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Lymphangioleiomyomatosis and Tuberous Sclerosis Complex

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Abstract

Lymphangioleiomyomatosis (LAM) is a rare multisystemic disease of women of child-bearing age and affects mainly the lungs, promoting cystic destruction of lung parenchyma or leading to abdominal tumor formation (e.g., angiomyolipomas, lymphangioleiomyomas). LAM can arise sporadically or in association with tuberous sclerosis complex (TSC), an autosomal inherited syndrome characterized by hamartoma-like tumor growth and pathologic features that are distinct from manifestations of pulmonary LAM. A substantial body of evidence has now been gathered suggesting that the two diseases share a common genetic origin. TSC is caused by mutations in two genes, TSC1 on chromosome 9q34 and TSC2 on 16p13. Both of these genes are tumor suppressor genes encoding hamartin (TSC1) and tuberin (TSC2). Sporadic LAM is correlated with a mutation in the TSC2 gene and tuberin appears to play a central role in the pathogenesis of the disease. A TSC2 loss or mutation leads to disruption of the tuberin-hamartin heteromer and dysregulation of S6K1 activation leading to aberrant cell proliferation seen in LAM disease. The extremely diverse clinical and radiologic features of the disease and the complex therapeutic approach are reviewed in detail. Although new therapeutic agents have been tested, to date no effective treatment has been proposed and the prognosis of patients with LAM remains poor. As long as newer therapeutic agents do not change this picture, lung transplantation remains the last hope for patients with respiratory failure at the advanced stage of the disease.

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Abbreviations

LAM:

Lymphangioleiomyomatosis

TSC:

Tuberous sclerosis complex

LOH:

Loss of heterozygosity

PFTs:

Pulmonary function tests

AMLs:

Renal angiomyolipomas

LCC:

Lymphatic endothelial cells

MMPs:

Matrix metalloproteinases

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Authors and Affiliations

  1. 1st Department of Respiratory Medicine, University of Athens Medical School, “Sotiria” General Hospital, Athens, Greece

    Dimitrios Chorianopoulos

  2. 5th Department of Internal Medicine, “Evaggelismos” Hospital, Athens, Greece

    Dimitrios Chorianopoulos

  3. 23rd November str., Ilion, Athens, 13121, Greece

    Dimitrios Chorianopoulos

  4. Critical Care and Pulmonary Services Unit, University of Athens Medical School, “Evaggelismos” Hospital, Athens, Greece

    Grigoris Stratakos

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  1. Dimitrios Chorianopoulos
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Correspondence to Dimitrios Chorianopoulos.

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Chorianopoulos, D., Stratakos, G. Lymphangioleiomyomatosis and Tuberous Sclerosis Complex. Lung 186, 197–207 (2008). https://doi.org/10.1007/s00408-008-9087-5

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