Mesonephric-like Adenocarcinoma (MLA) Diagnostic Criteria and Controversies: Perspectives and Guidance From Pathologists in the MLA Consortium

Mesonephric-like adenocarcinoma (MLA) is a rare and aggressive gynecologic malignancy that has only been recognized in the last decade. It arises in the endometrium, ovaries, and other extrauterine sites (often in association with endometriosis) and closely mimics a variety of other tumor types that occur in these locations. While it shows significant morphologic, immunohistochemical, and molecular homology with cervical mesonephric adenocarcinoma, there are many clinicopathologic features that suggest müllerian derivation, and this is now well established. As research on MLA has accumulated, questions have emerged about optimal practices for the diagnosis of these challenging tumors. In 2022, faculty at M.D. Anderson Cancer Center convened the Mesonephric-like Adenocarcinoma (MLA) Consortium, comprised of international pathologists, gynecologic oncologists, medical oncologists, radiation oncologists, and basic science investigators with expertise in MLA, with the goals to enhance understanding of these tumors, refine diagnostic criteria, improve treatment options, and facilitate research collaborations. An initial review from the consortium was published in 2025, and included diagnostic recommendations from the group's pathologists. Controversies remain, however, about the morphologic, immunohistochemical, and molecular criteria that should be used to establish a diagnosis of MLA. Herein, the pathologists from the MLA Consortium provide a comprehensive evaluation of the literature on MLA diagnostic criteria, address ongoing controversies in this area, and provide practical guidance for pathologists considering this entity.