Ovarian Combined Low-grade Serous and Mesonephric-like Adenocarcinoma: Further Evidence for A Mullerian Origin of Mesonephric-like Adenocarcinoma

Mesonephric-like adenocarcinomas are rare neoplasms occurring in the uterine corpus and ovary which bear a close morphologic resemblance to cervical mesonephric adenocarcinomas. They also have a similar immunophenotype and harbor similar molecular abnormalities to mesonephric adenocarcinomas and it is debated whether they are truly of mesonephric origin or represent Mullerian neoplasms closely mimicking mesonephric adenocarcinomas. We report an unusual case with bilateral ovarian serous borderline tumors and extraovarian low-grade serous carcinoma (invasive implants). In one ovary, there was a component of mesonephric-like adenocarcinoma. The immunophenotypes of the serous and the mesonephric-like components were distinct and as expected for the individual tumor types (serous component diffusely positive with WT1 and estrogen receptor and negative with GATA3, TTF1 and CD10; mesonephric-like component WT1 and estrogen receptor negative and GATA3, TTF1, and CD10 positive; both components diffusely positive with PAX8 and exhibiting "wild-type" p53 immunoreactivity). In all components (bilateral serous borderline tumors, low-grade serous carcinoma and mesonephric-like adenocarcinoma), an identical KRAS mutation was detected (NM_004985.4): c.35G>A, p.(G12D) proving a clonal association between the serous and mesonephric-like components and excluding a collision neoplasm. This represents the second reported case of a combined ovarian low-grade serous tumor and mesonephric-like adenocarcinoma; in the previously reported case, an identical NRAS mutation was present in both components. These 2 cases provide evidence that ovarian mesonephric-like adenocarcinomas have, at least in some cases, a Mullerian origin and differentiate along mesonephric lines. We present additional evidence for this by reviewing associated findings in published and unpublished ovarian mesonephric-like adenocarcinomas; 8 of 11 of these neoplasms contained other Mullerian lesions in the same ovary, mainly endometriosis and adenomas/adenofibromas.