lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare, multisystem disorder in which smooth muscle–like LAM cells proliferate and create cystic destruction of lung tissue and lymphatic abnormalities. It almost exclusively affects women and occurs as a sporadic disease or in association with tuberous sclerosis complex (TSC).

LAM cells harbor mutations in TSC1 or TSC2, leading to constitutive activation of the mTOR pathway and ongoing proliferation. Estrogen may influence disease progression, and LAM commonly involves the kidneys and lymphatics, causing angiomyolipomas and lymphatic lesions that can result in chylous effusions.

Most patients present with progressive dyspnea and a nonproductive cough. Pneumothorax is a common and often recurrent complication. Chylous pleural effusions or ascites may occur, and renal angiomyolipomas are frequent. Symptoms can worsen during pregnancy.

Diagnosis relies on imaging and biomarkers. High-resolution CT shows diffuse, round, thin-walled cysts throughout the lungs. Pulmonary function tests typically reveal obstructive limitation with reduced DLCO. Serum VEGF-D is often elevated and above about 800 pg/mL supports a noninvasive diagnosis; biopsy is reserved for uncertain cases. LAM cells are typically HMB-45 positive on immunohistochemistry.

Management aims to slow progression and treat complications. Sirolimus, an mTOR inhibitor, stabilizes or improves lung function and can reduce angiomyolipoma size. For pneumothorax, chest tube drainage and pleurodesis may be used. Estrogen avoidance is advised, and lung transplantation is considered in advanced disease. Regular monitoring for renal and lymphatic involvement is recommended.