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Lymphangioleiomyomatosis

  • Elizabeth P. Henske
  • Francis X. McCormack
Chapter
Part of the Respiratory Medicine book series (RM)

Abstract

Lymphangioleiomyomatosis is a rare, cystic lung disease of women that most commonly presents with progressive dyspnea on exertion and recurrent pneumothorax in the third or fourth decade of life (1). LAM can also be associated with abdominal and thoracic lymphadenopathy, renal and extrarenal angiomyolipomas, and chylous fluid collections in the abdomen, chest, or pericardium. LAM occurs almost exclusively in females, for reasons that are not understood, but biopsy-documented LAM in males has also been reported. Cystic changes consistent with LAM are found in about 30–40% of women who have the heritable disease tuberous sclerosis complex (TSC), a neurocutaneous tumor suppressor syndrome. TSC-associated LAM (TSC-LAM) is frequently asymptomatic. LAM also occurs in patients who do not have TSC, and despite an estimated prevalence that is 10-fold lower than that of TSC-LAM, these “sporadic LAM or S-LAM” patients generally outnumber TSC-LAM patients 6:1 in pulmonary clinics and registries around the world. S-LAM is also associated with TSC mutations, but they are found only in the neoplastic lesions in the lung, kidney, and lymphatics, and not in normal tissues or in the circulating blood cells. The histopathologic hallmark of LAM in the lung is interstitial expansion with benign-appearing smooth muscle cells, which infiltrate all lung structures, including alveolar septa, airways, blood vessels, lymphatics, and pleura. The origin of the invading cells is unknown, but available evidence suggests an extrapulmonary source. Two metastatic mechanisms have been proposed: dissemination from angiomyolipomas and pulmonary microvascular dissemination of LAM cell clusters originating in the lymphatics and gaining access to the venous circulation at the level of the thoracic duct. The prognosis in LAM depends on the mode of presentation and is more favorable in patients who are ascertained through screening, pneumothorax or incidental findings on studies obtained for other purposes rather than through shortness of breath. There are currently no treatments which are known to be effective. Antagonism of estrogen action, using progestins or GnRh agonists, is the most commonly employed empiric therapeutic strategy. Advances in our understanding of the molecular pathogenesis of LAM have far outstripped progress in the clinical arena, and clinical trials directed at molecular targets identified through basic investigation are underway in the United States and Europe.

Keywords

interstitial lung disease chylous effusion HMB-45 pneumothorax tumor suppressor syndrome perivascular epithelioid cell tumor sirolimus 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Elizabeth P. Henske
    • 1
  • Francis X. McCormack
    • 2
  1. 1.Department of MedicineHarvard Medical SchoolBostonUSA
  2. 2.Department of Internal MedicineUniversity of Cincinnati Medical CenterCincinnatiUSA

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