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Lymphangioleiomyomatosis

Yamashita, Cory M. MD*; Lynch, David MD; Downey, Gregory P. MD‡§

doi: 10.1097/CPM.0b013e31818cbafb
Interstitial, Inflammatory, and Occupational Lung Disease

Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease occurring almost exclusively in women of childbearing age. Genetic analysis has revealed common mutations in both the TSC1 and TSC2 genes that lead to both sporadic cases of LAM (S-LAM) and those associated with the tuberous sclerosis complex (TSC-LAM). S-LAM is characterized by multiple pulmonary and nonpulmonary complications including progressive airflow obstruction, recurrent pneumothoraces, chylothoraces, and renal angiomyolipomas. Despite the putative role of estrogen in the pathogenesis of this disease, antiestrogen therapies have not shown benefit in prospective clinical trials. Recent insights into the molecular pathogenesis of LAM have offered hope for newer therapies targeting specific signaling pathways that are believed to drive LAM cell proliferation. Patients should be encouraged to participate in clinical trials that will help determine the efficacy of these novel therapies. However, until these therapies are proven to be beneficial, lung transplantation remains the only viable option for patients with progressive end-stage lung disease.

Lymphangioleiomyomatosis is a rare cystic lung disease resulting in progressive obstructive lung disease and recurrent pneumothoraces that affects women of childbearing age. Genetic studies have revealed that mutations in the TSC1 and TSC2 genes are responsible for lymphangioleiomyomatosis, and that this disorder may represent a type of neoplastic process involving myofibroblast-like lymphangioleiomyomatosis cells. Recent insights into the molecular pathogenesis of lymphangioleiomyomatosis have spurred the development of specific therapies that target signaling known to drive lymphangioleiomyomatosis cell proliferation.

From the *Division of Respirology, Department of Medicine, University of Western Ontario, London, ON, Canada; †Division of Radiology and ‡Division of Pulmonary and Critical Care Medicine, Department of Medicine, National Jewish Medical and Research Center; and §Division of Pulmonary Medicine and Critical Care Sciences, Department of Medicine and Integrated Department of Immunology, University of Colorado Denver Health Sciences Center, Denver, Colorado.

Supported by the National Institutes of Health Grant 5R01HL090669-02 (to G.D.).

Address correspondence to: Dr. Gregory Downey, Academic Affairs, K701b, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206. E-mail: downeyg@njc.org.

© 2008 Lippincott Williams & Wilkins, Inc.