INTERSTITIAL LUNG DISEASE | Lymphangioleiomyomatosis

Abstract

Lymphangioleiomyomatosis (LAM), a rare multisystem disease affecting women, is characterized by cystic lung disease and abdominal tumors (e.g., angiomyolipomas (AMLs) and lymphangioleiomyomas). Proliferation of abnormal smooth muscle-like cells (LAM cells) is observed throughout the lung, along axial lymphatics in the thorax and abdomen, and in AMLs. Patients can present with progressive dyspnea, recurrent pneumothoraces, hemoptysis, chylous pleural effusions, and/or ascites. Diagnosis may be made by lung biopsy or by clinical and roentgenographic data. LAM occurs sporadically or in association with tuberous sclerosis complex (TSC), an autosomal dominant disorder with variable penetrance caused by mutations in the tumor suppressor genes TSC1 and/or TSC2 . LAM cells from sporadic LAM patients contain TSC mutations. TSC1 encodes hamartin, a protein with a role in cell adhesion; TSC2 encodes tuberin, a protein involved in cell-cycle progression and control of cell growth and proliferation, in part, through its regulation of mammalian target of rapamycin (mTOR). The natural course of LAM is highly variable. Therapy includes hormonal manipulations, bronchodilators, supplemental oxygen, and lung transplantation. Clinical trials are under way to study the effects of rapamycin, an inhibitor of mTOR.