Heme/Lymphvasculogenesis, Hem/Lymphangiogenesis, Hem/Lymphangiotumorigenesis, and Tumor Hem/Lymphangiogenesis: Need for a Terminology Adjustment

The lymphatic and blood vasculatures develop and function as parallel yet interacting systems. In part because of the prominence of the latter and the dire sequelae of some blood circulatory disturbances, the lymphatic vasculature has been appropriately recognized only in lymphogenous spread of cancer and in congenital and acquired peripheral lymphedema. From the perspective of the last century’s landmark contributions in basic and clinical lymphology leading to current understanding of structure–function relationships in the lymphatic system, coupled with recent advances in molecular lymphology, a terminology adjustment in the angiogenesis field is needed and indeed overdue. The prefix terms hem/heme- or lymph- should be used routinely to designate which of the two distinct vasculatures are “arising de novo” (vasculogenesis), “sprouting from preexistent vessels” (angiogenesis), “forming vascular tumors” (angiotumorigenesis), or “newly supplying or draining tumors” (tumor angiogenesis). Nondesignation of the prefix heme- or lymph- should be reserved for general reference to vasculatures or to an unknown or undetermined vasculature. In this presentation, the molecular and developmental pathways thought to be involved in these lymphatic and blood vascular processes will be summarized and specific clinical entities and examples along the spectrum of angiogenic disorders from benign to malignant highlighted to illustrate the importance of distinguishing the physiologic and pathophysiologic including neoplastic processes involving each of the two vasculatures and where they may interact, merge, or become indistinct and indistinguishable. Indeed, the success of targeted therapy directed at either or both depends on such understanding, clear terminology, and precisely addressing and articulating unanswered questions and unquestioned answers.