Pituitary Chromophobe Adenoma in a Cat

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1 Vet. Path. 10: (1973) Pituitary Chromophobe Adenoma in a Cat F. A. ZAKI and S.-K. Liu Department of Pathology, The Animal Medical Center, New York, N.Y. Abstract. Chroniophobe adenoma was diagnosed in the pituitary gland of an I I-year-old domestic shorthaired cat. Histologically, the tumor consisted of a mass of cells with scant sinusoidal arrangement and connective tissue stroma and few blood vessels. In areas the neoplastic cells contained large vacuoles that occupied the entire cytoplasm and pushed the niiclei aside. Hypophyseal neoplasms rarely occur in domestic animals. Chromophobe adenoma is the commonest of these tumors and is found mainly in the dog, horse and ox [l]. To the best of our knowledge, only one case of pituitary tumor has been reported in a cat [6]. The present report describes a chromophobe adenoma in the pituitary gland of an I 1-year-old male domestic shorthaired cat. Case History An I I-year-old male domestic shorthaired cat was admitted to The Animal Medical Center on 1 1 November I970 because of marked personality changes, including a lack of response to people, a tendency to hide and spend most of his time in the house, and a tendency to defecate outside his litter box. A diagnosis of organic mental syndrome caused by brain tumor was made. No treatment was given. During the next few weeks the cat was periodically feverish, and the nervous signs became more intense. Antibiotics were given, but had no effect. Although the cat remained responsive to his owners, he continued to lose strength and died at home on 25 June Gross PuthoIogy The carcass, which was extremely obese, weighed 4.3 kg and was 41 cm long. Body cavities were normal. Peritoneum, pleura and pericardium were

233 Fit. 1. Sagittal sectio.1 of the brain. The tuinor has compressej and destroyed the hypothalamus, thalamus, mamillary body and part of the brain stem. The lateral ventricle is d i laled.

2 233 Fit. 1. Sagittal sectio.1 of the brain. The tuinor has compressej and destroyed the hypothalamus, thalamus, mamillary body and part of the brain stem. The lateral ventricle is d i laled. smooth, glistening and translucent. The heart was normal in shape and size. The lungs were edematous and congested. The liver was swollen and pale, and its borders were rounded; it also had small dark areas up to 0.5 mm in diameter, mainly in the right lateral lobe. The adrenal and thyroid glands were of normal shape and size, but the parathyroid glands were moderately enlarged. Both testicles were atrophied. The pituitary gland was large (1.7 x 1.6 x 1.2 cm), dark red and firm and contained a mass that had occupied and destroyed the greater part of the ventral part of the thalamus and adjacent structures (fig. 1). The lateral ventricles were dilated and contained an excessive amount of clear fluid. Examination of the hematopoietic, urinary and locomotor systems and the gastrointestinal tract showed no lesion. Microscopic Examination Tissues from all organs were fixed in 10 '2, buffered formalin, embedded in paraffin, sectioned at 6 pm and stained with hematoxylin and eosin. In

3 234 ZAKI/LIU Fig. 2. This section of the tumor shows irregularly packed cells arranged in acinar patterns with scant strorna. HE. addition, the pituitary tumor was stained with azocarmine, Mallory's phosphotungstic-acid, hematoxylin and eosin, and periodic acid-schiff. Oil red 0 stain for neutral fat was applied on frozen sections of the tumor. The pituitary tumor consisted of cylindrical, polygonal and round cells that were agranular and contained ovoid or round nuclei. The cell s were densely aggregated with undefined sinusoidal patterns and scanty connective tissue stroma (fig. 2). Other areas of the neoplasm contained cells with large vacuoles that occupied almost the entire cytoplasm, pushing the nuclei aside (fig. 3). The vacuoles were neutral fat, as determined by oil red 0 stain. Blood sinusoids and vessels were in a few areas of the neoplasm. The cells were negative for acidophilic granules by Mallory's stain. The capsules of the adrenal glands were thickened, and there were nodules of cortical hyperplasia. In the zona fasciculata vacuolated areas of neutral fat were detected. Foci of coagulative necrosis were seen in the zona reti-

Pituitary Chromophobe Adenoma in a Cat 235 Fig. 3. Neoplastic cells with ovoid nuclei. Others have large vacuoles in the cytoplasm and eccentric, crescent-shaped nuclei. HE. culata.

4 Pituitary Chromophobe Adenoma in a Cat 235 Fig. 3. Neoplastic cells with ovoid nuclei. Others have large vacuoles in the cytoplasm and eccentric, crescent-shaped nuclei. HE. culata. Extravasated erythrocytes were noted at the corticomedullary junction. The medullae were normal. The parathyroid glands were entirely composed of clumps of small, dark chief cells associated with a few small capillaries and vessels. These cells had undefined boundaries and finely granular eosinophilic cytoplasm. Their nuclei were round or oval and were centrally located. The chromatin was clumped and attached to the rim of the nuclear membrane. The thyroid glands were normal. The seminiferous tubules of the testicles were lined with inactive germinal cell layer. Sperms or other stages of spermatogenic process could not be detected (fig. 4). The lungs were edematous and congested. There was centrilobular congestion in the liver, and the hepatic cords were dissociated. Most of the hepatocytes were swollen, and some had vacuolated cytoplasm. Wide cavities were lined by hepatocytes and contained erythrocytes.

236 ZAKI/LIU Fig. 4. The seminiferous tubules of one testicle were lined with inactive germinal cell layer. There was no indication of spermatogenesis.

5 236 ZAKI/LIU Fig. 4. The seminiferous tubules of one testicle were lined with inactive germinal cell layer. There was no indication of spermatogenesis. Microscopic examination of representative tissue sections of the hematopoietic, locomotor, urinary and digestive systems, including the pancreas, indicated that they were normal. The diagnosis was pituitary chromophobe adenoma. Discussion Histologically, chromophobe adenoma differs from ordinary tumors of the adenohypophysis in domestic animals in that there are fat vacuoles in the cytoplasm of a large number of neoplastic cells. The characteristic perivascular or sinusoidal arrangement of the neoplastic cells, or irregularly packed cells separated by scant stroma and vessels in certain areas, identifies the tumor as chromophobe adenoma in domestic animals [5] and man [3]. In addition, the cells took neither acidophilic nor basophilic stain by the azocarmine method.

6 Pituitary Chromophobe Adenonia in a Cat 237 Clinical, histologic, biochemical and ultrastructural studies show that chromophobe adenomas actively secrete adrenocorticotrophic hormone associated with a syndrome of hyperadrenocorticism (Cushing s disease) in the dog [I, 21. Extreme obesity and testicular atrophy of the cat in this report are compatible with the adiposogenital syndrome in the dog associated with extension of a chroinophobe adenoma into the hypothalamic nuclei [5]. Nodular hyperplasia was evidenced bilaterally in the adrenal cortex, but other signs of hyperadrenocorticism were not recognized. Accessory cortical nodules, possibly alternating phases of hyperplasia, are most common in older cats [4]. Diffuse hyperplasia, consisting mainly of chief cells, was seen in all the parathyroid glands, but signs of hyperparathyroidism were not detected. Adenomatous parathyroids have been seen in some human patients with chromophobe pituitary tumors, and pituitary, parathyroid and pancreatic islet neoplasms have coexisted in human patients [7]. References 1 CAPEN, C.C. and KOESTNER, A.: Functional chromophobe adenomas of the canine adenohypophysis. An ultrastructural evaluation of a neoplasm of pituitary corticotrophs. Path. Vet. 4: (1967). 2 CAPEN, C.C.; MARTIN, S. L., and KOESTNER, A.: Neoplasms in the adenohypophysis of dogs. A clinical and pathologic study. Path. Vet. 4: (1967). 3 KERNOHAN, J. W. and SAYRE, G.P.: Tumors of the pituitary gland and infundibuluni; pp (Armed Forces Institute of Pathology, Washington 1956). 4 JUSB, K.V.F. and KENNEDY, P.C.: Pathology of domestic animals; 2d ed., vol. I, pp (Academic Press, New York 1970). 5 MOULTON, J.E.: Tumors in domestic animals; p. 201 (Univ. of California Press, Berkeley 1961). 6 SMITH, H. A. and JONES, T.C.: Veterinary pathology; 2nd ed., p. 239 (Lea & Febiger, Philadelphia 1966). 7 WILLIAMS, R. H.: Endocrinology, pp (Saunders, Philadelphia 1962). Addendum Subsequent to the preparation of this manuscript, another cat with a similar chroniophobe adenoma of the pituitary was studied. The morphological appearance of the neoplastic cells was identical to that in the described case. There was, however, a greater tendency to form rosettes, and there were fewer cells with fat. Request reprints from: Dr. FAROUK A. ZAKI, Department of Pathology, The Animal Medical Center, 510 East 62nd Street, New York, NY (USA)

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