The literature indicates that mesonephric carcinoma (MC) and mesonephric-like adenocarcinoma (MLA) typically lack mucinous and squamous features/differentiation. We report 4 cases of ovarian mucinous tumors (1 mucinous cystadenofibroma and 3 mucinous borderline tumors/atypical proliferative mucinous tumors [MBT/APMT]) co-existing with mesonephric-like lesions which were highlighted by Gata3 and Pax8 expression. All cases contained benign mesonephric-like proliferations (MLP) which focally displayed gastrointestinal-type mucinous metaplasia/differentiation and some were intimately admixed with mucinous glands associated with the mucinous tumor. Metaplastic mucinous epithelium retained expression of Gata3 and Pax8 in some areas while 1 mucinous cystadenofibroma and 1 MBT/APMT were focally positive for Pax8. Along with these mesonephric components, case 1 exhibited features of mesonephric hyperplasia and in 2 cases, 3 and 4, MLA was identified. In case 4, a KRAS c.35G>T (p.Gly12Val) somatic mutation was detected in both the MBT/APMT and the MLA, indicating a clonal origin. This same mutation was also detected in the benign MLP, indicating that it was likely an early genetic event. A CTNNB1 c.98C>T (p.Ser33Phe) somatic mutation, FGFR2 amplification, and CDKN2A/p16 deletion were only detected in the MLA but not in the MBT/APMT. Our result provides evidence to demonstrate the clonal relationship between these morphologically distinct components. Although speculative, we postulate that benign MLPs may give rise to lineage-specific mucinous and mesonephric-like lesions and propose that the MLPs are a new possible origin of some ovarian mucinous tumors. Whether these MLPs arise through transdifferentiation of Müllerian tissue or represent true mesonephric remnants, however, remains largely unknown.

Ovarian combined serous borderline tumor/low-grade serous carcinomas (SBT/LGSC) and mesonephric-like adenocarcinomas (MLA) have been previously reported and the presence of identical oncogenic somatic mutations in both components supports the concept that at least some of MLAs arise from a Müllerian origin. We report 2 cases of ovarian combined SBT/LGSC and mesonephric-like lesion. Case 1 was a 70-yr-old woman presented with a liver lesion and omental carcinomatosis. Histologic examination revealed biphasic tumors in bilateral ovaries consisting of conventional SBT and invasive MLA with extraovarian spread. The right ovary also had a component of cribriform variant of SBT/noninvasive LGSC. The SBT/LGSC component was diffusely positive for Pax8, WT-1, and ER, focally positive for PR, and negative for GATA3, while the MLA component was diffusely positive for GATA3 but negative for WT-1, ER, and PR. Molecular analysis revealed a KRAS G12V mutation in both the SBT/LGSC and MLA components, indicating their clonal origin. Case 2 was a 58-yr-old woman who presented with conventional type SBT in both ovaries. In addition, the left ovarian tumor demonstrated a few areas (each <5 mm) of mesonephric-like differentiation/hyperplasia in close proximity to the serous-type epithelium, with an immunophenotype of focal GATA3 expression, luminal pattern of CD10 staining and negative WT-1, ER, and PR staining. This phenomenon has been reported in endometrioid borderline tumor but not in any serous type lesions. The findings in case 1 provide further evidence to demonstrate the clonal relationship between these morphologically and immunophenotypically distinct components. It also supports the theory that, unlike cervical mesonephric carcinomas originating from mesonephric remnants, MLAs are derived from a Müllerian-type lesion with differentiation into mesonephric lineage. The presence of a hyperplastic mesonephric-like lesion/differentiation in case 2 indicates that a precursor lesion in the same lineage with the potential to develop into MLA exists in the ovary.