CHARACTERIZATION OF THE PATHOGENESIS OF LYMPHANGIOLEIOMYOMATOSIS (LAM)

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Lymphangioleiomyomatosis (LAM) is a multisystem disorder characterized by cystic lung disease and abdominal tumors (lymphangiomyomas and angiomyolipomas). The disease, which presents almost exclusively in women of childbearing age, is characterized by the proliferation of abnormal smooth muscle containing premelanosomal structures similar to those found in melanoma cells. A clinical protocol has enabled the Branch to assemble a large cohort of patients with LAM and to document the natural history of the disease, the histopathological findings, the radiographic abnormalities, and characteristic pulmonary function abnormalities. It has enabled us to obtain tissue to examine gene expression and cell regulatory pathways. We have been able to grow LAM cells from lungs of patients with LAM, obtained at transplant or autopsy. Cells from angiomyolipoma, obtained immediately following surgical removal are also growing in culture. Several clinical observations have changed clinical care for patients with LAM. First, patients were found to have an increased frequency of bone loss, with about 80% of patients exhibiting either osteopenia or osteoporosis. Second, patients with LAM have been known to develop pleural and pericardial effusions. Closer analysis of patients with pericardial effusions revealed that they may develop constrictive pericarditis. Third, patients with LAM are known to have abdominal tumors termed lymphangiomyomas. The tumors are benign. However, we have observed that their enlargement may result in neurological compromise in the lower extremities, abdominal bloating, peripheral edema, and lymphedema. Fourth, we have observed that a high percentage of patients with LAM have airway hyperresponsiveness. - lymphangioleiomyomatosis, cystic lung disease, osteoporosis,asthma - Human Subjects