Expanded Histologic Lineage and Origin of Mesonephric-Like Adenocarcinoma: A Clinicopathologic Study of 9 Cases

Mesonephric-like adenocarcinoma (MLA) is a rare gynecologic malignancy primarily arising in the uterine corpus and ovaries. It shares remarkable similarities in its histomorphology, immunophenotype, and molecular features with mesonephric adenocarcinoma of the cervix. Controversy remains regarding whether the MLA originates from the mesonephric or Müllerian ducts. In this study, we retrospectively analyzed the clinicopathologic, immunohistochemical, and molecular characteristics of 9 MLA cases. Among these, we observed 2 unique cases for the first time: 1 case of ovarian MLA coexisting with a benign mucinous cystadenoma and 1 case of MLA located on the cervical mucosal surface. In addition, 1 case presented with a mesenteric MLA component intermixed with clear cell carcinoma, and endometriosis was detected around the cancerous tissue and in the adjacent ovary. Of the remaining 6 cases, 3 were associated with endometriosis or adenomyosis. Next-generation sequencing of 7 cases revealed KRAS mutations in 5 cases and mutations in PTEN/BRAF and ERBB3 in 1 case each. The identification of MLA in atypical locations such as the mesentery and cervical mucosa expands the histologic spectrum of this tumor and provides further support for the hypothesis of a Müllerian epithelial origin. The findings of this study broaden the known morphologic and anatomic distribution of MLA and contribute to a better understanding of its pathogenesis.