fat cells, the blood-vessels are dilated, and no longer have connective tissue around them. This zone of irritation often extends to many areolae of the spongy (issue, in which the osseous trabeculse are found notched as in (i.stiti.s. These phenomena of irritation are not only observed round the granulation, but at points far removed, so that it is logieal to suppose tliat formative irritation precedes the appear- aii(<' of granulations; in one wcutI, that in bone, ostitis precedes tubercle. The tissue of the granulation is composed of small, refractive cellular elements, which diminish progressively in size 36o LESIONS OF THE BONES. from the periphery towards the centre ; they are contained in a firm granular substance. Confluent tubercular granulations in bone. — It is probable that some of the changes which Nelaton described under the name of tubercular infiltration were lesions caused by confluent tubercular granulations ; but his description applies equally well to caries with caseous degeneration of the pus, to eburnated sequestra, and to certain syphilitic gummata. In fact, without the microscope, it is often impossible to know if a lesion be tubercular, for though the granulation is the unique characteristic product of tuberculosis, yet confluent tubercular granulations cannot be diagnosed with Fig. 199. — Confldent Tdbekclb ik Bone. rt, osseous frabecolse ; e, embryonic medullary tissue ; 6, tubercles. Magnified 20 diameters. the naked eye. When a great number of granulations are formed contemporaneously in the same medullary space (6, fig. 181), they do not attain so large a size as discrete granulations, they rapidly undergo caseous degeneration, and induce a similar degeneration of the medulla contained between them. The development and structure of tubercle are always identical, whether the granulation be discrete or confluent. It is now proved that a tubercular granulation developed in bone causes the obliteration of the blood-vessels which traverse it ; hence it is obvious, that if many granulations are scattered over the same medullary space, the eirculation in all the vascular branches of this space may be CASEOUS DEGENERATION OF THE MEDULLA. 361 arrested ; if, moreover, some areolae of spongy tissue, free from granulations, were surrounded by areolae filled with tubercle, they would also have their blood-supply cut off. All parts of the bone in which the circulation has been arrested undergo caseous degen- eration, for the same reason that infarcts become caseous. The areolae, which have become caseous from vascular obliteration, frequently have a different appearance to those which have under- gone the same change from breaking down of tubercular granula- tions. In the former, the adipose cells are preserved, or their plaxje is marked by groups of stearic acid crystals ; in the latter, the adipose cells, having disappeared in the ostitis which preceded tubercle, have left no traces. Caseous degeneration of the medulla. — The medulla in under- going caseous degeneration first becomes semi-transparent, and the medulla cells seem pressed and blended together ; but this condition does not last long, and is observed only in a very limited area ; it is soon followed by caseous degeneration, when what was previously medulla and tubercle are no longer distinguishable. The osseous trabeculae contained in a caseous mass do not gener- ally undergo either condensation or rarefaction. Except in tuberculosis it is rare to find such extensive lesions of osseous tissue without rarefaction ; we have, indeed, seen cases in which bones, or fragments of bone, have remained in the midst of a mass of caseous pus, without being either wholly or partially dissolved ; while osseous trabecule', even when necrosed, which are in contact with an active medullary growth, are generally absorbed. When, in consequence of the tubercular process, the areolae of the spongy tissue become rapidly filled with a caseous mass resulting from the degeneration of the granulations or of the intermediate medulla, it is comprehensible that the adjacent osseous trabeculas may per- sist indefinitely. The bone corpuscles are not implicated in the caseous degeneration of the elements of the medulla ; their nuclei become irregular, but there are no fatty granules around them. This fact, ascertained by means of staining with anilin red, allows of the distinction being made between caseous degeneration following confluent tubercle and that which accompanies caries. While in the latter the bone corpuscles undergo granular fatty degeneration, the bone tissue affected by tuberculosis becomes necrosed by having its blood-supply cut off, and elimination occurs when the tubercular eruption has reached a certain point. Elimination probably occurs in the same way as in simple necrosis, that is, as the result of rarefying ostitis which, set up on the margin of the 362 LESIONS OF THE BONES. tubercular centre, determines the absorption of the osseous trabe- culee and the formation of granulation tissue. In this manner a cavity is formed which lodges for a longer or shorter time a seques- trum bathed in pus. If in bone a cavity is found, lined either with granulations or a smooth membrane, and which is filled with pus or caseous matter, it cannot, in the present state of science, be concluded that it is of tubercular origin, unless tuberciilar granu- lations are found in the peripheral tissue. A sequestrum of can- cellous tissue immersed in pus or infiltrated with caseous matter cannot be attributed to confluent tubercle, unless confluent or discrete granulations are found in the surrounding bone tissue. In fact, simple ostitis, caries, and gummata may in osseous tissue produce changes which, in their naked-eye appearances, resemble confluent tubercle in the period either of evolution or of elimina- tion. Crummata of the bones have been studied by Dufour, Grosselin, Virchow, and ourselves. Like tubercle, they are frequently located in the bones which contain red medulla ; in the bones of the skull, however, in which tuberculosis is unknown, gummata are frequent. Anatomical descriptions of gummata of the bones are rare, for, though they are clinically common, patients rarely succumb to syphilis. Grummata of the bones are seen under two forms : well defined, with the appearance and consistence of sarcoma, or infil- trating the osseous tissue, and justifying the name of gummatous osteomyelitis which has been given them. Circumscribed gummata have been studied by Virchow in the bones of the skull. We have ourselves seen many cases. They first develop under the epicranial periosteum or above the dura- mater, and sometimes simultaneously at both these points ; they advance in a conical form into the osseous tissue, of which they determine progressive rarefaction (the structure of gummata has been described on p. 191). They then undergo caseous larda- ceous change, and, if the description given by Virchow be accepted, they are slowly absorbed, probably as the result of treatment. In their place is formed a stellate cicatrix of osseous tissue mixed with fibrous "tissue. Notwithstanding that Virchow allows that these cicatrices are those of old gummata, he calls them by the name of dry syphilitic caries. It is evident from the description we have given of caries that there is nothing in common between this lesion and that caused by syphilis. Those singular losses of substance, which are truly characteristic of syphilis, are bounded DIFFUSE GUMMATA OF BONE. 363 by sclerosed osseous tissue, and are often surrounded by flattened osteophytes. Diffuse gummata are particularly frequent in bone which is sub- cutaneous, and in the palatine arches. They develop simultaneously under the periosteum and in that portion of the bone covered by it, in the form of a soft, slightly gelatinous tissue, which is at first rose-coloured, but subsequently becomes opaque and firmer. On section of the bone at this stage a whitish surface is seen, caseous in appearance and resembling confluent tubercle ; but a phenomenon which will serve to dififerentiate the bone is already present, and is Fig. 200. — Syphilitic Ostitis. 1, oseeouR tmboculas with orodod and dentate borders, in which, at 3, unl- nucleatod Itono corpuscles are seen, and multi-nucleated at 2 ; 4, medullary tissue ; />. blood- vessels of which the lumen is patent. At the upper part of the figure the colls are atrophied and arc undergoing caseous change. to be found in a white pulpy layer which is seen under the peri- osteum over the area corresponding to the bone lesion. In delicate sections, made after maceration of the bone in a '5 per cent, solution of ihromic acid, the osseous trabeculae are seen to be notched as in rarefying ostitis, and the enlarged medullary spaces contain gummatous nodules {vide p. 333), in which the blood-vessels are permeable, a fact which differentiates them from tubercle. At the margin of the gummata there are all the appearances of simple ostitis. To the question what becomes of diffuse gummata of the bone, an answer cannot be given based on an accurate knowledge of const'cutive histological facts ; we only know from clinical obser- vations that gumniatu, for example those of the sternum and tibia, 364 LESIONS OF THE BONES. may completely disappear under the influence of anti-syphiUtic treatment, and leave in their place hyperostoses similar to those which accompany circumscribed gummata of the frontal bone. Cases of syphilitic necrosis have, moreover, been observed in which the sequestra, instead of being eburnated, are, on the contrary, found to be riddled with numerous cavities filled with a caseous detritus at the moment of examination, and which probably formerly contained gummatous tissue. Virchow even thinks that every case of syphilitic necrosis has a similar origin, but we con- sider that necrosis of the bone very often results from condens- ing ostitis or sclerosis, continued till the vascular canals are obliterated. Chondromata of bone. — Osseous tissue is more often affected by chondromata than any other. They are called perichondromata when located under the periosteum, and enchondromata when developed in the substance of the bone itself. They may be diffuse or lobxilated: the latter is the more common variety. All the varieties described on page 215 may be met within bone, namely, hyaline, ossifying, mucous chondromata, lobulated or fibro-cartilaginous chondromata, or the variety formed of branching cells. They develop in the way we have already described (mcZe p.219),andwe have nothing to add regarding their prognosis (vide p. 222). Primary osteoid tumours are always developed from osseous tissue. (For description of them see p. 222.) Osteomata of osseous tissue are called exostoses, hyperostoses, or osteophytes, according to the form affected on the surface of the bone {vide p. 225). The name of enostoses has been given to those osseous growths which are developed within the medullary canal. Osseous tumours found in other organs will be described when treating of the organs in which they are met with. Lymphadenoma of bone. — In leucocythsemia, lymphatic tumours or lymphadenomata of the bones may be met with. In a case which we published in 1867 the tumour was of considerable size: it was composed of a whitish tissue, which on scraping yielded a milky juice, which contained cells resembling white blood corpuscles. At some points the tumour had undergone caseous degeneration. In sections cut after hardening in alcohol and chromic acid the retiform stroma of adipose tissue was found everywhere. With the unaided eye this tumour might have been mistaken for carcinoma. OSTEOMALACIA. 365 Since this first case, several similar ones have been published, particularly by M. Kelsch. Epithelioma of bone. — It is doubtful if there has ever been a case of primary epithelioma of bone, but its extension from neighboming tissue is common. Thus epithelioma of the lips may be propagated to the maxilla ; that of the palate to the pala- tine arch, that of the limbs may become deeper and attack the underlying bones. The morbid growth develops by means of epithelial buds, which are pushed forward and grow in the midst of an embryonic tissue, which is itself formed from osseous tissue as in ostitis {vide pp. 265 and 266, and figs. 154 and 155). Tubular pavement epithelioma is met with in bone ; it is rather frequent in the superior maxilla, where it is consecutive to tumours of the soft palate and the Antrum Highmori ; lobulated epithelioma is also observed here, where it is consecutive to cancroid of the Ups. A single case of cylindrical-celled epithelioma has been reported by Gawrilofi", which is not surprising considering that this form of epithelioma causes secondary growths like carcinoma. Cysts, showing all their usual characters, are sometimes met with in bones. VII. Osteomalacia. True osteomalacia is a disease which is most frequently seen in women after one or many confinements. It has become extremely rare in France, while it is observed rather frequently in Bavaria. It is characterised by a nutritive lesion of the bones, which ter- minates in absorption of the calcareous salts and solution of the osseous trabeculae ; at the same time, important changes take place in the medulla. In the first period the volume of the bones is preserved, and there is no rarefaction ; they can, however, be cut through with a sharp knife. Under the microscope it is then seen that the centre of the osseous trabeculje contain calcareous salts, while the margins are quite deprived of them. According to Kindfleisch these parts stain with carmine. Now it is known that a non-decalcifying bone does not stain with carmine. The bone corpus- cls :ire similar to those obtained in preparations of bone decalcified by chromic or hydrochloric acid. The blood-vessels of the medulla are full of blood. The fat cells are less abundant than usual, and in their place are found cells which may be round or irregular, fusi- form or flat. Hsemorrhagics soon occur in the medulla, and appear 366 LESIONS OF THE BONES. as ecchymotic spots or foci ; they may also take place under the periosteum, which adheres but feebly to the subjacent osseous tissue. In a second period the bones undergo considerable changes of form : they bend over, fall together, and become fractured, and it is then that those extraordinary malformations are seen of which so remarkable a specimen is preserved in Dupuytren's Museum (Paris). The osseous trabeculas are then not only decalcified throughout their whole thickness, but are also partly absorbed. The enlarged medullary spaces are filled with a foetal medulla having the appearance of splenic pulp. In consequence of extra- vasations of blood, the hsemoglobin of the blood, in the form of Fig. 201. — Section of the Cancellous Substance of a Kib affected with osteomalacia. a, normal osseous tissue ; 6, part deprived of calcareous salts ; c, Haversiau canal. Magnified 300 diameters. (After Bindfleiscli.) yellow, red, or brown pigment, is frequently found in the medullary cells. The firactures produced in osteomalacic bones do not gener- ally unite well, though some cases of bony union have been reported, but in these cases the disease was progressing towards cure. A satisfactory explanation has never yet been given of the decalcification and absorption of the osseous tissue. An attempted explanation has been given by the formation of an acid which dissolves out the calcareous salts ; what this acid is, is not known. Weber has found free acid in the urine of osteomalacic patients ; Eindfleisch thinks that the solution of the calcareous salts might be attributed to an excess of carbonic acid gas ; he considers that the venous congestion of the medulla, observed in the first period, RACHITIS. 367 is caused by stasis, and hence that the blood is charged with carbonic acid, which being brought into relation with the osseous trabeculaj dissolves out the calcareous salts. This is, however, only an ingenious hypothesis. Senile osteoporosis. — Under the name of senile osteomalacia has been described rarefaction of the osseous tissue caused by enlargement of the medullary spaces. In this disease the friability of the bone is simply related to its rarefaction ; there is not here, as in true osteomalacia, softening due to decalcification. The rare- faction of the bone is accompanied with important changes in the medulla, similar to those observed in true osteomalacia. They consist in the disappearance of the adipose cells, and the formation of cells similar to those of foetal medulla. Sometimes young connective tissue of new formation is produced in the medullary spaces. The bones most frequently affected with this disease are the ribs and the vertebrae. The vertebral column bends, the ribs fracture from the slightest exertion, and curiously enough perfect consolidation is effected by the ossification of a cartilaginous callus. Adipose osteoporosis. — We call by this name a form of rarefac- tion of the bone ; it is seen particularly in the epiphysial extre- mities of the long bones or in short bones, and is characterised by an abundant formation of fat cells in the medullary spaces and Haversian canals. The osseous trabeculse of the spongy tissue become very thin and finally disappear ; the bone is then reduced to a parchment-like shell pierced with numerous vascular holes. Adipose osteoporosis is met with in cases where joints have been long immobilised, and in chronic articular affections. VIII. Eachitis. Rachitis is a disease of the bones occurring during the period of active growth . It is histologically characterised by disturbances of nutrition, and the formation of tissues which tend towards ossi- fication. These tissues are the epiphysial cartilages, the perios- teum, and the medulla. Rachitis is a very common disease, esj)ecially in large towns and among the children of the poorer classes. In the first period of the disease, rachitis exhibits no de- formity, and, to ascertain its frequency, the bones of all cadavers of children should be examined. Three periods may be distinguished in rachitis : in the first the affected bones are not deformed ; in the second there are considerable deformities ; and the third period is 368 LESIONS OF THE BONES. characterised by consolidation of the diseased bones. If the histological lesions be alone considered, there is no well-marked difiference between the first and second periods : the same process continues, extends, and causes modifications appreciable in the living subject. We will now proceed to study the evolutions of these lesions in the cartilage of ossification in the medulla and in the periosteum, comparing them constantly with normal ossification. Normal ossification of cartilage occurs with great regularity {vide p. 22). The cells of the foetal cartilage swell, while the Pig. 202. — Ossification fkom Cartilage, a, primary capsule filled with, secondary capsules; d, cartilage cell, the capsule of which is about to disappear ; e, proliferation of the cells which eventually form, the embryonic medulla; g, the spaces filled with this new medullary tissue are bounded by the calcified ground substance. At the lower part of the figure, stellate bone corpuscles are already apparent. Magnified 250 diameters. capsules surrounding them become spherical; the cells then divide" and become surrounded with secondary capsules, so that each primary capsule contains four to ten secondary capsules. The enlarged primary capsules elongate by reciprocal pressure, so PROGRESS OF RACHITIS. 369 as to converge towards the point of ossification. The layer in which these phenomena occur is bounded by two parallel lines from 1 mm. to 1^ mm. apart ; this layer is visible to the naked eye by its semi-transparent and bluish look, placed as it is between the ossiform and cartilaginous tissues. It has been called chon- droid by Broca, a name which however gives the impression that it is formed of a tissue having only the appearance of cartilage, though it is in reality formed of cartilage in a state of proliferation. At the commencement of rachitis changes are observed in this layer which are continued during the whole course of the disease. With the naked eye the layer is seen to have increased in thick- Fio. 203. — Zone ok Prohkeratino Cartilage in Racihtis. A, oellB pressed together and stained brown-violet with an aqueous solution of iodine, which stain is duo to the glycogenio matter they contain. B, secondary capsule. Section made in the fresh state and examined in water. ness ; it may even attain a diameter of many centimetres. In- stead of being regular, its margins, both on the cartilage and the bone side, are very irregvdar and sinuous. Sometimes it sends out long processes into the bone which frequently form separated fragments by thinning of their bases. The layer is moreover furrowed by medullary canals of cartilage containing dilated blood- vessels. On microscopically examining preparations of this layer, its resemblance to cartilage undergoing physiological proliferation is very striking. The primary capsules are however much longer, and contain a greater number of secondary capsules, which are also more voluminous. Beneath this layer, and continuous with it, there is a red, vascular, spongy tissue, of a consistence similar to that of bone partially softened by an acid. To perfectly under- B B 370 LESIONS OF THE BONES. stand the significance of this layer, the tissue which normally exists at this spot must be considered. Beneath cartilage which is proliferating there is normally a thin layer formed of areolar tissue, the trabeculse of which are composed of a cartilaginous matrix infiltrated with calcareous salts ; the alveoli contain em- bryonic medulla and blood-vessels. Beneath this true osseous tissue is formed. We have given the name of ossiform to this' layer which is interposed between the cartilage and bone. In rachitis there is not, as Broca thought, a simple increase of this layer, but the formation at the same level of a peculiar tissue, to which Gruerin has given the name of spongeoid, because of its spongy appearance. Spongeoid tissue. — This tissue, which often extends from the margin of the cartilage to the diaphysis, sometimes even invading it, is red, composed of very irregular alveoli, and seems to contain much blood. The tissue is of the same consistence as a fine sponge, or as the osseous tissue of an epiphysis partially softened by an acid. The boundary line between this spongeoid tissue and cartilage KiG. 204. — Eachitis. Foematios of Spongeoid Tissue prom Proliferating Cartilage. A, cell shrunk by action of the reagf.nt ; E, segmented ground substance; c. ground substance infiltrated with calcareous granules ; M, medullary cavity filled with young connectiTe tiSMue. v, -vessel. is, though sinuous, very distinct. Sometimes islets of hyaline cartilage are found in the midst of it, so that it is often quite impossible to indicate in a precise manner where the old bone ends. At the level of the periosteum the spongeoid layer becomes blended, particularly on the margin of the diaphjsis, with a tissue formed of nested ossiform lamella, separated from one another by a soft tissue described further on. In microscopic examination of fresh sections, the trabecules of the spongeoid tissue are seen to contain angular corpuscles irregularly scattered through a granular and non-laminated substance. These corpuscles, larger than bone THE PHENOMENA OF RACHITIS. 371 corpuscles, have no anastomotic canaliculi. To understand the significance of the tissue composing these trabeculae, its develop- ment from hyaline cartUage should be followed. Calcareous infil- tration of the segmented ground substance which separates the large capsules is observed ; but the infiltration also extends to the secondary capsules, which never occurs in physiological ossifi- cation ; hence we find the cartilaginous tissue invaded throughout its entire mass by calcareous granules, which remain distinct, that is to say, separated from one another by a cartilaginous substance which retains its flexibility. The secondary capsules are not dissolved, which is essentially difiierent from what occurs in physiological ossification. At the same time that this calcareous incrustation is taking place, the vascular canals of the cartilage, springing from the medullary cavities of the old bone, enlarge by solution of the calcified tissue surrounding them, and opening int, articular surface of the cartilage ; v^ n, amorphous and acicular urates ; o, cartilage capsules. Magnified 200 diameters. that they were everywhere deposited in the cartilage itself. The solvent reagent acts on each group of crystals from the periphery towards the centre, so that the urates may be entirely dissolved out of the matrix, while the cells remain infiltrated. When acetic acid is used, at the same time that the crystals of urate of sodium disappear may be observed the formation of the lozenge- shaped or hexagonal, transparent, and colourless crystals of uric acid. The connective tissue of the synovial membrane shows small white opaque spots, produced by deposits of urate of sodium ; though apparently superficial, these deposits are located in the midst of the fibrous tissue, and cannot be removed by scraping. Chalk stones. — The synovial fringes, the ligaments, periosteum, SECOND PERIOD OF GOUTY ARTHRITIS. 403 sheaths of the tendons, peri-articular connective tissue, sheaths of the nerves, external sheaths of the blood-vessels, and the skin itself may be invaded by deposits of urate of sodium. The salts seem to be deposited between the fibres of the connective tissue, so that the white opaque mass cannot be isolated, and in its sub- stance, besides granules and crystals of urates, are found fibres of connective tissue. When these peri-articular deposits attain such a size that they are recognisable during life, they are called tophi or chalk stones. In the centre of a tophus there is often a white softened chalky mass, on removing which can be seen the wall of the cavity in which it was contained. This wall may be very thick, and is formed of a kind of felting of connective tissue Fig. 219. — Solution of Ukates by Acetic Acid. c, cartilage cell and capsule bristling with acicular crystals ; those crystals are the first to disappear, then the amorphous urates, c', c", c"', are gradually dissolved and form uric acid crystals, «. Figure partly diagrammatic. infiltrated with urates. On mixing the soft chalky mass with water, beautiful acicular crystals of urate of sodium are obtained. Second period. — In the second period of the disease the cartilages, irritated by the presence of the urate of sodium, undergo changes which may be regarded as inflammatory. This irritation is recognised by a peculiar appearance of the deep layer of cartilage which is not infiltrated with urates, and by the formation of ecchondroses. Beneath the superficial layer which is incrusted with urates, the cartilage becomes more transparent than usual, and is of a bluish colour ; this bluish layer varies in thickness, sometimes it is as thick as the normal cartilaginous covering, at others it is hardly distinguishable. Sometimes the whole cartilage is infiltrated with urates, and the cartilage may even entirely dis- appear. Histological examination reveals how this bluish line is formed, and by what process the cartilage disappears. In this layer is observed proliferation of the cells with enlargement of the primary capsules : these form lines between which the matrix becomes transparent and splits up. These phenomena of irritation, which are much more marked here than in chronic rheumatism or scrofulous arthritis, cannot, however, lead to the formation of villi, D D 2 404 PATHOLOGICAL ANATOMY OF THE ARTICULATIONS. for the inert and infiltrated superficial layer prevents the enlarged capsules opening into the articular cavity. There is frequently, therefore, an accumulation of new cartilage elements resulting in hypertrophy. Disappearance of the cartilage is brought about by progressive erosion of the superficial infiltrated layers, which, having lost their elasticity, are unable to resist articular friction ; the two opposed surfaces hence become eroded by the normal movements of the joint. On treating a section, cut perpendicularly to the surface, with a 40 per cent, solution of potash, this process may be studied. It is then seen that in the superficial layer of cartilage the cap- sules are round or oval, clearly indicating that the normal super- ficial layer, formed of flattened capsules, has entirely disappeared. This erosion of cartilage is only seen in very movable joints, the metatarso-phalangeal articulations for example, while in the tarsal articulations, those of the cuneiform bones for instance, it is never seen, even in cases of gout of long standing. When the cartilages have disappeared, a softened chalky mass is left in their place, and separates the two bones, or, as we once had occasion to observe in the metatarso-phalangeal articulation of the big toe, true ankylosis may occur. In place of the articular cavity there were areolae of cancellous tissue which contained urate of sodium, so that the interarticular line was only represented by a white line. The bones, sawn in two in a longitudinal direction and dried, distinctly showed this singular arrangement. The ankylosis evidently resulted from formative ostitis Hmited to the extremities of the two bones. These are not the only conditions under which the medullary tissue of bone may be infiltrated with urates ; it may be met with, in fact, in extremities of bones in which the investing cartilage has been preserved. Irritation of the cartilages may, in gouty arthritis, as in other forms of chronic arthritis, induce the formation of ecchondroses. They are developed beneath the synovial membrane, round the margin of the heads of the phalanges, for example ; they are generally much smaller than in chropic rheumatism. The peri- articular nodosities of gout are principally due to chalk-stones, though they may also be partly produced by ecchondroses. Gout is never the cause of suppurative arthritis, though in consequence of inflammation, a fluid, having the appearance of pus and containing numerous pus cells, may accumulate in the ioint ; such a puriform fluid also contains crystals of urate of sodium. Sometimes a very slow form of suppurative and TUMOURS OF THE ARTICULATIOXS. 405 eliminative inflammation is seen near to subcutaneous tophi. The pus then contains, besides pus cells, granules and crystals of urates. The two periods in the histological lesions of gout are not as marked as the description we have given might lead one to suppose. Deposit of urates may indeed occur in cartilage which is undergoing proliferation ; for primary capsules inclosing a great number of secondary capsules or large spherical capsules, the presence of both of which indicate formative irritation, are often found to contain crystals of urate of sodium. Considering the clinical symptoms, it is very probable that the deposit is con- tinued during the whole duration of the disease. The exacerba- tions of gout are related to accesses of inflammation in the joints. We know, on the authority of Garrod, that there is no excess of lu-ates in the blood during these exacerbations, while it has been proved, at least in birds in whom the ureters have been tied, that infiltration of urates is dependent on an excess of urates in the blood. VI. Tumours of the Articulations. Primary tumours of the tissues which form part of a joint are extremely rare, exception being made for ecchondroses which are formed as the result of arthritis. Ecchondroses. — The ecchondroses which are found in the inter- vertebral disks do not seem to be due to inflammation ; we are ignorant of their cause. They are observed at the autopsy of patients who are generally advanced in age, and they are usually multiple. It is known that the intervertebral disks are like diarthrodal cartilages, intimately adherent to the bodies of the vertebrae. On each osseous surface is observed a layer of calcified cartilage, succeeded by a layer of homogeneous or segmented hyaline cartilage which limits a cavity filled with a mucoid sub- stance. The vertebral ecchondroses are developed from the hyaline cartilage. They take the form of two masses held together and separated by a layer of fibro-cartilage which indicates the inter-articular line. In patients advanced in age, these ecchondroses often become ossified, and the osteophytes which result are frequently divided by a horizontal plane, in which fibro- cartilaginous tissue can still be found. This fibro-cartilaginous layer may be invaded by ossification when the two vert«br£B become ankylosed. 4o6 PATHOLOGICAL ANATOMY OF THE ARTICULATIONS. Arborescent lipoma. — J. Miiller has described a variety of lipoma, called arborescent by him, and which is characterised by a series of isolated lobules united in a racemose manner. The synovial fringes normally contain adipose tissue, and arborescent lipoma is simply an exaggeration of this condition. This disease is so rare that we have never met with it. Tubercle of the synovial membrane. Tubercular arthritis.— Miliary tubercular granulations of the synovial membrane are frequent, though they have only recently been described. In such cases the articular cavity contains pus, the synovial mem- brane is thickened and transformed into a pulpy membrane, resembhng the pyogenic, in which semi-transparent or opaque granulations are observed ; on section these granulations are seen to invade the whole thickness of the membrane, they may be discrete or confluent, semi-transparent or caseous (p. 201), and between them is an embryonic tissue, traversed by dilated blood- vessels ; the adipose tissue which lines the synovial membrane has disappeared. The cartilage, examined with the naked eye, seems to be normal, or rather it has lost its elasticity, and the surfece is no longer smooth. In a case which we examined, there were signs of acute arthritis, the cartilage was superficially softened and spHt up ; the most superficial capsules seemed to have disappeared, and there was cellular proliferation in the deeper capsules. The cancellous tissue of the epiphyses, contrary to what is observed in white swelling, was not rarefied, and the bone corpuscles did not contain fat granules. It is certain that the arthritis which accom- panies and follows tuberculous deposit has been hitherto con- founded with scrofulous arthritis or white swelling ; but it must not hence be concluded that every white swelhng is a case of tubercular arthritis. The relative proportion of tubercular arthritis and white swelling cannot be determined on present data. Tumours developed in adjacent parts and extending into articular cavities. — Tumours of the bones, sarcoma in particular, which is certainly the most frequent variety, rarely penetrate into a joint. The calcified layer of cartilage is not absorbed as readily as bone is under the influence of a neoplasm, and often arrests its progress for a long time. Sometimes, however, this layer gives way, and the morbid mass then penetrates into the joint. This accident is preceded by all the phenomena previously described as those of chronic arthritis by continuity (p. 400). TUMOURS OF THE ARTICULATIONS. 407 In the articular cartilages of some subjects, more particularly in children, may be seen holes, looking as if they had been punched out ; by means of these communications are established between the joint and a cavity varying in size and which is hollowed in the tissue of an epiphysis. The osseous tissue bordering this cavity is rarefied and filled with granulations infiltrated with pus, or it may be condensed. Inside the cavity, pus or more or less solid caseous matter is found. In such a case the articulation also con- tains pus, and presents all the morbid appearance of suppurative arthritis. All surgeons, Nelaton in particular, have regarded this lesion as tubercular in origin. Our own histological study of the subject does not enable us to formulate a definite opinion, since we contend that there is nothing specific in caseous degeneration. In the osseous tissue adjoining these losses of substance, we have only found changes due to ostitis, and in the edges of the perforation of the cartilage, proliferation of the cartilage cells as in every other case of chondritis. Before deciding the question, therefore, we must wait for new data based on more recent appearances, or for cases in which, side by side with long-standing alterations, spots may be found presenting the characters of tuberculosis of the bones, such as are observed in Pott's disease ; in which disease, side by side with cavities filled with cheesy matter, are found dis Crete miliary granulations or masses of confluent granulations. 4o8 CHAPTER IV. ALTERATIONS OF CONNECTIVE TISSUE. I. Congestion and Hsemorrhage of Connective Tissue. Congestion of connective tissue is often observed during life without leaving traces after death ; when, however, it is connected with inflammation or haemorrhage, the blood-vessels of the con- nective tissue are, in the cadaver, often found filled with blood. On removing fragments of this congested tissue with the scissors and examining them in serum, the capillaries are found to be filled with red blood corpuscles, which are crenated twenty-four hours after death. In inflammation the capillaries are dilated in a regular or fusiform manner. Extravasations of blood into connective tissue are extremely common in contusions, wounds, and diseases accompanied with haemorrhages. The blood corpuscles escape from the vessels, and are effused between the bundles of connective tissue separating them. In order to study this lesion soon after the haemorrhage has taken place, the preparation should be hardened in alcohol and sections cut, which, softened in water, stained with carmine, and examined in glycerine rendered slightly acid, show the follow- ing appearances : bundles of connective tissue cut across longi- tudinally or transversely and separated by spaces filled with red blood corpuscles, among which the white corpuscles, solitary or in groups, are easily recognised by the carmine stain which they take. These preparations closely resemble those of cavernous angioma (p. 241). Ecchymosis. — Later and in a variable space of time, the efiused blood undergoes considerable changes ; the fibrin which coagulates round the corpuscles and fixes them undergoes molecular meta- morphosis ; the red blood corpuscles are destroyed, and in their place are found the products of their decomposition, granular haematoidin, or at least a red, yellow, or brown substance, one of the derivatives of haemoglobin, as well as albuminoid granules, and ECCHYMOSIS. 409 finally fat granules. But at the same time that these meta- morphoses of the blood occur, changes of an irritative character are taking place in the connective tissue, the end of which is the elimination of all the products of decomposition. The white cor- puscles are seen to be present in large numbers, and when near red blood corpuscles which are still intact, or the coloured granules derived from them, they absorb them, re-enter the circulation of the lymph or blood, and carry away the particles with which they are Fio. 220. — Transverse Section of Subcutaneous Connective Tissue from A Wound powdered with Vermilion. c, connective-tlfisue cells arrangod in the form of a semicircle around the conn ective- tissue bundles ; /, connective-tissue bundles rendered transparent by glycerine ; c' and c", con- nective-tissue cells seen lengthwise ; ;>, lymph cells infiltrated with vermilion, r^een in the inter-fascicular spaces, which are enlarged and filled with a granular exudation. The connective-tissue colls represented here are slightly swollen and also contain granules of Termilion. charged. At the same time the fixed cells of the connective tissue swell and absorb coloured granules. It is to these two histological facts that the complete disappearance of ecchymoses must be at- tributed, and also the persistent pigmentation of some cicatrices. This description of phenomena following haemorrhage into cellular tissue is based on observations made on man, and on experiments practised on animals. To these observations others should be added in which the substance efiFused into the connecti\e tissue was not blood, but a 4IO ALTERATIONS OF CONNECTIVE TISSUE. solid and finely pulverised coloured substance always capable of being recognised in the midst of the tissues. Such are powdered vermilion held in suspension in water, and anilin blue precipitated by water from an alcoholic solution. If a cubic centimetre of water, holding one of these substances in suspension, be injected into connective tissue, no free granules will be discovered in the tissue five or six days after the operation. All the granules will be found to have passed either into the lymph cells, or into the tumefied connective-tissue cells, which are more numerous than normally (fig. 220). The lymphatic glands, with which the vessels of the region are in communication, are also found to contain a variable quantity of the coloured granules. The various tints observed in the skin in ecchymosis are due to the haemoglobin, which, originally soluble, is changed into coloured granules of hsematin and hsematoidin. These granules behave, with regard to the Kving elements which surround them, in the same way as finely pulverised coloured granules injected into the connective tissue. As described above, they set up an irrita- tion and determine the appearance of a great number of white corpuscles, which absorb and carry them away. Such is the method of absorption in ecchymosis. The irritation produced by coloured granules derived from the blood may be more or less intense ; sometimes it passes unperceived, at others it is decidedly suppurative and may give rise to an abscess consequent on extrar vasation of blood. II. (Edema. From the histological point of view, oedema is essentially characterised by an effusion of albuminous serum between the fibres of connective tissue, which it separates from one another. On incising cedematous loose connective tissue, it is found to be transformed into a tremulous, transparent, gelatinous mass, in the midst of which are seen delicate fasciculi, adipose collections, and red lines corresponding to blood-vessels. This appearance results from the serum between the fibres of connective tissue being re- tained in the same way that water is held in cotton wool. But on isolating a fragment of cedematous connective tissue and leaving it alone, the connective-tissue bundles and the elastic fibres contract, expel the serum, and the tissue returns to its primitive condition. The expulsion of the serum is really due to contraction of the fibres, for on placing the cedematous fragments in serum they (EDEMA. 411 still undergo contraction. This property which connective-tissue fibres possess, and which preserves them for a long time in spite of distension, also explains the easy and continuous flow of serum irom punctiu-es made in the skin of dropsical patients. The fluid which flows from these punctures is transparent and albuminous ; it neither coagulates on contact with the air, nor spontaneously, nor after the addition of red blood corpuscles, which fact indicates that it does not contain fibrinogen. By this fact alone it may be dis- tinguished from the serum of inflammatory fluids. A small number of white blood corpuscles is always found in the serum of oedema. The histological examination of inflamed connective tissue is easily made : it is enough to remove fragments with curved scis- Fio. 221.— Adipose Cells of the SuBcuTANEons Tlssue of the Doo IN Artificial (Edema, pkoducbd by Ligature of the Inferiok Vena Cava asd by Section of the Sciatic Nerve. a, globe of fat ; jt, nucleus of the cell ; p, protoplasm infiltrated with granules of fat; r, conneotivo-tiBSUo cell infiltrated with granules of fat. Magnified 400 diameters. sors, place them on a slide, and cover with a cover glass. The manipulation should be rapid so as not to allow the fluid to escape. in such preparations the connective-tissue bundles are seen to be separated from one another, and in the interspaces serum is present containing a larger number of white blood corpuscles or lymph cells than in the normal condition ; the cells along the fasciculi, the fixed cells of connective tissue, are seen to be more or less globular, and contain a very distinct nucleus and refractive granules. These granules contain fat, but axe not entirely com- posed of it, for chromic, acetic, and picric acids act upon them in a way which is never seen in granules purely fat; these reagents diminish their diameters whUe increasing their refractive index. It is probable that they are a combination of fatty principles with an albuminoid substance, which is broken up by the action of the 412 ALTERATIONS OF CONNECTIVE TISSUE. acids. This is, however, only a hypothesis which we feel ourselves bound to give in the absence of precise chemical data. In the cells of cedematous connective tissue, light yellow granules, very small in size and often angular in shape, are often seen ; they are probaly formed from the colouring matter of red blood corpuscles ; they are almost constantly met with in the serum of oedema. This pig- mentation is particularly observed in long-standing cases of dropsy. The connective-tissue bundles and the elastic fibres undergo no appreciable change. The blood-vessels which traverse the cedema- tous parts are filled with red blood corpuscles ; the proportion of white corpuscles is increased, and they are easily seen along the vascular walls. In some cases the red corpuscles are so numerous and pressed together that they cannot be distinguished, and the blood-vessels appear as if injected by a homogeneous mass. The blood-vessels are easily studied, for they, like the connective-tissue bundles, are isolated by the seruru. The fat cells in oedema generally undergo more or less appre- ciable changes. In oedema produced artificially in the dog, the protoplasm, which is between the cell wall of the vesicle and the central drop of fat, undergoes granulo-fatty degeneration, from which it results that the entire adipose cell, instead of being formed of a single refractive mass, shows a circle of granules round the central drop of fat. In the oedema of cachexia the fat contained in the cells undergoes partial absorption. This is seen particularly in phthisis. Fragmentation of the fatty mass into minute droplets is also sometimes seen in adipose cells ; this phenomenon is due to the presence of an albuminous fluid in the interior of the adipose cells, and is somewhat analogous to the artificial emulsion of fat m albumen. The nuclei of these adipose cells are always distinctly visible. In csdema which develops rapidly, the large connective- tissue cells are infiltrated with a larger quantity of fat granules than in oedema which occurs slowly, as in heart disease for ex- ample. Cause of oedema. — Till recently it was thought that oedema was the result of stasis of the blood. The physiologist Lower explained in a precise manner the method by which dropsy was produced, and his theory was accepted by all pathologists without exception. He thought that when the veins were obliterated and the blood was no longer able to pass from the arteries into the veins, the serum was transuded through the walls of the vessels as through a filter. Hence he explained dropsy by blood stasis. Hodgson, however, on tying a vein in a human subject was unsuccessful in producing CAUSE OF (EDEMA. 413 cedema. The theory of Lower was then abandoned, when Bouillaud showed that in most cases of localised dropsy obliteration of the corresponding veins was found. Nevertheless it may be observed that clinically dropsy may occur without obliteration of the veins, and that vice versa a vein may be obliterated without producing dropsy. In animals, simple ligature of a vein does not produce dropsy, owing to the fact that the collateral circulation is always sufficient to prevent the tension of the blood passing the limit of resistance of the vascular walls ; but if, in an animal in which a vein has been tied, the vaso-motor nerves be also divided, a much larger quantity of blood reaches the dilated arteries, and the tension becomes sufficient to cause transudation of the serum. This ex- aggerated tension is the true cause of dropsy, and all forms of cedema, excepting, perhaps, the cedema of cachexia, may be referred to the same cause. Hence obliteration of the veins is one con- dition of dropsy, since it augments the blood tension in the corresponding capillaries, and it produces cedema in cases where there is at the same time atony of the vascular system. It suffices to irritate the skin by scratching it with the finger nail for some time to determine a localised oedema, due to paralysis of the blood- vessels. This phenomenon, which is difficult to produce when there has been no previous morbid irritation of the skin, is effected with the greatest facility in a skin affected with urticaria, or in the neighbourhood of stings from insects, pustules of acne, etc., in these cases an oedematous swelling of the skin is seen to rise under the nail. The csdematous swelling which characterises the commencement of phlegmon is related to atony of the vascular walls, and to an increase of blood tension in the vessels. In this way we are able to refer all cases of oedema, whatsoever may be their nature, to the same physiological cause. III. Inflammation of the Connective Tissue. When subcutaneous connective tissue is divided by a cutting instrument, inflammation is produced which ends in resolution, and is itself the necessary process by which this end may be attained. From an open wound of the connective tissue blood first escapes; at the end of some hours the surface of the solution of continuity is covered by a thin, opalescent, greyish layer, the plastic lymph of John Hunter. This great anatomist, and many surgeons even to the present day, have main- tained that this plastic lymph, which is exuded fioin the blood- 414 ALTERATIONS OF CONNECTIVE TISSUE. vessels, is susceptible of becoming organised and reproducing the various tissues met with in cicatrices. In this grey layer are found filaments of fibrin, white and red blood corpuscles, and pus cells ; beneath this superficial layer it may be observed that the con- nective-tissue bundles and the capillaries axe separated from one another by some coagulated substance, so as to form a kind of continuous and extremely delicate membrane. From this descrip- tion it is seen that at the moment this so-called plastic lymph takes a solid form, it contains cellular elements. In the present condition of science these facts might be explained by the passage of white corpuscles from the blood-vessels, and of fibrinogen which undergoes coagulation ; but this explanation does not prob- ably cover all the ground, for it is possible that the lymph cells contained in the lymphatic vessels and in the meshes of connective tissue may also play an important part in these phenomena. We have indeed already seen that white corpuscles or lymph cells exist in a free state between the fasciculi of connective tissue, and, on the other hand, the conditions of the formation of fibrin are far from being well understood ; we only know that the plasma of blood brought into contact with paraglobulin, and a series of other substances contained in histological elements, takes the form of fibrin. The difficult point is to know why blood plasma, lymph, and serum of the pericardium which contain fibrinogen, never give origin to fibrin in the living organism, though these fluids are in contact with elements containing fibrinoplastin. Suppuration. — The phenomena of superficial exudation, which are originally but slight, soon become exaggerated and take on the characters of suppuration. The connective tissue then becomes more profoundly altered, it loses for the depth of some millimetres its fasciculated appearance, it becomes pulpy, semi-transparent, and embryonic in character. On the second or third day fasciculi of connective tissue are still found in this embryonic layer ; they are however swollen, less distinctly fibrillar, and seem to be no longer enveloped by that peculiar layer which limits them and causes them to swell irregularly when acted upon by acetic acid. They are separated from one another by round or angular cells, formed of a mass of protoplasm containing a nucleus. The large flat cells of connective tissue are not generally found in this layer. The infiltration of the connective tissue by an increased number of round cellular elements generally extends to a distance of from two millimetres to one centimetre from the solution of continuity; but this lesion can only be recognised with the microscope. The INFLAMMATION OF CONNECTIVE TISSUE. 415 enlargement of the fixed cells of the connective tissue, the division of their nuclei, and their subsequent proliferation, may be clearly seen in this peripheral zone. Hence we see that the abundant production of new cellular elements between the constituent parts of connective tissue may originte from two sources, from diapedesis of white blood corpuscles, and from multiplication of connective- tissue cells ; but in the present condition of science it is impos- sible to determine the part played by each of these processes in the phenomena of the repair of wounds. As we have already said, the connective-tissue fasciculi, com- prised in the embryonic layer, lose their fibrillar state and become swollen; they are afterwards entirely dissolved, so that not a vestige of them can be found. The granular layer on the surface of wounds or the pyogenic membrane, composed solely of cells and capillaries with embryonic walls, give origin to granulations. The evolution of granulations has already been described when treating of cicatrisation (p. 111). IV. Purulent Inflammation of Connective Tissue or Acute Phlegmon. We call acute phlegmon purulent inflammation, for, even when the disease terminates in resolution, there are a great number of pus cells in the meshes of the connective tissue. It is well known with what rapidity acute phlegmon is developed : redness, increase of temperature, cedematous swelling, and acute pain show themselves at once and simultaneously. The opportunity of studjdng in man the histological changes which occur at the onset in the connec- tive tissue is rarely offered, but the phenomena can be followed in phlegmon produced artificially in animals, and everything leads one to suppose that they are the same in both cases. To produce acute phlegmon in a dog, a few drops of a five per cent, solution of nitrate of silver must be injected into the connective tissue ; at the end of from ten to twelve hours there is an cedematous and pain- ful swelling of the region ; the connective tissue is gelatiniform, the blood-vessels dilated and filled with blood. At first sight there seems to be no difference between this tissue and that of oedema ; but the serum does not flow so easily as in simple oedema, and there are different histological lesions in the two states. In phlegmon, as in oedema, a great number of white blood corpuscles or pus cells may be observed between the connective-tissue bundles, separating them from one another; there is, besides, a 4i6 ALTERATIONS OF CONNECTIVE TISSUE. fibrinous reticulum which is never seen in simple oedema. We have here indeed acute inflammatory oedema which is very prob- ably related to the same cause as simple oedema, in that it results from paralysis of the blood-vessels and increased blood tension. The capillaries are in fact dilated and filled with blood, fi-om which results an increase of temperature in the affected part. At this period the connective-tissue bundles do not show any appreciable ^^^^^^^^ Fig. 222. — Inflammatouy OSdema of the Connective Tissue of the Dog, produced by a '1 per cent. injection of nitkate of silver. The preparation was made by removing a fragment o£ the cedematous tissue with scissors and slightly pressing it between two slides ; at the end of a few hours a fibrinous reticulum was formed, and which is here indicated by the dotted lines r ; a, connective-tiasue cdte becume granular ; 6, pus-cells ; c, elastic fibres j e, connective-tissue bundles. Magnified 600 diamieters. change ; the large flat cells swell and tend to take the spherical form, some contain two nuclei and become granular, and even fat granules may be distinguished. This first period of phlegmon is especially characterised by the production of numerous pus cells and a fibrinous exudation ; soon the pus cells increase in num- ber, the fibrin becomes more abundant, so that the substance CIRCUMSCRIBED PHLEGMON. 4,7 effused between the fibres solidifies, and the inflammatory tumour becoming firmer, gives on pressure a sensation of resistance to the finger. Fluid which may be displaced as in oedema is, in fact, no longer present. To the presence of fibrin, filHng the meshes of the connective tissue, must be attributed the limitation of phlegmon in cases where it develops slowly and in a circum- scribed region. In man to this first period succeeds resolution, induration or suppuration. When resolution takes place it is probable that the extravasated white blood corpuscles are taken up by the lymph- atics, either in their normal condition or after having undergone molecular dissociation, and that the fibrin and red blood corpuscles disappear in the same way. Induration without suppuration is very similar to induration which takes place after opening an abscess : the histological phenomena are probably the same in both cases. Between the connective-tissue fasciculi fresh cellular ele- ments are formed, and around them may be seen a new transparent ground substance of soft consistence, so that the tissue resembles that of fasciculated sarcoma. Later, these cellular elements un- dergo fatty degeneration, and all the new tissue is absorbed. All the phases of this process, which are extremely difficult to follow, have not yet been accurately studied. In every case of phlegmon, pus cells are found in the meshes of the connective tissue ; but when they are produced in great numbers, and the connective- tissue fasciculi are separated from one another or undergo inflam- matory softening or absorption, a purulent collection or abscess is formed, and the phlegmon is said to have suppurated. Circumscribed phlegmon. — In circumscribed phlegmon the pus is creamy, homogeneous, and does not contain bundles of connec- tive tissue. Examined under the microscope it presents : first, round cells exactly similar to white blood corpuscles and containing only one nucleus ; secondly, cells of the same diameter containing many small nuclei ; thirdly, similar cells containing a variable number of fat granules ; fourthly, large cells measuring 20 /* in diameter and containing fatty granules, — granular bodies ; fifthly, entire or broken-up red blood corpuscles. The sac which contains the pus is generally anfraxjtuous, and lined by a layer similar to that which is produced on the surface of a wound on the second day ; in this layer, the softened connective tissue fasciculi are united by a layer of coagulated fibrin, inclosing pus cells. When the abscess is opened and emptied, the walls of the emptied sac being brought 1-: li 41 8 ALTERATIONS OF CONNECTIVE TISSUE. into contact unite, an induration resulting which lasts a few days. The floor and edges of the abscess secrete pus, in which case the consecutive phenomena are those of a simple wound. Diflfuse phlegmon. — In diffuse phlegmon or diffuse celluhtis, the inflammatory phenomena are so intense that more or less extensive flakes of connective tissue have not time to undergo inflammatory absorption ; they are necrosed in situ, and act on the neighbouring parts as foreign bodies. In diffuse cellulitis there is a true necrosis of the connective tissue, and it resembles diffuse phlegmonous ostitis. On opening the purulent foci necrosed flakes of connective tissue are found mixed with pus. On the wall of the abscess are also seen masses of greyish filaments, formed by detached bundles of connective tissue infiltrated with pus. If the patient succumbs at this period, incisions made across the phlegmon show that all the connective tissue of the limb is infiltrated with serum, blood, and pus variously combined. In the midst of the infiltrated parts, opaque whitish masses are observed formed of filaments of mortified connective tissue, more or less free or still adherent, the whole exhaling an odour of gangrene. On histologically studying this gangrenous connective tissue we find a fibrillar mass in which it is difficult to distinguish fasci- culi ; in the midst of the dissociated fibrils are found pus cells, albuminoid granules, yellow or blackish pigment, fat granules, and drops of fat. The latter are probably derived from the destruc- tion of the fat cells. The flakes of connective tissue which are detached and float in the pus show a similar structure. Macera- tion in the purulent fluid dissolves the cementing substance of the fibrils and sets them free, exactly as if they had been treated by the reagents which are used with this object. V. Chronic Phlegmon. The name chronic phlegmon is given to long-continued in- flammation of the connective tissue, characterised by lardaceous induration and accompanied most frequently by suppuration. Chronic phlegmon is not a primary disease of the connective tissue, it accompanies chronic affections of the bones or vascular system. The connective tissue is sometimes thickened for a considerable depth, and simulates a tumour, which tumour is, however, never well defined, but blends with the neighbouring sound parts, so that it is difficult to assign to it a limit. On the surface are seen CHRONIC PHLEGMON. 4,9 fistulae, ulcers, or hypertrophied papillae, regarding which fuller details are given in the article on the pathological anatomy of the skin. On dividing the morbid mass the tissue is seen to have a lardaceous appearance, and a serous or opalescent fluid flows from it. On attentively examining the divided surface there may be seen portions distinctly fibrous which correspond to tendons or aponeuroses ; parts which are semi-transparent and infiltrated with fluid as in oedema ; opaque, purulent, and irregular spots, dilated vessels gorged with blood, and haemorrhagic points. In order to examine this complex tissue under the microscope, many methods are used. The elements obtained by dissociation from fresh specimens are pus cells, granular bodies, and cells larger than pus cells and of various forms, globular, fusiform, flat, or irregular, resembling, in fact, those observed in sarcoma. Beside these cellular elements there are fat granules, drops of fat, and connective-tissue fibres. In microscopical sections made after hardening in a '2 per cent, solution of chromic acid and preserved in glycerine, bundles of connective tissue are found divided in different planes and separated from one another by collections of cells. Some of these cells resemble white blood corpuscles, others, which are larger and fusiform, are fixed connective-tissue cells, more or less modified. The blood-vessels have thickened walls, which have become embryonic in structure, and they are sur- rounded by an irregular zone of pus cells. Sometimes groups of atrophied adipose cells are found the nuclei of which have multi- plied ; they are generally separated from one another by masses of embryonic or pus cells. Finally, here and there, cells similar to those of sarcoma predominate and form collections varying in size. From this description it is seen that there is no fundamental difference between the structure of this morbid tissue and that of some sarcomata. If two preparations of these different tissues were selected from among those most nearly similar to each other, it would be hardly possible to distinguish one from the other. But on making a complete and comparative analysis of diff'erent por- tions of these neoplasms, characters differentiating the two will be found. Sarcomata, for example, do not contain purulent centres like chronic phlegmon, at least if they are not inflamed. Moreover, in chronic phlegmon the constituent elements of the tissue per- sist much longer than in a diff'use sarcomatous tumour. Since chronic phlegmon is the result of a cause that can always be determined, such as white swelling, diseased bones, or varicose ulcers, while the cause of the development of sarcoma is unknown, V. r 2 420 ALTERATIONS OF CONNECTIVE TISSUE. the diagnosis would be always easily made if all the data furnished by the clinical and pathological study of the subject were taken into consideration. Another very important distinguishing cha- racter is afforded by therapeutical surgery. When the anatomical cause of chronic phlegmon has been removed, recovery follows • when in a surgical operation, an amputation for example the flaps contain tissue indurated by chronic phlegmon, a regular cicatrice is still produced, whereas if sarcomatous parts were pre- served the tumour would be reproduced with renewed activity. VI. Tumours of the Connective Tissue. All tumours, without exception, may be developed in connec- tive tissue, but it must not, therefore, be concluded that the con- nective-tissue cells are the sole source of these, as Virchow has maintained. We have, in fact, shown that at the commencement of almost all neoplasms constituting tumours, embryonic tissue may be found, and is the point of departure of the new tissue. The method by which embryonic tissue is formed from connective tissue is identical in simple inflammation and at the commence- ment of a tumour. The cells which compose embryonic tissue are probably white blood corpuscles escaped from the vessels and also coimective-tissue cells multiplied by division. We base the opinion that these elements are probably white blood corpuscles on Cohn- heim's experiments on the frog; no one has yet attempted to elucidate direct experiments by the development of embryonic tissue in tumours. The most frequent tumours of loose connective tissue are those which have their analogues in the varieties of this tissue— fibroma, myxoma, lipoma, sarcoma, carcinoma, and syphilitic gummata. On the other hand, tubercular granulations are rare, though it is known that they may be developed on the edges of a wound, the base of an ulcer, and in the inflammatory tissues which surround a fistulous tract, in the walls of scrofulous abscesses, and in certain forms of periostitis (Graujot and Kiener). Hence the possibility of the primary development of tubercular granulations in loose con- nective tissue may be conceived, and it is probable that they may be discovered there on looking for them attentively. As to epithe- lioma developed in connective tissue, it always originates in the interpapillary or glandular epithelial tissue, or in embryonic tissue in contact with pre-existing epithelial masses. All the other varieties of tumours, osteomata, chondromata, etc., may he de- veloped in connective tissue. CYSTS OF THE CONNECTIVE TISSUE. 421 Serous cysts of the connective tissue axe always lined with endothelial cells similar to those of the serous membranes. Their walls are formed by superimposed connective-tissue fibres, between which are flat cells parallel to. the surface of the membrane. The development of these cysts has not been studied, but it is probably the same as that of serous bursas {vide p. 296). In subcutaneous connective tissue, hydatid cysts with ecchinococci have been ob- served. The mother vesicle is surrounded by a complete connec- tive-tissue membrane containing numerous blood-vessels. Hydatid cysts formed by cysticerci have also been met with. A solitary worm occupies the cyst. 422 CHAPTER V. LESIONS OF THE SEROUS MEMBRANES. I. Hsemorrhage of the Serons Membranes. The lesions of the serous membranes are placed here because they closely resemble those of the connective tissue. We present only a few generalities concerning the lesions of these membranes, as we propose to return to them and describe more minutely the changes of each one, when considering the organs covered by serous membranes. Hsemorrhage into serous membranes is common ; it is enough to cite meningeal haemorrhage, circum-uterine haematocele, and hasmatocele of the tunica vaginalis. The effused blood coagulates and undergoes the series of metamorphoses always observed in such extravasations, and determines an inflammation of the serous membrane, which inflammation is generally slow, and does not cause suppuration. It produces exudations and new formations in the form of false membranes on the surface, or in the form of adherent bands between the two surfaces of the serous membrane. The retrogressive modifications of the effused blood consist in the disappearance of the red corpuscles, the liberation of the haemo- globin, the formation of granules of haematin, or crystals of hsematoidin, and the dissociation of the fibrin, etc. In traumatic haemorrhage of the serous membranes, notably in haemorrhage into the peritoneum following a wound of the abdomen, the haematin produced by decomposition of the red blood cor- puscles is sometimes so abundant that on opening the abdomen it might be thought that soot had been scattered over the great omentum and the intestines. Upon the great omentum a dark substance is seen in the form of opaque, spherical, or angular granules of a very dark brown colour, which are located in the masses of white corpuscles present between the fibres of the reticulum, in the epithelial cells lining these fibres, and in the small cells grouped round adipose cells and which they nearly hide. INFLAMMATION OF SEROUS MEMBRANES. 423 In the intestine the peritoneal epithelium is equally infiltrated with black granules, so that it resembles the epithelium of the choroid. Absorption of the haematin granules is probably here affected, as in the connective tissue, by aid of the lymphatic vessels, to which they are conveyed by the white corpuscles. This process may be elucidated by experiment on animals. If into the peritoneal cavity of the rat is injected fresh blood which has been defibrinated and passed through linen, and which has been taken from an animal of the same species, the phenomena observed during the following days are : spherical swelling and proliferation of the epithelial cells of the serous membrane ; the penetration of fragmentary or entire red blood corpuscles into the interior of these cells, some of which are detached and float free in the cavity ; then the accumulation of lymph cells, which absorb the entire or fragmented red blood corpuscles, and the formation of a fibrinous exudation. The red blood corpuscles undergo modifications, which were first studied by Eindfleisch, and which are similar to those observed on heating the blood to a temperature of 132°; they are decomposed into spherical, refractive, coloured, and perfectly distinct granules, and may be observed in different stages of division. II. Inflammation of the Serous Membranes. The essential changes met with in all inflamed serous membranes consist in the formation of exudations, and in the mortification of the epithelial cells. All exudations of inflamed serous membranes contain fibrin, which is not surprising, considering that the fluid of serous cavities normally contains a notable quantity of fibrinogen. The existence of this substance has been ascertained in pericardia] fluid, where it always exists in sufficient quantity to be analysed (A. Schmidt). In acute inflammation of the serous membranes this fluid becomes more abundant, and contains a larger quantity of fibrinogen. If, for example, an inflamed pleura be tapped, a limpid fluid is obtained which, when exposed to the air, coagulates in a few hours into a gelatinous mass. Virchow justly remarked that fibrin does not exist ah-eady formed in the exudation, but that this simply contains a substance susceptible of producing fibrin when acted upon by the air ; hence he called this substance fibrinogen, a name which was adopted by A. Schmidt. It is certain, however, that the action of the air is not the sole cause which determmes 424 LESIONS OF THE SEROUS MEMBRANES. coagulation of fibrin in this fluid ; the addition of red blood corpuscles, or even the serum of blood obtained after coagula- tion, will give rise to the immediate appearance of fibrin. These changes are very important, for they explain the process of the formation of fibrin, when it is deposited in the form of laminae on the surface of an inflamed serous membrane, while the distended cavity of the serous membrane simply contains a limpid fluid; this fluid may, however, show fibrinous flakes, or a more or less considerable portion of its mass may undergo coagulation. When the exuded fluid is abundant and limpid, the exuda- tion is generally called serous, though on the surface of membranes there is always a more or less thick layer of fibrin. This serous fluid nevertheless contains a rather considerable quantity of pus cells held in suspension, and which can only be recognised under the microscope ; red blood corpuscles may also be met with. When layers of coagulated fibrin are present on the surface of an inflamed serous membrane, and the fluid contains neither blood nor pus perceptible to the naked eye, the exudation is said to be fibrinous ; when the exudation contains blood it is said to be haemorrhagic, and when it contains a large quantity of pus it is piarulent. Fibrinous inflammation. — The fibrinous exudation formed on the surface of serous membranes varies in its arrangement and appearance. When recent, a reticulum of delicate meshes, with slight depressions between them, is seen on its surface. It is at first thin, but it soon thickens by the deposition of new layers ; it is yellowish grey, semi-transparent, gelatinous, soft, and friable. It may be detached with the nail in the form of flakes, which show clean edges when broken. In pericarditis the fibrinous exudation has a peculiar arrangement ; its free surfacB^ has been compared to the dorsum of the tongue of a cat ; it is villous, covered with granulations and laminse, the arrangement of which is produced by the agitation of the fluid caused by the move- ments of the heart. When these exudations are old they become smooth, opaque, and are formed of superimposed layers which may be separated by dissection. In order to study the structure of fibrinous exudations under the microscope, and the modifications of the subjacent serous membrane, recourse may be had to many methods. The simplest consists in removing fiakes of the exudation, and examining them after spreading them on a slide. When the exudation is FIBRINOUS INFLAMMATION. 425 very thin, a beautiful reticultiin may be distinguished with a low power ; from a thick central point radiate threads of fibres which become thinner as they divide ; more delicate threads of fibres unite the latter. When the exudation is thick, or has existed long, this reticulated arrangement cannot be recognised under the microscope. Only on the borders of the specimen may be distinguished torn flakes with sharp edges, or filaments of fibrin. In the midst of these laminae and fibrils cells may be observed, to examine which recourse must be had to dissociation in a 1 per cent, neutral solution of picro-earminate, or in iodised serum. They vary greatly in form and size ; some resemble white blood corpuscles ; most of them contain large, distinct, oval nuclei with one or many large brilliant nucleoli, similar to the nuclei formerly considered characteristic of cancer. Some of the Fig. 22;!. — Aci TK Rheumatic Pericarditis ; Cells froji the riiiuiNOLS EXIIUATION OBTAINED BY DISSOCIATION IN A 1 PEIl CENT. SOLUTION OF PiCRO-CARAIINATE OF AMMONIA. a, cell with many nuclei ; 6, racket-shaped cell similnr to those found in carcinoma ; c, e, email cells ; d, flat cell seen sideways. MagniSed 400 diameters, cells containing these nuclei are flat, similar to the epithelial cells of serous membranes ; others show long processes ; some are flat and contain a great number of nuclei (giant cells), and resemble the mother cells of the medulla of bone. Langhans pointed out the existence of these giant cells roimd the tubercular granulations of serous membranes, but we, as well as Ernest Wagner, have found them in all fibrinous inflammations, as well as in other forms of inflammation of these membranes. To study well the position of these cells in the exudation, and the relations of the exudation with the subjacent membrane as well as the modifications of the latter, vertical sections should be cut, after hardening in alcohol or picric acid — the latter reagent is prefer- able. The process is as follows : after detaching the serous mem- brane with the exudation, it should be stretched and fixed with 426 LESIONS OF THE SEROUS MEMBRANES. pins on a layer of cork, so that the under-surface of the serous membrane rests on the cork ; then the whole is immersed in a concentrated solution of picric acid, of which there must be at least 100 grammes for a specimen of four centimetres square. At the end of two days the process of hardening is complete ; delicate sections may then be cut, stained with carmine, and preserved in glycerine. On the surface of the serous membrane a layer of amorphous or granular fibrin is seen, generally bordered by a distinct though sinuous line ; beneath are seen the successive layers of cells previously described, and fibrin arranged in a very different manner according to the case. Generally the fibrin forms a network of flattened meshes, which limit elongated alveoli containing cells. The border of the serous membrane is generally very distinct, the exudation is simply applied to its surface, being here and there separated from it by collections of epithelial cells, forming many layers, and similar to those found in the alveoli of the exudation. It is probable that all these cells proceed from the swollen, proliferating, and detached epithelial cells of the serous membrane. In the present state of science it may be logically maintained that the epithelial cells, modified by inflammation, act like a fibrinoplastic substance and determine the formation of fibrin from the fibrinogen of the originally fluid exudation. The superficial elastic layer of the serous membrane does not seem to be modified in the majority of cases. Between the bundles of the subjacent connective tissue a greater number of cells are observed than normally, which cells resemble white blood corpuscles or lymph cells. Circular, elliptical, or cylindrical, and well-defined spots are also seen, which are the transverse or longitudinal sections of the lymphatic vessels of the serous membrane filled with lym^h cells. Ernest Wagner,' in a careful analytical study of fibrinous pleurisy, observed that the lymphatic vessels become loaded with fibrin, and concluded that this obstruction of the vessels presented, for some time, a barrier to the absorption of the exudation. We have also found lymphatics filled with fibrin in fibrinous pericarditis and peritonitis, and we have moreover ascertained the existence of modified epithelial cells in the sub- stance of the exudation, and the dilatation of the lymphatics by an accumulation of lymph cells. Hsemorrhagic inflammation. — Hsemorrhagic inflammation of the ' Beitriige ziir Path, der Pleura (^Arok. der lieilk. vol.,xi. 1 Heft). HEMORRHAGIC INFLAMMATION. 427 serous membranes is characterised by the presence of a more or less considerable quantity of blood added to the fibrinous or fluid exudation. Between simple fibrinous inflammation and true haemorrhagic inflammation of the serous membranes there are numerous intermediate varieties. In the simplest case ecchymotic spots are scattered over the fibrinous exudation, and may be seen distinctly on its under surface when detached. At other times the fibrinous membrane is red throughout its whole extent, the serous portion of the exudation being also stained with blood. This haemorrhagic inflammation is most frequently related to the formation of new blood-vessels, which spring up on the surface of the serous membrane and penetrate the under surface of the exudation. It is very probable that most of the newly formed blood-vessels in the false membrane of serous cavities are developed from vaso- formative cells which enlarge, send out ramifying processes which anastomose and form a complete system already containing blood before communicating with the vascular system. We have not hitherto been able to verify this hypothesis, but the development of blood-vessels in the great omentum on one hand, and on the other the rapidity with which extensive capillary networks are formed in the false membrane of serous cavities, authorise us to admit the hypothesis a, priori, though unable to verify it by direct observation. The blood-vessels of new formation have embryonic walls, and are surrounded by an embryonic tissue ; they form a network in which the principal branches spring in a radiating manner from a central vessel. Thus in haemorrhagic meningitis (pachymeningitis), small, nummular, red plaques are often found on the internal surface of the dura mater, in which, on examination, fine vascular branches and ecchymotic spots are also discovered. These small plaques, which axe the rudiments of extensive new membranes, may be easily detached. The numerous blood-vessels which they contain are filled with blood, and they form a network in connection with the blood-vessels of the dura mater, which fact may be easily recognised on making vertical sections, after hardening with Muller's fluid or with giun and alcohol. When the process is old, false membranes are formed of embryonic tissue and blood-vessels, with layers of fibrin inter- posed ; they are of considerable thickness, and are bathed m a blood-stained exudation. The blood extravasated into the exudation undergoes a series of modifications, ending finally in the formation of granular or 428 LESIONS OF* THE SEROUS MEMBRANES. crystalline hsematoidin. When hsemorrhagic inflammation termi- nates by suppuration, the fluid contained in the serous cavity contains pus, in which, on careful examination, red granules may be seen with the naked eye. On microscopical examination these red granules are found to be composed of large crystals of h^matoidin isolated or in groups. These crystals are met with in haemorrhagic inflammation of the pleura, peritoneum, and tunica vaginalis. It should be added that hsemorrhagic exudations of the serous membranes are particularly observed in alcoholic subjects, and in inflammation resulting from tuberculosis or cancer. Purulent inflammation. — Purulent inflammation of the serous membranes is primary, or secondary to fibrinous or hsemorrhagic inflammation. Thus, in certain cases of fibrinous pleurisy, in which thoracentesis gives, the first time, a sero-fibrinous fluid, a second puncture, practised many days after the first, may give issue to creamy pus. Inflammation, however, which is purulent from the beginning is much commoner than that which succeeds fibrinous pleurisy ; it occurs in puerperal fever, purulent infection, glanders, rheumatism, tuberculosis, etc. In such cases the organs covered by the serous membrane almost always show the different lesions of the disease which has determined the purulent inflammation (metastatic abscess, purulent inflam- mation, vomicae, ulcerations, lymphangitis, phlebitis, etc.). When the progress of purulent inflammation is very rapid, the serous cavity is filled with pus, and there is no solid exudation on its surface ; the blood-vessels are dilated, their walls embryonic, and the connective tissue of the serous membrane is infiltrated with pus cells located between the vessels. It is almost certain that these pus cells proceed from the blood, and that the epithelium of the serous membrane only takes a small part in their pro- duction. In man, the modifications of the epithelium cannot be followed, for at the time that the serous membrane is examined the epithelial lining has disappeared. In the midst of the pus which fills the serous cavity, yellowish flakes of variable form and size may be met with, composed of a fibrinous reticulum, the meshes of which are filled with pus cells which have generally undergone granulo-fatty change. When the progress of purulent inflammation is less rapid, a fibrinous exudation is formed on the surface of the serous membrane, resembling in structure that of the fibrinous flakes just described. The number of pus cells are so considerable that they may com- PURULENT INFLAMMATION. 429 pletely mask the fibrinous reticulum, whether the exudation be examined in sections cut after hardening, or without the addition of any reagent. The lymphatics and blood-vessels of the serous membrane show changes similar to those described as present in fibrinous inflammation. If purulent inflammation follows simple fibrinous inflammation, thick false membranes are found at the autopsy infiltrated with pus, and new vascular formations, similar to those described above as present in hsemorrhagic inflammation ; red blood corpuscles or blood pigment derived from them are almost always present. The pus formed in serous cavities rapidly undergoes nutritive changes ; the cells become filled with fat granules, and undergo caseous change if the fluid is partly reabsorbed. This caseous pus forms opaque, yellowish masses of the consistence of mastic ; these masses were formerly regarded as tubercular in origin. When the pus remains in a fluid state, the cellular elements are destroyed, or at least in a great part. Crystals of fatty acids and cholesterin are formed, as in caseous foci ; most frequently also pigment granules and crystals of hsematoidin are found. Solid fibrino- pm^lent exudations undergo similar changes ; they become caseous. From their surface are detached flakes which float in the serous cavity ; these, as well as the adherent exudation, are formed of a granular substance, the product of the molecular disintegration of fibrin, and elongated collections of fat granules, crystals of fatty acids, cholesterin, and blood pigment. In old chronic cases of inflammation the serous membrane is considerably thickened and highly vascular, or it may be cartilagini- form. It is then composed of parallel laminae of connective tissue separated by flat cells ; this indurated tissue is exactly similar to that of fibroma with parallel laminae and flat cells, or lamellar fibroma {vide p. 163). This new tissue is very subject to calcareous infiltration, which determines the formation of hard or ossiform plates, more or less regular and extensive. We have never seen true bone corpuscles in these ossiform plates. Thickening of the pleura is especially seen around masses of caseous pus. Sometimes the alteration is limited to a portion of the serous membrane, which then forms a cyst with thickened walls, containing caseous matter, around which there is, in some rare cases, a transparent gelatinous substance studded with opaque spots. Such an old encysted pleurisy resembles in its entirety an old hydatid cyst. The gelatinous substance which it contains is nothing more than fibrin. 43° LESTOXS OF THE SEROUS MEMBRANES. Hyperplastic and adhesive inflammation. — H}'perplastic and adhesive inflammation of the serous membranes is characterised by the formation of connective tissue traversed by blood-vessels which becomes definitely organised and gives origin to thickenings or adhesions. The latter are seen in the form of bands, or there is a complete fusion of the opposed surfaces of the serous mem- brane, so that often the pleural cavity is entirely effaced. These adhesions are seen as the consequence of inflammation which shows an adhesive character from the beginning, or they are the result of fibrinous or purulent inflammation ; but most frequently it is Fig. 224. A, filamtmtons bands of tbe pleura, lined witli epifchelium ; b, blood-vessels. The epithelium is stained with nitrate of silver. Magnified 80 diameters. impossible, when examining old adhesions, to determine their origin. It is even probable that a certain number of them date back to intra-uterine life, and may be due to vices of formation. In some post-mortems soft vascular growths, composed of embryonic tissue and blood-vessels, may be seen on the surface of serous membranes, particularly on the pleura. These buds in- crease in size, and if they meet with similar buds springing from the opposite surface, they unite, become fibrous, and form bands varying in form and extent ; sometimes they are very thin, some- TUMOURS OF THE SEROUS MEMBliAh'ES. 431 times thick, and are always composed of vascular fibrous tissue. Their surface is covered with flat epithelial cells, similar to those lining the rest of the serous cavity. When union is complete, a homogeneous layer of fibrous tissue is found between the two leaves of the serous membrane, uniting them closely together. Thickening of a serous membrane, or hyperplastic inflammation, seems to have the same origin. When only slightly prominent, these thickenings are called milky spots {plaques laiteuses), by reason of their whitish appearance, due to the fibrous tissue being composed of superimposed laminae. When the new growth is thicker, it is composed of cartilaginiform plates; described above. In both the milky and cartilaginiform plates there are a few blood- vessels, or they may be absent altogether. The cartilaginiform plates are sometimes infiltrated with calcareous salts, forming the .JX^< Fig. 225. Epitiiklium co\EuiNii the Filamentou.'; Bands WHICH UNITE TWO LAYEKS OF THE PlEUKA. Stained with nitrate of silver. Magnified 400 diameters. solid carapaces met with in the pericardium, pleura, peritoneum, and tunica vaginalis. (For further details, see Inflammation of each Serous Cavity.) III. Tumours of the Serous Membranes. Primary tumours of the serous membranes are rare, while secondary tumours by propagation or generalisation are common. Primary tumours of the serous membranes are those of which the type is found in the connective tissue : fibroma, lipoma, myxoma, carcinoma, and tubercle. Fibroma, lipoma, and myxoma. -The most common form of fibroma of the serous membranes is lamellar or corneal fibroma 432 LESIONS OF THE SEROUS MEMBRANES. {vide p. 1 63). In many serous cavities villous appendages may be observed, formed of adipose tissue and blood-vessels, and covered by glove-like prolongations of the serous membrane. Such are the appendices epiploicse of the intestine, the cellulo-adipose folds of the peritoneum, the villosities of the pleura, and the synovial fringes of the articulations. These cellulo-adipose appendages are subject to hypertrophy and form arborescent lipomata, which are slow in their evolution ; they are only discovered after death. In these same appendages mucous or fibrous tissue may be formed, constituting pedunculated myxomata or fibromata. Tubercle. — Miliary tubercular eruptions of the serous mem- branes are common. They may be primary or related to general miliary tuberculosis, or they may be developed in the neighbour- hood of tubercular foci of organs covered by serous membranes. These granulations are prominent, lenticular, whitish, semi- transparent, non-vascular, sometimes opaque at their centre. The smallest are hardly visible to the naked eye. When numerous they unite and form more or less extensive masses with festooned borders and uneven surface. The largest may attain the size of a lentil. In their neighbourhood the serous membrane is con- gested, and ecchymotic spots may even be observed. These spots are frequent in the peritoneum, where tubercular granulations may often be seen surrounded by red, violet, slate-coloured, or blackish ecchymoses. These granulations are more common on the visceral layer of serous membranes, though it is not rare to see a larger number on the parietal than on the visceral layer. Tubercular granulations of the serous membranes are very superficial, appearing sometimes as if they were superimposed on the membrane. They are often seated in the substance of the various layers of the serous membrane, which then acquires a con- siderable thickness, and presents the signs of interstitial inflam- mation. Thus in the peritoneum, particularly in the great omentum, the united layers and destroyed trabeculse may be replaced by a solid mass, one or two centimetres in thickness, formed of tubercular granulations, imbedded in a soft and vascular tissue. This alteration is sometimes mistaken for cancer. The development of tubercle determines various forms of in- flammation in serous membranes, fibrinous, hsemorrhagic, purulent, or formative inflammation. Most frequently, when the tubercular eruption is recent, the whole surface of the serous membrane is covered with a thin and transparent fibrinous layer, which is easily TUBERCLE OF SEROUS MEMBRANES. 433 detached, some granulations being often removed with it. Beneath this Mse membrane the serous membrane does not seem to have suffered any loss of substance. In other cases the fibrinous ex- udation is so profuse that at first sight the tubercular granulations which are beneath are not perceived : this is generally the case when the exuded fluid is haemorrhagic or purulent, but on detaching the exudation and washing the surface of the serous membrane the granulations are perceived. Chronic tubercular inflammation nearly always gives origin to soft vascular buds, of variable extent, covered with exudation ; and in their tissue new tubercular granulations are developed. These buds undergo caseous degeneration, in which case the connective tissue of the serous membrane is seen to be thickened, softened, and transformed into embryonic tissue, in which numerous tuber- cular granulations are developed. Under the influence of the inflammation which accompanies tubercle filamentous buds or bands, which are also often invaded by granulations, are formed between the opposing surfaces of the serous membrane. The tubercular granulations of serous membranes are at their commencement formed of small cellular elements pressed together, and which blend insensibly with the cells of the superficial or the deep layers of the membrane. These peripheral cells are similar to those which have been described above in fibrinous exudation. They are round or flat, some are many hundredths of a millimetre in diameter, and are filled with nuclei — mother cells or giant cells. They have been described in tubercular pleurisy by Langhans. When the tubercular eruption is profuse the connective tissue of the serous membrane is modified, and between its fasciculi a variable quantity of embryonic cells are found. The blood-vessels are dilated, and the lymphatics are filled with lymph cells. The exudation which accompanies tubercular granulations presents the characters studied already when considering forms of inflammation (wde p. 100). As to the thickenings and buds developed on the surface of serous membranes, they are composed of embryonic tissue containing capillaries, the walls of which are formed of tumefied cells. When there is an evolution of tubercles in these buds, the blood-vessels present the modifications which have been described on page 202, Tubercular granulations on the surface of serous mem- branes are certainly not always developed fi:om the connective tissue of these membranes, for beneath the tubercles cells are found which seem to be derived from the epithelial layer, and, V F 434 LESIONS OF THE SEROUS MEMBRANES. further, the layer of connective and elastic tissue which forms the corium of the serous membrane has not at these points suffered any loss of substance ; the question is therefore if the cellular elements of tubercle are derived from the epithelium of the serous membrane, or from the white blood corpuscles, or from these two sources simultaneously. In the present state of science it is difficult to answer this question decisively. Eindfleiseh main- tained, at the time when diapedesis of white blood corpuscles was unknown, that proliferating epithelial cells were the origin of tubercle : it is very probable that these cells take some part in the formation of superficial granulations, but it has not been shown that they are their sole source. M. Martin is of opinion, after exam- ining tubercles of the peritoneum produced by inoculation in the rabbit, that they are developed under the epithehum from migratory cells derived from the blood-vessels. When tubercular granulations are developed in the substance of the connective tissue of serous membranes,' or in the buds of inflammatory tissue, we think that they are developed from an embryonic tissue, which is derived either from the proliferating fixed cells of the connective tissue, or from the white corpuscles of the blood. Carcinoma. — Primary carcinoma of the serous membrane is rare, but secondary carcinoma by extension or generalisation is, on the contrary, very frequent. Of all forms of prirflary carcinoma the most frequently observed is colloid carcinoma of the peritoneum, situated either on the peritoneal surface of the Uver, or stomach, or in the great omentum. It takes the form of gelatinous plates, with vascular niar kings and ecchymotic spots. It is developed in the corium of the serous membrane, or in the sub-serous connective tissue. In the great omentum, the reticulated layers are trans- formed into a matted mass, in which nothing is found recalling the structure of the omentum, but simply that of coUoid carcinoma. Other species of carcinoma are developed in the ' According to MM. Keiner and Poulet (^Comptes renAus de VAcadhnie des Sciences, January 26, 1880), tubercle of the serous membranes is in its simplest fomi produced by a spherical or fusiform swelling of a blood-vessel, more rarely of a lymphatic vessel, and by the accumulation around this swelling of a certain number of cells. In the case of a true capillary vessel, the vascular swelling is caused by hypertrophy and hyperplasia of the endothelial cells of a limited portion of the vessel. These cells undergo vitreous degeneration and become fused into a solid cylinder, which on transverse section has the appearance of a giant cell with a marginal circle of nuclei. A tubercle of the peritoneum visible to the naked eye has, according to M. Keiner, the appearance of a milky spot on this membrane in young rabbits (vide p. 1 10). TUMOURS OF THE SEROUS MEMBRANES. 435 organs covered by serous membrane, and they increase till they form round or budding masses; they produce an inflammation in the membrane the exudation of which is almost always hsemor- rhagic. When a carcinomatous mass is formed upon a serous membrane, secondary smaller masses, which are disconnected, nummular, and have an umbilical central depression, are gener- ally developed around it. The depression is caused by the granulo-fatty degeneration of the centre, and particularly by the more active development of the periphery of the nodule. The lymphatic vessels which pass from these morbid masses often form on the serous membrane hard, knotty, whitish cords, isolated or arranged in a network, and small carcinomatous secondary nodules are developed in their track. The tissue of the serous membrane round these degenerated lymphatics and secondary nodules is always highly vascular ; the blood-vessels are dilated and have embryonic walls. Cylindrical-celled epithelioma may be propagated to the serous membranes, but it is rare ; more frequently an epithelioma of this kind, when developed in the intestine, stomach, or bile ducts, de- termines secondary growths, often of considerable size, in the liver without the serous membrane being affected, while the contrary is generally the case in carcinoma. Sarcoma, pavement epithelioma, and chondroma are very rare, and are never found except as secondary growths. Osteoid tumours are often propagated to serous membranes. 43^ CHAPTER VI. TSE ALTERATIONS OF MUSCULAR TISSUE. I. Normal Histology of the Striated Uuscles of Animla Life. There are three species of muscular tissue : iirst, the striated mus- cles of the trunk and limbs ; second, the cardiac muscle ; and third, the smooth muscles. Smooth muscle fibres enter into the composi- tion of blood-vessels ; hence we may consider the anatomical lesions of blood-vessels immediately after describing the pathological anatomy of unstriped muscular tissue. The muscle fibres of the heart, by reason of their peculiar structure, have lesions which diflfer in certain points from those of the striated muscles of the limbs. These lesions will be described in the chapter which treats of the pathological modifications of the endocardium and pericardium. Consequently, with muscular tissue, and following it, we shall study, first, the pathological changes of the blood; second, morbid changes in the heart ; third, changes in the blood- vessels ; fourth, lesions of the lymphatic system. The striped voluntary muscles are essentially characterised by striated muscular fasciculi, described on page 28. These fasciculi are arranged parallel to one another, and they are united by ex- tremely delicate fibres of connective tissue, so as to form distinct groups known as secondary fasciculi. These are not surrounded by a continuous amorphous membrane such as the sarcolemma which limits the primitive fasciculi.' The arteries and veins ramify between the secondary fasciculi, into which the capillaries penetrate, to insinuate themselves between the primitive bundles, round which they form a network with oblong meshes. These vessels . are always outside the sarcolemma. The entire muscle is enclosed in an aponeurosis, formed of closely united bundles of connective tissue ; these bundles are, how- ever, capable of separation, for on injecting a fluid into the muscle ' In England the term muscular fibre is generally used for that here trans- lated primitive fasciculus {fmseeam primitif) ; but I have thought it well to adhere to the terms primitive and secondary fasciculus, used in the original, as they are evidently preferred by MM. Cornil and Eanvier, — ^Te, LESIONS OF THE PRIMITIVE MUSCULAR FASCICULI 437 under the aponeurosis it will penetrate this fibrous covering, and be found on the external surface of the muscle. By the same pro- cess, also, it may be seen that fluid can penetrate throughout the whole thickness of the muscle, between the primitive bundles, the connective-tissue fibres, and the blood-vessels ; from which the conclusion is drawn that a muscle possesses a vast lacunar interstitial system belonging to the connective tissue, and in communication with the lymphatic system. Muscles are inserted by means of tendons. For a long time it was thought that the primitive fas- ciculi of the muscles were directly continuous with the fibres of the tendon. Kolliker, however, had already ascertained that when muscular fasciculi are inserted obliquely on to a tendinous surfece, there is no continuity ; but he still thought that, in the case in which the tendinous fibres have the same direction as the muscular fibres, they were continuous. Since Weismann used the chemical method of dissociating by a 40 per cent, solution of potash, the insertion of muscular fasciculi into tendons has been understood ; the union is accomplished by means of an organic cement of uniting substance, which, acted upon by the potash, softens, and is finally completely dissolved. The termination of nerves in muscles is, from the physiolo- gical point of view, a subject of great interest, but hitherto no lesions of the special organs of the nerve ends called the motor plates have been discovered, hence we shall not consider this subject. In lesions of the muscles we have to study those which relate to the primitive fasciculi on the one side, and to the connective tissue on the other. The lesions of the connective tissue of muscles are those of this tissue generally considered, but the elementary lesions of the primitive fasciculi necessitate a special description, which we shall give before studying the pathological lesions of muscles considered as organs. II. Lesions of Nutrition of the Primitive Huscular Fasciculi, and of the Muscles themselves. The lesions of the primitive muscular fasciculi consist in changes of nutrition of their striated substance or multiplication of their nuclei ; frequently, however, lesions of nutrition are ac- companied with division of the nuclei, but these two phenomena are not always associated, and there are cases in which, without any nutritive modification of the striated substance, multiplication of the muscular nuclei are observed : on the other hand, very advanced 438 ALTERATIONS OF MUSCULAR TISSUE. lesions of the contractile substance may occur without any altera tion of the nuclei. Atrophy of the muscular fasciculi. — Atrophy of the muscular fasciculi may be coincident with general atrophy of the muscle ; or, on the contrary, with the preservation and even with increase in size of the whole muscle, when it is the connective tissue or in- terstitial adipose tissue which increases. The different tumours of the muscles also constantly cause atrophy of the muscular fasciculi. In emaciation, the muscular fasciculi of the whole body are atrophied, and in infantile paralysis all the fasciculi of a single muscle may be affected simultaneously, or, as in the case of serious febrile disease, only a few may be affected. It is a doubtful point if in man the muscular fasciculi are normally renewed, for in an adult very considerable variations of diameter may be observed in the different fasciculi of the same muscle : some are hardly 'OX mm. in diameter, while others are from "03 to "07 mm., or even more. In persons advancing in age this difference is still more marked, and in their muscles fasciculi are constantly found in an atrophied condition, and containing fat granules. Atrophy is simple or caused by some one of the nutritive changes considered later. These changes generally cause an increase in the size of the fasciculi at the beginning, the atrophy only occurring later. Atrophied muscular fasciculi are of the most varied forms and sizes. If in an adult the fasciculi do not exceed '04 mm. in diameter, it may be concluded that there is muscular atrophy ; when all the fasciculi have a mean diameter of •01 mjn., the atrophy is considerable. Finally the muscular sub^ stance may be found to have completely disappeared, at least some of the fasciculi are only represented by rectilinear filaments, formed of collapsed sarcolemma. It is concluded that these are the sarcolemmic sheaths, for between them and recognisable mus- cular fasciculi all intermediate forms may be found. In some cases in which the muscular atrophy is very considerable and regular, the characteristic striation may be manifestly preserved in fasciculi having only a diameter of "003 mm. These fasciculi contain nuclei, at which slight swellings are seen. This form may be observed in progressive muscular atrophy, in the last period of infantile muscular paralysis, and in all forms of atrophy dependent on the nervous system. In some cases of club-foot and infantile paralysis there is an in- crease of the connective tissue which counterbalances the atrophy of ATROPHY OF THE MUSCULAR FASCICULI. 439 the muscxilar fasciculi, so that, though the muscle is really atrophied in its active elements, it is considerably larger than normally. This increase in size is particularly shown when adipose tissue is deposited in large quantities between the atrophied muscular fasciculi ; this is what occurs in the disease called by Dachenne pseudo-hypertrophic paralysis. The atrophied muscular fasciculi, which are few in number, preserve their normal structure, and show neither fat granules nor anything abnormal, excepting decrease in diameter. These thin fasciculi are to a certain extent lost in a mass of very abundant cellulo-adipose tissue, which is substituted for the atrophied fasciculi. This lesion of the muscles is the only one which can be found in the post-mortem examination A Fig. 226.— Atrophied Muscular Fasciculi undekooino Fattk Degeneuation. From a Myxoma. «, priinitivo tasoioali in which nuclei, n, are seen ; J>, atrophied and fusiform fasciculus. of patients who have succumbed to this disease ; the nerves of the medulla were normal in the cases reported by various authors, more particularly by Cohnheim, Charcot, and Joffroy, and more recently by one of us in a case of M. Bergeron's. In tumours of the muscles the pathological growths develop in irregular spots ; the muscular fibres undergo in places complete atrophy, while throughout the rest of their extent they may pre- serve their original size ; from which it results that the fibres are divided into irregular segments, the extremities of which are round or drawn out into a point ; generally in the preserved por- tions, numerous nuclei are disseminated in a granular substance. 440 ALTERATIONS OF MUSCULAR TISSUE. which replaces the striated substance. These spots resemble cells with multiple nuclei (fig. 210). muscular hypertrophy. — This subject has been hitherto little studied. The histological analysis of muscular hypertrophy is very difficult, and raises problems which are far from being solved. When a muscle increases in size from exercise, in a perfectly normal manner, as for example in consequence of gymnastics, or pathologically, as occurs in the intercostal muscles in emphysema, it is very difficult to say if the hypertrophy is due to the forma- tion of new muscular fasciculi, or to the enlargement of old fasciculi. The difficulty is caused by the fact that the fasciculi normally have very different diameters in the same muscle. A fasciculus of '03 mm. may, for example, attain a diameter of -05 or '06 mm, in the course of the process, without our knowing if this size is accidental. When hypertrophy of a muscle is due to the formation of new muscle elements, the process of this new formation may be followed. Thus Bardeleben studied the genesis of new muscular fasciculi from connective-tissue cells, in hypertrophied intercostal muscles from prolonged dyspnoea. The reproduction of muscular fasciculi in the adult takes place, moreover, in a constant manner, when in consequence of an acute disease a certain number of muscular fasciculi have been destroyed, by one of the nutritive changes to be studied further on. The physiological reconstruction of the muscles, after febrile emaciation, is due, not only to an increase in the size of the atrophied muscular fasciculi, which have preserved their structure, but also to the formation de, novo of muscular fasciculi, which originate and are developed between the old ele- ments. These phenomena have been well studied by Zenker in various febrile affections — ^typhoid fever, variola, scarlet fever, etc. — in which he has described the changes and reproduction of mus- cidar fasciculi. The same year that Zenker made these researches, Colberg discovered a similar regeneration of muscles after trichi- nosis. New muscular fibres are always developed from cells situated outside the fasciculi ; the nuclei of these cells multiply, their protoplasm increases and sends out blunt or pointed processes presenting a striking resemblance to the mother cells of bone medulla. The extremities of adjacent cells unite, their substance becomes segmented transversely, and takes the characters of striated muscular substance. But it is improbable that this is what takes place ; we know, in fact, that striated muscular fasci- GRANULAR CHANGE IN MUSCULAR FASCICULL 441 culi axe not formed from cells placed end to end and imited together, but that each fasciculus is developed from a single cell, the nuclei of which multiply. Hypertrophy of a muscle is not always related to increase of size of its fasciculi, nor to their new formation ; it may be due, as we have already said, to increase of connective or adipose tissue, or even to the abnormal development of blood capillaries or lymphatics. We have already spoken of pseudo-hypertrophic paralysis of the muscles : it must also be added that congenital hypertrophy of the tongue is principally due to considerable thickening of the connective tissue of this organ, or to dilatation of the lymphatics. Oranular change of the muscular fasciculi. — This change corre- sponds to what Virchow has called cloudy tumefaction. It is very often the first stage in fatty degeneration. In this lesion the muscular fasciculi are more opaque than usual, their substance shows numerous fine granules, their striation is indistinct or has even entirely disappeared. When acted upon by acetic acid these fine granules disappear, the fasciculi become transparent, and the striation is less distinct than when normal fasciculi are treated by the same reagent : the striation may even disappear. In other cases, acetic acid, in causing the disappearance of these fine granules, discovers other transparent and refractive granules of a fatty natmre, existing in small or large numbers. The sarcolemma is as transparent as usual, the subjacent nuclei are normal, or show signs of proliferation. Whenever this granular state of the mus- cles is accompanied with proliferation of the nuclei of the sarco- lemma, parenchymatous inflammation is present; in fact, this lesion may be observed in inflammation of the muscles, for example, in suppurating intermuscular phlegmon ; but it is also met with in cases where the inflammatory nature is doubtful, for example, in all serious acute general diseases — typhoid fever, eruptive fevers, purulent infection, and acute phthisis, etc. In an acute fever this granular change is most frequently accompanied with fatty and vitreous change. When the existence of this change is suspected, the greatest care must be taken in the pre- paration of the muscles, and we will here indicate the method which should be employed in studying all the alterations about to be considered. An incision being first made in a muscle parallel to the direction of its fasciculi, a small flake of the muscular tissue is removed by 442 ALTERATIONS OF MUSCULAR TISSUE. four incisions made with a very sharp razor; this is placed on a slide, and slightly moistened ; then with needles, placed at one of the extremities of the divided fasciculi, the specimen is divided in two ; the needles are again used in the same ' way at the same extremity, and the secondary fasciculus is again divided. This method of division is continued till the primitive fasciculi are isolated, or delicate bundles of these fasciculi. The ends of these, which have been touched by the needles, may be disregarded in the examination, for they show an alteration of their contractile substance which might be mistaken for granular change. Fatty degeneration of muscles. — In a child, as well as in an adult, a few muscular fasciculi may always be found, containing extremely fine fat granules which are rendered visible by the action of acetic acid. These granules are few in number, and attentive care is necessary for their recognition. In old age, the number of granulo-fatty fasciculi is larger ; the fasciculi, moreover, contain larger fat granules, which may be easily seen without having recourse to acetic acid. A certain quantity of fat is always present in muscles, but it is in a state of soluble combination, that is to say, it exists as a soap, and is hence not visible under the microscope. When isolated, fat is seen in the form of an insoluble substance. Microscopical analysis does not, therfore, give any idea of the quantity of fat contained in a muscle, but only of that which is in the state of neutral or insoluble fat ; hence it results that chemical analysis of a muscle, in a moderate condition of fatty degeneration, does not yield more fat than a normal muscle (Eindfleisch). Nevertheless, the presence of a great number of fat granules in the primitive fasciculi always indicates an import- ant nutritive trouble, for fat in this condition cannot be utilised by the muscles during work like the fat of composition, and it even hinders the play of those organs. Muscular fasciculi, which have undergone fatty degeneration, are more friable than normal, hence more care must be used in preparing them for microscopical examination. The fat granules of the degenerated fasciculi have a certain regular arrange- ment ; they are deposited in series in the longitudinal striae of the primitive fasciculi ; their presence even marks the longitudinal striation of these fasciculi, while the transverse striation is less dis- tinct, or may even have disappeared. These details may be seen on examining fatty degenerated muscular fasciculi with a power magnifying 250 diameters ; with a lower power, only the granular PIGMENTARY DEGENERATION. 443 state and the opacity of the fasciculi can be perceived. The sarcolemma preserves its transparency, as may be easily observed at the points where the muscular substance is torn and contracted ; the nuclei are also preserved, the protoplasm surrounding them is fatty, and it is in the neighbourhood of these nuclei and the sur- rounding protoplasm that the process of degeneration commences. It is very probable that fasciculi having undergone fatty change may return to their normal condition, if what takes place in frogs may be considered as typical. In these animals during the winter a great number of fasciculi become fatty which in the summer return to their normal condition. But in man the fasciculi which have undergone this change in disease are most frequently destroyed by a process the dififerent phases of which may be followed. The granules of fat become more and more profuse, the fasciculi become opaque, striation is no longer distinguished, and at the end of the process the sarcolemmic sheath is filled with a formless mass containing a large number of fat granules ; these slowly disappear, until finally only the collapsed sarcolemma is left. It is principally in tumours of the muscles, and in callus when it has encroached upon muscular tissue, that the details of these changes may be followed. In infantile paralysis and in progressive muscular atrophy the muscular fasciculi totally or partly disappear in consequence of fatty degeneration. Fatty change of the muscles is also met with in fevers and in purulent infection ; it is very marked in me- tastatic inflammation of the muscles, while in the case of white infarcts consequent on arterial obliteration by an embolus, the muscular fasciculi are not found to undergo fatty degeneration. In wounds implicating the muscles a few fibres may sometimes be found in a state of fatty degeneration in the embryonic tissue at the base of the wound, but at a little distance, though there is a marked increase of new cells between the muscular fibres, the fasciculi are degenerated. In poisoning from phosphorus, arsenic, etc., fatty degeneration of the muscles is very marked. Pigmentary degeneration. — In the cardiac muscle physiolo- gically, but only pathologically in other muscles, may be found round or angular granules of a more or less dark-brown colour, located under the sarcolemma, or in the muscular substance itself. These pigment granules are very probably derived from the trans- formation of the colouring matter of the muscles, which is similar to that of the blood, and has been named muscular haemoglobin. 444 ALTERATIONS OF MUSCULAR TISSUE. This change of the muscular haemoglobm into pigment is produced when the muscle dies in the midst of a Kving organism (the heart being always excepted), for example in infarcts and in metas- tatic abscesses. The fcstus which has remained for some weeks in the uterine cavity after death also shows pigment granules in the muscles. Vitreous degeneration. — We have already spoken of this form of degeneration on page 68, and we have given it the name of vitreous degeneration, which seems to us preferable to that of waxy change, given by Zenker, who was the first to describe this lesion. This Fig. 227. — Muscular Fibres in a State of Vitreous Degekeration. a, altered fascLculi ; &, adipose cellB. Magnified 300 diameters. alteration of the muscles must not be mistaken for a modification of the muscular fibre, produced by the method of preparation. On removing a fragment of muscular tissue from the Hving animal, or from one just killed, the fasciculi contract and form refractive masses, in which striation cannot be distinguished, or only an extremely fine striation, which may be recognised with a high power on shading the field of the microscope. On extending the tongue of a frog with pins, as is usually done to study the circu- lation of the blood in this organ, it often happens that as a result of the tension the muscular fibres are ruptured and form refractive masses; but after studying the true characters of the lesion, VITREOUS DEGENERATION 445 vitreous degeneration cannot be mistaken for these altogether accidental changes. Vitreous degeneration consists in a change of the muscular sub- stance, by which it loses its striation, becomes hyaline, and trans- parent as glass. In this first stage the mucular fasciculi are increased in size, and have preserved their regular cylindrical form, their nuclei are more visible than normally, and the sarcolemma seems to have undergone no modification — indeed the nuclei and the protoplasm which surrounds them have entirely escaped the vitreous change. The vitreous substance stains deeply with neutral car- mine; acetic acid causes it to swell without dissolving it. It is much more brittle than muscular substance, so that if not dis- sociated with the greatest care numerous and irregular frac- tures are produced. When by means of this process a small cylinder of the muscular fasciculus has been isolated, it becomes separated firom the rest of the fasciculus. Thus in the same fasciculus may be seen a series of fragments, separated by spaces varying in size, at which the collapsed sarcolemma seems to be strangulated. The collapsed sarcolemma, compressing the broken extremities of these fragments, gives them the appearance of a number of superimposed casks. Vitreous degeneration is always limited ; it is never met with in all the fasciculi of a muscle, so that if, instead of examining an isolated primitive fasciculus, a group of fasciculi be examined with a low power, some among them are seen to have become homogeneous and transparent. Along their edges is seen a cha- racteristic brightness, due to the refirangibility of their substance ; the other fasciculi are intact, or only show granular change. Vitreous fasciculi have lost their physiological properties ; those which are intact are, however, still capable of contraction, and they act mechanically on the brittle and inert fasciculi, and by their movements determine the ultimate changes in the vitreous fibres. These changes are particularly well marked in chronic vitreous degeneration, such as may be observed in the neighbourhood of tumours, or better still in chronic phlegmon, aroimd fistulous tracts in caries, necrosis, or white swelling. Vitreous degeneration in such situations has been hitherto ill described, for it has been particularly sought for in acute diseases, such as typhoid fever. In chronic degeneration of the fibres it is impossible to assert if the peculiar appearance of the fasciculi is due to the method of pre- paration. Under the influence of the movements of the healthy muscular fibres the vitreous substance becomes fragmented in every 446 ALTERATIONS OF MUSCULAR TISSUE direction, and is separated into blocks, the arrangement of which often resembles that of bricks in a wall {vide fig. 228). To- wards the end of the process the fragments become smaller and smaller and form granules, each one of which preserves the optical characters of vitreous substance. It is then that absorption com- mences, the sarcolemma collapses, and the subjacent nuclei become larger and more numerous, many of them showing signs of multi- pHeation by division ; this proliferation of the nuclei seems to be a phenomenon consecutive to degeneration. In acute fevers, when a certain number of the muscular fasciculi have been destroyed, a new formation of muscular fibres may be observed by which the muscles are completely regenerated. This regeneration has been followed by Zenker, who gives a minute Fig. 228. — Advanced Vitreous Degeneration of Long Standing in a Muscular Fasciculus. Magnified 360 diameters. description of it. The cells of the connective tissue adjoining the diseased fasciculi increase in size, their nuclei multiply with- out division of their protoplasm, they then elongate in the direction of the fasciculi, and before they lose the character of cells to take that of primitive fasciculi they already show a manifest striation. There is here a development which does not essentially differ from the physiological development of striated muscle. The muscles affected by vitreous degeneration are brittle and easily ruptured : this accident is particularly seen in muscles still capable of use, such as, for example, the rectus abdominis in bed- ridden persons. The changes which take place in a rupture of the muscle, consequent on this degeneration, will be studied later when considering haemorrhage of the muscles. HEMORRHAGE INTO MUSCLES. 447 The cause of vitreous degeneration is local or general ; in the first case the lesion is limited to the seat of the affection which has caused it, as may be seen in the neighbourhood of tumours, abscesses, and chronic phlegmon. When the disease occurs in consequence of a fever, it is seen particularly in the internal muscles of the thigh and in the rectus abdominis, though it may also be found in other regions. It is very difficult or even impossible to recognise vitreous degeneration with the naked eye. Zenker, however, indi- cates a peculiar colour similar to that of the flesh of fish, but this colour may be found in muscles which do not show this degenera- tion, so that histological examination is necessary for its determi- nation. Hsemorrhage into muscles. — Simple congestion of- muscles is not shown by evident signs in the cadaver, except in the neigh- bourhood of inflammatory or hsemorrhagic foci. Ha3morrhage into muscles was called by the old French and German authors by the name of hsemorrhagic infarctus, but this name does not imply the idea of a primary vascular obUteration. Haemorrhage into muscles may be caused by contusions, wounds, rupture of a muscle, or may depend on a general hsemorrhagic disease, such as purpura, scurvy, exanthematous fevers, leucocythsemia, etc. When muscular haemorrhage is recent, it forms in the substance of the muscle a dark red mass, divided sharply from the bright red of the muscular tissue. This mass, of very variable form and extent, may be hmited or diffused. As the blood coagulates, the muscle at this point becomes firmer and loses its elasticity. The muscular fas- cicuH contained in these foci undergo no change or are simply granular. In order to study the relation of the blood with the muscular fasciculi and the blood-vessels, the specimens should be hardened in alcohol, and delicate transverse sections cut, stained with car- mine, and examined in glycerine : the muscular fasciculi are then seen to be separated from one another by masses of red blood corpuscles ; in these masses, and between the fascicuU, the capillaries and vessels of a larger calibre are dilated and filled with blood corpuscles. The blood is seen to be coagulated in the vessels, as well as in the inter-fascicular spaces, in con- sequence of the arrest of the circulation. When haemorrhage results from rupture of a muscle, the fragments of the torn muscle are separated, and the space between them is filled with blood, which is at first liquid and then 448 ALTERATIONS OF MUSCULAR TISSUE. undergoes coagulation; the torn fasciculi project into the focus, the blood infiltrating between them for a greater or less distance. The muscular fasciculi then undergo alterations, which differ according to the cause of the rupture : sometimes it is vitreous degeneration, sometimes granulo-fatty change, but at the point where the fibres are torn they are in a state of complete fatty degeneration ; this is particularly observed in the recti muscles of the abdomen when ruptured in the course of typhoid fever. All the blood-vessels found at the edge of the solution of continuity contain red corpuscles, which are well preserved if the lesion is Fig. 229. — Kdptured Rectus Muscle with Hjjmoruhage, is Typhoid Fever. 5, effusion of blood between dissociated muscular fibres ; m, a mus- cular fasciculus in a state of vitreous degeneration ; % dissociated muscular fasciculus, recent, and granulo-fatty if old. When blood is thus effused into muscle it seems to be easily absorbed. The muscular movements certainly exercise a great influence on the intra-muscular lymphatic circulation, and consequently on the transportation of substances derived from the transformation of extravasated blood; but hitherto the successive stages of this absorption have not been followed, neither in man nor in animals. We know, however, that severe contusions, accompanied with considerable intra-muscular haemorrhage, may heal in a few days, without leaving any trace. As to the changes of the blood, they do not differ from those already described in haemorrhage of the connective tissue ; the EMBOLIC INFARCrUS OF MUSCLE. 449 blood undergoes the usual metamorphoses, it then coagulates, after which it is decomposed, the fibrin is dissolved, or becomes disintegrated into very fine particles, which are taken up by the circulation. The mechanism of muscular haemorrhage varies according to its cause. When it is the result of direct traumatism, such as rupture of a muscle, fracture of a bone, contusion, etc., the torn vessels allow the blood to escape till it coagulates and occludes the divided vessels. Muscular haBmorrhage may also be related to obliteration and thrombosis of the veins; in such cases the arterial pressure transmitted to the capillaries is sufficient to cause their rupture. But obliteration of the arteries either by throm- bosis or emboli cannot cause intra-muscular haemorrhage, any more than ligature of an artery. The mechanism of muscular haemorrhages in general diseases, such as purpura and hsemor- rhagic fevers, is not understood. Embolic infarctus of muscles. — True embolic infarctus of mus- cles is very rarely seen. We mean by this term the change conse- quent on the obliteration of a muscular arteriole and its branches. This lesion differs from hsemorrhagic infarctus by the absence of extravasated blood. Embolic infarctus of muscles should also be distinguished from metastatic abscess, which will be described when considering inflammation. We have only met with two cases of muscular infarctus, which were the result of emboli from endocarditis and endarteritis. In these cases, whitish and slightly opaque masses of conical form were seen in the midst of the muscular tissue, contrasting strongly with the rest of the muscle, which was red and semi-transparent. On examining these parts microscopically the primitive fasciculi were still seen to be striated ; they contained only a few pigment granules derived from the muscular haemoglobin, but no fat granules. This pig- mentary change is similar to that already described as existing in foetuses dead before expulsion. In the case which we examined we could not assign a date to the lesion. The changes in the blood-vessels will be described when considering infarcts in general (vide Lesions of the Vascular System). Mtdtiplication of the nuclei of the primitive fasciculi. — As we have already shown, multiplication of the muscular nuclei is seen to be the result of vitreous change, and even of granular change, but it may sometimes occur separately. This lesion is observed in u G 4SO ALTERATIONS OF MUSCULAR TISSUE. inflammation of the muscles following a wound, in the vicinity of a tumour, for example, cancroid of the lips or tongue, in certain forms of paralysis, in acute ascending paralysis, and in animals after division of a nerve. When a nerve has been divided in a rabbit, the only modification found in the muscles two or three weeks after the experiment is multiplication of the nuclei of the primitive fasciculi ; they become larger, divide, and form elongated groups (Vulpian). In these groups the nuclei are arranged in series in a granular protoplasm : this is generally characteristic of proHferation of the muscular nuclei. The nuclei are contained in a common protoplasmic mass ; it is only in exceptional cases that the proto- plasm is seen to form distinct masses round each nucleus, as, for example, in the final stage of vitreous degeneration. In epithelioma, multiplication of the muscular nuclei is often very marked ; at the same time there is a more or less notable atrophy of the primitive fasciculi, so that the nuclei, and the proto- plasm surrounding them, axe much more evident than normally. As these nuclei are large and contain large nucleoK, some authors have thought that they concur in the formation of epithelial cells; but we have never observed any fact in support of this opinion. It is also far from certain that proliferation of the muscular nuclei takes any part in the formation of pus. Inflammation of muscles or myositis. — The simplest form of inflammation of muscles, and the easiest to study, is that which takes place in consequence of wounds. If a muscle is implicated in a wound, the denuded or divided portion gives origin to granu- lation tissue. This new granulation tissue is developed from the interfascicular connective tissue, by the production of em- bryonic tissue and blood-vessels. The embryonic cells are found, not only on the surface af the wound, but between the primitive fasciculi to a depth which varies according to the intensity of the inflammation and the stage of the morbid process. In contusions such as, for example, a gunshot wound, embryonic tissue may be found in the affected muscle to the depth of many centimetres, when the wound is suppurating freely. In such a wound on the twelfth day, in a vertical section carried from its surface through the muscle, there will be found, first a layer of simple embryonic tissue, in which are loops of dilated capillaries with embryonic walls ; beneath this layer, the thickness of which varies from 1 to 5 mm,, is found a second, in which the embryonic tissue is furrowed by atrophied primitive fasciculi, which instead of all having the same INFLAMMATION OF MUSCLE. 451 direction, as in a normal muscle, are arranged with the greatest irregularity. These atrophied primitive fasciculi have a diameter of '01 to -03 mm. ; in preparations obtained after maceration in a •2 per cent, solution of chromic acid, transverse striation of the fasciculi cannot be distinguished, and they seem to be composed of fibrils separated by an exudation. The muscular nuclei, multipHed to excess, form groups or series, some of which are on the surface, others at the centre of the fasciculus ; the sarcolemma seems to have completely disappeared. Round the atrophied primitive fasciculi, the embryonic tissue begins to become organised and forms a reticulum, the fibres of which, at many spots, are blended Fio. 230 — Mis( uLAu Fascicili oit the Gastkocnemius Mi sci.e ok Man I'llOM A LARGE CONTUSED WoUND OF THE CaLF. Section made through the muscular tissue beaeath the layer of granulations : a, muscular substance ; 6, protoplasm and nuclei, (/, situated between the sarcolemma and muscular substance ; c, inflamed connective tissue. with the muscular fasciculi. In the deeper layers, the inter- fascicular connective tissue contains fewer cells, and the atrophy of the muscular fasciculi is more marked ; they then show an increase in the number of their nuclei, which in transverse sec- tions are seen to form a circle round each fasciculus {vide fig. 230). It remains to be added that in many spots of the intei-fascicular connective tissue are found free globular cells containing brown granules of hsematin. This fact shows that there has been an infiltration of blood into the tissue, which has been in a great part absorbed by the same process as that described in hcemon-hages of the connective tissue. 452 ALTERATIONS OF MUSCULAR TISSUE. The changes described in a simple case are seen with slight variations in all cases of muscular inflammation observed in man, or in animals submitted to experiment. The muscles di\dded in stumps after amputation undergo the same changes. Recovery takes place definitely by the organisation of the embryonic tissue at the surface, and by the disappearance of that which is inter- posed between the muscular fasciculi ; but this simple and natural course towards recovery may be prevented by various accidents (haemorrhages, suppuration). Suppuration of muscles. — Muscles suppurate in limited foci or by diffuse infiltration. The limited foci are seen as accidents in the vicinity of a wound, or they are related to purulent infection, glanders, or farcy. The metastatic foci of purulent infection dififer entirely from white embolic infarcts. They vary in size from a hemp-seed to that of a fist. The pus contains a detritus composed of connective tissue and disintegrated muscular fasciculi. The purulent focus is surrounded by a greenish brown zone, in which the interfascicular connective tissue is infiltrated with lymph cells and red blood cor- puscles, and the muscular fasciculi contain proteid, fat, and pigment granules. This zone may be met with in the walls of all purulent foci of muscles, whatever may be their cause. In dififuse inflamma- tion, which is often seen in the divided muscles of amputated limbs in patients who have succumbed to purulent infection, or in inflammation of the psoas muscle, purulent infiltration causes fatty degeneration of the primitive fasciculi ending in necrosis. Chronic inflammation of the muscles. — This occurs as a secondary phenomenon round articulations affected with white swelling or chronic rheumatic arthritis ; it is also met with in the neighbour- hood of purulent fistulas leading from carious or necrosed foci. The lesions of the interfascicular connective tissue consist in hyper- trophy due to an exuberant production of cells, and to the forma- tion of an exudation, so that the divided surface of these muscles on section, instead of presenting their characteristic fasciculated appearance, show a marbled surface in transverse sections and fibrous in longitudinal sections. The muscle has lost its colour and is whitish or pink, its firmness is increased, and it has partly lost its elasticity. The muscular fasciculi are seen to have under- gone various changes; in some striation is preserved, and their nuclei are more numerous than normally ; others have undergone granular RUPTURE OF MUSCLES. 453 or granulo-fatty degeneration; finally, in a certain number of cases, most of the fasciculi show the lesions of vitreous degeneration. Some authors refer the fibrous nodules and even the needles of bone, which are produced in consequence of repeated contusions and firiction, to chronic inflammation. It is thus that Eokitansky explains bone formations in the biceps of German soldiers, and in the adductors of the thighs of riders who are accustomed to remain long in the saddle. Rupture of muscles. — Kupture of muscles caused by contused wounds is not considered here, but only those ruptures which are caused by muscular contractions. If the muscle is healthy, there must have been considerable strain to produce rupture, which is, however, not the case if the muscle is in a morbid condition. In acute typhoid fever, for example, when the muscles are degenerated, the rectus abdominis may be ruptured by the simple effort of sitting up in bed. This rupture has been more particularly studied anatomi- cally, for other muscular ruptures are generally followed by recovery. Rupture of the rectus abdominis in typhoid fever often occurs without the physician being aware of it, the lesion being only dis- covered on the post-mortem table. It is then seen to have occm-red in an irregular manner, so that the surface of the divided fragments is uneven, the space between them being occupied by a dark brownish-red blood-clot, marked with opaque whitish lines. On dividing the muscle longitudinally, a brown stain and rigidity are found at the solution of continuity, to the depth of from one to many centimetres. The blood-clot is formed of red cor- puscles contained in a fibrous reticulum, and shows the various changes observed in interstitial haemorrhage ; in the white lines, fibrin and white corpuscles are found chiefly. At their point of division the muscular fibres show very advanced granulo-fatty de- generation {vide fig. 229). Between the muscular fasciculi, the connective tissue is infiltrated with coagulated blood, with which the blood-vessels are also filled. On comparing the muscular fas- ciculi near the rupture with the fasciculi of the same muscle far removed, only a small number of the latter are found to be in a state of fatty degeneration, while many have undergone \itreous degeneration ; near the rupture, on the contrary, the fasciculi con- tain a great number of fat granules ; it is hence highly probable that fatty degeneration is at least in a great part consecutive to the rupture. 454 ALTERATIONS OF MUSCULAR TISSUE. III. Tumours of the Muscles. Sarcoma. — We know of no case of primary sarcoma of the muscles, but extension of sarcoma into muscle is frequent. Fas- ciculated sarcoma is the most common, but embryonic or encepha- loid sarcoma, lipomatous, mucous, erectile, and melanotic sarcoma are also observed. It is unnecessary to redescribe these different tumours, which in muscular tissue present the usual characters (vidi chapter on Tumours). The morbid mass always develops from embryonic tissue, previously formed in the interfascicular spaces. The new tissue compressing the primitive muscular fasciculi causes them to atrophy, which may be simple or accompanied with granulo-fatty degeneration : the latter is principally met with in those cases in which the formation of sarcomatous tissue has been very rapid. It is also observed in exuberant callus implicating muscular tissue, which at a certain stage of its development shows the structure of sarcoma. Fibroma. — Simple fibroma of muscles is generally the result of mechanical irritation ; these tumours, once established, do not increase, nor cause any marked disturbance of muscular function ; at least if those cases of muscular atrophy with increase of fibrous tissue between the muscular fasciculi are not considered to be primary fibromata ; but in these fibrous formation is a secondary phenomenon. Myxoma and lipoma are met with in muscles as separate tumours, or as compound ttimours, called lipomatous myxomata. They are most frequent in the muscles of the tongue, lips, and buccal walls, but they may be met with in other muscles of the body. Gummata of the muscles, though rare, are well known clinically. They have not however been made the subject of thorough histo- logical examination. Tubercle. — Tubercular ulcers of the tongue and pharynx are not rare. In the midst of the muscular fibres at the base or edges of these ulcers, tubercular granulations are always met with; which, in sections cut after hardening in alcohol or alkaline bichro- mates, are seen to be quite characteristic. In them may be recognised giant cells and masses of small cells pressed together in the form of nodules, as well as obliteration of the blood-vessels in the nodules. Finally, discrete or confluent tubercles may be found in different states of caseous degeneration ; when confluent, they form caseous masses visible to the naked eye. TUMOURS OF THE MUSCLES. 455 Carcinoma. — Carcinoma of the muscles is always secondary ; it is produced by extension, or by infection ; it is developed in the interfascicular connective tissue, where it shows the usual phases of evolution, while the primitive fasciculi undergo simple atrophy with multiplication of their nuclei, or atrophy with fatty degenera- tion. Encephaloid or scirrhus are more often met with in muscles, but the other varieties of carcinoma may also be found ; we may notice, in particular, the extension of scirrhus of the breast to the pectoral or intercostal muscles, and extension of encephaloid of the uterus to the psoas-iliacus muscles, etc. Epithelioma. — Epithelioma of the orbicularis oris occurs almost invariably in cancroid of the skin and labial mucous membrane. It is in this situation that the opportunity is most frequently given of studying the development and growth of epithelioma in mus- cular tissue. Long before the epithelial buds have advanced between the primitive muscular fasciculi, a development of em- •bryonic tissue may be observed in the interfascicular connective tissue separating the bundles : some of the fasciculi may remain grouped, but they are very few in number, and their nuclei are always seen to enlarge and multiply, while the muscular substance gradually atrophies, its characteristic striation being preserved. The epithelial buds advance into the substance of the muscle in the midst of the embryonic tissue developed between the fasciculi. The tongue is attacked in the same way in epi- thelioma of this organ. These tumours are of the lobulated variety. Tubular epithelioma, developed primarily in the antrum Highmori or the nasal fosssc, may also extend to the muscles of the face, and give origin there to diffused or circumscribed masses. Epithelioma may by extension or metastasis invade other muscles, notably the heart. Chondroma sometimes invades the intermuscular connective tissue, as may be seen sometimes in chondroma of the parotid. Osteoma of the muscles caused by mechanical irritation has been already described {vide \>. 453) : we may add that, in the vicinity of an articulation affected with long-standing chronic inflammation, osseous growths may be often seen in the tendons, and which extend to the muscles and form nodules or spiculse in the substance of the muscular tissue. Angioma, either simple or cavernous, is not very rare in muscles ; it must not be confounded with varices. 456 ALTERATIONS OF MUSCULAR TISSUE IV. Parasites of the Muscles. Three varieties of parasites are observed in muscles — cysti- cerci, echinococci, and trichinae. Cysticerci are rarely met with in human muscles : they do not generally cause accidents during life, and are hence only discovered on post-mortem examination. We have had the opportunity of examining the muscles of a cadaver, in which the cysticerci were contained in whitish cysts, the size of a pea, situated between the muscular fasciculi, and surrounded with a fibrous FlO. 231. — COXVOLUTED AND ENCYSTED TRICHINA. shell. The cysticerci were infiltrated with calcareous granules, but their heads, suckers, and booklets could nevertheless be found. There are a few cases on record of hydatid cysts with echino- cocci in muscles, the microscopical characters of which were indisputable. TricMna ( Trichina spiralis), discovered by Owen in the muscles, is found in the form of a small convoluted worm, contained in a cyst. These cysts, which are oval or egg-shaped, are situated in (he interior of the muscular fasciculi, or in the interfascicular con- TRICHINA IN MUSCLES. 457 nective tissue: they are hardly visible to the naked eye; they possess two envelopes, one formed by the sarcolemma or connective tissue, the other belonging to the animal ; they contain one, two, or three convoluted trichinas of characteristic form. If they re- main long in the organism, the cysts undergo calcareous infiltration, and the worms become brittle. The adjacent muscular fasciculi undergo granular change, and the irritation resulting from the presence of the cyst determines a new formation of blood-vessels round its edge. Trichinae are asexual in the muscles, but when swallowed by a mammalian they become free and attain sex in the digestive canal. Fig. 232. — Tuiciiina arrived at Complete Development. c, cephalic extremity terminating by the oesophagus and mouth ; 6, caudal extremity terminating by the anus ; c, genitul organs. The males are 1"5 mm. in length, the females .3 mm. Their .anterior extremity is pointed : it contains the oesophagus, and ter- minates by a mouth. The posterior extremity is blunt and rounded ; the sexual organs are simple, and are situated in the middle third of the body; the testicle is in the posterior third. Copulation takes place in the intestinal canal, and a few days afterwards the female produces a large number of young. These perforate the intestinal walls and distribute themselves throughout the economy, locating themselves finally in the striated muscles, with the exception of the heart. They are arrested in their migra- tion by the insertion of the tendons. Encysted in the muscles, they produce the various changes described above. 458 CHAPTER VII THE BLOOD The Pathological Histology of the Blood. Alterations of the blood in disease are numerous; they may almost all be ascertained by means of chemical analysis, only a few of them can be recognised by the microscope ; it is with the latter, however, that we are concerned. The histological changes of the blood consist in variations of the number of white and red corpus- cles, in the decrease of haemoglobin contained in the red corpus- cles, in variations of size of these elements, and in the change of resistance of the red corpuscles : finally, bodies may be found in the blood which do not exist there normally. Changes in the number of the corpuscles can be only appreci- ated by means of the direct methods of numeration {vide p. 48). An increase in the globular richness of the blood may be due, either to an actual increase in the total number of corpuscles, or to a loss of fluid resulting from concentration of the blood ; as, for example, after profuse perspiration, diarrhoea, etc. Estimation of the haemoglohin. — The red corpuscles do not always contain an equal quantity of hasmoglobin ; this has been proved by the researches of Duncan, Malassez, and Hayem. Malassez and Hayem have attempted to give an idea of the quantity of hasmo- globin contained in each corpuscle. To ascertain this the quantity of haemoglobin must be divided by the number of corpuscles contained in a given volume of blood. As chemical processes require too large a quantity of blood, recourse is had to colorimetric methods. The method of Hayem is derived from that of Welcker ; it consists in comparing a certain thickness of a given solution of blood with a series of conventional tints. The depth of the tint corre- sponds to a blood containing a certain determined number of normal red corpuscles ; the tint 5, for example, is equivalent to 4,000,000 normal red corpuscles. A blood which in solution ESTIMATION OF HEMOGLOBIN. 459 would give this tint should have as much haemoglobin as if it contained 4,000,000 red corpuscles per cubic millimetre. On dividing the number of corpuscles giving this tint by the number of corpuscles given by numeration, the relative proportion is obtained between the colour of a normal red corpuscle and that of the blood examined. If, for example, it is found that by the tint, 4,000,000 is the number of red corpuscles, and by numeration 5,000,000, the corpuscle only contains 0-8 of the haemoglobin it should contain normally. This method is inconvenient in many ways ; the colorimetric scale is difficult to produce mechanically, and thus is not found in commerce ; the unit chosen is arbitrary ; and, finally, the results are expressed by the relative quantity, and not by the absolute amount of haemoglobin present. The apparatus of Malassez is composed of a screen, which the observer places between himself and the Hght. The screen is pierced by two apertures placed near together ; behind one of the apertures is placed the bulb of a Potain's mixer, containing the solution of blood (the ordinary bulb is modified for this purpose, and has two plain and parallel surfaces) ; behind the other aper- ture is a coloiured prism, containing a solution imitating blood in colour (in the spectrum it gives two bands closely resembling those of reduced haemoglobin). This prism is moved up and down by means of a screw, so that the parts, of variable thickness, and hence more or less deeply tinted, are passed before the aperture of the screen, until the tint is found exactly corresponding to that of the solution of blood in the mixer. On one side of the prism is a graduated scale, which passes in front of a fixed needle, which indi- cates the degree of the scale corresponding to the blood examined; on referring the number obtained to a table gummed on the screen, the richness of the blood examined per cubic millimetre is ascer- tained. The scale has been established by means of series of examinations of solutions of blood accurately measured. Though this method is not rigorously exact, no more than any other colorimetric method, it is more than sufficiently precise for clinical needs. After having determined the proportion of haimoglobin contained in the red blood corpuscles, it would be well to ascertain the quality of this haemoglobin : certain facts seem to show that it undergoes changes, so that equal weights of haemoglobin do not absorb equal quantities of oxygen. Changes in the size of the corpuscles.— The blood corpuscles show changes in size, which, in the red corpuscles, is a very inter- 46o THE BLOOD. esting subject of study, when considered in connection with their modifications of number and colour. Numeration and colorimetry teach us, for example, that the red corpuscles of chlorotic patients contain less haemoglobin than normal corpuscles ; this is not owing to the fact that they are smaller, for on measurement they are found, on the contrary, to be larger than normal j the change in the corpuscles is in the corpuscular substance itself, in that it is less rich in haemoglobin. Mensuration of the corpuscles is not without difficulty, by reason of their small size, their mobility, and the great number of processes necessary to arrive at a reliable mean. The following is the process recommended by M. Malassez ; a drop of blood is deposited on a slide and spread out into a very thin layer, which is fixed either by rapid dessication or by exposing it in the vapour of osmic acid. The preparation is then drawn by aid of a camera lucida, a lens being used, the magnifying power of which has been accurately determined beforehand by means of a micrometre. The diameter of each outlined corpuscle is then measured with a compass, and the lengths thus obtained are placed end to end on a horizontal line, traced on a sheet of paper : the total length first divided by the number of corpuscles, then by the magnifying power,' gives the mean diameter of the corpuscles. The thickness of the corpuscles, less often sought for, is obtained in preparations of fresh blood by drawing straight rouleaux of corpuscles, and dividing the height of the pile by the number of corpuscles composing it. Changes in the resistance of the corpuscles. — In the presence of certain reagents the red corpuscles show changes in their power of resistance. In a preparation of normal blood diluted with arti- ficial serum, some corpuscles are seen to preserve their biconcave form for a long time, while others change rather rapidly, and become either crenated or spherical. In the pathological con- dition, these phenomena are often very marked, either in one direction or the other, even when the nature of the serum used, the strength of the dilution, and the time of the observation are exactly the same. In anaemia from lead-poisoning, for example, the red corpuscles show great resistance, while in chlorosis they alter and ' If a lens be selected and the tube of the microscope graduated so that the figure thrown by the camera lucida exactly magnifies 1,000 diameters, the process is much simplified. Care must be taken to correct the errors of refraction, which may be done by placing the paper at such an inclination that it is at right angles to the optic axis, as recommended by Malassez. — Tk. BLOOD CHANGES IN DISEASE. 461 become granular with great rapidity. Such alterations may have a marked influence on general nutrition, and it is most important that they should be studied in a thorough manner. We will now proceed to study changes of the blood met with in those diseases in which these alterations have a special importance. Inanition. — In inanition, according to the experiments made on the guinea-pig and fowl, the number of red corpuscles increases at the beginning, probably by concentration of the blood ; then the number diminishes and the animal dies, the normal number not being reached, or at all events hardly passed. This increase and diminution explain the contradictory results obtained by different observers. In a subject suffering from cicatricial stric- ture of the oesophagus, and who is ill nourished, and in animals that have undergone prolonged abstinence (frogs at the end of winter), the number of corpuscles falls below the normal. The richness of corpuscles in hsemoglobin is not always proportionate to their niunber (Malassez). In slow as in rapid inanition the total mass of the blood diminishes in a marked degree. Wounds and suppuration. — In wounds and suppuration there is a more or less considerable decrease in the number of red corpus- cles, due probably to concomitant haemorrhage. In an experiment on a dog, in which a wound was produced without haemorrhage, the number of red corpuscles was not modified (Malassez). The white corpuscles, on the contrary, rapidly increase in number. If there is no discharge of pus, nor formation of abscess, the number of white corpuscles gradually diminishes, and returns to the nor- mal, even before the wound is completely cicatrised. Similar phenomena are observed after amputation, and after parturition ; but if complications in the form of abscesses or purulent infection occur, the number of white corpuscles considerably increases, until there may be one white corpuscle to fifty-four red. Piuulent collec- tions, abscesses, empyema, etc., are also accompanied by an increase in the number of white corpuscles, which ceases as soon as the contained pus has free exit. This leukaemia or leucocythosis of suppuration may aid the diagnosis in doubtful cases of deep sup- puration. In malignant pustule there is also a considerable increase of white corpuscles. Hsemorrhage is followed by a decrease in the number of red corpuscles, more marked as the haemorrhage is more considerable. In women the same phenomena are observed during menstruation. The quantity of haemoglobin per corpuscle is not modified, if the 462 THE BLOOD. heemorrhage lias been moderate and not repeated. The white corpuscles are more numerous ; but it may be asked if this is a result of the hsemorrhage itself, or only of the accompanying wound. Experiments on dogs and rabbits show that a wound, without hsemorrhage, is followed by as great an increase in the number of white corpuscles as if there had been hsemorrhage, while a very insignificant hsemorrhage with a wound — blood-letting from the jugular vein with a trocar, for example — does not lead to a marked increase in the number of white corpuscles (Malassez). Hence it may be concluded that, if white corpuscles are more numerous than usual, it should be principally attributed to the wound. Diarrhoea. — Diarrhoea and purgation are followed by an in- crease in the number of red corpuscles, evidently produced by the concentration of the blood. This concentration is carried to its extreme in cholera ; it disappears when the loss of fluid ceases. In new-born children who are athreptic, cachectic, and affected with diarrhoea, the number of corpuscles increases ; sometimes it is normal, which is doubtless due to the fact that the decrease of corpuscles caused by the ansemia is masked by the concentration of the blood due to the diarrhoja. In a man affected with malarial cachexia, and in an equally cachectic tubercular person, both the subject of diarrhoea, the number of red corpuscles is extremely small, less than 1,000,000 per cubic millimetre. Here, however, there is no contradiction, for the cachexia balaiices the effect pro- duced by the diarrhoea. Perhaps diarrhoea may, in the end, produce a diminution in the number of the corpuscles, like prolonged abstinence. Lead-poisoning. — There is a marked decrease in the number of red corpuscles in lead-poisoning ; they are larger than normally, but the increase of size does not compensate for their numerical decrease, for the corpuscular mass is less in the subject of lead- poisoning than in the healthy man. In lead-poisoning the red corpuscles are preserved intact in artificial serum much longer than normal corpuscles. Malaria. — In malaria there are many conditions of the blood to be considered ; first, in simple intermittent fever, there is after each access a considerable diminution in the number of red cor- puscles ; repair then takes place, but, as it has not time to be accomplished before the return of the next access, the aneemia becomes progressive. As recovery is approached, the reverse is the case ; the destruction of the red corpuscles is less in each access, and between the attacks the blood recovers more than it BLOOD CHANGES IN DISEASE. 463 has lost. In malaria, the size of the red corpuscles is larger than normal. The white corpuscles diminish in number after each access, more so proportionately than the red. Secondly, in ma- larial cachexia there is diminution of the red cor]^)uscles, and more particularly of the white. On passing an electric current through the spleen an increase of the number of white corpuscles in the blood follows, which increase disappears when the spleen returns to its normal size. Thirdly, in pernicious malaria the white corpuscles increase after each access, and at the same time melanemie granules appear in the blood. Some time after the access the white corpuscles return to the normal standard, and the melanotic granules disappear (Kelsch). Erysipelas. — In erysipelas the number of both white and red corpuscles diminishes, the white decreasing particularly at the termination of the eruption. During convalescence the proportion of corpuscles returns to the normal ; but if the erysipelas becomes phlegmonous, the number of white corpuscles increases, and only diminishes when the pus has free exit. There is also an increase in the number of white corpuscles when erysipelas attacks patients who are the subjects of scrofulous or lymphadenic hypertrophied glands. The blood taken from the erysipelatous parts is less rich in white corpuscles than that which comes from healthy parts ; at the same time the serum, which infiltrates the tissues in which the erysipelas is situated, is very rich in white corpuscles, as if these elements were entangled in the parts affected with the erysipelatous inflammation. Variola. — There is a considerable decrease in the number of red corpuscles in variola, which condition persists for a long time after recovery. The white corpuscles are, on the contrary, more nmnerous, particularly at the period of dessication of the pustules : they then return to their normal proportion, if complications or phlegmon do not supervene (Verstraeten). Typhoid fever. — In typhoid fever there is a decrease of the red coqrascles, and an increase of the white during the first week ; these elements return to their normal relations in the following weeks (Bonne). Acute and chronic glanders.— In horses affected with this disease there is a characteristic increase of the white corpuscles. Syphilis.- Immediately after the first accidents of syphihs there is a marked decrease in the number of both white and red corpuscles, particulariy of the red. Moderate doses of mercury cause this anaemia to rapidly disappear (N\ ilbouchewicz). In 464 THE BLOOD. syphilis of the new-born the red corpuscles are more numerous and paler than normally (Ciiffer). Cancer. — In cancer the red corpuscles are greatly diminished in number : they are also deiicient in haemoglobin, and diminished in size ; but this diminution of volume is not considerable enough to explain the deficiency of haemoglobin, which proves that the corpuscular substance is changed. Tuberculosis, — At the commencement of tuberculosis the number of red corpuscles is not sensibly modified ; but in cachetic tubercular subjects the number is much lowered, and may descend below 1,000,000 per cubic millimetre. "When there is improve- ment of condition, the number of corpuscles increases. The quantity of haemoglobin per corpuscle is below normal in tuber- cular subjects. Rheumatism. — In acute general rheumatism, notwithstanding the profuse perspiration from which the patients suffer, and which ought to cause concentration of the blood, a marked decrease in the number of red corpuscles is found, which leads one to suppose that the actual decrease in the number of corpuscles is much more considerable than indicated by numeration. The blood returns very slowly to its normal condition. In subacute uni-articular rheumatism, decrease of red corpuscles is still very manifest. During attacks of gout the red corpuscles are found to diminish in number, to be of large size, and to show much resistance to reagents. Interstitial nephritis and ansemia. — In interstitial nephritis and anaemia the red corpuscles are diminished in number, increased in size, and more resistant ; the number of white corpuscles is increased. Injections of carbonate of ammonia and creatin into the blood will produce the same troubles (Ciiffer). . Icterus. — In cases of simple icterus a marked diminution in the number of the red corpuscles has been observed (Malassez). Anaemia. — In the ansemia of miners the number of corpuscles may be normal, and it is rare to find low figures ; but the red cor- puscles are paler than normally (Fabre). Chlorosis. — In chlorosis the number of red corpuscles is some- times normal, sometimes increased ; the elements are always deficient in haemoglobin ; they are at the same time larger, which shows a profound change in the corpuscular substance since the corpuscles, though larger, contain less haemoglobin. Adenia. — In adenia characterised by hypertrophy of the lymphatic glands, either simple or accompanied with lymphadeno- LEUCOCYTHMMIA. 465 mata, and in cutaneous lymphadenia (fungoid mycosis) there is no increase in the number of white corpuscles, but the number of red corpuscles may be singularly diminished. Leucocytliseinia. — Leucocythaemia (Bennet), or leukemia (Virchow), is a disease characterised by persistent increase in the number of white blood corpuscles. Towards the termination of the disease the white corpuscles are as numerous, or even more numerous, than the red ; the blood is then of a pink colour, with- out having the ichorous appearance observed in hydreemia. There is always at the same time decrease in the number of red corpuscles, and this decrease may be sometimes so considerable as to make the number of white corpuscles appear larger than it really is. On examining preparations of leukaemic blood, without the addi- tion of water, the white corpuscles are seen in the form of granular bodies, of a size varying between 7 /i and 12 /t ; on the addition of water these corpuscles swell, become more transparent, and in some is perceived a single spherical nucleus, measuring 6 yii to 7 /i, in others two or more nuclei placed side by side. Virchow distinguishes between leukaemia with splenic hyper- trophy, in which large white corpuscles, containing one or many nuclei, predominate, and that in which there is a series of gan- glionic tumefactions, and where small uni-nucleated corpuscles are more numerous. Upon these different characters he bases lienal leukaemia, related to hypertrophy of the spleen, and ganglionic leukaemia, related to hypertrophy of the lymphatic glands. This distinction cannot be maintained, for, on examining the blood of a leukaemic person several days in succession, sometimes the multi- nucleated white corpuscles are seen to predominate, at others the uni-nucleated. We may add, moreover, that this distinction of Virchow's, founded on the analogy of the white corpuscles, with the cells of the spleen in one case, and with those of the lym- phatic glands in the other, is no longer admissible. It is known, in . fact, that the glands or new lymphoid organs contain in leukaemia larger elements than those of the splenic parenchyma ; further, that in leukaemic patients changes of the spleen, lym- phatic glands, and other lymphoid organs are most frequently coincident ; new lymphoid organs are even frequently produced in these patients, in the form of tumours (vide Lymphadenoma, p. 245). Besides the ordinary white corpuscles, some authors (Klebs, Erb) have described in leukaemia nucleated red corpuscles, which they consider as intermediate elements between white and red H H 466 THE BLOOD. corpuscles. We have searched in vain for these intermediate corpuscles in the blood of many leuksemic patients, without ever meeting with them ; more particularly in a case of leukaemia in the wards of M. Tillaux, in which the alterations of the blood were so marked that the number of white corpuscles exceeded that of the red, but we were unable, after repeated and minute examina- tions, to find a single white corpuscle coloured by hsemoglobin. Hany white corpuscles, particularly the largest, contain very small spherical granules of an amber-yellow colour, grouped round the nuclei. This appearance may be explained by the destruction of the red corpuscles, particles of which have been absorbed by the white corpuscles. Melanaemia. — By this name is signified the presence of pig- ment particles in the blood. This alteration, described for the first time by Frerichs, is seen when the spleen has undergone a series of congestive attacks, notably in malarial poisoning. We have met with it in Paris in the subjects of pernicious malarial fever. In the cases which we have observed, the particles of pigment present in the blood were round or angular, of a positive black colour, extremely small, of about 8 /i or 9 /* in diameter ; they were either contained in the white corpuscles, or enveloped in a thin and colourless granular zone, which very probably represented the protoplasm of a white corpuscle. In post-mortem examinations of persons who succumbed, most of the organs, particularly the spleen and liver, were found of a slate colour. On making sections of these organs, after hardening the fragments in alcohol, pigment granules were seen in the white corpuscles contained in the blood-vessels, in the vascular cells, in the cells of the perivascular connective tissue, and even in the cells of the parenchyma. The ^pUnchnic lymphatic glands were equally pigmented. Pathological pigment behaves in the same way as an inert granular substance contained in the blood, vermilion for example. On injecting fiuB powdered vermilion, suspended in water, into the blood of an animal, the particles are taken up by the white cor- puscles, and carried with them into the different organs ; they traverse the vascular walls, become dispersed, and finally fixed in the elements, which are the seat of the pathological pigmentation. There is reason to suppose that mfilanaemia is produced by pig- mentary transformation of the blood in the spleen, and the transportation of the pigment by the white blood corpuscles. Pigmented lymph cells are generally larger than others, and there- fore liable to accumulate in some of the blood-vessels and impede PARASITES OF THE BLOOD. 467 the circulation. These do not cause true embolism, as Frerichs and Virchow maintain, but phenomena similar to that of stasis of the white corpuscles in leukaemia (vide p. 248). Parasites of the blood. — At the present day there is reason to believe that most infectious and contagious diseases are due to the existence of microbia, which, after penetrating into the organism, grow and multiply, and are carried to the different organs by the circulation of the blood and lymph. If this is actually the case, these microbia ought to be apparent in the blood, at least during some stages of the disease. The presence, however, in the blood of definite microbia has only been assured by microscopical examination in two diseases : charbon (anthrax), and recurrent fever. The bacteridium of charbon (Davaine), Bacillus anthrads (Cohn), has been found by Davaine in the blood of animals affected with charbon, malignant pustule, splenic disease, etc. These microbia are found in the form of articulated and motionless filaments, which in simple micro- scopical observation do not differ from the bacteria developed in animal fluids, at the commencement of putrefaction ; but while inoculation with these fluids has no effect, or is only followed by more or less pronounced septicaemia, inoculation with charbon blood, even when very diluted (Davaine), produces the infection of charbon. In the blood of animals which continue to live after inoculation, bacteridia are found in more or less considerable numbers. Hence we are led to look upon these microbia as the veritable agents of infection. It is true that inoculation with charbonous or anthracoid fluids produces the accidents of infection, notwithstanding their having been submitted to the agents which kill Bacillua anthrads — alcohol, compressed oxygen (Paul Bert). But, as the researches of Pasteur have shown, though the bacteri- dium is unable to resist these reagents, it is quite otherwise with its spores, which afterwards, placed in favourable conditions, reproduce the parasites. We will not here enter into the discussion which has been raised, as to whether the disease is the direct result of the presence of the parasite, or if it is produced by a virus which is formed and developed simultaneously with the bacteridia. Though the data hitherto collected induce us to lean towards the first of these hypotheses, that of direct parasitic action, which is Pasteur's opinion, it must nevertheless be remembered that it is not yet established on an indisputable basis. In the blood of persons affected with recurrent fever, Obermeier H II 2 468 THE BLOOD. has found another microbium, also belonging to the family of Schizomycetes of Nsegele, which instead of consisting of recti- linear rods, Uke the Bacillus, is spiral. This is the spirillum Obermeieri. Extremely thin, the spirillum of recurrent fever has a length of one and a half to five times greater than the diameter of a red blood corpuscle : while the bacteridium of charbon is motionless, the spirillum of recurrent fever moves about in the pre- paration, turning over and over. It is not known if it is a distinct species, or if it belongs to the same species as the spirillum dis- covered in water by Ehrenberg, or as that which exists normally in the mouth. All these questions still require study. It will be understood that we cannot give them a larger space in an ele- mentary manual, which ought only to contain facts completely established. The filaria sanguinis hominis is a parasite existing in the blood in immense numbers. Eesearohes into the life-history of this hsematozoon have been made, within the last few years, by Bancroft, Lewis, Cobbold, Manson, and Stephen Mackenzie, and it has been satisfactorily proved that filaria is the cause of ele- phantiasis and chyluria. The filaria sanguinis is the embryo of a worm first dis- covered by Bancroft in Australia in 1876, and called by Cobbold the filana Bancrofti. This parasite inhabits a lymph channel in the human body, and has been found in situ by Manson. {Trans, of the Path. Soe. Lond. 1881.) A male and female live together ; the female is a long slender hair-like animal, three inches in length, and jig" in breadth ; it is semi-transparent, and while lying in the tissues is animated by wriggling movements ; the male is smaller. Manson contends that the filaria is vivaporons, and that the ova found in the lymph are aborted specimens. The filariie are transparent, structureless, snake-like worms, jij" in diameter, and move about with great activity. They are absent from the blood during the day, but as the night advances they appear and increase rapidly, and may number 100 or even more in every drop of blood, decreasing again as the day approaches. Dr. Stephen Mackenzie found in a recent case under his care in the London Hospital {Brit. Med. Jowr. Oct. 22, 1881) that on reversing the habits of his patient, and turning night into day, the filarise were found during the daytime and disappeared at night. The ovum measures about jij" in diameter, nearly six times larger than the embryo, which is simply the ovum stretched out ; it is too large to pass the lymphatic glands, and being inactive it acts as an em- bolus, and produces lymph stasis. Dr. Manson of Amoy has traced the double generation of filarise, and states that the embryos are abstracted from the human body at night by mosquitoes ; in the stomach of this animal they mature, and at the end of five or six days show a definite structure ; on the death of the mosquito they pass into the water of the wells and rivers, which, being drunk by men, the parasite enters the human stomach. It then bores its way into a lymphatic vessel, and passing against the current become finally located in a distant lymphatic vessel. In South China, where filaria is endemic, the hsematozoa would be found between sunset and sunrise in the blood of 10 per cent, of the native population. In a large proportion of cases the parasite gives rise to no accidents whatever, but Dr. Manson, in an able paper (ut supra), seeks to demonstrate that all the phenomena of elephantoid disease may be explained by infarction of the lymphatic glands by the aborted ova of the parent worm. — Teanslatoe's Note. 469 CHAPTER VIII. MORBID CHANGES IN THE HEART. The anatomical changes in the three constituent parts of the heart, the pericardium, the myocardium, and the endocardium, will be successively considered. I. Lesions of the Pericardium. Esmorrhage. — Haemorrhage into the pericardium is of two kinds: first, ecchymosis of the membrane; secondly, haemorrhage into the pericardial cavity. Ecchymoses are more frequent in the visceral than in the parietal layer ; when recent, they appear as lenticular spots, of an uniform red colour ; they are sometimes confluent, forming extensive areas with sinuous margins ; they are seen in asphyxia from whatever cause, in leucocythaemia, purpura, scurvy, etc., or they complicate inflammatory lesions of the pericardium, in which case they properly belong to hemorrhagic pericarditis. Haemorrhage into the pericardial sac is consecu- tive to inflammation or to rupture of the heart, or a large vessel covered by the visceral layer of the pericardium; for example, rupture of an aneurism in the ascending arch of the aorta. Dropsy of the pericardium. — The quantity of fluid found in the pericardium twenty-four hours after death always exceeds thirty grammes ; if the fluid is much more abundant, as is observed particularly in general dropsy, there is said to be dropsy of the pericardium. In this fluid are found lymph cells and epithelial cells detached from the serous membrane, isolated or in flakes, and which almost always contain fat granules. In pericardial fluid which is normal or more abundant than usual, articulated and motionless bacteria of exceptional size are fre- quently found. We draw no conclusion from this fact regarding their genesis. Gas is sometimes present in the pericardium of subjects in which the process of putrefaction has already com- 470 MORBID CHANGES IN THE HEART. * menced : it must not, however, be concluded that these gases have been present during life, and the existence of a morbid pneumatosis be assumed. Inflammation of the pericardium. Pericarditis. — Fibrinous inflammation of the pericardium does not differ from fibrinous inflammation of other serous membranes, except by the naked-eye appearances of the solid exudation. It is most frequently general over the whole extent of the pericardium, but it may also be limited, particularly at the base of the heart, to the origin of the aorta and large vessels. The exudation is deposited on both sur- faces of the pericardium, in a layer which is papillary in appear- ance. They are not true papillae, for the connective tissue and blood-vessels of the serous membrane take no part in their formation ; this may be ascertained by detaching the false mem- brane, which is smooth at its union with the pericardium. The solid pseudo-membranous exudation is solely composed of fibrin, cells derived from the endothelium, and pus cells. The papillary filaments on its free surface have been compared to the papillae on the tongue of a cat ; they are more or less flat or elongated, and their form is very variable ; they are even observed when the layer of fibrin is extremely thin ; they are produced by the move- ments of the heart in the pericardium, when the fibrin is under- going coagulation. As to the formation of fibrin, we refer the reader to what has been said on inflammation of the serous membranes in general {vide, p. 422). In pericarditis of many days' standing, old dilated capillaries may be already found at the base of the fibrinous projections, or newly formed capillaries. These vessels are then surrounded by a variable quantity of embryonic cells. As to the exudation itself, it contains, besides fibrin, cellular elements, white corpuscles, and cells of various shape derived from the endothelium. Fibrinous pericarditis occurs in acute articular rheumatism, pneumonia, scarlatina, variola, Bright's disease, and in abscesses of the neck and mediastinum. Hsemorrhagic pericarditis is met with in tuberculosis, cancer of the lungs, and in cachectic disease. It differs from, the preceding only by the presence of red corpuscles in large numbers, or the products of their decomposition, hsematin and haematoidin, in the fluid and solid parts of the exudation. In this disease the limita- tion of the serous membrane and the exudation is not defined, as in simple pericarditis ; dilated blood-vessels with embryonic cells penetrate the serous membrane and form loops in the fibrinous PKRICARDJTIS. 471 exudation ; they are surrounded with embryonic cells, and they produce haemorrhages in the exudation itself. In tubercular pericarditis, in which haemorrhages are frequent, the tubercular granulations are formed in the substance of the pericardium, or in the vascular parts of the exudation. When the pericardium and exudation are invaded by a great number of tubercles, caseous degeneration of the exudation may occur. It may then become partly detached and form, together with blood clots undergoing retrogressive metamorphoses, grey or ochre- coloured irregular masses, which are free in the cavity of the peri- cardium. Under the microscope are found fat and haematin granules, and crystals of haematoidin, and, if the disease is chronic, calcareous granules. In certain cases of chronic tubercular pericarditis a thick layer of embryonic tissue, studded with tubercular granula- tions, is found on both layers of the serous membrane. In a case which we examined, these two layers of granulations were united by a layer of fibrous tissue which had been long formed ; the tuberculosis of the pericardium was primary, and accompanied only with a recent eruption of discrete tubercle in the left pleura. Purulent pericarditis is more rare than the preceding ; it is characterised by the presence of a large quantity of pus, which gives to the fluid parts of the exudation a creamy appearance, and makes the false membrane opaque. This purulent exudation may undergo caseous and calcareous degeneration like haemorrhagic exudations. Adhesions of the pericardium, in consequence of inflammation, are not very frequent, particularly on comparing them with those of the pleura. Incomplete adhesions are characterised by laminae or filaments of vascular connective tissue, and are_usually located at the base of the heart, between the visceral and parietal layers near the aorta and large vessels ; they are also found at the apex of the heart. Complete adhesion of the pericardium annihilating the cavity may be seen in consequence of acute pericarditis, chronic peri- carditis, or tuberculosis of the pericardium. It is most frequently impossible to ascertain the existence of these adhesions during life, and when found by chance at post-mortem examinations it is often diflicult to assign them a cause. Among lesions resulting from pericarditis, or as a form of subacute or chronic pericarditis, may be enumerated the small and wart-like vascular projections, or the projecting plates composed of lamellar connective tissue, which are found on the visceral layer, particularly at the origin of the aorta and the auricles. These growths are often covered with thin 472 MORBID CHANGES IN THE HEART. layers of fibrin. This tissue of new formation may, as we have already pointed out, undergo stony change in the pericardium as well as in other organs ; a calcareous carapace is then formed of variable extent, and which often sends processes into the sub- stance of the cardiac muscle. Most frequently the calcareous plate is not exposed in the cavity of the pericardium, but is covered by a delicate layer of fibrous tissue. Milky patches have been considered by most authors as having an inflammatory origin ; they are generally smooth, opaque, and pearly ; they usually form a slight elevation upon the surface of the membrane, and are particularly found on the anterior surface of the ventricle. They are very variable in size, and have irregular sinuous borders; they are very frequent (45 in 150 autopsies: Bizot), and are composed of lamellar connective tissue and elastic fibres. Primary carcinoma of the pericardium is very rare. Forster has seen a single example of it. Secondary carcinoma is, on the contrary, rather frequent ; it grows into the pericardial cavity in the forin of nodules, causing pericarditis which is generally hsemorrhagic. II. Lesions of the Myocardium. Atrophy. — Atrophy of the heart is met with in cases of general atrophy of the muscles of the economy ; in cachectic diseases of long duration, as in phthisis or at the end of typhoid fever, etc. The form of the heart is not modified when atrophy is general. The coronary arteries, which do not participate in the atrophy, are tor- tuous and prominent ; at certain points in their course the visceral pericardium forms a membrane over them. Atrophy may be so marked that the visceral layer of the pericardium is wrinMed. Great authorities on pathological histology — Forster among others — affirm that in atrophy there is a diminution of the size of the muscular fibres; but this is extremely difficult to appreciate, owing to their great variations in diameter in the normal con- dition. Atrophy of the heart may be observed, accompanied with an abundant formation of adipose tissue under the visceral pericar- dium, so that, though the cardiac muscle is atrophied, the heart appears at first sight to be normal in size ; but on dividing the organ with a scalpel, the sub-pericardial adipose tissue is found to be considerably thickened, and from it are sent out irregular pro- HYPERTROPHY OF THE HEART. 473 longations between the fasciculi of the myocardium. This lesion resembles in every way adiposity of the voluntary muscles. The degree of the lesion varies ; sometimes the atrophy is so pronounced that the muscular power of the ventricles is much reduced. Hypertrophy. — Hypertrophy of the heart is generally related to exaggerated action in disease of the valves or large vessels, when increased force is required to overcome an obstacle to the blood current. It most frequently affects only one ventricle, the left, for example, in lesions of the aortic orifice. Traube referred hyper- trophy of the left ventricle in atrophy of the kidney to the same cause. The coincidence of hypertrophy of the left heart and atrophy of the kidney is incontestable; but the explanation of Traube is nevertheless open to discussion, for it is difficult to understand how a hindrance to the circulation in so small a number of blood-vessels could produce so marked an increase of action on the part of the heart. Hypertrophy is general or partial. The shape of the heart is not notably modified in general hypertrophy ; in hypertrophy of the right ventricle the apex of the heart is large and blunt, being composed of the apices of both ventricles, which are then at the same level. In hypertrophy of the left ventricle the apex of the heart is, on the contrary, entirely formed by itself. Thickening of the endocardium is constantly observed in hypertrophy of the heart, and to it is due some of the indmration and rigidity of the cardiac walls. The muscular fibres of the hypertrophied parts show no lesions of nutrition, or they may have undergone fatty or pig- mentary degeneration. It is not known at present if hypertrophy is entirely due to an increase in size of the muscular fibres of the heart, or to a new formation of these fibres. The phenomena of the development of new muscular fibres have, however, never been observed in cardiac hypertrophy, so that the first of these hypotheses is the more probable ; it rests on the observations of Forster, who asserts that in cardiac hypertrophy the primitive fasciculi are increased in size. Fatty degeneration. — Of all the muscles of the organism, the heart is that which most frequently undergoes fatty degeneration. When all the muscles of the body are subjected to the same influ- ences capable of producing fatty degeneration, the heart may be alone affected. This is what occurs in the foetus which remains a 474 MORBID CHANGES IN THE HEART. week in the uterus after it has died ; the voluntary muscles do not contain fat granules, while the cardiac fibres are filled with them. Important changes are, however, found in the voluntary muscles ; the colouring matter is separated in the form of pigment granules, which are located under the sarcolemma in the protoplasmic sub- stance of the primitive fasciculi. Fatty degeneration of the heart may be found in atrophy and hypertrophy, in poisoning from phosphorus or arsenic, in acute diseases such as typhoid fever, variola, leucocythsemia, etc., and in endocarditis and pericarditis ; it may be present throughout the whole of the myocardium, or be only partial. The altered parts appear to the naked eye to be grey or yellowish, and slightly opaque, clearly distinguished from the healthy parts, which are Fig. 233. — Muscular Fibres of the Heart partially degenerated, FROM a case of Phosphorus Poisoning. slightly translucent and of a more positive red colour ; but it must not be thought that fatty degeneration can always be recognised with the naked eye, for occasionally the opinion formed a, priori is not confirmed on microscopic examination. The muscular fasci- culi present very varied degrees of granulo-fatty change ; some- times only a few fine granules are perceived scattered through aU the fascicuU, but which do not completely hide the striations ; at others the change is so advanced that the cardiac fasciculi resemble cylinders formed entirely of fat granules. Pigmentary degeneration.— In adult and old age yellow granules, the nature of which is unknown, are often found round the nuclei of fasciculi of the heart in the normal condition. From their colour it has been thought that they are formed of a pigment derived from muscular hasmoglobin. In chronic diseases producing HAEMORRHAGE OF THE MYOCARDIUM. 475 marasmus, and in feeble old age, the atrophied heart is seen to be of a brown colour, and its muscular fasciculi contain a much larger number of these peculiar granules than in the normal condition ; the dark colour is due to their presence. In simple melanosis, pigmentary infiltration of the heart is seen, differing from the preceding by the black colour of the granules, by their location in the connective tissue and muscular tissue simultan- eously, and by the limitation of the degeneration to points or small areas {vide p. 315). Hsemorrliage of the myocardium. — Congestion of the myocar- dium may exist during life, and be simply surmised after death. Haemorrhage, on the contrary, leaves evident traces. It generally occurs in the form of ecchymotic spots on the external or internal siuface of the heart. Ecchjrmoses are most frequently produced in diseases which terminate by asphyxia — diseases of the heart or lungs — and in certain cases of poisoning — by phosphorus, arsenic, etc. ; and in leucocy thsemia, purulent infection, and puerperal fever. The blood effused between the muscular fibres of the heart soon undergoes coagulation, so that hard nodules of a red or brown colour are formed ; the muscular fasciculi included in these no- dules undergo fatty degeneration. Sometimes at autopsies blackish spots are unexpectedly found in the myocardium, which were probably caused by old haemorrhages, since the interfascicular connective tissue is found in these spots to be infiltrated with pig- ment granules, and the muscular fasciculi are equally pigmented. Profuse cardiac haemorrhage occurs in consequence of ruptures of the myocardium, which may be primary, or the result of fatty degeneration or aneurisms. Eupture due to fatty degeneration is simple or multiple ; Andral reports a case in which there were five distinct rents in the myocardium. The rent is always from within outwards, and of irregular shape ; if death is not instan- taneous the blood infiltrates and separates the muscular fasciculi, causing diffused interstitial haemorrhage. If the rent does not extend as far as the pericardium, an aneurism is produced, diffuse at first, but which may become circumscribed later ; but most frequently the pericardium is also torn, in which case the peri- cardial cavity is, after death, found filled with partially coagulated blood. In a heart in which such a rupture has occurred, fatty degeneration of the muscular fasciculi will invariably be found, and the degeneration is always more marked in the vicinity of the hspmorrhagic focus. 476 MORBID CHANCES IN THE HEART. Aneurisms of the heart are principally seen in the ventricular septum and at the apex of the left ventricle. Aneurisms of the septum and base of the heart are generally the result of the extension of a valvular aneurism ; those at the apex of the heart — the most frequent of all — ai-e probably the result of fatty degeneration, or a combined inflammation of the endocardium and myocardium ; but all the phases of development of the aneurismal sac cannot be followed in this situation as in the aorta, whence it is only by conclusions drawn from analogy that the mode of their formation can be understood. Aneurism of the apex of the heart is in the form of a sac, varying in size from a nut to that of the heart itself. When the sac is very small, it may be said to be contained in the substance of the cardiac wall, and is only diagnosed on opening the heart. The communication between the ventricle and the sac of the aneurism is by means of a large funnel-shaped opening, or by a ring-like orifice. The wall of the aneurism is rigid, so that the aneurismal sac is not emptied at the moment of the ventricular systole ; stasis is nevertheless not so complete as to produce laminated clots, as in aneurisms of the aorta. At the autopsy, recent fibrinous clots are most frequently found in the sac, but when the aneurismal sac is anfractuous, dense fibrinous clots are seen adherent to the wall. The internal surface of the aneurismal sac is generally smooth ; sometimes it is irregular and anfrac- tuous. In order to examine the wall of an aneurism under the micro- scope, portions are removed and fixed with pins on to a sheet of cork, and then dried. It is better to immerse the specimen in alcohol for a few days before submitting it to dessication. Delicate sections are then cut in different planes, stained with carmine, washed and mounted in glycerine to which acetic acid has been added. In these preparations are observed collections of flat cells, which seen sideways seem to be thin and fusiform, owing to their centre being swollen by the nucleus ; they are separated by bundles of connective tissue and blood-vessels. The wall of the aneurism may be entirely formed of this tissue, but it is most frequently found only on the internal surface of the sac, muscular fibres grouped in small bundles, or isolated in the midst of collec- tions of small cells, being found on the external surface. In fresh specimens, the cells may be obtained by scraping, and may be examined on all sides. They closely resemble the cells of adult connective tissue, of which fact we have felt no doubt since INFLAMMATION OF THE MYOCARDIUM. 477 N. Pelvet made a remarkable research on this subject in our laboratory. When these cells float freely in the fluid of the pre- paration, they successively present edges, surfaces, and folds, by which they are recognised as flat cells of extreme thinness ; their outline is sinuous, and they send out processes which are flat like the body of the cell. The shape of these cells, their arrangement in collections parallel to the internal surface of the aneurism, are due to the pressure exercised by the blood. The same cells and the same tissue are found in aneurisms of the arteries, for they are produced whenever the blood in circulation is brought into con- tact with newly formed layers of connective tissue. Aneurisms produced by extension of valvular aneurisms (p. 484) are generally diffused, or the sac is very anfractuous and contains irregularly arranged clots. These aneurisms, which are generally lot'ated in the interventricular septum, bring about its destruction, and communication between the two ventricles. The tissues are torn or separated, so that shreds are pushed into the right ven- tricle. The muscular fibres bordering these aneurisms, the direc- tion of which is generally slanting, are torn and show granulo- fatty degeneration. Inflammation of the myocardium. — We do not consider myo- carditis to be characterised by fatty degeneration of the muscular fibres of the heart ; for this degeneration may exist in a number of cardiac afiections or general diseases, which have nothing in com- mon with inflammation ; on the other hand, fatty degeneration of the muscular fibres is not observed in those cases of myocarditis, which are characterised by increase of the connective tissue of the myocardium. Muscular fibres only undergo fatty degeneration in myocarditis when they are compressed by exudations or pus cells, as, for example, in abscess of the heart ; in which case the fatty degeneration does not differ from that observed in haemorrhage of the heart. This leads us to positively deny the existence of the parenchymatous myocarditis of Virchow, which is essentially characterised by fatty degeneration of the myocardium. Myocar- ditis may be produced by extension of endocarditis and peri- carditis, or as a symptom in purulent infection —puerperal fever, pyaemia — when it is characterised by intra-muscular abscess. Abscess of the heart is very rare ; it varies in size from a pin's head to a nut. The pus is either deposited between the muscular fibres, or it is encysted within a zone of embryonic tissue. In the 478 MORBID CHANGES JN THE HEART. first case, the muscular tissue in the vicinity of the abscess is slate-coloured ; the pus contains the debris of muscular fasciculi when the suppurative inflammation is recent. In the slate- coloured zone surrounding small non-cysted abscesses are found muscular fasciculi filled with fat and pigment granules, and separated from one another by pus cells, blood corpuscles, and brown granules. Encysted caseous masses are sometimes met with in the midst of the muscular tissue of the heart. Forster thinks they result from the metamorphoses of old abscesses. There are a few cases on record of anfractuous cavities hollowed in the cardiac muscle and opening into the left ventricle. These cavities h^ive been regarded as abscesses, which have opened and discharged their contents into the torrent of the circulation ; but at the present day these cases are interpreted as being aneurisms following endocarditis. Interstitial myocarditis, or cardiac sclerosis, is much more fre- quent than was formerly supposed ; it is often observed in cardiac hypertrophy, and particidarly in interstitial nephritis.' The newly formed fibrous tissue, which is developed between the muscular fasciculi, is generally continuous with the deep layer of connective tissue of the endocardium, thickening of the latter being also often observed. Connective tissue, composed of fibres and cells, is also found, particularly round vessels, arterioles, and small veins, the tunica externa of which is thickening. The muscular fasciculi contained in this new tissue are sometimes normal in size, sometimes atrophied. The connective tissue is sometimes arranged in a regular manner round the muscular fasciculi, or it may be found in the form of plates or islets. This lesion is diffi- cult to recognise with the naked eye, except in hardened specimens, which are divided and the surface stained with carmine : the sclerosed parts are then seen to be red. To justly appreciate this change the same parts of the heart, determined beforehand, must always be compared ; thus, transverse sections of the musculi papillares of the left ventricle, from a series of healthy and diseased hearts, would give perfectly comparable results. Tumours of the myocardium. — Grummata have been recognised in the cardiac muscle (Kicord, Virchow), and secondary nodules of ' LetuUe, Tkise de Doetorat, 1880 ; Debove and Letulle, Archiv. gen. de med. Mars 1880. HISTOLOGY OF THE ENDOCARDIUM. 479 carcinoma and epithelioma (Paget, Liouville). Eecklinghausen has published a case of striated myoma in the heart of a new- bom child. Thirty cases of hydatid cysts of the heart, almost always due to echinococci, have been recorded. These cysts may project into one of the cavities, for example into the right auricle, or they may rupture, or even become free without rupture. Normal histology of the endocardium.— The endocardium, which Hnes the whole internal surface of the heart, is composed of three layers : first, the endothelium formed of a single layer of flat cells • second, a layer of flat cells separated by a laminated ground substance ; third, a layer formed of elastic tissue and connective- tissue fasciculi. The first of these layers generally disappears twenty-four hours after death, that is to say, at the time the autopsy is made. The lamellar layer is very thin on the ventricles and on the two surfaces of the arterial and auriculo-ventricular valves ; it is thicker on the auricles, and more so upon the left auricle than the right. The cells of this layer are thin, and have more or less numerous processes ; they contain a lenticular nucleus, and are arranged parallel to one another, and are flattened towards the internal surface of the endocardium. The ground substance which separates them seems to be shghtly fibrillated, or almost hyaline, so that at first sight the endo- cardium seems to be limited by an anhistic membrane. The thickness of this layer, measured in preparations obtained after dessication, soaked in carmine, and treated with acetic acid, varies fi'om 6 /^ to 10 /I. This layer, as well as the endothelium, is con- tinuous without interruption, and passes from the superior to the inferior surface of the valves. The layer of connective and elastic tissue of the endocardium varies most according to the different regions of the heart ; and sometimes so considerably that, for example, in the left auricle, where it is most developed, it is almost ten times thicker than in the ventricles. This layer is on one side directly continuous with the layer of flat cells, and on the other with the connective tissue which separates the muscular fasciculi. Fig. 234 represents at A a section of the ventricular endocardium, in which the layer of flat cells is seen at a, the fibro-elastic layer at 6, and the connective tissue which unites these to the muscular fibres at c. It is composed of cells and elastic fibres ; the latter are very delicate, and are arranged in layers parallel to the surface in the endocardium of the auricles ; they are very niunerous and pressed together : it is these 48o MORBID CHANGES IN THE HEART. fibres which give the surface of the left auricle the opaque, yellowish-grey appearance which it has normally. In the elastic layer of the ventricular endocardium the fibres are much less close. In the auriculo-ventricular valves, the fibro-elastic layer of the auricle is continued upon the upper surfiace of the valves, becoming thinner ; the fibro-elastic layer of the ventricular endo- 1 Pig. 234. — A^ section of tlie Tentricular endocardium : a, internal layer of flat cells; b, fibro-elastic layer; c, transverse section of muscular fibres. Magnified 150 diameters. B, section of a sigmoid valve of the aorta : d, layer of flat cells on the superior surface of the valve ; d', the same , layer on the inferior or ven- tricular surf ace ; e,/, fibro-elasticlayerof the aortic portion of the valve; /', fibro-elastic layer of the ventricular portion of the valve. C represents a section of an entire sigmoid valve "with its insertion into the fibrous ring of the aorta : n, base of this ring ; m, fibro-elastic portion derived from the aorta ; p, fibro-elastic portion derived from the ven- tricular endocardium ; o, elastic fibres. Magnified 12 diameters. cardium is continuous upon their .under surface; it is much thinner than the preceding, and it gives origin to the tendons of the musculipajoillares. The two elastic layers are separated from one another, in the substance of the valve, by a very thin layer of connective tissue. Hence, on section of the valve, at its firee ENDOCARDITIS. 481 edge and both on its superior and inferior surfaces, may be dis- tinguished the endothelium and the lamellar layer ; then the two superior and inferior layers of the fibro-elastic tissue, the superior being the thicker, and finally at the centre a delicate layer of connective tissue. As we shall see later, it is always the superior or auricular surface of the auriculo-ventricular valves which is primarily altered, and also most extensively so in valvular endo- carditis. The arterial valves result from the union of the ventricular endocardium on the one side with the internal membrane of the artery upon the other (fig. 234, B and c). Beneath the epi- thelium is seen the lamellar layer (b, d and d'\ which is con- tinuous and reflected at the free border of the valves. This layer is thicker upon the ventricular surface d' than upon the arterial surface d. The fibro-elastic tissue, which separates the two imited layers, is very thick at the origin of the valve (c, m). The internal arterial membrane forms foiu: fifths of this thickness ; thus on treating a section with acetic acid, which causes the thickened connective tissue of the upper siu-face to swell, it curls over, as is shown in fig. 234, c. We shall see later that valvular endocarditis is generally found on the internal surface, near the free border of the arterial valves, in the layer of flattened cells, which is thicker here than upon the external siu-face (b, d'). Pathological Histology of the Endocardinm. Endocarditis. — Acute endocarditis occurs in acute articular rheumatism, puerperal fever, eruptive fevers, etc. The left ventricle is of all the cavities of the heart that in which it is most frequently met with, particularly on the aortic and mitral valves ; and it is the auricular surface of the mitral and tricuspid valves and the ventricular surface of the aortic valves which are always primarily affected ; that is to say, the surface of the valves which experiences the friction of the blood, in passing either from the auricles into the ventricles, or from the ventricles into the arteries. The old pathologists held redness to be of exaggerated importance in the anatomical diagnosis of endocarditis ; but, if not seen in the form of vascular aborisation, this redness simply indicates im- bibition, and is seen simultaneously upon the endocardium and upon the tunica interna of the blood-vessels. It is due to the impregnation of these membranes with the colouring matter of the blood, derived from the corpuscles which have been destroyed I J 482 MORBID CHANGES IN THE HEART. either by an infectious disease, such as pyaemia, variola, or by the rapid decomposition of the cadaver, as may be observed in hot and stormy weather. Endocarditis is essentially characterised by vegetations, and by erosion and ulceration of the endocardium, which often lead to perforation and laceration of the valves. The vegetations, which constitute the essential phenomena of endocarditis, are often extremely small and numerous, so that they give to more or less extensive areas of the membrane a roughened or granular appearance : they may extend uniformly over a large surface of the auricle or the left ventricle. They are observed in this state at the commencement of endocarditis, but if the disease lasts some time they attain a larger size, which may equal that of a pea ; they are extremely varied in shape, they may be conical, num- mular, or raspberry-shaped, or even of the form of very long and delicate villi. Some groups of vegetations are very irregular, and are sometimes arranged on the borders of the sigmoid valves, or on the borders of the auricular surface of the mitral valve, near the insertion of the tendineae, forming regular wreaths. Their situation is determined by the limit of the vascular network at the border of the valves. Thus, in the sigmoid valves they are not found on the sharp edge, but always at a little distance from it ; this arrangement is particularly well marked in endocarditis which has been rapid and related to puerperal fever or acute articular rheumatism. The largest vegetations are only found on the valves or on the fibrous zone of the cardiac orifices. When the course of endocarditis is irregular and slow, the vegetations are very unequal in size. In the chronic forms they are less prominent, and rest upon an indurated base, and are hard, cartila- ginous, and often opaque, while in the acute forms the recently formed vegetations are soft, friable, and semi-transparent- The semi-transparency and brittleness of recent vegetations caused them to be long considered as composed solely of fibrin, though their adherence to the endocardium should have destroyed this hypothesis. On removing them with the nail, a loss of sub- stance is seen in the membrane beneath, which shows very distinctly that the vegetation formed part of the membrane. This may be demonstrated by means of microscopical examination. After spreading the endocardium and the valves on a layer of cork, and submitting them to dessication, delicate vertical sections are cut, which, when stained with carmine, treated with acetic acid, iind mounted in glycerine, show the following characters : in acute THE VEGETATIONS IN ENDOCARDITIS. 483 endocarditis the vegetations are formed entirely of embryonic tissue, which is continuous with the endocardium beneath and around the vegetations for a more or less extensive zone. This zone of proliferation should be studied with care, if the mode of formation of endocardial vegetations is to be understood. It will be observed that it is not sharply defined, but that from the healthy parts to the inflammatory foci there is a progressive multiplication of cells. The neoplasm is produced in the layer of flattened cells ; the flat cells also concur, but it is nowhere shown that a certain number of cellular elements do not come from another source, for example by diapedesis of white corpuscles from the capillaries of the endocardium. The vegetations are coverd with a hyaline layer formed of fibrin, which is more or less thick, though occa- sionally extremely thin ; in covering the vegetations it may be prolonged in the form of delicate filaments, which may attain a great length. In chronic endocarditis the vegetations have a difi'erent struc- ture : the cellular elements, instead of being round, are elongated or flattened, they are separated by a fibrillar intercellular sub- stance, always very abundant, and which gives them their cartilaginous consistence ; the indurated plates on which they are implanted present a similar structure ; in a word, the tissue which forms these vegetations and their bases recalls the structure of the internal layer of the endocardium. According to what is known regarding the course of all inflammatory products, it may be aSirmed that all hard and prominent plates were originally soft vegetations, which have afterwards undergone fibrous organisa- tion. In the chordae tendinese of the mitral valves are observed the phenomena of acute or chronic endocarditis. In the first the chordae soften though increased in size, and become so brittle that they may break at the moment that the valve acts. In chronic endocarditis hypertrophied chordae tendinese are frequently met with ; they are diminished in length, are rigid, of cartilaginous consistence, and smooth upon their surface. Instead of undergoing ultimate fibrous change, the soft vegetations of endocarditis may, under the influence of the shock of the blood, become easily torn ofi" or into fragments, so that in their place are found irregularly torn shreds and loss of substance. The friable nature of these neoplasms results from the great number of cellular elements produced by acute inflammation. Exaggerated formation of cellular elements, coupled with insufficient nutrition, 484 MORBID CHANGES IN THE HEART. may sometimes cause their fatty degeneration, and the growing tissue of the neoplasm becomes disorganised, and an ulcerated anfractuous surface is then formed, in the borders of which are found granulo-fatty cells, free fat granules, and blood pigment. The portions which are torn, softened, and separated by the force of the blood-current are extremely small, and may be carried as far as the capillaries, or, if larger, they are arrested in the arterioles, producing septicaemia and embolism. This collection of symptoms has received the name of ulcerative endocarditis, but it does not constitute a distinct species apart from other forms of acute endocarditis. Some authors having, however, at the autopsy of persons who have died from ulcerative endocarditis, following puerperal fever for example, found bacteria in the base and edges of the fungoid ulcers of the endocardium, they have referred the septicsemic processes to these microscopical organisms, Klebs considers that the granular substance which covers the altered valves and the vegetations in ulcerative, rheumatic, or puerperal endocarditis is composed of a layer of micrococci. Valvular aneurisms. — The lesion described under the name of valvular aneurism (Thurnam, Forster, Pelvet) is a consequence of acute endocarditis, located in the valves. Multiplication of the cells, their embryonic condition, softening of the intercellular substance, and disappearance of the elastic fibres, phenomena due to endocarditis, cause the valve to lose its power of resistance, so that it is unable to support the pressure of the blood. "When, in acute endocarditis, all the layers of the valve rapidly undergo softening, it is first distended and may soon rupture ; if the pro- gress of the inflammation is, on the contrary, slow, the valve only becomes slightly less resistant, and is gradually distended without being ruptured. Valvular aneurism has hitherto been only observed in the left heart, in the aortic and mitral valves. In the semi-lunar valves the orifice of the aneurism is always to be found on the superior or arterial surface ; in the mitral valve it is always on the inferior or ventricular surface : this arrangement results from the direction of the blood pressure, which, the valves being shut, is from below upwards on the mitral valve during ventricular systole, and from above downwards on the semi-lunar valves during ventricular diastole. At post-mortem examinations two forms of these aneurisms are found : first, a valve softened by infiammation may become VALVULAR ANEURISMS. 485 distended throughout, and may remain in this state, which shows that, the inflammation having disappeared, the tissues of the valve have recovered their original firmness ; second, the endocar- ditis continuing to be acute, one or more valves show ruptured aneurismal sacs upon parts of their surface; they are cup or funnel-shaped, and the holes in them are regular or torn ; the edges of these rents are often formed of greyish, torn flakes, covered with a thin layer of fibrin, with projections towards the ventricle, on the sigmoid valves, and towards the auricle on the mitral valve. On examining these flakes by the method already indicated (section after dessication), nuclei and round cells are recognised, imbedded in a granular substance, and in the midst of Fio. 235. — Aneukism of a Sigmoid Valve of the Aorta. The aneurismal sac, d, projects at the lower part of the valve ; the orifice of the aneimsm situated on its upper surface is not visible in the figure. In this case, the sac is already ruptured at 6. a, vegetation in the adjoining valve. this embryonic tissue neither fibrillar connective tissue nor elastic fibres can be found. The entire wall of the aneurismal sac is composed of the same tissue which is always met with in the substance of recent aneurismal sacs, whether intact or ruptiured. Eound or funnel-shaped valvular aneurisms are rarely seen without lacerations. When the sac has not been broken up into fragments by the blood pressure at the moment the valves close, there are more or less extensive rents, though these may be very small. We have, for example, seen an aneurism of a sigmoid valve of the aorta, in the form ofa very long funnel, the extremity of which was simply perforated. The vegetations and thickening of the endocardium produced 486 MORBID CHANGES IN THE HEART. by acute inflammation near the valves is a cause of stenosis of the orifices ; but stenosis and incompetency are most frequently produced by simple chronic endocarditis. Chronic endocarditis. — To chronic endocarditis is referred a series of cardiac lesions particularly found round the orifices ; some of which are due to acute endocarditis which has become chronic^ and others, of which the evolution is slow, are often observed in alcoholic subjects, in old age, and in lead-poisoning, etc. Chronic endocarditis is essentially characterised by semi-transparent or opaque cartilaginiform thickenings. In a great number of eases these nodules become infiltrated with calcareous salts and ossi- form. Sometimes, however, these vegetations are formed of mucous tissue ; they may acquire a considerable size, and even become united so as to form a single mass. M. Curtis has published a remarkable example of this {ArcTvivea de 'physiologic, 1874). It is particularly upon the fibrous zone of the orifices, in the chordse tendineae and valves, that the lesions of chronic endocarditis are usually observed. They have a strong resemblance to the lesions of endarteritis deformans, about to be described, and it is probable that in the endocardium, as in the arteries, primary atheroma plays a certain part. The lesions of the valves in chronic endocarditis have the form of globular or wart-Uke vegetations, situated particularly on the ventricular surface of the sigmoid valves, and on the auricular surface of the auriculo-ventricular valves. The chordse tendinese of the auriculo-ventricular valves are thicker, shorter, and indurated ; the fibrous zone of the orifices is hypertrophied and indurated. When the heart is dilated in consequence of the blood pressure, the fibrous rings of the orifices often undergo similar dilatation. At other times, on the contrary, these rings are thickened and show marked contraction. The valves themselves are two, three, or four times their normal thickness, their tissue is rigid, and their edges are roughened and irregularly thickened ; equally thickened at their origin, the fibrous zone, to which they are attached, shows similar induration. It hence results that the general shape of the orifices is greatly changed. Incompetency and contraction may exist at the same time — incompetency from rigidity of the valves, and contraction from new growths on their edges : it is, in fact, rare for contraction not to be complicated by incompetency. FORMATION OF CARDIAC BLOOD CLOTS. 487 Microscopical sections of the indurated tissues show profound changes in the structure of the endocardium. Instead of finding the successive layers which have been described, and which are so characteristic of each part of the valves and orifices, only irregular collections of flat cells are found, separated by a fibrous substance or irregularly distributed elastic fibres. Cellular development has produced this disorganisation of the tissues, and has been the point of departure of a new organisation, which tends to reproduce the primitive structure, without ever completely succeeding. In this imperfect fibrous tissue, centres of fatty degeneration are constantly found, which, on becoming united, form atheromatous foci filled with granular detritus. These foci remain stationary or open on to the surface. The formation of calcareous plates and granules, or true petrifactions, are very often observed in the indurated tissues of chronic endocarditis. At the commencement of this disease the new formation of cells takes place in the layer of flat cells ; when, in consequence of this development, new fibrous layers are produced, they evidently tend towards cicatricial con- traction. Hitherto, however, this process has not been followed under the microscope. The formation of blood clots in the heart. — At the autopsy the left ventricle is most frequently found collapsed and emptied of blood, except a few filamentous clots between the columnae cameae of the mitral valve; it is only in the case in which death has been caused by syncope that the ventricle, aiTested in diastole at the moment of death, contains fluid blood and clots. The right ventricle is frequently distended and filled with coagulated blood : this phenomenon must be attributed to the fact that during the death agony asphyxia and hindrance to the pulmonary circulation prevent the right ventricle from emptying itself. The auricles, owing to the feebleness of their contraction, always contain blood during Life, and are consequently always filled with blood after death. When the heart ceases to beat, the blood contained in its cavities slowly coagulates, much more slowly than if it were con- tained in a vase : this fact was established by the experiments of Briicke, who observed that blood retained in the cavities of a heart removed from the animal did not coagulate for some hours, and he attributed this phenomenon to the influence of the endo- thelium of the endocardium. Now it is known, on the other 488 MORBID CHANGES IN THE HEART. hand, that whenever the blood coagulates slowly the red cor- puscles fall to the bottom, while the superficial part, deprived of corpuscles, coagulates into a colourless fibrinous mass. The clot is then composed of two layers, one superficial, composed of fibrin with serum entangled in its meshes (the bufiy coat of inflammation), and the deeper layer strongly coloured red by the red corpuscles. This is the mode of coagulation observed in the heart when there is a large quantity of blood in its cavities, and the body, for some hours preceding the autopsy, has lain, as is usual, on the back. All the large clots of blood are decolorised on their anterior superior surface, while they axe cruoric on their posterior inferior surface. Most physicians who perform autopsies consider that these clots are formed during the death agony ; on account of their decolorisation, they assign them a vital origin, and call them active clots. What we have already said regarding the formation of clots is sufiicient to show that this interpretation is erroneous, and it is useless for us to insist upon it further. Some clots may be called active clots, if by this name it is understood that they are formed during life : these are the fibrinous concretions developed in delicate layers, upon the de- nuded surface of the endocardium, in endocarditis, or upon vege- tations of the orifices or ruptured valves. These clots are white or yellowish ; they do not contain red blood corpuscles, but are solely composed of laminse of granular fibrin. According to the theory of A. Schmidt, which is generally accepted, their formation is the result of the coagulation of the fibrinogenic substance of the blood in contact with the inflamed wall. This explains why this coagulum, which is formed slowly, does not contain the figurate elements of the blood. Other larger clots are formed in consequence of the slowing of the blood ciurent, as may be observed in asystole of pulmonary origin, and in hypertrophy of the heart with dilatation. These clots are very variable in form and size; they are wedged in between the columnae cameae, and are adherent to the walls of the heart ; they are uniformly yellowish, and when not very old they may be separated into laminae by tearing, showing that at the centre they are as firm as at the periphery. When older, they are firm superficially, while their centre is softened, and forms a granular detritus in which white corpuscles may always be found, sometimes in very considerable numbers. When the blood is profoundly altered, as in htemorrhagic STRUCTURE OF BLOOD CLOTS. 489 variola, puerperal fever, phosphorus-poisoning, etc., the clots formed in the heart after death are soft, friable, and are not com- posed of distinct layers. In leukaemia the clots are quite colour- less, and beside them is found a fluid which has often the appear- ance and consistence of pus, as Virchow observed : this is due to the enormous quantity of white corpuscles contained in the fluid. 490 CHAPTER IX. LESIONS OF THE ARTERIES. I. Normal Histology of the Arteries. The arteries present for study internal, middle, and external coats. The internal coat of the large arteries is composed of two layers : first, an epithelial layer ; second, a delicate layer, from •003 mm. to •012 mm. in thickness, lying upon the middle layer. The epithelial layer is formed of a single row of soft polygonal cells, elongated in the direction of the vessel, and much flattened ; in preparations stained with nitrate of silver they are seen by trans- mitted light to be bordered by a black line ; each cell contains a flat, circular, or elongated nucleus, which may be made evident by staining with picro-carminate of ammonia. The sub-epithelial layer is formed of flat, irregularly stellate cells, anastomosing together, and containing flat nuclei; they are imbedded in a ground substance, which is fibrillated in a longitudinal direction. In the small arteries this layer is extremely thin, while in the aorta it is relatively thick, and composed of two fibrillated layers, in the most internal of which the fibres have a longitudinal direc- tion, while they are transverse in the external layer. The middle coat is, in the aorta and carotid, composed of elastic laminae and fibres which form by their anastomoses a continuous system, and limit lacunae in which are contained smooth muscle cells lying in a transverse direction, and a few connective-tissue fibres. Next the internal coat, the middle coat is bordered by an elastic layer, thicker than the others, and which is seen to have a festooned appearance in transverse sections. The recognition of this elastic layer is very important in the pathological histology of the arteries, and we have therefore named it the internal elastic layer of the middle coat. On the side of the external coat, the elastic fibres are detached from the elastic laminae of the middle coat, and are distributed between the fasciculi of connective tissue in various PATHOLOGY OF THE ARTERIES. 491 directions, and thus constitute the framework of the external or adventitious coat. In the femoral, brachial, and all arteries of a medium calibre, the middle coat has only one elastic layer, which is the internal elastic layer. The transverse muscle cells form flattened fasciculi, separ- ated from one another by connective tissue and elastic fibres, continuous with the internal elastic layer on one hand, and on the other with the large-meshed elastic network of the external coat. The internal and middle layers have no blood-vessels, the external coat is, on the contrary, supplied with arteries, capillaries, and veins, and with lymphatics whose lumina are seen as clefts in transverse section ; small nerve trunks and isolated nerve tubes are also present. The small arteries have a middle coat formed of smooth muscle cells arranged transversely side by side, so as to form a continuous membrane. The adventitious or external coat is com- posed of small fasciculi of connective tissue, having in general longitudinal direction. II. Pathological Histology of the Arteries. Arteritis. — The inflammatory lesions of the arteries are many and various. Inflammation of the arteries may be considered iiceording to its seat in the large, middle, and small arteries, or in the internal, middle, and external coats. Atheromatous and cal- careous degeneration should also be studied with arteritis ; finally, spontaneous aneurism and the histological changes which occur in arteries obliterated by a blood clot also belong to arteritis. "We shall therefore describe successively, fiirst, acute arteritis ; second, chronic arteritis and atheroma, so frequently combined ; third, aneurisms ; fourth, arterial obliteration. In this description we do not propose to divide inflammation of the arteries, with refer- ence to its seat in the tunica interna (endarteritis) or in the tunica externa (periarteritis), for endarteritis and periarteritis are most frequently combined: we shall, however, carefully indicate the cases in which these two lesions are seen separate. Acute arteritis. — Acute endarteritis, or acute inflammation of the tunica interna, is often seen in the aorta as an isolated lesion. It is characterised by swelling of the tunica interna in the form of prominent patches, more or less extensive, the contour of which is irregular or circular : some of these patches are small, regular, nd iituminated ; others, more extensive and irregular in outline, a 492 LESIONS OF THE ARTERIES. are evidently formed by the confluence of many similar round patches, and show prominences and depressions on their surface. They are generally pink, transparent, or more or less opalescent, and are elastic, soft, and gelatinous in consistence — thus they are generally known by the name of ' gelatinous patches of the aorta'; their surface is very rarely ulcerated. Eound them the tunica interna is not entirely healthy ; it is tumefied and slightly softer, appearing as if it had imbibed fluid ; it is sometimes pink, at others colourless. In some cases, in which the endarteritis is very intense, we have been struck with the pallor of the tunica interna, while, on the other hand, we have frequently seen the vessels and endocardium of a deep red, due solely to imbibition without there being any trace of endarteritis or endocarditis. It is, however, sufficient to macerate an artery in blood-stained water for its surface, which was originally pale, to become reddened by infiltration of the haemoglobin dissolved in the water. In subacute and less chronic forms of endarteritis the free surface of the artery is shagreened and deprived of its polish, which is due to the irregular tumefaction of the tunica interna of the vessel.' The gelatinous patches of acute endarteritis seem, in vertical sections, to be composed of the same transparent tissue which limits the middle coat of the artery. On removing one of these gelatinous patches, and dissociating it with needles, its consti- tuent elements are isolated without difficulty. They are, first, spherical or irregularly spherical cells, of a mean diameter of ■01 mm., and in which a nucleus is seen after the addition of acetic acid ; they have, in fact, the characters of embryonic cells. Secondly, a few large flattened cells, with multiple processes, con- taining sometimes two nuclei, and corresponding to the normal connective-tissue cells of the internal membrane. The round elements, obtained by dissociation, are cells and not simply nuclei, as might be thought on examining them merely in sections obtained after dessication, which is the process usually employed. In such sections the patches appear as a thickening of the tunica interna. With a low power, the considerable thickness of these patches compared with normal parts of the internal membrane, and even with the middle coat, may be appreciated ; they may be ' This roughened and unpolished appearance of the internal membrane in endarteritis has been often referred to exfoliation of the epithelium. We may here remark that exfoliation of the epithelium cannot be the cause of this appearance, for twenty-four hours after death the epithelium has disappeared, from the smooth as well as from the roughened surfaces, both in normal and pathological con- ditions. ACUTE ENDARTERITIS. 493 a hundred times thicker than the normal internal coat, and two or three times thicker than the middle coat. With a power mag- nifying a hundred diameters, which allows of the whole prepara- tion being seen, it will be observed that the cellular elements are extremely numerous, arranged close together in lines parallel to the surface, their number diminishing progressively, as the deep layers near the middle coat are approached. We cannot avoid seeing in this phenomenon a striking analogy with that which takes place in inflamed diarthrodal cartilages, in which the cells on the surface are also the first to multiply. The, fact of the Tnultiplication of elements on the surface of the i/ntemal membrane is peculiar to acute endarteritis, and separates it from endarteritis consecutive to atheroma, in which proliferation occurs, as we shall see, in the deep layer of the 200 Fig. 236. — Section of the Tunica Intkrna of the Aorta, in a CASE OF Acute Endarteritis. This section, made after dessioation of the artery, shows the proliferation of the elements of the internal membrane. Magnified 200 diameters, internal membrane. The same distinction mxiy be made hi endocarditis. At the periphery of the gelatinous patches where continuous with the tunica interna, a series of modifications of this membrane may be observed, and the process of their formation and develop- ment followed. Near the tumefied parts there is also in the tunica interna a large number of round cellular elements, while deeper are still found flattened cells with lenticular nuclei. With a higher power, and in preparations treated with acetic or formic acid, the substance of the cell cannot generally be seen round the nuclei, which seem to be simply imbedded in a ground substance. Thi-s as we have already pointed out, is an optical illusion, due to the method of rr.^raration. Upon the surface of the gelatinous patches the cellular elements are so close together that many of them seem to touch : nuclei may here be seen biscuit or hour- 494 LESIONS OF THE ARTERIES. glass-shaped, which indicate that division is about to occur, and also groups of from two to five nuclei in contact with one another {vide fig. 236). In the deep layers the ground substance is more abundant, and the groups of cells more separated. , The presence of numerous cellular elements in the superficial layers of the tunica interna cannot be explained by diapedesis, since this membrane does not contain blood-vessels. Migration through the internal coat of white corpuscles derived from the blood circulating in the diseased artery is the utmost that can be allowed. But it is much more probable that they are derived from cells normally present in the tunica interna, and these cells moreover show in the clearest manner signs of division of their nuclei {vide fig. 236). The gelatinous patches of arteries sometimes show superficial and fungoid ulcerations, which are covered by a thin layer of adherent fibrin. This soft, semi-transparent layer often shows red spots or lines, and sometimes it is stained throughout its whole extent. It cannot be determined, without examining micro- scopical sections, whether this layer be fibrin or the modified in- ternal membrane. The elements composing this transparent layer, when studied by dissociation, are easily isolated, and are seen to be numerous, round, small uni-nucleated cells. It cannot be deter- mined by their form alone whether these cells are embryonic elements such as we have described in the proliferating tunica interna, or white blood corpuscles ; but in vertical sections, cut after hardening in alcohol, fibrin may be recognised, including cellular elements. It is probable that the fibrinogen of the blood is transformed into fibrin by the presence of the fibrinoplastic substance of the inflamed parts, and that the elements entangled in its network are either white blood corpuscles, or the free and proliferating elements of the diseased surface. The middle coat does not usually present any alterations in acute endarteritis. Between the most acute endarteritis and the chronic form at its final stage, all intermediate forms may be found ; it may even happen that all the phases may be met with in the same segment of an artery. Periarteritis. — In almost every case of acute endarteritis, periarteritis is present, that is to say, an inflammatory thick- ening of the tunica externa. The tissue of this coat becomes homogeneous, gelatinous, and of an amber or pink colour. Micro- scopical sections show marked thickening and a new formation of PERIARTERITIS. 495 cells between the fasciculi of connective tissue. Acute peri- arteritis, characterised by purulent inflammation of the tunica externa, is seen in phlegmon ; the inflammation is most frequently limited to this membrane, or a slight lesion of the tunica interna may be present ; in all cases the middle coat is not modified in a marked manner. The resistance of the arterial walls is preserved, neither distension nor laceration occurring, and the function of the artery is not interfered with. Acute inflammation of arteries of middle and small calibre is rarely primary, but is frequently seen in consequence of inflam- mation of neighbouring tissues. Thus in the lips of a granulating wound, in the fungoid tissue of whitlow, in the base of a chronic ulcer, the small divided arteries will, on section, be seen, with the unaided eye, as minute red spots surrounded by a semi-transparent, thick, circular zone. On attempting to dissect out the arteries, it will be found difficult to trace them far, for their external coat, in61trated with inflammatory fluids and elements, is blended with the neighbouring connective tissue, and forms with it a single lardaceous mass. In this dissection also it will be found that the vessels are brittle, and slight traction in the process is sufiicient to tear them. Arteries thus thickened by inflammation are difficult to distinguish, with the naked eye, from neighbouring nerve cords. Histological examination of diseased blood-vessel is made in sections carried through its various coats and smrounding tissues, after hardening. Vegetations of the internal coat, that is to say, of the part comprised between the internal surface of the blood-vessel and the internal elastic layer, will' be then observed. In these growths, which vary in form and extent, are seen round cells, or cells flattened in different planes, separated from one another by a small quantity of intercellular substance. Blood- vessels from the tunica adventitia penetrate and form loops : this vascularisation is observed when the middle coat has disappeared, or has been transformed into connective tissue. As to the external coat, its connective-tissue fasciculi and elastic fibres are kept apart by a more or less considerable number of embryonic cells, which may determine, as in all inflammation of the connective tissue, absorption of the connective-tissue and elastic fibres. The middle coat is, as we have already seen, not always left intact ; in it may be observed multiplication of cells, which cells are undergoing differentiation from the muscular type, and are absorbed at the same time that the elastic fibres break up. Finally, the 496 LESIONS OF THE ARTERIES. different arterial coats are blended together for more or less extensive areas. Under the influence of inflammation the various tissues constituting the arterial walls tend to take the structure of the inflamed tunica interna. When considering aneurisms, we shall see some remarkable examples of the transforpiation of the external and middle coats into a tissue resembling that of the internal membrane. When vegetation of the internal coat is so considerable as to impede or arrest the course of the blood, it coagulates above the growth : this is one of the forms of arterial thrombosis. Chronic arteritis. — The lesions of chronic arteritis are similar to those of acute arteritis, only that they are complicated with fatty degeneration, calcareous change, and atheroma. Calcareous change is always accompanied with arteritis, which is not always the case in fatty degeneration, which may be alone, and which we consider to be one of the causes of arteritis. Thus we shall com- mence by studying primary fatty change of the arteries. Primary fatty degeneration of the arteries is seen principally in the aorta, immediately above the sigmoid valves, where, in almost Fig. 237. — Fatty Dkgeseeation of the Tunica Inteena, in a Flake of this Membrane. In tlie midst of the fibrillated tissue, 6, are seen masses of fat granules resulting from tSe fatty degeneration of tie flat ramifying cells of this layer. Magnified 200 diameters. all adult persons, will be found whitish, opaque spots, forming-a hardly perceptible elevation. These spots may be considered as the first stage in fatty degeneration with atheroma and calcareous CHRONIC ENDARTERITIS. 497 plates, which, in persons more advanced in age, may be of con- siderable extent. These white or yellowish patches may be examined in longitudinal sections, prepared according to the method already indicated (p. 492). They may also be examined in flakes detached from the tunica externa and extended on a slide. In these flakes are observed collections of granules and drops of fat, which frequently have the shape of the flat ramifying cells of the tunica interna (fig. 237). In vertical sections, it may be seen that the fatty degeneration is not limited to the tunica interna. The internal layers of the tunica media are also affected in the same manner. In the tunica interna the fat granules form flattened or fusi- form collections, in the midst of which nuclei may sometimes be distinguished ; they are recognised by being stained red, when the Fig. 238. — Fatty Degenkuation of the Tunica Interna of THE Aorta. m, nuclei of the flat cells ; g, fat granules. Magnified 400 diameters. preparation has been submitted to the action of carmine, while the fat granules are not coloured by the same reagent. Most of the collections, however, do not contain nuclei, these having atrophied and disappeared. In the tunica media the fat granules are deposited between the elastic fibres and laminae, and, when very profuse, the muscular elements are no longer distinguishable. At the edges of the parts which have undergone fatty degeneration the muscle cells are infiltrated with fat granules. It may be concluded from these data that fatty degeneration caust's atrophy of the affected elements ; that there is, in the full acceptation of the term, a fatty necrobiosis. Chronic endarteritis.— When a portion of the aiterial coats has undergone the fatty degeneration just described, it becomes K K 498 LESIONS OF THE ARTERIES. necrosed, and determines around itself the phenomena of irrita- tion. Chronic endarteritis is thus produced ; but this is not the sole cause of chronic endarteritis : it may be produced spontane- ously, or succeed rheumatic, puerperal, or alcoholic endarteritis. The lesions of chronic endarteritis, whatever may be its origin, are always complicated by fatty degeneration of the arterial coats, leading to the formation of atheromatous foci and calcareous plates. An analysis, as complete as possible, of all these pheno- mena ought to be made before determining their order of succes- sion. Fatty degeneration may, indeed, be the cause or the result of arteritis. In subacute arteritis the gelatinous patches may contain stellate cells in a state of fatty degeneration ; but this process of degeneration continuing when the inflammation has lost its first intensity, almost all the cellular elements of these patches become charged with fat granules, and thus lose their semi-transparency to become yellow and opaque. These groups of granules, which have the form of stellate cells, soon become fused together, and form small foci, which can at first only be recognised under the microscope, but which later on increase in size, and appear to the unaided eye like atheromatous foci. The atheromatous foci are situated in the thickened tunica interna. They are large and shallow, with anfractuous borders. They are at first separated from the blood current by a delicate cartilaginiform pellicle, composed of the most superficial layers of the internal coat ; this pellicle is tense though mobile ; at its peri- phery is often observed a cord-like swelling, formed by a thicken- ing of the tunica interna, so that the centre of a non-ulcerated atheromatous patch is slightly depressed. On making a vertical incision through the centre of the atheromatous patch, the scalpel, after being momentarily arrested by the hard superficial layer of the tunica interna, opens a focus, out of which escapes a thick whitish fluid, which, examined under the microscope, is seen to contain a large quantity of cholesterin, free fat granules, granular bodies, and crystals of fatty acids. Atheromatous foci open rather frequently during life into the artery, in consequence of the progressive thinning of the pellicle covering them, or from the friction and shock of the blood current against the vascular wall ; the opening is generally effected by a small slit or star-shaped rent. The contained detritus then passes into the circulation, and the blood penetrates the focus, the con- tents of which take a yellow, brown, or black stain, due to the transformation of the hsemaglobin. Such foci may be the point THE CALCAREOUS PLATES OF AliTERITIS. 499 of departure of small cup-shaped or crateriform aneurisms, which will be considered later. In microscopical section passing vertically through the athero- matous focus and its borders, it may be seen that its basis is com- posed of the deeper layers of the tunica interna, which shows the lesions of endarteritis with fatty degeneration. The most super- ficial layer of the tunica media also shows signs of primary fatty degeneration. On the borders of the patch of atheroma the swollen parts show microscopical atheromatous spots situated in a slightly fibrillated substance ; more distant from the focus are found nuclei of cells which stain with carmine, and are surrounded with fat granules ; still further, the fibrillated substance limits small cavities or laeunse containing cells resembling those of cartilage, but which are not surrounded by capsules. This is a ehondroid, but not cartilaginous, change of the tunica interna. When the evolution of atheroma is slow, the fibrillated ground substance becomes infiltrated with calcareous granules, at the same time that the cells undergo fatty degeneration. These granules, solitary at first, afterwards unite so as to form imbricated semi- transparent, brittle, and inelastic plates. Calcareous plates. — It is rare for calcareous plates to be com- pletely exposed on the surface of a vessel ; they are generally covered by a layer of the tunica interna. These plates, which are often extremely thin, are broken by the shock of the blood current, or their edges are raised, tearing the delicate layer of tissue which covers them, so that fenestrte are made, through wliich the blood insinuates itself beneath the plates, marking its track by black pigment. The before-mentioned properties of trans- parency, brittleness, and inelasticity, which these calcareous plates possess, distinguish them at once from osseous tissue, which is, on the contrary, resistant, opaque, and elastic. On making prepara- tions of them by the methods described for the study of bone (yhle p. 326, note), the structure of osseous tissue is never found; they only show irregular masses, black slits and striae, in the midst of a very transparent substance, which shows neither the lami- nated arrangement nor the blood-vessels of bone. These slits and £■( ri:r have no resemblance to bone corpuscles. Arteritis deformans.^In old age all the lesions already de- scribed are "ft en seen accompanied with dilatation of the vessel • to this complicated pathological condition the name of arteritis deformans has luen given. On removing and opening an aorta 500 , LESIONS OF. THE ARTERIES. affected with this disease, the increase of its diameter, the inequality of its calibre, the irregularity of its surface, and the variety of the lesions present are very striking. These lesions are generally more pronounced and older at the origin of the aorta than in the rest of its course ; they are, however, continued into its branches ; it seems as if the alteration commenced at the origin of the aorta, progressively invading the rest of the arteries. Above the sigmoid valves, which are generally indurated, are seen cal- careous plates, separated by slits or imbricated, and bounded on their borders by the swollen tissues of endarteritis. These calca- reous plates most frequently extend into the coronary, innominate, carotid, and subclavian arteries, invading them for a more or less considerable extent. At their point of origin in the aorta these arteries generally show almost complete ossiform rings. The arch of the aorta is usually dilated, from which it results that the thoracic aorta has the form of an elongated funnel. Beside the calcareous plates may be seen open atheromatous foci, atheromatous pustules, and cartilaginiform plates. The extent and thickness of the latter are variable ; they are semi-transparent or more or less opaque, and are often accompanied with nummular excrescences or vegetations covered with layers of fibrin varying in thickness. It frequently happens that the thin, vitreous, calcareous plates, formed in the hypertrophied and rigid internal membrane, or extended over atheromatous foci, crack, and the blood infiltrates through the narrow slit. The blood undergoes the usual pigmen- tary changes, and forms black or melanotic patches of various extent, giving the diseased part an altogether peculiar appearance. The preceding description applies particularly to the aorta ; but the same lesions are observed in arteries of medium and small calibre, in which calcareous degeneration, so frequent in old persons in the arteries of the limbs and brain, originates in the hyper- trophied tunica interna by chronic endarteritis. This endarteritis is histologically characterised by multiplication of the cells of the tunica interna, and by the formation of a resistant and slightly fibrillated intercellular substance, which soon gives a cartilagi- nous consistence to the membrane. This chondroid tissue may be developed regularly in the tunica interna so as to diminish the calibre of the vessel in every direction ; or its development may be exaggerated in certain spots, thus forming plates or buds pro- jecting into the lumen of the vessel. In consequence of this lesion the blood current is slowed in the affected arteries so that coagulation may take place This arterial thrombosis produces CHRONIC PERIARTERITIS. 501 gangrene in the extremities, softening in the brain, and fatty degeneration of the heart when located in one of the coronary arteries. Chronic periarteritis. — All forms of arteritis of long standing are accompanied with thickening of the tunica externa, and the production of numerous cells between the fasciculi of the connec- tive tissue ; in a word, it is complicated with chronic periarte- ritis. In dilatation of the aorta accompanying arteritis deformans, it constantly happens that the middle coat disappears at certain points, and the hypertrophied internal coat becomes united to the external. The destroyed portions of the middle coat are replaced by proliferating connective tissue of the external and internal .at Fio. 239. — SucTios of the Aorta at a Point wiieke the Middle Coat is ixteuuupteu by Connective Tissue. o, tiuiica tiitorna ; 6, tunica externa ; c, tanica media ; rf, blood-veseel in the midst of embryonic tissue, wllich unites the external and internal membrane. MogmHed 100 diameters. coats. Fig. 239 shows an interruption of this nature of the tunica media of the aorta ; it is seen as a bridge thrown across the solu- tion of continuity between the internal and external coats. The blood-vessels, often contained in these bridges of fibrous tissue, reach the tunica interna and ramify, thus showing how it is that tliis membrane may become vascular. The destruction of the tuuica media is the immediate cause of spontaneous aneurisms of the aort.i. Before the disappearance of the middle coat, in consequence of endarteritis and periarteritis, its elastic laminse and fibres are decomposed into .eculiar form of angioma, namely arterial varix, or chsoid 5'8 LESIONS OF THE ARTERIES aneurism. In these tumours the arteries are dilated, elongated, serpentine, and thickened ; they present numerous anastomoses and partial dilatations ; they are usually located in the temporal and occipital arteries. The arteries which supply a certain number of tumours, for example those of the mamma, thyroid body, etc., are extremely hypertrophied, and there is an actual new formation of arteries taking place simultaneously with the growth of the tumour. This new formation seems to be produced by a transformation of the capillaries into arterioles and larger arteries by the formation of smooth muscular elements developed from the embryonic cells 3-f Fig. 246. — Section of Tubeeculak Meninges. a, small obliterated, vessel ; v, v, much larger vessels. The internal coat of these veseels is greatly thickened, and in the internal layer of the vessel -which is in the centre of the figure are seen two giant cells ; n, vessel obliterated near the cerebral substance m. Magnified 40 diameters. surrounding the vessel. This evolution is, however, extremely difficult to follow, and there is still much uncertainty regarding the subject. Tumours, which develop rapidly round an artery of a certain calibre, determine phenomena in every way resembling those of arteritis, that is to say, the vegetations of endarteritis, disappear- ance of the middle coat, and an embryonic condition of the external coat. In arteries thus degenerated blood clots are frequently formed, or haemorrhage occurs due to rupture of the friable arterial coats. These lesions are particularly observed in rapidly growing sarcoma or carcinoma : the tissue of the tumour may often be seen to grow into the blood-vessel after the middle coat TUBERCLE IN ARTERIES. 519 has disappeared. When the circulation is impeded or arrested by these lesions of the arteries, the part supplied by them becomes mortified. If the mortified part is superficial, as occurs in tumours of the cervix uteri, it softens and ulcerates, and if the necrosed mass is located in the substance of an organ it produces a caseous focus. It is not rare to see tubercular granulations develop in the tunica adventitia of arterioles. Mugge has also described tuber- cular grranulations in the internal coat of the pulmonary artery, as well as in the pulmonary veins of tubercular lungs. One of us has observed, in a case of tuberculosis of the cerebral meninges, a Fio. 247.— Section of iNifLAiiED and Tubercular Internal Coat. o layer of flat endothelial ceUs indicating tne internal border of the 'inflamed inner coat ; g, red Wood corpuscleB circulating in the lumen of the vessel ; d, layer of round or polygonal cells ; b, b, b, giant cells ; ; layer of cylindrical and round ceUs at the base of the Inflamed inner coat ; /, middle coat. Magnified 200 diameters. lesion of the arterioles consisting in a peculiar form of endarteritis, characterised by the thickening of endarteritis, and by the new formation of a large quantity of cells of various forms in the thickened artery. In the midst of these cells there were a num- ber of very large giant cells {b b, fig. 247) ; the endothelium was perfectly preserved on the surface of the new formation developed in the internal membrane. The final lesion of such a process is the obstruction of the small artery, coagulation of the blood, and subsequently complete obliteration. 520 CHAPTEE X. LUSIONS OF THE CAPILLARY VESSELS. I. Normal Histology of tlie Capillaries. The capillary vessels are essentially formed of endothelial cells united at their edges, and arranged in such a way as to form a network of anastomosing capillaries (vide p. 38). The capillaries have everywhere the same structure, but their size and the arrangement of their networks vary in each organ and in each tissue. The vessels are surrounded with fasciculated or reticulated connective tissue, or they are contained in lymph spaces. In fasciculated connective tissue the capillaries, lined with flat cells, are found in the spaces of this tissue, alongside the fasciculi without adhering to them, the lymph being in direct relation with the vascular wall ; so that in reality a capillary of the connective tissue is situated in a lymph space. This arrange- ment does not only exist in the subcutaneous cellular tissue, but in the skin, muscles, nerves, and cellular tissue of the organs. In the lymphoid organs — lymphatic gland, follicles of the intestines, tonsils, glomeruli of the spleen, thymus, etc. — the capillaries are covered with a dense fibrillated layer from which the iibrils of the stroma spring. The lymph bathing this stroma is thus separated from the blood current by two layers, the cellular membrane of the capillary, and its reticulated investment. The capillaries of the glands are placed in the lymph spaces which surround the acini, and separate them from neighbouring acini ; those of the nervous centres are contained in perivascular sheaths. When a capillary occupies a lymph space, it is generally covered with a layer of endothelium, and is connected to the wall of this lymph space by bands of connective tissue, varying in thickness. From the constant existence of lymph spaces between capillaries and the constituent elements of the tissues and organs, it results that these elements are not in direct relation with the IXFLAMMATION OF THE CAPILLARIES. 521 plasma of the blood, but that this plasma is first effused into the Ijfmph spaces and absorbed by the elements found in these spaces, according to their physiological or pathological needs. It must not nevertheless be concluded that the exuded fluids have no influence on the functions of these elements : we have, in fact, shown, when considering oedema, the modifications of flat connec- tive-tissue cells, under the influence of a morbid serous exudation into the connective-tissue spaces. To recapitulate, it is not the blood which is the vehicle of nourishment to the elements, but the lymph derived from the blood. II. Pathological Histology of the Capillaries. Inflammation of the Capillaries. We will not here reconsider in detail the changes observed in inflamed vessels, and which have been already described {vide p. 109), but we propose to point out the pecuhar alterations of capillaries in inflammation. The capillaries of inflamed vascular tissues present two orders of phenomena; some consist in the modification of their wall, others in the extension of the old vessels and a new vascular formation. At the commencement of inflammation swelling of the endothelial cells of the capillaries is observed ; the cells which were flat, homogeneous, and could not be distinguished, then appear granular, and seen sideways they seem fusiform and distinct from one another. This arrangement is particularly well seen in transverse sections of inflamed vessels {vide fig. 249). In the mesentery of a frog which has been exposed to the air it is much more difficult to see the swelling of the cells, which may be, however, recognised with attention. Separation of the cellular elements results in dilatation of the capillary vessels, and also facilitates the escape of the white and red corpuscles and of the fibrinogenic plasma. In chronic inflammation of the mucous membranes, notably in catarrh, dilatation of the capillary vessels is considerable. In such cases the dilated capillaries remain full of blood after death, and are seen as spots or red markings, whUe normal capillaries are generally emptied in consequence of the contraction they undergo after death. This fact alone shows that blood-vessels, modified by inflammation, have lost one of their most important properties, that of elasticity. ]\Iodifications of the vascular walls, joined to increase of the blood pressure, cause vai-ious accidents, observed particularly in 522 LESIONS OF THE CAPILLARY VESSELS. the brain. In the foci of softening and hsemorrhage of this organ, or more particularly round these foci, small red spots or nodules Fig. 248. — Inflamed Connective Tissue. a, space occupying tte place of adipose cells the fat of which has been absorbed, and now filled with young nuclei, c, surrounded with granular protoplasm ; e, embryonic cells ; V, vessel, the wall of which is formed of tumefied endothelial cells, are often seen, and which are due to dilated capillaries or to effu- sion of blood into their perivascular sheaths. The latter lesion is Fig. 249. — Capillary Vessel of thi; Bkain, showing Extravasation OF Blood into its Peeivasculak Sheath. Magnified 260 diameters. very frequent, and has been called by Kolliker and Pestalozzi by the name of dissectvng aneurism of the capillaries. NUTRITIVE LESIONS OF THE CAPILLARIES. 523 As to the miliary aneurisms of the brain, described by Charcot and Bouchard, they are more frequently produced by dilatation of the arterioles than of the capillaries. They seem to be the result of inflammation located in the wall of the vessel itself, and from this point of view their pathogenesis does not differ from that of aneurisms of medium calibre. They are fusiform or saccu- lated, and are almost always accompanied with haemorrhage into the perivascular sheath, being, therefore, at the same time simple and dissecting {vide fig. 250). Regarding the new formation of vessels in inflamed tissues we have nothing to add to what has already been said in the chapter on inflammation, page 109. Fio. 200. — Miliary Aneurism of an Arteriole of the Brain. «, trank of the arteriole showing the gi'onnles m ; c, perivaacular sheath ; 6, V, aneurisms formed by a uniform dilatation of the arterial coats ; n, A, effusion of blood into the perivascular sheath c' ; d, d,/, capillary branches springing from the arteriole. Mag- nified 30 diameters. Nutritive lesions of the capillaries. — The most frequent lesion of the capillaries consists in fatty degeneration of their walls. It is met with in all vascular organs, but it is particularly frequent in the kidney and the nerve centres ; it may be observed when- ever nutrition is lessened or arrested, and it then accompanies fatty degeneration of the elements composing the organs. In the brain and spinal cord, however, of new-bom infants, and during the first month of life, a great numoer of granular bodies are found in the capillaries. In cerebral softening, the capillaries of the brain, which normally often contain in the adult a few dis- seminated refractile granules, are loaded with fat granules, which, at certain points give the capillary the form of a dark granular cylinder. The perivascular sheath contains blood and granules of 524 LESIONS OF THE CAPILLARY VESSELS. hsematoidin (vide fig. 251), which indicates that there has been diapedesis, or rupture of the morbid capillary vessel. At other times, the perivascular sheaths are dilated and contain granular ©00, (;3v ,, 0^ _ c^if I Fig. 261. — Crystals of Hsematoidin. a, free crystals ; 6, crystals contained in cells ; /, capillary vessel containing grantdes of haamatoidin, bodies (vide fig. 252), in which a nucleus may almost always be discovered, on staining the preparation with picrocarminate of ammonia. These granular bodies are either lymph cells loaded with fat granules, or endothelial cells of the perivascular sheath which have undergone the same alteration. After section of nerves, the capillaries of the peripheral segment also undergo fatty degeneration : the same change is observed in the neighbouring connective-tissue cells and migratory cells. In infarcts following obliteration of arteries, in chronic inflammation with consecutive Fig. 252. — Capili.aky Vessel of the Bkain, in the Distended Sheath of which are seen Free Fat Granules and Lymph Cells surrounded with Fat Granules. Magnified 250 diameters. fatty degeneration, in Bright's disease particularly (vide fig. 253), and in tumours which have undergone the same change, fatty degeneration invades the walls of the capillaries. Calcareous degeneration is rarely seen in capillaries. Calcareous salts are, however, met with, either in the form of granules or plates, particularly in angiolithic sarcoma of the dura mater. Also, sometimes, in angiolithic sarcoma, or in chronic encephalitis. AMYLOID DEGENERATION OF CAPILLARIES. 525 in general paralysis, for example, segments of capillaries are found infiltrated with calcareous salts. They appear vitreous and brittle, and are often broken up. Amyloid degeneration transforming the capillaries into vitreous tubes is frequent. The hypertrophy of the amyloid wall is some- times so great as to transform the vessels into solid homogeneous, vitreous cylinders, much larger in diameter than normal capil- laries. In this change the endothelial cells of the capillaries are Figs. 258 and 254.— Fatty Degeneration of Renal Vessels in a Cask OK Bkight's Disease. On the left Is part of the capillary network in a state of fatty degeneration, and on the right a glomerulus of Malphigi, showing similar lesions. Magnifled 250 diameters. preserved for a long time. This form of degeneration is par- ticularly well marked in the liver and kidney, and principally in the vessels forming the Malpighian tufts : sometimes the change is only found in the glomeruli, while in other organs amyloid change more frequently commences in the arteries. We will not reconsider the changes of the capillaries in the different kinds of tumours, simply recalling that in sarcoma, as in all inflamed tissues, the capillary wall returns to the embryonic condition. 526 CHAPTEE Xr. LESIONS OF THE VEINS. I. Normal Histology of the Veins. The three coats, generally admitted in the veins, are much less defined than those of the arteries ; moreover, veins of the same calibre have not, in different regions of the body, always the same structure, inasmuch as the muscular and elastic elements have neither the same arrangement nor the same thickness. The internal coat of veins is composed of flat cells separated by a fibrillated . substance, .and is lined with flat polygonal endothelial cells, shorter than those of the arteries. The middle coat commences by circular elastic fibres or laminse, and from this first elastic layer spring elastic fibres, which form a network, in which are arranged the smooth muscle cells and connective-tissue fasciculi. The line of demarcation between the middle and external coat is not clearly marked, but all that part of the vein which contains muscular fibres may be looked upon as the middle coat. We' should add that veins which have no elastic fibres — the sinuses of the dura mater, subclavian veins, and veins of the retina — have no middle coat. As there are no elastic laminee in the middle coat of veins, it is easily understood how that their walls allow of the passage from without inwards of fluids, or from within outwards of plasma and blood corpuscles. If absorption is much more easily accom- plished by the veins than by the arteries, as Magendie showed, this is not only due to the fact that the blood current is slower, but also that the venous walls are much more easily traversed. Diapedesis, which is very frequent in the walls of the veins, is exceptional in the arterial coats. The elastic framework of the middle coat of veins of large and medium calibre forms a close network near the internal coat, and becomes more and more open as the external coat is approached. The muscular fibres have in the middle coat a longitudinal or INFLAMMATION OF VEINS. 527 transverse direction, according to the vessels under consideration ; thus, in the inferior vena cava, portal and renal veins, the internal fibres are circular, and the external longitudinal ; the femoral and popliteal veins have an internal longitudinal layer ; the arrange- ment of the muscular fibres is still more complicated in the saphena veins, in which may be remarked an internal longitudinal layer, then a series of transverse and longitudinal layers super- imposed. The veins of the neck have only a few scattered muscular fibres situated in the first elastic meshes external to the intima. The valves of the veins are extremely thin, though they are formed of many distinct layers. Besides the endothelial lining which covers the two surfaces of the valve, three layers may be distinguished, two superficial and one intermediate. The internal, the valve being raised, is of the same structure and thickness as the internal coat of the Vein ; it is continuous at the fi-ee border of the valve with the external, which is, however, much thinner. This arrangement is similar to that of the sigmoid and auriculo- ventricular valves, in which the endocardiac layer, which receives the friction of the blood at the level of the endocardiac orifices, is much thicker than the other. The intermediate layer is an expansion of the middle coat, and like this contains a few muscle cells, but only at its base. The vasa vasorum are found in the veins wherever fasciculated connective tissue is present, and they penetrate into the substance of the middle coat. II. Pathological Histology of the Veins. Inflammation of the veins. Phlebitis. — Spontaneous phlebitis is hardly ever met with except in the veins of the uterus in con- sequence of pregnancy. Phlebitis is generally complicated with inflammation of the surrounding connective tissue, or it occurs in consequence of wounds, ligature of veins, aiid primary coagulation of blood in their interior, or thrombosis. In wounds of the veins, coagulation of blood and phlebitis occur together, so that the phlebitis is dependent, at least partly, on the thrombosis. In ligature of a vein, an almost obsolete operation in surgery, but which may be performed experimentally on animals, the blood coagulates in its peripheral end, as far as the first collateral branch, a clot being also formed in its proximal end. During the first few days nothing is seen but swelling and multiplication of 528 LESIONS OF THE VEINS. the endothelial cells. Soon, however, the entire internal coat swells, in consequence of the production of new cells which form granulations, particularly well marked at the level of the ligature. Later, these granulations become vascular, unite together, and complete obliteration of the vein takes place, exactly as in the arteries. If, as Bubnoif showed, a segment of the jugular vein of the rabbit be included between two ligatures, and vermilion be sprinkled on the wound, the pus cells found in the external coat and neighbouring connective tissue are full of granules of vermilion ; the corpuscles carrying the vermiUon are then found throughout the thickness of the vein, on its internal surface as well as in the interior of the clot ; but if, instead of a double ligature, a simple ligature only is practised, and vermilion sprinkled on the wound, it does not penetrate to the interior of the vein, nor reach the clot. We have already spoken of these experiments when treating of arteries {vide p. 5 11 ). Blood clots in veins do not undergo organisation any more than in arteries : they break down into a granular detritus and disappear gradually. Wounds of veins. — The simplest wound of a vein is that made in the operation of bleeding from the arm ; the wound made, implicating both the vein and the skin, unites by first intention, though, as has been already explained, such union is not effected without inflammation playing an important part. A thin blood clot is left between the two lips of the wound ; the following day redness and a slight oedematous tumefaction are observed; towards the fourth day the scab formed over the incision falls, and cica- trisation is complete. These simple phenomena have, however, not yet been studied histologically, but it is probable that union of the vein occurs, as in connective tissue of the skin {vide p. 413), by the interposition between the lips of the wound of embryonic connective tissue, and by its organisation into ordinary connective tissue. In a wound, if the connective tissue of the external coat of a vein participates in the inflammation, it becomes infiltrated, for a variable extent, with embryonic and pus cells. In inflammation, ending in the formation of abscess, the external middle and internal coats of the vein may all become ulcerated and destroyed. This ulceration, which is particularly observed in abscesses of the axilla, groin, and posterior mediastinum, is accompanied with coagulation in the interior of the vessel, the danger of direct introduction of pus into the circulatory system being thus avoided. Some- times, however, the clot ia insufl5cient, and the accidents of VENOUS THROMBOSIS. 529 septicaemia and pyaemia take place ; at other times, the clot undergoes changes, it softens at the centre, and at its cardiac end an irregular canal is formed which brings the focus of suppurative inflammation into communication with the vascular system. The losses of substance observed in such cases, in the walls of the veins, are more or less extensive ; the vein is blended by its external coat with the phlegmonous tissue surrounding it, it cannot therefore contract on being cut, but remains gaping like the hepatic veins. The external border of the loss of sub- stance is thus confounded with the indurated or fungoid layer limiting the purulent focus. On the side of the cavity of the veins the loss of substance is more defined, although at this point the various coats are infiltrated with pus, and consequently thickened or partially necrosed. This infiltration of the venous wall is easily recognised under the microscope by the presence of pus cells, but, as the inflammatory process has been rapid, organised vegetations are not produced in the internal coat of the vessel. In positive wounds of vessels, as those made in siurgical operations, particularly in amputations, all the blood contained between the point of division and the nearest valves flows out, and this segment of the vein remains empty. A clot is formed above the valves as far as the first collateral branch. The empty extremity of the vein participates in the inflammation of the wound, and adhesive periphlebitis and endophlebitis take place as after Uga- ture, obliteration of the vessel being the consequence. Hitherto we have seen coagulation of the blood accompanying phlebitis ; till recently it was thought that coagulation of the blood in the veins was always caused by phlebitis. "Virchow has attempted to prove that primary phlebitis is extremely rare, and that, when a clot and phlebitis are both produced in a vein, coagu- lation has most frequently preceded the inflammation. This theory, which seems to us to be too absolute, has been accepted by all German pathologists ; it has, however, the merit of inducing careful study of the condition of the formation of blood clots in the veins. Venous thrombosis. — The causes of venous thrombosis are of two kinds : slowing and arrest of the circulation, or changes in the internal coat of the veins. On arrest of the circulation after death, the blood which is accumulated in the venous system undergoes coagulation. Pathologists should be well acquainted with these post-mortem clots, so as not to mistake them for those M M 530 LESIONS OF THE VEINS. of thrombosis. They are chiefly found in the large veins, the vena cava, iliac veins, etc. These post-mortem clots only occupy a small part of the lumen of the vessel ; they never fill it, are not adherent to the wall, and they send long prolongations into the collateral branches. They are of a reddish-brown colour, veined with white, and are partly fibrinous, partly cruoric, the upper layer is generally white or pink, the lower layers red, owing to the dorsal position of the cadaver. These clots vary greatly in thickness in the same vein, when recently coagulated they have the consistence of fibrin. Thromboses occurring during life are due to arrest, or impedi- ment of the local or general circulation. Thus asystole causes the formation of clots in the right heart and large veins. It is thus also that tumours and abscesses are often the cause of coagulation of the blood in the veins with which they are con- nected. Pressure of the gravid uterus acts in the same way on the hypogastric and iliac veins, etc. Slowing of the blood in varicose dilatation may also be the cause of thrombosis. When the circulation of the blood is impeded or arrested in the capillaries of a region, the vein carrying away the blood may also be the seat of thrombosis ; thus in pneumonia clots may be formed in the pulmonary veins, by the pressure exerted on the capillaries by the exudation distending the alveoli. Thromboses of the veins of the kidney and spleen, in caseous infarctus, etc., are also produced by stasis of the capillary circulation. It is the same in leukaemia ; the capillary circulation being impeded by the large number of white corpuscles, blood clots are formed in the veins. In thrombosis occurring during life, the clot completely fills the vessel, is adherent to its wall, and terminates towards the heart in a point or groove. It is formed of a series of nested layers, of which the most superficial are the most recent, and may be still cruoric, while the central and middle layers are of a grey or yellowish colour. When the clot is old, at its centre is often found an anfractuous cavity filled with a fusiform, whitish, opaque detritus. Under the microscope this detritus is seen to be com- posed of a number of white corpuscles in a state of caseous de- generation, they are irregular in shape, the nuclei are no longer apparent, but fat granules are seen in their interior ; beside these corpuscles are found granules, which disappear when acted upon by acetic acid, and free fat granules. A section of the clot, cut after hardening in alcohol, stained with carmine and examined in PHLEBITIS. 531 acidified glycerine, shows red blood corpuscles still recognisable at the periphery of the thrombus, separated by layers of fibrin in ■which are seen white corpuscles stained red by the carmine. In the interior of these layers the fibrin forms still closer laminae, between which are seen granular collections containing masses of pigment of different shapes and sizes. In the clots of spontaneous thrombosis of veins there is always a large number of white corpuscles, a phenomenon which can be attributed neither to the new formation of these elements nor to their migration. We have already shown that whenever the blood current is slowed in a vessel, the white corpuscles accumu- late ; now, since thrombosis is preceded by slowing of the circula- tion, this condition favours both accumulation of leucocytes and coagulation of the blood ; hence therefore it is quite natural that in blood clots formed spontaneously during life a large number of white corpuscles should be present. They become free in the centre of the clot when the fibrin breaks down. The arrangement of the thrombus in concentric layers is due to the fact that the primitive clot, which is formed of blood coagulated in the vein, undergoes contraction throughout its whole extent, leaving, therefore, a space between itself and the wall of the vein, through which the blood passes, but with diflSculty ; it therefore coagulates, and coagulation is again followed by contrac- tion, and the same phenomena are repeated till the distended vein exactly fits the clot, when circulation is arrested. Until the coagulum entirely fills the vein, it is frequently retained in situ, by the prolongations it has sent into the collateral veins ; this explains why a thrombus is not often detached and thrown into the blood current. Whether phlebitis be primary or consequent on thrombosis, it produces a series of inflammatory alterations in the diseased vein, similar to those produced in inflamed arteries (p. 491). Swelling and proliferation of the endothelial cells is first observed ; the entire internal membrane soon participates in the inflammation, and it thickens either regularly or in the form of granulations. The thickening is due to the new formation of numerous cells, some round similar to lymph cells, others elongated, fusiform, or flat- tened. Five or six days after the commencement of this endo- phlebitis, capillaries of new formation are akeady visible in the internal membrane ; they are most probably developed from the large fusiform cells just spoken of. These vaso-formative cells unite by means of their thread-like protoplasmic processes, and M M 2 532 LESIONS OF THE VEINS. form a network, or else they are arranged one after another and form embryonic capillaries perfectly distinct and easily recognised, even when they contain no red blood corpuscles. These capil- laries anastomose with the vessels of the middle coat, and circu- lation of the blood is thus established in the morbid internal membrane. This membrane is often continuous, without a definite line of demarcation, with the fibrinous portion of the clot ; the newly formed capillaries may even penetrate into the midst of the fibrinous trabeculse. Fine fibrils of connective tissue soon show themselves in the thickened internal membrane, and a fibro-vascular growth is produced which surrounds the fibrinous clot. The circulation of the blood and the arrangement of the blood- vessels in the internal coat deserve a special description. At the base of the thickened internal coat, and quite close to the internal limit of the middle coat, may be observed large sinuses or lacunar spaces, which receive the blood from the capillaries of the middle coat. These sinuses are lined with an endothelium, and their walls are simply formed by the adjacent connective tissue. They give origin to a network of fine capillaries, which send ramifi- cations throughout the internal part of the thickened internal membrane. The circulation of the blood in this new system, composed of aflferent capillaries, cavernous lacunae, and efferent capillaries, is eff'eeted easily and regularly, the proof of which is given on microscopical examination, for all the vessels are found filled with normal corpuscles. In the external coat also new cellular elements may be seen between the fibres, and it is decidedly swollen — 'periphlebitis. The middle coat does not generally undergo change ; in cases, how- ever, in which the inflammation is very acute, the wall of the vein may be the seat of true suppuration, which may invade even the middle coat. Thrombosis may thus become the origin of .a peripheral venous abscess. Suppuration is far from being the usual termination of thrombosis ; sometimes the blood clot is partly or entirely de- tached, and the blood current, re-established in the vein, bears along the thrombus, which finally obstructs a branch of the pul- monary artery, if it was formed in the general venous system, or an artery of the aortic system, if it originated in the pulmonary vein. Phlebitis rather frequently terminates by cavernous change of the vein. After absorption of the clot, the thickened internal mem- brane fills up all the original lumen of the vessel, but its blood- VARIX. 533 vessels may dilate at the same time that the septa separating them become thinner, from which it results that the connective tissue plugging the vein is traversed by lacunae full of blood, recalling the stnicture of certain cavernous angiomata (Pitres). The most frequent termination of venous thrombosis is, however, the definite obliteration of the vein, which is then transformed into a fibrous cord. Varix. — The term varix is given to a dilatation of veins accompanied with persistent modifications of their walls. The word varix is not absolutely synonymous with phlebectasis, for simple dilatation in phlebectasis may be seen, for example, around tumours, vrithout varix being present; indeed, if the tumour be removed, the simply dilated veins return to their original condition. Varices are especially observed in the superficial veins of the lower limb. To understand the arrangement of varicose veins, they should be dissected out throughout their whole length ; they are then found to be not simply dilated, but much more elongated and tortuous than examination of the living subject would have led one to suppose. The calibre of these veins is very irregular, and fusiform or ampullar dilatations are observed ; their walls have not everywhere the same thickness ; their valves are incompetent, and are often reduced to narrow bands flattened against the wall, or partly destroyed. At their level, considerable thickenings, in the form of nodules, are generally observed. The vein shows on its internal surface longitudinal projections and depressions. Its wall is thickened in places, so that in dividing the vein transversely it remains gaping like an artery. Calcareous incrustations in the form of plates, nodules, or nested balls are formed in the coats of varicose veins. Small calcareous plates are not always visible in a vein in the fresh state, but after dessication the calcified parts become evident by their opacity and prominence, while the adjacent parts have con- tracted and become transparent. Calcareous infiltration is seen in the form of balls or phleboliths in the varicose diverticula ; but calcareous induration of a vein may be seen for a length of several centimeters, the vein being then transformed into a solid tube with ramifications, continuous with other varicose veins. \Mien varices are old, and have reached a high state of development, the dilated tortuous veins form a kind of cavernous tumour with large meshes ; they are folded on themselves, and mixed with a mass of connective tissue, so that it is difficult. S34 LESIONS OF THE VEINS. sometimes even impossible, to isolate them ; it is equally impossible to dissect them out, and to separate the wall of each one of the veins constituting the tumour. Around all old varices the sub- cutaneous cellular tissue has undergone the changes of chronic inflammation ; it is infiltrated with fluid, is very vascular, and of a lardaceous consistence. To make a histological examination of varicose veins, the process already described for arteries should be employed, that is, dessication, transverse or longitudinal section, staining with carmine, and preservation in glycerine, to which formic acid is added. The changes shown consist in hypertrophy of the middle coat, caused by multiplication of its muscular .elements, and particularly by a new formation of fibrous tissue. The internal coat is not sensibly hypertrophied, vegetations are also not generally found on its internal surface, except near the insertion of the valves, and when there has been coagulation of the blood. This coat has the appearance of a band formed of two or three rows of lenticular nuclei, and it stains slightly with carmine. Beneath is an elastic network, the meshes of which are filled with large fasciculi of connective tissue, generally having a direction parallel to the axis of the vessel ; it is these which pro- duce the longitudinal prominences seen with the naked eye on the internal surface of the vein. To this internal layer of the middle coat, which is always of considerable thickness, succeed fasciculi of muscular fibres, which in longitudinal sections of the veins appear as islets formed of a series of clear circles showing centrally the section of a nucleus. In the external layer of the middle coat these fasciculi have almost all a transverse direction, and intersect the longitudinal fasciculi at right angles. They are generally separated from one another by connective tissue, so that this tissue is continuous without interruption from the internal coat to the external. Between the connective-tissue fasciculi, granules or masses of granules of blood pigment are often observed, which show that the venous wall has been in- filtrated with red blood corpuscles. The middle coat, thus modified, is from two to ten times thicker than normally. The trunk of the vein does not alone undergo dilatation, but all its branches, and even their vasa vasorum. These minute vessels then become tortuous and dilated, and their walls thickened ; when the dilatation of a vein is very marked, they may acquire a considerable diameter in the substance of the middle coat, and extend to its most internal layer; sometimes the dilated and TUMOURS OF THE VEINS. 535 tortuous vasa vasorum form in conjunction with the principal vein very complicated cavernous tumours. The calcareous plates of veins are developed in the fibrous and internal portion of the middle coat ; calcareous granules are first deposited in or between the fasciculi of connective tissue ; they soon increase in size, and join together to form transparent plates, grooved with irregular, opaque, and granular striae. Instead of being regularly dilated, varicose veins are more frequently enlarged only at certain points of their course, and present fusiform or sacculated dilatations. At these spots their walls are much thinned, and in sections comprising their entire thickness changes similar to those of the arterial walls in an aneurismal sac are observed. The muscular coat has more or less entirely disappeared, only a few scattered fragments of it remaining, and the blended external and internal coats alone constitute the wall of the dilated vein. These varicose sacs may become so thinned as to rupture and cause haemorrhage. The indurated connective tissue and hypertrophied skin near varices show the histological alteration of chronic phlegmon or elephantiasis. Small purulent foci are often formed which unite and open, leaving an ulcerating wound, the base and edges of which are indurated ; these ulcers then continue to enlarge and, blending with others, may attain considerable size. The inflam- mation often gains the surface of bones and causes osseous growths in the form of stalactites, sometimes of great extent. Tumours of veins. — Primary tumours are not observed in veins, with the exception of angioma which is developed in their walls (p. 239). Secondary tumoiu-s of veins are, on the contrary, fre- quent. When a vein is included in a malignant tumour, carcinoma or sarcoma for example, its wall often gives origin to the morbid tissue which grows in the form of vascular granulations into the lumen of the vessel. These granulations impede the circulation and cause coagulation, so that they may be found inclosed in the substance of a blood clot. Portions of these granulations may also become detached and form emboli. It is probable that the generalisation of certain sarcomata, encephaloid sarcoma par- ticularly, is brought about by the transportation of fragments of the morbid tissue, which are carried away by the blood current and engrafted in various organs, particularly in the lungs, and become the origin of secondary tumours. Also primary tumours of the kidneys, testicles, and limbs become generalised in the lungs. 536 LESIONS OF THE VEINS. while those which are primarily seated in the stomach and intestine are specially generalised in the liver. In the first case, trans- portation of the metastatic product is efi'ected by the general venous system, while in the second it occurs through the portal system. The sarcomata seem to be especially diffused by venous metastasis, while the carcinomata give origin to secondary tumours which almost always develop in the course of the lymphatic vessels. 537 CHAPTER XII. LESIONS OF THU LYMPHATIC VESSELS. I. Normal Histologry of the Lympliatic Vessels. The structure of the lymphatic trunks and vessels is similar to that of the veins of the same calibre. Three coats, an external adven- titious, a middle muscular, and an extremely delicate internal coat lined with endothelial cells, are described, as in the veins. The valves are much more numerous in the lymphatics than in the veins ; above the valve the vessel is enlarged, and at this spot the middle coat shows a number of muscular fibres crossing in every direction. In other regions the muscular elements have, on the contrary, a transverse direction. The supra-valvular en- largements seem to play an important part in the circulation of the lymph. The lymphatic capillaries, like the blood capillaries, have no muscular elements ; they are seen in the form of cylin- drical or flattened tubes lined by characteristic endothelium ; the cells composing it show, after being stained with nitrate of silver, blunt lateral teeth, which cog with others on neighbouring cells. While the veins have their origin in capillary networks, the lymphatics originate from the midst of the tissues, and have, at their commencement, no direct communication with the vascular system. The lymphatics empty into the subclavian veins, on the left side by the thoracic duct, and on the right side by the great lymphatic trunk; thus the lymph absorbed directly from the tissues is mixed with the venous blood after having circulated in the lymphatic system. From the discovery of the lymphatics to the time of Magendie an exclusive activity had been attributed to lymphatics in the phenomena of absorption ; but though Magendie proved that the veins absorb actively, the lymphatics must still be considered the principal agents of absorption. One of the most interesting and the most disputed questions is the origin of the lymphatic vessels in the tissues. At the time 538 LESIONS OF THE LYMPHATIC VESSELS. that these vessels were studied by means of injections of mercury under strong pressure, it was thought that the network thus in- jected was the sole origin of the lymphatic system ; but since much more penetrating fluids have been made use of, such as Prussian blue dissolved in water, for example, numerous lymphatic vessels can be injected into which the mercury could not penetrate. It is even sufficient to make an interstitial injection of Prussian blue into the connective tissue for this fluid to penetrate some lymphatic vessels, though the lymphatic reticulum cannot be completely filled in this way. To do so it is necessary for the point of the cannula to be inserted directly into a vessel. It must nevertheless be admitted that the lymphatic vessels open into the meshes of the connective tissue, since on injecting the latter the fluid constantly penetrates into some of the lymphatic vessels. We have already shown how the serous cavities are appendages of the lymphatic system, in that there exist direct communications- between them and the lymphatic vessels ; hence there can be no pathological change of serous membranes without the corre- sponding lymphatics being simultaneously altered. II. Pathological Histology of the Lymphatic Vessels. lymphangitis, or inflammation of the lymphatic vessels, is a rather frequent affection, being sometimes acute, sometimes chronic, and varying in intensity. It has been particularly studied on the smrface of the serous membranes and in the uterus. In pleurisy, pericarditis, and peritonitis, sections passing through the exudation and the subjacent serous membrane show very dis- tinctly the lumina of lymphatic vessels divided in various direc- tions ; they are then seen to be dilated, and to contain a substance resembling the exudation on the surface of a serous membrane, and when the inflammation is purulent they contain pus or fibrin inclosing pus cells. Their endothelium is always swollen, des- quamated, and proliferating, and their walls are infiltrated with new elements and even with pus cells. In acute lymphan- gitis of the limbs the suppurative inflammation extends to the ■cellulo-adipose tissue surrounding the inflamed lymphatics, so that they, together with the indurated tissue, form hard cords infiltrated with pus, and of a much larger diameter than normal full lym- phatics. In puerperal metritis the lymphatic vessels, which are found at the angles of the uterus and in the broad ligaments. LESIONS OF THE LYMPHATICS IN TUMOURS. 539 are often found dilated and filled with pus, and their coats infil- trated with pus cells. The perivascular sheaths of the brain have been regarded as veritable lymphatics ; but they are in reality appendages of the subarachnoid spaces. The pathological changes observed in these sheaths will be described when considering the diseases of the encephalon. It should be added that in certain cases of carcinoma of the stomach, lymphatic vessels are met with in the pleura and lung completely filled and distended with more or less caseous pus. MM. Eaynaud, Troisier, etc., have published cases of this kind. We also have observed similar changes of the pulmonary lymphatic vessels in a case of syphilitic gummata of the stomach (for further details see article Lung). This repletion of the lymphatic vessels of the pleura and lung in tumours of the stomach cannot be regarded as resulting from the direct trans- portation of the products of the primary tumour into the lym- phatics. We consider that it should rather be attributed to secondary subacute lymphangitis, which is simply inflammatory in certain cases and of a carcinomatous nature in others, and which is related to the simple or cancerous inflammation of the bronchial glands. Dilatation of the lymphatic vessels (Lymphangiectasis). — In elephantiasis and congenital macroglossia the lymphatic vessels are dilated without undergoing any notable changes of structure ; their epithelial cells are well developed and easily seen. The injection of these vessels is always much easier than when in the normal state {vide p. 243). lesions of the lymphatic vessels in tumours. — Tuberculosis of lymphatic vessels is very often observed in the serous membranes — plexu-a, pericardium, peritoneum. In the visceral peritoneimi, near to tubercular ulcers of the intestine, knotty, white, opaque cords are often seen radiating from the indiu-ated base of the ulcer ; these cords, which are raised on the peritoneal surface of the intestine, cross the mesentery to reach the neighbouring lymph- atic glands. Upon their surface prominent tubercular granula- tions are often seen, and on cutting them across a white or yellowish opaque caseous substance can be turned out. In these vessels are found ordinary lymph cells, much larger corpuscles filled with fat granules, and free fat granules. In histological preparations all the phases of development of tubercular granula- 540 LESIONS OF THE LYMPHATIC VESSELS. tions may be observed. In the first stage tbe vessels are filled with cellular elements, some of which are ordinary lymph cells, others very probably derived from the vascular endothelium. The walls of the lymphatics and the neighbouring connective tissue are infiltrated to a great extent with embryonic cells. In the second stage the cells grouped in the wall of the lymphatics and in the connective tissue form nodules, having all the cha- racters of tubercular granulations ; these nodules are rather far apart ; sometimes, however, they almost touch, and blending with neighbouring granules form a mass of confluent tubercles. Tubercular inflammation' of the lymphatic vessels may also be 1 i Sj.i. .:;. < ■l\T^•.■ .^->i-4.A^^^n%-^^ ptifleu^ Fig. 255. — Transverse Section of a Tuceecular Lymphatic Vessel on THE Surface of the Intestine, a, cavity of the lymphatic vessel, which is seen to have undergone contraction and to be filled with lymph cells ; c, sub-peritoneal connective tissue, in the midst of which passes the lymphatic vessel, the walls of which are much thickened by the development of tubercular tissue ; i, tubercular tissue, the external zone of which is formed of round cells much larger than those of the internal zone which are caseous ; v, capillary vessels ; », layer of longitudinal smooth muscle cells ; m, layer of transverse muscle cells of the intestine. propagated to the thoracic duct, which is often found filled with caseous pus, while tubercular granulations are formed in its wall. When carcinoma produces inflammation in the lymphatic vessels which pass from the tumour, they form hard cords, gra- dually increasing in size until they reach that of a crow's quill. This may occur in certain hard carcinomata of the mamma, in which many repeated attacks of angioleucitis terminate by trans- forming the lymphatic vessels into hard full cords, entirely scirrhous in structure. In secondary carcinomata of the lungs and pleura, knotted networks of grey, indurated, semi-transparent or opaque lymphatic vessels are sometimes seen upon the THE LYMPHATICS IN CARCINOMA. 541 surface of the serous membrane. The vessels composing these networks contain a milky juice, formed of large cells resembling those of the tumour. Small carcinomatous nodules are often found in their walls. The same carcinomatous degeneration of lymphatic vessels may be observed in other serous membranes, particularly in the peritoneum. Lymphatics communicate with the alveoli of carcinoma (p. 179), and it is hence very probable that the carcinoma cells they contain penetrate into these vessels, and are carried for a variable distance ; they then undergo mul- tiplication and become the starting-point of carcinomatous change in the walls of the lymphatics, and of secondary nodules in their neighbourhood. >!42 CHAPTER XIII. LESIONS OF THE LYMPHATIC GLANDS. I. Normal Histology of tlie Lymphatic 'Glands. From the descriptions given by various authors, it might be thought that the structure of lymphatic glands is very com- plicated, but it is in reality extremely simple. A lymphatic gland presents for consideration a fibrous capsule, a cortical sub- stance, which is interrupted only at the hilus, and which contains the follicles and the sinuses, and, finally, a medullary substance which extends as far as the hilus, and which contains the follicular cords and cavernous lymphatic spaces. In the fibrous capsule the connective-tissue fasciculi form a kind of felting, much more closely woven than ordinary loose connective tissue. From this capsule spring fibrous trabeculse, which divide, anastomose, and finally converge towards the hilus of the gland where they terminate. The capsule is traversed by afferent lymphatic vessels at dififerent points on its surface, the hilus excepted, and they open into a cavernous system, the ar- rangement of which will be described later. The efferent vessels also originate in this cavernous system, and may be recognised as distinct canals in the hilus of the organ at which they issue. The cavernous system, which corresponds to the lymphatic sinuses and channels of His, is permeated by the arteries and veins of the gland. These blood-vessels are not only found in the spaces of this system but in the centre of the fibrous trabecule, which are derived from the capsule and converge towards the hilus. From these fibrous trabeculse spring small fasciculi of connective tissue, which, dividing and anastomosing with neigh- bouring fasciculi, form a complicated network, which, from the histological point of view, does not essentially differ from the structure of the great omentum, excepting that these trabeculse radiate in every direction, while in the great omentum they are placed in the same plane. In sections of glands cut perpendicu- larly to an artery the artery is seen to be surrounded by a ring, STRUCTURE OF THE LYMPHATIC GLANDS. 543 which represents a transverse section of a fibrous trabecular septum ; from the margin of this ring spring radiating fasciculi of retiform connective tissue. Thes^ trabeculse have no nuclei either within them nor along their tract, nor at the points where they intersect ; they are covered with flat endothelial cells similar to those observed on the fine trabeculse of the great omentum. The meshes of this reticulum of the cavernous system are filled with lymph which is extremely rich in cells ; thus, in order to Fio. 256.— Section of the Medullary Tissue of a Lymphatic Gland OK THE Ox. o folUoular Bubstanco ; 6, flbrooB eepta ; c, lymph channels ; d capillaiy blood-vessels. Magnified 800 diameters. (Figure borrowed from Eeoklinghaasen.) examine the structure of a lymphatic gland, the ceUs must be removed with a camel's-hair brush. If a lymphatic gland be injected with a solution of Prussian blue, the coloured fluid fills ail the system of lymphatic channels, and returns by the efferent vessels. In sections of a gland thus injected it will be seen that the injection has not found its way into all parts of the gland ; it has only penetrated mto the channels filled with lymph from the afferent to the efiferent vessels, marking out, in the cortical substance, the lymph smuses, and m S44 LESIONS OF THE LYMPHATIC GLANDS. the medullary substance the cavernous spaces which lead to the efferent vessels ; but it has left the follicles and follicular cords entirely unstained. The follicles are best seen in the glands of the mesentery at the moment of digestion, for they are then slightly translucent, while the lymphatic channels described above are filled with chyle and form opaque sinuses. These follicles are round upon the free surface of the gland, while at the hilus they form one or more sinuous and characteristic prolongations, to which the distinctive name of follicular cords has been given. We designate the entire follicle by the name of the follicular system, reserving to the channels through which the lymph circulates the name of the cavernous lymphatic system. The arteries and veins of the gland contained in the great fibrous trabeculse ramify in the cavernous spaces, while the blood capillaries are only found in the follicular system, where they form a network. The tissue composing the follicles and follicular cords is similar to that present in the whole cavernous system ; it differs from it only by the extreme thinness of its trabeculse, and by the smaller size of its meshes. The capillaries which ramify in the folUcular substance are surrounded by a special layer of fine fibrils, which divide and anastomose, and finally blend with the trabeculse of the connective-tissue reticulum of the follicular substance. There are neither nuclei nor cells in the substance of these trabeeulae, nor at their points of intersection. The nuclei, described by some authors, belong to the extremely delicate endothelial cells which line the surface of the trabeculse of the reticulum, covering them like a varnish.' ' To be convinced that the nuclei observed on the trabeculse of the reticulum of the follicular substance, as well as of the cavernous system, are not contained within the trabeoulEe, recourse must be had to the following methods. Two similar lymphatic glands are removed from a dog which has just been killed; into one of them a cubic centimetre of a 1 per cent, solution of osmic acid is injected ; the gland is then hardened by submitting it to the successive action of alcohol, and gum and alcohol, and sections are cut from which the cells are brushed away. Along the trabeculse, and at their points of intersection, distinct oval nuclei will be recognised. The other gland is placed for twenty-four hours in a 33 per cent, solution of alcohol, and is then hardened with gum and alcohol. The sections cut are immersed, in water, brushed with a camel's-hair brush, when the reticulum of the reticulated substance, as well as the cavernous system, is seen to be entirely deprived of any cellular elements. Two different preparations are thus made, showing the structure of the reticulum ; in one all the nuclei are preserved, in the other all the nuclei have disappeared ; in the first preparation, the endothelial cellular elements acted upon by the osmic acid have been fixed ; in the other they have, on the contrary, been removed from the trabeculse by the STRUCTURE OF LYMPHATIC GLANDS. 545 The limit between the follicles and the cavernous lymphatic system is tolerably distinctly seen in preparations made after the interstitial injection of Prussian blue, or in preparations hardened with alcohol, and from which the cells have been washed away with a camel's-hair brush. In the cavernous tissue the meshes of the reticulum being larger and the lymph cells less numerous than in the follicular system, they are easily removed, and the cavernous system is seen to form so many clear spaces, but no true limit- ing membrane can be distinguished between the two systems ; it may in fact be proved by experiment that there is easy communication between them. To demonstrate this fact, fine powdered vermilion suspended in water is injected into the deep connective tissue surrounding the sciatic nerve of a rabbit. The animal being killed forty-eight hours afterwards, the lymphatic vessels proceeding from the region where the vermilion had been introduced are found filled with it, as if they themselves had been injected. The lumbar glands, to which these vessels pass, also contain vermilion, which is found particularly in the cavernous system, so that on the surface of the organ the follicles appear as white circles surrounded with red bands. In sections made after hardening, it is seen that the particles of vermilion are contained in the cells, namely in the lymph cells and in the endothelial cells lining the trabeculae of the reticulum ; but particles of vermilion may also be observed in a few of the lymph cells of the follicular substance. In the physiological phenomenon of the transportation of the chyle through the mesenteric glands during digestion, fat granules are found, not only in the spaces of the cavernous lymphatic system, but also, though in smaller numbers, in the cells of the follicular system. It is hence probable that the meshes of the retiform tissue of the follicles are in communication with the meshes of the cavernous system, from which it may be concluded that a lymphatic gland is nothing more than a complicated lymphatic cavity, or a serous cavity placed along the course of lymphatic vessels. The afferent vessels enter this cavity at different points on the surface of the lymphatic gland, and the eflFerent vessels issue from it at the hilum ; they are here side by side with arteries and veins which have distinct walls, while the efferent lymphatics action of the dilute alcohol, which acts as a dissociating fluid. It may hence be concluded that nuclei existed on the surface of the trabeculae, and that they were removed by the camel's-hair brush, which would not have affected them if the nuclei were located in the substance of the tfabecula?. 546 LESIONS OF THE LYMPHATIC GLANDS. are simply canals hollowed in the substance of the connective tissue and lined with an endothelium. If circulation of the lymph is easy in the cavernous system it is not the case in the follicular system. It is probable that the parts composing it, the follicles and follicular cords, play an important part in the formation of the lymph cells, which after being developed in the folUcular substance penetrate into the cavernous system, and thus enter the great lymphatic circulation. II. Pathological Histology of the Lymphatic Glands. Pigmentation of glands. — The peri-bronchial lymphatic glands of adults and old persons may be often seen to be of a black colour. A similar pigmentation may be seen in other glands, when the regions from which their afferent vessels are derived have been the seat of infiltration of blood or foreign granular and coloured substances. Thus in tattooing, the coloured powders introduced into the skin are subsequently found in the corre- sponding lymphatic glands. If the coloured particles, instead of being deposited in the connective tissue, existed or were intro- duced into the blood, pigmentation of the lymphatic glands would not occur or would be very limited ; this fact results from the experiment of Langerhans. It has already been described with what rapidity coloured particles penetrate the lymphatic glands when deposited in the connective tissue ; it has also been seen that when extravasated blood undergoes a series of metamorphoses ending in the formation of pigment granules, they are taken up by the lymphatics and become fixed in the glands. Thus, the coloured particles found in glands are of two kinds — they are either derived from the blood, or they are foreign to the organism; the former are yellowish-red, brown or black, round or angular, some observers having also found alongside them true crystals of haematoidin (Eebsamen) ; the latter, formed of opaque substances, always appear black or dark to transmitted light, and may be carbon, vermilion, metallic powders, etc. G-lands infiltrated with pigment are of a grey slate colour, black, or marbled grey, white and black. The pigmentation is particularly seen in the cavernous lymphatic system, the follicular system being very faintly coloured. If there are a few blackish strioe, they exclu- sively occupy the spaces of the cavernous system. Glands infiltrated with pigment are generally larger and ACUTE ADENITIS. 547 firmer than normally. The increase in size of a gland by pene- tration of pigment may be easily reproduced in experiments on animals. If half a cubic centimetre of water holding particles of vermilion in suspension be injected into the peri-sciatic tissue of the rat, one of the two lumbar glands deeply stained by the ver- milion will, at the end of twenty- four hours, be found twice as large as the corresponding gland. This increase in size is not solely due to accumulation of foreign particles, but chiefly to the congestion and inflammation they have caused. In man certain pigmented glands are hard, and show on section a hard spiny surface, from which no juice can be pressed. The slow irritation caused by the presence of the pigment has produced a true fibrous change. In sections it will be seen that the arteries are surrounded with thickened fibrous zones, and that the connective tissue cells are infiltrated with pigment ; the trabeculse of the reticulum of the cavernous substance are hyper- trophied, and their endothelial cells contain pigment granules ; the lymph cells which crowd the meshes of the reticulum also contain them. The follicular substance is no longer distinct from the cavernous system, the retiform tissue may even have entirely disappeared, and the perivascular connective tissue, infiltrated with pigment, may fill up the whole organ. But these examples of complete transformation of the glands, and interstitial adenitis with pigmentation, are only found in old persons or in miners. Glands which are only slightly pigmented, as, for example, the bronchial glands after pneumonia, the glands of the articular folds after phlegmon or haemorrhage into the connective tissue of the limbs, show very different appearances. They are hypertrophied, and yield a very abundant jiiice, in which are found small, spherical cells containing yellowish-red or brown pigment granules, also large stellate or angular cells, containing many oval nuclei and pigment granules. When the change is old, all the pigment granules are absolutely black. On dividing the glands it is seen that the cavernous substance is principally the seat of pigmenta- tion and that side by side with pigmented lymph cells there are others which are colourless. The endothelial cells of the reticulum of the follicular substance also contain coloured granules ; they are then slightly tumefied and can be more easily detached. Acute adenitis. — Inflamed glands are sometimes considerably increased in size ; they then tend to take a spherical form, or if in contact with neighbouring glands equally tumefied they become N N 2 548 LESIONS OF THE LYMPHATIC GLANDS. flattened one against the other. The surrounding connective tissue is the seat of inflammatory oedema, the blood-vessels are dilated, and around them small ecchymoses are found. In acute adenitis this cBdematous connective tissue shows purulent foci, or even abscesses may be formed, so that the lymphatic gland may be entirely surrounded with a layer of pus ; this lesion has been called peri-adenitis. In the gland itself are found lesions which vary according to the degree of the inflammation. In the first stage there is inflammatory oedema, which is particularly well marked; in the cavernous lymphatic system the follicles and follicular cords are much more distinct than usual, and they form dark spots or lines on a slightly transparent groundwork. In some cases, the hyperaemia and effusion of blood which accompany adenitis cause, with increase of volume, a red or reddish-brown pigmentation of the entire gland, which then resembles splenic tissue. Such is the lesion generally observed in the bronchial glands after pneumonia or acute capillary bronchitis. The juice of these glands contains, besides ordinary lymph cells, other lymph cells in which red blood corpuscles or fragments of them are found. A great number of red corpuscles also float in the fluid of the preparation. At a more advanced period the distinc- tion between the two systems of the gland is no longer possible, and on scraping the divided surface a very abundant juice is obtained, as in soft carcinoma. In section of a normal gland, twenty-four hours after death, a slightly milky fluid is obtained similar to that yielded by encephaloid sarcoma, but in inflam- mation this juice is much more abundant and more milky. Examined under the microscope this juice is seen to contain a large number of lymph cells, and large tumefied endothelial cells containing one or more nuclei ; sometimes the latter, which may reach a diameter of '03 mm., resemble the multi-nucleated cells of bone medulla ; they are smaller, and contain fewer nuclei than those found in certain forms of subacute or chronic inflammation, to be studied further on. In diffuse suppuration of glands their divided surface yields, on scraping, creamy pus, the afferent and efferent lymphatic vessels being filled and distended with the same fluid. Suppurative inflammation of glands may extend to the formation of distinct purulent foci, or to complete purulent infiltration ; it is sometimes accompanied with more or less extensive heemorrhage, the blood infiltrating into the parenchyma of the inflamed gland. The pus cells which fill the purulent foci do not differ greatly from normal ACUTE ADENITIS. 549 lymph cells ; they contain, however, a much larger number of fat granules, and beside them may be seen large granular bodies. In sections of an inflamed gland in the first stage of inflamma- tion, that of swelling and oedema, cut after hardening in picric acid and removal of the cells by brushing, the modifications of cells already described are seen, notably swelHng and multipli- cation of the nuclei of the endothelium. The trabeculae of the cavernous system are tumefied, and instead of being formed of a homogeneous substance they seem to be composed of a fibrillar and granular substance ; they may even attain five or even ten times their normal diameter. In the follicular substance the trabe- culaB of the retiform stroma are less swollen, and seem simply strewn with granules. When the inflamed gland is of a red colour like the spleen, the capillaries of the follicular substance are found to be largely dilated and filled with red blood corpuscles, and between the lymph elements, which crowd the meshes of the retiform stroma, collections of red blood corpuscles may be observed, or are regularly disseminated. To accurately observe this change the gland should be hardened in alcohol, delicate sections cut, stained with carmine and mounted in glycerine ; the red blood corpuscles will then be seen as small clearly defined rings, unstained by the carmine. When the adenitis is purulent, irregular loss of sub- stance may, in microscopical sections, be observed near the purulent foci, and at their margins the process of destruction of the fibrils of the retiform stroma may be followed. These fibrils are seen to swell, soften, and finally break down into a granular detritus, which is absorbed by the neighbouring lymph cells. It will also be observed that the loose connective tissue around the large vessels is infiltrated with pus cells. Acute adenitis is rarely primary ; it is most frequently ob- served in glands of which the lymphatic radicles originate in an inflammatory focus. It is thus very probable that inflammation of the gland is related to absorption of irritating substances— still ill determined — which are elaborated in the inflammatory focus, or derived from the exterior. As examples of inflammatory foci causing adenitis, we may mention pneumonia, bronchitis, im- petiginous eczema, chancre, blennorrhagia, excoriations and ulcera- tions, ulcerations of the intestine, especially those of typhoid fever. Adenitis may also be observed in infectious diseases — syphilis, plague, scarlatina, variola, etc. — in which there is most probably transportation of the virulent matter by the lymphatic channels. 550 LESIONS OF THE LYMPHATIC GLANDS. Chronic adenitis. — Simple fibrous degeneration, simple or scrofulous caseous degeneration, and, finally, calcareous degenera- tion of lymphatic glands, are generally referred to chronic inflam- mation. Fibrous induration is rather common in the bronchial and ingmnal glands of persons advanced in age ; it is most frequently accompanied with slight hypertrophy and pigmentation; it consists in an increase in thickness of the perivascular connective tissue of the cavernous system; the reticulated trabeculse of this system may become double or triple their normal size, and at numbers of points they appear to be fibrillated. The follicular parenchyma appears, on the other hand, to be more or less considerably atrophied, and may even entirely disappear ; generally, only a few disseminated, irregularly shaped fragments are found, particularly towards the periphery of the gland. In lymphatic or scrofulous subjects, enlargement of the glands generally follows catarrhal inflammation of the mucous membrane, or moist eruptions of the skin, and ends in the degeneration of glands, which were previously hypertrophied. Hypertrophied and strumous cervical glands are frequently discovered after death or after surgical operations. They are generally united into one large mass ; in the same individual they may have very various appearances, some being in an advanced morbid condition, while others show all the different phases of evolution of scrofulous adenitis ; some are simply hypertrophied and congested, others show the characteristic appearances of scrofulous adenitis fully established. The shape of the glands is preserved, though they are extremely large, of a pale grey yellowish colour, and soft elastic consistence. Their surface on section is generally dry, and, on looking attentively with a magnifying glass, a crowd of small grains or opaque points on a grey semi-transparent base is perceived. These small opaque points form by their growth and union small yellowish caseous foci, more or less resistant. In a later stage these foci are fused together, and form an opaque whitish grumous mass, varying in firmness and dryness according to the age of the lesion. When this degeneration is old the hypertrophied gland seems to be composed of a chalky, dry, non- vascular substance, which breaks up into grumous fragments, and is enveloped by the thickened capsule of the gland. Calcareous degeneration occurs as the final stage of this lesion. In old persons, glands are rather frequently found formed of a fibrous capsule, containing a slightly lobulated calculus, held to the CHANGES IN STRUMOUS GLANDS. 551 capsule by fibrous filaments which penetrate into its interior. This calculus is friable, or is sufficiently firm to rebound if let fall on a hard surface. It is rare, however, for petrifaction to be so complete, for petrified glands generally only contain one or more calcareous masses varying in size and shape. On examining stnunous glands under the microscope, at the period when they are hypertrophied, yellowish-grey in colour, and sprinkled over with small points or opaque foci, two lesions are found : thickening of the fibrous trabeculae, and granulo-fatty degeneration of the cellular elements of the follicular system. Quite at the commencement, the fibrous tracts which pass from the periphery of the gland towards the hilum are thickened, and form bands of connective tissue which accompany the blood-vessels, and divide the adenoid tissue into distinct islets. As the connec- tive tissue becomes more abundant the islets of adenoid tissue, which it surrounds, take a spherical form. Here the same phe- nomenon occurs as in certain forms of cirrhosis of the liver, in which the hepatic lobule is divided and subdivided into small groups of round cells, surrounded by bands of fibrous tissue. Sections, stained with picrocarminate of ammonia and examined under a low power, show small islets stained orange-red, formed of the retiform tissue of the follicles, and surrounded by broad bands of embryouic or fibrous connective tissue stained red by the carmine ; in these islets are found large cells, containing one large ovoid nucleus with a nucleolus, and formed of a delicate, soft, granular protoplasm., often including fat granules. These cells, the nucleus of which stains easily with carmine, are elongated, slightly flattened, or globular ; they rarely contain two nuclei. The structure of these foci can be better studied in sections cut as fine as is possible in the fresh state, and from which the lymph cells have been removed by a camel's-hair brush, and afterwards stained with picrocarminate. They are then seen to be composed of a reticulum, the fibrils of which are softer, thicker, and more granular and friable than the normal fibres of the follicular reti- form tissue. When examined under a very high power, small granules axe seen on the margins of these fibrils, and their surface is rough ; they are infiltrated, tumefied, and softened ; the meshes which they form are much larger than normally, and inclose large granulo-fatty cells with ovoid nuclei, just described. At the points where the cells have been altogether washed away by the camel's- hair brush a few fatty granules still remain, fixed to the fibrils of the reticulum. 552 LESIONS OF THE LYMPHATIC GLANDS. In sections made after the gland has been immersed for some time in dilute alcohol, and from which the cells have been washed away by agitation of the section in water, a clear space is seen with the naked eye in the place of the formerly dark spot, and is found under the microscope to be the framework of retiform tissue with its capillary vessels. The fibrous tissue surrounding the opaque spots is formed of fibrils belonging to the primary retiform tissue, but thickened and rigid ; they run in a direction parallel to the surface of the small foci, and contain small round cells between them. In sections obtained after complete hardening in Miiller's fluid, or in gum and alcohol, the islets and the bands of fibrous tissue which separate them are well seen ; the fibrous capsule of the gland is also seen to be thickened, but the retiform tissue of the islets cannot be cleared by means of a camel's-hair brush. When the caseous islets are older, the vessels crossing them are obliterated, and in transverse sections, made at right angles to their axes, they are seen as so many circles filled with nuclei, and resemble giant cells. The cells contained in the reticulum then become more and more granular, and finally atrophy. The caseous islets become more or less completely separated from the tissue which surrounds them, and seem to be limited by septa. In consequence of the confluence of the caseous islets, or of the caseation of a group of islets and the connective tissue sur- rounding them, the gland becomes yellow and friable for a more or less considerable extent. The caseous parts are almost always spherical, and surrounded by a fibrous membrane ; in them are only seen round atrophied cells, slightly transparent or granular, lying in contact with one another. The fibrous tissue is dense, homogeneous, and semi-transparent, and is united to the thick- ened capsule of the gland. The surrounding cellulo-adipose tissue has disappeared, and is replaced by sclerotic tissue which is often closely united to neighbouring parts, to the submaxillary or parotid glands, for example. This change, which differs in a marked degree from tubercle, properly so called, of the lymphatic glands, is of the same order as the caseous changes which occur in other organs in scrofulous subjects. It is possible that in certain cases it is related to tuberculosis, for, as we have ahready said (p. 201;, this disease may manifest itself, not only by cha- racteristic tubercles, but also by inflammation which has a ten- dency to terminate in caseous degeneration ; in the same way as syphilis is shown simultaneously, by gummata, and by various inflammatory neoplasms ending in caseous degeneration, and AMYLOID DEGENERATION OF GLANDS. 553 which differ essentially from those of tuberculosis by the tendency they show to form connective and osseous tissue. The stony masses of the lymphatic glands do not possess the structure of bone ; examined in delicate sections they are seen to be transparent, and to contain irregular fissures, and striae ; they are partly soluble in hydrochloric acid, when they give off carbonic acid gas. Amyloid degeneration of lymphatic glands. — This lesion is met with in connection with similar changes in the spleen, kidneys, and liver under the same circumstances, that is to say, in cachexia due to suppuration of long standing. It is accompanied with a regular hypertrophy of the gland, which may be sometimes very marked. On dividing the gland, grey semi-transparent spots will be seen either throughout its whole extent or in its cortical substance, which spots become of a mahogany-red colour when treated with a solution of iodine, and sometimes violet, bluish, and green bands appear on adding sulphuric acid to the parts already stained by the iodine. The lymph cells are infiltrated with amyloid substance, and are transformed into small, trans- parent, and homogeneous blocks, made angular by reciprocal pressure. The capillaries and arterioles have equally undergone amyloid degeneration and show the appearances already described on pages 517 and 525. The amyloid lesion is limited to the follicles of the cortical substance and follicular cords, to the ex- clusion of the cavernous substance and lymph channels. In deli- cate sections, made after hardening in alcohol, and staining with Paris violet, amyloid degeneration of the retiform tissue of the follicles may be recognised. In much hypertrophied glands, the anatomical signs of chronic inflammation may also be observed. The lymph channels and sinuses are very much enlarged and filled with spherical cells, containing one or more nuclei ; at the same time the endothelial cells lining the walls of the lymph channels and their septa are tumefied and granular, and show multiplica- tion of their nuclei. The connective tissue of the gland may also be thickened. Colloid change. — We have frequently met with a lesion of lymphatic glands, consisting in colloid degeneration, the cause of which iie were unable to discover. In sections cut after hardening in alcohol, the degenerated parts are seen to be formed 554 LESIONS OF THE LYMPHATIC GLANDS. of a series of alveoli of various sizes, filled with a colloid and refractive substance. These alveoli are separated by fibrous trabe- culse, on the margin of which are often seen rows of spherical cells, some of which are vesicular and contain colloid matter. This morbid change is without clinical interest ; it is particularly seen in subjects advanced in age, and seems to be related to an arrest of the function of the gland. Tumours of the lymphatic glands. — Almost all tumours of the lymphatic glands, with the exception of hypertrophy due to leu- kaemia or oedema {vide pp. 248 and 465), are secondary. It may be said, in a general way, that all glandular tumours resulting from a primary tumour, such as sarcoma, carcinoma, tubercle, chon- droma, epithelioma, etc., faithfully reproduce the anatomical form and structure of the primary tumour with which they are con- nected by their afferent lymph vessels. The glands affected in the vicinity of the tumour sometimes even better enable us to deter- mine the nature of a tumour than examination of the primary tumour itself: if, for example, an ulcerated and gangrenous tumour of the cervix uteri is under examination, study of the glands of the lower pelvis, secondarily affected, would serve better to determine the nature of the neoplasm than examination of the organ primarily affected. Sarcoma is much rarer in the lymphatic glands than carcinoma and epithelioma. We have already seen, in fact, that carcinoma and epithelioma are particularly propagated by lymph vessels, while sarcoma becomes generalised by the circulation. If, however, sarcoma is developed in the vicinity of lymphatic glands, they may be affected by extension of the tumour, in which case the capsule and parenchyma of the gland are seen to be successively changed into sarcomatous tissue. A species of tumour, called by Billroth adeno-sarcoma, is on the contrary generalised by means of the lymph channels. It is difficult to fix the place adeno-sarcoma should occupy in the classification of tumours ; it may be only a variety of carcinoma. It causes the successive transformation of a chain of glands, a change charac- terised by considerable hypertrophy of the glands affected. These glands, which are quite encephaloid in appearance, are often fused with neighbouring glands into a single mass ; they yield an abundant juice, in which large cells of various shapes, and con- taining large nuclei, may be seen. In sections cut after hardening, CARCINOMA AND TUBERCLE OF GLANDS. 555 fibrous trabeculae are recognised, and from them springs a large- meshed fibrillar reticulum, the fibrils of which are covered with flat cells, these meshes containing the polymorphous and volumi- nous cells spoken of above. Carcinoma of the lymphatic glands is very common ; thus carcinoma of the mamma is almost always complicated with what is called induration of the axillary glands. Some of these glands are small, firm, and fibrous in appearance, others are composed of a tissue resembling that of the primary tumomr. We have already seen, on page 179, that fibrous degeneration of the lymphatic glands often precedes the formation of characteristic carcinomatous tissue. Fibrous change is brought about by a very simple histologi- cal process. All the fibrils of the reticulum, in the cavernous as well as in the follicular system of the gland, hypertrophy so that the alveoli between them become smaller and smaller, and sometimes even entirely disappear. In this way the lymph channels of the gland may become almost entirely obliterated. The gland thus altered is, for a certain time, a barrier to the propagation of cancer ; but after having undergone this remarkable fibrous alteration it shows later on the characters of carcinoma, and becomes itself a new focus of infection. When secondary carcinoma of the lymphatic glands develops rapidly, the cellular elements contained in the trabeculae of the reticulum take at once the form of the so-called cancer cells, while the trabeculae gradually increase in thickness, to form the septa of carcinomatous tissue. Eegarding the formation of cancerous alveoli in fibrous tissue (see p. 176), we have already shown that when lymph vessels proceed from a cancerous tumour, they con- tain large polymorphous cells ; the afferent vessels of lymph glands undergoing cancerous degeneration often also contain simi- lar cells ; it may hence be supposed that infection is produced by the transportation and grafting of cancer cells, or that these cells having once reached the gland are the starting-point of the change. Tubercle of the lymphatic glands.— Tuberculosis of the lym- phatic glands is very common : the glands of an organ affected with tuberculosis, as the lung or intestine, almost always show tubercular granulations. We recommend the mesenteric glands for this study, for they are not encumbered with coloured particles like the bronchial glands. In tubercular ulceration of the intestines, if the lymph vessels, which are generaUy inflamed and tubercular, are traced from the intestine to the lymphatic 5S6 LESIONS OF THE LYMPHATIC GLANDS. glands of the mesentery, the latter will almost invariably be found to be tubercular. Tubercular granulations are often observed on the surface of the glands, in the fibrous capsule itself, and some- times round the afferent vessels, where they have the same rela- tions as in other lymph vessels, such as on the surface of the perito- neum, for example {vide p. 540 and fig. 255). Tubercular glands vary greatly in size ; they are often small, hardly larger than normal, though they may contain one or more discrete granulations, or even groups of confluent granulations. The size is more particularly related to the various processes of inflammation which complicate tubercle. Thus at the begin- ning, granulations are accompanied with intense inflammatory congestion, when it is not rare for the glands to attain a very large size ; their surface on division is thin, red, and saturated with a milky fluid more or less blood-stained. Tubercular glands of the mesentery are sometimes infiltrated with pus, in which case they become still larger. On examining, with the imaided eye, a tubercular gland which has been divided in its long diameter, the granulations cannot always be seen, the surface only looking a httle drier than normally without change of colour ; it is rare for the granulations to make marked prominences in section ; they are more frequently seen in the form of grey or yellowish-grey spots, more opaque and drier than the rest of the section. Such an appearance, however, sig- nifies that the granulations are confluent. When they are older they are yellow and caseous. Sometimes, in glands near the bile duct, the tubercles are seen to be of a bright yellow colour, which is due to the fact that they are infiltrated with the colouring matter of the bile. We once had occasion to see tubercles in the bronchial and cervical glands stained with bile. Sections of glands, containing a small number of recent granu- lations, show that they are most frequently located in the retiform tissue of the follicles near to the capsule. In shape they are more or less regularly circular, of a diameter of '05 to -10 mm., and by the fusion of many together they may extend and form irregular masses. The blood-vessels surrounding them are very much dilated. The granulations are composed, at their commencement, of reti- form tissue, in which the lymph cells seem to be heaped together, and to have become granular and atrophied ; the capillary blood- vessels are soon obliterated and giant cells are formed. The reti- form tissue near the granulations is continued into their interior, they not differing from normal retiform tissue except by some FIBROUS AND CASEOUS DEGENERA TION OF GLANDS. 557 slight modifications of the lymph cells and capillaries they contain. In granulations the lymph cells are atrophied and pressed together, and the fibrils of the retiform tissue become thinner and granular, till the reticulated stroma and the cells are closely united, and the whole tissue, with numerous giant-cells scattered through it, ultimately undergoes caseous degeneration. The development of tubercular granulations is almost always accompanied with more or less acute inflammation ; the sinuses and the whole cavernous system are then filled and distend^ with large granular cells, containing one or more oval nuclei and some- times red corpuscles ; these cells are derived from the endothelial or lymph cells. This inflammation of the sinuses and cavern- ous substance is, when intense and general, shown by hypertrophy of the gland, which on section is seen to be pinkish or grey, and saturated with a milky and blood-stained juice. Small colloid spots are sometimes seen in the cortical substance, or in the midst of the follicular tissue of inflamed and tubercular glands ; these spots are formed of masses of clear, transparent, non-nucleated lymph cells, with colloid contents, and are two or three times larger than normally ; they stain with picro-carminate of ammonia, and they give none of the usual reactions of amyloid substance. Another inflammatory lesion, namely fibrous degeneration of the retiform tissue, is frequently observed in tubercular lymphatic glands. The fasciculi of the newly formed connective tissue are thick and homogeneous, and resemble those of the skin; they stain red with picro-carminate of ammonia; they are at first found round the small arteries, and they follow the capillaries and reach the retiform tissue. On dividing a gland this new fibrous formation is plainly seen in the form of small, clear, transparent islets, which stain easily with carminate of ammonia- This chronic interstitial inflammation is even met with in tubercular glands which have undergone suppuration ; in fact, suppuration of tuber- cular glands is not rare; it is observed when tubercles of the organ primarily affected, the intestine or lung, are themselves rapidly destroyed by suppuration, as when, for example, there are numerous tubercular ulcers of the intestine, trachea, or bronchi undergoing rapid destruction, or freely suppuratmg pulmonary cavities. In such cases one or more glands may be found at the root of a bronchus in a state of suppuration, communicatmg by a fistulous tract with a purulent focus. Tubercular granulations finally undergo caseous degeneration, which may affect a part or the whole of the gland, which then 558 LESIONS OF THE LYMPHATIC GLANDS. presents entirely the same appearance as a scrofulous gland in the stage of caseous degeneration. But though termination by caseous degeneration is identical in tuberculosis and scrofula, the initial lesions are very different ; at the commencement of tuberculosis, inflammation, characterised by the accumulation of large cells in the lymph sinuses, is observed between the granulations ; at the commencement of scrofula, generalised interstitial adenitis is pro- duced, and the small islets already described, which must not however be confounded with tubercular granulations. Syphilis may cause inflammatory hypertrophy of the lymphatic glands, ending in caseous degeneration. Among syphihtic adenites should be distingioished those which occur at the commencement of the disease simultaneously with chancre and which are continuous throughout the secondary period, and those which show themselves in the tertiary period. On scraping the surface of a divided gland, affected with adenitis in the secondary period of syphilis, there are found, first, normal lymph cells; secondly, much larger cells, with an ovoid nucleus ; thirdly, large mother-cells, containing one large ovoid nucleus and many other nuclei, generally round. These large cells have agranular proto- plasm, are of different shapes, and often contain red blood cor- puscles. They are found in the peri-foUicular sinuses. The fibrous trabecula of these glands are often thickened when the lesion is no longer recent. Syphilitic cervical glands of young subiects may attain an extraordinary size, and persist for years ; they have all the gross and microscopic appearances of strumous glands ; we have examined some showing the lesions of interstitial adenitis, and which had at the same time undergone caseous degeneration. The condition of the lymphatic glands in the tertiary period of syphilis is extremely variable ; they may be cirrhotic, caseous, or tumefied, of a whitish colour and yielding a milky juice on division. The tumefaction gives the glands a medullary appear- ance, which has been described by Virchow, who was, however, content with gross appearances. We have made a microscopical examination of a case in which gummata of the stomach and liver were simultaneously present. (' Mem. de la Societe Medicale des Hopitaux,' 1874.) All the lymphatic glands situated in front of the cceliac axis, on the superior margin of the pancreas, in the vicinity of the pylorus, and round the bronchi, were white, tume- fied, and hard, and from their divided surfaces a few drops of TUMOURS OF THE GLANDS. 559 puriform fluid could be squeezed out. This fluid contained, together with round and granular lymph cells, a great number of large swollen endothelial cells, containing one oval nucleus or many nuclei. These glands, hardened by the successive action of Muller's fluid and gum and alcohol, and examined in delicate sections, showed all the circum-glandular and capsular lymph vessels, the lymph channels and sinuses, and all the cavernous tissue, filled and distended by large globular epitheloid cells, derived from the lymph cells and endothelial cells lining the lymphatic cavities and channels. On washing away the cells with a camel's-hair brush, large alveolar cavities, representing sections of afferent lymph vessels, were seen at the centre of the glands ; the meshes of the retiform tissue of the cavernous substance were also much enlarged. Wherever an islet of fine retiform tissue was discovered in a section, around it were seen the large meshes of cavernous tissue and the lymph sinuses and channels distended commensurately ; these cavities had, however, partly lost their contents, and showed at places large swollen granular endothelial cells, containing one or more ovoid nuclei ; these cells were elongated or flattened, and had angular prolongations ; sometimes they were of a regular pavement-shape with blunt edges, a shape due to their being flattened by reciprocal pressure. Here, then, was produced an inflammation of all the lymph channels of the gland, an inflammation consecutive to that of the afi"erent lymph vessels, and originating in the syphilitic lesions of the liver and stomach. Chondroma of the lymphatic glands is rare, and is chiefly caused by extension of a neighbouring chondroma. Epithelioma. — Every variety of epithelioma may be met with in the lymphatic glands. In development it differs from car- cinoma, in that the first epithelial nodule commences in the cavernous lymphatic system, while the structure of the gland is still preserved ; it sends out in various directions buds, surrounded with embryonic tissue, always of the same structure as the primary tumour. Thus in pavement epithelioma with epidermic globes, the glands are transformed into a series of large branching cavities, which are filled with crenated cells, and showing epidermic globes here and there. In cylindrical-celled epithelioma cavities are pro- duced, which are separated by delicate septa lined with cylindrical cells, and filled with a semi-fluid mass containing cellular ele- ments. From the fibrous walls of these cavities often spring vas- cular fibrous processes, also lined with cylindrical cells. CHAPTER XIV. LUSIONS OF THE NERVES. I. Normal Histology of the Nerves. Medullated nerve tubes and non-medullated, or Eemak's, fibres (already described on p. 31) form nervous fasciculi, varying in diameter ; one of these fasciculi may alone constitute a nerve, but they are more frequently associated in varying numbers. In man the large nerves of the limbs contain a great number of fasciculi. Each nervous fasciculus is surrounded by a sheath, which in the terminal branches is formed of a single layer, and which we call the sheath of Henle ; in much larger fasciculi it is composed of a series of superimposed laminge, anastomosing together, and hence named by us the laminated sheath. The laminse of the laminated sheath are formed of a trellis-work of fine connective-tissue fibres, covered with extremely delicate endothelial cells. The nerve fibres are not placed simply side by side within the laminated sheath, they are separated by delicate longitudinal* fibres of con- nective tissue, between which are disposed large flat connective- tissue cells, which make impressions on one another. The differ- ent fasciculi composing a nerve are separated and united by ordinary connective tissue, composed of large fibres, between which connective-tissue cells, and sometimes adipose cells, are found. The blood-vessels of the nerve first ramify in the perifascicular connective tissue, then penetrating the interior of the fasciculi, they traverse the laminated sheath, and continue to ramify, finally forming a capillary network, with meshes elongated in the axis of the nerve. The lymph vessels do not penetrate the nervous fasciculi, but terminate in the perifascicular connective tissue. The plasma, however, which is exuded from the blood capillaries, after assisting in the nutrition of the nervous elements and becoming charged with their waste products, insinuates itself between the laminse of the laminated sheath, and following a very INFLAMMATION OF NERVES. 561 complicated tract between them is finally lost in the perifasci- cular connective tissue, where it may be taken up again by the lymph vessels. II. Pathological Histology of Nerves. Congestion, haemorrhage, and inflammation of nerves. — Conges- tion of nerves occurs rather frequently, as it is seen in all nerves implicated in an inflammatory focus ; it may often extend beyond this focus : in phlegmon of the leg, for example, it is not rare to find congestion of the sciatic nerve extending as far as the sciatic notch. On carefully dissecting out the nerves involved in a wound they are found to be slightly swollen, and upon their surface are seen red lines parallel to their axes which indicate that congestion existed during life. Some observers, having ex- amined nerves in wounds which were followed by tetanus, con- cluded that congestion of the nerves was the cause of the tetanus; thus Lepelletier, Cmrling, and Eokitansky refer trau- matic tetanus to the extension of the congestion and inflammation to the nerves implicated in the wound. But this is surely an error, since such congestion may be observed in nerves in almost all slightly inflamed wounds, a condition which is however very rarely followed by tetanus. Congestion of nerves is much more frequent than is generally thought. Hyperaemia particularly affects the perifascicular vessels, and may be easily recognised ; hyperaemia of the intrafascicular vessels may also exist, but it is not so easily recognised by the naked eye, for the laminated sheath must be stripped ofi" before the vessels filled with blood can be seen in the nervous fasciculi. To estimate the dilatation of capillaries, transverse sections of the nerve should be made, after hardening in chromic acid. Thus in a transverse section of the internal saphenous nerve, in a soldier who was suffering from a wound of the leg produced by the explosion of a shot, the intrafascicular capillaries were found dilated and filled with blood. In deep whitlow we have seen the collateral nerves present a similar lesion, and it is very prob- able that intrafascicular hyperemia of nerves is an important cause of the acute pain accompanying this lesion. Congestion of nerves causes an increase of the blood tension and serous exudation into the perifascicular connective tissue; miliary hfpmorrhages may also be produced. More extensive blood foci S62 LESIONS OF THE NERVES. may be fornied directly, when the nerves are denuded, as in wounds, for example. Inflammation of nerves, characterised by congestion and serous exudation, is frequent as we have already seen, but suppurative inflammation is on the other hand rare in the nervous fasciculi. The laminated sheath opposes an almost insurmountable barrier to the diffusion of pus into the interior of the fasciculi : thus in a freely suppurating focus, nerves may be seen the peri-fascicular tissue of which may be the seat of hyperaemia, serous exudation, and even of diffuse suppuration, they having nevertheless preserved their functions. It is not without astonishment that on examin- ing such nerves under the microscope, the nerve tubes are found to be completely normal. This resistance of the nerves may be attributed in a great part to the laminated sheath, but it is possible also that the numerous anastomoses of their blood-vessels, both in the perifascicular and intrafasciculax connective tissue, put them, by securing independence of circulation, out of reach of morbid influences in their neighbourhood. This independ- ence may be demonstrated by experiment, in fact it is possible to denude and separate the sciatic nerve throughout its whole extent in the thigh of a living animal, without the functions of the nerve being disturbed, or it becoming necrosed. The resist- ance of the laminated sheath to suppuration may also be proved by a similar experiment. If, after denuding the sciatic nerve, vermilion suspended in water be sprinkled on the wound, the lymph cells become charged with the coloured granules and carry them in various directions, but none of these coloured lymph cells are able to traverse the laminated sheath and fix themselves between the nerve tubes. It is not the same if this sheath has been torn ; for example, if the nerve be traversed by a thread, the cells filled with the colour granules then find an open path and reach the interfascicular connective tissue. Chronic inflammation or growing neoplasms have a much more important effect on nerves. The new ceU formation, which char racterises their evolution, being continued into the perifascicular connective tissue, and between the laminae of the laminated sheath of the nervous fasciculi, separates them, compresses the fasciculi, and the nerve tubes undergo, below the diseased spot, the series of changes which are observed in the peripheral end of a divided nerve. The nerves of paralysed limbs in chronic hemiplegia accompanied with contracture of the extremities, are manifestly increased in size, so that they may be double their normal SECTION OF NERVES. 563 diameter. The nerve tubes have however preserved their normal structure, and the hypertrophy is solely due to thickening of the connective tissue. In order to study the development of inflammatory and other neoplasms in nerves, it is not enough to dissect or dissociate them, but sections must be cut after hardening in a "2 per cent, solution of chromic acid ; in such sections it may be seen how first the perifascicular connective tissue, then the laminated sheath, and finally the intrafascicular connective tissue are successively invaded by cells of new formation. Lesions following the section of nerves. — To study the various phenomena occurring after the section of nerves, recourse must be had to experiments on animals. The opportunities of studying these changes are rare in man, though in war wounds of the nerves are frequent, but the wounded either rapidly succumb or recover, exhibiting a series of symptoms similar to those seen in animals submitted to experiment. Some observers, Forster among others, speak of the immediate union of nerves ; it is very probable that they base their views on actual clinical facts, such as the rapid re-establishment of sensi- bility in a zone corresponding to the divided nerve. Arloing and Tripier have explained these facts by the existence of peripheral recurrent branches, and they based their interpretation on ana- tomical observations and physiological experiments. In animals, division of a nerve is never followed by immediate union, even when the two segments are kept together by a suture ; hence, a similar union is doubtful in man. When a nerve is divided, the peripheral segment undergoes a peculiar degeneration, and after a variable time,never less than three months, it becomes regenerated. By this time union of the two segments of the nerve has taken place, though not by any of the processes admitted by surgeons ; there is, in fact, neither immediate union, nor union by first inten- tion, nor by second intention, nor by the aid of granulations : there is here a quite peculiar histological evolution. Forty-eight hours after division of a nerve in a rabbit, and four days in a dog, the peripheral end of the nerve has lost its excito- motor power ; but already before this period, important changes have taken place, in both the central and peripheral ends, and are continued till they finally end in the regeneration of the nerve, which first undergoes degeneration. In the first period, the peripheral segment of the divided nerve undergoes a series of o o 2 564 LESIONS OF THE NERVES. changes, which have been considered as degenerative in nature ; in the second, the nerve tubes which have been destroyed, at least in their essential parts, give place to new nerve tubes, which reconstitute the primary nerve. Degeneration of divided nerves. — The changes which occur in the peripheral end of a divided nerve in the first few days following the operation were long looked upon as being entirely degenera- tive in nature ; they seem to consist essentially in division of the myelin into fragments, drops, or granules, and finally its more or less complete disappearance by absorption. But in reality this decomposition of the medullary sheath of the nerve tubes is the consequence of an active development of the protoplasm of the interannular segment, so that if we preserve the name of degenera- tion for this process which ends in the destruction of the myehn, it must be remembered that it in no way signifies a passive process. Twenty-four hours after section of the nerve, when the functions of the peripheral segment are still preserved, the nucleus of each interannular segment of the nerve tube may be observed to be swollen, and the protoplasm surrounding it notably increased. The best method for .observing these facts is to dis- sociate the nerve after allowing it to remain in a 1 per cent, solution of osmic acid. At the time that excitability is abolished, that is, forty-eight hours after division in a rabbit and four days in a dog, the nuclei and surrounding protoplasm of the inter- annular segments are so increased in size as to fill the whole calibre of the nerve tube ; the medullary sheath and the axis cylinder are thus divided in two. The protoplasm is accumulated in the same way at different points in the length of the inter-annular segment, and, extending towards the axis of the tube, divides the medullary sheath and axis cylinder in two ; thus the myeUn is not only interrupted at the level of the interannular nucleus, but also at several other points in the length of the segment, some- times even at its two extremities. It is thus seen that at the same time that the function of the nerve is abolished, the axis cylinder, which is essentially the physiological portion, is segmented, and is no longer able to transmit motor impulses. The relation is thus exact between the physiological phenomena and the histo- logical changes observed. These lesions are completed in the following days, so that a week after division of the nerve the medullary sheath of the nerve tubes is decomposed into fragments, drops, or granules. Scattered in the protoplasm of the inter- DEGENERATION OF DIVIDED NERVES. 565 annular segments are fine fatty granules, which stain a blackish yellow with osmic acid, while the myelin stains a bluish black with the same reagent. The nuclei of the interannular segments are multiplied, so that the activity of the interannular cells is shovm, not only by increase of their protoplasm and hyper- trophy of their nuclei, but also by their multiplication. At this time, therefore, the axis cylinders are decomposed into a series of fragments of unequal lengths, more or less folded and twisted, each being still surrounded by a layer of myelin. At the same period, on the seventh day, granulo-fatty de- generative changes are observed in the cells of the interfascicular connective tissue, and in the endothelial cells of the blood-capilla- ries ramifying in it. These changes commence much earlier, but are now marked. The fat granules are probably derived from the myelin. The constituent fat of this substance is dissolved, passes in this state through the membrane of Schwann, to be finally fixed in the protoplasm of the connective-tissue cells and the endothelial cells of the capillaries. But these are not the only cellular elements located between the nerve tubes, which become loaded with fat granules ; the lymph corpuscles also absorb fat and become changed into granular bodies. The function of these lymph cells seems to be to transport into the general circulation part of the debris arising from the de- generation of the medullary sheath and axis cylinder. They are more numerous in the peripheral segment, near the point of section, than in the rest of the nerve, and at this spot they are loaded, not only with fat granules, but with actual droplets of myelin, which have escaped from the divided nerve tubes, and been taken up by the lymph cells. Some of the cells even penetrate the open tubes, travel into their interior, and become loaded with the granules of myelin they meet with in their passage. This migration of the lymph cells into the interior of the nerve tubes is particularly seen during the days following division of the nerve, and is seen not only in the peripheral but also in the central end. The phenomena observed in the central segment must arrest our attention for a moment. Some observers (Neumann, Eichorst) have maintained that the changes in the nerve tubes in the cen- tral segment are the same as in the peripheral segment. These observers, unaware of the migration of the lymph cells into the meduUated fibres, which we only recently discovered, have, doubt- less, mistaken the modifications following this migration, for those constituting degeneration, properly so called, of the nerve 566 LESIONS OF THE NERVES. tubes of the peripheral segment. In all points of the nerve tubes attacked by the lymph cells, the myelin is devoured by them ; the axis cylinder itself cannot always resist them, and is itself sometimes partially destroyed. Changes in the nerve fibre result from this process, dififering entirely from the lesions called de- generative ; the myelin, instead of being simply broken into large fragments, which subsequently become smaller and smaller, is rapidly reduced into fine granules, which, acted upon by osmic acid, take a yellowish-brown stain. The migration of lymph cells into the central segment is generally arrested by the first annular constriction; sometimes, however, they pass it and may very rarely be found beyond the second node of Eanvier, In from ten to eighteen days' time, when the wound of the cellular tissue and integuments has united by first intention, the extremities of the divided segments are swollen and are separated, though held together by a cicatricial tract. This cicatricial tract, which is much thinner than the nerve itself, is grey, and semi- transparent, and has the appearance of a non-meduUated nerve filament, or a bundle of connective tissue ; there is then no union of the essential parts- of the nerve, though the path of regeneration is traced. Eegeneration of divided nerves. — ^Eegeneration of a nerve, or rather the preparatory phenomena, commence in the central segment, a short time after division ; but regeneration does not begin in the peripheral segment till many weeks later, and is continued for some months. Two or three days after division of a nerve in a rabbit, the axis cylinders of the nerve tubes of the central segment undergo hjrpertrophy near the point of sec- tion. They then seem to be very distinctly composed of fibrils — elementary nerve fibrils. Later, they divide longitudinally, bud and extend into the cicatricial cord. They are then non- meduUated, and they divide and subdivide, so that a single nerve tube may give origin to a considerable number of new nerve fibrils. Still later, at a peiiod which has not yet been accurately deter- mined, for the process proceeds irregularly, the nerve fibres, hitherto without myelin, become covered with a medullary sheath, and assume all the characters of medullated nerve tubes ; they have a membrane of Schwann and interannular segments, though these are relatively very short. It is only when the nerve tubes have attained all these characters that they can be easily recognised in preparations obtained by dissociation, after the action of osmic acid. REGENERATION OF DIVIDED NERVES. 567 The new nerve tubes having thus reached the cicatricial cord, they may be seen to travel towards the peripheral segment and penetrate it. They are quite isolated in the midst of the old degenerated tubes, or, what is more frequent, they penetrate their interior. On dissociating the peripheral segment when regeneration has become tolerably advanced, that is from the seventieth to the hundredth day in the rabbit, old nerve tubes are found from which the myelin has entirely disappeared, except at certain spots where it still exists in the form of a granular mass. Within these tubes are found one, two, three, or even a much greater number of delicate medullated nerve fibres, with short interannular segments, and alongside them are found non-medullated fibres. Eemak, who had already observed this important fact, explained it by an endogenous generation, resulting from the longitudinal segmenta- tion of the old axis cylinder, which had been preserved. But we know now that in the peripheral segment of divided nerves the axis cylinders are first broken up and then entirely absorbed. The explanation of Remak cannot therefore be accepted, and in its stead we propose the following : the newly formed nerve tubes, developed within the old degenerated tubes, do not simply result from genesis in situ, but are produced from buds of the axis cylinders of the central segment, which, continuing to grow, first reach the cicatricial cord, then the degenerated segment, and extend either into the interior of the old nerve tubes, or between them. The membrane of Schwann, the cellular elements which line it, and the medullary sheath are alone formed from the pro- liferating cellular elements, which have accmnulated in the interior of the old tubes.' Waller has shown by numerous and ingenious experiments that the cause of degeneration of the peripheral segment of a divided nerve is separation from its trophic centre. The nutrition of nerves depends on certain nervous or ganglionic cells, which act as trophic centres to the nerves, so that they degenerate when spparatt'd from them. Thus the motor roots of the spinal cord have their trophic centres in the cord itself, while the sensory roots have their trophic centres in the spinal ganglia. Hence, on cut- ting both roots of a pair of nerves in the vertebral canal, the perii)henil segment of the anterior root, and the spinal and central segment of the posterior root are only degenerated ; if a mixed nerve be divided at its issue from the vertebral canal, all ' For fuller details on this subject see Leqong sur Vlmtologie du systhne lurreiir, hy L. Ranvier 1878. 568 LESIONS OF THE NERVES. that part of it "whicli has been separated from its ganglionic centres undergoes degeneration. Tumours of nerves. — Besides myelinic and amyelinic neuroma (p. 237), fibroma (p. 166), and myxoma (p. 159), formerly called neuroma, are observed in nerves. Carcinoma and epithelioma generally aflfect nerves in consequence of extension of a tumour developed primarily in a neighbouring region. The perifascicular W E M BADOUHEAU Fig. 257. — ^Tkansvebse Section of the Sciatic Nerve in a case of Cylindrical-celled Epithelioma, extending i-rom the Uterus to the Nekve. The interfascicular connective tissue N is invaded by epithelial lobules of new formation E, which are also developed in the laminated sheath. The nervous fasciculi, M, are on the contrary respected. Magnified 40 diameters. tissue is first invaded, the laminated sheath is dissociated by the new growth, and the nerve tubes undergo fatty degeneration and disappear. Forster has observed a case of primary carcinoma of the nerves which, increasing from the size of a lentU, finally developed and completely destroyed the nerve. 569 CHAPTEE XV. LESIONS OF THE CEREBRUM AND CEREBELLTIM. I. Normal Histology of the Central Nervous System. The central nervous system consists of the cerebrum, cere- bellum, Pons varolii, medulla oblongata, and spinal cord. The spinal cord will be considered in the next chapter. Cerebrum. — The cerebrum, like all other parts of the central nervous system, is composed of two symmetrical halves or hemi- spheres, and is produced by the expansion of all the nervous fasciculi, which pass from the spinal cord through the medulla oblongata, Pons varoUi, and crura cerebri. The nervous filaments which convey sensory impressions, or conduct voluntary motor impulses to the periphery, terminate in the cerebral grey centres, which are essentially composed of nerve cells. These centres are found in the grey matter of the cortex of the convolutions, and in the central grey nuclei, or ganglia of the brain — the optic thalami, corpora striata, corpora quadragemina, and the ganglionic origins of the cranial nerves. The cerebrum is, in a general way, composed of a covering of grey matter, in which terminate the white fasciculi, which have entered through the pyramids, and spread out into the white substance of the centrum ovale and corona radiata. In the midst of this white substance the ven- tricles are excavated, in the walls of which appear the grey matter of the optic thalami and corpora striata. We do not propose to give here an exhaustive description of the structure of the brain, nor to describe in detail the course, still so ill understood, of the nervous fasciculi which pass from the crura to the cortex of the convolutions, nor the course of the radi- cular fasciculi of the cranial nerves to their deep origins ; we shall content otirselves by recalling the external topography of the con- volutions and their structure. The topographical anatomy of the convolutions, regarded as the expansion of certain fasciculi of the 570 LESIONS OF THE CEREBRUM AND CEREBELLUM. peduncles, should indeed always be present to the memory when making an autopsy, so as to be able to exactly determine the seat of any lesion. Studies on the localisation of cerebral diseases have been prosecuted by Broca, Fritch and Hitzig, Ferrier, Charcot, Buret, Lepine, Pitres, Grrasset, etc, with such important results that we are obliged to consider them, even in a treatise of patho- logical histology ; otherwise we should be unable to indicate the lesions which correspond to perfectly well-defined pathological types, such as aphasia, hemi-ansesthesia, hemi-chorea, etc. Topography of the cerebral convolutioiis. — ^The surface of the hemispheres is divided into four lobes, the frontal, parietal, tem- FiG. 258 (from Eoker). — Lateral View of the Human Bkain. p, frontal lobe ; p, parietal lobe ; o, occipital lobe ; t, temporo-spheuoidal lobe ; s, fissure of Sylvius; ^, borizontai, 8", ascending sulci of the same ; c, sulcus centralis, or fissure of Bolando ; K, ascend- ing frontal convolution ; B, ascending pariei^l convolution ; ?„ superioi*, Fa, middle, Pg, inferior frontal convolution ; /i, superior, /g, inferior frontal sulcus ; /a, sulcus prsecentralis ; Pi, superior or posterior parietal lobule ; Pa, inferior parietal lobule, or gyrus supramarginalis ; P,', gyrus angularis; ip, intraparietal sulcus; cm, termination of tlie caUoso-marginal fissure; o^, first, Oa, second, O3, third occipital convolution ; po, parieto-occipital fissure ; o„ transverse occipital sulcus ; Oa, inferior longitudinal occipital sulcus ; T^, first, Ta, second, T^, third temporo-sphenoidal convolutions ; /„ fixst, t,, second temporo-sphenoidal fissure, poral, and occipital lobes. To fix the limits of these convolutions STRUCTURE OF THE GREY CORTEX. 571 the fissure of Sylvius and the fissure of Kolando must first be determined. First, in front of the fissure of Eolando is the frontal lobe, consisting of four principal convolutions, the ascending frontal (A, fig. 258), along the anterior margin of the fissure of Eolando, and three convolutions running horizontally from behind forwards, and called respectively the first, second, and third frontal convolutions. Second, the parietal lobe is Hmited in front by the fissure of Rolando which separates it from the frontal lobe, and below by the fissure of Sylvius (s' and s") which separates it from the temporal lobe, its posterior border being formed by the parieto-occipital fissure, fio, which is not, however, well marked in man. The parietal lobe consists of two principal lobules or convolutions, the ascending parietal convolution, b, bordering the fissure of Eolando and continuous with the superior parietal lobule P„ and the inferior parietal lobule Pj and gyrus angularis. At the upper part, the ascending frontal convolution A, and the ascend- ing parietal convolution b, are continuous on the internal surface of the hemisphere with the paracentral lobule. Third, the tem- poral lobe is formed of three parallel and similar convolutions, which have been called the first, second, and third temporal convolu- tions, T„ Tj, and Tg, fig. 258. Fourth, on the internal surface of the hemisphere, above the corpus callosum, is found the gyrus fomicatus or marginal convolution of the corpus callosum, then the caUoso-marginal fissure, above which is met with, from before backwards, the internal surface of the third frontal convolution, the paracentral lobule, the quadrate lobule or Prsecimeus, the parieto-occipital fissure (po, fig. 258), the cuneate lobule, and the occipital lobe with its three convolutions (Op Oj, O3, fig. 258). Structure of the convolutions. — The grey cortex of the cerebral convolutions contains, in the frontal and parietal lobes, cells, vary- ing in size and shape, round, pyriform, and fusiform, as well as nerve fibres and a granular ground substance. These elements are arranged in such a way that three more or less definite layers may be distinguished. They have been described by Meynert, The most superficial, just beneath the pia- mater, contains delicate medullated nerve tubes parallel to the surface of the brain, and a few small nerve cells disseminated in a granular ground substance. The second layer contains a large number of small pyramidal nerve cells pointing towards the surface of the convolu- tion ; these cells give this layer a grey colour (2, fig. 259). The 572 LESIONS OF THE CEREBRUM AND CEREBELLUM. third layer is characterised by pyramidal cells, some of medium size, others so large that they deserve the name of giant cells ; they may even attain the diameter of 40 /i or "^^ v-j^'r"''^ 50 /*, and equal in size the large cells of the 'i L ' "^ anterior horns of the spinal cord. Their bases are turned towards the deep layers of the convolutions, and their elongated bodies ter- minate in a point directed towards the surface of the brain ; they give off more or less numerous and ramifying branches, which spring either from their body or from their attenuated extremity; at thefr base they receive a single nerve tube, which loses its myelin before entering the cell, and which corresponds to Deiters' process. Between these large cells, which are especially found at the bottom of the third layer, pass fasciculi of medullated nerve tubes in a direction perpendicular to the surface of the convolu- tion. The fomth layer contains a few small globular cells, and the fifth fusiform nerve cells. These two layers are traversed by the fasciculi of nerve tubes, which terminate in the pyramidal cells. The large pyramidal cells are not found in all parts of the cor- tex; they are, according to Betz, localised in portions of the frontal and parietal lobes, which are, according to Fritch and Hitzig, the psycho-motor centres, and also in the mar- FiG. 259. — Section of THE Grey Cortex of THE Third Fkontal Convolution (after Meynert). 1, superficial layer of scat- tered corpuscles; 2, dense layer of small pyramidal corpuscles ; 3, layer of large pyramidal corpuscles ; 4, dense layer of small irre- gular corpuscles; 5, layer of fusiform corpuscles ; m, medullary fasciculi. Mag- nified 7S diameters. ginal convolutions of the fissure of Eolando and the paracentral lobule. The convolu- tions of the occipital and sphenoidal lobes are constituted on the same model, with the exception that pyramidal cells are rarer, and giant cells are altogether wanting. Localisation of fanction. — -According to data furnished by physiological experiments, and by observations in human pathology, the grey motor centres of the limbs are local- ised in the convolutions bordering the fissure of Sylvius and the paracentral lobule. These centres are repre- LOCALISATION OF FUNCTION, 573 sented in the adjoining diagram (fig. 260), which we have bor- rowed from the memoir of Charcot and Pitres, on motor locali- sation in the grey matter of the brain.' The middle third of the ascending frontal convolution is the centre of isolated movements of the inferior extremity (3, £[g. 260). The para- central lobule, the superior third of the ascending frontal con- volution, and the two superior thirds of the ascending parietal convolution, are the centres for movement of the superior ex- tremity on the opposite side of the body (4, fig. 260). The Fio. 2i;o. motor centre of the lower part of the face is localised in the lower extremity of the ascending frontal and ascending parietal convolu- tions (2, fig. 260). The posterior part of the third left frontal, or Broca's convolution, is the seat of articulate language ; it should be added, however, that the convolutions of the island of Eeil, touching the base of the third frontal convolution, also participate in presiding over the function of speech. According to Charcot and Pitres, from whom we have borrowed this resume, it must not be concluded that these centres, attri- buted from experimental data to motor functions, have exact geometrical limits ; they vary in a certain measure among different animals, but it is none the less true that, in the superior mammifers, monkeys for example, motor zones are distributed in ' See The LocalUatim of Cerebral DUcasct, by David Ferrier, M.D. Smith, Elder, k Co. 574 LESIONS OF THE CEREBRUM AND CEREBELLUM. the cerebral grey matter according to a general plan, which ia found again in man. It is generally admitted that the anterior part of the frontal lobe is the seat of intelligence, and it is believed that the posterior region of the cerebral cortex, the posterior part of the parietal and temporal lobes and the occipital lobe, receive sensory impressions. The internal capsule. — Most authors admit that the motor fibres which constitute the inferior plane of the cms cerebri, are connected with the cells of the corpus striatum, before passing to the convolutions, and that the sensory nervous fasciculi, which pass through the superior half of the crus, are in relation with the optic thalamus. Much, however, remains to be discovered before an Fig. 261. — Section of the Fkontal Lobe (aftek Pitkes). 1, ascending frontal convolution ; 2, island of Kfiil ; 3, Bphenoidal lobule ; 4, 5, 6, superior, middle, and inferior fronte-l convolu- tions ; 7, sphenrudal convolntiou ; 8, corpus caUosujn ; ft, nucleus caudatns or interventricular portion (rf the corpus striatum ; 10, optic thalamus ; 11 , internal capsule ; 12, nucleus lenticularis or extraventricular portion of the corpus stiiatum; 13, external capsule ; 14, the claustrum. exact knowledge of the structure and functions of these organs is obtained. It is, however, at the present time pretty completely established that destructive lesions, produced by softening or haemorrhage of the internal capsule, cause, according to the spot affected, either motor hemiplegia, with permanent contracture of the extremities, or hemi-anaesthesia, general or special. The internal capsule (11, fig. 261) situated between the optic thalamus LESIONS OF THE INTERNAL CAPSULE. 575 and the corpus striatum is an emanation from the inferior stage of the crus cerebri ; it contains fibres passing directly from the crus Fio. 262. — Transverse Section of the Bkain of a Doo at the Level oif THE Corpora Albicantia (Cakville and Duret). o, 0, optic thalamf ; s, 8, nuclens caudatus of tbe corpus striatum ; L, L, nucleus lenticularis of the corpus striatum ; P, P, internal capsule or peduncular expansion ; ii, a, hippocampus ; x, section of tbe posterior part of the internal capsule producing hemi- aniesthesia. to the grey cerebral cortex, and particularly a fasciculus which, according to Meynert, is exclusively sensory, and which encircles the lenticular nucleus to pass to the surface of the occipital lobe. The Fio. 263.— Vertical Transverse Section of the Brain of a Doo, Five Millimetres in front of the Optic Cosimissure (Carville and Dieet). B, B, nuclens candatus of the corpus striatum ; l, l, nuclens lenticularis of the corpus striatum ; P, peduncular expan- sion ; cA, chlasma of the optic nerves ; x. secti-n of the peduncular expansion producing motor hemiplegia ; r, a stylet by which the Internal capsule is divided. indirect fibres, which pass from the crus to the nucleus lenticularis, and to the optic thalamus, or which pass from these centres, reach 576 LESIONS OF THE CEREBRUM AND CEREBELLUM. the cerebral cortex by traversing the internal capsule ; hence, it gives passage to almost the whole of the fibres which unite the cortex and the central nuclei to the periphery. Observations, which are now very numerous, the first of which were published by Tiirck in 1859, have established the fact that lesions of the most posterior part of the internal capsule, cause hemiplegia with hemi-ansesthesia of cerebral origin, and troubles of all the special senses. If, on the contrary, the lesion falls on the middle or anterior part of the internal capsule, there is complete hemiplegia without hemi-anaesthesia, but with permanent contracture of the extremities ; descending degeneration of the pyramidal fascicuH is then observed in the Pons Varolii and medulla oblongata (see later, Secondary Degenerations of the Spinal Cord, p. 612). Experiments on dogs have confirmed these facts. Carville, Duret, and Veyssike have succeeded in reaching and lacerating the internal capsule. If the posterior segment is torn, as at x, fig. 262, hemi-ansesthesia is produced ; if the anterior segment, as at x, fig. 263, is divided, motor hemiplegia results. The cerebellum. — ^The cerebellum is formed on the same general plan as the cerebrum, namely, of white fasciculi passing "7^ Fig. 264. — Section of the Cerebral Cortex (after Metnert). 1 a, external layer of grey matter ; 1 5, internal part of the same layer containing fusiform cells and arched fibres ; 2, layer of the cells of Purtinie ; 3, granular layer ; m,. white Buhstance of the medullary nerve tissue. from its crura, which bring it into communication with the medulla oblongata and with the grey centres of the cerebrum, so that each cerebellar hemisphere is connected with the cerebral hemisphere. CEREBRAL CIRCULATION. 577 of the opposite aide. A nucleus of grey subtance, the coqDus den- tatum is situated at the centre of the white substance, the cortex being also formed of grey matter, which however dififers greatly in structure from that of the cerebrum. According to Meynert, on proceeding from the surface to the deep parts there may be seen successively : first, a rather thick granular layer containing a few ganglionic cells (1 a, fig. 264) ; secondly, a thin layer traversed by meduUated nerve tubes and fusiform cells ; thirdly (16, fig. 264), a layer of large nerve cells, the cells of Purkinje, which send their ramifying protoplasmic processes into the two preceding layers, they have also a single axis cylinder process, called the process of Deiters, which penetrates the deep layers ; fourthly, a granular layer of small round cells, and finally the white sub- stance composed of nerve fibres. Cerebral circulation. — The internal carotid and the vertebral arteries, united in the basilar trunk, contribute to form the circle of Willis at the base of the brain. The three principal arteries given ofi' from the circle of Willis are the anterior cerebral, the middle cerebral or Sylvian artery, both springing from the internal carotid, and the posterior cerebral, a branch of the basilar. We do not propose to trace all their branches, notwithstanding the interest attached to some of them, for example the various ramifications of the Sylvian artery ; but, referring our readers to the works of Duret, we would here simply draw attention to certain peculiari- ties of their distribution, which are important in the pathogenesis of the brain. The branches of the three cerebral arteries, dis- tributed to the convolutions, penetrate the grey matter after crossing the pia mater. The first layer of the cortex is less vascular than the succeeding layers ; that which contains the pyramidal cells possesses a rather close capillary network. The same arteries, after furnishing this capillary network, continue their course perpendicularly to the surface of the brain, and, penetrating the white substance, they anastomose by their extremities with the arterioles of the white substance. These anastomoses take place by means of extremely fine twigs, an arrangement which favours the production of infarctus by embolism. Cortical infarctuses (softened yellow patches of the convolutions) implicate thus, to a certain depth, simultaneously the cortex and the white substance of the convolutions. The arterioles, given ofif at the origin of the cere- bral arteries, penetrate at once to the base of the brain to reach the grey nuclei and central parts ; thus the Sylvian artery furnishes p P 578 LESIONS OF THE CEREBRUM AND CEREBELLUM. arterioles, which perforate the locus perforatus to be distributed in the corpus striatum. Most of these arterioles belong to what Cohnheim has called the system of terminal arteries, that is, those which do not anastomose together, but which terminate in an isolated manner, an arrangement most favourable for the produc- tion of infarctus, and softening by vascular obstruction. In the territories of those arteries which are distributed to the grey centres of the brain, haemorrhages are also frequently foimd. White ischsemic softening is frequent in the cerebral cortex, haemorrhage is rare. This lesion is, however, very frequent in the corpora striata, optic thalami, etc. The causes of haemorrhage in the central organs are, according to Buret: first, the mode of origin of the arteries, which spring almost directly from the circle of Willis ; secondly, the size of the arterioles, which is relatively considerable — these two conditions cause the cardiac impulse to be directly transmitted with great force ; thirdly, the absence of anastomoses, which renders rupture easy, there being no possibility of collateral circulation of the blood when sorhe obstacle is pre- sented to its course. II. Lesions of the Meninges. The lesions of the cerebral and spinal meninges being similar, a general description is only given here, anything peculiar to the spinal meninges being separately considered. Congestion and inflammation of the meninges. — Congestion, varying in intensity, is very frequent in the pia mater where it may be active or passive. Active congestion, when severe, causes desquamation of the epithelium lining the great arachnoid cavity, exudation of an albuminous fluid and extravasation of a varying number of white blood corpuscles. In cerebral rheumatism the pia mater is congested throughout its whole extent, and shows patches where the congestion is more intense, and effusion of blood may take place. These patches are of a bright red colour, as if the blood in the vessels was highly oxygenated ; shreds of the arachnoid and pia mater, thus altered, show, when examined without the addition of water, regular or fusiform dilatation of the blood-vessels, around which the red corpuscles are often extravasated. The choroid plexuses are congested, as well as the velum interpositum. The fluid con- tained in the arachnoid cavity in the ventricles and the sub- arachnoid spaces is increased in quantity, and in it are found a number of large granular epithelial cells and white blood cor- CEREBRAL MENINGITIS. 579 puscles, though it is not very turbid. When cerebral rheumatism has lasted twenty-four hours or more, the fluid contained in the arachnoid, ventricles, and sub-arachnoid spaces is more abundant and cloudy, and even slightly puriform, which appearance is due to the larger number of epithelial cells and white blood corpuscles it then contains. This condition is not peculiar to cerebral rheumatism, it may be found in all forms of cerebral congestion accompanied with delirium, such as may be caused by pneumonia, variola, typhoid fever, etc. Primary cerebral meningitis is extremely rare ; it may be caused by sunstroke. When the inflammation extends over the whole surface of the nervous centre, as in cerebro-spinal meningitis, it is generally epidemic, such as breaks out in armies and hospitals. The most frequent form of meningitis is that which follows tuberculosis, or tumours of the meninges or brain. Acute meningitis is characterised by the presence of pus on the surface of the pia mater, by thickening and cloudiness of the connective tissue of this membrane, and by the accumulation of pus cells around and along the vessels where the connective tissue is most abundant. The blood-vessels appear to the naked eye to be surrounded by an opaque zone, and on examining them under the. microscope the loose connective tissue around them is seen to be filled with lymph cells, which accumulate also in the perivascular sheaths, and envelope them like a sleeve. The sero- purulent fluid found on the surface of the membrane, and accu- mulated in the anterior and posterior sub-arachnoid spaces, is sometimes very thin, at others thick and mixed with fibrin, as in peritonitis. When the meningitis is acute and has lasted many days, the pus, mixed with fibrin, forms under the visceral arachnoid a con- tinuous, opaque, yellowish layer, which is thicker over the sulci, and separates the convolutions. The blood-vessels are partly imbedded in this false membrane, and appear like red lines covered with a veil. This fibrinous layer may be 5 mm. in thickness above the sulci. On raising the meninges, infiltrated with pus, the cerebral grey matter is seen beneath covered with red spots. On section it is seen that each red spot corresponds to a blood-vessel, which, examined under the microscope, is seen to be surrounded by a layer of pus mixed with a varying number of blood corpuscles. In cerebro-spinal meningitis a similar exudation is found round the spinal cord and pons varolii. The pus fills the sub- p p i 58o LESIONS OF THE CEREBRUM AND CEREBELLUM. arachnoid cavity of the spinal cord, and the meshes of the spinal pia mater, but it does not penetrate beneath the fibrous part of this membrane. The grey matter of the spinal cord is of a pinkish colour. In sections, made according to the classic method, no modification of the nerve elements can be found, but simply hypersemia of the blood-vessels of the pia mater, and pus cells between its connective-tissue fasciculi. Sometimes suppuration is so rapid that the quantity of pus is considerable, even when the symptoms of the disease have hardly lasted a few hoius. Tubercular meningitis. — The lesions of tubercular meningitis do not differ from those of simple meningitis just described. ^UJ\G-Vff, Fio. 265. — Blood-vessel of the Pia Mater, passing through a Tubercular Granulation, the limits of which are indicated by the dotted line. A, perivascular sheath ; B, vascular wall ; F, elements contained in the sheath ; 0, coagulated fibrin in the blood-vessel. Magnified 100 diameters. except by the presence of tubercles which are found chiefly along the blood-vessels of the pia mater ; the exudation is the same in the two diseases. Tubercular meningitis is, however, frequently mistaken for acute primary meningitis, for the tubercles are apt to be overlooked, but the presence of small and numerous granu- lations will be discovered on attentive examination. To find them the pia mater should be removed from those regions where tubercle is most frequently found, such as the fissure of Sylvius, and the superior crura cerebelli. The piece of membrane should then be agitated in water till the adhering fragments of cerebral tissue are separated, and on holding it up to the light small whitish spots will be seen in the membrane. This examination TUBERCULAR MENINGITIS. jgj must not, however, be considered sufficient. The pia mater should be carefully spread upon a glass slide, when with a low power granulations will be perceived which were not before recognisable with the naked eye, and which are seen to be particularly numerous in that part of the pia mater which dips down between the convolutions springing from the fissure of Sylvius. In studying one of these granulations minutely, it is seen to be formed of lymph or embryonic ceUs accumulated round\ blood- vessel. The large granulations encroach upon the neighbouring tissue and completely surround the perivascular sheath. The blood-vessel which is in the centre of the granulation is generally obliterated by a fibrinous coagulum. These masses of cells are ,/ — -r Uk -^ ;B ;*sA :i. !cS^^5:i3 ^ ^t.^- - > I . 5 I ^ ™»1 Fig. 266. — Section of Tubercular Meninges. a, small obliterated vessel ; v, v, much larger vessels. The ioterual coat of these vessels is greatly thickened, and in the internal layer of tlie vessel, which is in the centre of the figure, are seen two giant cells ; n, vessel obliterated near the cerebral substance, vu Magnified 40 diameters. most frequently found at the point of bifurcation of a small blood- vessel, where the perivascular sheath is wider ; it is also not unusual to see many granulations arranged like a rosary, at short distances from each other along the same blood-vessel. The new tissue often ensheathes the blood-vessel for a certain distance ; it is composed of small elements, pressed closely together, and situ- ated both in the perivascular sheath and pia mater. In order to make a thorough examination of meninges infil- trated with tubercle, the membranes and subjacent cerebral tissue should be well hardened, first in IMiiller's fluid and then in gum and alcohol. Sections cut perpendicularly to the surface 582 LESIONS OF THE CEREBRUM AND CEREBELLUM. show more or less altered blood-vessels contained in the tuber- cular tissue. In the deep layers of the thickened pia mater the capillaries, surrounded with a mass of newly formed cells, are seen to pass vertically into the cerebral substance (in fig. 266). These small vessels are often included in a true tubercular granulation, at the spot where they pierce the grey matter which is itself inflamed. The small arteries and veins of a tubercular pia mater show a very remarkable thickening of their intima. In a case published ' by one of us, the thickened internal coat of the arteries showed quite a peculiar structure. It was bordered internally by the usual endothelial layer; but it contained, besides, large cells, Fig. 267. — Transverse Section of the Internal Coat of an Artery, affected with Tubercular Endarteritis, at its Junction with the Middle Coat. m, middle coat ; «, triangiilar cells witlL their bases attactfid to this coat ; c, p, very long prismatic cells inserted on to the middle coat by their pointed extremities ; a, b, isolated cells of the internal coat ; g^ multinucleated cells. Magnified 300 diameters. flattened by reciprocal pressure, drawn out to a point and im- planted perpendicularly on the surface of the middle coat {vide fig. 267), forming a series of superimposed layers. In the midst of these, still larger cells were found containing two or three nuclei, and true giant cells containing fifteen to twenty nuclei. In fig. 267 the isolated elements are shown, and in fig. 268 the giant cells, seen in a section of tubercular endarteritis, under a high power. The internal coat, affected with tubercular inflam- mation characterised by the formation of giant cells, was almost uniformly thickened without definite tubercular nodules being produced. Thus, in the midst of discrete or confluent tubercles, ' Journal de VAnatomie, t, xvi, p. 213 ; 1880, CHRONIC MENINGITIS. 583 blood-vessels may be found affected with a peculiar form of en- darteritis, in which the coats and perivascular sheaths are infil- trated with'small cells, and are lodged in a connective tissue filled with the same elements. The giant cells, which are so common in tubercle of all the other organs, are very rare in tuberculosis of the meninges : we ourselves have only observed them in the solitary case reported above, and in which their presence was limited to the inflamed internal coat. The absence of giant cells in tubercular meningitis may be explained by the rapidity with which the meningitis is developed, which is too great to allow them time to form. This i G.M Fio. 268. — Section of Inflamed and Tubercilak Internal Coat. a, layer of flat endothelial cells indicating the internal border of the inflamed Inner coat ; g, red blood corpuscles circulating in the lumen of the vessel ; d, layer of round or polygonal cells ; 6, 6, 6, giant cells ; /, layer of cylindrical and round cells at the base of the Inflamed inner coat ; /, middle coat. Magnifled 200 diameters. is only a hypothesis which seems plausible till fuller information be forthcoming. In certain cases of tubercular meningitis, the pia mater and arachnoid of the spinal cord are scattered over with granulations. Chronic meningitis. — The most common form of chronic meningitis is diffuse meningo-encephalitis, a, disease chaxacterised by that group of symptoms called general paralysis of the insane. The principal morbid phenomenon is thickening of the pia mater, caused by a new formation of connective tissue ; the walls of the blood-vessels undergo a similar thickening ; those which pierce the cerebral tissue are adherent to it, so that this substance is torn on 5 84 LESIONS OF THE CEREBRUM AND CEREBELLUM. removing the pia mater ; there is also proliferation of the connec- tive tissue of the cerebrum, diffuse interstitial encephalitis, and atrophy with pigmentation of the cells of the cortical layer of the convolutions {vide p. 596). In some cases there is also a peculiar degeneration of the walls of the blood-vessels, which lesion, described by Magnan as that of colloid degeneration, seems to us to consist in chronic endarteritis and periarteritis. Pachymeningitis. — Inflammation of the dura mater has received the name of pachymeningitis ; it may be external or internal, and is generally chronic. In internal pachymeningpitis small granulations or buds are formed on the internal surface of the inflamed dura mater ; they contain vascular loops continuous with the pre-existing blood- vessels of the membrane ; these granulations spread over the surface of the dura mater, and constitute a thin and very vascular false membrane of newly formed connective tissue. When recent the blood-vessels it contains have embryonic walls; they are fragile and often rupture, and blood is effused into the arachnoid sac or into the tissue of the false membrane, which is then ecchymosed. These ecchymoses may be easily mistaken for simple spots of blood on the surface, if, after spreading the mem- brane carefully on a slide, a close network of blood-vessels are not distinguished and new connective tissue, the meshes of which contain extravasated red blood corpuscles. When the false mem- brane is older, large masses of reddish-brown blood pigment are found round the blood-vessels, and even crystals of hsematoidin. The membrane is often composed of several superimposed parallel layers. When in consequence of vascular ruptures a quantity of blood is effused between the layers of these multiple false mem- branes, blood cysts are produced, known by the name of hmma- tomata of the dura mater. For a long time it was thought that, in these cases, the blood was effused upon the surface of the dura mater, and surrounded with a layer of fibrin, which became organised into a false membrane, encysting the hsematoma. External chronic pachymeningitis, or inflammation of the external sm'face of the dura mater, differs from the preceding. By adhering to the bones of the skull, the dura mater plays the role of a periosteum, and its lesions are most frequently related to those of the internal plate of the bones of the skull ; thus, external pachymeningitis is generally caused by disease of the bones, due to syphilis or wounds; in alcoholism, thickening of the whole SYPHILIS, TUMOURS OF THE MENINGES. 585 dura mater may often be observed, accompanied with hsemorrhagic internal pachymeningitis. Syphilis, in its tertiary period, often simultaneously affects the dura mater and the bones of the skull. Inflammatory and gummatous new growths are then developed in the layer of the dura mater in contact with the bone, so that inflammatory granu- lations, or gummata, are developed simultaneously on the external surface of the dura mater, in the medullary canals of the in- ternal plate, and in the diploe. The pathological phenomena then observed between the dura mater and the bone are similar to those observed between the latter and the epicranial periosteum. External syphilitic pachymeningitis is characterised by nu- merous conical buds and excrescences, in the form of pointed papillae, or which ramify like a cauliflower ; they are grey or pink and semi-transparent, and composed of a rather friable tissue, which is exposed when the calvarium is removed. These ex- crescences extend over a great part of the dura mater ; they are lodged in hiatuses of the bone substance, and are directly continuous with the medullary tissue. In structiure they resemble the granu- lations of inflammation. The medullary tissue inflames, the bony lamellae of the diploe undergo absorption, and show the same histological appearances as were described in rarefying ostitis {vide, p. 332). When in contact with the osseous lamellae, the granulations, which spring from the dura mater and the inflamed medullary tissue, contain a great number of giant cells, lodged in the notches left by the absorbed osseous tissue. In cases where external syphilitic pachymeningitis is very intense, the ostitis extends to the external siu-face of the bone, and granulations are developed on the epicranial periosteum, similar to those of the dura mater : the entire bone then becomes riddled with holes like a colander. Tumours of the meninges. Fibroma. — The Pacchionian bodies may be described with fibroma, for when developed in great num- bers they form true tumours, capable even of causing perforation of the bones of the skull ; they also contain numerous and dilated blood-vessels. They are composed of layers of fibrous tissue and flattened cells, resembling in structure the fibrous plates of the spleen— lamellar fibroma {vide p. 163). They exist in the normal condition, and only acquire pathological importance by their exaggerated development, which often seems to be due to S86 LESIONS OF THE CEREBRUM AND CEREBELLUM. alcoholism. Their structure is quite characteristic, and has nothing in common with that of tubercular granulations, for which these bodies have been mistaken ; they are often incrusted with cal- careous salts. True fibromata, adherent to the dura mater, have been seen, but they are very rare. Cysts. — Small serous cysts, developed from vascular buds, are often found in the choroid plexuses ; similar cysts are also found in the sub-arachnoid cellular tissue, particularly near the fourth ventricle. Syphilitic gummata, — The cerebral meninges are rather fre- quently the seat of gummata. They form small spherical tumours, generally about the size of a small pea, on the external surface of the dura mater. They are located in cavities, hollowed in the bones of the skull ; their centre is caseous when they are old ; they may be followed by all the accidents of ostitis and necrosis, with the for- mation of purulent foci, as already described on page 340. Gum- mata of the pia mater and arachnoid, which are much rarer than those of the dura mater, may attain a much larger size. They develop towards the brain, which they invade for a more or less considerable extent, producing a surrounding zone of encephalitis. Tubercle. — Tubercles are generally found only in the pia mater and sub-arachnoid cellular tissue : they may, however, be met with in the false membranes of the dxura mater. Sarcoma is very frequent in the dura mater, in which the lesions of pachymeningitis are consecutively produced. Two forms of sarcoma may be seen, as in the brain — neurogliac sarcoma, often developed in the course of the cranial nerves, and angiolithic sarcoma, frequently observed on the internal surface of the dura mater, in the sub-arachnoid cellular tissue, and in the choroid plexuses {vide p. 144). Carcinoma and Epithelioma are very rare in the meninges, where they are always secondary. All tumoiu's of the dura mater may perforate the bones of the skull. Such perforations are therefore not peculiar to syphilitic gummata, for secondary sarcomata and carcinomata may cause similar lesions. Thus inspection of a dried cranium, showing losses of substances similar to those produced by gummata, cannot decide what was the nature of the neoplasm causing the lesion. CEREBRAL CONGESTION AND CEDEMA. 587 III. Lesions of the Cerebrum and Cerebellum. Cerebral anaemia is solely characterised by pallor of the nervous substance, unaccompanied with any appreciable change in the cells. Cerebral congestion. — When cerebral congestion has lasted some time, it always leaves traces after death ; injection of the blood-vessels is marked, the convolutions are pink, increased in size, and sometimes so closely pressed together that the sulci are almost effaced. Upon the surface of the brain reddish patches or spots are sometimes met with. On making a section of the brain at one of these patches, the cortex is seen to be of a pinkish grey colour, and the white substance to be spotted over with red points, caused by the division of capillaries filled with blood. These red points, when numerous and near together, give the brain tissue a speckled appearance. On examining microscopic sections cut at the level of the red patches, red blood corpuscles, and even yellow and red pigment granules may be recognised in the perivascular sheaths ; they are accumulated at the spots where the blood-vessels bifurcate, and the sheath is separated from the vascular wall by a wide space. The nerve cells and elements of the neuroglia do not seem to be altered, neither in the red patches nor around them. It may be noted in passing that repeated attacks of congestion, accompanied with diffuse meningo-encephalitis, cause pigmentation of the nerve cells. (Edema of the cerebrum. — Accumulation of fluid in the ven- tricles and sub-arachnoid spaces, accompanied with anaemia and softening of the fornix, is called oedema of the cerebrum. No histological lesion corresponds to this condition, which is simply due to imbibition of serum by the cerebral substance. The principal cause of oedema is pressure upon the veins of G-alen, and the development of tubercular granulations around them. Softening of the fornix, which coincides with an accumulation of serum in the ventricles, occurs as a rule in tubercular meningitis. Lesions of the cerebrum in melansemia. — In malarial melanaemia, the capillaries of the brain contain a large number of lymph cells, loaded with black pigment, so that the circulation is impeded. The arterioles may be more or less filled with the same elements, 588 LESIONS OF THE CEREBRUM AND CEREBELLUM. small aneurisms being formed, the waUs of whieh are also pig- mented. Cerebral hsemorrliage. — Cerebral hsemorrbage is sometimes con- secutive to blood changes, as in variola, scurvy, leucocythsemia, and is sometimes due to changes in the heart and blood-vessels. Hypertrophy of the heart, coincident with atheromatous indura- tion of the walls of the aorta, internal carotid, and branches of the circle of WilUs at the base of the brain, has been regarded as a very frequent cause of cerebral haemorrhage. It is the fact that atheromatous arteries, having lost their elasticity, can no longer render continuous the intermittent blood-wave projected by each ventricular systole. The jerking impulse of the blood transmitted then into the cerebral capillaries is most probably one of the causes of their dilatation and rupture. But the most frequent lesion which coincides with cerebral haemorrhage and which may be regarded as its most immediate cause, is aneurismal dilatation of the small arteries and capillaries of the encephalon. Sometimes the capillaries (Pestalozzi and KoUiker), sometimes the arterioles, are the seat of these aneurisms : they have been recently described by Charcot and Bouchard, who consider they play an important part in the pathogenesis of cerebral haemorrhage {vide p. 523). Two forms of cerebral haemorrhage may be distinguished — capillary haemorrhage and focal haemorrhage. Capillary hsemorrliage. — The capillary apoplexy of CruveUhier is seen either in the convolutions or in the central parts of the brain : the portion of the brain affected is softened and scattered over with small red points, which resemble at first sight small drops of coagulated blood. On dissociating the cerebral tissue with needles, these red spots are seen to correspond to blood- vessels, which may be followed and isolated for a certain distance; around them the cerebral tissue is slightly softened, and coloured bright red. On isolating one of these haemorrhagic spots with its corresponding blood-vessel, and examining it under the micro- scope, nothing but a mass of blood is at first distinguished ; but, by careful washing, a capillary vessel is seen at the centre, the lymphatic sheath of which is distended and filled with blood cor- puscles. The red blood corpuscles are also extravasated beyond the perivascular sheath, between the nerve fibres, which are separated and broken. Each one of these small haemorrhagic foci is thus found to be composed of a blood-vessel, with its perivascular CAPILLARY HEMORRHAGE. 589 sheath distended with blood, and of a small mass of nervous tissue infiltrated with blood. Fatty degeneration of the wall of the central capillary is often observed ; its perivascular sheath is considerably enlarged, but generally no laceration or fissiure can be discovered, through which the blood escaped from the vessel or its sheath, to be infil- trated between the elements of the nervous tissue. These small aneurisms of the perivascular sheath may be cyhndrical, fusiform, or spherical, and have been described under the name of dissecting a/neurisms. The nerve tubes are broken or dissociated, but, when the capillary haemorrhage is recent, they have undergone no further Fig. 269.— Capillary Blood-vessel op the Brain and its Pekivascular Sheath, filled with Red Blood Corpus- cles, FROM a Case of Capillary Apoplexy. degeneration than fragmentation of their myelin. Patients often succumb in the first few days following hemorrhage ; if they su - vive longer, round the vascular dilatations yellow or brown pigment is found, which is free or contained in the lymph cells. These cells also contain fatty granules, which are probably derived from the myelin of the destroyed nerve tubes. The blood contained in the dilated vessels has become brown ; blood pigment may also be found in the interior of the vessels and in their perivascular The" small nuclei of old capillary apoplexy are brown or slate- coloured, and are chiefly characterised on microscopic exammation by pigmentary changes of the colouring matter of the blood. Brown or black pigment, and even crystals of haematoidm, ai-e found in the white blood corpuscles, and in the perivascular 590 LESIONS OF THE CEREBRUM AND CEREBELLUM. sheaths of the arterioles and capillaries. These sheaths, and the peripheral nervous tissue, also contain granular bodies. Simulta- neously with these lesions, lacunae are also found in the brain, about the size of a pin's head, and filled with a transparent fluid. Their walls are more or less stained with blood pigment ; they are round or long, and their centre is filled by a blood-vessel the wall of which is infiltrated with fat granules, and the sheath filled with granular bodies. Hsemorrliagic foci. — A hsemorrhagic focus may be produced by the rupture of a large arteriole, or be the result of the conflu- ence of a large number of capillary hsemorrhagic points ; indeed, small capillary hsemorrhagic foci, situated near together, may be so numerous as to form a single focus of considerable size. This view is supported by the fact that around haemorrhagic foci, even the largest, a certain number of small points or capillary heemor- rhagic foci are found : once formed, a large focus may extend by invading and destroying the neighbouring parts. If situated in the corpus striatum or optic thalamus, it may break into one of the lateral ventricles ; if originally seated in the cortical layers of the brain, it may break through the pia mater and arachnoid, and open into the arachnoid sp'ace. The most frequent seat of haemorrhage is the corpus striatum and the optic thalamus, more rarely the white substance of the convolutions. Haemorrhage may also occur in the cerebellum, the pons varolii, and the medulla oblongata ; it is almost always unilateral ; sometimes several foci may be found of different ages in various parts of the brain. Large effusions cause tumefaction, with softening of the cerebral tissue, and flattening of the convolutions of the hemisphere affected, so that its existence may be asserted, before cutting into the brain. A hsemorrhagic focus, formed by the rupture of a large vessel, or by the union of many small foci, has the form of a cavity full of blood excavated in the midst of lacerated brain substance; the walls of the focus are simply formed of rugged cerebral sub- stance, stained red with blood. When the accident has occurred only two or three days before death, the blood is partly coagulated ; this is the best time for studying the state of the vessels surrounding the focus, and to ascertain the direct cause of the hsemorrhage. According to the method of Charcot and Bouchard, the focus should then be opened, and together with the surrounding parts of the brain be re- moved and placed in a vase filled with water, which should be changed with every precaution during the next few days. When HEMORRHAGIC FOCI. 591 the cerebral substance has been sufficiently macerated, it may be washed away by small jets of falling water, the vessels alone remaining. These are then spread upon a glass slide and ex- amined. A ruptured aneurism is often found, belonging, not to a capillary, but to a small arteriole ; or miliary aneurisms, which may explain the quantity of blood and the large size of the focus ; or, as Charcot and Bouchard have described, a vessel may be found, at the end of which is a ruptured lymphatic sheath, or an artery equally dilated and open, inside which is a fibrinous clot continuous with the coagulum of the focus. By this method the cause of the haemorrhage may be accurately ascertained. - Miliary aneurisms are most frequently found in the optic Fio. 270. — Miliary Aneurisms of an Arteriole of the Brain. a, trunk of the arteriole sliowinf; the granules m ; c, perivaBcnlar slieath ; 6, y aneurisms formed by an uriform dilatation of the arterial coats ; n, A, effusion of blood into the perivascular sheath d ; d, d, f, capillai-y branches springing from the arteriole. Mag- nitied 80 diameters. thalami, corpora striata, cerebral convolutions, and, finally, in the pia mater. Charcot and Bouchard think that they are pre ceded by arterio-sclerosis, and particularly by periarteritis, to which morbid process they are due. They insist that haemorrhage is specially caused by miliary aneurisms and periarteritis, while softening is due more to endarteritis and atheroma ; but it must not be forgotten that the lesions of atheromatous periarteritis and endarteritis are most frequently combined. In all cases of spontaneous cerebral hemorrhage occurring in old persons, miliary aneurisms are found scattered over the cerebral substance, which, by increasing in size, have excavated round spaces m the white or grey matter. , . , , , j- Sequelae of cerebral hsemorrhage.-If the patient does not die 592 LESIONS OF THE CEREBRUM AND CEREBELLUM. during the first few days following cerebral hsemorrhage, the effused blood undergoes the following changes ; the serum exuded from the coagulum is gradually absorbed ; the hsemo- globin is changed into yellow and red pigment, and forms crystals of hsematoidin, and the fibrin breaks down into a granular debris. In the meantime the wall of the focus becomes smoother, a quantity of connective tissue is developed from the elements of the neuroglia, and a true fibrous membrane is formed, which may be found a month after the injury. All the nervous elements contained in the hsemorrhagic focus undergo fatty degeneration, and the myelin is broken up into granules. The formation of a fibrous membrane, inclosing the focus, is the result of the inflam- matory process, which is continued till a fibrous cicatrix is pro- duced, in which fatty granules and hiematoidin are disseminated. Fig. 271. — Crystals of H^ematoidin. a, free crystals ; 6, crystals contained in cells ; /, capillary vessel containing granules? of hjematoidin. At the end of four or five years the shrunken focus is only repre- sented by a cicatrix, which is often quite colourless, but not un- frequently contains numerous crystals of hsematoidin. Sometimes, however, cicatrisation is not complete, and in the place of the old hsemorrhagic focus a cyst is found, filled with citron-coloured fluid, and bounded by a fibrous membrane. These cysts are difficult to differentiate from similar cysts produced by softening, the mode of formation of which will be described later. In the majority of cases the cerebral tissue, surrounding a hsemorrhagic focus, under- goes a series of changes, consisting in the infiltration of the colouring matter of the blood between the nervous elements and into the perivascular sheaths. The latter then contain deformed red blood corpuscles, granules, and crystals of hsematoidin, which are generally found in the lymph cells. It is to the presence of EMBOLIC SOFTENING OF THE BRAIN. 593 these granules that the nervous tissue round about a hEemorrhagic focus owes its ochrous colour ; this coloured zone is opaque, owing to the number of granular bodies contained in the perivascular sheaths ; the granular bodies may also contain pigment granules ; these bodies are indeed nothing more than lymph cells loaded with fat granules derived from destroyed nervous elements. Cerebral softening.— Cerebral softening is caused either by embolism, or by arterial thrombosis, following atheroma. Embolic softening. — Hemiplegia may often suddenly occur in the course of articular rheumatism accompanied with cardiac lesions, or in consequence of atheromatous degeneration of large blood-vessels. This accident is caused by the obstruction of one of the vessels of the brain by a fibrinous clot, which was originally formed in the diseased heart or large vessels. The left Sylvian artery is the cerebral artery most frequently obstructed. The first phenomenon observed is blood stasis in the part of the brain supplied by the obstructed artery, followed by more or less rapid fatty degeneration of the nerve cells and tubes. In one form the elements simply slowly undergo fatty de- generation. The myelin of the nerve tubes becomes segmented, and transformed into fine fat droplets ; the nerve cells break down into a granular debris and disappear. The cells of the neuroglia become filled with fat granules, and changed into granular bodies. We have abeady seen that all granular bodies are derived from living cellular elements, especially white blood corpuscles, which have absorbed fat granules, and that a nucleus can always be discovered on treating them with picrocarminate of ammonia. Finally, in the vessels filled with coagulated blood and fibrin the pigment separates and the fibrin becomes granular, leaving the vessels full of fat granules and blood pigment. The repletion of the vessels explains how at the commencement of this process the morbid part is tumefied, and projects, if situated on the smrface of the brain. Soon, however, the altered elements undergo retro- gressive changes, and the infarctus dries, and gradually flattens. The liberated fat often undergoes changes, resulting in the forma- tion of margarin and stearic acid, which are found in the form of round bodies, resembling granular bodies by their opacity, but which, when examined under a high power, appear to be formed of a multitude of acicular crystals united together. The cerebral pulp, which is thus dried and flattened, is yellowish-white, opaque, and firm ; but this solidity is only apparent, for it is easily dis- QQ S94 LESIONS OF THE CEREBRUM AND CEREBELLUM. sociated by a falling stream of water. This form is particularly met with in infarctuses which are seated near the surface of the brain, and dip down into the cerebral substance. A second form is characterised by pulpy softening of the centre of the infarctus, which is particularly observed in the white substance of the brain. The centre of the infarctus softens more and more, and is finally transformed into a white fluid mass like chalk and water. This fluid is contained in a cavity limited by irregular downy walls, the ragged shreds of which, composed of the debris of blood-vessels which have resisted degeneration, float freely in the cavity. On examining the walls of this focus of softening, only the debris of nerve elements and granular bodies are found. The vessels themselves are covered with fat granules, which can be washed away by agitating the shreds in water, when the following changes may be observed in the blood-vessels : they are empty Fig. 272. — CAriLLAKY Blood-vessel in a Focus of Cekebkal Softening. The granular bodies wliioh covered it have been partly removed with a camel's-bair brush, and only a few fat grannies are seen ranged round nuclei in the extremely distended perivascular sheath. or filled with a yellowish granular mass ; they sometimes still contain blood; their perivascular sheath is dilated, generally irregularly so, sometimes in the form of a crumpled sack ; inside it are cells loaded with pigment and fat granules — granular bodies, and endothelial cells, adherent or partly detached, which also con- tain a few fat granules. These foci of softening may cicatrise by a process similar to that described in apoplectic foci : part of the fluid is absorbed, the elements of the neuroglia surrounding the focus proliferate and soon constitute a thick limiting membrane, containing many blood- vessels. After the lapse of one or two years a cyst filled with serous transparent fluid can only be found, the wall of which does not contain any marked amount of blood pigment, a fact which differentiates such a cyst from that produced by an apoplectic focus. Infarctuses, occupying only the surface of the convolutions, undergo similar but less marked changes. They soften and are ENCEPHALITIS. 595 changed into a soft diffluent patch of a peculiar yellow colour, which might be thought to be due to the presence of hsematoidin, although no trace of it can be found. These yellow patches can be completely dissociated by a stream of water. They are some- times very extensive, and may occupy the whole surface of a lobe. Again these patches may dry, flatten, and form what appears at first sight to be hard plates ; but their firmness is only apparent, for, like the preceding, they may be dissociated by a stream of water. The cerebral convolutions in which this lesion is found are simply wrinkled, flattened, and yellowish, but their general shape is unmodified. Softening from atheroma and arterial thrombosis. — This is generally the residt of atheromatous change in the blood-vessels, a change commencing most frequently in the arteries at the base of the brain. Endarteritis first causes narrowing of the lumen of these vessels, and is followed by blood stasis, which in its turn produces necrosis of the nervous elements. Sometimes irregu- larities in the internal surface of atheromatous arteries lead to the formation of blood clots which obstruct the circulation ; such may occur, for example, in chronic or acute endarteritis of one of the arteries at the base of the brain, chiefly the Sylvian artery, when vegetations may project into its lumen, impede the circula- tion, and become the starting-point for the formation of a coagulum plugging the vessel entirely. The subsequent lesions of the brain tissue are identical to those produced by embolism. The infarcts produced by thrombosis cause a pinkish coloured softening when the lesion is recent, and soft or hard yellow patches, dried and flattened, when older. When the convolutions are affected and the lesion dates back several months, they are seen to be ex- tremely atrophied, though their general shape is preserved. The pia mater covering them is oedematous, and fills up the hiatus produced by the atrophy. In the central parts of the brain an infarctus due to atheroma, such as embolic infarctus, softens, and forms a fluid resembling chalk and water. The histological lesions are the same in both cases. Encephalitis. — Encephalitis, or inflammation of the brain, may be diffused or circumscribed : the latter form is related to abscess. Sometimes the cerebral tissue is red, when the change has been described as red inflammatory softening, especially by Eostan and Andral ; at other times it is yellow, on account of the quantity o o 2 596 LESIONS OF THE CEREBRUM AND CEREBELLUM. of pus cells present : such is the so-called white or yellow soften- ing. Bouchard and Hayem have made an experimental study of the histological process in inflammation of the brain. They used direct irritation of the brain tissue by means of foreign bodies and chemical substances. They ascertained that in cerebral softening, proliferation of the cellular elements of the neuroglia takes place. It is very probable, however, that some of the nevr cellular elements are simply white blood corpuscles from the blood-vessels ; indeed, they are principally found in the perivascular sheaths, and they form more or less voluminous masses in the nervous tissue. At the same time the nerve elements undergo fatty degeneration. The same lesions are observed in acute primary inflammation, ending either in abscess or softening of the brain. The inflam- matory softening may be yellow, white, or red ; when red it is due to haemorrhage into the perivascular sheaths, or to an extremely congested condition. Inflammation of the brain may be subacute. It is this form of encephalitis which is observed on the surface of the convolutions in tubercular meningitis, and diffuse meningo-encephalitis (general paralysis of the insane). In tuberculisation of the meninges the surface of the con- volutions, particularly at the base of the brain, is the seat of intense congestion, with proliferation of the neuroglia, resulting in softening of the brain tissue. Diffuse meningo-encephalitis is characterised by various lesions. First, the pia mater and the blood-vessels of that part of the membrane which dips down into the sulci are thickened by an increase of tlieir elements. On raising the pia mater, it is detached from the brain with difficulty, and morsels of the grey matter, adherent to the walls of the blood-vessels, are torn away with it. As the vessels are the seat of frequent congestion, red and yellow pigment is found in their perivascular sheaths, the result of the destruction of the extravasated red blood corpuscles. Finally changes, consisting in multiplication of the elements of the neuroglia, degeneration of the nervous elements, and soften- ing of the grey matter, take place in the brain substance. These lesions are limited to the cortical layer of the convolutions, which may be easily removed by scraping, the white substance appearing firm and distinct beneath, though it is sometimes thought to be denser than normally, owing to thickening of the neuroglia. The whole surface of the brain is affected in the same manner, and the ependyma lining the ventricles is also altered and thickened. Fine transparent granulations are also freq;uently visible to the ABSCESS OF THE BRAIN. 597 naked eye, on the surface of the ventricular ependyma, espe- cially in the fourth ventricle. These granulations are composed of embryonic elements, supplied by a few blood-vessels. The nerve cells present a series of successive lesions, which have been described by Meschede : they become granular, then pigmented, and finally atrophy. Under the name of diffuse congenital encephalitis Virchow has described a peculiar condition of the brain observed in new- bom children. In this lesion the cells of the neuroglia first proliferate and then undergo fatty degeneration; the nervous elements also become granular, an abundant formation of granular bodies resulting, and an actual softening, to which capillary haemorrhages give a red or pinkish colour. But these facts are not very conclusive, and the appearances may be simply due to the normal condition of the foetal brain. In new-bom children indeed, as well as in old persons, granular bodies will be found on the surface of the blood-vessels of the brain, and in the perivascular sheaths. In badly nourished infants, these granular bodies are much more numerous than usual, as Parrot has pointed out. Abscess of the brain. — Abscess of the brain occmrs in purulent infection, from whatever cause, and in consequence of wounds of the cranium. It may also be consecutive to ostitis or necrosis of the bones of the skull, particularly in tubercular ostitis of the petrous portion of the temporal bone, and in syphilitic necrosis of the frontal bone. Such abscesses are continuous with the purulent focus of the diseased bone, or they are developed near the focus, from which they are, however, separated : for example, the dura mater may remain intact between the abscess of the brain and the diseased bone. Cerebral abscesses are generally small, and are formed in the same way as in other organs ; they are either solitary, or disseminated in large numbers throughout the brain. They are characterised by a yellow, ropy, often viscous fluid, which contains mucin, precipitated by acetic acid, and also a large number of cellular elements. This fluid is inclosed in a cavity with downy and irregular walls, in which connective-tissue elements may be developed, ending in the production of fibrous tissue. Sometimes these abscesses may increase in size and open into the arachnoid space, or into one of the ventricles; sometimes they remain as purulent cysts in the substance of the brain. 598 LESIONS OF THE CEREBRUM AND CEREBELLUM. Chronic encephalitis, or Sclerosis. — This lesion, which is often primary in the brain, may also follow a similar lesion begun in the spinal cord. Two distinct periods or degrees must be admitted in its evolution. In the first period, rapid multiplication of the elements of the neuroglia causes the brain tissue to become soft and gelatinous, like all embryonic tissues. The second period is distinguished by atrophy of all the new elements, and by the development around them of numerous and extremely delicate fibres interlacing in every direction ; the cerebral tissue is hard and resisting, and, on examining a delicate section of the morbid part under a high power, the fibrils are seen to form a perfect matting, and between them are found atrophied nervous elements, and small cells with a round or oval nucleus. These two stages of the same disease may be found in the same brain. Idiopathic sclerosis of the cerebrum and cerebellum may be met with in the brains of idiots, cretins, and sometimes of epileptics, in which cases the morbid change is generally localised. Duguet has collected three cases of localised sclerosis of the brain in epileptics at the Salpetriere. When the lesion affects several cerebral convolutions, some may be swollen, semi-transparent, soft and gelatinous, while others are, on the contrary, small, flattened, and so hard that they can be hardly indented with the finger nail: thus the various stages of sclerosis may be met with in the same brain. At the beginning of the disease the nerve cells seem to be quite colourless and transparent, and slightly atrophied though pre- serving their angular form. "When the lesion is old and the tissue very hard, the nerve cells and tubes have almost all atrophied, sometimes even they have entirely disappeared. A great number of amyloid corpuscles are generally, in sclerosis of the brain, scattered over the surface of the atrophied convolutions and in their substance. Finally, those lesions which are formed round cerebral tumours, and particularly round large tubercles, are related to sclerosis : they are characterised by the formation of new fibrillar connective tissue, sometimes of considerable thickness. Tumours of the brain. Sarcoma. — In the brain as well as in the meninges two distinct forms of sarcoma are seen : neurogliac and angiolithic sarcoma {vide p. 144). Fibroma.— Fibroma of the brain is rare. We have had the opportunity of examining one which was located in the white sub- stance of the right crus cerebri. It was about the size of a filbert, TUMOURS OF THE BRAIN. 599 extremely hard, and composed of fine imdulating fibrils and small uni-nucleated cells. Lipoma. — A solitary case of lipoma of the brain, part of which was ossified, has been reported by Benjamin. Carcinoma is rare in the brain, sarcoma is frequently con- foimded with it. Papilloma. — We have seen one case of papilloma of consider- able size. It was seated upon the ependyma of the third ven- tricle, projecting into the lateral ventricles through the foramen of Monro. This granulating mass, engorged with milky juice, and surrounded with softened cerebral tissue, might have been mistaken for carcinoma. It was composed of a cauliflower excrescence formed of dilated blood-vessels, lined with pave- ment cells, which by desquamating gave- the fluid its milky appearance. Tubercle. — Tubercles of the brain form tumours resembUng sarcoma in external appearance. Instead of being small, like the tubercles of other organs, they may reach the size of a pea, or even of a doubled fist. Their microscopical characters are Fig. 273. — Section of a Blood-vessel in the Midst of a Tubercle of tub Brain. The lumen of the vessel c Is filled with granular fibrin ; b, white blood corpuscles contained in the vessel and clinging to its internal surface ; a, cellular elements contained in the lymph Bheath. Magnified SOU diameters. generally marked. They are hard, compact, and so intimately connected with the brain tissue that they can only be enucleated with diflBculty. On cutting across one of them and the sur- rounding tissue, its centre is seen to be yellow, and its peripheral layer grey, semi-transparent, and directly continuous with the cerebral tissue. In the cerebral tissue surrounding the tubercle active proliferation of the neuroglia is observed, as well as large multi-nucleated cells and blood-vessels showing tubercular changes. On microscopically examining a blood-vessel of the brain passing 6oo LESIONS OF THE CEREBRUM AND CEREBELLUM. towards a tubercular mass, its perivascular sheath is found to be filled with a large number of embryonic elements, and this while the vessel is still in the midst of normal nervous elements. When it penetrates the grey and semi-transparent zone of the tubercle, the sheath suddenly dilates and seems triple its original size; once it has reached the caseous zone of the tubercle it becomes blended with it. The vessel itself becomes obliterated by fibrin, throughout its whole course through the tubercular mass. Though at first sight tubercular masses in the brain seem to be actually single tumours, discrete or confluent tubercles are frequently seen at their margins. On examining deHcate sections of cerebral tubercle, cut after hardening in alcohol or chromic acid, the same characters and the same details of structure will be observed as in tubercle of all other organs : small cells imbedded in a granular substance, vessels obliterated by fibrin, granular degeneration of the cerebral elements of the tumour, etc. Syphilitic gummata. — ^While gummata of the dura mater are frequent, those of the cerebral substance are rare. They present all the appearances already described as characteristic of gummata in general. They vary in size from that of a pea to that of a nut, in shape they are generally angular, and they are located in the hemispheres, the pons varolii, and the cerebellum. On cutting across them two zones are recognised, one central, opaque, yellow, caseous, and hard, the other peripheral, grey, semi-transparent, and blending with the neighbouring cerebral tissue, which is afifected with secondary encephalitis. The cellular elements at the centre of the gumma are small and in a state of fatty degene- ration, and the blood-vessels are here partly obliterated. In the semi-transparent zone, branching cells — the cells of Deiters — are found in the midst of an embryonic tissue composed of small round cells, and also blood-vessels with their perivascular sheaths filled with lymph cells. Neuroma. — MeduUated neuromata, that is, composed of nerve cells and neuroglia, have been found on the surface of the brain {vide p. 235). Cysts are chiefly developed in the choroid plexuses : they may be serous and transparent. CHAPTEE XVI. LESIONS OF THE SPINAL CORD. I. Normal Histology of the Spinal Cord. Configuration of the spinal cord. — The spinal cord, situated in the middle of the vertebral canal, is surrounded with membranes similar to those of the brain, namely, the dura mater, the arach- noid, the sub-arachnoid connective tissue, and the pia mater. The cephalo-rachidian fluid is contained in the sub-arachnoid tissue. The spinal marrow is elongated in the form of an almost cylin- drical cord, and presents two enlargements, the cervical and the lumbar enlargement ; it ends in a cone at its lower extremity, where it is continuous with the filum terminale. The pia mater, which is very thick, adheres closely to the cord ; beneath this membrane may be distinguished, on the surface of the cord, several longitudinal fissures, the anterior median fissure, the posterior median fissure, and the lateral fissures from which the anterior and posterior nerves spring. These nerves on emergence from the spinal cord unite to pass through the vertebral notches ; the posterior, after emerging from the dura mater, are connected with the spinal ganglia ; they are much larger than the anterior. The anterior and posterior fissures divide the spinal cord into two symmetrical halves, united by a commissure. The white tract of the spinal cord, contained between the anterior fissure and the anterior roots, is called the anterior column, and the tract between the posterior median fissure and the posterior roots is called the posterior column; the lateral columns comprise all that part of the white cortex of the cord lying between the anterior roots in front and the posterior roots behind. On dividing the spinal cord transversely it is seen to be composed of a peripheral white sub- stance, and of a central grey substance ; the latter has somewhat the form of the letter H, the two anterior branches forming the anterior horns, and the posterior, the posterior horns, the hori- 2ontal line representing the grey commissure. 6o2 LESIONS OF THE SPINAL CORD. Structure of the spinal cord. — The white cortex of the spinal cord, which forms the anterior, lateral, and posterior columns, is largely composed of medullated nerve fibres, passing in a longitudinal direction ; thus, in their transverse section, they appear as small circles, in the centre of which is seen a section of the axis cylinder. Oblique and horizontal fibres are found in the white commissure, in the lateral columns, and in the posterior columns, near to the posterior cornua, at the spots where the nerves emerge.' The grey matter of the anterior and posterior cornua contains a large number of nerve cells, the arrangement and shape of which difi'er according to the parts of these cornua under examination. The nerve cells of the anterior cornua, called motor cells, because of the important function they exercise, are very large, so large indeed that they may be distinguished with the naked eye, when stained and isolated. They have a great number of ramifying or protoplasmic processes, and one process which does not ramify, called the axis cylinder, or Deiters' process {vide a, fig. 20, p. 30). They form distinct groups in the cord, particularly in the cervical and lumbar enlargements. The cells located in the most anterior part of the anterior cornua are divided into two groups, an antero- intemal, and an antero-extemal ; the latter is again, at the lumbar and cervical enlargements, separated into several distinct groups. At the angle projecting outwards, which is seen at the posterior part of the anterior cornua, there is another group of smaller cells. The columns of Clarke (the dorsal nuclei of Stilling), which are ' In order to study the spinal cord, either in the normal or pathological state, its different elements must he first examined, namely the cells of the anterior and posterior cornua, and the nerve-tubes, either by dissociating them in the fresh state, or after they have been acted upon by colouring reagents — carmine, pioro-carminate of ammonia, or osmic acid. Examination in the fresh state must be supplemented by study of sections of the spinal cord, but there are elements which can only be well seen in the fresh state, such as, for example, cells in the condition of fatty degeneration, and granular bodies ; but on the other hand the arrangement of the elements, their grouping, their pathological changes, such as atrophy of certain groups of cells or fasciculi, more particularly sclerosis, or hyper- trophy of the coimective tissue of the spinal cord, can only be exactly appreciated in sections. These are generally cut horizontally. Previous hardening of the spinal cord is necessary, to obtain which various methods are employed : either immer- sion in a '2 per cent, solution of chromic acid, which should be changed frequently, or in Miiller's fluid or bichromate of potash or bichromate of ammonia, or first in alcohol for twenty-four hours followed by the action of chromic acid and the bichromates. Two or three months at least are necessary to obtain complete hardening. Delicate sections may be then cut, stained with carmine or picro- carminate, rendered transparent by the successive action of alcohol and the essence of turpentine or cloves, and preserved in Canada balsam or Damar resin. STRUCTURE OF THE SPINAL CORD. 603 situated at the union of the anterior and posterior comua, eon- tain a rather considerable number of nerve cells of medium size. The posterior comua, and the gelatinous substance of Rolando, contain much smaller nerve cells, most of which are fusiform with two or three processes. The posterior comua decrease in size as they pass directly into the posterior foots, while the anterior comua do not reach the cortex of the cord. The sensory roots penetrate the posterior comua, partly passing through the substantia gela- tinosa, where they form small separate fasciculi. The grey commissure, situated behind the white commissure, is pierced in its centre, by the canal of the ependyma, which is continuous above with the fourth ventricle, and below with the filum terminale. The cavity of this canal, which is generally obliterated, is lined with a layer of cylindrical cells ; on each side of it are seen two large arterial and venous trunks, behind it is the posterior commissure of grey matter, traversed by a few nerve fibres, passing in a transverse direction. The connective tissue of the neuroglia is continuous with the pia mater, and supports the blood-vessels which ramify from the circumference to the centre ; it also surrounds all the nerve tubes of the white columnus. It is rather abundant in the grey substance of the cornua, as well as in the posterior commissure, around the central canal, and near the posterior median fissure. It is essentially composed of delicate and extremely long fibres, though it also contains flat or round cells, which are particularly numerous in the grey matter. The longitudinal white tract of the cortex of the spinal cord may be divided, as we have already said, into anterior, lateral, and posterior columns, each one of these colmnns being also divided into two secondary fasciculi : for example, anterior internal and anterior external fasciculi, anterior lateral and posterior lateral fasciculi, are distinguished. This division, which is a little arbi- trary, is only visible externally in the posterior columns, which are separated into two fasciculi by the intermediate posterior fissure. The fasciculus comprised between the posterior median fissure and the intermediate fissure is called the column of GoU, and that between this fissure and the posterior root the cuneiform column ; the latter, which is adjacent to the posterior comua, and which is traversed by the fibres of the posterior roots, is also called the posterior radicular zone. Probable course of the fibres of the spinal cord.— Though the 6o4 LESIONS OF THE SPINAL CORD. structure of isolated elements of the spinal cord, nerve tubes, and cells is at present tolerably well known, little is understood regarding their reciprocal relations, and we are reduced to more or less rational hypotheses based on physiological and pathological data. It is known that each nerve cell of the anterior cornua is connected with a nerve tube of the anterior roots by the process of Deiters, and that the numerous ramifying processes which spring from nerve cells are either lost in the tissue of the neuroglia or anastomose with processes proceeding from neigh- bouring cells. The white fascicuU of the antero-lateral columns are considered to be the receivers of motor impulses emanating from the brain and the anterior cornua of the spinal cord. The posterior roots are connected with the posterior cornua; their most external fibres pass between the longitudinal fibres to enter the grey matter, then traverse the substantia gelatinosa, and bend round to take a vertical direction in the posterior columns. They may also be inflected to pass to the anterior part of the posterior cornua, or even into the anterior cornua. The internal fibres of the posterior roots curve over in the shape of an arc or s, and take a horizontal direction across the external portion of the posterior columns, and penetrate the anterior part of the posterior cornua, or are lost in the anterior cornua ; they doubtless terminate in the cells of the columns of Clarke. On examining the spinal cord, from the cervical to the lumbar region, the white fasciculi are seen to diminish in thickness, in comparison with the grey matter; they are, in fact, reinforced from below upwards, by the nerves proceeding partly to the grey centres of the spinal cord, and partly to the cerebrum and cerebellum, II. Histological Lesions of the Spinal Meninges. Although most of the facts described regarding the cerebral meninges are also applicable to the membranes of the spinal cord, yet since certain lesions of the latter are not found in the former, or differ from themi greatly, we have thought it well to devote a special description to lesions of the spinal meninges. Haemorrhage into the spinal meninges. — More or less consider- able effusions of blood may occiu-, either round the dura mater, or between this membrane and the osseous canal, or into the arachnoid cavity, or the sub-arachnoid spaces. In the first case the blood is diffused and partly coagulated in the cellulo-adipose tissue, HYPERTROPHIC CERVICAL PACHYMENINGITIS. 605 and round the roots of the nerves. In the second, it exists either as small ecchymoses on the internal surface of the dura mater, or as an actual effusion of blood varying in extent. These hsemorrhages are due, either to direct or indirect wounds, lesions of the blood- vessels, and sometimes even to aneurisms. They are also met with in tetanus, asphyxia, and meningitis. Meningitis. — Acute meningitis and epidemic cerebro-spinal meningitis have been already described on page 579. Chronic spinal meningitis, which differs in a marked manner from cerebral meningitis, will, however, be described here. Chronic spinal meningitis is not rare ; it may affect either the dura mater, the arachnoid, or the pia mater. Chronic pachymeningitis is met with whenever inflammatory or other tumom's, springing from the vertebrae or the vertebral articulations, project into the vertebral canal, and cause irritation of the dura mater. There are two forms of chronic pachymeningitis, which should be treated separately : hypertrophic cervical pachymeningitis, and tubercular meningitis, or Pott's disease. Hypertrophic cervical pachymeningitis. — This very rare lesion, which had been merely indicated by many authors, was first fully described by Charcot and Joffroy (' Archives de Physiologic,' 1869). In this disease the cervical spinal cord and its membranes form a fusiform enlargement, which fills the vertebral canal, and adheres to the vertebral ligaments. The meninges, thickened and ad- herent together, form, with the spinal cord which they surround, a mass in which the component structures cannot be separated from one another. In a transverse section, passing through the whole tumour, the dura mater is found considerably thickened, mea- suring several millimetres in diameter. When the line of demar- cation between the dura mater and the pia mater is still visible, the latter is seen to be thickened in a very marked manner. In the deformed spinal cord, flattened from before backwards, the white and grey substance can sometimes be tolerably distinctly recognised. Microscopical examination of the dura mater shows that it is composed of a great number of laminae of connective tissue, arranged in concentric layers, resembling in structure the cornea, or lamellar fibroma. The nerve fibres of the roots passing through the diseased dura mater are more or less compressed and altered. In the midst of this envelope of fibrous tissue, formed in a great part by the dura mater, the spinal cord itself is found to have 6o6 LESIONS OF THE SPINAL CORD. undergone great changes : the white substance, for example, may be sclerosed and have become grey and semi-transparent, so that it is hardly possible to differentiate it from the central grey matter. Histological study of the sclerosed part of the white substance shows all the lesions of sclerosis of the spinal cord, described later ; if, in some parts of the spinal cord, islets of grey and white matter may be found, elsewhere the lesions are more pronounced. This more or less extensive partial destruction of the cervical spinal cord determines secondary degeneration below and above the diseased part, which is ascending in the posterior columns and descending in the anterior columns. Chronic tubercular pachymeningitis, or Pott's disease. — In most of the cases of Pott's disease, accompanied with tubercular ostitis or fungoid arthritis, the dura mater is more or less affected ; it is rare for it not to be thickened and covered externally, at the level of the diseased vertebrae, by a thick layer of caseous pus. Its external surface is generally covered with fungoid granulations of a dirty grey colour, and infiltrated with caseous pus {external caseous 'pachymeningitis). The anterior vertebral ligament is dissociated and destroyed in parts, so that the pus passes from the vertebrae, and that which is secreted on the surface of the dura mater burrows between the external surface of the dura mater and the osseous canal, and often communicates directly with a sac full of pus, which projects in front of the vertebral colunon, beneath the common anterior vertebral ligament. Inflammation of the dura mater is limited exactly to the parts of the vertebra diseased. The membrane is infiltrated either in its external layers alone, or throughout its whole thickness, by numerous embryonic cells. When affected throughout its whole thickness, its internal surface, which is in contact with the arachnoid and pia mater, also shows manifest signs of inflammation : Vulpian has seen new vas- cular false membranes produced. Michaud,' who made a histo- logical study of pachymeningitis, has seen the deep layers of the dura mater infiltrated with embryonic elements between the fibrous fasciculi and laminae, while prominent granulations on its external surface were filled with the same elements compressed into a thick layer and infiltrated with fat granules : he has also noticed in the substance of these new formations small foci, containing round cells in a condition of fatty degeneration, and which he regarded as microscopic purulent foci. One of us, having observed many • De la meningite et de la myelite dans le mal vcrUbral. Th6se de dootorat. CHRONIC TUBERCULAR PACHYMENINGITIS. 607 of these facts, has found tubercular granulations in different stages of evolution in the thickened dura mater, and in the caseous granulations on its external, and even on its internal, surface. These granulations, which are very characteristic, are discrete or confluent, and contain numerous giant cells,' a certain num- ber of which undergo caseous melting. It is probable that in most cases of caseous pachymeningitis, related to Pott's disease, the disease must be attributed to tubercular inflammation of the dura mater. Consecutive to these lesions of the vertebrae, dura mater, arachnoid, and pia mater, the spinal cord and nerves are altered to a variable degree ; sometimes, however, the spinal cord may entirely escape morbid change. The pathological changes of the spinal cord and nerves are not solely due to compression, but generally to the extension of inflammation. The spinal cord is often softened, diffluent, or converted into an atrophied yellow- ish mass, in which the grey cornua and white columns can no longer be distinguished ; it is also infiltrated with numerous granular bodies. Michaud and Charcot have reported a case in which a patient, originally paralytic in consequence of Pott's disease, recovered from paraplegia so as to be able to walk. The autopsy showed partial atrophy of the spinal cord, which was reduced to a fifth of its normal size, and sclerosis of the white substance, only one of the anterior cornua remaining. The nerve fibres which were preserved showed no change. The authors supposed that these nerve fibres were regenerated nerve tubes, but this was not proved. It might be thought that the spinal cord, filled at first with the products of degeneration, such as granular bodies, and unable to perform its functions on account of their presence, resumes its activity when these inflammatory products have been reabsorbed. Masius and Van Lair have observed regeneration of the spinal cord and recovery of its functions in frogs, not only after simple ' In the first case presented by one of us to the Society de Biologie {Comptes Renduf, 1873, p. 263), there were in the midst of the dura mater cavities filled with rather large epithelioid cells. These cavities had previously been mistaken for sections of inflamed lymph vessels. Later, we had the opportunity of examining many other cases of pachymeningitis, in which the granulations and thickened embryonic tissue oE the dura mater also showed very characteristic tubercle. On examining then again the sections of the dura mater made from our first case, we easily recognised that the cavities, which we had regarded as sections of lymphatics, were nothing more than masses of epithelial and giant cells, such as are found in tubercle. 6o8 LESIONS OF THE SPINAL CORD. section, but also after ablation of a portion of this organ. At the end of a few months they found in the grey tissue interposed between the two portions of the divided spinal cord, bi-polar and multi-polar cells, regarded by them as nerve cells, and fibres described as fibres of Eemak. If however experiments on frogs have given positive results, those which have been performed on mammals have hitherto given negative results. An opinion cannot yet be formulated on the regeneration of nerve elements in the spinal cord in man, in cases of atrophy following the myelitis of Pott's disease. Chronic spinal meningitis, characterised by more or less con- siderable thickening of the pia mater, and adhesion of the two layers of the arachnoid, is particularly observed, after chronic affections of the spinal cord, softening, or sclerosis. Thus, in sclerosis of the posterior or lateral columns, the pia mater is chronically inflamed at the level of the diseased parts of the cord. On opening the spinal cord of old persons, fibrous or calcareous plates are frequently unexpectedly found in the arachnoid ; they are seated generally in the posterior and inferior part of the cord, near the cauda equina ; the visceral layer of the arachnoid is the most frequently affected. These plates, varying in length from a half to two centimetres, may be rather numerous, and are composed of fibrous tissue generally calcified. They are slightly transparent, and resemble cartilaginous tissue ; they, however, never contain cartilage cells ; they sometimes undergo a kind of ossification, that is to say, that in the midst of the calcified con- nective tissue may be found lacunae furnished with canaUculated processes, inclosing a small elongated cell: it might be con- cluded that these were bone corpuscles; but the tissue is not vascular, and contains no Haversian canals. In two cases published by Jaccoud and Vulpian, these plates seem to have caused acci- dents which were referred to pressure on the spinal roots ; but in most cases in which they are found at the autopsy they have caused no appreciable symptoms during life. III. The Pathological Histology of the Spinal Cord. Eecent and numerous researches on the spinal cord have thrown light on a series of diseases of the nervous system which were formerly obscure, or were regarded as simple neuroses. Pathological lesions and their connection with the symptoms PATHOLOGY OF THE SPINAL CORD. 609 observed are better understood in the spinal cord than in the brain or sympathetic system, which is due to the fact that the structure and physiology of the spinal cord are better understood than in the case of the encephalon. In the scientific progress of recent years the researches of French physicians, particularly Duchenne of Boulogne, Charcot, Vulpian, and their pupils, have without doubt greatly advanced our knowledge of the lesions of the nervous system, and ia this treatise we propose to profit largely by their researches. The pathological histology of the spinal cord difi"ers little from that of the brain, and is in reality extremely simple. It includes nutritive modifications of the nerve cells, their hypertrophy, atrophy, and pigmentation, and even their complete disappearance in consequence of insufiicient nutrition, a not unfrequent conse- quence of chronic inflammation ; also similar lesion of the nerve tubes, which, in recent myelitis, sometimes show atrophy of their axis cylinders, and at the same time nutritive lesions of the myelin, which we have already studied when considering division of the nerves. Later the myelin may completely disappear, but the axis cylinders exist much longer, sometimes even indefinitely, although atrophied. Simultaneously with changes in the elements of the nervous tissue, the connective tissue of the neuroglia undergoes parallel modifications ; such as, in acute processes, tumefaction of the flat cells of the neuroglia, and the new formation of small round elements or lymph cells, and granular bodies. Later, in chronic processes, either inflammatory or degenerative, the fibrous tissue and neuroglia thicken, and the nerve tubes, or rather the axis cylinders left after the total disappearance of the myelin, become surrounded with numerous fibrils thicker than normal. This change constitutes what is called by the name of sclerosis. Sclerosis ends in making the tissue of the organ much denser, and in atrophy of the nerve elements, the functions of which are abolished. It is not produced suddenly, for it is the consequence of acute or subacute inflammation, which first affects either the grey centres or the white fasciculi of the spinal cord or brain. In all cases of sclerosis, as well as in atrophy from whatever cause, and in all chronic processes, the spinal cord, particularly its peri- pheral layers and the fibrous tissue surrounding the central canal, contain a considerable quantity of amyloid corpuscles. They are small, spherical bodies, vitreous and refractive, and stain violet with a solution of iodine; it is owing to this reaction that they have been called amyloid, though they are formed of R K 6io LESIONS OF THE SPINAL CORD. a proteid substance, the chemical composition of which differs entirely from starch. Simultaneously with these lesions of the elements of the nervous tissue and neuroglia, the blood-vessels show changes already considered, congestion, exudation, granular bodies, etc. These two series of nutritive and inflammatory troubles, some affecting the nerve cells and tubes, others the connective tissue, though most frequently united, may neverthe- less be referred, the former to parenchymatous inflammation, the latter to interstitial inflammation. But interstitial inflammation, or sclerosis, is rarely primary ; it more often follows lesions of the trophic centres, either in the spinal cord or in the encephalon. Affections of the spinal cord, reduced to degenerative or inflam- matory processes, the histology of which is simple, would not furnish subjects for so many investigations, did not the most elementary lesions, carefully studied, furnish data for general deductions. To describe lesions corresponding to the different diseases of the spinal cord, which have been defined for the last twenty years by thefr symptoms, as well as by thefr pathological anatomy, we should have to enter into fuller details regarding the topographical pathological anatomy of the spinal cord. We have already, on page 601, briefly described the various columns of white substance, and the masses of grey matter. These data, borrowed from descriptive anatomy, are useful at each step in the pathology of the spinal cord ; in fact, most of the diseases of the spinal cord are essentially and originally localised in some one of the columns of white substance or grey substance, and most frequently throughout the whole length of the cord. In locomotor ataxy, for example, the primary seat of the disease is in the pos- terior radicular columns (Pierret) or cuneiform columns, implicat- ing later the columns of Groll, that is to say, affecting the whole of the posterior columns. Such is again peri-ependymar myehtis, limited to the connective tissue surrounding the central canal (Hallopeau) ; such are infantile paralysis, spinal paralysis of the adult, progressive muscular atrophy, which diseases, though dis- tinguished from each other by their symptoms and duration, have none the less a common point of origin in an acute or subacute inflammatory lesion ending in atrophy of the grey anterior comua {acute or subacute anterior poliomyelitis); such is, again, amyotrophic lateral sclerosis (Charcot and Grombault), shown by the symptoms of spasmodic paraplegia. Degenerative myelitis, consecutive either to localised destruc- tion of the spinal cord in a transverse direction, as may occur in H^MATOMYELIA. 6ii Pott's disease and tumours, or to foci of softening or apoplexy in the brain, always takes a longitudinal course in the spinal columns. Most of the primary or secondary diseases of the spinal cord may be included in a group of systeTnatic lesions, according to Vulpian's expression. They are invariably localised in certain fixed columns, without implicating adjacent parts of the cord. In opposition to systematic lesions, other lesions of the spinal cord are called Mffuse. In spite of the progress effected during the last thirty years in cerebral and spinal pathology, it must not be thought that the lesion of every nervous affection has been deter- mined. Hysteria, true epilepsy, paralysis agitans, have not yet been referred to any persistent lesion of the nervous tissue, nor in tetanus and hydrophobia can any constant lesions be always recognised after death. With these preliminary remarks we shall now proceed to examine successively the various lesions of the spinal cord. Congestion. — Congestion of the spinal cord is seen simul- taneously with congestion and inflammation of the meninges, in typhoid fever, certain forms of rheumatism, febrile diseases, and in chronic cardiac disease. It is characterised by distension of the blood-vessels. Schroder van der Kolk has advanced the opinion that the medulla oblongata is congested in every case of epilepsy, but this opinion has not been coniirmed. In postr-mortem exami- nations it is very difficult to say if the fulness of the blood- vessels and staining of the spinal tissue are due to the position of the body after death, to cadaveric stasis, or to hypersemia which existed during life. Congestion can only be positively affirmed when blood pigment is found round the vessels, in the perivascular sheaths, or in the spinal tissue. Spinal haemorrhage, or Hsematomyelia. — Haemorrhage into the spinal cord is rare ; it is seen either as an infiltration of blood, or as an isolated blood clot in the midst of dissociated and destroyed spinal tissue ; it is generally seated in the grey centres of the cord, and may extend for a considerable distance. The lesions of the blood-vessels, the ultimate changes of the clot and nervous tissue, are similar to those already described in cerebral apoplexy. According to Charcot and Hayem, this accident is always consecu- tive to myelitis, of which it constitutes a peculiar form— apoplec- tiform myelitis. It may also be the result of sudden variations of barometric pressure on the spinal cord. In animals subjected by R B 2 6i2 LESIONS OF THE SPINAL CORD. M. Bert to high atmospheric pressure, which was suddenly relaxed, the expansion of gases contained in the blood produced lacerations of the blood-vessels of the spinal cord, and even sudden death by capillary haemorrhage and laceration of the nervous tissue. The same causes sometimes produce the same effects in man. Softening. — Softening, consequent on arterial embohsm and atheroma of the blood-vessels of the cord, is very rare ; the lesion is localised in a limited region of the organ. The colour, con- sistence, and structure of the softened part vary exactly in the same way as in cerebral softening, already described. Sometimes the softened part is soft, diffluent, whitish, and opaque, and yields a milky fluid on section ; at other times the altered part is, on the contrary, dry, yellow, shrunken, and atrophied. On letting a stream of water fall upon it, however, this hardness is seen to be only apparent ; the water carries away the dissociated elements, which give it a milky opacity. On examining fresh specimens under the microscope a considerable number of granular bodies, derived from the granular destruction of the myelin of the nerve tubes, is found in both cases, as well as altered blood-vessels, the perivascular sheaths of which are full of the same morbid elements. Softening of the spinal cord is very frequently observed in compression of this organ by a tumour located in the spinal meninges. In such a case, two series of lesions must be dis- tinguished : the first consists in a focus of softening, or in diffused inflammation, related to vertebral caries or tubercular pachymeningitis ; the second is characterised by secondary degen- erations above and below the diseased point. These secondary degenerations, some ascending in the columns of GoU, others descending in the pyramidal fasciculi, are constant, whatever may be the nature of the lesion producing the transverse solution of continuity in the spinal cord. They are extremely interesting, for they assist us in determining the course of the fibres of the spinal cord, and the physiological function of the white columns, and also in explaining and interpreting the motor and sensory symptoms observed in Pott's disease. Similar degeneration of the antero- lateral fasciculi result from lesions of the brain, for example, when hsemorrhage or softening has destroyed a large part of one of the cerebral hemisphere*. Secondary degenerations of the spinal cord. — The parts of the spinal cord which are altered, either in consequence of a destruc- SECONDARY DEGENERATION. 613 tive lesion or focus in the brain or cord, show changes resembling those of myelitis. Sometimes the affected parts appear normal to the naked eye ; at other times they are more opaque, which is due to the great number of graniilar bodies present, or they are semi-transparent, owing to the absorption and disappearance of the myelin. The diseased spinal tissue is generally rather softened, though it may be condensed; the altered fasciculi are usually much atrophied. Examined under the microscope in the fresh state, granular bodies are generally seen to be present in great numbers. In sections hardened with chromic acid, Miiller's fluid, or the bichromates, stained with carmine, cleared with tiupentine, and mounted in Canada balsam, the granular bodies are no longer visible, but the lesions of chronic sclerosis can always be dis- tinguished by this method. The nerve tubes are seen to be atrophied and deprived of their myelin, though the axis cylinders are still preserved. The degenerated fasciculi first show the appearances of myelitis with softening, then those of sclerosis. We will proceed now to examine each case in particular, with special regard to the seat of the lesion. Secondary degeneration of the spinal cord, consecutive to an apoplectic focus or to softening of the brain. — It is necessary to recall here the cerebral origin of the pyramidal fasciculi, their course in the brain, pons varolii, and medulla oblongata, and their termina- tion in the spinal cord. Taking the pyramidal fasciculi in the medulla oblongata, where they form the anterior pyramids, and following them as they pass upwards into the brain, they are found to pass under the transverse fibres, intersect with those of the pons, and to be collected again into a distinct fasciculus, in the lower plane of the crus cerebri. According to the researches of Flechsig, they occupy the middle third of the inferior stage of the crus ; they then, with the cerebral expansion of the crus, penetrate the internal capsule between the optic thalamus and corpus striatum, pass upwards into the centrum ovale, and from there into the cerebral convolutions. According to Flechsig and Pitres, the pyramidal fasciculus passes through the posterior part of the internal capsule, to end in the frontal and ascending parietal convolutions and the paracentral lobule, which con- volutions border the fissure of Rolando (the psycho-motor centres of the limbs). To return now to the medulla oblongata, where the i)yramids decussate before descending into the spinal cord. This'decLi,^sation of the pyramids takes place in the three 6i4 LESIONS OF THE SPINAL CORD. following ways : First, the most frequent is, that the pyramid divides into two fasciculi, one direct, which descends in the anterior column of the cord of the same side, and the other larger, which decussates with the opposite fasciculus, and passes into the lateral column of the cord on the opposite side. This decussated pyramidal fasciculus is, in a transverse section of the spinal cord, found in the most posterior part of the lateral column, in contact with the posterior roots. The relative sizes of the direct and decussated fasciculi vary ; the latter may be extremely small, thus explaining direct paralysis of cerebral origin, which is, however, extremely rare. Secondly, in one person in six, decussa- FiG. 274 — Tbansvekse Section of the Cervical Enlaeqement op the Spinal Cord. (After Charcot.) A', A', direct anterior fasciculi ; A, A, the decussated pyramid fasciculi or TUrck's fasciculi ; B, B, posterior radicular zones ; c', tf, posterior coruua ; D, D, anterior comua ; F, anterior radicular zones ; e, columns of Gk>ll. tion is complete and there is no direct fasciculus. Thirdly, one only of the pyramids may divide into direct and decussating fasciculi, the second pyramid crossing in its entirety. Thus, in the spinal cord, the fasciculi of the pyramids usually occupy two distinct regions : the direct fasciculus (a', fig. 274) is situated at the most internal part of the anterior column, alongside the anterior median fissure ; the decussated fasciculus (a, fig. 274), or Tiirek's fasciculus, is larger, and is situated at the most posterior part of the lateral column, in contact with the posterior comua, never extending, however, as far as the cortex of the cord, the surface of SECONDARY DEGENERATION. 6is the lateral column being bordered by the direct cerebeUax fasciculus. The pyranudal fasciculi appear to be lost in the anterior comua of the cord. These data result from researches on the development of <4^ Fio. 276.— Secondary Deqenkbation op the Spinal Cord. The three figures A, b, and c represent a case of old lesion of the right hemisphere. The shaded ports indicated the seat of the secondary degeneration ; a, altered direct fasciculus ; h, seat of the lesion in the left lateral f aacioulus in the cervical region of the cord ; 6' the same lesion in the dorsal region ; V<, the same lesion in the lumbar enlargement. The figures D, b, p show sections of the spinal cord in the dorsal and lumbar regions, below the spot where the cord has been entirely destroyed by compression. The shaded parts c, d, and c" represent the seat and extent of the descending degeneration. Fig. 276. A, degeneration in the cms cerebri — the pyramid fasciculus ; b, internal peduncular fasci- cnluB, Bometimea sharp and exceptionally degenerated ; 0, external fasciculus (centripetal), never degenerated ; D, pons Tarolil ; it is asymmetrical, and depressed on the side of the lesion ; B, degenerated pynunidal fasciculus ; F, decussation of the pyramids. (After Charcot.) the pyramidal fasciculi, which in new-bom infants are sooner provided with medullary sheaths than the neighbouring parts. 6i6 LESIONS OF THE SPINAL CORD. They have been confirmed by pathology. Every time that a focus of softening or haemorrhage occurs, implicating and destroying a part of the brain in the form of a truncated pyramid, the base of which is formed of the ascending frontal and parietal convolutions and the paracentral lobule, and the apex by the two anterior thirds of the posterior part of the internal capsule, the motor fibres derived from this part of the brain, and which pass into the spinal cord, are there found to be degenerated. The crus cerebri on the side of the lesion is grey and atrophied ; the pyramid continuous with it shows the same atrophy and colour, and the olivary body is more exposed than at the same level on the opposite side {vide fig. 276). Below the decussation of the pyramids, sections of the Fig. 277.- -Transvekse SEcrioN of the Spinal Cord in the Cervical Kegion. A, degeneration of the decussated pyramidal fasciculus in a case of lesion of the motor centres of the cerebral hemispheres ; B, degeneration of the direct fasciculus ; 0, white substance corresponding to the cerebellar fasciculus ; D, intermediate region between the posterior horn and the pyramidal fasciculus ; this region is always respected in descending degeneration. (After Charcot.) medulla show double degeneration, on the same side as the cerebral lesion in front, near the anterior median fissure {a, A, fig. 275, and B, fig. 277), and on the opposite side in the lateral column for a variable distance. Softening of the lateral fasciculus is localised in the most posterior part of this column, between the collateral posterior fissure and the dentate ligament (vide fig. 275, b, h', h", and A, fig. 277). These secondary degenerations of the spinal cord were first described by Tiirck, and afterwards verified by Grubler, Charcot, Vulpian, Bouchard, etc. When secondary degeneration is very SECONDARY DEGENERATION FOLLOWING MYELITIS. 617 marked, it may be recognised in a section of the spinal cord in the fresh state, by a change of colour of the white substance, which has become grey and yellowish ; but, in order to localise exactly the seat of the degeneration, sections must be cut after having been hardened by the classic method of Lockhart Clarke. In preparations made in the fresh state, numerous uni- nucleated granular bodies are found, either free or contained in the perivascular sheaths ; atrophy or almost entire disappearance of the nerve tubes is also seen. In cases in which the disease has been of long duration, the granular bodies are less numerous, but there is a much larger number of fibres and cells of the neuroglia and embryonic cells than in the normal condition — in a word, chronic inflammation of the spinal cord is present. This atrophy of the pyramidal fasciculi may be followed by atrophy of the motor cells of the anterior comua. Where these spinal lesions are present, recovery of mobility on the paralysed side is impossible, permanent contraction of the extremities — consecutive contracture of hemiplegia — is produced, and always accompanies secondary degeneration of the pyramidal fasciculi (Bouchard). It may be remarked that haemorrhage or softening of the brain, occupying other regions than those indicated above, do not cause secondary degeneration of the spinal cord. Secondary degeneration following myelitis or loss of substance of the spinal cord. — In Pott's disease, the spinal cord, compressed and irritated by the inflammatory products which are formed around it, undergoes complicated lesions. Tumours, developed either in the spinal meninges or in the vertebrae, may produce the same efifects. The spinal cord is then softened, opaque, of a whitish or yellowish tint, for an extent corresponding to the tumour, that is to say, for a Hmited horizontal segment. When such a segment is destroyed, the spinal cord above and below undergoes changes, which, in the cases examined by Tiirck, Charcot, Vulpian, Bouchard, and by ourselves, seem to be constant, and are as follows : the posterior columns degenerate above the softened spot (vide fig. 278), and the lateral columns below. In the posterior columns the lesion soon becomes localised in the columns of Goll, which are degenerated throughout their whole length and thickness, as far as the floor of the fourth ventricle (vide fig. 278). The descending lesion first invades, near the focus of softening, the whole extent of the antero-lateral columns (vide fig. 275, d), it then becomes limited to the most posterior part of 6i8 LESIONS OF THE SPINAL CORD. the lateral columns, near the posterior comua (fig. 275, E, c', and F, c") : it never affects the cortex of the cord. The degenerated portion becomes less and less extensive as it descends. In the degenerated parts are found nerve tubes which have undergone fatty degeneration and atrophy, and between them numerous granular bodies. Degeneration of the spinal cord in consequence of compression of the nerves of the Cauda equina by a tumour. — In a case of sarcoma of the cauda equina, observed by ourselves, the nerves were compressed and degenerated at the level of the tumour, and the posterior columns of the cord had undergone similar degenera- tion (fig. 279). Several other cases, since observed, show that FiQ. 278. — Ascending Degeneration of the Posterior FASOIOUIil OF THE SpINAL CorD, IN A CASE OF COM- PRESSION of the Spinal Cord at the Lowes Part OF THE Dorsal Eeqion. e, lesion ol the posterior colmnns at the dorsal region abOTe the spot compressed ; c*, a more limited lesion above ; e!' and ef'*, lesions less and less extensive as the cervical region Is approached, the columns of GroU undergo degeneration, in consequence of compression of the nerves of the cauda equina. To the question what is the cause of secondary degeneration, ascending in the posterior columns, and descending in the lateral columns, it may be answered, that nerve tubes divided in any part of their course become granular in that part which is separated from their trophic centre. The experiments of Waller proved that, on dividing the anterior or motor roots of the spinal CAUSES OF SECONDARY DEGENERATION. 619 nerves, the peripheral part of the motor nerves undergoes degen- erative change, while the central portion, by preserving its con- nections with the nerve cells of the anterior comua of the cord, remains normal. The same observer showed that degeneration of the nerves took the reverse course when the posterior roots were cut ; the end which remains connected with the spinal ganglion is normal, while the central segment becomes granular. The morbid changes, observed in the nerve tubes of the spinal cord in secondary degenerations, have been explained by separation from their trophic cells. There is, however, still much obscurity in this subject, due to the fact that the course of the nerve fibres in the spinal cord is far from being perfectly elucidated. In their first physiological experiments, Vulpian and Westphal did not Fio. 279.— Secondaky Degeneration of the Posterior Fasciculi of the Spinal Cord, from a case op Com- pression OF THE Nerves in the Cauda Equina. d, lesion of the posterior column In the inferior part of the lumbar enlargement; d', the same lesion at the superior part of the lumbar enlargement ; d", lesion at the dorsal region ; d'", the same lesion much diminished in extent at the cervical enlargement. succeed in reproducing ascending and descending lesions in the spinal cord of guinea-pigs and pigeons, by destruction of a portion of the spinal cord ; but in more recent experiments, performed on dogs, they observed phenomena of degeneration similar to those observed in man. Schiefiferdecker, having succeeded in keepmg alive for several weeks dogs in which he had divided the spmal cord at the level of the twelfth dorsal vertebra, also always observed the ascending and descending lesions of degeneration. 620 LESIONS OF THE SPINAL CORD. There were traces of morbid change at the end of the first week, and the most complete degenerative changes were attained at the end of four or five weeks. Ascending degeneration was found, as in man, in the columns of GoU and in the direct cerebellar fasciculi; descending degeneration was very apparent in the antero-lateral columns. There is in man, however, an exception to secondary degenera tion of the spinal cord. In the disease, to be described presently, called sclerosis in plaques, in which the grey centres and white fasciculi of the cord are irregularly destroyed, no secondary degeneration of the nerve tubes is observed. Vulpian concludes from this that secondary degeneration is not alone caused by separation of the nerves from their cells, but that persistent irritation plays an important part in these changes. We may add, in conclusion, that on examining the spinal cord of subjects who had suffered amputation a long time previously, or of animals in which the sciatic nerve had been divided, the consecutive, lesions of the spinal cord were found to implicate not only the white posterior columns but also the anterior columns and the cells of the anterior cornua (Vulpian). Myelitis. — Under this name may be described a series of very different pathological conditions, in which there is acute or chronic inflammation of the various elements of the spinal cord. Indeed, under the name of myelitis is included not only uncomplicated inflammation, characterised by the formation of new elements, embryonic cells, white blood corpuscles, or pus cells effused between the elements of the spinal cord, but also multiplication of the elements and thickening of the neuroglia, known as sclerosis. Eeasoning from the same sequence of facts, atrophy of the nerve elements, which in certain cases of poliomyelitis is the only lesion found at the autopsy, would be referred to inflammation. Myelitis may be acute or chronic. According to the classi- fication given by Vulpian, and generally adopted, we divide myelitis into diffuse or systematic. Myelitis is said to be system- atic when limited to a column of either white or grey substance and when it has a regular evolution. Acute and chronic, diffuse and systematic, myelitis will now be studied in order. DIFFUSE ACUTE MYELITIS. 621 A. Acute Myelitis. a. Acute diffuse suppurative myelitis is very rare ; it may be met with in epidemic spinal meningitis, and in consequence of eschars of the sacrum having invaded the membranes of the spinal cord • the myelitis is then superficial and consecutive to meningitis. In certain cases of gangrenous eschars observed in the insane the purulent exudation and the inflamed spinal meninges, as well as the cord itself, have all the characters, the colour, and odour of gangrene : these lesions may extend to the medulla oblongata, the pons varolii, and the base of the brain. Metastatic abscesses are seen exceptionally in the spinal cord in the case of purulent infection. 6. Diffuse simple acute myelitis has various causes — wounds chills, meningitis, tumours of the meninges, acute infectious diseases, such as typhoid fever, variola, etc. The lesions are some- times limited to a very small extent of the spinal cord, and at others occupy almost its whole length. Its naked-eye appearances are variable ; sometimes the spinal tissue is softened, whitish, pink yellowish, or brown in colour, according as the blood-vessels are more or less congested, or as the red corpuscles are extravasated in greater or less numbers ; sometimes ecchymotic spots and dilated vessels are seen ; in other cases the spinal cord is on the contrary rather hardened than softened, and on microscopic ex- amination there are found granular nerve tubes, a large quantity of white corpuscles, some of which are normal, others filled with blood, pigment cells, and free fat granules, and granular bodies : the latter are found in the perivascular sheaths. When the spinal cord is softened, microscopical examination is not possible in the fresh state ; if, however, it has preserved a certain con- sistence, it may be hardened by the usual methods, and examined in delicate sections. In such preparations the state of the blood-vessels, their dilatation, the fibrinous exudations, the effusion of lymph cells into the perivascular sheaths, and the new formation of nuclei and small cells in the grey cornua and commissures, may be recognised ; the stellate or Deiters cells are more numerous and more apparent than in the normal condition. The nerve cells of the anterior cornua sometimes undergo extreme hypertrophy in acute myelitis (Charcot); they may 622 LESIONS OF THE SPINAL CORD. even measure 80 fj, in diameter ; they are filled with an amyloid substance, vitreous in appearance, and in which one or more vacuoles filled with blood may be recognised; the nucleus of these cells is more or less modified, their nucleolus has often dis- appeared, and they themselves may be either transparent orgranu- lar. Alongside these hypertrophied cells others are foimd, which are hardened, atrophied, without nuclei or processes, irregular in shape, and staining badly with carmine, or else transformed into masses of small granules. The axis cylinders are hypertrophied, varicose, and granular, or excavated with vacuoles. (Frommann, Charcot and Joffiroy, etc.) This state of the axis cylinders was observed by Jofifroy in myelitis produced experimentally in the dog. Foci of granular disintegration (Lockhart Clarke), in which all the nerve elements are reduced to granules, have also been described in myelitis. As these foci have been seen in spinal cords, the freshness, careful preparation, and hardening of which may be suspected, it seems probable that they are often the result of accident, and are really artificial changes. The lesions of acute myelitis are distributed in a very varying manner ; in some cases they predominate in the grey central part of the spinal cord ; in others the cortex is more particularly affected, especially when myelitis is consecutive to meningitis or to a tumour of the meninges ; sometimes they are localised in only one half of the spinal cord. Inflammation of the meninges, and degenera- tion or interstitial inflammation of the roots of the nerves near the diseased parts, are generally present at the same time. Haemorrhage may be, according to Charcot and Hayem, the con- sequence of inflammatory softening ; the effusion of blood which is then produced hastens the fatal termination. Localised myelitis is, on the contrary, followed by ulterior changes, such as complete degeneration and atrophy of the parts in which it is seated. It is then undistinguishable from limited chronic softening. c. Acute ascending paralysis. — These cases of diffuse acute mye- litis are closely related to those described by Landry, and since called by the name of acute ascending paralysis. At the autopsy of persons affected with this disease, which runs the same course as very acute myelitis, no lesions, either gross or microscopic, can be discovered m the spinal cord. In the autopsies made by Landry, Vulpian, Levy, Hayem, Dejerine, Westphal, and by ourselves, no lesions were dis- covered capable of explaining the paraplegic symptoms. It should SYSTEMATIC ACUTE MYELITIS. 623 not however be concluded that no lesions exist, but only that hitherto they have escaped our methods of investigation. It should be added, however, that in two recent observations made by Keinhard and Eisenlohr, spinal lesions, corresponding to a very mild degree of myelitis, were found, namely, swelling of the axis cylinders and motor cells, fibrinous exudation round the blood- vessels, and capillary haemorrhages. Dejerine found these lesions in the anterior roots of the spinal nerves in two cases of ascending paralysis ; the nerves presented the same lesions as are observed in the peripheral segment of a divided nerve. Dejerine thought that these alterations of the nerves were consecutive to a lesion of the cells of the anterior cornua, which lesion, however, he did not find. It is therefore necessary to wait before deciding as to the value of the lesions hitherto described ; they do not appear to us to be in proportion to the serious nature of acute ascending paralysis. d. Acute systematic myelitis. — Acute systematic myelites are not numerous, and are limited entirely to the anterior cornua of the spinal cord. The myelites of the anterior cornua, still called sys- tematic anterior poliomyelitis, form a natural group, on which much light has been thrown of late years by Duchenne, Charcot, JofiFroy, Damaschino, etc. They comprehend the spinal paralysis of infants, the spinal paralysis of adults, and progressive muscular atrophy. The myelitis of infantile paralysis is acute, the spinal paralysis of the adult is subacute, and progressive muscular atrophy pursues a chronic course. The common phenomena of these polio-myelites are that motion and the voluntary muscles are alone affected, the sensibility remaining intact, and that they are accompanied with trophic troubles, chronic fatty degeneration, and atrophy of the muscular fibres. The lesions found after death in infantile paralysis are various, for, the disease having lasted for a variable length of time, some- times the lesions of recent myelitis are found, and at others atrophic changes, which originated many years previously. Thus in the autopsy of a patient of Charcot, in which one of us made a micro- scopical examination of the spinal cord, and showed for the first time (1863) that there was a positive lesion, the paralysis had existed forty-seven years ; there was very pronounced atrophy of the antero-lateral columns, which contained a considerable numbet- of amyloid corpuscles. Prevost and Vulpian described the lesion of the anterior cornua, and the disappearance of the 624 LESIONS OF THE SPINAL CORD. motor cells, in 1865. Lockhart Clarke and Laborde published similar observations at the same time. In 1870 Charcot and Joffroy published a histological analysis of the spinal cord of a woman who had been the subject of infantile paralysis for thirty- eight years. In this case the anterior cornua were profoundly altered throughout almost the whole length of the cord ; the motor cells were atrophied, and groups of them had entirely disap- peared. The substance of the antferior cornua was sclerosed in places, but the connective 'tissue was not equally altered every- where ; finally, the anterior columns were atrophied and partially sclerosed, as well as the roots &f the anterior nerves. These observations showed the distant anatomical consequences of infantile paralysis, but not the myelitis of its commencement. Eoger and Damaschino, Dujardin-Beaumetz, Eoth and Leyden, have published cases in which the lesions were recent, and the foci of myelitis were characterised by the presence of granular bodies, and by sclerosis of the anterior cornua, accompanied with atrophy of the motor cells, and atrophic degeneration of the lateral columns and the anterior roots. Thus at the present time the pathological anatomy of infantile paralysis is perfectly well defined in its most important points. Acute spinal paralysis of the adult corresponds entirely by its lesions, as well as by its symptoms, with infantile paralysis, but cases followed by autopsy and complete examination of the spinal cord are still very rare. We know of no observation thoroughly made but that of Gombault's, in which atrophy of the nerve cells of the anterior cornua was present. In an autopsy Leyden found a cystic focus in the lumbar enlargement of the cord, in the right anterior cornua, due to hsemorrhagic softening, and near it the motor cells were atrophied. B. Chronic Myelitis. Under the name of chronic myelitis are included a series of pathological states of various origin, which are far from presenting similar anatomical characters; thus, the lesions of softening of the spinal cord, described above, the various sequelae of acute myelitis, such as atrophy of the nerve tubes and cells, the formation of new connective tissue in the grey and white centres of the cord, the cysts and foci which follow softening or circumscribed hsembrrhagic myelitis, the inflammation and soften- SCLEROSIS OF THE SPINAL CORD. 625 ing, caused by lesions of the meninges and vertebra in Pott's disease, vertebral cancer, and the cortical leuco-myelitis which result, and the subacute or chronic cortical myelitis, which so often accompanies general paralysis of the insane, form so many distinct chapters in a complete description of chronic myelitis. But the histological lesions met with in these pathological conditions so different in their causes, are actually the same, and may be all included in the general description which we have already given of softening and acute myelitis, or in that of sclerosis, which still remains for us to furnish. Chronic spinal myelitis is in fact gener- ally interstitial myelitis or sclerosis. Interstitial myelitis or sclerosis of the spinal cord. — When a part of the spinal cord is affected with sclerosis, a lesion which generally occupies systematically either certain fasciculi or irregularly distributed patches, the diseased parts may be recog- nised with the naked eye by their grey or greyish-yellow tint, and by their semi-transparency. This semi-transparency, which is quite characteristic when present in the white fasciculi, is due to the fact that the nerve tubes have lost their myelin without the nervous tissue being infiltrated with opaque elements. The nerve tubes are reduced to their axis cylinders, and the tissue of the neuroglia thickening around them, the fibrils of the connective tissue resemble the nerve tubes, and are undulated so as to appear thicker. This kind of condensation of the fasciculi of the fibres of the neuroglia, which coincides with a diminution in the diameter of the nerve tubes, almost always causes, particularly if the lesion is old, an actual thickening of the connective-tissue fasciculi which radiate from the centre of the cord to its periphery in company with the blood-vessels, thus the fasciculi of the cord are separated by thicker septa than what normally divide the nerve tubes from one another. The cells of the neuroglia are easily isolated ; they contain one large nucleus. In the cornua of the spinal cord sclerosis manifests itself, at first by a greater abund- ance of small cells, and afterwards by a new formation of fibrils of connective tissue, at the same time that the nerve cells, at first tumefied and granular, as in all myelites, gradually atrophy and finally disappear. In the ultimate stages of sclerosis, the septa which separate the nerve tubes— reduced to their axis cylinders— and the fasciculi of tubes, are gradually thickened, and are always formed of fibrils. The cells of the neuroglia are smaller than at the commencement 626 LESIONS OF THE SPINAL dORD. of the process, and they do not always seem to be increased in number. Throughout this tissue amyloid corpuscles are found, more particularly alongside the fibrous septa. At the same time the capillary vessels and the small arteries and veins contain granular bodies in their perivascular sheaths, or in their external . coats ; later, their walls undergo thickening. This interstitial myelitis may be compared to chronic inflam- mations of the same nature, observed in the liver, kidneys, and lungs ; but it differs from it in many respects, quite as much as the connective tissue and extremely delicate fibres of the neuroglia differ firom bundles of fasciculated connective tissue. In sclerosis of the spinal cord, thickening and new formation of con- nective-tissue fascieuU, comparable by their extent, thickness, and importance to those found in cirrhosis of the liver, or in inter- . stitial pneumonia, must not therefore be looked for. With the exception of sclerosis in plaques, all chronic sclerotic myelites belong to the group of systematic myelites. We shall therefore describe in order chronic anterior poliomyelitis, which corresponds to progressive muscular paralysis ; bulbar progressive paralysis, or labio-glosso-pharyngeal paralysis; sclerosis of the posterior cords, or progressive locomotor ataxy ; amyotrophic lateral sclerosis, or spasmodic paraplegia, and sclerosis in plaques. a. Chronic anterior poliomyelitis. — Paralysis, or progressive muscular atrophy, has been long regarded as the result of primary atrophic fatty degeneration of the muscles. Cruveilhier, however, observed in an autopsy of this disease a very remarkable atrophy of the anterior roots (1853).' Vulpian,^ Trousseau, and Jaccoud also ascertained that the anterior roots were thin and grey in this disease. Later, Schneevogt^ and Jaccoud* discovered that the cervical trunk and part of the abdominal cord of the sympathetic were altered in this disease. Many other observers noticed ill-defined lesions in the spinal cord; Luy' discovered atrophy of the cells of the anterior comua ; Lockhart Clarke, 1868, observed atrophy of the multipolar cells of the spinal cord ; but the pathological anatomy of the disease was only • Bulletin de VAcad. de med., t. xviii. no. 12, p. 546. ^ Soc. med. des Mpitavx, Mars 1863, and L' Union medioale, 1863, no. 49, t. xviii. p. 159. » Neederl. Lancet, 1854, Sept. and Oct, * Soc. mSd. des hop., 1865, and Gaiette des liop., 1865, p. 20, » Gazette med., 1860, p. 30. PROGRESSIVE BULBAR PARALYSIS. 627 established when Charcot and Joffroy ' published their memoir which was based on cases studied in the Salpetriere, as well as in Charcot's and Vulpian's wards. Considering these cases in connection with those already pub- lished, it was found that the constant and essential lesion of pro- gressive muscular paralysis is atrophy of the cells of the anterior cornua of the spinal cord, followed by their complete disappear- ance. The grey substance of these cornua is also diminished in size and sclerosed, and the anterior roots are atrophied and degen- erated. The regions of the cord affected are more or less extensi\ e, the nuclei of Stilling and the medulla oblongata may be affected as well as the motor centres of the spinal cord. Another spinal lesion, which is often coincident with progressive muscular atrophy, is the formation of a central cavity in the cord, or hydromyelia (cases reported by Clarke, Schiippel, and Grimm, quoted by Leyden). 6. Progressive bulbar paralysis. — The lesions of progressive bulbar paralysis, or labio-glosso-pharyngeal paralysis, are the same as those of progressive muscular paralysis, and do not differ except by the muscles affected, and by the seat of the morbid changes in the nerves and centres. In this disease it is particularly the muscles of the tongue which are atrophied, and in a state of fatty degeneration. The trunks of the facial, hypoglossal, pneumo- gastric, and spinal nerves are more or less affected by granular degeneration, implicating particularly the nerve tubes, and they iinally show the lesions of sclerosis with atrophy. The anterior cornua of the cord, and the grey centres of the medulla oblongata, are modified in the same way as in progressive muscular atrophy. The atrophy of the nerve cells is most marked in the deep origins of the hypoglossal, spinal, and facial nerves ; complete disap- pearance of the cells is the final result. The atrophy may also affect the nuclei of origin of the glosso-pharyngeal and the pneumogastric, which are mixed nerves. The intrabulbar nervous fasciculi, particularly the transverse fasciculi of the medulla oblongata, are more or less atrophied at the same time. Sclerosis of the posterior cords. Locomotor ataxy. — Sclerosis, or grey atrophic degeneration of the posterior cords, corresponding to progressive locomotor ataxy, offers us one of the most remark- able examples of the progress made in nervous pathology during 1 Ari-h. (Je phys. norm, rt pnth., 1860, p. 356. s s 2 628 LESIONS OF THE SPINAL CORD. the last thirty years. The symptoms of this disease, separated from those of paraplegia and sclerosis by Duchenne of Boulogne, its pathological anatomy elucidated by Cruveilhier, described by Bourdon and Luys, Charcot and Vulpian, Axenfeld, Jaccoud, Leyden, Pierret, etc., have now established a perfectly well-known type, recognisable still in its unusual localisations and in its abnormal forms. On examining a spinal cord affected with this disease, the pia mater is almost always found to be thickened and adherent to the posterior columns, which appear transparent through this membrane; and on making a transverse section, the posterior columns are seen to be of a peculiar transparency and of a grey colour. Two phases may be distinguished in the course of this disease : at the commencement there is an increase in the number of the elements of the neuroglia, and the diseased parts appear slightly tumefied ; in the second stage there is, on the contrary, atrophy of the cellular elements of the neuroglia, thickening of its fibrous tissue, and atrophy of the nerve tubes. On examining under the microscope a small fragment of the semi-transparent grey substance of the diseased part in the first period, and in the fresh state after soaking in water, a rather considerable number of embryonic cells are at first seen imbedded in a granular amor- phous substance ; the nerve tubes are preserved as well as the nerve cells of the anterior and posterior comua ; the perivascular sheaths of the blood-vessels of the morbid part are dilated and filled with granular lymph cells. To obtain a complete idea of the lesion, the spinal cord should be hardened in weak chromic acid or in Miiller's fluid, and it is essential that it should not be dragged or pressed between the fingers. The hardening effected, transverse or longitudinal sec- tions are cut, stained with carmine, treated with absolute alcohol, then cleared with essence of turpentine or oil of cloves, and pre- served in Canada balsam or Damar resin. In such preparations the diseased parts are seen to be more highly coloured than the healthy fasciculi, for they contain more elements which fix the carmine ; thus, even with the naked eye, the extent of the lesion can be recognised in transverse sections which have been hardened in chromic acid and stained with carmine. On microscopically comparing delicate sections of healthy fasciculi with those of the diseased posterior columns, it wiU be seen that in the first the divided nerve tubes are regularly separated from one another by delicate septa of the neuroglia, and by blood-vessels {vide B, fig. THE LESIONS OF LOCOMOTOR ATAXY. 629 280), and here and there a few small cellular elements are found in the neuroglia ; in the posterior columns the nerve tubes are, on the contrary, of various diameters, some are very small, though still retaining their axis cylinders and an envelope of myelin, others are of normal size or even larger than in the healthy con- dition, their axis cylinders being often considerably hypertrophied. Between the nerve tubes tracts or masses of small cells of the neuroglia are seen, the nuclei of which are only Adsible when the Fig 280.— Section of the Spinal Cord in Locomotor Ataxy— Gkey Atrophic Degeneration ok Sclerosis of the Posterior CioLUMNS. Tho flg. represents a complete section of the spinal pord i t^ P^J* oomprteed between the posterior comua is seen to be ^^^f'^^ fintiettra under this low power (10 diameters) to be more nneiy ^SrTC the lateral columns. The P.0*?,™^^^'-"? tans fnlted so that the posterior median fl^^^^^^'nlvtS 'sec'tS^ of ^ZT^^.'tt^^'^''^^^^ -ne^ir^rr^Sran-i flbrillated. method Of preparation given above is employed Longitudinal sections of the spinal cord show similar histological details m every ^^^irr:' advanced sUge of the disease the posterior columns •. A f^„ofV,^r hv the formation of new connective tissue. 630 LESIONS OF THE SPINAL CORD. unites the two columns of Groll, which before were simply placed side by side. In consequence of these changes, the posterior columns become considerably atrophied. Transverse sections under a high power show that the nerve tubes are separated by very fiine connective-tissue- fibrils, intersecting in every direction. (a, figi 280). In the midst of these fibrils a few nuclei are seen. The nerve tubes are thin, but their axis cylinders are always pre- served. Some observers have asserted that the nerve tubes have disappeared by the time sclerosis has reached this stage ; but as a matter of fact they may be always found, when sections are well made and stained with carmine ; when the lesion is far advanced, the tubes may be reduced to their axis cylinders, the medullary sheath having completely disappeared. The walls of the capillaries and small blood-vessels are thickened and rigid, and their calibre diminished ; a large number of amyloid corpuscles are at the same time found in their course as well as in the tissue of the neuroglia, Fig. 281. A, sclerosis of the whole of the posterior columns— the oolnmns of Soil and the radicular zones are simultaneously altered, (common locomotor ataxy) ; b, sclerosis of the two pos- terior radicular zones, the columns of Goll being respected (locomotor ataxy at its oom- meucement) ; c, sclerosis limited to the columns of Goll : ascending degeneration. (After Charcot.) especially beneath the pia mater. The posterior roots of the spinal nerves become transparent, and so small that, instead of being, as in the nornial condition, double the size of the anterior roots, they may be only half their diameter, or even less. In locomotor ataxy the lesion is not always limited to the posterior columns; it encroaches sometimes a little on the cortical substance of the contiguous lateral columns, in which case new symptoms of paralysis occur related to these lesions. The lesion of the posterior columns is generally more advanced and older in the lumbar region than in the dorsal or cervical regions, where the lesions are almost always less marked. The tubercula qua- dragemina, the optic tracts, the optic nerves themselves, may be atrophied, greyish, and semi-transparent ; sometimes even the hypoglossal nerve and the auditory nerve show the same atrophy. AMYOTROPHIC LATERAL SCLEROSIS. 631 The characteristic symptoms of ataxy are due, not as was formerly thought to a lesion of the whole of the posterior columns, but only to sclerosis of the radicular or cuneiform columns. In several observations, the first of which was published by Pierret, only the fasciculi of these columns were altered which are adherent to the posterior comua ; the lesions of the columns of GroU being simply consecutive, and caused by ascending degeneration. In the majority of autopsies of locomotor ataxy hitherto published, the radicular fasciculi and the columns of GroU are affected in the . same degree. The cells of the spinal ganglia and of the grey centres of the cord are perfectly normal in most cases. Amyotrophic lateral sclerosis. — In 1866 ' Charcot published the first clinical case referred to symmetrical sclerosis of the lateral cords ; since then a definite symptomatic type, called spasmodic paralysis, has been defined, based on a series of new cases collected by Gombault,^ Joffroy, Debove, etc. The histology of sclerosis, or grey degeneration of the lateral columns, is exactly similar to that of locomotor ataxy, hence there is no occasion to redescribe it. Its seat corresponds exactly to the course of the pyramidal fas- ciculi, and is the same as that of descending degeneration {vide p. 612). The lesion commences in the medulla oblongata on each side of the olivary bodies, and after decussation of the pyramids, it is seen on each side of the spinal cord as two spots at the most posterior part of the lateral fasciculi, and at the inner side of the anterior columns. It becomes more and more attenuated as the lower parts of the cord are reached. When very marked it is easily recognised on the surface of the spinal cord, through the pia mater, even with the naked eye. When the spinal cord has been hardened and sections cut and stained with carmine, the diseased spots are easily recognised by the red stain they take. Charcot distinguishes two stages in this disease : in the first the white columns are alone affected; in the second the multipolar cells of the anterior comua are atrophied and deeply pigmented, the lateral nerve cells and the columns of Clarke remaining in- tact. The cells of the grey nuclei of the medulla oblongata are often altered and atrophied. The roots of the anterior spmal nerves, and the nerves themselves, axe degenerated when the motor cells are affected, and the muscles to which they are dis- tributed are atrophied. These lesions, which closely connect ' BnlUtin do la &wh't,- v,cd. de> Iwjntaii.v, 1866, PP- 24-31. ' (iumbauH, Etudt sur la, scUro.o am'^ottoiM.iM (thfee de Pans, Ife, 7) 632 LESIONS OF THE SPINAL CORD. amyotrophic lateral sclerosis with progressive muscular atrophy, induce many pathologists, Leyden among others, to deny to amyo- trophic lateral sclerosis a distinct pathological entity. Sclerosis in disseminated plaques.— This disease differs from all the preceding by its irregularity, and by the fact that it is not systematically localised in any spinal fasciculus. Cruveilhier de- scribed this sclerosis in his atlas, but it remained simply a curiosity till Leyden (1863),' Eindfleisch, Vulpian, and Charcot, by careful autopsies compared with clinical observations, were enabled to give a complete account of the disease.'^ On the surface of the spinal cord and the medulla oblongata, semi-transparent grey patches are seen, varying both in extent and number ; they may be from 2 to 70 cm. in length, and are asymmetrical, irregular, and occupy indiscriminately the various white columns and grey centres of the spinal cord. They are sometimes unilateral, or more marked on one side than on the other ; but their extent and limits are often difficult to appreciate with the naked eye. Thus, in order to determine exactly the parts affected, and to what degree, the spinal cord must be hardened and examined in sections, stained with carmine and mounted in Canada balsam. Such preparations, examined under the micro- scope, show that the sclerosed tissue presents all the characters already indicated as typical of sclerosis in general, and of sclerosis of the posterior columns in particular ; the same thickening and condensation of the neuroglia is seen, the stellate cells of Deiters are sometimes very numerous, and the nerve tubes have more or less lost their medullary sheaths. The nerve cells included in a plaque resist for a certain time, but they ultimately become infiltrated with numerous yellow granules, a state corresponding to their exaggerated pigmentation ; they then retract, take on a shiny appearance, and finally atrophy, and may even completely disappear. The lesions of the spinal roots and nerves axe related to those of the nervous centres. With regard to their location, sclerosis iu plaques is sometimes cerebro-spinal, sometimes purely spinal.. In tetanus Demme has described lesions similar to those of ' Beutsehe KMnih, 1856. ' Vide Ordenstein, La paralysie agittmte et la sclerose en plaques generalisees (these de Paris, 1867). — Bourneville, Scleroses en plaques generalisees {Mouvement med., 1868). PERI-EPENDYMAR SCLEROSIS. 633 sclerosis, and which at their commencement are disseminated throughout the whole cord. In tetanus Michaud has described hypertrophy of the elements of the neuroglia of the grey com- missure and round the central canal. We ourselves have ex- amined a certain number of the spinal cords of subjects who have died from traumatic tetanus, but we have never been able to discover a single morbid change. Central or peri-ependymar sclerosis. Cystic formations in the centre of the spinal cord. — A small number of cases have been reported in which the connective tissue surrounding the central canal of the spinal cord was thickened, transformed into an elon- gated fibrous plaque, or into a positive tumour situated along- side the central canal : this was particularly the fact in a case quoted by Lancereaux. At the same time that this thickening of the peri-ependymar tissue takes place, the central canal of the spinal canal is almost always found to be more or less dilated, and filled with fluid for a variable extent. The fibrous plaque is generally continuous with the extremity of one of these dilatations, or it is seated in the wall of the abnormally dilated cavity. These dilatations have been variously explained. Hallopeau' looks upon them, and the new formation of the peri-ependymar connective tissue, as the simple result of myelitis. Th. Simon" and Westphal found the longitudinal cystic cavity to be in similar cases quite distinct from the central canal, and situated behind it in the posterior columns. In the case recently published by Schiippel, and reported by Leyden,^ this cavity extended so far into the posterior columns as to almost completely destroy them. According to these authors, this condition was not due to central myelitis, but to tumours, belonging to the class of glioma or gliosarcoma, de- veloped around the canal of the ependyma, and containing in their interior cysts which were continuous or not with the central canal. The presence of these tumours in the midst of the spinal cord might become the starting-point of inflammatory lesions of this organ. In some cases, in which the cystic cavity has been observed alongside the central canal, the former might have been developed at the expense of the latter, for Vulpian has in the same spinal cord observed two cavities placed side by side, one was ' Arch. gin. de mcd., 1871 and 1872, and Xouveau Die. t. xvii. p. 461. « Beitrdge zur Path.und Path. Amt. del centraleii iXervensi/stems Ureh. /. pii/eh. vnd Mnrii-A'rankheiteit, BA.v.i. p. W8). • TraU6 cUnique des maladies nerveum, French trans., 1873, p. bad. 634 LESIONS OF THE SPINAL CORD. dilated and transformed into a cyst, while the other remained normal. Tumours of tlie spinal cord.— Tumours of the spinal cord are rare, and are generally located in the meninges ; they do not differ from tumours of the brain and the cerebral meninges. Lancereaux has observed a fibrous tumour developed in the central canal of the cord, and occupying a part of its length ; we have also seen a small fibroma developed in the pia mater of the spinal cord. Neurogliac and angiolithic sarcoma may be found in the spinal meninges. We have abeady described tubercle of the meninges {vide pp. 580 and 606). A very small number of indisputable cases of syphilitic gummata of the spinal cord have been reported : they resemble those of the brain {vide p. 600). BIBLIOGRAPHICAL REFERENCES TO TREATISES ON LESIONS OF THE TISSUES. On page 85 will be found the titles of the'principal treatises on general patho- logical anatomy. The following is a list of the principal works on each division of the subject as classified in this manual. Lesions op the Bones. — Tboja, JDe novorum ossiv/m, in integris ant maximU, oi ntorios, deperditionii'M regeneratione em^jerimenta. Paris, 1775, in-12. DuHAMEL, Observations sv/r la reunion des fraatures des os {Mem. de VAcad. des se., 1742-1743). Tenon, Memoire sv/r I'eafoliation des os(Mem. de VAcad. des sc, 1758). Ceuvbilhiee, Bssai sur Vanatomie pathologique, t. ii. p. 426, Paris, 1816. Gbbdy, RecTierohes sxm la carie (^Gazette hebdomadai/re, 1864, t. i. No. 27); Me- moire sw Vetat materiel ou anatomique des os malades {Archives de mcdeeine, f^vrier 1836, 2° serie, t. x. p. 129) ; De la periostite et de la medullite {Arclimes generales de medecine, aoiit 1853, 5' serie, t. li. p. 130). Ollibb, Traite experi- mental et elinique de la regeneration des os, 2 vols. Paris, in-8, fig., 1867. V. Masson. Eanvibe, Considerations sv/r le developpement du tissu osseum {These de doctorat, Paris, 1865) ; Description et definition de I'ostSite, de la carie et des tubercules des os {Archives de pht/siologie, t. i. janyier 1868). Chassaignac, Des abces aigus sousperiostiques {Mem. de la Soa. de chi/rv/rg., vol. iv. p. 286) ; Memoire sur I'osteo my elite {Gaz. mid., 1854, No. 33). Vbrnbuil, Note sv/r les cellules du tissu medullaire des os et sur lev/r etat dans Vosteomyelite {Gaa. med. de Pans, 1852, No. 26). 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PhilippeAUX et Vulpian, Sivr la riginiration des nerfs {Mim. de la Soc. de biol., 1859, p. 343). Aeloing et Teipieb, JtecJwrches expirimentales sur la pathoginie du titanos {Arch, de Physiol., 1870, p. 235) ; Physiol, des nerfs vogues (mfime recueil, juillet 1872). Ranviee, Mecherches sur I'histol. et la physiol. des nerfs {Archives de physiol., mars et juillet, 1872). Schifp, Comptes rendus de I'Acad. des sc, 1854. Wallee, No^melle mithode anatomique pov/r I'investigation du systeme nen-cux. Bonn, 1852. Lent, Zeitschrift fiir reias. Zoologie, t. vii. 1855, p. 145. Eemak, Archiv fiir path. Anat., t. xxiii. p. 441, 1862. Coenil, Lixlons des nerfs dans les himipUgies anciennes {Soc. de biol., 1863) ; Tumeurs ipithiUales des nerfs {Journ. de Vanat., 1864, p. 183) ; Du tvhercU dam ses rapports axec Ift vaisseaux {Arch, de physiol, 1868, p. 99). Liouville, Miningite ciribro-spinale tuberevleuj esBpirimentaUs tur la regeneration anatomique et fonctionnelle de la nwelle ^pinUre. Bruxelles, 1870. Schibppebdeckee, I'cber Itegeneration Degeneration mid AroUtectur des Riichenma/rJies {Virchorv'g Archir t Ixvli ' 1876, p. 542). E. Leyden, Traiti cliniqne des maladies de la moelle fjnnVere. Charcot, Le<;ons sur les maladies du systhne nerrenx, faites ^ la SalpetriJre, recneillies et publi^es par Boumeville. Paris, 2 vols, in-8, 2" Edition, 1875-1880 ■ Leiions mr les localisations dans les maladies du ccneau, faites k la Faculty de mMecine de Paris, recneillies et publifies par Bourneville, 1876-1880, 1 vol. in-8 • Leqons cUniques sw let maladies des vieilla/rds et les maladies chroniques, recueillies et pubMes par B. Ball, 4« 6dit., 1 vol. in-8. Paris, A. Delahaj-e ; Le Fatty emboli, 516 Tibrm, 47 Fibrinous exudation, 102 644 INDEX. FIB INT Fibrinous inflammation, 424 Fibroma, definition of, 161 — description of, 162 — diagnosis of, 167 — prognosis of, 167 — seat of, 166 — species of, 163 — fasciculated, 167 — lamellar, 163 — mucoid, 164 — mulluscoid, 164 — of the brain, 598 — of the muscles, 454 — of the meninges, 585 Fibrous carcinoma, 180 Fibrous connective tissue, 14 Filaria sanguinis hominis, 468 Formative ostitis, 334 Fracture, compound, 348 — simple, 349 — of rachitic bone, 373 eANGEBNB, 117 — dry, 61 — moist, 60 Glanders, 211 Glioma, 144 Glycogen in cells, 6 Gouty arthritis, 401 Granular change in muscular fasciculi, 441 Granulation tissue. 111 Gummata syphilitic, 187 description of, 191 development of, 193 diagnosis of, 199 prognosis of, 199 — — seat of, 199 structure of, 195 of the bones, 362 of the brain, 600 of the lymphatic glands, 558 of the meninges, 586 of the muscles, 447 HEMOGLOBIN, 43 • — estimation of, 458 Hsmatin, 44 Heematoidin, 45 Haemorrhage of the bones, 327 . brain, 588 connective tissue, 408 muscles, 447 myocardium, 475 -^ serous membranes, 422 spinal cord, 611 spinal meninges, 604 Hsemorrhagic exudation, 103 -^ foci in the brain, 590 Hsemorrhagie inflammation, 426 Heart, lesions of the, 469 Heteroplasia. 82 Hodgkin's disease, 245 Horns, 279 Horny papilloma, 279 Hydatid cysts, 318 Hydatid mole of the placenta, 157 Hydarthrosis, 387 Hygroma, 296 Hypersemia, 100 Hyperplasia, 82 Hypertrophic cervical pachymeningitis, 605 Hypertrophy of the muscles, 440 — • of the myocardium, 473 TNFAEGTUS, 514 X. Infection, 119 Infiltration, amyloid, 69 — calcareous, 78 — mucoid and colloid, 65 — serous and albuminous, 64 — uratio, 80 Inflammation, analysis of, 100 — artificially induced in bone, 92 cartilage, 88 connective tissue, 94 epithelial tissue, 89 non-vascular tissues, 88 vascular tissues, 92 — definition of, 86 — degeneration consequent on, 117 — diapedesis in, 97 — new formatiori of vessels in, 109 — caseous, 120 — congestive, 119 — exudative, 119 — interstitial, 120 — purulent, 415 Inflammation of carcinoma, 185 — of the arteries, 491 articulations, 381 brain, 595 capillaries, 521 connective tissue, 413 lymphatic glands, 547 vessels, 538 meninges, 578 muscles, 450 myocardium, 477 nerves, 561 pericardium, 470 serous membranes, 423 spinal cord, 620 Inflammatory congestion, 100 — exudations, 101 — nevir formations, 105 Inoma, 161 Internal capsule, lesions of the, 57 INDEX. 645 LESIONS of the arteries, 490 articulations, 379 bones, 325 brain, 669 capillaries, 520 cartilaginous tissues, 876 connective tissues, 408 heart, 469 lymphatic glands, 542 vessels, 537 in tumours, 539 muscles, 436 nerves, 560 serous membranes, 422 spinal cord, 601 veins, 626 Leucocythsemia, 465 Ligature of arteries, 508 Lipoma, definition of, 168 — description of, 168 — development of, 171 — diagnosis of, 172 — prognosis of, 172 — seat of, 169 — varieties of, 170 — of the bones, 356 — of the brain, 599 — arborescent, 406 Lipomatous carcinoma, 182 — sarcoma, 148 Lobulated pavement epithelioma, 258 Localisation of function, 572 Locomotor ataxy, 627 Lymph, 41 — cells, 7 Lymphadenia, cutaneous, 252 Lymphadenoma, 245 — description of, 247 — development of, 254 — diagnosis of, 255 — prognosis of, 255 — seat of, 248 — of bone, 364 Lymphangiectasis, 539 Lymphangioma, 243 Lymphatic glands, amyloid degenera- tion of, 553 colloid degeneration of, 553 lesions of, 542 pigmentation of, 546 structure of, 643 syphilitic lesions of, 568 tubercle of, 555 — — tumours of, 554 Lymphatic vessels, normal histology of, 537 pathological histology of, 538 MYX M EDULLARY carcinoma, 181 Mcdullated neuroma, 235 Melansemia, lesions of the cerebrum in, 587 Melanotic carcinoma, 183 — masses, 315 — sarcoma, 148 Meninges, lesions of the, 678 — tumours of the, 585 Meningitis, cerebral, 579 — cerebro-spinal, 579 — chronic, 583 — spinal, 605 — tubercular, 580 Meningo-encephalitis, 596 Miliary aneurisms, 507 of the brain, 623 Milium palpebrae, 293 Milky patches of the pericardium, 472 Mucoid carcinoma, 182 — infiltration, 65 Mucous papilloma, 279 — tissue, 10 Muscles, embolic infarctus of, HH — fatty degeneration of, 412 — granular change in, 441 — haemorrhage into, 447 — inflammation of, 450 — multiplication of nuclei of, 437 — parasites of, 456 — pigmentation in, 443 — rupture of, 453 — suppuration of, 452 — tumours of, 454 — vitreous degeneration of, 411 Muscular fasciculi, cardiac, 27 smooth, 26 striped, 28 atrophy of, 438 granular change in, 441 hypertrophy of, 440 new formation of, 440 — tissue, normal histology of, 26 pathological histology of, 436 Myeloid sarcoma, 140 Myelitis, acute, 621 — chronic, 624 Myocarditis, 477 Myocardium, atrophy of the, 472 — fatty degeneration of the, 473 — haemorrhage of the, 475 — hypertrophy of the, 473 — inflammation of the, 477 — pigmentary degeneration of the, 474 — tumours of the 478 Myoma of smooth fibres, 232 development of, 233 diagnosis of, 235 prognosis of, 235 seat of, 234 — of striated fibres, 231 Myositis, 450 Myxoma, definition of, 154 — description of, 154 646 INDEX. MYX Myxoma, diagnosis of, 160 — prognosis of, 161 — seat of, 158 — varieties of, 155 — hydatidiform, 157 — lipomatous, 155 — of the bones, 356 — of the muscles, 454 — of the nerves, 159 Myxo sarcoma, 147 PIG N^VI, 279 Necrobiosis of cells, 59 Necrosis, 338 Necrosis of elements, 58 Nerve cells, 29 Nerve fibres, medullated, 31 non-medullated, 34 Nerves, congestion of, 561 ■ — degeneration of divided, 564 — hsemorrhage of, 561 — normal histology of, 560 — regeneration of divided, 566 — section of, 563 — tumours of, 568 Nervous tissue (normal), 29 Neurogliac sarcoma, 144 Neuroma, fasciculated, 236 diagnosis of, 238 — prognosis of, 238 seat of, 237 — medullated, 235 — of the brain, 600 Normal tissues, 10 Nucleus of the cell, 4 Numeration of the blood corpuscles, 48 Nutrition, excess of cell, 81 — insufficiency of cell, 62 OBLITERATION oi arteries from endarteritis, 512 from ligature, 508 from VFOunds, 511 — of veins from thrombosis, 529 — of vessels in gummata, 198 in tubercle, 203 Obstruction of arteries from embolism, 513 Odontoma, 230 (Edema, 410 — of the cerebrum, 587 Organisation of the blood clot, 510 Osseous grovfths, 227 Osseous tissue (normal), 19 Ossification, intra-oartilaginous, 22 — intra-membranous, 25 — sub-periosteal, 24 — of cartilage, 368 — of the callus, 377 — of the central medulla, 336 Ossiform tissue, 23 Ossifying sarcoma, 141 Osteoblasts, 24 Osteoid tissue, 222 — tumours, 222 Osteoma of bone, 225 — of muscle, 456 Osteomalacia, 365 Osteophytes, 335 — in rheumatic arthritis, 393 — syphilitic, 375 Osteoporosis, adipose, 367 — senile, 367 Ostitis (artificially induced), 92 — (pathological), 327 — formative, 334 — rarefying, 333 — simple, 332 — syphilitic, 363 PACHYMENINGITIS (cerebral), 584 syphilitic, 585 (spinal), chronic bulbar, 606 hypertrophic-cervical, 605 Papillary sarcoma, 150 Papilloma, horny, 279 — mucous, 279 development of, 281 diagnosis of, 283 prognosis of, 283 seat of, 282 of the brain, 599 Paralysis, acute ascending, 622 — acute spinal, of the adult, 624 — bulbar, 627 — infantile, lesions in, 623 Parasites of the blood, 467 muscles, 456 Pearly pavement epithelioma, 267 Peri-arteritis, acute, 494 — chronic, 501 Pericarditis, hsemorrhagic, 470 — purulent, 471 — tubercular, 471 Pericardium, adhesions of the, 471 — dropsy of the, 469 — haemorrhage of the, 469 Periosteum, 21 Periostitis, 336 Phlebitis, 527 Phleboliths, 533 Phlegmon, acute, 415 — chronic, 418 — circumscribed, 417 — diffuse, 418 Pigmentary degeneration of muscles, 443 ■ of the myocardium, 474 Pigmentation of elements and tissues, 75 — lymphatic glands, 546 lA'DEX. 647 POL Polio-myelitis, chronic anterior, 626 I'olypus, mucous misal, \'>1 Pott's disease, 606 Progressive bulbar paralysis, 627 Proliferous cysts, 299 Purulent arthritis, 386 — iniiammation, 119 Pus, theory of the formation of, 107 Pus cells, 106 degeneration of, 108 RACHITIS, 367 Barefying ostitis, 333 Bed blood corpuscles, 43 Kegeneration of divided nerves, 566 Betiform tissue, 16 Bheumatic arthritis, chronic, 390 Bheumatism, nodosum, 391 Rupture of muscles, 453 SARCOMA, definition of, 126 — description of, 128 — development of, 150 — extension of, 151 — generalisation of, 152 — prognosis of, 152 — species and varieties of, 132 — angiolithic, 145 — encephaloid, 135 — fasciculated, 136 — lipomatous, 148 — melanotic, 148 — 'mucoid, 147 — myeloid, 140 — neurogliao, 144 — ossifying, 141 — papillary, 150 — of the bones, 354 — of the brain, 598 — of the meninges, 58fi — of the muscles, 454 Sarcous elements, 28 Sclerosis, cerebral, 598 — spinal, 625 — amyotrophic lateral, 631 — in disseminated plaques, 032 — of the posterior columns, 027 — peri-ependymar, 633 Scirrhous carcinoma, 180 Scrofulous arthritis, 396 Sebaceous cysts, 293 Section of nerves, 663 Septicaemia, 119 Sequelie of aneurisms, 606 — of arterial obstruction, 514 cerebral haemorrhage, 591 Sequestra of caries, 346 Sequestrum, 338 — action of pus on the, 340 ~- separation of the, 339 TUB Serous cysts, 296 of the connective tissue, 421 of the meninges, 586 — exudation, 101 — infiltration, 64 — membranes, hsemorrhage of the, 4 22 inflammation of the, 423 tubercle of the, 432 tumours of the, 431 Simple angioma, 239 — ostitis, 332 Softening of the brain from embolism, 593 Softening of the brain from tlirombosis, 595 Spinal cord, congestion of the, 6 1 1 hsemorrhage of the, 611 normal histology of the, 601 pathological histology of the, 608 probable course of the fibres of the, 603 secondary degeneration of the, 61 :) aJter apoplexy, 613 after myelitis, 617 from compression, 618 softening of tlio, 612 structure of the, 602 tumours of the, 634 Spindle-celled sarcoma, 136 Spongeoid lissiif, 370 Strumous glands, 551 Sub-ungueal exostosis, 142 Suppuration, 106 — of the connective tissue, 414 — of the muscles, 452 Synovial membranes in acute arthritis, 380 in rheumatic artliritis, 395 tubercle of the, 406 Syphilitic gummata, 187 — lesions of the bones, 362 lymphatic glands, 558 — osteophytes, 375 — pachymeningitis, 584 Syphilis, 188 TAENIA echinococcus, :!L'l — solium, 318 Tetanus, 632 Thrombosis, arterial, 512 — venous, 529 Trichina spiralis, 456 Tubercle, 199 — description of, 201 — development of, 205 — diagnosis of, 210 — prognosis of, 211 — secondary Iesicin>< of, 208 structure of, 207 — varieties of, 207 _ of the arteries, 519 648 INDEX. TUB Tubercle of the bones, 357 — of the brain, 599 — of the lymplaatlc glands, 555 — of the meninges, 586 — of the muscles, 454 — of the serous membranes, 432 — of the synovial membranes, 406 Tubercular arthritis, 406 Tubular adenoma, 286 Tubular epithelioma, 268 Tumours, analytical table of, 306 — classification of, 123 — definition of, 121 — adipose, 309 — cartilaginiform, 307 — caseous, 313 — cystic, 314 — erectile, 314 — fibroid, 311 — gelatiniform, 310 — melanotic, 312 — mixed, 302 — multilocular hydatid, 322 — osteoid, 222 — ossiform, 306 — sarcomatous, 309 — soft, with grumous contents, 308 — soft, with milky juice, 307 Tumours formed of blood-vessels, 239 cartilaginous tissues, 214 embryonic tissues, 126 epithelial tissues, 265 '- granulations, 312 lymphatic glands, 245 lymphatic vessels, 243 melanotic masses, 315 muscular tissue, 231 nervous tissue, 235 osseous tissue, 225 Tumours of the arteries, 517 articulations, 405 bones, 353 brain, 598 WOU Tumours of the connective tissue, 420 lymphatic glands, 554 meninges, 585 muscles, 454 myocardium, 478 nerves, 568 — — serous membranes, 431 spinal cord, 634 veins, 535 URATES, deposit of, in the articula- tions, 401 Uratic infiltration, 80 YALVULAR aneurisms, 485 Varix, 533 Vaso-formative cells, 110 Vegetations in chronic endocarditis, 483 Veins, normal histology of, 526 — inflammation of, 527 — ligature of, 527 — tumours of, 535 — woiluds of, 528 Venous thrombosis, 529 Vessels, new formation of, 109 Villous carcinoma, 185 Villous change in rheumatic arthritis, 390 Vitreous degeneration of muscles, 68, 444 WARTS, 279 Waxy degeneration of muscles, 68 Wens, 293 White blood corpuscles, 45 White swelling, 396 Wounds, cicatrisation of, 114 Wounds of veins, 528 END OF THE FIRST VOLUME. 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