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Xp11 translocation renal cell carcinoma (RCC), a member of the microphthalmia-associated transcription factor (MiTF) family, is a rare renal tumor characterized by different translocations involving the  TFE3  gene. Here, we reported a case of Xp11 translocation RCC with a rare  MED15-TFE3  gene fusion by RNA sequencing. Morphologically, the tumor cells were arranged in a solid and small nest pattern. The cytoplasm was voluminous, flocculent eosinophilic, and vacuolated. The nuclei were round or polygon with fine granular chromatin, and the nucleoli were unconspicuous. Psammoma bodies were observed in mesenchyma. Immunohistochemically, the tumor cells were diffuse moderately or strongly positive for CD10, P504S, vimentin, PAX8, RCC, AE1/AE3, and SDHB and focally positive for CK7 and CA IX while negative for cathepsin K, HMB45, Melan-A, Ksp-cadherin, and CD117. The Ki67 proliferation index was approximately 3%. However, TFE3 labeling showed an uncertainly weak nuclear staining and been considered negative. Fluorescence in situ hybridization (FISH) demonstrated a positive result that splits signals with a distance of > 2 signal diameters. Subsequently, RNA sequencing confirmed a fusion of  MED15  gene exon 11 on chromosome 22 with  TFE3  gene exon 6 in the tumor. The patient was alive with no evidence of recurrence. Our report contributes to the understanding on  MED15-TFE3  RCC.

A Rare Partner of TFE3 in the Xp11 Translocation Renal Cell Carcinoma: Clinicopathological Analyses and Detection of MED15-TFE3 Fusion