Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms that can arise in various anatomical locations, including the female genital tract, with the uterus being the most affected site. Malignant uterine PEComas are extremely uncommon and pose significant diagnostic challenges, particularly when they lack conventional immunohistochemical (IHC) marker expression. This report presents a rare case of a high-grade, TFE3-rearranged malignant PEComa of the uterus that defied routine diagnostic approaches.

This case underscores the diagnostic complexity of TFE3-rearranged PEComas, which can lack smooth muscle marker expression and mimic other high-grade uterine malignancies. Recognition of the nested vascular arrangement and utilization of melanocytic and TFE3 markers are key for diagnosis.