Xanthomatous giant cell renal cell carcinoma: clinicopathologic and molecular characterization of 2 additional cases with biallelic TSC2 mutations.

Abstract

To characterize the clinicopathologic, immunohistochemical, and molecular features of 2 new cases of xanthomatous giant cell renal cell carcinoma, a rare TSC2/MTOR-altered renal neoplasm. Both tumors underwent histologic evaluation, immunohistochemical profiling, and DNA-based targeted next-generation sequencing. Fluorescence in situ hybridization for TFE3 rearrangement was performed in 1 case. Both patients were men (aged 27 and 64 years) with incidentally detected renal masses showing infiltrative growth and discohesive large cells with a xanthomatous-eosinophilic cytoplasm, basophilic stippling, vacuolization, and prominent nucleoli. Both tumors were positive for PAX8, CD10, vimentin, and GPNMB; keratin 20 was diffusely strong in 1 patient and isolated in the other. One case showed TFE3 and Melan-A coexpression without TFE3 rearrangement. Biallelic TSC2 mutations were identified in both cases, corroborated by loss of TSC2 protein expression. Both patients were disease-free at 15 and 40 months postsurgery. Xanthomatous giant cell renal cell carcinoma represents a distinct morphologic variant of TSC/MTOR-altered renal neoplasms with indolent behavior despite aggressive histologic features.