Clinical meaning
Lymphangioleiomyomatosis (LAM) is a rare, progressive, cystic lung disease that occurs almost exclusively in women of reproductive age. It is caused by the proliferation of abnormal smooth muscle-like cells (called LAM cells) that infiltrate the lung parenchyma, airways, lymphatic channels, and pulmonary blood vessels. LAM cells harbor loss-of-function mutations in the TSC1 or TSC2 tumor suppressor genes (tuberous sclerosis complex genes). These genes normally encode the proteins hamartin (TSC1) and tuberin (TSC2), which together form a complex that inhibits the mammalian target of rapamycin (mTOR) signaling pathway. When TSC1 or TSC2 is mutated, mTOR becomes constitutively activated, driving uncontrolled cell growth and proliferation. LAM occurs in two forms: sporadic LAM (isolated lung disease without other features of tuberous sclerosis) and TSC-LAM (occurring in patients with tuberous sclerosis complex, a genetic disorder also causing benign tumors in the brain, kidneys, heart, and skin). The proliferating LAM cells cause three major pathological consequences in the lungs: (1) cyst formation from obstruction and destruction of small airways (air trapping creates thin-walled cysts throughout the lung parenchyma), (2) lymphatic obstruction causing chylous pleural effusions...