Risk factors and molecular features

Benign PEComas are common in patients with tuberous sclerosis, an autosomal dominant syndrome that also predisposes to renal cell cancer and brain tumors. Tuberous sclerosis is caused by germline pathogenic inactivation of either TSC1 (9q34) or TSC2 (16p13.3), and the same tumor suppressor genes are inactivated somatically in sporadic PEComas.[140] Inactivation of either gene results in stimulation of the mTOR pathway, providing the basis for the treatment of nonsurgically curable tumors with similar genetic inactivation (lymphangioleiomyomatosis and angiomyolipoma) with mTOR inhibitors.[141,142] A small proportion of PEComas have TFE3 rearrangements with fusions involving various genes, including SFPQ and RAD51B.[143]