Ovarian Intermediate Trophoblastic Tumors: Genotyping Defines a Distinct Category of Nongestational Tumors of Germ Cell Type.

Trophoblastic neoplasms involving the ovary are uncommon and include gestational tumors, which are either metastatic from the uterus or ectopic and nongestational tumors, which include those of germ cell type/origin and somatic tumors with trophoblastic differentiation; in all these types, most are pure choriocarcinoma. Intermediate trophoblastic tumors, which include placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT), are rare in the ovary, with most assumed to be gestational; this is the only category formally recognized in 2014 World Health Organization (WHO) classification, likely due to few well-documented nongestational examples. We report the clinicopathologic features of 6 ovarian intermediate trophoblastic tumors, including 3 PSTTs, 2 ETTs, and 1 ETT with choriocarcinomatous differentiation. DNA-based short tandem repeat genotyping identified 4 of these as nongestational (3 PSTTs and 1 ETT), as evidenced by sharing of alleles between tumor and normal tissue at all informative loci. Interestingly, all 3 of the nongestational PSTTs coexisted with mature cystic teratoma. The remaining 2 tumors (1 ETT and 1 ETT with some choriocarcinomatous differentiation) were gestational (likely ectopic due to lack of evidence of a uterine tumor), as evidenced by the presence of both maternal and novel/nonmaternal alleles at informative loci in tumor compared with normal tissue. It is important to recognize a distinct category of primary ovarian nongestational intermediate trophoblastic tumors of germ cell type/origin, including PSTT and ETT, in classification systems to guide clinical management, as gestational and nongestational tumors have different genetic origins and may require different therapy. Genotyping is useful for classification as nongestational versus gestational, particularly as traditional clinicopathologic findings cannot always predict the nature of a trophoblastic tumor.

Nonchoriocarcinomatous Trophoblastic Tumors of the Testis: The Widening Spectrum of Trophoblastic Neoplasia.

Tumors of trophoblastic derivation other than choriocarcinoma are very rare in the testis but have been reported on occasion in association with other germ cell tumors. Their morphologic spectrum is analogous to the trophoblastic tumors of the female genital tract including epithelioid trophoblastic tumor (ETT) and placental site trophoblastic tumor (PSTT). Herein we report our experience with 8 cases of trophoblastic tumors of testicular origin that lacked the features of choriocarcinoma; these included 4 ETTs, 1 PSTT, 1 unclassified trophoblastic tumor (UTT), 1 partially regressed choriocarcinoma with a monophasic morphology, and 1 hybrid tumor showing a mixture of adenocarcinoma and a UTT. All tumors occurred in young men 19 to 43 years old. Five arose de novo within the testis (2 ETTs, 1 UTT, 1 regressing choriocarcinoma, and the hybrid tumor) as a component of mixed germ cell tumors, and 3 (2 ETTs and 1 PSTT) were found in metastatic sites after chemotherapy. The trophoblastic component was minor (5% to 10%) in 6 tumors but was 95% of 1 metastatic tumor (ETT) and 50% of the hybrid tumor. Other germ cell tumor elements were identified in all cases, most commonly teratoma. The ETTs consisted of nodules and nests of squamoid trophoblast cells showing abundant eosinophilic cytoplasm, frequent apoptotic cells, extracellular fibrinoid material, and positivity for p63 and negativity for human placental lactogen (HPL). The PSTT showed sheets of discohesive, pleomorphic, mononucleated trophoblast cells that invaded blood vessels with fibrinoid change and were p63 negative and HPL positive. The UTT showed a spectrum of small and large trophoblast cells, some multinucleated but lacking distinct syncytiotrophoblasts, and was patchily positive for both p63 and HPL. The hybrid tumor had ETT-like and adenocarcinomatous areas that coexpressed inhibin and GATA3 but were negative for p63 and HPL, leading to classification of the trophoblastic component as UTT. Seven of the patients were alive and well on follow-up (8 to 96 mo; median, 39 mo), whereas the patient with the hybrid tumor died of liver metastases at 2 years. Our study verifies that trophoblastic neoplasms often having the features of nonchoriocarcinomatous gestational trophoblastic tumors may arise from the testis, occur either in the untreated primary tumor or in metastases after chemotherapy, and should be distinguished from choriocarcinoma given what appears to be a less aggressive clinical course.