(P 160) UTERINE PECOMA: REPORT OF MOLECULAR AND CLINICAL FEATURES IN A SERIES OF PATIENTS TREATED AT A REFERRAL INSTITUTION

Objective: Perivascular Epithelioid Cell Tumors (PEComas) are rare mesenchymal neoplasms with a typical myomelanocytic and smooth muscle differentiation at immunohistochemistry. They can show an aggressive behavior that has been correlated with histological features such as tumor size and increasing mitotic activity. The uterus represents a common visceral site of origin, sometimes making it difficult to distinguish PEComa from the more common smooth muscle tumors. From a molecular point of view, PEComa commonly harbors mutation in TSC1 and TSC2, which are modulators of the mTOR signaling pathway, providing the rationale for mTOR inhibitor therapy. Only case reports or a limited number of series of patients have been reported in literature, so far, thus resulting in a lack of clinical and histopathological data that could help understand the aggressiveness and the history of the disease. Here we present the pathological and clinical behavior of a series of patients affected by localized uterine PEComa treated with surgery.

Methods: All consecutive patients affected by stage I-II FIGO uterine PEComa, treated with surgery at our institution between January 2000 and December 2023, were included. Eligible pts had a pathologically confirmed diagnosis of uterine malignant PEComa. Hereby, we reported the following histologic and molecular features: tumor size, growth pattern, necrosis, mitotic count (num x 10HPFs); nuclear atypia, lymphovascular invasion, TFE3 fusion, Melan A and HMB45 expression. Disease free survival was also reported.

Results: We included 10 patients. Median age was 50 years old (range 26 – 75). None of them reported a genetic history of tuberous sclerosis. Median tumor size was 7.5 cm (range 0.6-18cm); the growth pattern was reported as infiltrative for 5/10 patients, while other 3/10 had an expansive pattern; necrosis was reported in 40% of patients as well as high nuclear atypia. Mitosis were >10/10HPFs in 40% of patients; half of them presented hypercellularity and in half of them lymphovascular invasion was reported. According to Folpe criteria 5 were classified as malignant PEcoma, 4/10 as Pecoma with uncertain grade of malignancy and 1/10 as benign. From a molecular point of view, TFE3 rearrangements were detected in 2/10 patients while Melan A and HMB45 were positive respectively in 5/10 and in 9/10 patients. At a median follow up of 25 months (range 3 – 80), 4 out of 5 patients with malignant PEComa according to Folpe criteria had relapsed: in 2 cases a new surgery was performed,; the other 2 patients were treated with sirolimus, achieving respectively partial response (PR) and stable disease (SD) as best response.

Conclusion: Almost all patients with malignant PEComa, according to Folpe criteria, relapsed after surgery, thus confirming the aggressiveness of the disease. However, more data and analyses need to be performed in order to correlate the PFS with the pathological criteria to better identify and stratify patient at higher risk of relapse.