CHARACTERIZATION OF THE PATHOGENESIS OF LYMPHANGIOLEIOMYOMATOSIS (LAM)

Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

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 appearance, 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. These cells have now been cloned and transformed. Cells from angiomyolipoma, obtained immediately following surgical removal are also growing in culture.The abdominal computed tomographic (CT) and ultrasonographic findings in patients with LAM were related to the severity of pulmonary disease. Sixty-one (76%) of 80 patients had positive abdominal findings. The most common were renal angiomyolipoma (AML) in 43 patients (54%), enlarged abdominal lymph nodes in 31 (39%), and lymphangiomyoma in 13 (16%). Less common findings included ascites in eight (10%), dilatation of the thoracic duct in seven (9%), and hepatic AML in three (4%). A significant correlation (P = .02) was observed between enlarged abdominal lymph nodes and greater severity of lung disease. The characteristic abdominal appearance in patients with LAM, in conjunction with the classic thin-section CT finding of pulmonary cysts, are useful in establishing this diagnosis.The findings on ventilation-perfusion (V-P) scintigrams, computed tomographic scans, and chest radiographs were correlated with pulmonary function tests. Imaging abnormalities were found on 92% of ventilation scintigrams, 92% of perfusion scintigrams, 79% of chest radiographs, 100% of CT scans, and 100% of thin-section CT scans. On ventilation scintigrams, 28 patients (72%) demonstrated a speckling pattern. On CT scans, all patients had pulmonary cysts. Univariate analysis showed that extent of disease on chest radiographs and CT scans, cyst size, V-P abnormalities, and degree of speckling were inversely correlated with forced expiratory volume in one second (FEV1), diffusing capacity of lung for carbon monoxide, and the ratio of FEV1 to forced vital capacity (FVC) (P less than .01) but not with FVC or total lung capacity. These scintigraphic and radiologic abnormalities were seen in a majority of patients with LAM. On ventilation scintigrams, the frequently seen speckling pattern may be related to accumulation of radionuclide in pulmonary cysts a hallmark of the disease at CT. Findings with each imaging modality correlated with pulmonary functions.