Primary Renal Perivascular Epithelioid Cell Tumor with CLTC::TFE3 Gene Fusion: A Rare Gene Fusion and Masquerading as Renal Cell Carcinoma.

We report a primary perivascular epithelioid cell tumor (PEComa) of the kidney harboring a novel CLTC::TFE3 gene fusion in a 51-year-old woman. The tumor was composed of high-grade epithelioid cells with clear to eosinophilic cytoplasm arranged in nested and alveolar architectures, closely mimicking clear cell renal cell carcinoma, which posed a significant diagnostic pitfall. Immunophenotypically, the tumor lacked multiple epithelial and renal lineage markers but showed diffuse positivity for melanocytic markers and cathepsin K. TFE3 rearrangement was confirmed by fluorescence in situ hybridization and an in-frame CLTC::TFE3 fusion involving exons 1-17 of CLTC and exons 6-10 of TFE3 was identified by subsequent RNA sequencing. The patient developed an aggressive clinical course, with early brain metastasis and multiple recurrences over a five-year period despite multiple radical surgical resections, radiotherapy, and systemic therapy. This tumor represents the first reported primary renal PEComa harboring a CLTC::TFE3 fusion and the second tumor with this fusion reported in the literature. Our findings expand the molecular spectrum of TFE3-rearranged PEComa and underscore the importance of comprehensive immunohistochemical and molecular profiling in accurately diagnosing these rare tumors and distinguishing from their morphologic mimics.