Angiomyolipoma : Molecular Pathogenesis

Angiomyolipoma (AML) - Molecular Pathogenesis: A massive angiomyolipoma (AML) with extension into the perirenal soft tissues. About one-third of patients with AML have tuberous sclerosis and about 80% of patients with severe form of tuberous sclerosis develop angiomyolipomas. Tuberous sclerosis is an autosomal dominant complex associated with mutations in two genes: TSC1 (located at 9q34; protein product hamartin) and TSC2 (located at 16p13.3; protein product tuberin). Both genes are characterized as tumor suppressor genes. Hamartin and tuberin function together as a complex and negatively regulate mTOR signaling pathway which plays a role in cell growth and migration. The clinical symptom complex includes mental retardation, seizures, and hamartomas (renal AML, cardiac rhabdomyomas, pulmonary lymphangiomyomas, subependymal giant cell astrocytomas, and facial angiomyofibromas). A small subset of AML harbor TFE3 mutations which can be detected with TFE3 immunohistochemical stain or break-apart FISH assay.