Napsin-A Expression in Mesonephric and Mesonephric-like Adenocarcinomas: Implications for Distinction From Clear Cell Carcinoma

Mesonephric adenocarcinoma (MA) and mesonephric-like adenocarcinoma (MLA) are rare gynecological neoplasms that sometimes exhibit morphologic overlap with clear cell carcinoma (CCC), which may lead to diagnostic challenges. Napsin-A is regarded as the most specific immunohistochemical marker of CCC, but its expression in MLA and MA has not been widely investigated. This study investigated the expression of Napsin-A in a series of MAs and MLAs to determine its utility in distinguishing these neoplasms from CCC. The cohort included 32 MLAs arising in the ovary, endometrium, abdominal wall, and sigmoid mesocolon, 13 cervical MLAs, 2 ovarian mesonephric-like carcinosarcomas, and 1 cervical mesonephric carcinosarcoma, with Napsin-A immunohistochemistry performed on whole-slide tissue sections. Napsin-A staining was positive in 17 of 48 cases (35.4%), with focal granular cytoplasmic expression ranging from 1% to 40%. In all, 13/32 (40.6%) MLAs, 2/13 (15.4%) MAs, and 2/3 (66.7%) mesonephric or mesonephric-like carcinosarcomas were positive. Our results demonstrate that Napsin-A is expressed in a significant subset of MLAs and MAs. Given the morphologic and immunohistochemical overlap, this may contribute to misclassification as CCC, especially in cases with ambiguous morphology. Pathologists should be aware of this diagnostic pitfall and employ a panel of markers rather than relying on a single marker.