Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare, progressive, systemic disease that typically results in cystic lung destruction and predominantly affects women, especially during child bearing years. It occurs in more than 30% of women with tuberous sclerosis complex (TSC-LAM), a heritable syndrome that is associated with seizures, cognitive impairment and benign tumors in multiple tissues. Most LAM patients who present for medical evaluation have the sporadic form of the disease (S-LAM), however, which is not associated with other manifestations of tuberous sclerosis complex. Mild cystic changes consistent with LAM have been described in 10-15% of men with TSC, but symptomatic LAM in males is extremely rare. Sporadic LAM occurs exclusively in women, with one published exception to date. Both TSC-LAM and S-LAM are associated with mutations in tuberous sclerosis genes. Lung destruction in LAM is a consequence of diffuse infiltration by neoplastic smooth muscle-like cells, which invade all lung structures including the lymphatics, airway walls, blood vessels, and interstitial spaces. The consequence of obstruction of the vessels and airways include chylous fluid accumulations, hemoptysis, airflow obstruction and pneumothorax. The typical disease course is characterized by progressive dyspnea on exertion, punctuated by recurrent pneumothoraces and, in some patients, chylous pleural effusions or ascites. Modern estimates for median survival in LAM have varied from 10 to 30 years, based on whether hospital based or population based cohorts are studied. Most patients have dyspnea on exertion with daily activities by 10 years after symptom onset and many will require supplemental oxygen over that interval. An FDA approved drug for treatment of LAM, sirolimus, is now available for stabilization of lung function decline. Lung transplant remains the option of last resort for patients with advanced disease.