History
A 2-year-old sexually intact female Savannah goat was evaluated at the University of Georgia Theriogenology Section because of failure to conceive despite breeding. Initially, the goat appeared to have completely normal estrous cycles. The duration of the estrous cycles then became slightly prolonged, and although the goat bred normally, it failed to conceive. Owing to the value of the goat, the owner requested an ultrasonographic examination, and the right ovary was found to be substantially enlarged and multicystic. This observation was confirmed during laparoscopic artificial insemination. The owner requested unilateral ovariectomy, and the goat was referred to the Large Animal Veterinary Hospital for surgery.
Clinical and Gross Findings
During surgery, the right ovary was found to be 15 to 20 cm in diameter and multicystic in appearance and was removed. The entire right ovary was placed in neutral-buffered 10% formalin and submitted for histologic evaluation. On cut surface, the fixed specimen had multiple small cystic spaces and scattered areas of hemorrhage and necrosis (Figure 1).
Photograph of the formalin-fixed right ovary of a 2-year-old sexually intact female Savannah goat that was evaluated because of a clinical history of irregular estrous cycles, which had progressed to failure to conceive despite breeding. An enlarged right ovary had been detected during laparoscopic artificial insemination. The goat underwent right ovariectomy. On cut section of the removed ovary, notice the multiple cystic spaces and scattered areas of hemorrhagic necrosis. Bar = 1.0 cm.
Citation: Journal of the American Veterinary Medical Association 244, 10; 10.2460/javma.244.10.1159
Photograph of the formalin-fixed right ovary of a 2-year-old sexually intact female Savannah goat that was evaluated because of a clinical history of irregular estrous cycles, which had progressed to failure to conceive despite breeding. An enlarged right ovary had been detected during laparoscopic artificial insemination. The goat underwent right ovariectomy. On cut section of the removed ovary, notice the multiple cystic spaces and scattered areas of hemorrhagic necrosis. Bar = 1.0 cm.
Citation: Journal of the American Veterinary Medical Association 244, 10; 10.2460/javma.244.10.1159
Photograph of the formalin-fixed right ovary of a 2-year-old sexually intact female Savannah goat that was evaluated because of a clinical history of irregular estrous cycles, which had progressed to failure to conceive despite breeding. An enlarged right ovary had been detected during laparoscopic artificial insemination. The goat underwent right ovariectomy. On cut section of the removed ovary, notice the multiple cystic spaces and scattered areas of hemorrhagic necrosis. Bar = 1.0 cm.
Citation: Journal of the American Veterinary Medical Association 244, 10; 10.2460/javma.244.10.1159
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histopathologic Findings
Samples of the formalin-fixed right ovary were routinely processed, and sections were stained with H&E stain. Additional ovarian tissue sections were immuno-histochemically stained to detect vimentin, pancytokeratin, and desmin. Histologic examination revealed that normal ovarian tissue was replaced by a proliferative, multicystic, highly cellular neoplasm (Figures 2 and 3). Neoplastic cells lined variably sized cystic spaces that contained lightly eosinophilic fluid. Fewer cells were arranged in solid sheets. Cells were cuboidal to polygonal with a moderate amount of pale eosinophilic cytoplasm and a small, round nucleus with dense chromatin. Anisocytosis and anisokaryosis were minimal; there were 10 mitotic figures in ten 400× fields. One section had a large focal area of hemorrhage and necrosis. In certain sections of the ovarian tissue, there were small solid sheets of plump polygonal cells that resembled luteal cells and contained abundant eosinophilic cytoplasm and small, round nuclei.
Photomicrograph of a section of the ovarian tumor removed from the goat in Figure 1. Notice the multiple variably sized cystic spaces as well as solid sheets (S) of tumor cells, some of which have abundant eosinophilic cytoplasm resembling luteal cells (L). H&E stain; bar = 1.0 mm.
Citation: Journal of the American Veterinary Medical Association 244, 10; 10.2460/javma.244.10.1159
Photomicrograph of a section of the ovarian tumor removed from the goat in Figure 1. Notice the multiple variably sized cystic spaces as well as solid sheets (S) of tumor cells, some of which have abundant eosinophilic cytoplasm resembling luteal cells (L). H&E stain; bar = 1.0 mm.
Citation: Journal of the American Veterinary Medical Association 244, 10; 10.2460/javma.244.10.1159
Photomicrograph of a section of the ovarian tumor removed from the goat in Figure 1. Notice the multiple variably sized cystic spaces as well as solid sheets (S) of tumor cells, some of which have abundant eosinophilic cytoplasm resembling luteal cells (L). H&E stain; bar = 1.0 mm.
Citation: Journal of the American Veterinary Medical Association 244, 10; 10.2460/javma.244.10.1159
Higher-magnification view of the section of the ovarian tumor removed from the goat in Figure 1. Cystic spaces are lined by single (long arrow) and multiple layers (short arrow) of neoplastic cuboidal to polygonal granulosa cells. H&E stain; bar = 200 μm. Inset—Photomicrograph of a section of the ovarian tumor following immunohistochemical staining for vimentin. Neoplastic granulosa cells that form the cystic spaces have strong cytoplasmic expression of vimentin. Vimentin immunohistochemical stain and 3,3′-diaminobenzidine tetrahydrochloride chromogen; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 244, 10; 10.2460/javma.244.10.1159
Higher-magnification view of the section of the ovarian tumor removed from the goat in Figure 1. Cystic spaces are lined by single (long arrow) and multiple layers (short arrow) of neoplastic cuboidal to polygonal granulosa cells. H&E stain; bar = 200 μm. Inset—Photomicrograph of a section of the ovarian tumor following immunohistochemical staining for vimentin. Neoplastic granulosa cells that form the cystic spaces have strong cytoplasmic expression of vimentin. Vimentin immunohistochemical stain and 3,3′-diaminobenzidine tetrahydrochloride chromogen; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 244, 10; 10.2460/javma.244.10.1159
Higher-magnification view of the section of the ovarian tumor removed from the goat in Figure 1. Cystic spaces are lined by single (long arrow) and multiple layers (short arrow) of neoplastic cuboidal to polygonal granulosa cells. H&E stain; bar = 200 μm. Inset—Photomicrograph of a section of the ovarian tumor following immunohistochemical staining for vimentin. Neoplastic granulosa cells that form the cystic spaces have strong cytoplasmic expression of vimentin. Vimentin immunohistochemical stain and 3,3′-diaminobenzidine tetrahydrochloride chromogen; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 244, 10; 10.2460/javma.244.10.1159
Immunohistochemical staining of sections of the ovarian mass with antibody against vimentin revealed strong expression of that protein in the cytoplasm of the neoplastic cells. The neoplastic cells had no immunoreactivity with antibodies against pancytokeratin or desmin. Immunohistochemical staining was not performed on a section of tissue that contained the luteal-like cells.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: granulosa cell tumor (GCT) of an ovary of a 2-year-old Savannah goat.
Comments
Granulosa cell tumors are ovarian sex-cord stromal tumors. There are only a few published reports1,2 of GCTs in goats. Although rare neoplasms in all species, GCTs account for approximately 2.5% of all tumors in horses.3 These tumors have the potential to be hormonally active and therefore can cause signs of hyperestrinism, masculinization, or persistent anestrus.4 For the goat of this report, there was no history of behavioral changes or signs of hyperestrinism; however, the doe did have a recent history of slight prolongation of estrous cycles. The biological behavior of these tumors varies between species. All reported GCTs in goats and most in horses have been benign, as in the case described in the present report, but malignant GCTs in horses, cows, dogs, and cats have been identified.5–10
The gross morphologic features of GCTs are described as presence of both solid and cystic areas and areas of hemorrhagic necrosis; these tumors grow to a large size.4,6 Often, concurrent clinical signs resulting from the hormonally active tumor and the gross appearance of the ovary can be highly suggestive of a GCT.6 In the case described in the present report, differential diagnoses included ovarian carcinoma or other sex-cord stromal tumors because of their capability of being hormonally active and interfering with normal estrous cycling. In mammals in general, all of the sex-cord stromal tumors, such as Leydig cell tumor of the ovary, luteomas, thecomas, and stromal tumors, are uncommon, compared with GCTs.4 Hematomas can also cause enlargement of an ovary; however, they can be distinguished from GCTs on the basis of the lack of behavioral or hormonal changes and the fact that the affected animal continues to have normal estrous cycles.6 Following ovariectomy, the goat of this report was returned to the herd and has conceived multiple times and had multiple offspring.
Another clinical finding often associated with GCTs is atrophy of the contralateral ovary. Research in horses suggests that the atrophy and resultant inactivity of the contralateral ovary is a result of higher serum concentrations of inhibin in horses with GCTs, compared with findings in clinically normal horses. This difference in serum inhibin concentration between horses with and without GCTs is thought to be due to the production of inhibin by the neoplastic granulosa cells, which normally acts to suppress pituitary follicle-stimulating hormone release.7,11 Unfortunately, serum hormone concentrations in the goat of this report were not assessed.
Histologically, neoplastic granulosa cells can be arranged in a variety of patterns within the same tumor, including macro- and microfollicular, solid, trabecular, or nest arrangements that are supported by a stroma of spindle cells.4,7 In the case described in the present report, the predominant arrangement was follicular with scattered solid areas. Call-Exner bodies, characterized by radial aggregates of tumor cells surrounding central eosinophilic proteinaceous material, may also be present in some GCTs4 but were not observed.
Results of immunohistochemical staining of sex-cord stromal tumors, specifically GCTs, in domestic animals have not been adequately described. One study7 characterized benign equine GCTs with coexpression of vimentin, glutathione-S-transferase α, inhibin-α, and cytokeratin (albeit weak) in degenerating cells and no expression of desmin or actin. These staining characteristics can help to differentiate GCTs from other sex-cord stromal tumors that develop from Leydig, thecal, or stromal cells. Leydig, thecal, and stromal cells do not express inhibin-α, and thecal and stromal cells express desmin and actin.7 The strong expression of vimentin and lack of desmin or cytokeratin expression in the neoplastic ovarian tissue removed from the goat of this report further support the diagnosis of GCT.
Prior to the case reported here, we had reviewed goat biopsy or necropsy submissions to the University of Georgia College of Veterinary Medicine Department of Pathology and Athens Veterinary Diagnostic Laboratory from 2007 to 2011.a Tumors were reported for only 21 of the 189 (11%) cases. Most tumors were detected in female goats, and the mean age was 9 years. Results indicated that overall tumor prevalence in goats was relatively low. Squamous cell carcinoma was the most common tumor, accounting for 35% of the 21 tumors. In addition to the GCT in the goat of the present report, there were 2 other reproductive tract tumors reported in the records: a uterine adenocarcinoma and a squamous cell carcinoma of the vagina. Findings of that retrospective studya and a recent review12 of tumors in 1,146 goats submitted to the Veterinary Diagnostic Laboratory at Oregon State University where only 6 reproductive tumors were found among 102 tumors, none being ovarian, underscores the low prevalence of reproductive tract tumors, specifically GCTs, in goats.
Howerth EW, Butler A. Survey of goat tumors, Department of Pathology and Athens Veterinary Diagnostic Laboratory, College of Veterinary Medicine, UGA, from 2007–2011 (abstr). Vet Pathol 2011;48:E21.
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