Lymphangioleiomyomatosis: a disease involving the lymphatic system.
BACKGROUND
Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease in which abnormal smooth muscle-like cells (LAM cells) proliferate in the lungs and along the axial lymphatic systems, including the lymph nodes and thoracic ducts. LAM cells are transformed due to loss-of-function type mutations of either the TSC1 or TSC2 tumor suppressor genes. The pathological features include the proliferation of benign-looking LAM cells and the existence of abundant lymphatic vessels that are associated with clinical conditions such as chyle leakage. LAM cells produce potent lymphangiogenic growth factors (VEGF-C and VEGF-D) and the lymphatic vessel density within LAM lesions correlates with the histologic severity of LAM. The serum VEGF-D level increases in LAM, especially in patients with lymphatic involvement. LAM cell clusters (LCCs), which are postulated pathologically to be generated by lymphangiogenesis-mediated fragmentation and subsequent shedding into the lymphatic circulation, are observed in both chylous effusion and LAM-associated lymphatics within LAM tissue specimens. The identification of LCCs in chylous effusion together with the characteristic clinical manifestations can therefore be an alternative for a lung biopsy if LAM patients are complicated with chylous effusion.


CONCLUSIONS
LAM appears to be a disease involving a dysfunction of the lymphatic system and a fascinating model of tumor dissemination that is exclusively lymphangitic. LAM-associated lymphangiogenesis that mediates the shedding of LCCs seems to play a central role in the dissemination of LAM cells and progression in LAM and it may also be a potential therapeutic target as well as the dysregulated mTOR signaling pathway.
Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan. kseyama@juntendo.ac.jp
Kuniaki
K
Seyama
Toshio
T
Kumasaka
Masatoshi
M
Kurihara
Keiko
K
Mitani
Teruhiko
T
Sato
D000818:Animals; D006801:Humans; D018192:Lymphangioleiomyomatosis / Q000378:metabolism* / Q000473:pathology; D008208:Lymphatic System / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*
D009363:Neoplasm Proteins