Infantile Hemangiomas: A Disease Model in the Study of Vascular Development, Aberrant Vasculogenesis and Angiogenesis

Abstract

Infantile hemangiomas (IHs) belong to a family of lesions called vascular anomalies. Vascular anomalies are classified into either vascular tumors or vascular malformations, with the IH being the most common vascular tumor, affecting approximately 5% of infants (Frieden, Haggstrom et al 2005). Despite their prevalence, the origin and pathogenesis of IHs remains poorly understood. Clinically, IHs undergo a predictable course of rapid proliferation shortly after birth, followed by stabilization and involution throughout childhood. Occasionally, a fibrofatty residuum results after involution is complete. Despite its predictable clinical course, the regulatory mechanisms throughout different phases are only recently being elucidated (Frieden, Haggstrom et al. 2005). During the proliferative phase, IH can cause serious morbidity and even mortality. Rapidly proliferating hemangiomas can be dangerous as they have potential to ulcerate and bleed. While disorganized, IHs are high-flow lesions; occasionally, life-threatening bleeding can occur. The location of the IH can also be detrimental. Hemangiomas in the peri-orbital area can cause obstructive amblyopia and astigmatism, and airway hemangiomas can cause stridor and respiratory distress. Visceral hemangiomas of the liver can cause congestive heart failure, hepatomegaly, and anemia; the mortality rate with treatment is significant, up to 30% (Arneja and Mulliken, 2010; Bitar et al., 2005; Boon et al., 1996; Ceisler & Blei, 2003; Chamlin et al., 2007; Haggstrom et al., 2006a; Schwartz et al., 2006). In recent years, PHACE syndrome has been described and characterized. PHACE syndrome comprises a constellation of findings including Posterior fossa anomalies, large facial Hemangioma, Arterial anomalies, Cardiac abnormalities/aortic Coarctation, and Eye anomalies (Frieden et al., 1996). Infants with PHACE syndrome are at increased risk for strokes, neurological and cardiac consequences (Burrows et al., 1998; Drolet et al., 2006). Another syndrome featuring a large hemangioma over an area with aberrant underlying anatomical structures have also been described. PELVIS syndrome describes Perineal hemangioma, External genitalia malformations, Lipomyelomeningocele, Vesicorenal anomalies, Imperforate anus, and Skin tag (Girard et al., 2006). PHACE and PELVIS syndromes suggest that there may be an association between a cutaneous hemangioma and