TSC2-mutated perivascular epithelioid cell tumor with partial response to mTOR inhibition: a case report and literature review

Abstract

Perivascular epithelioid cell tumors (PEComas), rare mesenchymal neoplasms with heterogeneous behavior, are molecularly characterized by TSC2 inactivation driving mammalian target of rapamycin (mTOR) pathway activation. We present a typical case of a 63-year-old female with metastatic high-grade PEComa featuring a TSC2 mutation (68.57% VAF) and elevated tumor mutational burden (19.7 mut/Mb), manifesting as peritoneal carcinomatosis and pulmonary metastases. Everolimus therapy following multidisciplinary assessment induced a radiologically confirmed partial response within 4.5 months with sustained clinical benefit. This outcome validates mTOR inhibition in TSC2-mutated PEComas and underscores the imperative of molecular profiling in mesenchymal tumor management. The significant mutational burden suggests potential immunotherapy responsiveness, informing future combination strategies. These findings emphasize molecularly guided precision approaches in rare malignancies and warrant systematic exploration of therapeutic sequencing and resistance mechanisms in mTOR-driven tumors.

Keywords: TSC2 mutation; mTOR inhibitor; Case report; Everolimus; PEComa.

Fig. 1

Diagnosis and therapeutic response in this PEcoma patient. (A) Chest CT imaging findings before and after treatment in this PEcoma patient; (B) Abdominal and pelvic CT imaging findings before and after treatment in this PEcoma patient. TCSA, Tumor cross-sectional area; MTD, Maximum tumor diameter; STCSA, Sum of tumor cross-sectional area of tumor; SMTD, Sum of the maximum tumor diameters

Fig. 2

Hematoxylin and eosin (HE) and immunohistochemical (IHC) staining in this PEcoma patient. (C) HE and IHC staining of pulmonary nodules in this PEcoma patient; (D) HE and IHC staining of abdominal mass in this PEcoma patient

Fig. 3

Schematic representation of the TSC1/2-mTOR signaling pathway