97 - Lymphangioleiomyomatosis

Abstract

Lymphangioleiomyomatosis(LAM) is a rare low-grade neoplasm that results in progressive cystic destruction of the lung. LAM is caused by mutations in tuberous sclerosis complex (TSC) genes that lead to constitutive activation of the mechanistic target of rapamycin (mTOR) pathway. LAM predominantly affects girls and women and arises both in the setting of TSC (TSC-LAM) and in a sporadic form (S-LAM) in patients who do not have germline mutations in TSC genes or the clinical syndrome of TSC. The rate of lung function decline in patients with LAM is approximately three to four times faster than historical age-matched control subjects, with estimated transplant-free median survival of more than 20 years following diagnosis. LAM presents unique diagnostic and management challenges, including recurrent spontaneous pneumothoraces, bleeding, pain or abdominal distention from benign renal tumors (angiomyolipomas), and lymphatic obstruction leading to chylous effusions (chylothorax or chylous ascites). Unparalleled synergistic efforts of patients, scientists, and clinicians have driven tremendous growth in our understanding of LAM, resulting in a clinically useful diagnostic biomarker (serum vascular endothelial growth factor-D), a Food and Drug Administration–approved targeted treatment (sirolimus, an oral mTOR inhibitor), a diverse international LAM clinic network, and international clinical practice guidelines that provide a framework for the optimal diagnosis and management of LAM.