ASPSCR1: TFE3 Fusion-Positive Epithelioid Angiomyolipoma/PEComa Lacking Melanocytic Markers: A Case Report.

Epithelioid angiomyolipoma is a rare perivascular epithelioid cell tumor subtype with malignant potential. Its morphology mimics renal cell carcinoma, posing diagnostic challenges. Half of these cases harbor TSC1/TSC2 alterations, and a small subset features TFE3 rearrangements, mutually exclusive of TSC mutations. Recently, "perivascular epithelioid cell tumor-like neoplasms" with ASPSCR1::TFE3 fusion lacking melanocytic markers were described. A 25-year-old woman presented with a 4.5-cm renal mass. Biopsy suggested TFE3-rearranged renal cell carcinoma because of diffuse TFE3 positivity and no HMB45 immunoreactivity. Postoperatively, despite a complete lack of melanocytic markers, the tumor was diagnosed as TFE3-rearranged epithelioid angiomyolipoma based on its epithelioid morphology and PAX8 negativity, including a retrospective biopsy study. Fluorescence in situ hybridization confirmed ASPSCR1::TFE3 fusion, suggesting this rare, newly recognized entity. TFE3-rearranged epithelioid angiomyolipoma can lack melanocytic markers. PAX8 immunohistochemistry and genetic testing help distinguish this potentially aggressive tumor from renal cell carcinoma and TSC-mutated subtypes.