Extrarenal perivascular epithelioid cell tumors (PEComas) respond to mTOR inhibition: Clinical and molecular correlates

Perivascular epithelioid cell tumors (PEComas) are a group of rare mesenchymal tumors that typically show both melanocytic and smooth muscle cell features. Some types of PEComa are seen at high frequency in tuberous sclerosis complex (TSC). The TSC1 and TSC2 genes are commonly mutated in both TSC-associated and sporadic PEComas, and mTOR signaling pathway activation is also common in these tumors. Preliminary reports have indicated that the mTOR inhibitors sirolimus and related drugs have activity in some patients with non-TSC-associated PEComa. Here, we report on the use of these medications in the treatment of five consecutive patients with extrarenal nonpulmonary PEComas seen at one institution. Three complete responses, one partial response and one case of progression were seen. Molecular studies identified TSC2 aberrations in four of these patients, and TFE3 translocation was excluded in the resistant case. A review of all published cases as well as those reported here indicates that partial or complete response was seen in 6 of 11 PEComas, with 5 of 6 having a complete response. These findings highlight the consistent though incomplete activity of mTOR inhibitors in the treatment of PEComas. What's new? Perivascular epithelioid cell tumors (PEComas) are a rare but increasingly recognized subset of mesenchymal tumor that commonly involve mTOR-activating mutations. In this clinical investigation, four out of five PEComa patients benefited significantly from treatment with the mTOR inhibitors sirolimus and everolimus. Two of the patients experienced long-lasting complete responses. Genetic aberrations in TSC2 and positive staining for the protein marker pS6 correlated with response. The results suggest that mTOR inhibitors could be important therapeutic options in PEComa.