Ovarian Mucinous Neoplasms Associated With Mesonephric-like Lesions

The coexistence of benign mesonephric-like proliferation (MLP), mesonephric-like hyperplasia (MLH), and mesonephric-like adenocarcinoma (MLA) with ovarian mucinous cystadenoma or mucinous borderline tumor (MBT) has been previously reported; however, this phenomenon is exceedingly rare, and understanding of the pathology and biology remains limited. Here we report additional cases, with an emphasis on expanded observations and novel pathologic features. This series included 9 cases: (1) 2 cases of mixed MLA and endometrioid adenocarcinoma associated with cystic mucinous neoplasm of lower gastrointestinal (GI) type (case 1) or mucinous cystadenoma (case 2); (2) 1 case of MLA associated with MBT and mucinous adenocarcinoma (case 3); (3) 4 cases of MLA associated with MBT (cases 4 and 5) or mucinous cystadenoma (cases 6 and 7); and (4) 2 cases of MLP/MLH associated with MBT (cases 8 and 9). All mesonephric-like lesions were diffusely positive for PAX8 and either diffusely (7 cases) or focally (2 cases) positive for GATA3. Focal TTF-1 expression was observed in 4 cases (4/9, 44.4%). All mucinous tumors, except for case 1, showed either focal (4 cases) or diffuse (4 cases) PAX8 positivity. Molecular analysis in case 1 revealed a common KRAS p.G12A driver mutation in all 3 tumor components (MLA, endometrioid adenocarcinoma, and mucinous tumor), indicating clonal relatedness. In contrast, pathogenic somatic mutations in ARID1A, DNMT3A, PIK3CA, and TET2 were detected only in the MLA and endometrioid adenocarcinoma, but not in the mucinous tumor component, suggesting lineage-specific differentiation. Notably, case 1 represents the first reported example of a mesonephric-like lesion associated with a mucinous tumor exhibiting lower GI morphology and immunophenotype. Case 3 represents the first case with mucinous adenocarcinoma in this scenario. Case 9 represents the first reported instance in which both ovaries were independently involved by MLP/MLH and MBT. The presence of benign MLP/MLH alongside MLA suggests that the former may represent noncancerous precursor lesions with the potential to develop into MLA; they may represent benign (MLP) or borderline (MLH) mesonephric-like lesions. Whether mesonephric-like lesions serve as precursors of ovarian mucinous tumors remains debated, but their coexistence in the ovary, as documented in 20 cases to date (including previously published cases and the current series), may represent a unique biological process and provide an ideal model for investigating mechanisms of transdifferentiation and tumorigenesis.