TY - JOUR AB - <p>Lymphangioleiomyomatosis (LAM) is a slowly progressive, low grade, metastasizing neoplasm, associated with cellular invasion and cystic destruction of the pulmonary parenchyma. Although the source of LAM cells that infiltrate the lung is unknown, available evidence indicates that the disease spreads primarily through lymphatic channels, often involving abdominal, axial, and retroperitoneal nodes, suggestive of an origin in the pelvis. LAM cells harbor mutations in tuberous sclerosis genes and produce lymphangiogenic growth factors, which facilitate access to and movement through the lymphatic system and likely play an important role in destructive tissue remodeling in the lung. Lymphatic manifestations of LAM include thoracic duct wall invasion, lymphangioleiomyoma formation, chylous fluidcollections in the peritoneal, pleural, and pericardial spaces, chyloptysis, chylocolporrhea/chylometrorrhea, chyle leak from the umbilicus, chylous pulmonary congestion,and lower extremity lymphedema. LAM lesions express lymphangiogenic growth factors VEGF-C and VEGF-D; growth factor receptors, VEGFR-2 and VEGFR-3; and markers LYVE-1 and podoplanin, and are laced with chaotic lymphatic channels. Serum VEGF-D is elevated in 70% of patients with LAM and is a clinically useful diagnostic and prognostic biomarker. Molecular targeted therapy with sirolimus stabilizes lung function, is anti-lymphangiogenic, and is highly effective for the lymphatic and chylous complications of LAM. Future trials inpatients with LAM who have lymphatic manifestations or elevated serum VEGF-D will likely focus on the VEGF-C/VEGFD/VEGFR-3 axis.</p> AU - R Gupta, M Kitaichi, Y Inoue, R Kotloff, FX McCormack DA - 2014/1// IS - 3 VL - 47 PB - International Society of Lymphology and the University of Arizona Libraries PY - 2014 TI - LYMPHATIC MANIFESTATIONS OF LYMPHANGIOLEIOMYOMATOSIS T2 - Lymphology UR - http://journals.librarypublishing.arizona.edu/lymph/article/id/3768/ ER -