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[41] observation and
certain experimental work, notably of Vincent and Jolly[42] and Carlson,
Rooks and McKie[43]. 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.[44] 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.[45] 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
───────────┴───────────┴───────────┴──────┴───────┴───────
[Illustration:
FIG. 31.—HYPERPLASIA WITH COLLOID. AMERICAN BADGER (TAXIDEA TAXUS).
MEASUREMENTS; 3 × 1.5 CM.; 3 × 1.5 × 1½ CM.
]
[Illustration:
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.
[Illustration:
FIG. 33.—COLLOID GOITRE WITH HEMORRHAGE FROM LEFT GLAND WHICH KILLED
THE BIRD. BLACK AREA IS CLOTTED BLOOD. MUTE SWAN (CYGNUS OLOR ♂ ).
]
[Illustration:
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_.
[Illustration:
FIG. 35.—PATHOLOGICAL FRACTURE OF FEMUR. CRETIN GRAY WOLF PUP.
]
[Illustration:
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.
[Illustration:
FIG. 37.—ADENOCARCINOMA SARCOMATODES. SARCOMATOUS PORTION. RACCOON-
LIKE DOG (CANIS PROCYONOIDES).
]
[Illustration:
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.
[Illustration:
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.”