Brain lesions in tuberous sclerosis complex. Review

Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disease characterized by the development of multiple hamartomas and benign or rarely malignant neoplasms distributed at various sites throughout the body, especially in the brain, skin, retina, kidney, heart, and lungs. Brain lesions in TSC include: cortical/subcortical glioneuronal tubers, subependymal glial nodules (SENs), and subependymal giant cell astrocytomas (SEGAs). Cortical tubers are characterized by a markedly disorganized cortical lamination with dysplastic aggregates of abnormal glial and neuronal elements, including giant cells. SENs consist of large cells, somewhat similar to the giant cells seen in tubers, accompanied by elongated glial cells. SENs are typically covered by a layer of ependyma and can grow over time and develop into subependymal giant cell astrocytomas. SEGAs consist of a mixed cell population of large ganglioid-like cells, spindle and giant cells with nuclear pleomorphism. Mitotic activity and necrosis might be observed in SEGAs but they should not be considered as features of malignancy. The clinical presentations of TSC result from mutations in either of two tumour suppressor genes: TSC1 (located on 9q34) or TSC2 (located on 16p13). The proteins encoded by TSC1 and TSC2 genes, hamartin and tuberin, respectively, form a heterodimer which suppresses the mammalian target of rapamycin (mTOR), a major cell growth and proliferation controller. Oral rapamycin therapy may induce regression of astrocytomas associated with TSC. In this review, the clinicopathological features of TCS and recent advantages in the diagnosis and genetics of TSC are presented.