Signalment:  

Female mouse (Mus musculus), age and strain not given.Incidental finding at sentinel health monitoring.

Gross Description:  

The left ovary was enlarged and hemorrhagic.

Histopathologic Description:

The enlarged ovary contains a mass, characterized by sheets of large pleomorphic cells with abundant eosinophilic cytoplasm, in a large focus of hemorrhage within the ovarian bursa. The cells have a large round to oval, sometimes irregular, nucleus, with vesicular chromatin and multiple nucleoli, with occasional dark staining nuclei, and rare binucleate cells. Mitoses are rare.

Morphologic Diagnosis:  

Ovary: choriocarcinoma.

Condition:  

Choriocarcinoma

Contributor Comment:  

Tumors of the ovary are divided into three groups based on the presumed tissue of origin: tumors of surface epithelium, including adenomas and carcinomas; germ cell tumors including teratomas, dysgerminomas, choriocarcinomas; and sex cordstromal tumors including granulosa cell tumors, thecomas, fibromas.(1)

The choriocarcinoma is a malignant neoplasm of trophoblastic cells, which in women often has widespread metastases. Choriocarcinoma is one of the rarest ovarian tumors in women, estimated to occur in only 1 in 369,000 women.3 Most choriocarcinomas in women occur in the uterus, post pregnancy. These tumors are also rare in animals, although they have been reported in rhesus and cynomolgus macaques, rabbits, a cow, dogs, mice and rats.(1,2,3,4,6,7) Choriocarcinomas may arise in the uterus, ovary or testis. 

The incidence of ovarian tumors in mice varies with the strain.(2,4) Ovarian tumors are also more common in older mice (> 18 months of age). In mice, ovarian neoplasms are more common in the B6C3Fl mouse, but ovarian choriocarcinoma is only 1% of ovarian tumors.(4) The most common ovarian tumors in B6C3F1 mice are epithelial, granulosa cell tumors and teratomas.(1) In our laboratory, we have identified six ovarian choriocarcinomas in the last 10 years, all in sentinel mice as an incidental finding during health monitoring.

JPC Diagnosis:  

Ovary: Choriocarcinoma.

Conference Comment:  

Malignant trophoblastic tumor variants are classified as choriocarcinomas (CC), epithelioid trophoblastic tumors (ETT), or placental site trophoblastic tumors (PSTT). Trophoblastic tumors usually develop either during or following gestation, but have rarely been reported to develop from germ cells in the absence of pregnancy.(7) Choriocarcinomas, as seen in this case, are characterized by a bilaminar pattern composed of cytotrophoblasts and syncytiotrophoblasts often associated with prominent hemorrhage.(5) Although pure nongestational choriocarcinomas are extremely rare in humans, CC can be a component of a mixed germ cell tumor of the ovary,(7) ETTs are composed of a relatively uniform population of mononucleate trophoblastic cells with eosinophilic or clear cytoplasm; these cells are intermediate trophoblastic cells that resemble chorion laeve.(5) PSTTs originate from large, polygonal intermediate trophoblastic cells of the placental bed. Although nongestational trophoblastic tumors are rare in humans, several have been described in captive non-human primates, including CC and ETT. Additionally, a pure nongestational malignant PSTT of the ovary was recently reported in a young rhesus monkey.(7)

References:

1. Alison RH, Morgan KT. Ovarian neoplasms in F344 rats and B6C3F1 mice. Environ Health Perspect. 1987;73:91-106.
2. Alison RH, Lewis DJ, Montgomery CA. Ovarian choriocarcinoma in the mouse. Vet Pathol. 1987;24:226-230.
3. Farman CA, Benirschke K, Horner M, Lappin P. Ovarian choriocarcinoma in a rhesus monkey associated with elevated serum chorionic gonadotropin levels. Vet Pathol. 2005;42:226-229.
4. Frith CH, Evans MG. Spontaneous ovarian choriocarcinoma, yolk sac carcinoma, and teratoma in B6C3F1 mice: a case report. Toxicol Pathol. 1993;21:91-98.
5. Horn LC. Intermediate Trophoblastic Tumors and Tumor-like Lesions-the Clinicopathologic Aspects. IAP 2006 Annual Congress. Symposium #41, section 3. Accessed online at http://www.uscap.org/index.htm?iap2006/symp41-3.htm on 3 February 2013. 
6. Kaufmann-Bart M, Fischer I. Choriocarcinoma with metastasis in a rabbit (Oryctolagus cuniculi). Vet Pathol. 2008;45:77-79.
7. Marbaix E, Defrere S, Ho Minh Duc K, Lousse JC, Dehoux JP. Nongestational malignant placental site trophoblastic tumor of the ovary in a 4-year-old Rhesus Monkey. Vet Pathol. 2008;45:375-378. 
8. Pirak M, Waner T, Abramovici A, Scolnik M, Nyska A. Histologic and immunohistochemical study of a spontaneous choriocarcinoma in a male Sprague Dawley rat. Vet Pathol. 1991;28:93-95.

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4-1. Ovary

4-2. Ovary

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