Endometrial Mesonephric-Like Carcinoma With Prominent Clear Cell Carcinoma-Like Features

This report details findings from a morphologic, immunohistochemical, and molecular analysis of an example of endometrial mesonephric-like adenocarcinoma (MLA) with prominent clear cell carcinoma (CCC)-like features, with an assessment of whether such tumors represent mixed MLA/CCC or a morphologic subtype of MLA. Approximately 40% of an otherwise prototypical MLA was comprised of spatially discrete zones with prominent CCC-like morphology. The MLA-like nuclear features of both components were similar, as were their immunoreactivity patterns for estrogen receptor, progesterone receptor, SOX17, and calretinin (all negative), GATA3, and TTF1 (patchy positive). Diffuse immunoreactivity for CD10 and Napsin-A was limited to the CCC-like areas. Next generation sequencing of each macro-dissected component showed both to display the same <i>KRAS</i> variant (G12V), with similar variant allelic frequencies (42.5% [MLA]; 48.2% [CCC-like]). Although <i>KRAS</i> G12V lacks specificity for MLA, the totality of findings supports the interpretation that the CCC-like areas represent morphologic mimicry of CCC by MLA. Additional supportive factors include the similarity in nuclear features between the 2 components, absence of other architectural patterns of CCC in the CCC-like areas, co-expression of GATA3 and TTF1, as well as negativity for SOX17 in both components. This tumor highlights the potential for MLA to display striking CCC-like morphology, possibly leading to misclassification in a sampling specimen, and adds to the emerging literature on the potential for MLA to express Napsin-A.