History
A 5-year-old 32.2-kg (70.8-lb) spayed female Doberman Pinscher was evaluated because of a history of abnormal behavior and inappropriate urination for 5 weeks, circling to the right for 1 week, and mydriasis of the left eye for approximately 3 days.
Clinical and Gross Findings
Physical examination abnormalities were limited to the nervous system. The dog had obtunded mentation. The left eye had a dilated pupil that was nonresponsive to light directed into either eye, ptosis, abnormal menace response, and absence of a vestibulo-ocular reflex. The dog compulsively walked in wide circles to the right with otherwise normal gait, postural reactions, and segmental spinal reflexes in all 4 limbs.
Results of a CBC, serum biochemical analysis, and 3-view thoracic radiography were considered normal. Magnetic resonance imaging of the brain identified a well-defined, extraparenchymal, mass contained within the middle cranial fossa. Compared with the cerebral gray matter, the mass was heterogeneously iso- to hypointense on T2-weighted images and heterogeneously hypointense on T1-weighted and T2* gradient-recalled echo images. The mass had strong heterogeneous contrast enhancement on T1-weighted images after IV administration of gadopentetate dimeglumine.a The mass extended from the optic chiasm to the level of the rostral colliculi. The dorsal expansion of the mass resulted in displacement of the third ventricle and compression of the diencephalon and piriform lobes of the cerebral hemispheres. A normal pituitary gland was unidentifiable. Evaluation of a CSF sample revealed normal RBC and WBC counts and moderately high protein concentration (65.9 mg/dL; reference range, 15 to 35 mg/dL).
The owner elected not to pursue further treatment, and the dog was discharged from the hospital. Three days later, the dog was euthanized at the primary care veterinary clinic because of owner-perceived poor quality of life. On gross examination of the head and brain at the University of Georgia, a smooth-surfaced, nodular, 2.5 × 1.5 × 1.0-cm, dark reddish-brown and tan mass was found originating from the sella turcica and extending across the ventral surface of the cranial cavity along the midline. The mass was firmly adhered to the basisphenoid bone and expanded dorsally to compress the overlying brain parenchyma (Figure 1). The mass also compressed the adjacent cranial nerves as they coursed rostrally alongside of the cavernous sinus to the orbital fissure. On cut section, the right cingulate gyrus was herniated across midline and to the left.
Photographs of coronal sections through the ventral portion of the skull (A) and the brain at the level of the sella turcica (B) of a 5-year-old Doberman Pinscher that was evaluated because of a history of abnormal behavior and inappropriate urination for 5 weeks, circling to the right for 1 week, and mydriasis of the left eye for approximately 3 days. In panel A, notice the 2.5 × 1.5 × 1.0-cm, black and white mass that has filled the sella turcica, replaced the pituitary gland, and firmly adhered to the underlying basisphenoid bone. Bar = approximately 1 cm. In panel B, there is dorsal compression of the brain parenchyma overlying the sella turcica with slight herniation of the right cingulate gyrus to the left. Bar = approximately 1 cm.
Citation: Journal of the American Veterinary Medical Association 250, 8; 10.2460/javma.250.8.855
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic Findings
The entire brain and a caudoventral section of the skull with the mass were fixed in neutral-buffered 10% formalin. Sections of the mass, surrounding bone, and overlying brain were processed routinely for histologic examination. The mass was a partially encapsulated, densely cellular neoplasm composed of polygonal cells arranged in packets and nests supported by a fine, fibrovascular stroma. Neoplastic cells often palisaded around the edges of the nests and packets and were occasionally separated by variably sized, sinusoidal spaces filled with blood (Figure 2). Neoplastic cells lacked distinct cell borders and contained moderate amounts of microvacuolated, lightly eosinophilic cytoplasm, and were most consistent with chromophobe cells. The nuclei were round to ovoid with finely stippled chromatin and contained 1 distinct moderately sized nucleolus. Anisocytosis and anisokaryosis were mild, and no mitotic figures were observed in 10 hpf (400X). Moderate amounts of hemorrhage were present throughout the neoplasm. Some neoplastic cells were in the process of traversing across the fibrous capsule, and others were present in the lumen of vessels.
Photomicrographs of a section of the mass (A) and a large vessel adjacent to the neoplasm (B) from the dog in Figure 1. In panel A, the neoplasm is composed of packets and nests of polygonal cells supported by a fine fibrovascular stroma. H&E stain; bar = 100 μm. Inset—Neoplastic cells are occasionally separated by variably sized, blood-filled, sinusoidal spaces. H&E stain; bar = 50 μm. In panel B, clusters of neoplastic cells are present within the lumen of the vessel. H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 250, 8; 10.2460/javma.250.8.855
Sections of the overlying brain revealed dorsal compression by locally extensive hemorrhage. The neuroparenchyma had mild rarefaction as well as a few necrotic glia and neurons admixed with low numbers of gitter cells, lymphocytes, and plasma cells. Sections of the adjacent cranial nerves had no evidence of invasion.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: pituitary chromophobe macroadenoma with hemorrhage, vascular invasion, and compression necrosis of adjacent brain parenchyma.
Case summary: benign pituitary tumor in a dog.
Comments
Pituitary tumors typically originate from the adenohypophysis; the most common site of origin is the pars distalis in dogs, whereas it is the pars intermedia in horses. Benign pituitary tumors, or adenomas, are classified as functional or nonfunctional; they are further classified as microadenomas or macroadenomas on the basis of whether the tumor diameter is < 10 mm or ≥ 10 mm, respectively.1 Adenomas are considered invasive if they infiltrate local dura mater, bone, or blood vessels.2,3 Malignant pituitary tumors, or adenocarcinomas, are defined by the presence of metastasis to brain parenchyma, the subarachnoid space, or distant nonnervous system-associated tissue sites.2 A diagnosis of pituitary macroadenoma was made on the basis of tumor size, suspected origin from the pars distalis, and the characteristic histologic pattern.1 The tumor was further classified as invasive because of infiltration of neoplastic cells into local blood vessels.2,3
Although there was no metastasis to the brain or subarachnoid space, a diagnosis of adenocarcinoma could not be definitively ruled out because a full necropsy was not performed. The young age of this dog was also consistent with a previously reported finding that dogs < 7.7 years old with a pituitary mass are most likely to have an invasive adenoma.2
Pituitary adenomas and adenocarcinomas are the most common neoplasms to arise within the sella turcica, but other neoplasms can affect the sellar and suprasellar regions and must be differentiated from pituitary tumors. These include suprasellar germ cell tumor, meningioma, lymphoma, and craniopharyngioma. A germ cell tumor was considered because these neoplasms are overrepresented in Doberman Pinschers between 3 and 5 years of age, but they are embryonal in origin and often contain mixed cell populations, including germinomatous areas, nests of hepatocyte-like cells, and acini and tubules of tall columnar epithelial cells.4 Meningiomas have a meningothelial origin from the arachnoid and pia mater; they can have a variable histopathologic appearance but are most commonly composed of whorls of spindle cells in dogs.5 Lymphoma is an uncommon primary tumor of the nervous system and is composed of dense sheets of lymphocytes, most often lymphoblasts.6 Craniopharyngioma is a benign tumor of young animals that is derived from the epithelial remnants of the oropharyngeal ectoderm of the Rathke pouch. Histologically, craniopharyngiomas are composed of solid areas of epithelial cells with prominent keratinization and cystic areas filled with keratin and colloid.1
Dogs with pituitary tumors can have signs of endocrine dysfunction (most commonly secondary to hyperadrenocorticism from functional adenomas), neurologic dysfunction, or both. The dog of the present report did not have evidence of endocrine dysfunction other than the historical report of inappropriate urination, which could have been a result of polyuria and polydipsia. Although endocrine testing was not performed, the dog did not have other clinical features of hyperadrenocorticism such as a pot-belly appearance, alopecia, increased appetite, or high serum alkaline phosphatase activity. It is also possible that this dog's inappropriate urination was the result of abnormal mentation or was secondary to decreased antidiuretic hormone synthesis or secretion secondary to compression of the hypothalamus, infundibular stalk, or neurohypophysis.1
Neurologic signs secondary to pituitary tumors are variable and include abnormal mentation or behavior, seizures, cranial nerve deficits, circling, head tilt, blindness, and ataxia.7 The dog of the present report had signs of right prosencephalic dysfunction secondary to compression of neuroparenchyma by the tumor and associated hemorrhage as well as a nonresponsive, dilated left pupil and left-sided ptosis, which was consistent with left cranial nerve III compression. Abnormal eye movement on the left side additionally supported compression of the left cranial nerve III but was also suggestive of compression extending to the left cranial nerves IV and VI, because these nerves innervate the extraocular muscles. Compression of these nerves within the orbital fissure as they passed lateral to the sella turcica and cavernous sinus was evident on MRI examination and on gross pathological evaluation.
Although the owner of this dog elected not to pursue extensive treatment, pituitary tumors can be treated with definitive radiation or surgical debulking via transsphenoidal hypophysectomy. Survival times for dogs with pituitary tumors that receive radiation therapy vary, but recently a mean survival time of 1,405 days was reported with 1-, 2-, and 3-year estimated survival rates of 93%, 87%, and 55%, respectively.8 In another study,9 1-, 2-, 3-, and 4-year estimated survival rates for dogs with pituitary tumors that underwent transsphenoidal hypophysectomy were 86%, 83%, 80%, and 79%, respectively, with endocrine remission achieved in 63 of 180 dogs with macrotumors.
Footnotes
Magnevist, Berlex Imaging, Wayne, NJ.
References
1. Capen CC. Tumors of the endocrine glands. In: Meuten DJ, ed. Tumors in domestic animals. 4th ed. Ames, Iowa: Iowa State Press, 2002;610–625.
2. Pollard RE, Reilly CM, Uerling MR, et al. Cross-sectional imaging characteristics of pituitary adenomas, invasive adenomas, and adenocarcinomas in dogs: 33 cases (1988–2006). J Vet Intern Med 2010;24: 160–165.
3. Hansen TM, Satra S, Lim M, et al. Invasive adenoma and pituitary carcinoma: a SEER database analysis. Neurosurg Rev 2014; 37: 279–286.
4. Summers BA, Cummings JF, de Lahunta A. Veterinary neuropathology. St Louis: Mosby, 2005;380–384.
5. Nyska A, Harmelin, A, Baneth, G, et al. Suprasellar differentiated germ cell tumor in a male dog. J Vet Diagn Invest 1993; 5: 462–467.
6. Capen CC. Tumors of the nervous system. In: Meuten DJ, ed. Tumors in domestic animals. 4th ed. Ames, Iowa: Iowa State Press, 2002;697–754.
7. Wood FD, Pollard RE, Uerling MR, et al. Diagnostic imaging findings and endocrine test results in dogs with pituitary-dependent hyperadrenocorticism that did or did not have neurologic abnormalities: 157 cases (1989–2005). J Am Vet Med Assoc 2007;231: 1081–1085.
8. Kent MS, Bommarito D, Feldman E, et al. Survival, neurological response, and prognostic factors in dogs with pituitary masses treated with radiation therapy and untreated dogs. J Vet Intern Med 2007; 21: 1027–1033.
9. Hanson JM, Teske E, Voorhout G, et al. Prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism. J Neurosurg 2007; 107: 830–840.
