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The occurrence of tumours in the domesticated animals
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THE OCCURRENCE OF TUMOURS IN THE DOMESTICATED ANIMALS.
By J. M'FADYEAN, M.B., B.Sc., F.R.S.E., Royal Veterinary College, Edinburgh. DU~ING the past year there was inserted ilJ each number of this Journal a notice to subscribers requesting them to send to the Editor all tumours excised by them, with the view of collecting information regarding the occurrence of cancer among the domesticated animals. This appeal has brought to me a considerable number of specimens, and in fulfilment of the promise made it is now my duty to report the result of a careful microscopic examination of the material that has thus come into my hands. In order to render such a description intelligible and useful to all the readers of the Journal, it may be necessary, at the outset, to devote some space to a consideration of (I) what is meant by the words tumour and neoplasm, and (2) what is the import of certain terms used in the classification of such formations. The word tumour may be applied to any circumscribed morbid swelling or enlargement. In this sense an actinomykoma, an abscess, a cyst, or a neoplasm proper is a tumour. In the same way we are accustomed to speak of "splenic tumour" in referring to what is merely a congestive swelling of the spleen, and of the tumour of black quarter (symptomatic anthrax), where the enlargement is due to congestion, blood extravasation, and inflammatory exudate. The term neoplasm is much more restricted in its application. To define briefly and accurately the meaning of the word is a matter of some difficulty, as is exemplified by the fact that no two authors give exactly the same definition. The essential nature of a neoplasm may be best explained by stating what it is not, as well as what it is. A neoplasm is an abnormal, non-inflammatory, new growth. It is composed of newly formed histological elements, a.nd does not result from a mere transformation of pre-existing normal textures. An actinomykoma-that is the tumour-like formation caused by the presence of the actinomyces in the tissT,les-is not a neoplasm. I t is in reality a slowly growing inflammatory tumour. Thus, by using the term non-inflammatory in our definition, we separate from the neoplasmata almost every instance of abnormal new growth occurring in the adult animal, save hypertrophy. The fundamental difference between the new elements formed in hypertrophy (such as the increase of muscular tissue in the left ventricle of the heart in aortic stenosis), and those that constitute a neoplasm, is that the former comport themselves like the normal elements of the part, in that they obey the same morphological laws, and therefore do not distort the organ in which they are formed. A neoplasm, on the other hand, does not obey the laws that govern the form of the organ or part in which it has its origin. Speaking metaphorically, it is composed of rebellious elements, which have broken away from the normal parts, and which, henceforth, maintain towards the rest of the organism a state of semi-independence. Neoplasms have, therefore, been aptly compared to parasites, growing in, and at the expense of, some tissue or organ of the body.
GENERAL ARTICLES.
Although most recent authors on pathology draw this distinction between tumour and neoplasm, the former term is still in very general use, the tendency being towards restricting the original meaning of the word, so as to make it synonymous with the term neoplasm as above defined. It is in this restricted sense that it is used throughout this article. Classificatioll of TUJIlouys.-When the pathologist comes to study the minute anatomy of the neoplasmata, he finds a close correspondence between their histological elements and those that compose the normal textures of the animal body. Thus we have tumours composed of muscular fibres, others of fibrous connective tissue, others of cartilage, and so on. In modern pathology the classification of tumours is based upon their minute structure, as is shown in the subjoined table. CLASS A. SIMPLE HISTIOID NEOPLASMATA, resembling one of the simple textures of the body. Histological Type. Neoplasm. Embryonic connective tissue. I. Sarcoma 2. Fibroma Fibrous and areolar connective tissue. Gelatinous connective tissue. 3. Myxoma Connective tissue of brain and spinal cord. 4. Glioma* Adipose tissue. 5. Lipoma 6. Chondroma Cartilage. Bone tissue. 7. Osteoma*" 8. Odontoma Dentine. Muscular tissue (plain or striated). 9. Myoma 10. Neuroma*" Nerve fibres. CLASS B. COMPOUND HISTIOID NEOPLASMATA, more complex in structure than those of Class A. Comprise elements of two or more simple tissues.
jVeoplasm. Angeioma 2. Papilloma } 3. Adenioma 4. Carcinoma I.
Component Textures. Blood or lymph vessels and connective tissue. Epithelium and vascular connective tissue.
I have thought it well to thus set forth in tabular form the chief varieties of neoplasmata that have been met with in human pathology; but, so far as the main purpose of this article is concerned, the three classes marked with an asterisk might have been omitted, inasmuch as no example of these is included in the list of tumours here to be reported upon. EPITHELIAL TUMOURS.
I have selected for first consideration the epithelial tumours, as in several respects these form the most interesting group of new formations. The term epithelial, as it is here used, is not intended to imply that these neoplasmata are entirely composed of epithelium, but that in all of them epithelium is the essential histological element. The group comprises three distinct classes of growths, differing fundamentally as regards the arrangement of the epithelium and its relationship to the other elements of the tumours. These are-(I) the papillomata, (2) the adenomata, and (3) the carcinomata.
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THE PAPILLOMATA. A papilloma has a structure comparable to that of one of the normal papilla: found in mucous membranes, such as those of the tongue in all mammals, or of the first stomach of the domestic ruminants. It possesses a core of vascular connective tissue and a surface covering of epithelium. A common wart of the human hand has this type of structure, and is, therefore, a papilloma. The axial connective tissue is in direct continuity with the corium of the skin or the corresponding stratum of connective tissue in a mucous membrane, and, in like manner, the investing epithelium is continuous with and originally derived from the normal epidermis or epithelium. As a rule the connective tissue core of the tumour gives off secondary branches, which may again branch, the ultimate divisions being always invested by epithelium. In this way considerable tumours may be formed. As illustrative of this class of epithelial tumours I may describe, in the first place, a very interesting example sent by Mr S. Beeson, of Hereford.
FIG. I.-Section from a large cauliflower papilloma of the penis of a horse (x 20). 1. Connective tissue stem; 2. A branch of the same cut longitudinally; 3. Another branch cut transversely; 4. EpIthelium. The darker shading in the epithelium indicates the younger cells, corresponding to those of the rete mucosum.
Tumour /.- This tumour was removed by Mr Beeson from the end of the penis of an aged grey gelding. It was attached to the glans immediately behind the meatus urinarius. The growth had been first observed during the spring of r889, and it had been removed by another practitioner about the month of April. It immediately began to form again, and it was excised by Mr Beeson in the following July. The owner had an idea that the tumour had its starting point in an injury to the penis, inflicted by the horse falling across a rail while hunting during the previous season. The tumour weighed about 4 ounces, and it had a most striking resemblance to a cauliflower head, having a main stem from which proceeded secondary and tertiary branches. The minute structure of one of the small surface projections of the growth is depicted in the accompanying illustration (Fig. I). The wart-like nodule, of which this represents a section, measured about ~-th of an inch in diameter at its widest part. It is seen to have an arborescent core of connective
GENERAL ARTICLES.
tissue, the ultimate branches being imbedded in a mass of epithelial cells. The axial substance has the characters of young, succulent connective tissue. It is richly nucleated and provided with conspicuous blood-vessels, and from it branches pass in all directions. The lighter areas on the right half of the figure are ramifications of the connective tissue core cut transversely. The epithelium, where it is in contact with the connective tissue, is identical with the deepest stratum of the rete mucosum of the skin, forming a continuous layer of actively multiplying cells with a relatively small amount of protoplasm and a deeply staining nucleus. Farther outwards the cell body is larger and in a condition of incomplete horny transformation, while the nucleus is distorted and imperfectly stained. In this particular projection the epithelium, even in its outermost strata, is comparatively soft, but in some other branches of the tumour there is a distinct stratum corneum. Lastly, it may be mentioned, as a point of interest, that in sections of the main stem of the tumour there are occasional cell groups lying remote from, and apparently unconnected with, the surface mass of epithelium. At these parts it looks as if the growth had been on the point of assuming a carcinomatous character. Tumour Il.-This tumour had a structure identical with the one just described. It was removed by Mr Shillingford, of Buckingham, from the hard palate of a horse. The growth weighed about 8 ounces. Tumour III.-This specimen, which was sent by Mr Menzies of St. Austell, Cornwall, was not a single tumour, but a large number of papillomata growing on the hard palate and cheeks of a dog. The largest of these were slightly branched, and about i: of an inch in length. Their epithelial covering was almost white. The mouth of the dog is a not uncommon seat of these mUltiple warts, and I am constrained to quote here a reference to a mode of treating them which appears to yield eminently satisfactory results. In the Noulleau D£ct£01l1Ia£re Pratique (p. 399), Professor Trasbot, of the Alfort Veterinary College, says :-" To-day we possess an agent, one of the most inoffensive, which appears to yield surprising results, viz., calcined magnesia. Lambert, of Haguenau, was the first to speak of it; M. Gueneau of Mussy recalled it to the Societe de Therapeutique. We have employed it for nearly two years; at first, we confess, without any hope of success, and with a certain amount of astonishment we have proved its remarkable efficacy. All the dogs to which we have administered it-and they are now numerous-have recovered in from one to three weeks. From half a gramme (a gramme = 15 grains, nearly) to a gramme or a gramme and a half is administered daily according to the size. After some days one sees the warts become blanched and shrivelled, and they gradually disintegrate and disappear." THE ADENOMATA AND THE CARCINOMATA.-These two varieties of neoplasmata embrace the greater number of the new growths which popularly are known as cancers. At the present day the tendency in pathological nomenclature is to discard the term cancer altogether, or, if retaining it, to use it synonymously with the word carcinoma. I fear it must be admitted that in veterinary pathology there is still considerable looseness in the mode of using these terms. In this connection it ought to be remembered that the
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malignancy of a tumour is no criterion of its proper place under the modern system of classifying such formations. In order to illustrate. that point, a word may be necessary regarding the use of the term " malignant" as applied to tumours. A neoplasm deserves to be called malignant (I) when it steadily invades and destroys the surrounding textures, and exhibits a marked tendency to recur at the primary seat after excision, or (2) when it reproduces itself by metastasis-that is to say, when secondary tumours, identical in structure with the first, grow in the nearest group of lymphatic glands or in some of the internal organs. Both of these characters of malignancy are exhibited in common by growths which are now excluded from the neoplasmata, and by several distinct varieties of true neoplasmata. For example, an actinomykoma is apt to recur locally after an attempt to remove it, and not rarely secondary growths of the same nature form in the nearest lymphatic glands. The same may be said of tubercular tumours. But, as already explained, these growths are not neoplasmata, and the explanation of their tendency to local recurrence and to metastasis is now clear to us since their micro-parasitic nature has been proved. But, putting aside the micro-parasitic tumours, which are sometimes, but not very appropriately in veterinary pathology, grouped together under the term granulomata, it is to be observed that three distinct classes of neoplasms proper possess the characters of malignancy. These are the two now under consideration, and the sarcomata. By referring to the table on page 36, it will be seen that the sarcomata belong to the class of simple histioid tumours, and that they are, therefore, totally distinct from the adenomata and the carcinomata. Their detailed consideration, illustrated by examples found in the series of tumours sent to me, must be reserved for a subsequent article. The adenomata and the carcinomata resemble each other in so far as the chief element in their structure is epithelium. In the adenomata the epithelium is arranged after the manner of a gland, while in the carcinomata it exhibits no regularity in its arrangement, but presents itself in the form of irregular columns and groups of cells burrowing into the connective tissue of the part. The fundamental difference between the two classes will be best brought out by describing and figuring a few examples of each. Tumour IV, Adenoma of the Liver of a SlleeP.-This tumour, which was sent by Mr Tailby of Birmingham, is a typical example of the adenomata, and, in several respects, it is one of the most remarkable tumours of the series. It was situated in the liver of a ewe, and it formed an irregularly rounded mass, about as large as the two fists. The animal, which was pregnant, and within one month of parturition, had died somewhat suddenly after a short illness, in which the only symptoms noticed were dulness, loss of appetite, and injection of the conjunctival vessels. The general tint of the tumour was similar to that of the grey matter of the brain, and in consistence it was a little firmer than the brain substance. It had a well defined boundary, and a distinctly lobulated character, being traversed by fine strands of vascular connective tissue. . On examining a section cut from it in the fresh state, I found that
GENERAL ARTICLES.
it appeared to be mainly composed of roundish nucleated cells, each of which contained a large fat globule. Surmising that this was a degenerated portion of the growth, I cut sections from other parts, and thus soon discovered that I had to deal with an adenoma.· The accompanying figure will illustrate the minute structure of the tumour. A glance suffices to show that there is here present a most remarkable simulation of gland structure, the organ which is most strongly recalled being the mammary gland. There are seen cut in various directions large and smaller acini lined by epithelium. Between these acini there is a delicate vascular connective tissue. Save in respect of the irregular size of the glandular spaces, the tumour at many parts so closely resembles the mammary gland of the cow, that even an experienced histologist might readily be mistaken. What renders the resemblance all the more striking is, that in many instances the lining epithelium contains conspicuous fat droplets, such as are formed in the gland cells of the active udder. Moreover, in some of the acini (see
FIG. 2.-Adenoma. from the liver of a s heep ( x 40). 1. Transverse section of" mrg. acinus lined by a single layer of cubical or short columnar epithelium ; 2. An irregular group of acini; 3. Delicate interacinous connective tissue.
the large acinus above the line leading from 3 in the figure) the lumen contains a granular material which appears to be a product of the lining epithelium. At some places the vesicular or glandular appearance is obscured or lost, apparently in consequence of irregular proliferation of the epithelial cells and subsequent infiltration of them with fat. Lastly, it may be mentioned that the entire tumour is divided into lobules by septa of connective tissue carrying the larger blood-vessels, the lobulation being almost as distinct and regular as in the normal mammary gland. One of the most interesting questions raised by this tumour is, What was its starting point? From the large size of the growth, and the fact that no others were detected at the post-mortem, there can be little doubt that it was a primary growth; and if so, according to present beliefs, we must conclude that the epithelial cells of the tumour had their origin in liver cells, or in epithelium of the bile ducts. But, on the other hand, if such was the starting point of the tumour, it
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is remarkable that its type of structure should be so different from that of either the liver parenchyma or the bile ducts. Tumour V. Carcinoma of a Cat's TOllglte.-I select this in the next place as an excellent example of a carcinoma. The tumour grew on the tongue of a cat, as shown in Fig. 3, and it was handed to me by Professor Walley. The cat was a male, and aged twelve years. It had been ill for about two months prior to the date at which it was killed, the symptoms observed being discharge of saliva
FIG. 3.-Mesially divided tongue of a cat shpwing carcinoma (natural size). 1. The twnour; 2. Ulcerating surface of the SRme.
with occasional streaks of blood, difficulty of mastication and deglutition, and progressive emaciation. The minute structure of the tumour is shown in Fig. 4. Here, as in the previous tumour, we have epithelium and vascular connective tissue, but in this c~se there is no regularity in the grouping of the epithelial cells, nor are the latter arranged so as to leave any lumen or acinus in the group. The tumour is composed essentially of
FlO. 4.-Carcinoma of the tongue of a cat (x 80). 1. Irregular group of epithelial cells with large nuclei; 2. Colloid material in the centre of another group, resulting from degeneration of the epithelium; 3. The delicate" stroma" or connectIve tissue of the tumour.
masses of epithelium burrowing along the lymphatic spaces between the muscular fibres of the tongue. The epithelium resembles pretty closely that of the deepest layer of the buccal mucous membrane. Each cell has a large nucleus and ,a deeply-staining (carmine) nuc-· leolus. The central cells in the larger masses of epithelium, probably in consequence of defective nutritive supply, have undergone colloid degeneration. ' This tongue has afforded very beautiful sections 'showing, at' the
GENERAL ARTICLES.
peripheral part of the tumour, the penetration of the epithelium into the muscular bundles, and the mode of origin of the fine connective tissue which forms the so-called "stroma" of the new growth. In transverse sections of the normal bundles of muscular fibres the connective tissue is very s.paring in amount; indeed, at many places it is limited to an occasional connective tissue corpuscle between the adjacent muscular fibres, or between the latter and the capillaries. But, coincidently with the penetration of the advancing epithelium into the fasciculus of muscular fibres, the connective tissue cells begin to proliferate. The new cells speedily assume a spindle shape, and unite to form a very fine variety of connective tissue, with numerous nuclei, all elongated in the same direction. The proportion of stroma to epithelium varies greatly in different carcinomata, and upon this depends the consistence of the tumour. When the stroma is very sparing in amount, the tumour is soft or "medullary;" when, on the other hand, it is present in large amount, it confers on the tumour a " scirrhous" character. These terms are of little value, for all gradations in firmness are found in the carcinomata.
FIG. 5.-Anal adenoma of the dog (x 80). 1. Large epithelial cells, limited outwardly by-2. The basement membrane formed by a single layer of small flat (endothelioid) cells. 3. Delicate interacinous connective tissue containmg capillary vessels.
Sometimes the stroma is in large measure composed of the original connective tissue framework of the part that the epithelium is invading, but at other times, as in this case, it is almost entirely a new formation. In this tongue the invasion of the muscular fasciculi by the epithelium appears to excite the connective tissue to proliferate, as under the influence of a mild and sustained irritation; and as this proliferation proceeds, the intervening muscular fibres steadily become atrophied, and eventually disappear. The starting point of this tumour was probably at some spot of mucous membrane on the under surface of the tongue. At that part the integrity of the mucous membrane was destroyed, but the membrane was still intact over the sides and dorsum of the organ. Tumours VI., VI!., and VIII. Adenomata from the Anal Region of the Dog.--These also are very interesting growths. They are absolutely identical in structure, and all grew in the same region, viz.,
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near the anus. One of them was removed by me from an aged retriever dog which was poisoned at the college, and the second was recently excised by Mr Archibald Baird from a terrier. Both of these formed free projections at the point mentioned, and indeed the latter of the two was attached merely by a narrow pedicle. The tumours were about as large as a pullet's egg and were covered by a thin and hairless but intact continuation of the skin. Their consistence was about equal to that of the normal pancreas. The third tumour, which was sent by Mr F. G. Ashley of Bath, grew in still closer proximity to the anus, so close indeed that it had proved an obstacle to defecation. The owner would not consent to having the tumour excised,and the dog had eventually to be destroyed. The tumour was about as large as a walnut, and it did not appear to have any connection with the anal pouches, both of which were intact and normal. These tumours show a distinctly adenomatous type of structure, but, nevertheless, they differ in one important respect from the adenoma of the sheep's liver already described. This difference is apparent on comparing Figs. 2 and 5. In Fig. 5 we have, as before, a simulation of gland structure, the epithelium being arranged after the manner of a tubulo-acinous gland. Here, however, the epithelium forms solid masses, without any lumen. Furthermore-and this forms one of the most notable features of the tumours-there are here two
FIG. 6.-Epithelial cells from anal adenoma of dog.
distinct varieties of cells. Each tube or acinus is limited next the interglandular tissue by a sort of basement membrane of small flat cells with round deeply-staining nucl~i, and within this there is a mass of large polygonal epithelial cells, with faintly-staining nuclei. It will be noted that the presence of this basement membrane, and the regularity of the proportion between epithelium and stroma, distinctly mark out the adenomatous nature of the tumours, and sharply distinguish them from the carcinomata. A remarkable feature of the epithelium is the great variety of shapes exhibited by the cells, four of which are accurately reproduced in Fig. 5. As will be observed, they bear some resemblance to transitional epithelium, such as that of the ureter or bladder. The interacinous connective tissue in these tumours is arranged with as much regularity as in any normal gland, forming thicker septa that divide the tumour into lobular segments, and sending delic~te prolongations to support the capillaries within each lobule. As a point of practical importance, it may be mentioned that these tumours are very vascular, and a good deal of h
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GENERAL ARTICLES.
Tumour IX. Carcinoma from the Anus of a Dog.-I take this tumour, in the next place, as forming a contrast to the two just described, although it arose at nearly the same point. It was removed by me from the anus of a fox-terrier, which had been poisoned on account of the growth, and which was brought to me by Mr C. D. Watkins. It was situated in immediate proximity to the anus, having rectal mucous membrane on its upper, and ulcerating skin on its posterior, aspect. It had a firm semi-fibrous consistence,
P IO. 7.-Cell-nests from a carcinoma o f the anus o f a dog (X 40). 1. Unaltered m arginal epithelium; 2. A "concentric globe " of closely-pressed and horny epithelial cells ; 3. The stroma of the tumour. (The space arounfl the" concent ric globes " is due to greater shrinking o f these in the alcohol employed to hal'den t he t urnout.)
and it was about the s ize of a walnut. In structure it is a typical carcinoma, belonging to that variety which is sometimes termed epithelioma. The most n oteworthy feature of the growth is the large number of so-called "concentric globes " or "birds'-nest bodies." Th ese are very common in carcinomata that have their starting point in cutaneous epithelium. They are simply transverse sections of groups of epithelium in which, apparently as the result of continued prolifera-
FlO. S. -Carcinoma from t he orbit of a horse (x 80). 1. A group of epithelial cella; 2. A group of cella undergoing colloid degeneration; 3. Stroma of the tumour.
tion of the marginal cells. the central elements have become compressed into the form of spindles arranged concentrically around one or more points in the group. The deformation is somewhat similar to that experienced by the cells o f the stratum corneum of the skin, and, as in that layer, so here, the deformed cells have undergone a horny transformation. No doubt this tumour had its origin in the skin on the
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verge of the anus, which, as already mentioned, was ulcerating, while the rectal mucous membrane appeared to be intact. TUllZour X. Carcinoma of the Orbital Structures of a Horse.- This tumour was brought under my notice by Professor Baird. I t formed a large ulcerating mass, which completely filled up the orbit, and it had also invaded the eyelids, the upper one especially being greatly thickened. About a year prior to the time at which the horse was killed on account of the growth, Professor Baird had excised the eye, which was partially destroyed by a tumour. I had not the opportunity to examine the primary tumour, but in all probability it was of the same nature as the one which speedily re-formed, and whose structure is shown in the annexed figure. The tumour had a scirrhous consistence, and, as the illustration shows, it possesses a rather abundant stroma. The connective tissue in this case is for the most part coarsely fibrous and sparsely nucleated, but at some points there is a notable proportion of nuclei, indicating the young growing parts of the stroma. The epithelial cells resemble those of the rete mucosum, and in many of the larger groups the central cells are in a condition of colloid degeneration, but there are no " concentric globes." [In the next article the other epithelial tumours of the series, numbering about a dozen, and mainly mammary growths, will be described and illustrated.]
ED I TO RIAL
ART I CLES.
--0--
VOMITION AND RUPTURE OF THE STOMACH IN THE HORSE.
A T a recent meeting of the Pathological Society of London,1 Mr Spencer described an unique case, in which a portion of the wall of a horse's stomach had become prolapsed into the duodenum. The cardiac end of the stomach had become inverted, and the inversion had extended across the cavity of the stomach into the duodenum. The prolapse beyond the pylorus formed a sausage-shaped mass about a foot in length and nine inches in circumference. It consisted of all the coats of the stomach much thickened by inflammation and congestion. In commenting upon this case, Mr Spencer said, that whilst the horse's stomach did not differ materially from man's, except by having an intra-abdominal cesophagus, the animal hardly ever vomited except when the stomach was ruptured. We confess to having read with surprise that a member of the Pathological Society of London had gravely adopted this venerable but absurd opinion regarding the cause of vomition in the equine species. It is well- known to every horse1
British Medical Journal, lIIarch S, 1890, p. 543.
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THE OCCURRENCE OF TUMOURS IN THE DOMESTICATED ANIMALS.
By J. M'FADYEAN, M.B., B.Sc., F.R.S.E., Royal Veterinary College, Edinburgh. DU~ING the past year there was inserted ilJ each number of this Journal a notice to subscribers requesting them to send to the Editor all tumours excised by them, with the view of collecting information regarding the occurrence of cancer among the domesticated animals. This appeal has brought to me a considerable number of specimens, and in fulfilment of the promise made it is now my duty to report the result of a careful microscopic examination of the material that has thus come into my hands. In order to render such a description intelligible and useful to all the readers of the Journal, it may be necessary, at the outset, to devote some space to a consideration of (I) what is meant by the words tumour and neoplasm, and (2) what is the import of certain terms used in the classification of such formations. The word tumour may be applied to any circumscribed morbid swelling or enlargement. In this sense an actinomykoma, an abscess, a cyst, or a neoplasm proper is a tumour. In the same way we are accustomed to speak of "splenic tumour" in referring to what is merely a congestive swelling of the spleen, and of the tumour of black quarter (symptomatic anthrax), where the enlargement is due to congestion, blood extravasation, and inflammatory exudate. The term neoplasm is much more restricted in its application. To define briefly and accurately the meaning of the word is a matter of some difficulty, as is exemplified by the fact that no two authors give exactly the same definition. The essential nature of a neoplasm may be best explained by stating what it is not, as well as what it is. A neoplasm is an abnormal, non-inflammatory, new growth. It is composed of newly formed histological elements, a.nd does not result from a mere transformation of pre-existing normal textures. An actinomykoma-that is the tumour-like formation caused by the presence of the actinomyces in the tissT,les-is not a neoplasm. I t is in reality a slowly growing inflammatory tumour. Thus, by using the term non-inflammatory in our definition, we separate from the neoplasmata almost every instance of abnormal new growth occurring in the adult animal, save hypertrophy. The fundamental difference between the new elements formed in hypertrophy (such as the increase of muscular tissue in the left ventricle of the heart in aortic stenosis), and those that constitute a neoplasm, is that the former comport themselves like the normal elements of the part, in that they obey the same morphological laws, and therefore do not distort the organ in which they are formed. A neoplasm, on the other hand, does not obey the laws that govern the form of the organ or part in which it has its origin. Speaking metaphorically, it is composed of rebellious elements, which have broken away from the normal parts, and which, henceforth, maintain towards the rest of the organism a state of semi-independence. Neoplasms have, therefore, been aptly compared to parasites, growing in, and at the expense of, some tissue or organ of the body.
GENERAL ARTICLES.
Although most recent authors on pathology draw this distinction between tumour and neoplasm, the former term is still in very general use, the tendency being towards restricting the original meaning of the word, so as to make it synonymous with the term neoplasm as above defined. It is in this restricted sense that it is used throughout this article. Classificatioll of TUJIlouys.-When the pathologist comes to study the minute anatomy of the neoplasmata, he finds a close correspondence between their histological elements and those that compose the normal textures of the animal body. Thus we have tumours composed of muscular fibres, others of fibrous connective tissue, others of cartilage, and so on. In modern pathology the classification of tumours is based upon their minute structure, as is shown in the subjoined table. CLASS A. SIMPLE HISTIOID NEOPLASMATA, resembling one of the simple textures of the body. Histological Type. Neoplasm. Embryonic connective tissue. I. Sarcoma 2. Fibroma Fibrous and areolar connective tissue. Gelatinous connective tissue. 3. Myxoma Connective tissue of brain and spinal cord. 4. Glioma* Adipose tissue. 5. Lipoma 6. Chondroma Cartilage. Bone tissue. 7. Osteoma*" 8. Odontoma Dentine. Muscular tissue (plain or striated). 9. Myoma 10. Neuroma*" Nerve fibres. CLASS B. COMPOUND HISTIOID NEOPLASMATA, more complex in structure than those of Class A. Comprise elements of two or more simple tissues.
jVeoplasm. Angeioma 2. Papilloma } 3. Adenioma 4. Carcinoma I.
Component Textures. Blood or lymph vessels and connective tissue. Epithelium and vascular connective tissue.
I have thought it well to thus set forth in tabular form the chief varieties of neoplasmata that have been met with in human pathology; but, so far as the main purpose of this article is concerned, the three classes marked with an asterisk might have been omitted, inasmuch as no example of these is included in the list of tumours here to be reported upon. EPITHELIAL TUMOURS.
I have selected for first consideration the epithelial tumours, as in several respects these form the most interesting group of new formations. The term epithelial, as it is here used, is not intended to imply that these neoplasmata are entirely composed of epithelium, but that in all of them epithelium is the essential histological element. The group comprises three distinct classes of growths, differing fundamentally as regards the arrangement of the epithelium and its relationship to the other elements of the tumours. These are-(I) the papillomata, (2) the adenomata, and (3) the carcinomata.
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THE PAPILLOMATA. A papilloma has a structure comparable to that of one of the normal papilla: found in mucous membranes, such as those of the tongue in all mammals, or of the first stomach of the domestic ruminants. It possesses a core of vascular connective tissue and a surface covering of epithelium. A common wart of the human hand has this type of structure, and is, therefore, a papilloma. The axial connective tissue is in direct continuity with the corium of the skin or the corresponding stratum of connective tissue in a mucous membrane, and, in like manner, the investing epithelium is continuous with and originally derived from the normal epidermis or epithelium. As a rule the connective tissue core of the tumour gives off secondary branches, which may again branch, the ultimate divisions being always invested by epithelium. In this way considerable tumours may be formed. As illustrative of this class of epithelial tumours I may describe, in the first place, a very interesting example sent by Mr S. Beeson, of Hereford.
FIG. I.-Section from a large cauliflower papilloma of the penis of a horse (x 20). 1. Connective tissue stem; 2. A branch of the same cut longitudinally; 3. Another branch cut transversely; 4. EpIthelium. The darker shading in the epithelium indicates the younger cells, corresponding to those of the rete mucosum.
Tumour /.- This tumour was removed by Mr Beeson from the end of the penis of an aged grey gelding. It was attached to the glans immediately behind the meatus urinarius. The growth had been first observed during the spring of r889, and it had been removed by another practitioner about the month of April. It immediately began to form again, and it was excised by Mr Beeson in the following July. The owner had an idea that the tumour had its starting point in an injury to the penis, inflicted by the horse falling across a rail while hunting during the previous season. The tumour weighed about 4 ounces, and it had a most striking resemblance to a cauliflower head, having a main stem from which proceeded secondary and tertiary branches. The minute structure of one of the small surface projections of the growth is depicted in the accompanying illustration (Fig. I). The wart-like nodule, of which this represents a section, measured about ~-th of an inch in diameter at its widest part. It is seen to have an arborescent core of connective
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tissue, the ultimate branches being imbedded in a mass of epithelial cells. The axial substance has the characters of young, succulent connective tissue. It is richly nucleated and provided with conspicuous blood-vessels, and from it branches pass in all directions. The lighter areas on the right half of the figure are ramifications of the connective tissue core cut transversely. The epithelium, where it is in contact with the connective tissue, is identical with the deepest stratum of the rete mucosum of the skin, forming a continuous layer of actively multiplying cells with a relatively small amount of protoplasm and a deeply staining nucleus. Farther outwards the cell body is larger and in a condition of incomplete horny transformation, while the nucleus is distorted and imperfectly stained. In this particular projection the epithelium, even in its outermost strata, is comparatively soft, but in some other branches of the tumour there is a distinct stratum corneum. Lastly, it may be mentioned, as a point of interest, that in sections of the main stem of the tumour there are occasional cell groups lying remote from, and apparently unconnected with, the surface mass of epithelium. At these parts it looks as if the growth had been on the point of assuming a carcinomatous character. Tumour Il.-This tumour had a structure identical with the one just described. It was removed by Mr Shillingford, of Buckingham, from the hard palate of a horse. The growth weighed about 8 ounces. Tumour III.-This specimen, which was sent by Mr Menzies of St. Austell, Cornwall, was not a single tumour, but a large number of papillomata growing on the hard palate and cheeks of a dog. The largest of these were slightly branched, and about i: of an inch in length. Their epithelial covering was almost white. The mouth of the dog is a not uncommon seat of these mUltiple warts, and I am constrained to quote here a reference to a mode of treating them which appears to yield eminently satisfactory results. In the Noulleau D£ct£01l1Ia£re Pratique (p. 399), Professor Trasbot, of the Alfort Veterinary College, says :-" To-day we possess an agent, one of the most inoffensive, which appears to yield surprising results, viz., calcined magnesia. Lambert, of Haguenau, was the first to speak of it; M. Gueneau of Mussy recalled it to the Societe de Therapeutique. We have employed it for nearly two years; at first, we confess, without any hope of success, and with a certain amount of astonishment we have proved its remarkable efficacy. All the dogs to which we have administered it-and they are now numerous-have recovered in from one to three weeks. From half a gramme (a gramme = 15 grains, nearly) to a gramme or a gramme and a half is administered daily according to the size. After some days one sees the warts become blanched and shrivelled, and they gradually disintegrate and disappear." THE ADENOMATA AND THE CARCINOMATA.-These two varieties of neoplasmata embrace the greater number of the new growths which popularly are known as cancers. At the present day the tendency in pathological nomenclature is to discard the term cancer altogether, or, if retaining it, to use it synonymously with the word carcinoma. I fear it must be admitted that in veterinary pathology there is still considerable looseness in the mode of using these terms. In this connection it ought to be remembered that the
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malignancy of a tumour is no criterion of its proper place under the modern system of classifying such formations. In order to illustrate. that point, a word may be necessary regarding the use of the term " malignant" as applied to tumours. A neoplasm deserves to be called malignant (I) when it steadily invades and destroys the surrounding textures, and exhibits a marked tendency to recur at the primary seat after excision, or (2) when it reproduces itself by metastasis-that is to say, when secondary tumours, identical in structure with the first, grow in the nearest group of lymphatic glands or in some of the internal organs. Both of these characters of malignancy are exhibited in common by growths which are now excluded from the neoplasmata, and by several distinct varieties of true neoplasmata. For example, an actinomykoma is apt to recur locally after an attempt to remove it, and not rarely secondary growths of the same nature form in the nearest lymphatic glands. The same may be said of tubercular tumours. But, as already explained, these growths are not neoplasmata, and the explanation of their tendency to local recurrence and to metastasis is now clear to us since their micro-parasitic nature has been proved. But, putting aside the micro-parasitic tumours, which are sometimes, but not very appropriately in veterinary pathology, grouped together under the term granulomata, it is to be observed that three distinct classes of neoplasms proper possess the characters of malignancy. These are the two now under consideration, and the sarcomata. By referring to the table on page 36, it will be seen that the sarcomata belong to the class of simple histioid tumours, and that they are, therefore, totally distinct from the adenomata and the carcinomata. Their detailed consideration, illustrated by examples found in the series of tumours sent to me, must be reserved for a subsequent article. The adenomata and the carcinomata resemble each other in so far as the chief element in their structure is epithelium. In the adenomata the epithelium is arranged after the manner of a gland, while in the carcinomata it exhibits no regularity in its arrangement, but presents itself in the form of irregular columns and groups of cells burrowing into the connective tissue of the part. The fundamental difference between the two classes will be best brought out by describing and figuring a few examples of each. Tumour IV, Adenoma of the Liver of a SlleeP.-This tumour, which was sent by Mr Tailby of Birmingham, is a typical example of the adenomata, and, in several respects, it is one of the most remarkable tumours of the series. It was situated in the liver of a ewe, and it formed an irregularly rounded mass, about as large as the two fists. The animal, which was pregnant, and within one month of parturition, had died somewhat suddenly after a short illness, in which the only symptoms noticed were dulness, loss of appetite, and injection of the conjunctival vessels. The general tint of the tumour was similar to that of the grey matter of the brain, and in consistence it was a little firmer than the brain substance. It had a well defined boundary, and a distinctly lobulated character, being traversed by fine strands of vascular connective tissue. . On examining a section cut from it in the fresh state, I found that
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it appeared to be mainly composed of roundish nucleated cells, each of which contained a large fat globule. Surmising that this was a degenerated portion of the growth, I cut sections from other parts, and thus soon discovered that I had to deal with an adenoma.· The accompanying figure will illustrate the minute structure of the tumour. A glance suffices to show that there is here present a most remarkable simulation of gland structure, the organ which is most strongly recalled being the mammary gland. There are seen cut in various directions large and smaller acini lined by epithelium. Between these acini there is a delicate vascular connective tissue. Save in respect of the irregular size of the glandular spaces, the tumour at many parts so closely resembles the mammary gland of the cow, that even an experienced histologist might readily be mistaken. What renders the resemblance all the more striking is, that in many instances the lining epithelium contains conspicuous fat droplets, such as are formed in the gland cells of the active udder. Moreover, in some of the acini (see
FIG. 2.-Adenoma. from the liver of a s heep ( x 40). 1. Transverse section of" mrg. acinus lined by a single layer of cubical or short columnar epithelium ; 2. An irregular group of acini; 3. Delicate interacinous connective tissue.
the large acinus above the line leading from 3 in the figure) the lumen contains a granular material which appears to be a product of the lining epithelium. At some places the vesicular or glandular appearance is obscured or lost, apparently in consequence of irregular proliferation of the epithelial cells and subsequent infiltration of them with fat. Lastly, it may be mentioned that the entire tumour is divided into lobules by septa of connective tissue carrying the larger blood-vessels, the lobulation being almost as distinct and regular as in the normal mammary gland. One of the most interesting questions raised by this tumour is, What was its starting point? From the large size of the growth, and the fact that no others were detected at the post-mortem, there can be little doubt that it was a primary growth; and if so, according to present beliefs, we must conclude that the epithelial cells of the tumour had their origin in liver cells, or in epithelium of the bile ducts. But, on the other hand, if such was the starting point of the tumour, it
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is remarkable that its type of structure should be so different from that of either the liver parenchyma or the bile ducts. Tumour V. Carcinoma of a Cat's TOllglte.-I select this in the next place as an excellent example of a carcinoma. The tumour grew on the tongue of a cat, as shown in Fig. 3, and it was handed to me by Professor Walley. The cat was a male, and aged twelve years. It had been ill for about two months prior to the date at which it was killed, the symptoms observed being discharge of saliva
FIG. 3.-Mesially divided tongue of a cat shpwing carcinoma (natural size). 1. The twnour; 2. Ulcerating surface of the SRme.
with occasional streaks of blood, difficulty of mastication and deglutition, and progressive emaciation. The minute structure of the tumour is shown in Fig. 4. Here, as in the previous tumour, we have epithelium and vascular connective tissue, but in this c~se there is no regularity in the grouping of the epithelial cells, nor are the latter arranged so as to leave any lumen or acinus in the group. The tumour is composed essentially of
FlO. 4.-Carcinoma of the tongue of a cat (x 80). 1. Irregular group of epithelial cells with large nuclei; 2. Colloid material in the centre of another group, resulting from degeneration of the epithelium; 3. The delicate" stroma" or connectIve tissue of the tumour.
masses of epithelium burrowing along the lymphatic spaces between the muscular fibres of the tongue. The epithelium resembles pretty closely that of the deepest layer of the buccal mucous membrane. Each cell has a large nucleus and ,a deeply-staining (carmine) nuc-· leolus. The central cells in the larger masses of epithelium, probably in consequence of defective nutritive supply, have undergone colloid degeneration. ' This tongue has afforded very beautiful sections 'showing, at' the
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peripheral part of the tumour, the penetration of the epithelium into the muscular bundles, and the mode of origin of the fine connective tissue which forms the so-called "stroma" of the new growth. In transverse sections of the normal bundles of muscular fibres the connective tissue is very s.paring in amount; indeed, at many places it is limited to an occasional connective tissue corpuscle between the adjacent muscular fibres, or between the latter and the capillaries. But, coincidently with the penetration of the advancing epithelium into the fasciculus of muscular fibres, the connective tissue cells begin to proliferate. The new cells speedily assume a spindle shape, and unite to form a very fine variety of connective tissue, with numerous nuclei, all elongated in the same direction. The proportion of stroma to epithelium varies greatly in different carcinomata, and upon this depends the consistence of the tumour. When the stroma is very sparing in amount, the tumour is soft or "medullary;" when, on the other hand, it is present in large amount, it confers on the tumour a " scirrhous" character. These terms are of little value, for all gradations in firmness are found in the carcinomata.
FIG. 5.-Anal adenoma of the dog (x 80). 1. Large epithelial cells, limited outwardly by-2. The basement membrane formed by a single layer of small flat (endothelioid) cells. 3. Delicate interacinous connective tissue containmg capillary vessels.
Sometimes the stroma is in large measure composed of the original connective tissue framework of the part that the epithelium is invading, but at other times, as in this case, it is almost entirely a new formation. In this tongue the invasion of the muscular fasciculi by the epithelium appears to excite the connective tissue to proliferate, as under the influence of a mild and sustained irritation; and as this proliferation proceeds, the intervening muscular fibres steadily become atrophied, and eventually disappear. The starting point of this tumour was probably at some spot of mucous membrane on the under surface of the tongue. At that part the integrity of the mucous membrane was destroyed, but the membrane was still intact over the sides and dorsum of the organ. Tumours VI., VI!., and VIII. Adenomata from the Anal Region of the Dog.--These also are very interesting growths. They are absolutely identical in structure, and all grew in the same region, viz.,
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near the anus. One of them was removed by me from an aged retriever dog which was poisoned at the college, and the second was recently excised by Mr Archibald Baird from a terrier. Both of these formed free projections at the point mentioned, and indeed the latter of the two was attached merely by a narrow pedicle. The tumours were about as large as a pullet's egg and were covered by a thin and hairless but intact continuation of the skin. Their consistence was about equal to that of the normal pancreas. The third tumour, which was sent by Mr F. G. Ashley of Bath, grew in still closer proximity to the anus, so close indeed that it had proved an obstacle to defecation. The owner would not consent to having the tumour excised,and the dog had eventually to be destroyed. The tumour was about as large as a walnut, and it did not appear to have any connection with the anal pouches, both of which were intact and normal. These tumours show a distinctly adenomatous type of structure, but, nevertheless, they differ in one important respect from the adenoma of the sheep's liver already described. This difference is apparent on comparing Figs. 2 and 5. In Fig. 5 we have, as before, a simulation of gland structure, the epithelium being arranged after the manner of a tubulo-acinous gland. Here, however, the epithelium forms solid masses, without any lumen. Furthermore-and this forms one of the most notable features of the tumours-there are here two
FIG. 6.-Epithelial cells from anal adenoma of dog.
distinct varieties of cells. Each tube or acinus is limited next the interglandular tissue by a sort of basement membrane of small flat cells with round deeply-staining nucl~i, and within this there is a mass of large polygonal epithelial cells, with faintly-staining nuclei. It will be noted that the presence of this basement membrane, and the regularity of the proportion between epithelium and stroma, distinctly mark out the adenomatous nature of the tumours, and sharply distinguish them from the carcinomata. A remarkable feature of the epithelium is the great variety of shapes exhibited by the cells, four of which are accurately reproduced in Fig. 5. As will be observed, they bear some resemblance to transitional epithelium, such as that of the ureter or bladder. The interacinous connective tissue in these tumours is arranged with as much regularity as in any normal gland, forming thicker septa that divide the tumour into lobular segments, and sending delic~te prolongations to support the capillaries within each lobule. As a point of practical importance, it may be mentioned that these tumours are very vascular, and a good deal of h
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Tumour IX. Carcinoma from the Anus of a Dog.-I take this tumour, in the next place, as forming a contrast to the two just described, although it arose at nearly the same point. It was removed by me from the anus of a fox-terrier, which had been poisoned on account of the growth, and which was brought to me by Mr C. D. Watkins. It was situated in immediate proximity to the anus, having rectal mucous membrane on its upper, and ulcerating skin on its posterior, aspect. It had a firm semi-fibrous consistence,
P IO. 7.-Cell-nests from a carcinoma o f the anus o f a dog (X 40). 1. Unaltered m arginal epithelium; 2. A "concentric globe " of closely-pressed and horny epithelial cells ; 3. The stroma of the tumour. (The space arounfl the" concent ric globes " is due to greater shrinking o f these in the alcohol employed to hal'den t he t urnout.)
and it was about the s ize of a walnut. In structure it is a typical carcinoma, belonging to that variety which is sometimes termed epithelioma. The most n oteworthy feature of the growth is the large number of so-called "concentric globes " or "birds'-nest bodies." Th ese are very common in carcinomata that have their starting point in cutaneous epithelium. They are simply transverse sections of groups of epithelium in which, apparently as the result of continued prolifera-
FlO. S. -Carcinoma from t he orbit of a horse (x 80). 1. A group of epithelial cella; 2. A group of cella undergoing colloid degeneration; 3. Stroma of the tumour.
tion of the marginal cells. the central elements have become compressed into the form of spindles arranged concentrically around one or more points in the group. The deformation is somewhat similar to that experienced by the cells o f the stratum corneum of the skin, and, as in that layer, so here, the deformed cells have undergone a horny transformation. No doubt this tumour had its origin in the skin on the
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verge of the anus, which, as already mentioned, was ulcerating, while the rectal mucous membrane appeared to be intact. TUllZour X. Carcinoma of the Orbital Structures of a Horse.- This tumour was brought under my notice by Professor Baird. I t formed a large ulcerating mass, which completely filled up the orbit, and it had also invaded the eyelids, the upper one especially being greatly thickened. About a year prior to the time at which the horse was killed on account of the growth, Professor Baird had excised the eye, which was partially destroyed by a tumour. I had not the opportunity to examine the primary tumour, but in all probability it was of the same nature as the one which speedily re-formed, and whose structure is shown in the annexed figure. The tumour had a scirrhous consistence, and, as the illustration shows, it possesses a rather abundant stroma. The connective tissue in this case is for the most part coarsely fibrous and sparsely nucleated, but at some points there is a notable proportion of nuclei, indicating the young growing parts of the stroma. The epithelial cells resemble those of the rete mucosum, and in many of the larger groups the central cells are in a condition of colloid degeneration, but there are no " concentric globes." [In the next article the other epithelial tumours of the series, numbering about a dozen, and mainly mammary growths, will be described and illustrated.]
ED I TO RIAL
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VOMITION AND RUPTURE OF THE STOMACH IN THE HORSE.
A T a recent meeting of the Pathological Society of London,1 Mr Spencer described an unique case, in which a portion of the wall of a horse's stomach had become prolapsed into the duodenum. The cardiac end of the stomach had become inverted, and the inversion had extended across the cavity of the stomach into the duodenum. The prolapse beyond the pylorus formed a sausage-shaped mass about a foot in length and nine inches in circumference. It consisted of all the coats of the stomach much thickened by inflammation and congestion. In commenting upon this case, Mr Spencer said, that whilst the horse's stomach did not differ materially from man's, except by having an intra-abdominal cesophagus, the animal hardly ever vomited except when the stomach was ruptured. We confess to having read with surprise that a member of the Pathological Society of London had gravely adopted this venerable but absurd opinion regarding the cause of vomition in the equine species. It is well- known to every horse1
British Medical Journal, lIIarch S, 1890, p. 543.