Overview
Historically, prior to the mid-1800's and Virchow's establishment of the "cell theory" of cancer, the "lymph theory" and later the "endothelial theory" of the origin and spread of cancer prevailed; it was also recognized that cancer spread to lymph nodes. Currently, the central importance of the lymphatic system (lymphatics, lymph, lymphocytes, and lymph nodes and its study - lymphology) is increasingly recognized as the environment in which cancer develops, is immersed in and surrounded by, and provides the key route for dissemination to regional lymph nodes and likely also to the blood circulation and distant organs. This brief overview will review fundamental concepts of the lymphatic system as a vasculature, key component of the blood-lymph loop circulation of extracellular fluid, route of entry and transport of large molecules, particles and cells, and also encompassing the immune system. How these concepts bear on cancer development and spread will then be highlighted and specifically related to ECM alterations, epithelial-mesenchymal and mesenchymal-epithelial transition, cancer stem cells, lymphangiogenesis, sentinel lymph nodes, lymphogenous dissemination, benign metastasizing tumors, lymphedema, and tumor immunotherapy.