Pathology in Practice

Raphael A. Malbrue Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Carmen B. Arsuaga Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Alexandra N. Jay Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Natasha Smith Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Shannon D. Dehghanpir Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Atsushi Kawabata Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Britton J. Grasperge Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Fabio Del Piero Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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History

A 2-year-old 96.3-g (0.21-lb) female Mongolian gerbil (Meriones unguiculatus) kept at the Division of Laboratory Animal Medicine of Louisiana State University was noted to have a swollen abdomen, unthrifty coat, decreased appetite, and lethargic attitude. This animal was involved in a research project to investigate the complete life cycles of Brugia pahangi and Brugia malayi. These species are arthropod-transmitted nematodes known to be causative agents of lymphatic filariasis—a tropical disease commonly known as elephantiasis—in humans. However, this gerbil was specifically used as an uninfected control.

Clinical and Gross Findings

Initial physical examination revealed severe abdominal distension; organs were not palpable, and no signs of abdominal pain or discomfort were elicited. Further abdominal evaluation revealed a fluid wave when the contralateral side of the animal's abdomen was manually manipulated. On ultrasonographic examination, all intra-abdominal structures were obscured by fluid, and a large, moveable hypoechoic cystic structure was observed. Abdominocentesis yielded approximately 35 mL of serosanguineous fluid. After removal of abdominal fluid, a solitary freely moveable mass was palpated in the left cranial abdominal quadrant. Given the clinical signs and presumptive poor prognosis, the gerbil was euthanized in a CO2 induction gas chamber. A necropsy was performed. A 4 × 2 × 1-cm pale, soft, lobulated, cystic mass encompassed the left ovary (Figure 1). A fine-needle aspirate specimen of the ovarian mass was also obtained for cytologic evaluation. No other gross abnormalities were evident.

Figure 1—
Figure 1—

Photograph of the abdominal cavity of an approximately 2-year-old female Mongolian gerbil that was evaluated because of a distended abdomen, unthrifty hair coat, decreased appetite, and lethargic attitude. A unilateral pale, soft, lobulated, cystic mass has encompassed the left ovary. B = Urinary bladder. GI = Gastrointestinal tract. L = Liver. LK = Left kidney. LO = Left ovarian mass. LU = Left uterine horn. RU = Right uterine horn.

Citation: Journal of the American Veterinary Medical Association 250, 9; 10.2460/javma.250.9.989

Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→

Cytologic and Histopathologic Findings

Abdominal fluid analysis revealed adequate cellularity and cellular preservation. Many erythrocytes with fewer nucleated cells were seen. Nucleated cells consisted of small lymphocytes (81%) and large mononuclear cells (19%) that were considered likely macrophages. Rare reactive mesothelial cells were observed. Erythrophagocytosis by the large mononuclear cells was also occasionally seen. The abdominal fluid had a bloody and cloudy appearance and contained 800 nucleated cells/μL, 630,000 RBCs/μL, and 4.2 g of protein/dL. The cell counts, protein concentration, and presence of erythrophagia were interpreted as acute hemorrhagic effusion.

Microscopic examination of the fine-needle aspirate specimen from the left ovarian mass revealed high numbers of adequately preserved nucleated cells and a moderate amount of blood contamination. Nucleated cells consisted predominantly of large round to polygonal cells with fewer blood leukocytes. The round to polygonal cells were loosely to densely clustered and had minimal anisocytosis and anisokaryosis (Figure 2). Nuclei were round to oval and variably located, and contained coarsely clumped chromatin and multiple, variably sized, indistinct nucleoli. The cells contained moderate amounts of lightly to deeply basophilic cytoplasm that was sparsely to moderately vacuolated. Rarely, the cells were arranged in an acinar pattern. Erythrocytes occasionally contained basophilic stippling, a normal species variation. Cytologic findings were consistent with a sex cord–stromal tumor; the primary differential diagnosis was a granulosa cell tumor, although an adrenal cortical tumor could not be definitively excluded.

Figure 2—
Figure 2—

Photomicrographs of a fine-needle aspirate specimen of the left ovarian mass in the gerbil in Figure 1. A—Notice the nucleated cell population composed of large, round to polygonal cells that are loosely to densely clustered. Modified Wright stain; bar = 50.0 μm. B—The nuclei are round to oval and variably centrally and eccentrically located, and contain coarsely clumped chromatin and multiple, variably sized, indistinct nucleoli. Cells have moderate amounts of basophilic cytoplasm, which is sparsely to moderately vacuolated. Modified Wright stain; bar = 50.0 μm.

Citation: Journal of the American Veterinary Medical Association 250, 9; 10.2460/javma.250.9.989

Histologic evaluation of sections of the mass revealed a well-circumscribed, nonencapsulated, expansile, partly cavitated, ovarian neoplastic mass. The cavity contained RBCs and fibrin with necrotic debris. This moderately cellular neoplasm was composed of polygonal cells arranged in cords, trabeculae, and follicles separated by a very thin fibrovascular stroma with multiple spaces filled with erythrocytes and fibrin (Figure 3). The neoplastic cells had distinct cell borders, small to moderate amounts of eosinophilic to clear foamy cytoplasm, and round to oval nuclei with stippled chromatin and inconspicuous nucleoli. Mild anisocytosis and anisokaryosis were evident. The mitotic index was < 1 mitotic figure/10 hpf (40X). There were multiple necrotic foci with hemorrhage. The uterus and right ovary had no notable lesions. No evidence of intravascular invasion was observed within any of the examined sections. The histologic findings were compatible with a granulosa cell tumor.

Figure 3—
Figure 3—

Photomicrographs of sections of the left ovarian mass in the gerbil in Figure 1. A—Low-magnification cross section of the ovarian mass with large blood-filled cavitation (asterisk). H&E stain; bar = 2.5 mm. B— At higher magnification, the mass has polygonal granulosa cells arranged in cords (S) and multiple spaces that are filled with erythrocytes and small amounts of fibrin (F). H&E stain; bar = 100 μm. C—Solid areas of the neoplasm have polygonal granulosa cells that are arranged in cords (S). H&E stain; bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 250, 9; 10.2460/javma.250.9.989

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: granulosa cell tumor in the left ovary of a Mongolian gerbil.

Comments

Granulosa cell tumors are the most common ovarian neoplasms in horses, cattle, and dogs.1 The tumors are often unilateral, smooth surfaced, and round and can be solid, cystic, or polycystic.1 Treatment of affected animals usually consists of surgical removal alone or in combination with chemotherapy. Granulosa cell tumors are part of the group of neoplasms known as gonadal stromal tumors. They constitute < 5% of all ovarian tumors and > 70% of the sex cord–stromal tumors in humans.2 Microscopically, the neoplastic granulosa cells resemble their normal counterparts and are often arranged as they would be in normal Graafian follicles, namely in single or multiple rows of round to columnar cells lining fluid-filled spaces.1

Neoplasia has been most often detected in gerbils > 2 to 3 years of age, but the overall incidence of spontaneous tumors in gerbils is 24% to 39%.3 There are a variety of surveys and research projects that have investigated neoplasia in laboratory colonies of gerbils.4–7 For gerbils, the 2 most commonly reported tumors are squamous cell carcinoma of the ventral marking gland in males and ovarian granulosa cell tumor in females. These 2 tumors account for 80% of all neoplasms in gerbils > 3 years of age.8 Unlike findings in larger animals, granulosa cell tumors in gerbils are frequently bilateral, vary from fleshy and lobulated to cystic masses, and can be either benign or malignant.4 After cytologic review of the ovarian mass in the case described in the present report, the large mononuclear cells in the abdominal fluid sample may have represented a neoplastic population, given that their morphologic characteristics were similar to those of granulosa cells. Additional diagnostic testing, including immunocytochemical staining of sections of the mass, would be required to determine whether the large mononuclear cells were histiocytic or neoplastic; however, inhibin, a marker for sex cord–stromal tumors, has not been validated for use in tissue samples from gerbils. Therefore, the possibility of a neoplastic effusion or exfoliation should be considered. Gerbils that have granulosa cell tumors commonly develop clinical signs similar to those of the gerbil of this report: lethargy, distended abdomen, decreased appetite, and unthrifty coat. Adrenocortical tumors, cutaneous squamous cell carcinoma, malignant melanoma, and renal and splenic hemangiomas are other tumors commonly identified in gerbils.8

Although the etiopathogenesis of granulosa cell tumors is unclear in not only gerbils but also humans, epidemiological data indicate an increased incidence of ovarian cancer with early menarche, late menopause, and nulliparity in humans. Granulosa cell tumors are regulated by and can synthesize hormones; furthermore, it has been hypothesized that the molecular changes that occur in granulosa cells lead to a neoplastic transformation involving specific endocrine pathways.9 Although there was no evidence of metastases in the gerbil of the present report, granulosa cell tumor–associated metastases in the abdomen of gerbils, with the omentum being the most commonly affected organ, have been reported.10 Other sites of metastases include lymph nodes, kidneys, pancreas, liver, and diaphragm.4 Most granulosa cell tumors in gerbils are classified as malignant tumors.10 Incipient granulosa cell tumors in gerbils most frequently develop in animals < 2 years of age, especially those in which breeding has not been attempted.10 Gerbils may potentially be useful laboratory animals for further elucidation of the genetic, hormonal, and immunological pathogenesis of granulosa cell tumors in addition to evaluation of antineoplastic treatments.10 The current veterinary medical literature is lacking reports of treatments of and prognosis for gerbils with granulosa cell tumors.

References

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