Original ArticlesOvarian Intermediate Trophoblastic Tumors Genotyping Defines a Distinct Category of Nongestational Tumors of Germ Cell TypeXing, Deyin MD, PhD*,†; Zhong, Minghao MD, PhD‡; Ye, Fei PhD‡; O’Malley, Michael T. MD§; Li, Shaotiao MD∥; Vang, Russell MD*,¶; Ronnett, Brigitte M. MD*,¶Author Information Departments of *Pathology †Oncology ¶Gynecology and Obstetrics, The Johns Hopkins Medical Institutions §Department of Pathology, Sinai Hospital, Baltimore, MD ‡Department of Pathology, New York Medical College, Valhalla, NY ∥Department of Pathology, Longgang Hospital, Zhejiang, China D.X. and M.Z. contributed equally. Conflicts of Interest and Source of Funding: Supported by the Career Enhancement Award by the Cervical Cancer SPORE program (P50CA098252) at Johns Hopkins (D.X.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Deyin Xing, MD, PhD, Department of Pathology, The Johns Hopkins Hospital, Weinberg 2242, 401 North Broadway, Baltimore, MD 21231 (e-mail: [email protected]). The American Journal of Surgical Pathology: April 2020 - Volume 44 - Issue 4 - p 516-525 doi: 10.1097/PAS.0000000000001402 Buy SDC Metrics Abstract 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. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.