SECTION XI. The Ductless Glands

THE DUCTLESS GLANDS

THE THYROID BODIES.

The ductless glands occupying the anterior cervical regions, known as the thyroids and parathyroids are structures to be found in some form in all vertebrates, but increase in distinctness of outline and construction upward in the zoological scale. In the bird they present themselves as discrete rounded bodies lying well to the side of the midline resting usually upon the carotid artery or jugular vein or both. As one removes the skin reddish brown globular masses will be exposed to view, sometimes showing an irregular lobular outline, a variation due to separate but attached masses of parathyroid glandules; the latter may be yellowish or even white. For the most part, however, distinct thyroid and parathyroid bodies are separated with difficulty, and one must discover the latter by microscopical section. In the mammal these organs are by no means so readily found when removing the cervical integument, for they are usually buried beside the trachea and covered by sternohyoid and sternothyroid muscles. Their position, relative to the larynx and upper end of the sternum, varies considerably but this seems to have little importance in the enlargements to which the gland is liable. It is, however, lower, that is more posterior, than in the human being, rarely rising as high as the lateral thyroid cartilages. The principal lobes are elliptical or roughly triangular masses with their long axis corresponding to that of the animal’s body and apposed mesially to the trachea. When enlargement occurs it develops in the anterior or ventral direction, pushing through the cleft between the muscles and the trachea to present under the cervical skin. In quadrupeds it may become dependent and the swelling is nearer the sternum than is the case in man. The isthmus is a very variable structure, and its presence or absence cannot be said to be a constant character in any order, or indeed in any family. I have seen in old animals a fibrous band extending over the face of the trachea connecting the capsule of the lateral lobes, which might have been an isthmus at one time. From these few observations the idea of atrophic fibrosis occurred to me. Such may be the reason for the absence of this transverse link in some adult specimens.

The amount of thyroid tissue possessed by an animal might be judged by measurement or weight. The former is misleading since the density might vary, as it certainly does in the two classes and between certain orders in mammals. Actual weights would afford little comparison, whereas the weight in terms of total body weight may supply a guide to the amount of gland normal to an animal. There are given in Table 15 the grams-per- kilogram-body-weights of the thyroid bodies (thyroid and parathyroids both sides combined) of twenty animals whose gland seemed entirely normal at autopsy. They are all adult specimens, free of cretinoid characters and of bone or heart diseases, conditions which might reflect abnormalities to these glands. The list is too small to warrant any conclusions, but in one respect confirms Murray’s observation and certain experimental work, notably of Vincent and Jolly and Carlson, Rooks and McKie. The carnivores have more thyroid than ungulates (averages .55 gm. vs. .18 gm.), but the marsupials on our list have nearly as high an average as the former, namely .44 gm. To these figures might be added others which I have worked out from the list given by Murray; it is only possible to compute the gram-perkilogram value for a few of his examples since the body weights are not given in all. Using 2.2 pounds as equal to one kilogram, the seal of 432 kilos had .03 gm. of thyroid, lion had .18 gm., leopard had .46 gm., a serval .36 gm., a skunk 2.35 gm., (was this normal?) while a single herbivore with the weight given was a porcupine having .25 gm. per kilo. The average of Murray’s carnivores is therefore .67 gm. per kilo of body weight, whereas our figure is .55 gm. That the incidence of thyroid abnormalities stands in direct relation to carnivorous character has been recognized before, and is abundantly borne out by our statistics, as will appear at a later place.

TABLE 15 Showing Weights of Animals, of Their Thyroid Bodies and the Relation of These Weights Per Kilogram. ═════════════════════════════╤═════════════╤═════════════╤═════════════ │Grams of Body│ Grams of │ Grams of │ │ Thyroid │ Thyroid per │ │ │Kilo of Body ─────────────────────────────┼─────────────┼─────────────┼───────────── Primates: │ │ │ Woolly Monkey │ 2,370│ 2.│ .84 Lagothrix lagotricha │ │ │ Carnivora: │ │ │ Wild Cat │ 8,180│ 2.│ .24 Felis ruffus │ │ │ Silver Fox │ 3,325│ 4.│ 1.2 Canis chama │ │ │ Kamchatkan Bear │ 31,800│ 22.│ .63 Ursus beringiana │ │ │ Lynx │ 9,500│ 1.│ .1 Felis canadensis │ │ │ Jaguar │ 29,500│ 16.│ .54 Felis onca │ │ │ Rodentia: │ │ │ Ground Squirrel │ 550│ 2.│ 3.6 Xerus capensis │ │ │ Ungulata: │ │ │ Zebra │ 340,000│ 64.│ .19 Equus burchelli │ │ │ Giraffe │ 384,000│ 45.│ .12 Giraffa camelopardalis │ │ │ Barasingha Deer │ 56,800│ 8.│ .14 Cervus duvanceli │ │ │ Kashmir Deer │ 56,800│ 20.│ .35 Cervus cashmirianus │ │ │ Urial │ 22,700│ 2.5│ .11 Ovis vignei │ │ │ Marsupialia: │ │ │ Kangaroo │ 18,000│ 10.│ .55 Macropus robustus (?) │ │ │ Tasmanian Devil │ 3,120│ 4.│ .13 Sarcophilus ursinus │ │ │ Wombat │ 26,000│ 7.│ .27 Phascolomys mitchelli │ │ │ Wallaby │ 3,360│ 3.│ .9 Genus and species (?) │ │ │ Edentata: │ │ │ Anteater │ 3,300│ 2.│ .6 Myrmecophaga tetradactyla│ │ │ Accipitres: │ │ │ Wedgetailed Eagle │ 2,300│ 1.│ .43 Aquila audax │ │ │ Struthiones: │ │ │ Rhea │ 18,000│ 5.│ .27 Rhea americana │ │ │ Emu │ 36,300│ 23.│ .63 Dromæus novæ-hollandiæ │ │ │ ─────────────────────────────┴─────────────┴─────────────┴─────────────

ANATOMY.

The minute anatomy of the normal thyroid is fully given in text-books, and is doubtless pictured in the minds of all but students of the subject as a fixed and definite affair. Such is not the case. There is certainly a variation in gross size under conditions of seasonal and sexual activity, and it would seem acceptably demonstrated that changes in diet, especially where meat is concerned, are associated with swellings or shrinkage of the glands. These gross changes must be due to alterations in histology. In youth also the bulk is larger, a condition due to cellular activity, while as middle age advances the thyroid becomes smaller and more balanced in its colloid and cellular proportions. I need not detail the ultimate constituents of the gland, but it is well to emphasize a few points which must be taken into consideration in microscopical diagnosis. In the first place, the lobules or acini are not all of the same size in normal organs. This is especially true in the normal adult gland but may be so in youth. The cells which form the inner lining of the acinus are low cuboidal in shape but the elements which lie under them are oval and do not change with hyperplasia of the former. The colloid which fills the glandular spaces is very susceptible to mechanical and chemical agencies. In material preserved in alcohol it may be shrunken away from the cells or heavily vacuolated, while in tissue preserved a long while in any liquid it may be found contracted or broken. Large vacuolated or vesicular cells are characteristic of the human parathyroid; this type is by no means so prominent in the lower animals, and in the few examples studied closely the arrangement is less definitely glandular than in man.

The avian thyroid is distinct from the mammalian in the delicacy of its fibrous framework and the flatter character of its epithelia. Acini are usually of more uniform size. Capsular vessels are prominent but internal vascularity is less in birds than in mammals and their goitres are not solid.

PHYSIOLOGY.

The physiological value of the thyroid-parathyroid complex has been the subject of extensive study and voluminous literature without exhaustion of the possibilities, but with the result that we are possessed of knowledge explaining certain phases of abnormality, even if the normal functions be not unexceptionally demonstrated. The accepted alterations of functions are hypothyroidism—inadequate physiology, and hyperthyroidism—excessive activity. Absence or atrophy of the thyroid bodies is usual in hypothyroidism, while enlargements, collectively called goitre, commonly accompany excessive function. Exemplifying the former, cretinism is the result of failure of normal function and development during fetal life while myxedema is the expression of the disappearance of thyroid secretion after it has once been operative; the latter may occur in infancy after nursing has ceased, or at any time that the thyroid may atrophy, during some of the forms of goitre for example. Hyperthyroidism may express itself, with or without visible enlargement of the thyroid body, in nervousness, gastrointestinal disturbances, tachycardia, loss of weight and exophthalmos. The first group, which might be called athyroidism, is often associated with alterations in the bony skeleton in the form of chondrodystrophy or of rickets, while some degree of osseous change is observed with myxedema. Goitre, be it simple or exophthalmic, may be followed by cardiac enlargement or by myocarditis.

The character of the thyroid secretion is not known except that it is influenced by the availability of iodine in the diet, but there are some other as yet unexplained features. The normal thyroid fed to cretins or persons suffering with myxedema, has the power to improve the condition apparently by supplying iodine and the other essential elements. Iodine is an important constituent of the gland, being present in combination with protein. Its quality varies indirectly with the amount of colloid and of hyperplasia (Marine). The administration of this element is beneficial in colloid goitre but is harmful in the toxic variety. Even though the administration of thyroid extract may relieve athyroidism, this procedure in normal animals fails to produce typical pictures of hyperthyroidism. Carnivora fed thyroid gland do not show toxic symptoms until excessive amounts are given, whereas herbivorous varieties are much more sensitive to this feeding. Tachycardia, nervousness and exophthalmos are not produced by these experiments, an interesting observation since these signs are not recorded in wild animals, and only vaguely reported by veterinarians. Man is apparently very sensitive to thyroid dysfunction.

On the other hand, meat-eating animals are more sensitive to excision of the thyroid body than are grain eaters. Chemical studies have shown that the thyroid is concerned in basal metabolism since this is increased in hyperthyroidism and decreased in myxedema; nitrogen output is much elevated.

Thyroid physiology stands probably in some relation to the cardiac mechanism since in simple colloid or simple hyperplastic goitre if of long duration, cardiac enlargement and disease may be greater than the excess work occasioned by the mere physical bulk of the enlarged gland in the neck would seem to warrant. A detoxicating function has been ascribed to the gland, but Murray discredits this on the ground that congestion occurs in infectious disease of warm blooded animals but not in snakes. He thinks the gland more likely stands in some connection with the thermoregulatory mechanism.

It is evident from the foregoing that the thyroid is closely related to protein metabolism, and that this is in some way connected with the ability the body possesses to use iodine in the food if it can get it. Feeding of meat to fish was found by Marine to increase the size of the thyroid. With all this in mind it is not astonishing that two-thirds of our cases of thyroid abnormalities were found in the order Carnivora.

The anatomical changes of the human thyroid that precede or accompany the various clinical pictures cannot be said to be uniform to a degree that one can even approximately predict in every case what will be found at operation, at autopsy or by the microscope. Furthermore, much discussion has existed upon the importance of the several changes, the association with clinical phenomena and the nomenclature. I shall not enter the academic discussion with our material because so much has depended, in human medicine, upon symptoms, signs and chemistry—data that we cannot adduce. Upon many occasions I have seen animals with very evident goitres, but have not been able to detect bulging of the eyes or especial nervousness. One striped hyena carried his mass for several years. It swelled up occasionally and seemed to cause dyspnœa. At one examination of the beast, to see if anything could be done for him, a large cyst broke under the examining hand, whereupon a deep inspiration was heard and relief was apparent. This handling was repeated twice, these times with the purpose of breaking cysts and when this was successful disappearance of the dyspnœa was observed. However, a similar attempt upon another hyena and a wolf failed possibly because no large thin-walled cyst was present. These and the case of the lion cub (page 170) are the only instances in which the enlarged thyroid seemed to have given serious difficulty, and the symptoms were probably due to pressure. Many, indeed most, enlarged thyroids have been found at autopsy, when the Garden personnel was unaware of their existence. Interesting notes of familial cretinism will be found under the appropriate heading.

PATHOLOGICAL ANATOMY. CLASSIFICATION.

And now to return to the question of morbid anatomy of the thyroid gland, I shall begin by outlining briefly the classification to be used in analyzing our cases, a system which combines those of many pathologists, yet which I believe contains the essentials of all. The changes in the gland being hyperplastic and recessive, at times to a stage of atrophy, no clear cut definite line of demarcation separates all these pictures; instead they must be thought of as merging into one another. When the thyroid enlarges more or less continuously with a maintenance of considerable colloid, the picture is that of COLLOID GOITRE. The gland is pale, gelatinous, tense but resilient and may show large cystic areas with fluid contents. Microscopically studied the acini are overfilled with colloid yet the lining cells are retained but flattened. The cysts may show the ruptured septa of the original acini. Enlarged soft reddish glands are found at times to contain much colloid, nearly every acinus being distended with it, but in such organs the epithelia are high or even reduplicated; the amount of contents is the striking feature. These are termed HYPERPLASIA WITH COLLOID. Hyperplasia may go on with the absorption of colloid, HYPERPLASIA WITHOUT COLLOID. The gland is then a darker body of more solid character, red, dull purple or uniformly pale pink, somewhat dependent upon the blood content. By magnification one sees smaller acini with prominent high cuboidal or cylindrical epithelia and little or no colloid. The increase of cells seems to be due both to an increase in their size and number. As the proliferation increases the lining layer must be accommodated so that it bulges out into the lumen as a bud or papilla which, if it be extensive or universal in the thyroid, gives rise to the ADENOMATOID GOITRE OF PAPILLOMATOUS type. This growth is accompanied by much congestion and small or large hemorrhages may occur, forming cysts containing a blood stained fluid. Grossly such a gland has solid and cystic areas, is mottled red and gray or brown from old pigmentation and is usually of very irregular shape. These forms are more or less uniform and general, but in certain instances the hyperplasia tends to remain in isolated areas or nodules, and in these develop solid masses of thyroid epithelium, sometimes with a small lumen usually devoid of colloid, and a rather rich but loose fibrous supporting tissue, the whole picture resembling the microanatomy of the fetal gland; to these the name fetal adenoma has been given, but since they are not fetal in origin and do not behave like tumors I have called them NODULAR ADENOMATOID HYPERPLASIAS. The next step in hyperplasia would remove it from benign to malignant in pathological character, and the term NEOPLASTIC HYPERPLASIA is used; this must of course be limited to the epithelial growths, since sarcomata, while they occur in the gland, come from other cells.

The changes in atrophy consist in irregular distortion of the gland by fibrous tissue to which may be added large colloid or fluid cysts. There is no uniform finding in the thyroid for the diseases believed to be due to its atrophy, functionally at least, namely cretinism and myxedema. In the former there may be no thyroid, or it may rather closely resemble the normal organ while in the latter definite scarring and distortion is the rule. The gland acini are compressed, the cells vacuolated or crushed out of existence or there may be colloid cysts.

Inflammations occur as swellings of the interstitial tissues and of the acinus cells during many acute infections. Repetitions of this may leave a definite increase of connective tissue with large cells in the acini, a lesion which many observers have looked upon as underlying certain goitres and myxedema.

HYPERPLASIAS.

The cause of progressive hyperplasias has been ascribed to infection, to chemical substances in water and food, endogenous toxins, heredity and many other factors. While we can add nothing definite in this matter it is worthy of notice that all our animals are exposed to the same general climatic conditions, receive the same water, are fed from the same stocks and many varieties may be in charge of the same keeper. The influence of preëxisting infections cannot of course be measured. Inbreeding or captive breeding seems to have a very definite effect upon thyroid insufficiency as is well known and so sharply emphasized by McCarrison in his reference to intermarriage among certain Moslems; I shall cite the history of a wolf bitch which gave birth to three cretin litters while apparently well but mated to a goitrous male. These facts concerning the etiology are given merely to emphasize the high degree of probability that the distribution of the lesions of the thyroid gland among our specimens indicates the susceptibility of the various orders. This perhaps needs no emphasis for the carnivores, but it does for the marsupials. The literature contains many references to goitre in domesticated ungulates; this would give the impression that they are common among them, and so they may be, but this is not the case for wild ungulates. There being no doubt that the Carnivora have the highest incidence of thyroid enlargement, man being especially prone to it, and since goitre may be induced in fish by feeding meat, the inference is direct that high protein diet stands in some relation to this condition. Thirty-nine of our sixty thyroid lesions occurred in the order Carnivora; all the families of land varieties are represented; 8.1 per cent. of the specimens coming to autopsy showed definite thyroid alterations. However, marsupials have also a decided thyroid vulnerability as indicated by 4 per cent. of the specimens presenting abnormalities at death. Four of the seven cases were among the carnivorous opossums and “devils,” the remaining three being in herbivorous kangaroos. The influence of high protein diet is not evident in birds.

A discussion of the essential pathology can be based upon the accompanying table. In making a diagnosis care was used to exclude mild swelling of the gland seen in acute infectious disease and under conditions of sexual activity. The gross diagnosis was checked by microscopical section, and all but a very few have been reëxamined for the purpose of making the table.

TABLE 16. Showing Distribution of Lesions in the Thyroid Body by Giving the Number of Cases Met in the Autopsies upon the Various Orders, According to the Classification Given in the Text.

═══════════╤═══════╤═══════╤═══════════╤═══════════╤═══════════ Order │ Cases │Colloid│Hyperplasia│Hyperplasia│ Papillary │ of │Goitre │ with │ without │Adenomatoid │Thyroid│ │ Colloid │ Colloid │Hyperplasia │Disease│ │ │ │ ───────────┼───────┼───────┼───────────┼───────────┼─────────── Carnivora │ 39│ 7│ 6│ 5│ 4 Rodentia │ 1│ │ │ │ Ungulata │ 2│ 1│ │ │ Marsupialia│ 7│ 1│ 1│ 1│ 1 Passeres │ 2│ 2│ │ │ Psittaci │ 2│ │ │ │ 1 Accipitres │ 1│ │ 1│ │ Galli │ 2│ 1│ │ 1│ Alectorides│ 1│ │ 1│ │ Anseres │ 3│ │ 2│ │ ───────────┼───────┼───────┼───────────┼───────────┼─────────── Total │ 60│ 12│ 11│ 7│ 6 ───────────┴───────┴───────┴───────────┴───────────┴───────────

═══════════╤═══════════╤═══════════╤══════╤═══════╤═══════ Order │ Nodular │ Malignant │Mixed │Sarcoma│Atrophy │Adenomatoid│Hyperplasia│Tumors│ │ │Hyperplasia│ │ │ │ │ │ │ │ │ ───────────┼───────────┼───────────┼──────┼───────┼─────── Carnivora │ 9│ 1│ 1│ 1│ 7 Rodentia │ │ │ │ 1│ Ungulata │ │ │ │ │ 1 Marsupialia│ 3│ │ │ │ Passeres │ │ │ │ │ Psittaci │ │ 1│ │ │ Accipitres │ │ │ │ │ Galli │ │ │ │ │ Alectorides│ │ │ │ │ Anseres │ │ │ │ │ ───────────┼───────────┼───────────┼──────┼───────┼─────── Total │ 12│ 2│ 1│ 2│ 8 ───────────┴───────────┴───────────┴──────┴───────┴───────

FIG. 31.—HYPERPLASIA WITH COLLOID. AMERICAN BADGER (TAXIDEA TAXUS). MEASUREMENTS; 3 × 1.5 CM.; 3 × 1.5 × 1½ CM. ]

FIG. 32.—ADENOMATOID GOITRE. RACCOON-LIKE DOG (CANIS PROCYONOIDES). ]

This rather diversified group of pathological lesions would warrant one to expect a notable number of instances of disease observed during life, suggesting that the thyroid was at fault; such, however, is not the case. In the first place, no case of exophthalmic goitre, as the symptom complex is known in man, has been observed, yet the anatomical alterations, hyperplasia without colloid, and with papillary or solid adenomatoid character, are abundantly represented. For the pathologist to accept a case as toxic goitre I would ask evidence of enlargement of the heart and perhaps in addition degeneration of the myocardium. The animal showing the closest resemblance to the disease in man was a Raccoon-like Dog (Canis procyonoides) whose history and notes are given in brief.

Raccoon-like dog (Canis procyonoides) ♀ . Acute hemorrhagic splenitis. Acute fermentative gastritis. Subacute catarrhal enteritis. Acute general infection. Hypertrophic cirrhosis of liver. Chronic interstitial nephritis. Hypertrophy of heart with acute myocarditis- infiltrative and parenchymatous. Chronic lymphadenitis with acute exacerbation. Epigastritic and gastric venous stasis. Nodular adenomatous goitre. The right thyroid is lower, both measure 4 × 3 × 2 cm., are soft, resilient with dense gray capsule. Section shows cysts filled with blood separated by pale septa of soft tissue of varying thickness. One similar mass under angle of jaw seemed like a lymph node but on section is like thyroid. Parathyroids not found. Pleuræ negative. Lungs are gray, collapsed except lower half of lower lobes which are slightly emphysematous and edematous. No consolidations. Pericardium contains about 3 cc. clear, colorless fluid. Epicardium is glistening, transparent and pale. Heart muscle is soft flaccid, pale mottled gray-brown. All chambers are distended with mixed clot. The coronary muscles and columnæ are mottled brown and gray. The tips at insertion of chordæ are pale. Streaks of gray run through muscles. One area 1 × 2 cm. of softening found in middle of left auricular muscle. Aorta negative. The liver is enlarged, surface rough and irregular, edges rounded and uneven, consistency firm and tough, color mottled deep red-brown. Section surface glistening, moist, granular, opaque. Lobular markings not lost but obscured. Connective tissue lines not clear but surely diffuse in lobules. Scars on surface leading to definite connective tissue strands about vessels and irregularly placed. Gall-duct patulous with limpid bile. Spleen is well forward in front and below stomach. It is much enlarged, soft, tough, has a smooth, tense capsule. Section surface shows homogeneous purple pulp with faint, narrow but tough trabeculæ. Follicles distinctly outlined, slightly large but merely of a slightly paler purple than pulp. On surface are many round 2–5 mm. sharply outlined gray thickenings of the capsule and immediately subjacent pulp. The right kidney’s lower half has been replaced by a thin-walled clear cyst 3 × 2.5 × 2 cm. The left kidney is small, capsule strips with difficulty tearing surface slightly. Surface and section are mottled pink and gray, glistening and opaque. It is firm, dense and tough, cortex narrow, medulla wide. Cortex has obscure, irregular markings with few small cysts, striæ and glomeruli, faintly visible, margin between layers irregular. Veins are distended over surfaces of stomach, under surface of diaphragm, in peritoneum over liver but not in abdominal wall. Stomach contains sour gas and water. Mucosa especially near cardia is deep purple. Rugæ are large and permanent but mucosa and submucosa are soft and on section congestion does not extend deep. The tips of the rugæ near pylorus are infiltrated and the infiltration is surrounded by a zone of congestion. Mucosa seems about to slough but has not separated. At pylorus mucosa becomes deep brown-red, dense, swollen, opaque and covered with a slimy, soft brown mucus. Folds are prominent but temporary. In jejunum and ileum mucosa is still swollen and opaque and rugæ are still larger than normal and temporary with a dense sensation on compressing them. The color is not brown but deep pink and yellow with areas of submucous injection. Follicles not visible. Colon is negative except for slight thickening of mucosa unaccompanied by congestion or opacity. Lymph glands of small omentum are small, firm, yellow, homogeneous; those of the mesentery are large, edematous, yellow brown and tense with lymph which escapes on section. Lymph channels up to mesenteric stalk can be traced.

HISTOLOGICAL NOTES.—Liver architecture much altered by passively dilated hepatic capillaries chiefly toward the centre of the distorted lobules. This distortion is in the form of irregular liver columns separated by irregular vessels and interlobular connective tissue. This latter is increased everywhere but is abnormal in distribution within the lobules. The connective tissue at the portal spaces is not so much increased but it shows most around arteries. Bile ducts seem not increased in numbers. Much bile pigment in large, coarse, dark brown masses chiefly settled within portal spaces. The cells show slight fatty infiltration. No multinucleation. Organ is not seriously robbed of functionating tissue. Alterations are not equally distributed over section. Spleen shows enormous congestion with edema of the few chords and perifollicular tissue left unengorged with blood. Follicles are negative. No connective tissue increase. Blood destruction not now active but there are many hemosiderotic masses irregularly scattered. The subcapsular areas are loose edematous follicles. Heart muscle fibres have lost all transverse striations, some are hyaline while others are fibrillar. The nuclei are decreased in number but there is no increase of connective tissue nuclei. No pigmentation. There are several areas of round and polynuclear cell infiltration and one distinct abscess in section. The perivascular tissues are edematous. Muscle fibres are large and wide. Thyroid made up largely of slightly enlarged acini in most of which a slightly eosin-stained hyaline collection is found. There are a few cysts containing a thrombus and hemorrhage. There are no typical colloid cysts. Some scars from old hemorrhages may be seen. There is much free blood in and between acini. Blood pigment free and in granule cells is abundant. Some acinus cells show fat droplets. Lung shows old interstitial tissue increase especially about vessels and a few scars, some of which are forming cartilage. These are deeply encapsulated. Mesenteric lymph nodes show trabecular thickening with active connective tissue formation which is also present about follicles and along edges of chords. Follicles lack germ centres, solidly lymphatic. About them and in and along chords are many tissue cells some of Maximov type and a few eosinophiles. Many of these and endothelial cells are phagocytic of red blood cells. (Fig. 32.)

Just at the time of completing this book another case strongly resembling exophthalmic goitre in man was encountered in a Gray wolf (Canis lupus). This animal had a history of enlarged neck and enlarging abdomen for about six months. His appetite and discharges remained about normal but weight was lost and activity reduced to a minimum. Attempts at removing the fluid believed to be in the peritoneum, by the use of diuretics, failing and the beast being in such poor shape, he was killed. An enormous adenomatoid goitre, concentric hypertrophy of the heart, passive dilatation of all cervical and thoracic veins, passive congestion of the liver and congestion of the portal area were autopsy diagnoses. It will be noted that no exophthalmos and nervousness were observed during life.

Bone disease and atheroma are at times associated with thyroid insufficiency in man. The former, aside from osteogenesis imperfecta of cretinism, occurred only once in a carnivore and once in a marsupial. There is but one case of atheroma among the sixty cases of thyroid disease.

The reaction of the avian thyroid in its hyperplasias is somewhat different from that of the mammalian. The delicacy of the septa and the relative paucity of vessels is perhaps the reason that the gross and microscopic pictures differ from those found in mammals. It should be emphasized, however, that while one can perceive a hyperplasia of the gland of both classes when the testes or ovaries are active, there appears less participation of the thyroid in birds in infectious diseases than is the case for mammals. In simple functional hyperplasia the capsular vessels are prominent, but the cross section need show no change. In the continued hyperplasias the organ remains more solid, being less apt to develop cysts; large cysts are occasionally seen, however, and in one case the entire gland was composed of them. Microscopically the differences are largely of degree in that the process is less frank in development, but the essential changes of swollen epithelia and condensed colloid remain the same.

ATROPHIES.

The thyroid gland in its functional capacity, may be considered to undergo hyperplasia and then atrophy of the parenchyma cells. Normally this would leave the colloid, the epithelia and the supporting tissue in proper balance, but in the presence of low grade inflammation or where an abnormally hyperplastic process retrogresses, the connective tissues may exceed their norm, the epithelia may be shed or remain high and the colloid be irregular in distribution. Such a state of atrophy may exist in fetal life, arise from unknown cause during a course of toxic goitre, or perhaps insidiously in chronic toxic conditions. When this occurs in fetal life cretinism or myxedema arises, when in later life, only the latter appears. Judged entirely by microscopic findings, eight instances of atrophic changes in the thyroid have been found. Three of these were in Carnivora and were secondary to definite goitres, but were not followed by myxedema; one of these three was a cretin. A brother of this cretin but not himself a cretin, died at the age of five months from acute dilatation of the heart, and with a decidedly atrophic thyroid gland. A lion showed a distorted gland, the result of chronic inflammation, a condition also present in a leopard, in the latter possibly in association with a general infection of the heart, vessels and kidneys of long standing. A case in a bear can only be explained on the basis of chronic intestinal toxemia. A camel is the only other variety of animal to show this regressive change. The beast suffered with a marked anemia with marrow atrophy and hydatid disease; calcification was found in the thyroid.

FIG. 33.—COLLOID GOITRE WITH HEMORRHAGE FROM LEFT GLAND WHICH KILLED THE BIRD. BLACK AREA IS CLOTTED BLOOD. MUTE SWAN (CYGNUS OLOR ♂ ). ]

FIG. 34.—AT THE LEFT, THE INSIDE OF THE CALVARIUM SHOWING HEMORRHAGIC PACHYMENINGITIS. AT THE RIGHT IS A FEMUR, SHORT AND HEAVY BUT WITH THIN CORTEX; CONSTRUCTION IS ORDERLY. CRETIN GRAY WOLF PUP (CANIS MEXICANUS). ]

As has been repeatedly stated, myxedema has not been seen, but hypothyroidism has expressed itself in these animals as cretinism. The most interesting pathological fact concerning the relation of the thyroid to this maldevelopment is that there is absolutely no uniform gross or microscopical change constantly present in the typical cases. This will become more evident as the following records of our cases are perused. In 1914 an apparently normal Gray Wolf bitch threw two normal young ones which died of lack of maternal care; they were not posted. The father of this litter died shortly and was found to have a sarcomatous hyperplasia of the thyroid. A year after the first lot a second litter was born of an apparently perfect father which still lives. This animal was purchased in the same lot with the mother, and the two could be related. The first father was not related to the female. This litter consisted of seven, two dying almost at once and burned, the other five not being especially good specimens. They died at ages ranging from two to five months and were all cretins or cretinoid. Two showed hemorrhagic pachymeningitis, one external, one internal, and the usual bulky skeleton of cretinism (Fig. 34). The bones were constructed in a rather orderly and somewhat graceful manner, the uncalcified epiphyses being only occasionally distorted. The same two animals, mated again in 1916, had as offspring seven pups. One evident cretin was killed while another runt was sacrificed and found to have fractures of both femora around which no trace of callus was discoverable (Fig. 35). Two other cubs were apparently normal, while the remaining three did not develop and soon showed the cretin characters. When this group was about three months old they were fed chopped horse thyroid; one improved decidedly, one slightly, the third not at all, but it might have been too weak to get its share. These animals lived from eight months to three years; the two good ones remain alive. In 1919 the mother was killed by her cubs, probably because she was weakened by long sickness. A papillary adenomatoid goitre, endocarditis, nephritis and chronic enteritis were found. The pathological changes in the thyroids of the cretins were as follows: In the second litter two cubs had hyperplasia with colloid, one had nodular adenomatoid change and the fourth showed distinct atrophy secondary to colloid increase. In the third group two had distinct colloid changes, once pure and once as a secondary process with some evidence of atrophy to alter the fibrous tissue and shape of the acini. The remaining four seem to be all colloid in character, but I am not satisfied with the description or sections so that I shall not offer an unqualified diagnosis. The adrenals of these animals all showed some medullary congestion but no change in the chromaffin or lipoidal content.

The deformative lesions of bones are frequently associated with lesions in the pituitary body. Several of our thyroid cases have been studied for such changes without their discovery. Indeed no gross alterations have been noted among many hundreds of hypophyses seen in removing the brain nor in a small number studied histologically. Those examined under the microscope have seemed to correspond to the descriptions given by Stendell in Oppel’s Handbook of Comparative Microscopic Anatomy.

FIG. 35.—PATHOLOGICAL FRACTURE OF FEMUR. CRETIN GRAY WOLF PUP. ]

FIG. 36.—ADENOCARCINOMA SARCOMATODES. ADENOMATOUS PORTION ATTACKING CAPSULE. RACCOON-LIKE DOG (CANIS PROCYONOIDES). ]

TUMORS.

True malignant hyperplasias of the thyroid epithelium in man are being more thoroughly studied in recent times so that similar lesions in the lower animals gain interest. The notes given below are of value as individual observations only, but since three were in carnivores, another indication is at hand of the vulnerability of this order. One of the cases is admitted upon diagnosis alone, the slides and records having been lost, but since the determination was made by Dr. C. Y. White, I am satisfied to accept it. The four of which notes are at hand are as follows:

Raccoon-like Dog (Canis procyonoides) ♂ . Adenocarcinoma sarcomatodes. Metastases to liver and lungs. Fatty degeneration of liver and kidney. Acute diffuse splenitis. Submucous hemorrhages in stomach. At level of thyroid cartilage on each side and removed 1 cm. from same is a rounded encapsulated nodule measuring 2.5 × 2 × 1 cm. Portions are hard, others fluctuate suggesting cystic degeneration. Below these nodules are two bodies also bilateral, evidently lobes of thyroid, each measuring 5 × 2.5 × 2.5 cm. They are firm with some foci of cystic softening. From a ruptured cyst of the right lobe grumous, red, malodorous material exudes. Peripheries of such cyst show greenish discoloration. Bodies as a whole are greenish black in color. They are well encapsulated, do not meet in midline but are joined at lower pole by firm, apparently colloid, material. All through lung especially under pleura there are dark red, rounded, firm, well circumscribed foci measuring 2–8 mm. diameter. They project markedly on pleural surface. No capsule can be made out. Upon incising they have lighter red centres and deeper peripheries. They cut with resistance and have no inclination toward a wedge shape. Surface is for most part smooth except where tumors are present. Organ is soft and distinctly yellow. All portions of liver contain rounded and irregular nodules, some deep, others superficial. They vary in size from 2 mm. to 3.5 cm. diameter. No capsule can be made out, yet they are circumscribed. The central portions of larger nodules are dirty gray and friable. Peripheral parts dark red. Smaller lesions are solid red and of fleshy consistency. Spleen is deep dark red, homogeneous. Histological section of thyroid shows firm, old, dense capsule very irregular in thickness seemingly on account of the penetration of the enclosed tumor cells. Such infiltration gives the inner outline of capsule a very irregular, bizarre appearance, and at times thins the capsule until it is reduced to nil. In one place the tumor elements appear outside the capsule at a point where a large vessel is apposed to outside capsule. The appearances within this capsule vary; in places the picture is that of a carcinoma. Small, round, interspersed with larger irregularly shaped acini are seen lined by a single layer of low cuboidal epithelium. Very frequently indeed the lining cells contain fine granules of golden brown pigment even where their lumina contain no blood. Some of the larger acini contain altered blood cells and a smooth, pink material, knife streaked and vacuolated peripherally. In some parts of section these acini are regular and well formed, in others they are very irregular and appear to be eroding the capsule. A second appearance concerns the connective tissue. Appearing in almost any part of the section and bearing no regular relation to the epithelial elements or the section in general are areas of closely packed large spindle cells with hyperchromatic nuclei. In another place such spindle cells are arranged purposefully to form irregular capillaries containing blood. A third appearance results from a combination of the first two. Here there are acini, between which run blood capillaries with remarkably rich and numerous embryonic lining cells. A section stained by Van Gieson stain proves that part of the pink intra-alveolar material is colloid. Every gradation can be made out in tint of this material from pink to salmon to orange. It is often very difficult or impossible to state whether a given blood-filled space is a blood vessel or an acinus with hemorrhage. In both structures the lining consists of flattened cells. In one there is the possibility of colloid, in the other of hematogeneous hyaline, both with peripheral vacuolization. Lung shows walls of alveoli thickened by young type of cells. Nuclei of cells lining bronchi are prominent, in good condition. Much coal pigment through whole section. Air sacs empty. There are several rounded nodes through section consisting of closely packed spindle and round cells. Blood is abundant in such nodules both in small lined spaces like capillaries and in larger necrotic foci where there is abundant blood pigment. In one place an irregular, large acinus is seen containing a smooth pink material. A large part of the interstitial tissue is diffusely infiltrated by the large, round cells with hyperchromatic nuclei (Figs. 36 and 37).

Prairie Wolf (Canis latrans) ♂ . Mixed tumor of thyroid. Metastases to lungs. The neck of the animal is enormously enlarged, the diameter exceeding that of the body. Thyroid is enormously enlarged to about the size of a child’s head, rather firm before incision. When incised about 300 cc. blood stained fluid drained. It is rather soft and quite friable looking as if made up of fatty and hemorrhagic matter. The lung is of mottled deep red color with here and there on surface small hemispherical areas about the color of the surrounding tissue but of slightly increased resistance. They are raised above the surface and measure 2–7 mm. in diameter. Histological section of thyroid shows a mixed tumor. It is not possible to say that it is a pure thyroid gland tumor. It is largely sarcomatous, the round cell alveolar arrangement dominant at one place, at another the short spindle cell but not typical, so-called spindle celled type. There are many areas of small and a few of large hemorrhage. Cartilaginous deposit is occurring at some places in the field showing the latter type of sarcoma. Section of lung contains a large sarcoma nodule. The cells consist of round cells without the large cartilage-like cells found in the original tumor mass.

FIG. 37.—ADENOCARCINOMA SARCOMATODES. SARCOMATOUS PORTION. RACCOON- LIKE DOG (CANIS PROCYONOIDES). ]

FIG. 38.—ADENOPAPILLOMATOUS HYPERPLASTIC PORTION OF THYROID. UNDULATED GRASS PARRAKEET (MELOPSITTACUS UNDULATUS). ]

Coypu (Myocastor coypus) ♂ . Sarcoma of right thyroid. The thyroids occupy a position deep in the neck upon the anterior vertebral muscles, the left higher than right, being up to level of top of thyroid cartilage. Only a half-inch of lower pole of right remains and it is like the left which is soft, deep brown-red, delicately lobulated, closely bound to trachea but movable in fascia. It is 30 × 10 × 3 mm. The upper part of the right organ is occupied by, or at least within the same capsule as a 25 × 15 × 10 mm. encapsulated, pink mass with many small vessels on its exterior. It is soft and on section the surface is mushy, of gray-pink-yellow, and seems to have an exceedingly delicate trabecular network. Posterior and superior to this, lying near the salivary glands but back of them is a similar mass 15 × 12 × 5 mm. Still another lies anterior to what remains of the right thyroid and is about 8 × 5 × 4 mm. The adrenals are 30 × 13 × 8 mm. slightly hard and not unlike a long kidney in arrangement. The cortex is wide, regular, brown or tawny, the medulla rich in vessels and deep brown. Histological section of thyroid is an almost completely cellular mass with here and there delicate and incomplete trabeculations. Small blood vessels are numerous and consist of a delicate line with a cell nucleus here and there, that is no true wall. It seems as if the blood channels were simply regular spaces through the cell mass. The cell type is mononuclear with definitely acidophilic “granuloid” somewhat vacuolated protoplasm. The nucleus is almost without exception eccentric, rather poor in chromatin but in places diffusely staining. Mostly, however, the nuclear skein is in spots or threads and fairly dense around margins, therefore not unlike a thyroid cell and a plasma cell. Here and there one finds compressed remains of thyroid acini. There is decided irregularity of size and shape in these cells. Its origin is not clear but this seems like a sarcoma of the thyroid.

Undulated Grass Parrakeet (Melopsittacus undulatus) ♂ . Medullary carcinoma of thyroid. On opening the body a mass 10 × 6 × 4 mm. is found in the upper thoracic region on the right side. A similar mass measuring 5 × 3 × 2 mm. lies in similar position on the left side. They are identified as thyroid glands only from their position and from the numerous large vessels which radiate from them. An especially large vessel leads directly to the heart. Long axes extend anteroposteriorly. The masses are of a firm gelatinous consistency, the color of carpenters glue in lower portions, shading off to a dirty canary yellow above. They have a translucent appearance in lower portions. The surface is fairly smooth, adherent latterly and posteriorly. They are well circumscribed. At one end of the histological section thyroid tissue is easily identified. It varies from normal in that its spaces are often very large, contain villus projections or may be completely filled by large compound granule cells with no colloid. Other acini are atypical and contain typical colloid. Continuous to such thyroid tissue is a very large, rounded tumor. It consists of round cells with round nuclei in which many mitotic figures may be seen. An arrangement into acini cannot be made out nor is colloid material abundant. In one or two places an irregular collection of such material may be seen with peripheral vacuolization but its confines are always indefinite. As far as section goes the mass is well encapsulated but the lymphatics are infiltrated by the tumor cells. The tumor, too, is sharply separated from the relatively normal thyroid. Irregularly scattered through section are remarkable cells with nuclei three or four times the size of other nuclei. They may be hyperchromatic or normally staining. (Figs. 38 and 39.)

The THYMUS BODY is a structure encountered in our specimens with greater regularity than is the case in human autopsy experience. However, no great size of the gland is observed, and there is no record or recollection of anything which could resemble an enlargement suggesting status thymicolymphaticus nor has a tumor with this organ as its origin been observed. In one case only did the thymus present what was believed to be an unusual size. An adult Gray Lagothrix (Lagothrix lagotricha) died with an acute intestinal infection. Its thymus was a large, soft, deep pink body lying in the anterior mediastinum, running up to the clavicular joints and down along the sternum. The death had ample explanation without any state of this organ. The thymus body has not been found enlarged in association with thyroid disease.

FIG. 39.—MEDULLARY CARCINOMATOUS PORTION OF THYROID. UNDULATED GRASS PARRAKEET (MELOPSITTACUS UNDULATUS). ]

The SUPRARENAL or ADRENAL BODY is an organ of essentially the same general construction in the two classes here studied except that in birds the cortical portion may be imperfectly developed and in some of the lower groups is decidedly narrow. This outer zone may indeed be entirely missing since tissue comparable to it is distributed elsewhere in the body, notably with ganglia along the vertebral column. The organ is infrequently the seat of alterations, detectable either grossly or microscopically. Congestion and small hemorrhages are rather common in acute infectious disease especially when the respiratory system is involved, but these rarely destroy tissue or materially reduce the chromophilic cells. These circulatory disturbances have, however, been predominatingly among the mammals although birds have suffered with infections to a high percentage. The medulla is much more often the seat of congestion while, when hemorrhage has occurred, the cortex is apparently always involved. Lipoidal reduction has been seen in a few mammals, Primates and Carnivora, once to a state of complete exhaustion. More serious lesions have occurred eleven times, and since the cause and meaning of disease in this body are so vague it seems well to recite briefly each one.

A Weeper Cebus (Cebus capucinus) suffered for several months with constantly but slowly increasing skeletal deformity of the osteomalacic variety. He died after moving him to a new cage, his end being hurried by a scalp wound. At autopsy the skeletal condition was determined to be of the above named kind. The organs were in good condition. The adrenals were decidedly enlarged for a monkey of this size, measuring 1.8 cm. in length. The medulla was a solid, brownish, homogeneous portion covered with a very narrow, barely discernible cortical zone. This was apparently due to a uniform hypertrophy of the cells of the medulla. The testes were slightly atrophied and fibrotic. A Black Spider Monkey (Ateles ater) had a history of stiffness of legs for six months. This was probably a sign of osteomalacia since at autopsy this condition was found together with a secondary anemia, chronic gastritis, acute enteritis and brown atrophy of heart. The adrenal was knob-shaped, the cortex was wide, brown, regular, the medulla small gray-purple. “Histologically the capsule of the adrenal is thicker than is commonly seen in Primates and connective tissue bands between the units of the zona glomerulosa are somewhat stouter than common. The cells of this layer take the stain a little more deeply than usual, but are otherwise negative. The layer separating cortex and medulla is occupied by a band of well formed connective tissue which is not proceeding inward but outward and so encroaching upon the zona reticularis as to remove it completely in places, in others to make isolated islands of its cell groups. Fine lines of connective tissue are penetrating from this into the middle layer but not disturbing it as yet. The connective tissue septa penetrating the medulla are somewhat wider than one would expect but show no activity in their growth. The medulla is somewhat broken up, vacuolated and the chromophilic cells are not especially prominent, indeed some of them seeming to have undergone necrosis.” A puma (Felis concolor) died after a sickness of two weeks from acute gastroenteritis with its usual visceral associations, including acute nephritis, and with calcifications in the adrenals. These structures were quite firm and nodular, on section tough and resilient. “The cortex is irregular, brown, with paler brown medulla. Areas of calcifications appear as small dots, as linear formations and in some places seemingly around blood vessels. Histological section shows marked vacuolization of cells, particularly of cortex. There is a diffuse overgrowth of connective tissue which has become hyaline. Here and there small calcareous deposits may be seen but no massive areas as mentioned above.”

A Himalayan Thar (Hemitragus jemlaicus) came to his end, after a history of convulsions, from nephritis, which had resulted in general edema including the serous sacs, and an associated cardiac dilatation. His adrenal was egg-shape, of normal size, with a wide, irregular dull brown cortex and a homogeneous opaque, darker brown medulla. “Histologically the cellular structure of the cortex is partly destroyed, partly dropped out and partly disturbed by overgrowth of connective tissue. This connective tissue is quite prominent in the medulla where it is surely increased although it is made more prominent by absence of cells, some of which have been degenerated and some dislodged.” A Japanese Macaque (Macacus fuscatus) after drooping three weeks presented at autopsy the following numerous lesions: anemia, chronic atrophic gastritis, atrophy of heart muscle with regeneration, hemosiderin pigmentation of liver, perilobular fibrosis of liver, chronic diffuse nephritis (subcapsular type), congestion of spleen, fibrillar fibrosis of spleen, hemosiderin pigmentation of spleen, local amyloid infiltration of spleen, calcareous infiltration in medulla of adrenal. Grossly the adrenal showed a thick, orange yellow cortex and small solid, brown medulla. “Histologically the organ appears normal in all respects save for the presence of a few small irregular areas of calcification in the medulla. These occur apart from any recognizable necrotic or fibrous areas. In one place one appears to lie within the lumen of a blood vessel. No fibroses or special congestions found anywhere in the organ and cells show normal details and normal numbers of vacuoles.”

A California hair seal (Zalophus californianus) which had been refusing food and having loose stools for about ten days presented after death the following diagnosis: Hypernephroma of adrenal, chronic hypertrophic enteritis with acute exacerbation, hemorrhagic splenitis, passive congestion of liver, congestion and edema of lungs with catarrhal pneumonia, acute fibrinous pericarditis, chronic lymphadenitis, chronic interstitial nephritis. His right adrenal seemed about normal, being 5 × 2 × 1 cm. with a narrow, dull yellow cortex and a large mottled gray-brown medulla. The left one was 5 × 3 × 1 cm. The upper pole is swollen and contains in its centre a spherical tumefaction which is red, mottled, sharply outlined, with a suggestion of a capsule and slightly firmer than surrounding organ. “Histological section shows a capsule of very noticeable thickness but possibly not much in excess of normal. The cortex particularly in its deeper layers is much injected and in some places there has been hemorrhagic diffusion. In many places in the zona fasciculata, more especially near the periphery, there is breaking up of the cell tubes with an infiltration of large round cells and some chromatophilic cells. In other places this seems to have gone on to fibrous tissue increase and necrosis of the cortical fibrous cell types. The connective tissue layer below the cortex is wide and the spaces filled with blood. This connective tissue also surrounds islets of medullary cells which are not specially chromatophilic. The mass in the medulla is made up of varying sized alveoli surrounded by rather rare, highly vascularized connective tissue and enclosing islets of medullary cells. These alveoli may be subdivided by septa. Hemorrhage has occurred into many of them. The individual cell masses are made up of groups of rather large cells with illy defined margin, a granular, opaque but not vacuolated protoplasm. They have a bladder-like nucleus in which the centrosome is large and prominent. Definite mitotic figures could not be found, but mitosis is probably present. A few cells with double nuclei were seen and one with four. In many of these large islands the centre has gone to pieces from hemorrhage or necrosis. Some of the vessels are thrombotic and one shows a very pronounced periarteritis.” A brown cebus (Cebus fatuellus) was killed because of a poor tuberculin test chart. His organs were negative except the right adrenal body which was 3 × 1.5 cm., or four times the size of its fellow. It was a tense body with a smooth, mottled, deep yellow surface. On section there were deep yellow islands separated by pale brownish septa; the structure did not resemble adrenal. Histological section showed a hypernephroma of vacuolated cell type, roughly alveolar. Two other cases, which because of their microanatomy are to be called hypernephroma can be added to those just cited. One occurred in an undulated grass parrakeet (Melopsittacus undulatus), the other in a black duck (Anas obscura). As illustrative of this tumor the former will be cited in brief. “Hypernephroma of adrenal with hemorrhage into body cavity. A tumor approximating in size the head of the host extends from the region of the internal genitalia and adrenals lying more on the right than on the left side extending fully to cloaca and shoving all abdominal viscera forward. It has a pedicle springing from between the two upper lobes of the kidney where adrenals and internal genitalia are not distinguishable. Tumor is coarsely lobulated, well encapsulated, nowhere adherent. It has a pale, dirty yellow color, richly marked by red lines of congested vessels. It is fairly soft, i.e., about consistency of normal liver. Upon incising, the cut surface bulges markedly, is a dirty gray-yellow, blotched with darker gray areas, shows no internal hemorrhages or markings of special import. No metastases noted to any other organ. Microscopic section shows a light capsule surrounding the tissue of the tumor. The latter has a very scanty fibrous reticular framework showing no orderly or purposeful arrangement. Upon and between the reticulum, irregular and for the most part elongated collections of cells are placed. At times these present an elongated fascicular form, but this is not by any means a prominent feature. The cells themselves are large, rounded or polygonal, have coarsely granular cytoplasm which only in rare cases contains vacuoles. Nuclei of these cells stain very poorly, but it can be made out that they are of large epithelial type and of vacuolar appearance.”

A somewhat unusual tumor was encountered in a Polar bear (Ursus maritimus), an adenocarcinoma of the adrenal, when judged purely by its histology but a secondary tumor in the lung displayed the more familiar picture of large vacuolated cells as seen in hypernephroma. The diagnosis follows: “Scirrhous adenocarcinoma of adrenals, secondary carcinoma of lymph glands, secondary hypernephroma of lung, secondary carcinoma of diaphragm, acute mucopurulent bronchitis, acute catarrhal enteritis, chronic diffuse fibrous cholecystitis, cholelithiasis, slight acute interstitial pancreatitis, follicular hyperplasia of spleen with fibrosis, hydrothorax, hydropericardium, chronic hypertrophic osteoperiostitis, encysted trichina in diaphragm, fatty infiltration of diaphragm, chronic diffuse nephritis, chronic productive lymphadenitis, pigmentation of lymph gland. Both adrenals are smaller than normal, of woodeny consistency, the pale cortex and medulla are poorly separated from each other. The cut surface shows gray white and tawny mottling and occasional calcareous points. Histological section shows an extra capsule of fibrous tissue containing highly distended veins; the lining contains masses of tumor cells, many of which are necrotic. It is distinctly denser in type than normal and more abundant in places showing a proceeding fibrosis. Parenchyma shows but few irregular islands containing non-neoplastic cells, some of which are highly vacuolated, others are not. Interstitial tissues in peripheral parts are often grown together with the deeper portion where are intermixed tumor areas. The latter consist of small round acini of variable size lined by cells of active type. Nuclei are large and hyperchromatic, cytoplasm broad and disintegrating. Parts show necrosis and hemorrhage. Upon search transitionals from non-neoplastic to neoplastic cells can be discovered in same fasciculus.”