A Tumor of the Adrenal Medulla in a
Castrated Male Rat
W. C. Hueper, M.D., and Gustav J. Martin, Sc.D.
(From the Warner Institute /or Therapetttic Research, New Yor k, N. Y.)
(Received for publication January 7, 1942)
rare. I n some portions t h e r e w e r e areas of larger,
polygonal cells w i t h a loose, pink-stained cytoplasm.
Interspersed in this cellular m a t r i x w e r e strands of
elongated, large cells a r r a n g e d in loose bundles. T h e
oval-shaped and irregular-sized nuclei w e r e often
A d r e n a l t u m o r s in m a n are of interest not only because of their relative rarity, but also because of their
relation to h y p e r t e n s i o n and thus to arteriosclerosis
a n d because of their influence u p o n the secretion of
the sex h o r m o n e s resulting in precocious " p u b e r t y "
and masculinization.
The occurrence of spontaneous neoplasms of these glands
in animals is apparently highly exceptional. Peyron (3) observed adrenal paragangliomas in 3 cows, 1 sheep, and 5 horses.
L6wenthal (2) recorded the presence of several cortical adenomas
and of a medullary pheochromocytoma in mice. Three morphologically similar tumors in the medulla of the adrenals of
nlice, diagnosed as mesotheliomas, as well as one cortical
adenoma in these animals, were reported by Slye, Holmes, and
Wells (4).
The experimental production of blastomatoid and blastomatous conditions in these glands was accomplished in recent
years by various methods. Staemmler (6) noted the occurrence
of adenomatoid proliferations in the adrenal medulla of rats
subjected over prolonged periods to subcutaneous injections of
nicotine, a substance which activates the release of adrenalin.
Spiegel (5) observed the appearance of cortical tumors in old
male guinea pigs which had been castrated at an earl}, age.
Similar neoplastic reactions were found by Woolley, Fekete, and
Little (7, 8) in female mice ovariectomized immediately after
birth. Gardner (I) observed the occurrence of tumorous conditions in ovariectomized mice receiving intravaginal instillation
of benzpyrene dissolved in oil, in untreated ovariectomized mice,
or in mice receiving estrogens for prolonged periods. The
untreated ovariectomized mice were castrated from 5 to 9 weeks
after birth.
T h e f o l l o w i n g c o m m u n i c a t i o n deals w i t h an a d r e n a l
t u m o r f o u n d at autopsy in a m a l e rat castrated at the
age of I m o n t h a n d m a i n t a i n e d on a v i t a m i n E-deficient diet for a s u b s e q u e n t period of x2 m o n t h s .
T h i s a n i m a l was one of a series of 3 ~ similar rats
w h i c h w e r e killed w h e n !3 m o n t h s old. W h i l e the
adrenals of these rats w e r e in general grossly a n d
microscopically n o r m a l , the left a d r e n a l g l a n d of this
particular a n i m a l was f o u n d at autopsy to be a r o u n d ,
white-yellow n o d e s u r r o u n d e d by a s m o o t h capsule
a n d m e a s u r i n g I cm. in d i a m e t e r . T h e cut surface w a s
yellowish-white a n d h o m o g e n e o u s . T h e o t h e r i n t e r n a l
organs w e r e n o r m a l .
T h e histological e x a m i n a t i o n of the t u m o r s h o w e d
that it consisted m a i n l y of densely packed, ill-defined,
r o u n d or i r r e g u l a r l y shaped cells h a v i n g a r o u n d ,
m o d e r a t e l y c h r o m a t i c nucleus. Mitotic figures w e r e
Fro. i.--Photomicrograph of section of tumor of adrenal
medulla showing ill-defined and irregular groups of larger
lightly stained cells and of smaller more intensely stained
cells of indistinct outlines and oval or round shape with
transitions into elongated spindle-shaped cells, which are
often arranged in bundles. Hematoxylin and eosin stain.
Mag. X 200 (approx.).
h y p e r c h r o m a t i c , w h i l e the cytoplasm was relatively
a b u n d a n t a n d deeply p i n k - s t a i n e d ( F i g . I ) . T h e stroma
was scanty a n d consisted m a i n l y of t h i n - w a l l e d capillaries. T h e n e o p l a s m g r e w expansively c o m p r e s s i n g
the atrophic a n d vacuolated cellular cortical tissue,
w h i c h covered the t u m o r like a cap. T h e d e m a r c a t i o n
b e t w e e n the t w o tissues was indistinct. T h e r e was no
294
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Hueper and Martin~Adrenal Tumor in Rat
invasion of the surrounding tissue. Sections stained
for chromaffinic material by the method of Schmorl
(Giemsa staining) were free from any green-colored,
chromaffinic cellular granulation.
The examination of the other internal organs revealed moderate arteriolosclerotic lesions in the myocardial, pulmonary, and renal tissues. The walls of
the cerebral vessels were often thickened and hyaline,
and occasionally surrounded by small hemorrhages.
Small degenerative and fibrobtastic loci were present
in the myocardium.
SUMMARY AND CONCLUSIONS
The adrenal tumor described was found in one of
3 ~ castrated male rats kept on a vitamin E-deficient
diet and was apparently of medullary origin. The
location of the tumor in the gland, the presence of
nervous tissue elements in the neoplastic parenchyma,
and also, to a certain extent, the occurrence of arteriolosclerotic lesions in various internal organs support this
diagnosis. In view of the absence of chromaffinic matter in the cells of the neoplasm, the diagnosis of
ganglioneuroma of the adrenal seems to be justified.
It is uncertain whether or not the development of
this blastoma is causally related to the endocrine and
vitamin disturbances experimentally produced in this
rat. Investigations now under way may clarify this
question, which is important, as Gardner concluded
295
that the adrenal tumors observed in ovariectomized
mice are of cortical derivation and originate from the
zona glomerulosa; i.e., remote from the androgenic
ZOIle.
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Research.
A Tumor of the Adrenal Medulla in a Castrated Male Rat
W. C. Hueper and Gustav J. Martin
Cancer Res 1942;2:294-295.
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