Clinicopathological and molecular features of gynecologic perivascular epithelioid cell tumors: a single-center study.

Background: Perivascular epithelioid cell tumors (PEComas) are rare neoplasms characterized by the expression of both melanocytic and myoid markers. Gynecologic PEComa may show overlapping with smooth muscle tumors and other uterine tumors. The rarity and ill-defined risk stratification make the diagnosis challenging. The current study was aimed to more fully characterize gynecologic PEComas. Methods: We investigated the clinicopathological and immunohistochemical features of nine gynecological PEComas from a single center. The molecular landscape was assessed using a combined DNA-RNA hybrid capture-based comprehensive genomic profiling assay. Results: Patients, aged from 27 to 79 years old, presented with the disease predominantly located in the uteri (5/9) and cervix (3/9). Histologically, six cases were classified as malignant and three as having uncertain malignant potential. All tumors were composed of epithelioid or spindled cells arranged around the vessels, with variable nuclear atypia and necrosis. Immunohistochemical analysis revealed universal HMB45 and TFE3 positivity, and variable myoid marker expression. HMB45 was confirmed as the most sensitive diagnostic marker. Mutually exclusive genetic alterations were identified in all six tested cases with TSC2 mutations/deletions in three tumors and TFE3 fusions in another three. And here we reported a novel YAP1-TFE3 gene fusion in gynecological site. It was found TSC2-altered tumors harbored more additional mutations, whereas TFE3-rearranged tumors occurred in younger patients. Most cases showed malignant potential or malignancy, necessitating risk stratification according to the current WHO algorithms. Conclusions: This study highlights the key histological and molecular features, and advocates for integrated DNA/RNA sequencing to guide prognosis and targeted therapies.