MITF-Overexpressing Perivascular Epithelioid Cell Tumor of the Urinary Bladder Lacking TSC1/TSC2 Alterations and TFE3 Rearrangement: A Case Report and Review of the Literature.

Perivascular epithelioid cell tumors (PEComas) are mesenchymal neoplasms characterized by melanocytic and smooth muscle differentiation, commonly associated with TSC1/TSC2 alterations or TFE3 rearrangements. Herein, we report a rare case of urinary bladder PEComa with MITF overexpression and without identifiable TSC1/TSC2 mutations or TFE3 rearrangement. A 50-year-old man underwent partial cystectomy for a bladder mass. Histologically, the tumor was well circumscribed and composed of mixed spindle and epithelioid cells with cytologic atypia and low mitotic activity. Immunohistochemistry revealed diffuse expression of SMA, HMB45, and MITF, with negative staining for TFE3. Quantitative reverse-transcription PCR revealed increased MITF mRNA expression in PEComa tissue. Next-generation sequencing identified a truncating ATRX mutation but no alterations in TSC1/TSC2 or TFE3, and no MITF copy number gain. By Folpe criteria, the tumor was classified as malignant, whereas alternative models suggested a lower-risk category, highlighting the limitations of histologic risk stratification systems. The absence of canonical TSC/mTOR or TFE3 alterations, together with MITF overexpression, suggests a distinct molecular mechanism potentially involving dysregulation of the MiT/TFE pathway. This case expands the molecular spectrum of PEComa and supports the existence of a MITF-driven subset, highlighting the need for integrated histologic and molecular evaluation for prognostic assessment.