Clinicopathological features and prognosis analysis of 11 patients with TFE3-rearranged perivascular epithelioid cell tumors.

e23551 Background: To explore the clinicopathological features and prognostic analysis of TFE3 -rearranged PEComas. Methods: FISH data from PEComas patients diagnosed with TFE3 gene disruption between January 2014 and October 2024 were collected. The clinical features and pathology of the patients were analyzed. Results: A total of 11 patients with confirmed TFE3 rearrangement detected by FISH were included in the study, including 7 females and 4 males aged 25-70 years at diagnosis. The primary tumor sites were as follows: the retroperitoneum and abdominal cavity, kidney, transverse colon, urachal duct, uterus, and left lung. The maximum diameter of the tumor was 18 cm, the minimum diameter was 0.5 cm (accidentally discovered during other surgeries), the median value was 6 cm, and the mean value was 8.46 cm. The imaging manifestations of TFE3 -rearranged PEComas vary depending on the location and size of the tumor. RNA sequencing was performed on samples from 4 patients, revealing that 2 patients had SFPQ::TFE3 fusion, 1 patient had ASPSCR1::TFE3 fusion, and 1 patient had no known gene fusions. As of December 31, 2024, 2 patients were lost to follow-up after diagnosis, and among the 9 patients followed up, the median follow-up time was 31 months (4-139). With regard to treatment, all nine patients who completed follow-up underwent resection of the primary tumor. During follow-up, 6 patients achieved disease-free survival (4-94 months). Patient 1 developed liver metastasis 80 months after surgery. After that, the patient received surgical treatment for the liver metastasis. When the disease progressed, the patient was treated with everolimus. Patient 3 was diagnosed with lung metastasis following surgery for a renal lesion and did not undergo any further treatment. Patient 4 had multiple recurrences and underwent 4 surgeries. She successively received treatments of apatinib, everolimus, anlotinib combined with tislelizumab. She died 34 months after diagnosis. Conclusions: TFE3 -rearranged PEComas have unique clinicopathological features, with the majority of primary lesions occurring inside the abdominal cavity. After TFE3 rearrangement, PEComas are highly invasive, with potential for recurrence and metastasis, and the overall disease progression is relatively slow. At present, the primary treatment is surgery, and pharmacotherapy can increase the survival time of some patients. This study provides new clinical and molecular insights into TFE3 rearrangement in PEComa, emphasizing its significant role in the development of PEComa. It supports TFE3 rearrangement as a poor prognostic biomarker for PEComa and offers potential targets for the development of new therapeutic strategies. Future research is needed to further explore the molecular mechanisms of TFE3 rearrangement and to assess the efficacy of new treatment strategies.