Conference 7 - 2016 Case: 4 20161019

Signalment:

Nine-year-old, female, Papillon (Canis familiaris).The dog presented for the mammary masses near the right third nipple and under the left forth nipple. As a result of the physical examination, the ovarian mass was also found. The ovaries and uterus were surgically with masses were sent to our laboratory for pathological examination.

Gross Description:

The left ovarian mass after fixed in neutral-buffered formalin was 5.2 x 4.5 x3.2 cm and was soft with milky white smooth to nodular surface. The cut surface showed white to light yellow solid area with necrosis.

Histopathologic Description:

The left ovarian mass consists of multiple lobules surrounded by a thin connective tissue stroma with very few interstitial glands of original ovarian structures. There are occasional multifocal to coalescing areas of necrosis in the mass. Lymphocytes and plasma cells slightly infiltrated in stroma around tumor cells. Each lobule mainly composed of solid and irregular nests of round tumor cells. Ductal structures and keratinizing epithelial cell nests were often mingled. Neoplastic round tumor cells showed a high N/C ratio and resembled to germ cells of seminoma/dysgerminoma. The tumor cells have large round nuclei with scattered chromatin and one or a few large nucleoli. The cytoplasm is abundant with weak-eosinophilic or clear, and infrequently vacuolated. Mitotic figures are frequently seen. The nuclear figure of epithelial tumor cells are similar to that of round tumor cells.

Immunohistochemically, both round and epithelial tumor cells are cytoplasmic weakly positive for alpha-fetoprotein and cytoplasmic granular positive for CD30. Each tumor cell types also are positive for octamer 4 (OCT4). Cytokeratin AE1/AE3 and CAM5.2 is strongly-expressed in the cytoplasm of epithelial tumor cells and weakly positive in less than 50% of round tumor cells. However, cytokeratin 7 and 20 are negative in both tumor cells. Vimentin expression is seen in some part of round tumor cells, but is not observed in epithelial tumor cells.

Morphologic Diagnosis:

Mixed germ cell tumor in canine ovary (dysgerminoma with embryonal carcinoma).

Lab Results:

N/A

Condition:

Ovarian mixed germ cell tumor

Contributor Comment:

Canine ovarian tumors are divided into sex cord-stromal (gonadostromal) tumors, germ cell tumors, epithelial tumors, and mesenchymal tumors. Epithelial tumors and sex cord-stromal (gonadostromal) tumors are the most common (80-90%). Germ cell tumors are less common, and account for 6% to 12% of canine ovarian tumors. Germ cell tumors are further classified to dysgerminoma, teratoma and embryonal carcinoma according to the WHO classification.^1,2,6,9,

In addition, yolk sac tumor and polyembryoma, chorio-carcinoma, and mixed germ cell tumor are included among ovarian germ cell tumors of human WHO classification. In canine ovarian germ cell tumors, dysgerminoma is most common and followed by teratoma.^2,9

The present tumor is mostly composed of round tumor cells, which resemble seminoma/dysgerminoma. Positive immuno-reactivitiy for OCT-4 of round tumor cells was also consistent with that of dysgerminoma, because OCT-4 is sensitive and specific immunohistochemical marker for dysgerminoma, However, ductal structures and keratinizing epithelial cell nests were often mingled, and these tumor cells including round tumor cell showed positive for embryonal carcinoma markers (AFP and CD30). Embryonal carcinoma composed of undifferentiated cells of epithelial appearance with solidly cellular areas, glands, and papillary projections.^8,13,14

Areas of solid growth in embryonal carcinomas histologically resemble dysgerminomas.⁸ In humans, embryonal carcinoma is a rare germ cell tumor and occurs as a component of mixed germ cell tumors more than pure embryonal carcinoma.¹⁴ In animals, no pure embryonal carcinomas have been reported, but a combination (mixed) germ cell tumor with embryonal carcinoma has been reported in only two rats and a cynomolgus monkey.^11,15

Embryonal carcinomas are immuno-histochemically distinguishable from dysgerminoma based on testing for AFP, CD30, cytokeratin AE1/AE3, CAM5.2 and cytokeratin 7, which are positive in embryonal carcinoma.^3,6,7Thus, in the present case, immunoreactivity of tumor cells did not perfectly satisfy the diagnostic criterion for both dysgerminoma and embryonal carcinoma. In addition, round tumor cells, which resemble dysgeminoma, are only partially positive for vimentin. In contrast, epithelial tumor cells forming ducts and nests were mostly negative for vimentin. Vimentin is immunopositive in dysgerminoma, and the reactivity is higher than embryonal carcinoma.^4,8,13 We considered that the present tumor was partially differentiated from dysgerminoma, and have the characteristics of both dysgerminoma and embryonal carcinoma. Thus, the present tumor was diagnosed as dysgerminoma with embryonic differentiation (mixed germ cell tumor composed of dysgerminoma and embryonal carcinoma) rather than pure embryonal carcinoma.

JPC Diagnosis:

Ovary: Mixed germ cell tumor, papillon, Canis familiaris.

Conference Comment:

The contributor provides a challenging diagnostic case rare ovarian neoplasm in a dog. Due to near effacement of the normal structures of the ovary by the neoplasm, some conference participants had trouble identifying the tissue as ovary. However, at the periphery of the neoplasm in all examined sections, there is a small amount of subsurface epithelial structures and granulosa cell islands characteristic of canine ovary. As mentioned by the contributor, tumors of the ovary are uncommon and have been described in many species. They typically originate from three distinct embryologic cell types: epithelial tumors of Mullerian origin (adenoma or carcinoma), sex cord stromal tumors (granulosa cell tumor and thecoma), and germ cell tumors (dysgerminoma, teratoma, yolk sac tumors). Mixed germ cell tumors are a combination of germ cells and sex cord stromal cells. In male dogs, mixed germ cell tumors are the fourth most common primary testicular neoplasm and are typically characterized by a combination of seminoma and Sertoli cell tumor, with the tubular structures of Sertoli cell tumors containing neoplastic germ cells.^5,10,12 They are extremely rare in the ovary with reported cases in a Labrador retriever and a cynomolgus monkey.^10,11,15

Among canine ovarian tumors, granulosa cell tumors and epithelial tumors are by far the most common.¹² In this case, the contributors posit that this is a dysgerminoma mixed with an embryonal carcinoma, favoring the diagnosis of a mixed germ cell tumor. This interesting case stimulated discussion among conference participants. Some favored the diagnosis of mixed germ cell tumor and others favored a sex cord stromal tumor, dysgerminoma, or a collision tumor. We reviewed this case in consultation with physician genitourinary pathologists at the Joint Pathology Center, who agreed with the contributor and the majority of conference participants, that there are foci suggesting a yolk sac tumor (5%), embyronal carcinoma (~25%) and predominantly dysgerminoma (70%), thus favoring the diagnosis of a mixed germ cell tumor. This case was also studied in consultation with Dr. Robert Foster, a board certified veterinary pathologist and recognized expert with extensive experience in the area of veterinary reproductive pathology. He offers a dissenting view that the highly anaplastic cells may not be germ cells and instead favors the diagnosis of a poorly differentiated ovarian sex cord stromal tumor. He also notes that immunohistochemistry in ovarian tumors can be problematic in domestic species.

References:

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