Lymphangiogenesis-Mediated Shedding of LAM Cell Clusters as a Mechanism for Dissemination in Lymphangioleiomyomatosis

• DOI: 10.1097/01.pas.0000172192.25295.45
• Publication Date: 2005-09-13T08:09:29Z
• Authors: Toshio Kumasaka; Kuniaki Seyama; Keiko Mitani; Sanae Souma; Satoko Kashiwagi; Akira Hebisawa; Teruhiko Sato; Hajime Kubo; Kiyoshi Gomi; Kazutoshi Shibuya; Yoshinosuke Fukuchi; Koichi Suda
• Keywords: Lymphangioleiomyomatosis; Lymphatic vessel; Lymphangiogenesis; Lymph duct; Lymphatic Endothelium; Chylothorax; Chyle

Lymphangioleiomyomatosis (LAM) affects exclusively women of reproductive age, involves the lungs and axial lymphatic system, is frequently complicated with renal angiomyolipomas. LAM lesions are generated by proliferation cells mutations one tuberous sclerosis complex (TSC) genes. Recent studies indicate that can migrate or metastasize to form new in multiple organs, although they show a morphologically benign appearance. In previous study, we reported LAM-associated lymphangiogenesis implicated its role progression LAM. this further focused on abnormalities LAM: chylous fluid (5 pleural effusion 2 ascites), surgically resected diaphragm (1 patient), system including thoracic duct, lymph nodes at various regions, diaphragmatic autopsy cases). We demonstrated cell clusters enveloped endothelial (LCC) all examined. identified lesion (2 5 autopy cases surgical specimen), duct 5), (retroperitoneal mediastinal (4 left venous angle 5) total positive rate 68% 88% each region node, but less frequent none remote located away from trunk (cervical [1 5] axillary [0 5]). LCCs were intra-LAM lesional channels where proliferate along system. vitro culture LCC fragment into proliferating cell. These findings suggest demarcates bundle- fascicle-like structure eventually shed circulation play central dissemination lesion.