Pancreatic PEComa is a novel member of the family of tuberous sclerosis complex-associated tumors: case report and review of the literature

Excerpt

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with variable penetrance and a wide spectrum of disease manifestations even within the same family. Major diagnostic criteria for TSC include several distinct neoplasms, including facial angiofibroma, cardiac rhabdomyoma, lymphangioleiomyomatosis, subependymal giant cell astrocytoma, and renal angiomyolipoma. Germline mutations in either of two genes, TSC1 and TSC2, which code for hamartin and tuberin, respectively, cause TSC. Hamartin and tuberin, along with a third protein, TBC1D7, function as a heterocomplex to regulate activation of mTOR complex 1 (mTORC1) through regulation of the rheb GTPase. [5] Loss-of-function mutations in the TSC1 or TSC2 gene lead to activation of mTORC1, which is a direct contributor to the growth of these tumors, and this abnormal activation can be therapeutically blocked by rapamycin and its analogs, such as everolimus. [3] Although not completely separable clinically, TSC1 mutations are associated with overall milder disease severity than TSC2 mutations. …