Lymphangioleiomyomatosis

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

Background

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. 

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Pathophysiology

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]

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Epidemiology

Frequency

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]

International

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

Race

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

Sex

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

Age

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

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Prognosis

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]
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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.

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