Series of renal cell carcinomas with TFE3 overexpression by copy number gains and without TFE3 gene rearrangement.

This case series describes four renal cell carcinomas (RCCs) with positive TFE3 protein expression by immunostain and only copy number gains detected by TFE3 fluorescence in situ hybridization without TFE3 rearrangement. Three of the four cases were diagnosed as clear cell RCC, and one was unclassified. All four cases were staged as pT3a on nephrectomy. Three of them were grade 4 and had documented metastases. This raises the possibility that RCC with TFE3 copy number gains in the absence of gene rearrangement may be a poor prognostic factor and reinforces that TFE3 immunostain cannot be used alone to diagnose TFE3-rearranged RCC.