History
A 23-kg (50.6-lb) neutered male mixed-breed dog reported to be 8 years old was evaluated because of a 1-week history of sudden blindness, dull mentation, and hypernatremia.
Clinical and Gross Findings
A serum biochemical panel revealed hypernatremia (178 mEq/L; reference interval, 142 to 149 mEq/L), hyperchloremia (134 mEq/L; reference interval, 109 to 117 mEq/L), and high creatinine concentration (2.4 mg/dL; reference interval, 0.4 to 1.2 mg/dL); BUN concentration was considered normal. Results of a urine dipstick assessment were within reference limits, and the dog was isosthenuric (urine specific gravity, 1.011; reference interval, 1.001 to 1.065). Magnetic resonance imaging of the head revealed a large intracranial mass at the level of the sella turcica (which was causing marked dorsal deviation and compression of the third ventricle) with intralesional hemorrhage, perilesional edema, and potential bone destruction at the base of the mass.
Necropsy revealed a circular, tan, granular, 2-cm-diameter mass on the ventral aspect of the brain at the level of the sella turcica (Figure 1). On cut section, the mass extended further into the brain and measured 3 cm in diameter; it was soft, slightly gelatinous, pale tan, irregularly circular, and well circumscribed.
Photographs of the ventral aspect of the brain (A) and a cross section of the brain at the level of the optic chiasma (after formalin fixation; B) of an 8-year-old mixed-breed dog with sudden blindness and dull mentation. In panel A, notice the 2-cm-diameter, white to tan, irregular, and mildly granular mass (arrows) that is centered over the diencephalon, covers the optic chiasm, and is slightly to the right of midline. In panel B, the mass measures 3 cm in diameter and is soft, slightly gelatinous, pale-tan, and irregularly circular (arrows). Compression of the hypothalamus and thalamus and disruption of the optic chiasm by the mass are evident.
Citation: Journal of the American Veterinary Medical Association 249, 5; 10.2460/javma.249.5.487
Photographs of the ventral aspect of the brain (A) and a cross section of the brain at the level of the optic chiasma (after formalin fixation; B) of an 8-year-old mixed-breed dog with sudden blindness and dull mentation. In panel A, notice the 2-cm-diameter, white to tan, irregular, and mildly granular mass (arrows) that is centered over the diencephalon, covers the optic chiasm, and is slightly to the right of midline. In panel B, the mass measures 3 cm in diameter and is soft, slightly gelatinous, pale-tan, and irregularly circular (arrows). Compression of the hypothalamus and thalamus and disruption of the optic chiasm by the mass are evident.
Citation: Journal of the American Veterinary Medical Association 249, 5; 10.2460/javma.249.5.487
Photographs of the ventral aspect of the brain (A) and a cross section of the brain at the level of the optic chiasma (after formalin fixation; B) of an 8-year-old mixed-breed dog with sudden blindness and dull mentation. In panel A, notice the 2-cm-diameter, white to tan, irregular, and mildly granular mass (arrows) that is centered over the diencephalon, covers the optic chiasm, and is slightly to the right of midline. In panel B, the mass measures 3 cm in diameter and is soft, slightly gelatinous, pale-tan, and irregularly circular (arrows). Compression of the hypothalamus and thalamus and disruption of the optic chiasm by the mass are evident.
Citation: Journal of the American Veterinary Medical Association 249, 5; 10.2460/javma.249.5.487
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic Findings
Histologic examination of sections of the mass revealed a nonencapsulated, well-demarcated mass that compressed and replaced the surrounding brain and obliterated the pituitary gland. It comprised 3 types of neoplastic cells. The predominant cells were round (germinal), arranged in nests and packets, and separated by a fine collagenous stroma (Figure 2). These cells had variably distinct borders, scant to moderate amounts of light finely granulated eosinophilic cytoplasm, a central nucleus with vesicular chromatin, and no visible nucleolus. The mitotic rate in this population of cells was 14 mitoses/10 hpfs (400X). Scattered throughout these cells were islands of large polygonal (hepatoid) cells, each with a moderate amount of eosinophilic cytoplasm, a large nucleus with finely stippled chromatin, and usually 1 large eosinophilic nucleolus. This group of cells frequently had a clear cytoplasmic vacuole that repeatedly displaced the nucleus. Admixed with this population and scattered throughout the mass were acini lined by 1 to multiple layers of cuboidal (epithelial) cells; each cell had a basal nucleus and finely stippled chromatin and occasionally an eosinophilic nucleolus. Among these neoplastic cells, there were some areas of squamous differentiation with infrequent small concentric whorls of keratin or formation of cystic spaces that contained colloid. Although mitoses were common in the round (germinal) cell population, they were rare in the polygonal (epithelial) cell population. Throughout the neoplasm, moderate hemorrhage, light eosinophilic fibrillar material (fibrin), multifocal areas of necrosis, and multifocal small clusters of lymphocytes were present. There were several intravascular fibrin thrombi. Immunohistochemical analysis of replicate sections revealed that the neoplastic cells were strongly immunoreactive with an anti–α-fetoprotein antibody.
Photomicrographs of sections of the brain of the dog in Figure 1. A—Neoplastic germinal cells (arrows) are arranged in nests and packets and are separated by a fine collagenous stroma. H&E stain; bar = 20 µm. B—Islands of large vacuolated hepatoid cells (arrows) are present. H&E stain; bar = 20 µm. C—Cuboidal to columnar epithelial cells with occasional squamous differentiation have formed cystic spaces that contain keratin or colloid (arrows). H&E stain; bar = 20 µm. D—Multifocally, the cytoplasm of neoplastic cells is strongly labeled for α-fetoprotein. Immunohistochemical analysis with anti–α-fetoprotein antibody; bar = 20 µm.
Citation: Journal of the American Veterinary Medical Association 249, 5; 10.2460/javma.249.5.487
Photomicrographs of sections of the brain of the dog in Figure 1. A—Neoplastic germinal cells (arrows) are arranged in nests and packets and are separated by a fine collagenous stroma. H&E stain; bar = 20 µm. B—Islands of large vacuolated hepatoid cells (arrows) are present. H&E stain; bar = 20 µm. C—Cuboidal to columnar epithelial cells with occasional squamous differentiation have formed cystic spaces that contain keratin or colloid (arrows). H&E stain; bar = 20 µm. D—Multifocally, the cytoplasm of neoplastic cells is strongly labeled for α-fetoprotein. Immunohistochemical analysis with anti–α-fetoprotein antibody; bar = 20 µm.
Citation: Journal of the American Veterinary Medical Association 249, 5; 10.2460/javma.249.5.487
Photomicrographs of sections of the brain of the dog in Figure 1. A—Neoplastic germinal cells (arrows) are arranged in nests and packets and are separated by a fine collagenous stroma. H&E stain; bar = 20 µm. B—Islands of large vacuolated hepatoid cells (arrows) are present. H&E stain; bar = 20 µm. C—Cuboidal to columnar epithelial cells with occasional squamous differentiation have formed cystic spaces that contain keratin or colloid (arrows). H&E stain; bar = 20 µm. D—Multifocally, the cytoplasm of neoplastic cells is strongly labeled for α-fetoprotein. Immunohistochemical analysis with anti–α-fetoprotein antibody; bar = 20 µm.
Citation: Journal of the American Veterinary Medical Association 249, 5; 10.2460/javma.249.5.487
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: suprasellar germ cell tumor in the brain of a dog.
Comments
The histologic findings in the brain of the dog of the present report along with the location of the mass were consistent with a suprasellar germ cell tumor. The diagnosis was confirmed by the immunostaining of neoplastic cells for α-fetoprotein.
In dogs, meningiomas are the most commonly diagnosed primary CNS tumors, accounting for 30% to 45% of all primary intracranial tumors.1,2 Differential diagnoses for tumors in the sellar region of the brain of dogs include pituitary tumors, craniopharyngiomas, and suprasellar germ cell tumors.3,4 Suprasellar germ cell tumors are diagnosed on the basis of location (suprasellar region), the admixture of 3 types of neoplastic cell populations, and immunohistochemical staining for α-fetoprotein. The 3 types of neoplastic cells involved in this type of tumor are sheets and nests of round cells resembling seminomas (germinal cells), large vacuolated polygonal cells (hepatoid cells), and epithelial cells that can have an acinar or tubular shape with squamoid differentiation and keratinization and formation of cystic spaces that contain colloid.3,4 Germ cell tumors typically develop in the gonads; however, primary extragonadal tumors with identical histologic features also develop, most frequently at locations on the midline. The cells of origin for these tumors are presumed to be ectopic embryonic germ cells that have failed to migrate from the yolk sac to the developing gonad during embryogenesis.4,5
In people, as well as in dogs, tumors in the suprasellar region frequently result in visual disturbances, hypothalamic or pituitary gland dysfunction, or, more specifically, diabetes insipidus, lethargy, and anorexia.4,6,7 Diabetes insipidus—attributed to decreased production of antidiuretic hormone by the compression or destruction of the hypothalamus or pituitary pars nervosa8—in a heifer calf with a suprasellar germ cell tumor was recently reported.9 The dog of the present report had hypernatremia, hyperchloremia, and isosthenuria, which could be consistent with diabetes insipidus, but additional diagnostic testing was not performed to confirm that diagnosis. The dog's sudden blindness was likely the result of invasion and compression of the optic chiasm by the neoplasm. Moreover, it has been reported that a mass affecting the third ventricle can induce the development of hydrocephalus and compression of the midbrain with associated abnormalities of eye movement in humans.5,6
In humans, as in dogs, these tumors are rare and develop most commonly in young adults. Among affected humans, males are overrepresented,6 whereas a correlation between sex and incidence of suprasellar germ cell tumors in dogs has not been established.4 There are no statistical data to support a breed predisposition among affected dogs; however, of 10 previously reported cases, 4 involved Doberman Pinchers and 4 involved mixed-breed dogs,4 as was the dog of the present report. In previously reported cases,4 malignancy was based primarily on invasion of surrounding tissues. There are no published reports of distant metastases in dogs with suprasellar germ cell tumors, although in 1 report,4 neoplastic cells were also found diffusely throughout the leptomeninges covering the brain and cerebellum. Nevertheless, as pointed out by Valentine et al,4 several of the dogs in that report had been previously spayed or castrated; therefore, the possibility of a primary gonadal tumor with metastases in those cases could not be entirely ruled out although metastasis to the base of the brain and other sites was considered unlikely. In humans, there are a few reports of metastasis of germ cell tumors to extracranial sites, such as the lungs.6,10 To our knowledge, there are no reports concerning the treatment options for dogs with suprasellar germ cell tumors; however, germinomas in humans have been reported to be highly radiosensitive.11
Acknowledgments
The authors thank Dr. Amy Wood and Misty Bailey for technical assistance.
References
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