Part 46

Within the classes the comparative figures have less value because of the smaller and varying numbers. Such high percentages as are shown by the elephants and armadillos cannot be taken as indicators for their orders since too few specimens were examined. Judging by orders with more than one hundred autopsies the rodents stand at the head of the list followed by the marsupials and carnivores. It is interesting that the animal nearest to man, the monkey, and with greatest number of autopsies in its zoological class, has the lowest tumor incidence. Psittaci lead the avian orders, followed by the Fulicariæ, but as there are but thirty-five autopsies upon these, the second place rightly belongs to the Anseres. All the principal orders are represented but the only one of importance is the leader. The Psittaci are very prone to have tumors in the renal area, sometimes of the kidney, at others of the adrenal and occasionally of the sex glands. Some remarks have already been given to this matter in the sections devoted to the kidney and genitalia but it will be discussed again under tumor morphology.

Among these ninety-two animals, one bore multiple tumors, a Jaguar (_Felis onca_) with adenomata of the liver and uterus and angiomata of the mesentery. Careful study failed to reveal any parasitism as the cause of the growths and since the first two were of slightly varying structure it is not believed that one is a metastasis from the other.

The sex incidence stands in direct relation to the proportion of total males and females posted or in other words it is the same for the two. The figures might be somewhat affected were the gender of all the parrakeets available but the tumors growing in the upper renal area frequently destroy the sex gland.

Definite statements concerning the importance of breeding in the causation of neoplasms cannot be made since we cannot quote figures for the percentages of wild- and captive-born of our entire autopsy list. The data are confused by scanty information concerning the twenty-six parrots, the history of which is vague and I am perhaps too severe in accrediting the birth of sixteen of them to captivity. This was done because of a lack of exact information concerning these specimens and, because their variety is known to breed when captive by the residents of their habitat[94], the distribution into wild- and captive-born is based upon what information we have. If the order Psittaci be subtracted entirely, it leaves a total of 62 tumor-bearing animals of known breeding, 49 of which were born in the wild, thirteen in captivity, a fact which strengthens the thought that unnatural breeding increases the chance of neoplasms.

The known length of captivity has also a direct bearing on this point. The figures given in the columns “known captivity” and “average for tumor bearers” were compared with figures obtained by averaging the lives of fifty others (when possible) of the same order or of at least three times as many as bore tumors. Animals dying from injury were excluded. With one exception the average for “tumor bearers” exceeded that for “non-tumor bearers”; the exception, the Ungulata, had the same average for both groups. It seems then that tumors occur in animals in captivity longer than the average for their order, or in specimens that have the power to live under confined conditions until neoplasms develop. In this respect I recall the statements made by Harlow Brooks[95] that tumors will probably be found more commonly in animals when they live in a manner comparable to that of urban man and that racial degeneracy will favor their development. There is adduced here perhaps the first definite evidence that long captivity allows tumor tendency to express itself but it does not prove that confinement increases tumors. Nor does the expectation of life, average or potential, stand in any direct and definite relationship to the frequency of neoplasms. The only clear case of long life and high tumor incidence is to be found in Parrots; we feel however that some unknown factor increases tumors of the renal-adrenal region in these birds and that unqualified statements about age and tumor growth are not permissible. Since tumors grow in many wild-born specimens, a high percentage of which become known in the first few years of captivity, is it not highly probable that tumors are reasonably common in the wild and that we do not observe enough purely natural specimens to assume an immunity on the part of free living beasts.

One of the undesirable features of captive breeding is consanguinity of parents and there is good reason to believe that tumor susceptibility can be bred into or out of a line of animals by mating tumor bearers and non-tumor bearers, the tendency following the rules of Mendelian inheritance (Slye). Is there any proof that inbreeding does not occur in the wild and if it do, it is perfectly possible that tumor tendency may be transmitted as a dominant character; the effect of artificial or intentional inbreeding in captivity would only offer an opportunity for a summation of these influences.

If injury and animal parasitism have any importance in neoplasmata then this opportunity certainly occurs under natural conditions. Fibiger observed gastric tumors in rats arising under the influence of nematodes while Slye and Wells report facial neoplasms in mice apparently arising at points of old injuries. It seems to me that we have no right to assume an immunity of wild animals, in their native environment, to tumors; the incidence is another matter but it may be considerable.

It was thought possible that there might be some light shed upon the matter by an analysis of our sarcomatous and epitheliomatous tumors in wild- and captive-born animals. In our second paper[96] upon this subject I ventured the statement that sarcomatous growths occurred more frequently in captive-born, epitheliomatous in wild-born specimens. Greater data have not borne out this conclusion and information was sought as to the embryonal derivation of tumor-bearing tissue. Analyzing the cases in which all the factors could be obtained, it seems that among seven tumors of captive-bred animals, five came from the entoderm, two from the mesoderm, whereas in wild-bred animals, of the fifty-seven tumors, five came from the ectoderm, thirty-two from the mesoderm and fourteen from the entoderm. These figures do not include the parrots. The sex values have no significance.

It is interesting and noteworthy, that, as in the human being, the majority of the tumors came from tissues arising in the mesoderm and that the entodermic derivatives received the largest number of metastases; no ectodermic tissues were sites of secondary tumors. The visceral seats of metastases are probably of little value for comparison in so small a number; the lung and liver however occupy the prominent places.

Interesting as the foregoing facts may be, they do not shed light upon the question of breeding and degeneracy in the causation of neoplasms. Attention is arrested however by the paucity of tumors in derivatives of the ectoderm since in man new growths are common in the breast, at the rectal and labial mucocutaneous junctions and on the skin. The immunity of the ectodermic tissues to secondary growths is very distinct; this holds true in man.

SPECIAL TUMORS.

The diagnosis of fibroma offers the same difficulty in the zoological material as it does in man and even more care must be exercised for solid tumors in certain localities. The bird often presents hard nodular masses on the palmar and lateral aspects of the feet, sometimes surmounted by callosities, to which the term fibroma or fibromatous corns might be applied. Section of some of these will reveal areas of granulation tissue about points of inflammation so that we have considered them as infectious or the result of incorrect perches and excluded them from the tumors. True fibromata have been encountered thrice but in combination with muscle tissue as a fibromyoma thrice in addition. The “fibroids” seen in the elephants and armadillo have already been described.

The nodular growth sometimes accompanying degenerative disease of the osseous system followed by attempts at repair as discussed under osteitis deformans, leontiasis ossium and actinomycosis, are often productive of masses to which it is easy to apply the term osteoma. If one demand that an osteoma shall be a distinct neoplastic, localized bony growth of unnatural or greatly exaggerated structure, then the tumor is quite rare. We have seen one growing from the vertebræ and clavicle of a gerbille and a fibro-osteoma on one jaw of an Isabelline gazelle. The chondromata have been limited to one case, a unilateral mass growing from the nasal cartilage of a caracal.

Lipomata are localized collections of fat consisting of cells with greater fat capacity than normally, sometimes surrounded by an indefinite capsule. Judging by the observations of Joest and Johne they are reasonably common in horses and cows. We have not seen a single case in mammals but eight cases appeared in the birds. These were with one exception disposed under the skin mostly over the abdomen and chest and once under the scalp. In a hawk the tumor grew as a pelvic mass surrounding the cloaca and apparently caused decided obstruction to the lumen. The lipomata of the Psittaci usually grow as pendulous masses on the abdominal wall covered by thin, featherless, delicate skin, often showing dilated veins. Upon section they are rather rich in blood supply, “angiolipoma,” but fail to show any angiomatous or solid cellular areas under the microscope. The frequency of the growths in one variety (Roseate cockatoo—_Cacatua roseicapilla_) led to an attempt to transplant the tumor. The plant seemed to thrive in the recipient for a while but soon disappeared. Breeding experiments on the tumor bearers are now under way.

Angiomata of lymph channels were observed in the omentum and mesentery of a jaguar (_Felis onca_); this is the animal with three apparently separate and distinct tumors. “The omentum is normally fatty and slightly congested. In its meshes are myriads of tiny cysts containing gray fluid. The main peritoneal area is negative but in the pelvic region on anterior rectal wall, in the superior edge of the broad ligament and in Douglas’ pouch, are cysts from a few millimetres to several centimetres, with clear contents. The microscopic section of omentum shows the multiple cysts as cavities of varying size, from that of an arteriole to the diameter of a two-third lens field. They are lined with flat, closely placed pavement cells with well stained but vesicular nucleus. The septa are adult connective tissue. No contents or granular eosin-staining material. No swollen cells like in adenomata. No parasites seen.”

Two endotheliomata have been found, one of the flat variety with warty excrescences common on serous surfaces, located in the pleura of a leopard (_Felis nebulosa_), and one of the nodular variety, growing from the clavicle of a Moorhen (_Gallinula chloropus_).

The sarcomata present their usual morphology grossly and minutely and with the exception of the cases arising from the pectoral muscle and from the genital area offer little of interest. Two instances in the former location, observed in parrakeets, presented several puzzling features. The component cells were spindle in shape, similar to a muscle cell but were fitted with the round or elliptical nuclei of embryonal cells. In a few places they were exceedingly large and had shadowy outlines like a syncytium or they would be so arranged as to suggest a glandular structure. The dominant type of cell was, however, everywhere the spindle as it is seen in sarcoma. The sarcomata when they occur in the genital area usually assume the alveolar arrangement and are of the round or mixed cell variety. Only three of the sixteen sarcomata gave metastases.

Papillomata of minor character appear occasionally on the skin of animals as warts, but only one instance of any greater importance has been found. The duodenal mucosa of an owl (_Bubo virginianus_) presented a soft growth which partly obstructed the intestinal lumen. Papillary adenomata, on the other hand, have been observed several times, but since they have more importance as irregular hyperplasias of glandular origin have been included in the next group. An interesting case was seen in a baboon (_Papio hamadryas_) in which a large part of the gastric wall was the seat of adenomata, presenting in addition several distinct papillary outgrowths. A similar picture was found in the duodenum of the rhea (_Rhea americana_).

The greatest interest in the adenomata centres around these growths in the renal area in parrakeets, and as they have much in common with all the glandular tumors of this region, a general discussion of this subject may be introduced here. We have observed seven tumors constructed on a glandular basis of renal or adrenal character. Grossly these tumors develop as irregular masses usually of distinct brown color, constructed on a lobular plan, delicate barely visible septa dividing the growth. They seem devoid of large vessels, a gross observation confirmed microscopically. There is no criterion to the naked eye, which will distinguish the variety of epithelial hyperplasia or permit separation of these neoplasms from some sarcomata; the latter are usually gray but need not be so. Minutely studied, three of these tumors proved to be adenomata, all papillary, one cystic as well. Three had to be denominated carcinoma because of their distinct separate crowded nests and incomplete acini. The cells comprising these growths are comparable to the lining elements of the collecting tubules of the renal lobule in that they have relatively large nuclei and a tendency to basic staining protoplasm. The adenomatous picture is, however, more comparable to the cortex than to the medulla. The remaining tumor was a hypernephroma of the usual large cell, acinus-forming type and seemed to originate in the adrenal. None of these tumors in the parrakeets sent out metastases. Other hypernephromata have been diagnosed, to the number of six. Upon review of their descriptions and sections, the determinations are to be confirmed. However, it must be recorded here that none of the three in mammals gave metastases, while two of the three in birds did so. They are all of the usual type with large vacuolated cells in glandular groups or strands.

Three rather interesting examples of epithelioma have been observed. The first and most important was a basocellular growth of the tongue in a black bear (_Ursus americanus_). The local damage—ulceration and infiltration—and swelling sufficient to interfere with deglutition, were quite considerable. The basal cell nests had penetrated deeply into the muscle, but extension had taken place only to a single submaxillary gland. A squamous epithelioma was found on the skin of the thigh of a Tasmanian devil (_Sarcophilus ursinus_). The construction was somewhat unusual in that it was cystic but lined with squamous and keratinized plates. It could not be decided that it originated from glands like a trichoepithelioma; it was not like a basal cell cancer. No metastases had occurred. The third case was that of a tumor within the abdomen of an Amazon (_Chrysotis leucocephala_). It consisted of an illy defined basement membrane upon which were irregular stratified squamous epithelial cells. Upon the surface were wavy bands of horny material, very much like dried and cast-off epithelial scales, except more compact and extensive. These latter seemed to form the bulk of the mass. Beneath the membrane a few irregular accumulations of cells bearing a similarity to those on the surface could be found, but they were probably large plasma cells. The epithelial layer dipped down like in epithelioma. No pearls or separate nests were found. While this mass was not localized, it was doubtless an epithelioma, and should be included in this series. Its possible origin in the small intestine has been considered.

The question of the occurrence of tumors in wild animals seems fairly well settled when twenty-five examples of malignant epithelial neoplasms can be discovered in fifty-three hundred autopsies. It is interesting to note the incidence of these tumors in wild- and park-bred animals. Exclusive of the parrakeets there are twenty-one cancers, seventeen in known wild-bred, two in known park-bred specimens, and two with breeding uncertain. The average known duration of captivity of the wild-bred animals is about four years, while the two park-bred animals lived eight and eighteen years. Thirteen of the twenty-one cases were males, eight females. Adenocarcinoma was discovered twelve times, simplex nine times, medullary and squamous each twice. Three tumors of the pancreas and mammary gland were seen in which fibrotic or scirrhus areas were found, but in no case was there detected that hard cicatrizing cancer so commonly found in the human breast. All the interesting cases of carcinoma have been recorded in the discussion of organs from which they took origin. The only case of chorionepithelioma has been reported in detail on page 308. The two cases of mixed tumors are as follows: Mixed tumor of the thyroid and adenocarcinoma sarcomatodes in the liver; they have been discussed in detail on pages 334 and 242 respectively.

Analysis of the incidence of tumors according to organs is disturbed by the large number of cases in Psittaci. Including this order the first place is taken by the kidney, followed by the liver, uterus, muscle, gastrointestinal tract, bone and cartilage, thyroid, adrenal and lung in this order. Curiously enough, if these birds be subtracted the degree of organ susceptibility to new growths is not greatly altered. The lead is still held by the kidney, the uterus occupying the second place and then in sequence the liver, gastrointestinal tract, muscle, thyroid and adrenal. Examination of the figures for mammals shows the uterus to lead in numbers, followed by the liver, thyroid, and mammary gland. For the birds the kidney takes the undisputed head of the column with a total of twelve tumors (27 per cent. of all avian tumors); the next figures are shown by the liver, gastrointestinal tract and muscle.

ZOOLOGICAL AND PATHOLOGICAL LIST OF TUMORS

MAMMALIA PRIMATES (2) Cercopithecidæ—Hamadryas Baboon (_Papio hamadryas_) Papillary adenoma of gastric mucosa Cebidæ—Brown Cebus (_Cebus fatuellus_) Hypernephroma of right adrenal

LEMURES (1) Lemuridæ—Ring tailed Lemur (_Lemur catta_) Papillary adenoma of prostate

CARNIVORA (17) Felidæ—Clouded Leopard (_Felis nebulosa_) Endothelioma of pleura Caracal (_Felis caracal_) Osteochondroma of nose Lion (_Felis leo_) Malignant adenoma of cervix uteri Metastases to lung Jaguar (_Felis onca_) Fibroadenoma of uterus Fibroadenoma of bile ducts Lymphangioma of mesentery Viverridæ—Indian Paradoxure (_Paradoxurus niger_) Adenocarcinoma of pancreas Malayan Civet (_Viverra tangalunga_) Carcinoma of lung Canidæ—Corsac Fox (_Canis corsac_) Adenoma of pancreatic ducts Red Fox (_Canis vulpes pennsylvanicus_) Cystic adenoma of bile ducts Raccoon-like Dog (_Canis procyonoides_) Adenocarcinoma sarcomatodes of thyroid Gray Fox (_Canis cinereo argenteus_) Papillary cyst adenoma of bile ducts Prairie Wolf (_Canis latrans_) Sarcoma of thyroid region Metastases to lungs Prairie Wolf (_Canis latrans_) Sarcoma of thyroid region Procyonidæ—Common Raccoon (_Procyon lotor_) Adenoma of pancreas Ursidæ—Polar Bear (_Ursus maritimus_) Adenocarcinoma of adrenals Metastases to lungs, lymph nodes, diaphragm Black Bear (_Ursus americanus_) Medullary carcinoma of breast Metastases to lungs Black Bear (_Ursus americanus_) Epithelioma of tongue Phocidæ—California Hair Seal (_Zalophus californianus_) Hypernephroma of adrenal

RODENTIA (12) Sciuridæ—Beechy’s Spermophile (_Citellus grammurus beecheyi_) Osteoma of sternum Gray Squirrel (_Sciurus carolinensis pennsylvanicus_) Hypernephroma of kidney Woodchuck (_Arctomys monax_) Adenoma simplex of liver Muridæ—Waltzing Mouse (_Mus wagneri rotans_) Adenocarcinoma of thigh muscles White footed Mouse (_Peromyscus leucopus_) Carcinoma simplex of mammary gland White footed Mouse (_Peromyscus leucopus_) Spindle celled sarcoma of leg White footed Mouse (_Peromyscus leucopus_) Carcinoma of mammary gland Larger Egyptian Gerbille (_Gerbillus pyramidum_) Fibrosarcoma of shoulder region Heteromyidæ—Kangaroo Rat (_Perodipus richardsoni_) Sarcoma of urinary bladder Octodontidæ—Coypu Rat (_Myocastor coypus_) Sarcoma of thyroid Hystricidæ—Canada Porcupine (_Erethizon dorsatus_) Chorionepithelioma uteri Dasyproctidæ—Azara’s Agouti (_Dasyprocta azara_) Squamous carcinoma of larynx

PROBOSCIDEA (1) Indian Elephant (_Elephas indicus_) Leiomyoma, uterine cornua and fimbria

UNGULATA (7) Equidæ—Chapman’s Zebra (_Equus burchelli chapmani_) Fibroma peritonei with sarcomatous and osseous change and metastases to lung Bovidæ—Isabelline Gazelle (_Gazella isabella_) Osteofibroma of jaw with mucoid degeneration Nylghaie (_Boselaphus tragocamelus_) Fibroma uteri Dorcas Goat (_Capra hircus_) Lymphosarcoma of mediastinum with metastases to liver, kidney and lymph nodes Cervidæ—Common Deer (_Mazama virginiana_) Fibroadenoma of bile ducts Camelidæ—Alpaca (_Lama pacos_) Carcinoma of liver or bile ducts with extension to intestine Suidæ—Wild Boar (_Sus scrofa_) Carcinoma uteri

EDENTATA (1) Dasypodidæ—Nine banded Armadillo (_Tatu novemcinctus_) Fibroma uteri