Lymphatic research and biology
-
Comparative Study
Involvement of lymphatics in lymphangioleiomyomatosis.
Lymphangioleiomyomatosis (LAM), a rare multisystem disease, occurs primarily in women, with cystic destruction of the lungs, abdominal tumors, and involvement of the axial lymphatics in the thorax and abdomen. To understand the pathogenesis of LAM, we initiated a longitudinal study of patients with LAM; over 500 patients have been enrolled. LAM results from the proliferation of a neoplastic cell (LAM cell), which has mutations in the tuberous sclerosis complex (TSC) genes, TSC1 or TSC2. ⋯ LAM cell clusters have been isolated from chylous pleural effusions, and it is hypothesized that these clusters may be responsible for metastatic spread of LAM cells via lymphatic vessels. Consistent with a lymphangiogenic process, levels of VEGF-D, a lymphangiogenic factor, were higher in sera of patients with LAM and lymphatic involvement (i.e., lymphangioleiomyoma, adenopathy) than in healthy volunteers or LAM patients with cystic disease limited to the lung. These findings are consistent with an important function for lymphangiogenesis in LAM.