“Papillary Adenoma-like” Renal Tumor with TFE3 Gene Rearrangement,A Potential Precursor to or Early Event in the Development of TFE3 Translocation Renal Cell Carcinoma

Abstract

MiT family translocation renal cell carcinomas harbor gene fusion involving members of MiT family of transcription factors. Their precursor lesions have not been identified. Herein, we report the first case of small papillary tumors morphologically resembling papillary adenomas but harboring TFE3 gene alteration. The patient was a 23-year old man with multiple small papillary tumors in the right kidney discovered following a gunshot wound injury. These lesions were < 5 mm, well-circumscribed but not encapsulated tubulopapillary proliferation lined with a single layer of cuboidal cells with WHO/ISUP grade 1 or 2 nuclei. The tumor cells were immunoreactive to PAX8, AMACR, high molecular weight cytokeratin, and keratin 7 and negative for CD10, CA9, TTF1, and cathepsin K. Morphologically and immunohistochemically, these lesions were diagnosed as papillary adenomas. TFE3 gene rearrangement was confirmed by fluorescence in-situ hybridization (FISH) using a TFE3 break-apart probe. We term these tumors “papillary adenoma-like” renal tumor with TFE3 gene rearrangement. These tumors are likely a precursor to or represent an early event in the development of TFE3 translocation renal cell carcinomas. An understanding of such tumors to translocation renal cell carcinoma progression can provide insight into the pathogenic mechanism, and ultimately aid the diagnosis and management of translocation renal cell carcinoma.