Integrated Clinicopathologic and Genetic Characterization of Renal TFE3-Rearranged PEComa with Melanin Pigmentation: A Case Series and Comprehensive Literature Review

AimsTo investigate the clinical, histologic, and immunophenotypic features; genetic alterations; and prognosis of patients with renal TFE3-rearranged PEComa.MethodsThree patients were selected from the Department of Pathology, The Third Affiliated Hospital of Soochow University, between February 2017 and June 2023. Clinical, histopathologic, immunohistochemical, next-generation sequencing (NGS), and follow-up data were collected, and related studies were reviewed.ResultsAll tumors were detected by imaging studies. Ultrasound revealed well-circumscribed echogenic renal masses. Tumor tissue was separated by a fibrovascular network into nests, sheets, or acini, with varying amounts of melanin pigmentation. The tumor cells were epithelioid in shape, with clear or eosinophilic cytoplasm and prominent nucleoli. They were positive for TFE3 and HMB45 but negative for Melan-A, PAX8, CA9, CD10, keratin, vimentin, S100, SMA, and desmin. Notably, the tumor from the 28-year-old female patient demonstrated marked atypia, tumor necrosis, dystrophic calcification, and atypical mitotic figures. The <i>SFPQ::TFE3</i> fusion gene was detected in all 3 patients by NGS. Missense mutations in the <i>TP53</i>, <i>KRAS</i>, <i>MET</i>, and (tuberous sclerosis complex, TSC) <i>TSC2</i> gene were also detected. All patients survived without recurrence or metastasis.ConclusionsRenal TFE3-rearranged PEComa display unique clinicopathologic features, usually with insidious onset and potential for recurrence, metastasis, or death, and may represent an independent tumor subtype. Differential diagnoses include conventional perivascular epithelioid cell tumors and Xp11 translocation renal cell carcinoma. Patients with tumors confined to the kidney usually have a good prognosis after complete surgical resection.