Pathophysiology of capillary haemangioma growth after birth.

Capillary haemangiomas (CHs) are the most common soft tissue tumours of infancy. It is generally believed that the primary defect in CHs is intrinsic to endothelial cells, but their pathogenesis is yet poorly understood. The relatively low oxygen environment, in which the human foeto-placental unit develops, during the first trimester, is necessary to induce vasculo-angiogenesis via embryonic endothelial cells proliferation, since these cells are sensitive to hypoxia and acidosis. In newborn infants with haemangioma, persistent embryonic primitive endothelial cells trapped in the intimae underneath the developing vessels, and representing "leader" endothelial cells, can stabilise the labile vascular endothelial growth factor mRNA (VEGF mRNA), produce other angiogenic factors, degrade the underlying basement membrane and invade into the stroma of the neighbouring tissue. With bearing down, the transition from intra- to extra-uterine life is accompanied by more or less pronounced hypoxia. Consequently, in babies with haemangioma, hypoxia can act as a switch to activate these "leader" endothelial cells and thereby initiate a cascade of reactions leading to CH proliferation. As they are regulated by embryonic cells, the haemangioma growth mechanisms pursue the pathway of embryonic angiogenesis and it will stop at the end of the embryonic endothelial cell cycle. Addressing this mechanism in vivo has partly been done (the angiogenic peptide bFGF varies with haemangioma growth). Thus, early treatment seems necessary in infants with haemangioma, before the endothelial cells achieve their proliferative stage. The use of an antibody to interfere with VEGF receptors provides a particular attractive strategy.