-maumi] USSP^^' HX64064867 RD651 Ew52 S^labusot lectures RECAP 15 a: I Columbia (Hnitoem'tp College of ^tp^tetans; anb ^urgeonsi Hibrarp Digitized by tine Internet Arciiive in 2010 witii funding from Open Knowledge Commons http://www.archive.org/details/syllabusoflecturOOewin ^ SYLLABUS OF LECTURES QN TUMORS BY JAMES EWING, M.D., DEPARTMENT OF PATHOLOGY CORNELL UNIVERSITY MEDICAL COLLEGE. NEW YORK CITY, 1902; 1 ikfftMTii TUMORS. Definition. A tumor is an autonomous new growth of tissue. Scope of Term. Clinicall}^, any more or less permanent localized swell- ing is tentativel}' called a tumor. The pathological classi- fication separates among such swellings. ( 1 ) Inflammatory Hyperplasias. (2) Retention Cysts. (3) Triie tumors. Neoplasms. (1) Inflammatory Hyperplasia. Jt has already heen noted that a simple inflammatory process may produce a localized increase in the size of a part, simulating a tumor. Instances of this sort occur es- pecially in the skin and mucous membranes. (Nasal polyps, fungous endometritis and uterine polyps, chronic prostatitis, venereal warts, fungoid growth following ec- .cenia.) This increase in the size of the part is referable to moderate increase in the number and size of cells, to retention of secretion, and to inflammatory exudate. Such inflammatory hyperplasia may, however, pass by insensible gradations into a true tumor process, and this fact consti- tutes one of the strongest arguments against the parasite theory of the origin of tumors. (2) Retention Cysts. The retention of secretion in occluded glandular alveoli accounts for much of the bulk of many tumors, but not infrequently such retained secretion produces a marked swelling or tumor apart from any true neoplastic process. It is commonly seen in chronic inflammations of glandu- lar structures. {Galactocele, one form of goitre, ranula, simple and corpus luteum cysts of ovary, hydronephrosis, congenital cystic kidney f) (3) Neoplasms. This term applies to the autonomous new growths in which the process differs essentially from that of inflam- matory hyperplasia, in that the multiplication of cells is much greater and the new cells produced differ in type from the normal cells originating the tumor. The broadest conception of a tumor and one which per- haps best expresses the relation of a tumor to other pathological processes and to the originating tissue is that of a parasitic grozvth. In this sense a tumor grows for itself and at the expense of the harboring tissue and host. The parasitic relation is apparent in certain monsters where considerable portions of one individual are im- planted in another, while there appear to be all gradations between the extreme examples of parasitism, such as the Siamese twins, through the sacral teratomata, dermoids, embryonal tumors of the genito-urinary tract, even to the epithelioma of the lip which is believed by some to originate from misplaced epithelial cells which have taken on an independent and parasitic existence (Cohnheim, Ribbert). This conception of the parasitic nature of tu- mors is also one of the strongest arguments against the belief that neoplasms are caused by the invasion of the 3 cells by parasitic microorganisms. Thus it would seem that the tumor itself is the parasite. Characters of Tumor Cells. Anaplasia. Tumor cells are usually less differentiated than their cells of origin. They are usually larger, sometimes smaller, spindle cells may become spheroidal, but whatever the de- gree of change, tumor cells tend to revert to the less dif- ferentiated form of embryonal tissues. This reversion of the tumor cells to the embryonal type is one of the clearest distinctions between inflammatory and neoplastic processes, and is called anaplasia. (Hanse- mann.) The nuclei of tumor cells are usually larger than is normal and exhibit an abundance of chromatin, features which indicate greatly increased power of growth. On the other hand tumors of specialized epithelium possess diminished power to produce special secretions, i.e., special power of physiological function. It is believed that one of the essential characters of tumor cells is an excess of the tendency of growth gained at the expense of the capacity for function. (Adami.) This physiological fact should be included in the conception of anaplasia. Metaplasia. In some tumors the cells may exhibit distinct differ- ences from their original function. Thus, fibroblasts produce bone and cartilage, and col- umnar epithelium becomes flat and round. This change is called metaplasia. Metaplastic changes are not indiscriminate but follow inriuences based on the embrvological development of tis- sues. I'^ibroblasts may produce bone and cartilage because all of these are closely related mesoblastic tissues; but epithelial cells never assume the characters of fibroblasts in producing- bony or cartilaginous tissues. Cell- division. Tumor cells multiply by mitosis but instead of always dividing equally into two new cells three or more may be formed with varying quantities of chromatin and pro- toplasm. Such pathological mitosis increases with the anaplasia and malignancy of the tumor. Amitosis is also, to a less extent, concerned in the multiplication of tumor cells. Endogenous cell formation also occurs. Structure and Growth of Tumors. Tumor processes have been shown to originate in one or many very small groups of cells. The tumor may then grow by the multiplication of these cells alone, or other normal cells may be steadily excited to excessive prolifera- tion. Thus in carcinoma of the colon the edges of the growth frequently show all gradations from normal glan- dular epithelium through pronounced hypertrophy of epi- thelial cells up to the active tumor cells with excess of chromatin. - The former tendency produces an encapsulated growth, especially if benign, {lipoma'), or the tumor cells orig- inating from a small focus may rapidly push their way through lymph spaces and grow to a large size in neigh- boring parts. {Carcinojiia of a.villary nodes zi'ifJi minute nodules in breast.) The latter tendency yields locally spreading growths with or without metastasis. (Diffuse carcinoma of colon.) ^.S'HT^ 4^*tx^^f6^ ^, ?o 13 CLASSES OF TUMORS. Connective Tissue. Fibrillar connective tissue Fibroma Mucous tissue Myxoma Fat tissue Lipoma Cartilage Chondroma Bone Osteoma Embryonal connective tissue Sarcoma Endothelium Endothelioma Muscle Tissue. Smooth muscle Leiomyoma Striated muscle Rhabdomyoma Nerve Tissue. Nerve cells and fibres Neuroma Neuroe:lia Glioma 'in' Vessels. Blood Angeioma Lymph Lymphangeioma Epithelial Tissue. Glands Adenoma Epithelium, Glandular Carcinoma Epithelium, Squamous Epithelioma Skin Dermoid Complex Embryonal Implantations Teratoma 14 FIBROMA. Occurrence. Siibcutaneoits tissue, intermuscular septa, breast, and other organs. Cells of Origin. Usually from fibroblasts of support- ing connective tissue. Or from fibroblasts of vessel walls, when many new vessels and much endothelium may accompany the growth. Or from basement membrane- cells of alveoli. (Canalicular fibroma of breast.) Or from fibroblasts of nerve trunks. Structure. That of fibrillated connective tissue. The proportion of cells and fibres varies greatly, the more cel- lular tumors becoming fibrosarcomatous and recurring locally after operation. They are hard, from densely packed cells and fibres, or soft, from excess of cells and from oedema. Varieties: ^Multiple fibroma of skin, arises usually in nerve trunks and shows fibroblasts mingled with much endothelium, and sometimes with nerve fibres. Keloid is a term applied to very dense acellular fibrous thickenings of scars, with numerous lymph channels, but extending beyond them and following the line of blood channels. It is possibly of inflammatory origin, but is progressive, although not extending beyond the cutis. Fibrous papilloma is common on mucous surfaces and consists of fibrous tissue and vessels covered with hypertrophic epithelium. It is often largely inflamma- tory in origin. Combinations of fibroma with other tumors are very frequent. 15 i^YXOMA. Occurrence. In loose connective tissue of back, navel, cheek, vulva, scrotum,' mucous surfaces, bone marrow, breast, placental mole, nerve trunks, parotid. Cells of Origin, fibroblasts of supporting connective tissue, of basement membranes, of adenoid tissue, of nerve trunks ; and fat cells. Structure. Peculiar polyhedral cells lying in a mucin- ous matrix which shows precipitated basic fibrils and finely granular or homogeneous mucus. The proportion of cells and mucus varies greatly. The cells are often connected by radiating processes. Varieties: (i) Primary myxoma arises from embry- onal mucous tissue which precedes the formation of con- nective tissue and fat. This tumor is rare. (2) Secondary myxoma is an oedematous fibroma or lipoma which undergoes mucoid degeneration. Such tumors are common. It is usually difficult to distinguish primary from secondary myxomata. The primary myxoma is seen in the new born ; a typ- ical form in the hydatid mole, which is however largely an hydropic degeneration. Clinically the myxoma of the central and peripheral nervous systems is important. i\[u- cous polyps of the nares, etc., are largely inflammatory. Combinations with lipoma and sarcoma are frequent. i6 LIPOMA. Occurrence. Skin, often in neck and back, rarely in hairy parts. Fasciae, joint capsules, renal capsule, mus- cles (pseudo-hypertrophy), nerves (multiple symmetrical lipomata). Cells of Origin. Fat cells and fibroblasts. Structure. That of normal fat tissue, but the tumor cells var}' in size, are irregularly grouped into uneven lobules, blood vessels are usually more abundant, and fibrous tissue usually excessive or deficient. Growth is usually circumscribed, but may be diffuse. Varieties: Combinations are frequent with myxoma, fibroma, angeioma, and sarcoma. CHONDROMA. . Occurrence. One of the most widely distributed of tu- mors, arising from (i) cartilage, bone, or connective tis- sue; (2) forming frequently in other tumors of the con- nective tissue series, including endothelioma, and (3) very frequently present in tumors developed from mis- placed embryonal remnants. Cells of Origin. Fibroblasts, endothelium, bone and cartilage cells. Embryonal connective tissite cells. Structure. The type is usually that of hyaline cartilage, but may be fibrous, or fibro-elastic. The cells vary greatly in size, number, and arrangement. The stroma is hyaline. or fibrous, mucoid, or calcific. Blood vessels are more numerous than in normal cartilage but degeneration and necrosis is common. Varieties : Combinati6ns with fibroma, osteoma, lipoma, myxoma, and sarcoma, are common. The most peculiar and striking chondromata are those that develop from misplaced embryonal cells, as along the vertebrae, epiphy- ses, in the genital organs, parotid, and lung. OSTEOMA, Occurrence. On bone and periosteum, or in soft tissue as a part or secondary feature of fibroma, chondroma, and sarcoma. Cells of Origin. Bone or cartilage cells, and fibro- blasts. Structure. Dense ivory osteomata show very few Haversian canals or medullary spaces, while spongy os- teomata are more vascular and contain numerous medul- lary spaces. The structure may be that of bony tissue or the cells may have comparatively few processes, some- what resembling cartilage cells, and the matrix is less dense than that of bone (osteoid tissue). Varieties: Inflammatory exostoses are difficult to sep- arate from tumors. Pure osteomata are not common but are most frequent about the cranium. Osteo-fibroma, chondroma, and sarcoma, are the usual types. Osteoma occurs, rarely, in the brain and lung, from misplaced embryonal tissue. In the jaw one variety is the odontoma, containing bone, dentine, and enamel organ. SARCOMA. Definition. A sarcoma is a malignant tumor developed from cells of the connective tissue series, and of which the cells are more abundant than in normal connective tissue or in simple benign tumors of connective tissue, while the intercellular substance, although present, is usually very scanty. In these tumors the anaplasia is pronounced. Occurrence. Sarcomata develop wherever the simple tumors of the connective tissues are found. They are most frequently located in the skin, bones, lymph-nodes, and viscera. Cells of Origin. The fibroblast and all its derivatives, including cartilage, bone, fat, lymphoid, and smooth mus- cle cells, and from the fibroblasts of blood vessels, nerve trunks, basement membranes, and interstitial tissues. Cellular endothelial tumors are closely related to sar- comata. . . Structure and Varieties. (1) Simple Fibroblastic Sarcoma. (a) Small and large spindle cell sarcomata contain numerous spindle shaped fibroblasts, with little fibrillated inter-cellular substance, usually with very few blood ves- sels. Some of these tumors appear to be derived from the fibroblasts or endothelium or embryonal smooth muscle cells of many minute blood vessels, but the cells exhibit the characters of fibroblasts. They are common in the skin where they develop from nerve trunks and base- ment membranes of sweat or sebaceous glands or hair fol- licles. There are all gradations from simple fibroma to ^9 fibroblastic sarcoma and numerous combinations with other types of sarcoma. {b) Giant cell sarcoma contains large and small giant cells of the type of nVyeloplacques, many large or small spindle cells, and usually many blood vessels. Giant cells are most frequently seen in periosteal or medullary sarcoma where they represent the osteoclasts of developing bone or of marrow. Giant cells also form in sarcomatoid tumors of endo- thelial origin. They are common in the tumors called perithelioma. (c) Small round cell sarcoma is almost always de- rived from lymphocytes, and is called lymphoma or lym- pho-sarcoma. Possibly it may at times be of fibroblastic origin. (2) Lymphoma. (a) Simple lymphoma is a tumor of lymph nodes in which the cells are of the usual type of lymphocytes. The tumor growth remains within the distended capsule of the node, the outlines of the follicles are still partly preserved,' lymph sinuses are not obliterated, and a reticular stroma is present. This tumor is seen in pseudo-leukemia, and lymphemia. (b) Lympho- sarcoma contains sjnall and large lympho- cytes or larger cells, the outHnes of follicles are indistin- guishable, the capsules of the nodes are infiltrated and ruptured, and the sinuses obliterated. Some of the nodes in pseudo-leukemia and lymphemia may be of this type but the best examples are seen as more circumscribed but very malignant tumors of single groups of lymphnodes or of the viscera. 20 As one passes up the scale of malignancy in lymphoid tumors the cells become larger and eventually fall in the class of large round cell sarcoma. ( r ) Large round cell sarcoma must at present be treated as a heterogeneous group, as the origin of such tumors is not always clear. The group includes, (i) Large round cell tumors of fibroblastic origin. (2) Large round cell lympho-sarcoma. (3) Melano-sarcoma. In all but lympho-sarcoma the cells are apt to be not strictly sphe- roidal, but polygonal. (1) Fibroblastic Large Round Celled Sarcoma. Perithelioma (Telangiectatic sarcoma), a common tu- mor appears to be the sole example. It is composed of a congeries of blood vessels surrounded by thick sheaths of large round or fusiform cells. The tumor cells radiate out from these vessels. Or, the vessels are lost and the cells diffusely scattered. The exact origin of this tumor is uncertain but it may be regarded as a derivative of the large epithelioid fibroblasts of the sub-endothelial connective tissue of blood vessels. (2) Large Round Cell Lympho-sarcoma. These tumors are most frequently seen in lymph nodes and in the caecum. They are rapidly growing and are among the most malignant of tumors. Myeloma, a large round cell tumor developing from certain cells of bone marrow, may be classed here. The structure includes the cells, and a supporting framework of reticular connective tissue, with small blood vessels. The cells include a small proportion of lymphocytes, a majority of large mononuclear cells, and In well nourished tumors the multiplication of cells may be equally active in all parts {central grozvth). Frequently the nutrition is deficient in the central parts of a tumor and growth, is most active or exclusively lo- cated in the peripheral portions (peripheral grozuth). Some tumors consist exclusively of new cells of a single type, but most new growths contain, besides the specific tumor cell, nerves, blood vessels, and a supporting frame work of connective tissue. In carcinoma there is often an excessive amount of new connective tissue, usually as the result of productive infiammation. The new blood ves- sels in tumors may be the result of productive inflamma- tion, or the tumor cells when arising from cells of ves- -sel walls may persist in their normal functions and pro- duce many neoplastic vessels. Several varieties of tissue arising from embryonal remnants of the same type are found in the mixed tumors or teratomata. Degenerative Processes. Hydropic, mucoid, hyaline, glycogenic, and fatty de- generation, are commonly observed in tumors, ne- crosis is a frequent result of imperfect blood supply, and inflammatory processes occur as in normal tissues. These changes tend to limit the growth of tumors by diminish- ing the number of proliferating cells. (Gelatinous carci- noma.) The growth of tumors is usually much more active than that of the tissue originating them. The blood sup- ply must therefore be correspondingly large, and indeed the demands for nutrition of some tumors may cause atrophy of the other tissues of the body. (Lipoma in thin subjects; large sarcomata.) Function in Tumor Tissue. Tumor tissue usually retains some of the function of the original tissue; sometimes this function is exagger- ated in the tumor, and usually it is perverted while not inhibited. Thus, the adenomatous thyroid protects against the myxoedema which follow^s total extirpation of the thy- roid; there may be milk in the cysts of adenoma of the breast, urine in adenomatous alveoli of the kidney, bile in metastatic carcinoma from the liver, and many tumors of mucous surfaces secrete an excess of mucus. Metastasis. Tumor cells wdien detached from one another are still more or less capable of growing. Such detached cells are often carried by the lymph stream, less often by the blood, to distant parts where they lodge and develop into metastatic tumors. Vascular tumors and those which tend to grow into lymph spaces most frequently develop metastases and are therefore most malignant. In many tumors the paths and locations of metastases are very characteristic. Usually metastases are located in the nearest lymph nodes, but sometimes early metastases are far distant from the original tumor. (Secondary growth over scapula from cancer of stomach.) Numerous in- stances of retrograde metastasis have been recorded. (In pehic lymph nodes from cancer of liver.) A favorite seat of metastasis for carcinoma is the bone marrow. Malignancy of Tumors. Evidences of malignancy may be clinical as (i) rapid Towth, (2) pain and ulceration, (3) involvement of ad- jacent tissues, (4) local recurrence, (5) metastases. (6) cachexia. Histological evidences of malignancy include : (i) Markedly cellular character. (2) Relatively large size of cells and abundance of chromatin. (3) Abundance of mitotic nuclei. (4) Abnormal arrangement of cells. (5) Tendency to invade neighboring tissues. The first three of these histological features are really the means of estimating the grade of anaplasia which is therefore the criterion of malignancy. The sole feature of malignancy of a tumor may be an unfortunate position where it endangers vital structures, or its large size, or it may be capable merely of local recurrence, or it may possess all the elements of malignancy. The prognosis varies in each instance. The estimation of the malignancy of tumors requires an intimate knowledge of both their clinical and their histological characters. ETIOLOGY OF TUMORS. (a) General. Age and sex determine largely the types and locations of tumors. There is a very slight hereditary predisposi- tion affecting the occurrence and type of tumors. (b) Local. Trauma is frequently concerned with the development of tumors, {epithelioma of lip; sarcoma after fractures of hones). Local malformations, as nsevi of the skin, mis- placed portions of adrenal or thyroid, are frequent start- ing points of tumors. (c) Exciting Cause. The exciting cause of tumor growth is not known, and several theories regarding its origin are maintained. (1) Cohnheim's Theory of Embryonal Remnants. - Cohnheiin beheves that tumors develop from : (i) Masses of complex or simple tissue misplaced dur- ing embryonal development, yielding the mixed tumors or teratomata. (2) Small groups of embryonal cells, (a) misplaced or {b) not misplaced, which have failed to reach their full differentiation into specific tissues. The immediate exciting cause of the sudden growth of these cells is increased nutrition and irritation. Tumors therefore frequently develop in the breast and uterus which pass through many physiological changes in ac- tivity. Roux found 1-13 minute foci of cells misplaced from other layers in the entoderm of frogs' embryos, and Bar- furth produced dermoids by puncturing ova in the gas- trula stage, thereby misplacing cells. In order to elucidate the obscure nature of the in- ception of a tumor process in these misplaced cells, the idea of a disturbance in tissue tension has been suggested. The idea of tissue tension involves (a) ^Mechanical pressure of cells on each other, (b) the distribution of nutriment among the cells, and (c) the acquired demands on the cells for specialized function instead of on their embryonal habit of simple multiplica- tion. Tissue growth normally ends when the regenerative capacities of cells are restrained by tissue tension. Em- brvonal remnants being cut out of this circle of influ- ences are liable to resume their embryonal capacities of multiplication and feeling no restraint of neighboring cells and no demands for specialized function go to de- velop tumors. Scores of examples illustrate the partial truth of Cohn- heim's theory : adrenal tumors of kidney ; rhabdomyoma of kidney, genito-urinary organs, breast and heart ; em- l)ryoid tumors of ovaries, uterus, vagina; adenomyoma of uterus ; adenoma of supernumerary breast, thyroglossal duct ; chondroma of parotid from misplaced cartilage from the ear ; epithelioma from branchial clefts ; glio-adenoma from misplaced vertricular remnants in brain ; choleste- atoma of skull; osteoma of lung; peritoneal epithelial cysts in spleen ; and the entire group of dermoids and teratomata. In fact in every organ are well recognized types of tumors certainly developing from embryonal remnants. Such tumors producing a tissue differing from that of the harboring organ are called heterologous. Cohnheim's theory embodies one of the great facts in the etiology of tumors and is very likely a complete ex- planation of the group of heterologous tumors. It is equally certain that all tumors, especially most carcinomata, fibromata, sarcomata, of simple structure homologous with that of the harboring organ, are not de- rived from embryonal cells. At any rate there are no means of identifying such cells, in the breast for instance, and such a theory therefore appears not to admit of proof for all tumors. Ribbert's Theory. Ribbert endeavors to extend Cohnheim's principle to the development of tumors from groups of adult cells which by various means lose their relations to their neighbors and thus fail to feel the restraining effects of tissue ten- sion. He does not believe that the development of tumors requires any greater proliferative tendencies than are to lO be found in adult cells, which exhibit constant or intermit- tent powers of multiplication, as in the breast and uterus where malignant tumors are common. The initial separa- tion of the cells from the influence of the tissue tension he refers to tlic grozi'th of jiczv connective tissue of in- flammatory origin into the epithelial layer, and he de- scribes such fibroblasts between groups of epithelial cells in psoriasis of the tongue with early epithelioma and in an adeno-carcinoma of the stomach. This theory accords with many facts known in regard to the origin of homologous tumors ; with the frequent development of carcinoma in chronically irritated tissues, as epithelioma of muco-cutaneous junctions, adenomata of liver from ducts snared oft in cirrhosis; adenoma of kid- ney in old nephritis ; epithelioma following lupus ; mul- tiple chondromata of epiphyseal lines in the irregular os- sification of rickets; carcinomata after crushing injuries; syncytioma from misplaced chorionic cells, etc. It is rather a matter of wonder, if one accepts this theory, that tumors are not vastly more common, as mis- placement of adult cells must be frequent, and Ribbert's theory somewhat inadequately defines the particular forces precipitating the misplaced cells into the malignant tumor process. Numerous very painstaking attempts to produce tumors experimentally by separating without destroying tissue cells have failed. Some other factor appears to be needed. The principles involved in Cohnheim's and Rib- bert's theories represent the most mature judgment of the problem of tumors, probably reach as near the com- plete explanation as is at present possible, and separate the tumor process distinctly from parasitic disease. Theory of Parasitic Origin of Tumors. The possibility of a parasitic origin of tumors seems II to be inadmissible for the group of teratomata and it may be said that the above considerations render unhkely such an origin for the usual varieties of homologous tu- mors. The parasitic theory is applied by its adherents princi]3ally to the simple malignant tumors, carcinoma and sarconia. Are Microorganisms Present in Tumors? I\Iany observers have described in the cells of the grow- ing edges of carcinoma and sarcoma peculiar bodies which they believe to be parasites. The bodies are rounded, homogeneous, and refractive, in the fresh condition sometimes slightly amoeboid, 1-15 ,x in diameter, surrounded by a clear halo and some- times by a membrane, sometimes exhibiting a nucleus, often showing bud-like processes, in staining reaction sometimes acidophile sometimes basophile [Cancer bodies, Plinuiier's bodies, Russell's fuchsin bodies). These "cancer bodies" are regarded by the adherents of the parasitic theory as (i) blastomycetes or (2) pro- tozoa; and by the great majority of observers as (i) cell inclusions, of a variety of types, but not parasitic, (2) centrosomes, (3) extruded nucleoH, (4) products of cytoplasmic or nuclear degeneration. The great vari- ety of these bodies, their inconstancy and variability of oc- currence in tumors, and their presence in other conditions, speak against their parasitic nature. Relation of Blastomycetes and Protozoa to Cancer. In a few cases blastomycetes have been cultivated from cancer but the vast majority of attempts have failed and most tumors appear not to contain them. Attempts to produce timors by inoculation with blasto- mycetes obtained from tumors or from other sources have 12 invariably failed. The results of such inoculations have always been purely inflammatory. It must be concluded therefore that although blasto- mycetes are occasionally present in cancer their presence is accidental and they are not the cause of the disease. Protozoa have not been demonstrated in malignant tu- mors, although it is possible that some of the bodies rle- scribed as such are really protozoa. Transplantation of Tumors. If tumors contain a parasite it is reasonable to expect that the transplantation of a portion of the growth from one animal to another of the same species would be suc- cessful. Of many thousand such experiments only two or three have been partially successful, and even in these cases the resulting growth was transitory and^of doubtful nature. CLASSIFICATION OF TUMORS. Tumors are classified in order to display their relation to each other, and to furnish a basis for uniform nomen- clature. At present these objects are best attained by naming and classifying tumors as we name their adult cells of ori- gin, or the tissue Avhich the tumor most resembles. The endeavors to create and introduce a classification of tumors based on the ultimate embryological relations of the originating cells have not been successful and are not to be encouraged. Embryological relations have much influence in determining the type and structure of tumors, l3Ut the habits of tumor cells are much more often de- termined by the late acquired habits of the cells than by their earlv embrvoloeical tendencies. 29 tatioii, producing- the papillar}' cystic adenomata, which arc common in the ovary and kidney. Such tumors are usually circumscribed and peduncu- lated, since the hyperplasia may begin in and be limited to very few alveoli, possibly even to a single alveolus. (White.) Considerable anaplasia usually marks the cells of these tumors, but hypersecretion is also common. The membrana propria remains intact, and the supporting con- nective tissue is usually abundant and vascular. (3) Malignant adenoma. Adenoma sometimes proves malignant while its structure rigidly observes the type of simple adenoma (e.g., adenoma of stomach). Usually the malignant qualities of local recurrence, infiltration, or metastasis, are associated with marked anaplasia of cells, which increase in size, especially of the nuclei, and mul- tiply rapidly, increasing the depth of the epithelial lining of the alveolus. Such alveoli push their w^ay through fibrous or muscular tissue, and breaking through the membrana propria, they invade lymphatics and develop metastases. In such metastases anaplasia may increase or diminish, but the strong tendencies of the cells to assume the orderly alevolar arrang'ement, while exhibiting the other quali- tie of carcinoma, justifies for many of them the term adeno-carcinoina. Common examples of malignant ade- noma are seen in the gastro-intestinal tract, and uterus. In the ovary they are often of the papillary cystic type. In general it may be said that adenoma of the gastro- mtestinal tract and uterus are usually malignant. 3° CARCINOMA. Definition. Carcinoma is a malignant tumor of glan- dular epithelium. Structure. Carcinoma is distinguished from adenoma, by the greater anaplasia of the cells, their more rapid growth, and their failure to remain within the confines of a more or less specialized membrana propria. It is seldom that a carcinoma maintains a uniform structure in all its parts, or in all stages of its growth. Not only are minor variations commonly seen in the same growth, but frequently distinctly different types of growth may be observed in the different parts of the original tumor, while in metastasis the structure may be totally at variance with that of the main tumor. Characters of Cells. In all types of carcinoma the anaplasia of the cells is distinct. The cells are usually of increased size, their nuclei show an abundance of chromatin, and mitotic figures are numerous in rapid cases. The shape of the cells is determined sometimes by their natural tendencies, but very often by the local conditions of nutrition and pressure. The cells show abnormal and usually diminished functional ca- pacity. They are subject to various degenerations, fatty, hydropic, mucoid, hyaline, glycogenic. Advanced mu- cinous degeneration gives the tumor a swollen, elastic, gelatinous appearance, to which the term gelatinous car- cinoma is applied. This change tends to limit the growth. The tumor exerts an irritation on the invaded tissues with reactive inflammation of exudative or productive tvpe, which tends partially to limit the advance of the growth. 31 Sometimes the new fibrous tissue is excessive in amount and of neoplastic type, as in fibro-carcinoma, or of acellular type as in scirrhus. , Mucous dci^'eneration of the connective tissue, if prom- inent, is designated by' the term myxomatous carcinoma. Carcinomata of exposed surfaces frequently ulcerate, owing to traumatism of the poorly nourished tumor tis- sue, and various secondary iniiammations may result from infection by microorganisms, including pyogenic bacteria, bac. tnhercnlosis, or blastomycetes. Classification of Carcinomata. On general histological structure carcinomata may be divided into three classes, adeno-carcinoma, alveolar car- cinoma, and diffuse carcinoma. While the employment of these terms may indicate the general structure of a carcinoma and may thus serve a useful purpose, there is a growing tendency to name and classify these and other tumors according to their exact cell of origin, so far as that can be determined, since it appears that the structure of such accurately defined tumors is nearly always the same. Varieties. (i) Adeno-carcinoma. This type of growth is chiefly seen in those situations where mahgnant adenoma occurs, as in the gastro-intes- tinal and uterine mucosae. The cells are arranged in groups which maintain a somewhat orderly alveolar arrangement and central lu- men. In one variety the carcinomatous process develops extensively within the distended alveoli of papillary and cystic adenomata. Most adeno-carcinomata represent transitional stages 33 between malignant adenoma and alveolar or diffuse car- cinoma. Or a tumor may begin as adeno-carcinoma and maintain that type throughout, even in distant and late metastases. (2) Alveolar Carcinoma, (Medullary.) This is the most frequent type of carcinoma and occurs in many organs, most often in the breast. The cells appear in groups confined by the borders of tissue spaces, or walls of vessels, but they are not at- tached to these walls as to a basement membrane, and they do not preserve a central lumen. (3) Diffuse Carcinoma. \Mien the growth of cells is very rapid and profuse, little or no subdivision into orderly groups may exist and the term dift'use carcinoma may be applied. This struc- ture is seen in many very cellular tumors, which are rapidly growing, very malignant, and never show^ any tendency to observe the alveolar arrangement ; or the dif- fuse quality of the growth may result from the absence of supporting tissue, as in a lymph node or blood vessel ; or there may be a dift'use infiltration of an organ or tissue by cells appearing singly or arranged in rows, but not in alveoli. TUMORS DERIVED FROM STRATIFIED SQUAMOUS EPITHELIUM. These growths form two distinct classes : (i) Epithelial Papilloma. (2) Epithcliojiia. (i) Papilloma. Definition. Epithelial papilloma is a tumor in which the growth of epithelium is outward and papillary pro- jections are formed on the affected surface. There are many transitional phases between inflamma- tory hyperplasia of squamous epithelium and neoplastic hyperplasia, which it is difficult to distinguish. The ve- nereal wart is an inflammatory hyperplasia; eczema and psoriasis exhibit a uniform inflammatory hyperplasia of the prickle-cell layer; while the ordinary wart, and the papillomas of the bladder and larynx are examples of a true benign tumor of stratified epitheHum. (2) Epithelioma. Definition. An epithelioma is a malignant tumor de- rived from stratified squamous epithelium. Origin and Structure. The tumors derived from the so-called transitional epithelium, as in the bladder, are included in this class. All epitheliomata are derived from 34 the deeper layers of cells, but while in some {acaiithonia- ta), the cells assume the pavement type, in others they never progress in their natural development, but remain small and fail to exhibit the pavement type, or develop prickles, or hornification. There are several inflammatory conditions character- ized by a simple hypertrophy of the basal layers of strati- fied squamous epithelium, as in eczema and psoriasis, and sometimes hypertrophied papillae project distinctly into the connective tissue, but in epithelioma the growth of cells is more active and there is progressive invasion of the derma or submucosa by masses of cells of neoplastic type. The variety of structure in tumors of stratified squa- mous epithelium is very extensive and depends upon (i) the particular cell form giving origin to the tumor, and (2) the grade of anaplasia of the cells. No other tissue is capable of yielding such a multiplicity of tumor-cell forms. Varieties . (i) Prickle -cell Epithelioma. (Acanthoma.) In one very distinct class of epithelioma the cells are derived from the prickle-cell layer, and they retain their original flat pavement character, with prickles, and ten- dency to hornification. In such tumors the prickle cells are readily identified, the pavement tendencies give rise to concentric masses of cells, often with hornified centres, called epithelial "pearls." Such tumors frequently develop in the skin, at muco-cutaneous junctions, and in mucous membranes, and they constitute the most numerous class of epitheli- oma. Their malignancy depends on their situation and degree of anaplasia. In the skin they are less malignant 35 than in the mucous membranes, but all are characterized by tendency to local recurrence, early ulceration, and metastasis in the lymph nodes. In the metastases the same histological characters are usually maintained, but the prickles are the first features to be lost. Occasionally, in the original growth the prickles are partly lost, the cell bodies become more gran- ular, the cells are arranged in narrow anastomosing cords, and the term tubular cpithcUouia is sometimes applied. (2) Reticulated Epithelioma. This tumor occurs in the skin, in two rather distinct forms. ( i) The cells are small, cuboidal or fusiform, and densely packed in small or larger masses in the lymph spaces of the derma. These masses are connected by thinner cords of cells, giving to the growth on section a peculiar reticulated appearance. Rodent ulcer is such a reticulated epithelioma with large compact masses of cells and usually with ulceration of the surface. The above masses of cells may undergo lique- faction in one of several foci, with dilatation of in- closed spaces. An alveolar appearance is thus formed and the tumor is called adenoid cystic epithelioma. These tumors possess only slight malignancy, very sel- dom involving adjacent lymph nodes. (3) Papillary and Flexiform Epithelioma. A frequent form of epithelioma arising from mucous surfaces is composed of thick convoluted layers of epithe- lium irregularly twisted and supported by a variable amount of connective tissue. Sometimes this connective tissue is abundant, in which case the identity of the convoluted layers of epithelium is distinct. Sometimes the connective tissue is reduced to a verv thin coverino- 3