Case 4 - 171208-4

10-year-old, MC, Australian cattle dog/Cairn terrier mix

The dog had an approximately one month history of acute onset of abnormal behavior, including aggression (e.g. biting the owner), lethargy, difficulty going up stairs, restlessness, vocalizing, and urinating and defecating in the house. The referring veterinarian diagnosed him with pituitary-dependent hyperadrenocorticism with a low-dose dexamethasone supression test and began treatment with trilostane. The owners discontinued trilostane after reporting that his aggression worsened while on the drug. He was referred to UCD Internal Medicine and was sedated for his exam. He presented to the UCD Emergency Service the following day for becoming increasingly obtunded after sedation and head pressing. His owners elected humane euthanasia.

The ventral aspect of the brain at the level of the pituitary had a 1.8 x 1.1 x 0.5 cm, irregularly shaped, well demarcated, soft, pale tan mass attached to the brain by a broad stalk.

SeOne section of brain is examined. A large, expansile, well demarcated, unencapsulated, densely cellular mass is originating from the sellar region, dorsally compressing and replacing the overlying hypothalamus and thalamus, and laterally compressing the amygdala and piriform lobe. The neoplastic cells are arranged in nests, packets, and trabeculae supported by a fine, fibrovascular stroma, and occassionally resemble papillary projections. Cells often palisade around small vessels, forming pseudo-rosettes and tubules that are lined by a variably attenuated cuboidal epithelium adjacent to lumenal amorphous, amphophilic material. The cells are polygonal with indistinct cell borders, a moderate amount of eosinophilic, finely granular cytoplasm, and a single nucleus with finely stippled chromatin and 1-2 basophilic nucleoli. Anisocytosis and anisokaryosis are moderate. There are 33 mitoses in ten 400x fields, many of which are bizarre (mitotic catastrophe). Multiple large areas of necrosis, multifocal single cell necrosis, and multifocal mineralization are present. Polygonal cells with abundant, brightly eosinophilic, granular cytoplasm (acidophils) are randomly scattered throughout the mass. The compressed hypothalamus, thalamus, and amygdala have increased numbers of microglia and multifocal areas of rarefaction and vacuolation of the neuropil.

The neoplastic cells are strongly positive for synaptophysin.

Pituitary gland: atypical pars distalis corticotrophic adenoma Brain (hypothalamus, thalamus, amygdala): severe compression (secondary to #1) with moderate gliosis and edema.

Functional, ACTH-secreting pituitary adenomas are most common in the dog, and arise from either the pars distalis (more common) or pars intermedia. Pituitary tumors are also common in other domestic animals, including the horse (pars intermedia), somatotroph tumors in budgerigars, and several strains of mice, including PRL-secreting tumors of FVB mice. Clinical signs of functional pituitary adenomas in dogs include those associated with hyperadrenocorticism. Clinical signs directly associated with the mass are rare unless the mass is large enough to compress adjacent neural structures (1). Dogs have an incomplete diaphragma sella, the dura mater that separates the hypophysis from the cranial portion of the hypophyseal fossa. Because of this, the path of least resistance for an enlarging pituitary mass is dorsally into the infundibulum, third ventricle, and eventually the hypothalamus and thalamus. This is in contrast to humans who have a complete diaphragma sella, which forces enlarging pituitary masses ventrally causing erosion of the sphenoid bone (1). In this case, there was severe compression of the hypothalamus, amygdala, and nucleus accumbens, all of which are components of the limbic system. The amygdala and nucleus accumbens play an important role in emotional processing, including fear and aggression. While speculative, the changes identified in these regions of the brain are consistent enough to have resulted in altered neuronal function within these structures, leading to behavioral changes and aggression.

This case is interesting as it exhibits a number of uncommon features in pituitary adenomas. The mitotic index and anisocytosis/karyosis are both elevated. Additionally, regions of the tumor impart a papillary morphology, or have almost ependymal-like pseudo-rosettes, both of which are documented in human pituitary adenomas, but are most commonly associated with null-cell, non-functional tumors. Finally, the gland formation shows production of both a proteinaceous, secretory product, as well as a more basophilic mucinous material, which is also uncommonly identified in pituitary tumors. We thank Dr. Kevin Woolard and Dr. Chuck Mohr for providing this case.

1. Meuten DJ, editor. Tumors of domestic animals, 5th edition. Ames, IA: John Wiley & Sons, Inc.; 2017. p. 768-772.