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  • Author: Joel Moss, MD, PhD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
Updated: Jul 27, 2015


Lymphangioleiomyomatosis (LAM) is a rare disorder resulting from proliferation in the lung, kidney, and axial lymphatics of abnormal smooth muscle–like cells (LAM cells) that exhibit features of neoplasia and neural crest origin.[1, 2, 3] Cystic destruction of the lung with progressive pulmonary dysfunction and the presence of abdominal tumors (eg, angiomyolipomas [AML], lymphangioleiomyomas) characterize the disease. LAM typically occurs in premenopausal women, suggesting the involvement of female hormones in disease pathogenesis. LAM can occur with increased frequency in patients with tuberous sclerosis complex (TSC), an autosomal dominant disorder due, in part, to mutations in the TSC1 or TSC2 gene. 



Proliferation of lymphangioleiomyomatosis (LAM) cells may obstruct bronchioles,[1] possibly leading to airflow obstruction, air trapping, formation of bullae, and pneumothoraces. Obstruction of lymphatics may result in lymphangioleiomyomas, chylothorax, and chylous ascites. Excessive proteolytic activity, which relates to an imbalance of the elastase/alpha1-antitrypsin system or metalloprotease (MMPs) and their inhibitors (tissue inhibitors of metalloproteases [TIMPs]), may be important in lung destruction and formation of cysts.[4] Animal models suggest that estrogen may promote the metastasis of TSC2-deficient cells to the lungs.[5]




United States

Lymphangioleiomyomatosis (LAM) may occur sporadically or in association with tuberous sclerosis complex (TSC). To date, more than 1500 cases of sporadic LAM exist in the United States; LAM may occur in approximately 30-40% of patients with TSC.[6]


The international frequency of lymphangioleiomyomatosis (LAM) is unknown, although Europe and Japan report case series.[7]


No racial predilection has been reported for lymphangioleiomyomatosis (LAM).


Lymphangioleiomyomatosis (LAM) primarily is a disease of women; however, rare case reports describe LAM in men with TSC.


Although primarily a disease of women of childbearing age, lymphangioleiomyomatosis (LAM) has also been reported in postmenopausal patients.



Earlier reports indicated a grim prognosis for lymphangioleiomyomatosis (LAM), with progressive respiratory failure and death within 10 years of diagnosis. Recent reports, however, are more favorable, with 71% of affected patients alive at 10 years.[8] The statistics may improve further as patients are diagnosed earlier (lead-time bias) or with more benign disease.

Poor prognostic factors include the following:

  • Reduced forced expiratory volume in 1 second and/or diffusing capacity for carbon monoxide[25, 33]
  • A low LAM histology score, which quantifies the involvement of the lung with both LAM cells and cysts[8]

Patient Education

Inform patients about their disease because education is an important issue in this condition. Excellent resources can be found at the LAM Foundation and the National Heart Lung and Blood Institute.

Contributor Information and Disclosures

Joel Moss, MD, PhD Deputy Chief, Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health

Joel Moss, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American Society for Clinical Investigation, American Society for Biochemistry and Molecular Biology, American Thoracic Society, Association of American Physicians, Phi Beta Kappa

Disclosure: Nothing to disclose.


Arnold S Kristof, MDCM, FRCPC Associate Professor of Medicine, Department of Medicine, Respiratory and Critical Care Divisions; Associate Member, Department of Microbiology and Immunology; Research Director, Meakins-Christie Laboratories, McGill University Faculty of Medicine; Attending Physician, Respiratory and Critical Care Divisions, McGill University Health Centre, Royal Victoria Hospital, Canada

Arnold S Kristof, MDCM, FRCPC is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, Royal College of Physicians and Surgeons of Canada, American Society for Biochemistry and Molecular Biology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Harold L Manning, MD Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School

Harold L Manning, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.


John A Kelly, MB, BCh, MD † Assistant Professor of Medicine and Microbiology and Immunology, Dartmouth Medical School; Staff Pulmonologist, White River Junction Veterans Affairs Medical Center.


This work was supported in part by the Division of Intramural Research, National Institutes of Health, National Heart, Lung, and Blood Institute (J.M.) as well as National Institutes of Health R01-CA125436, Tuberous Sclerosis Alliance, LAM Foundation, LAM Canada (A.K.).

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