Unclassified renal cell carcinoma (RCC) accounts for ∼10% of renal tumors, and the most common histologic findings in these cases is eosinophilic cytoplasm. We previously demonstrated that a subset of eosinophilic renal tumors with heterogeneous morphology and immunohistochemical staining harbored pathogenic mutations in tuberous sclerosis complex (TSC) or mammalian target of rapamycin (MTOR) as the primary defining mutation. We identified an additional 8 cases of eosinophilic tumors with unusual morphology that were originally diagnosed as chromophobe RCC (CHRCC) or CHRCC, eosinophilic variant. As a comparison, we included four classic CHRCC cases and one CHRCC, eosinophilic variant case. Gross examination revealed solid or solid and cystic patterns. The solid areas were composed of eosinophilic tumor cells divided by congested vessels while the cystic areas were lined by cytologically bland eosinophilic cells with septae containing nests, ribbons, and single eosinophilic tumor cells. The tumor cells had abundant granular eosinophilic cytoplasm with round nuclei and inconspicuous nucleoli. IHC analysis demonstrated diffuse staining for CK7 and negative staining for CK20 and vimentin. Next generation sequencing identified pathogenic variants in three genes: TSC1, TSC2, and MTOR. They also lacked significant copy number variations in contrast to our control cases. We have demonstrated with our expanded study that cases previously diagnosed as CHRCC or CHRCC, eosinophilic variant with discordant histology and IHC staining patterns may represent a separate subtype of RCC characterized by mutations in the TSC/MTOR pathway.
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