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Lymphangioleiomyomatosis

Chapter
Part of the Cancer Metastasis – Biology and Treatment book series (CMBT, volume 13)

Abstract

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 cells due to loss-of-function type mutations of either the TSC1 or TSC2 gene, which are tumor suppressor genes originally identified to be the genetic cause for tuberous sclerosis complex. LAM shows an extreme gender predilection and it usually occurs in women of reproductive age. Its pathological findings are characterized by the existence of abundant lymphatic vessels resulting from LAM-associated lymphangiogenesis since LAM cells produce potent lymphangiogenic growth factors, VEGF-C and VEGF-D. Consequently its clinical manifestations include the symptoms and signs related with abnormalities in the lymphatic system, such as lymphangioleiomyomas, chylous leaks into body cavities and urine, from the airways or even the vagina, or lymphedema of the lower extremities as well as a progressive cystic destruction of the lungs, thus resulting in respiratory failure. The extent of LAM-associated lymphangiogenesis correlates with the histologic severity of LAM. The mechanism for the progression of LAM is now hypothesized to be a unique invasion-independent mechanism mediated with LAM-associated lymphangiogenesis. LAM cells are considered to disseminate and form a metastatic lesion in the lungs and axial lymphatic systems through the lymphangiogenesis-mediated fragmentation of LAM foci and followed by the subsequent shedding of LAM cell clusters into the lymphatic circulation.

Key words

Estrogen LAM cell cluster Lymphangiogenesis Tuberous sclerosis complex VEGF-C VEGF-D 

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Department of Respiratory MedicineJuntendo University, School of MedicineTokyoJapan
  2. 2.Department of Human PathologyJuntendo University School of MedicineTokyoJapan

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