Figure 5.

Based on the morphologic findings and molecular changes, two models are proposed to explain the histopathogenesis of the mixed tumors in our report as well as in other studies. In theory, a Müllerian-type progenitor cell can acquire KRAS or NRAS mutations and develop into a serous borderline tumor/non-invasive low-grade serous carcinoma (SBT/niLGSC) that continues to give rise to both invasive LGSC and mesonephric-like adenocarcinoma (MLA) (A). Our case 1 supports this model. Alternatively, the tumor with mixed histology may originate from a pluripotent stem cell in the embryonic ridge which acquires KRAS or NRAS mutations and differentiates in parallel along both Müllerian (SBT/niLGSC to invasive LGSC) and mesonephric lineage (mesonephric hyperplasia to MLA) (B). The presence of a non-malignant mesonephric-like component in case 2 indicates the latter possibility does theoretically exist, although a carcinomatous component, either serous or mesonephric-like, is not present in this case.