T H E AMERICAN JOURNAL OF CLINICAL PATHOLOGY
Vol. 38, No. 1, pp. 70-74
July, 1962
Copyright © 1962 by The Williams & Wilkins Co.
Printed in U.S.A.
THYROIDITIS IN A GROUP OF LABORATORY DOGS
A STUDY OF 167
BEAGLES
WALTER E. TUCKER, J B . , CAPTAIN, VC, USA
Veterinary Pathology Division, Armed Forces Institute of Pathology, Washington, D. C.
During the routine histologic examination of tissues from a large group of
beagle dogs used in a long-term study of
irradiated foods,* an impressive number
of the animals, including controls, were
noted to have changes in the thyroid glands
that were interpreted as inflammatory in
nature. Inasmuch as little has apparently
been written regarding inflammatory lesions
of the canine thyroid gland, it seemed
appropriate that a morphologic description
of the changes observed in this group of
dogs be published. The knowledge that
thyroiditis may occur spontaneously in the
beagle dog, a breed used in large numbers as
a standard laboratory animal, is believed to
be of particular importance.
METHODS AND MATERIALS
teins. The diets were formulated to achieve
proper nutritional balance.
The dogs were housed in adequate cages,
usually with provisions for outdoor exercise. At the end of the 2-year feeding period
they were sacrificed by means of the intravenous administration of pentobarbital
sodium. Necropsies were performed; the
tissues were fixed in formalin and, in 1
instance, Bouin's solution, then imbedded
in paraffin. The Armed Forces Institute
of Pathology received stained slides plus
paraffin-imbedded tissues. Additional sections cut from the paraffin blocks were
stained with hematoxylin and eosin, Masson's trichrome stain, Snook's reticulum
stain, the MacCallum-Goodpasture stain
for bacteria, Gomori's methenamine-silver
nitrate technic, the AFIP modification of
Mallory's reaction for iron, and the Mo vat
pentachrome stain.
For 2 years purebred beagles, registered
by the American Kennel Club, were fed
various foods preserved by irradiation.
OBSERVATIONS
The average age of the dogs at the onset
Neither clinical signs attributable to
of the experiment was approximately 12 thyroid dysfunction nor gross lesions of the
weeks and at the time of sacrifice, 119 thyroid gland were reported in the inweeks. There were 90 females and 77 males. dividual necropsy protocols. Upon histologic
The dogs had been obtained from a number examination, however, it was observed that
of sources and were fed at 6 different in- 27 (16.2 per cent) dogs of a total of 167
stitutions. The sources, as well as the in- had lesions of the thyroid gland that were
stitutions where the dogs were fed, were interpreted as inflammatory. The incidence
widely separated at inland locales in the of the lesions among males and females
eastern United States (Georgia, Alabama, was approximately equal.
Virginia, Illinois, and New York). IrradiThe microscopic lesions were characterized
ated foods were fed to the extent of 20 to
by
nodular and diffuse infiltration of the
35 per cent of the diet by dry weight. The
remainder of the diet consisted of com- thyroid gland by lymphocytes, plasma
mercial dog food, supplemented by added cells, macrophages, and also, in a few of
amounts of vitamins, minerals, and pro- the cases, neutrophils. The degree of involvement varied from the presence of
scattered foci of these cell types to diffuse
Received, February 21, 1962; accepted for
infiltration of the entire section (Figs. 1
publication April 6.
* This investigation was supported in part by and 2). Infiltration of the capsule occurred,
a research contract, Project Number 6X60-01- but in none of the cases did the process
001-02, from the Medical Research and Develop- seem to extend into the parathyroid gland
ment Command, U. S. Army, Washington 25, D. C. or perithyroid connective tissue. Lymphoid
70
July 1962
THYROIDITIS I N LABORATORY DOGS
71
FIG. 1 (left). Nodular infiltration of thyroid gland (AFIP Neg. 61-6445). Hematoxylin and eosin.
X 65.
FIG. 2 (right). Diffuse infiltration of thyroid gland. Note cells within acini, as well as vacuolization
and variable staining intensity of colloid. Periphery of a lymphoid nodule at upper right (AFIP Neg.
61-6444). Hematoxylin and eosin. X 65.
nodules, often with prominent germinal
centers, were frequently present in the
thyroid parenchyma. At the periphery of
these nodules plasma cells were often seen
in large numbers. The thyroid follicles were
often compressed and distorted by the
infiltrating cells (Figs. 3 and 4). In every
case there was infiltration of some follicles
by 1 or more cell types, often to the point
that, in a single section, occasional follicles
appeared almost filled. These cells consisted
of lymphocytes, plasma cells, histiocytes,
multinucleated giant cells, and sometimes
neutrophils. Complete destruction of follicles
frequently occurred, leaving only a small
residuum of colloid surrounded by numerous
leukocytes. Hemosiderin was present in
many of the cases, occurring in small
amounts, usually within macrophages in
the infiltrated areas. In none of the cases
was there an appreciable increase in fibrous
connective tissue.
Follicles containing scant, vacuolated,
extremely pale or darkly eosinophilic colloid
were observed in most cases, with complete
absence of colloid in some of the follicles.
Phagocytosis of colloid by histiocytes and
giant cells was a frequent finding.
In most of the cases there were numerous
small follicles formed by cells differing in
appearance from normal follicular epithelium (Figs. 5 and 6). The cells were
large and polygonal, and had abundant,
slightly eosinophilic, sometimes vacuolated
or foamy cytoplasm, and frequently a
distinct cell border. The nuclei were fairly
uniform in size and were usually pale, with
1 or 2 prominent nucleoli. An occasional
nucleus had a bizarre, hyperchromatic
appearance and was somewhat larger
than the nuclei of other similar cells. The
follicles formed by this type of epithelium
were usually quite small and had tiny lumens
that contained darkly eosinophilic colloid.
72
TUCKER
Occasionally, the epithelium of a follicle
was composed of both relatively normal
cells and the large cells. Frequently these
large cells formed solid packets arranged
in circular, irregular, or trabecular fashion
and fitted together in a mosaic pattern
with their cell borders clearly visible. Cells
with pyknotic nuclei and highly eosinophilic
cytoplasm suggestive of degeneration were
sometimes present among them. In some
instances, scattered groups of the large
cells were present in varying numbers,
whereas in others broad areas consisted
almost entirely of these cell groups. Occasionally, individual cells seemed to coalesce
to form sheets, but reticulum stains revealed
that such areas were actually aggregates
of smaller groups of cells surrounded by a
reticular membrane. A rare mitotic figure
was observed. Epithelial cells of similar
appearance and arranged in similar fashion
were also observed in the thyroid glands of
some dogs in which thyroiditis did not
occur. Usually, however, they were not so
numerous in noninflamed thyroid glands
as in those with inflammatory lesions.
Microorganisms were not demonstrated
in sections stained with hematoxylin and
eosin or with special stains for bacteria and
fungi. Viral inclusions were not observed.
Lesions occurring in other organs were
varied and mild in nature, and were the
type frequently seen in dogs in which
thyroiditis was not observed.
DISCUSSION
Sufficient histologic evidence was present
to warrant the designation of thyroiditis.
On the basis of the clinical observations,
pathologic findings, and information available in the literature, one can only speculate
on the etiology and pathogenesis of the
lesions described. Causative factors that
should be considered include infectious
agents, nutritional factors, aging, trauma,
endocrine imbalance, and autoimmunity. 8 ' 9
Although some of these factors seem unlikely, they can not be entirely dismissed.
It is clear, however, that the ingestion of
irradiated foods was not responsible, inasmuch as thyroiditis occurred with equal
Vol. 38
incidence and severity in both the control
dogs fed nonirradiated foods and in dogs
fed the irradiated foods.
Inasmuch as none of the dogs in the
experiment wore collars, trauma from that
source can be eliminated.
The incidence of thyroiditis in this
series is rather high, but is comparable to
that observed in the beagle colonies at the
Food and Drug Administration, Washington, D. C.3 (an estimated 10 per cent in
young adult dogs), and at the University
of California1 (approximately 20 per cent
in dogs more than 3000 days of age). Although it is possible that thyroiditis may
occur more frequently in the beagle dog
than in other breeds, such a conclusion
must await further investigation. Sufficient surveys have not been conducted on
the occurrence and types of thyroid lesions
among general populations of dogs to permit
a statement of the over-all incidence of
thyroiditis. Clark and Meier2 reported 3
cases of "struma lymphomatosa" in 119
dogs of various breeds. Schlotthauer and
associates7 reported 2 cases of "old thyroiditis with fibrosis" among 234 canine
thyroid glands examined. There are 3 cases
of thyroiditis in the Registry of Veterinary
Pathology at the Armed Forces Institute of
Pathology among approximately 5000 accessioned cases. A large percentage of the
latter group are surgical specimens, however, and do not include thyroid tissue;
therefore, the incidence of thyroiditis in
that group is probably much lower than it
would be if autopsy material including
thyroid glands constituted a greater proportion of the accessions.
The significance of the large polygonal
epithelial cells, described as occurring
with, as well as in the absence of, inflammatory lesions, is not apparent to the
author. Cells of similar type have been
described in normal thyroid glands of
postnatal dogs.4 • 5 • 6 They have been regarded as normally arising in the interfollicular spaces, in the follicular epithelium,6 and from the ultimobranchial
body.4 Attempts to determine the origin
of the cells were not made in this study.
July 1962
THYROIDITIS IN LABORATORY DOGS
73
FIG. 3 (upper left). Infiltration of thyroid follicle by numerous leukocytes (AFIP Neg. 61-5328).
Hematoxylin and eosin. X 255.
FIG. 4 (upper right). Similar to Figure 3, but with more cellular infiltration and distortion present
(AFIP Neg. 61-5329). Hematoxylin and eosin. X 195.
FIG. 5 (lower left). Small packets of large epithelial cells in heavily infiltrated thyroid gland (AFIP
Neg. 61-5325). Hematoxylin and eosin. X 160.
FIG. 6 (lower right). High magnification, packets of large epithelial cells (AFIP Neg. 61-5327). Hematoxylin and eosin. X 525.
74
SUMMARY
Thyroiditis of unknown etiology occurred in 27 (16.2 per cent) of 167 young
adult beagle dogs used in a long-term study
of irradiated foods. The lesions occurred
with equal incidence and severity in control
dogs as in those fed irradiated foods. A
morphologic description of the lesions is
included.
SUMMARIO IN INTERLINGUA
Thyroiditis de incognite etiologia occurreva in 27 (16.2 pro cento) de 167 juvene
adulte canes bigle usate in un studio a longe
vista de irradiate alimentos. Le lesiones
occurreva con equal incidentia e severitate
in canes de controlo e in canes tractate con
alimentos irradiate. Un description morphologic del lesiones es includite in le presente
communication.
1.
Vol. 88
TUCKER
ANDERSON,
REFERENCES
A. C : Personal communication.
2. CLARK, S. T., AND MEIER, H.: A clinico-
pathologic study of thyroid disease in the
3.
4.
5.
6.
dog a n d c a t . I . Thyroid pathology. Zentralbl. Vet. Med., 5: 17-31, 1958.
D A V I S , K . J . : Personal communication,
GODWIN, M . C : Complex IV in the*dog with
special emphasis on t h e . relatjfln of t h e
ultimobranchial body t o interfoHiculaf' cells
in t h e postnatal thyroid gland. A m . J .
Anat., 60: 299-339, 1937.
:
HAMPERL, H . : Onkocytes and t h e so-called
Hurthle cell tumor. Arch. P a t h . , 49: 563567, 1950.
NONIDEZ, J . F . : T h e " p a r e n c h y m a t o u s " cells
of Baber, t h e "protoplasmareichen zellen"
of Huerthle, and t h e "parafollicular" cells
of t h e mammalian thyroid. Anat. R e c ,
56: 131-141, 1933.
7. SCHLOTTHAUER,
C.
F.,
MCKENNEY,
F.
D.,
AND CAYLOR, H . D . : The incidence of goiter
and other lesions of t h e thyroid gland in
dogs of southern Minnesota. J . Am. Vet.
Med. Ass., 76: 811-819, 1930.
8. T E R P L A N , K . L., W I T E B S K Y , E . , R O S E , N . R.,
P A I N E , J . R . , AND E G A N , R . W . : E x p e r i -
mental thyroiditis in rabbits, guinea pigs
and dogs, following immunization with
thyroid extracts of their own and of heterologous species. Am. J . Path., 36: 213-239,
1960.
9. W I T E B S K Y , E . , R O S E , N . R . , T E R P L A N , K . ,
P A I N E , J . R., AND E G A N , R . W . : Chronic
thyroiditis a n d autoimmunization.
M. A., 164: 1439-1447, 1957.
J . A.