Mesonephric and Mesonephric-Like Proliferations of the Gynecologic Tract

Mesonephric remnants are vestiges of Wolffian ducts located adjacent to the Müllerian ducts. Proliferations arising from these remnants are uncommon and classified as benign, including mesonephric hyperplasia, Gartner and rete cysts, papillary cystadenoma, rete adenoma, and female adnexal tumor of probable wolffian origin (only rare cases of the latter exhibited malignant behavior), or malignant, including mesonephric adenocarcinoma and carcinosarcoma. Morphologic evaluation aided by immunohistochemistry, especially in carcinomas, is the cornerstone to establish the correct diagnosis. In contrast to mesonephric adenocarcinoma, which arises predominantly in the cervix and is frequently associated with mesonephric hyperplasia, mesonephric-like adenocarcinoma is currently considered to be a neoplasm of Müllerian derivation that undergoes transdifferentiation into a Wolffian phenotype. There is significant morphologic, immunohistochemical, genetic and epigenetic overlap between mesonephric carcinoma and mesonephric-like carcinoma. However, distinctive features are seen in each of these entities, including primary site (cervix vs. corpus/extrauterine locations), associated precursors (mesonephric remnants/hyperplasia vs. atypical endometrial hyperplasia/endometriosis/other Müllerian neoplasm), and some differences in the immunohistochemical (more frequent ER and TTF1 positivity in mesonephric-like carcinoma) and molecular profiles (mesonephric-like adenocarcinoma more frequently harbors genetic alterations reported in other Müllerian tumors, such as PIK3CA, PTEN, and CTNNB1). In this review, we provide a detailed overview of the clinicopathologic and molecular features of benign mesonephric proliferations, mesonephric-derived tumors, and mesonephric-like adenocarcinoma, as well as their differential diagnoses.