Renal cell carcinoma with TFE3 translocation and succinate dehydrogenase B mutation

Abstract

Translocation renal cell carcinoma and succinate dehydrogenase (SDH)-deficient renal cell carcinoma are now recognized as specific renal tumor types in the World Health Organization (WHO) classification. Both have limited immunohistochemical positivity for epithelial markers, and the spectrum of morphology continues to widen for both of these entities. We identified four renal cell carcinomas with positive TFE3 immunohistochemical staining and negative SDHB staining. The patients (2F, 2M) ranged in age from 19 to 65 years. All tumors were composed, at least in part, of eosinophilic cells. Cytoplasmic inclusions, prominent nucleoli, and mitotic figures were seen in three tumors. Psammoma bodies were also present in two tumors. Using immunohistochemistry, a broad spectrum of commonly used renal tumor markers yielded nonspecific, limited positivity, including uniformly positive reactions for PAX8 but negative results for cathepsin K and HMB45. Fluorescence in situ hybridization results showed the presence of TFE3 gene rearrangement in all four tumors, and molecular analysis revealed SDHB mutations in neoplastic cells of three tumors. In one case, the same SDHB mutation was confirmed in the adjacent non-neoplastic tissue. We report for the first time the presence of both TFE3 translocation and SDHB mutation in the same tumor.