Vascular anomalies are common birthmarks.1 Their classification has often been problematic, with contradictory and confusing descriptive nomenclature. A classification system first proposed by Mulliken and Glowacki was revised in 1996 by the International Society for the Study of Vascular Anomalies based on clinical, radiologic, and hemodynamic characteristics, into vascular malformations and vascular tumors.2 Vascular malformations (see Chapter 172) are errors of morphogenesis whereas hemangiomas and other vascular tumors grow by cellular proliferation.
There are several types of vascular tumors, many of which occur in childhood. These tumors have also had confusing nosology,3 with descriptive but imprecise terminology such as strawberry, capillary, and cavernous. Several types of hemangiomas have been described (infantile, rapidly involuting congenital, lobular capillary, etc.), so whenever possible, hemangioma should not be used as a stand-alone noun but rather qualified by an adjective based on the specific condition.
Infantile Hemangiomas at a Glance
- Infantile hemangiomas are the most common tumor of infancy.
- Hemangiomas in high-risk anatomic sites are likely to require further work-up and, often, intervention.
- Segmental hemangiomas have a greater risk for morbidity than localized hemangiomas.
- Kasabach-Merritt syndrome is not due to infantile hemangioma.
Infantile hemangiomas (IH) are the most common benign tumors of childhood, occurring in approximately 4% of children by 1 year of age.4,5 In contrast to other types of hemangiomas and vascular malformations, IH have a characteristic proliferative phase followed by a slower involution phase. They are more common in females (2–5:1 ratio) and in premature infants, especially those weighing less than 2,500 g.6,7 Other risk factors are Caucasian race, multiple gestation pregnancy, and maternal age greater than 30 years. Preterm infants are more likely to have multiple tumors, and the sex ratio is less skewed toward females.8 Contrary to prior observations, newer prospective studies do not support chorionic villus sampling as a risk factor.7,8
Etiology and Pathogenesis
IH are primarily composed of endothelial cells but also contain fibroblasts, pericytes, interstitial cells, and mast cells. Although the precise pathophysiologic mechanisms of the growth and involution of endothelial cells remains unknown, several recent discoveries have advanced our understanding of IH.9–13 The patterns found in segmental hemangiomas suggest at least some hemangiomas occur via developmental error as early as 4–6 weeks of gestation.14 IH only occur in humans, and adequate animal or laboratory models have been difficult to develop.
The recognition that a glucose transporter protein, GLUT1, is expressed in all stages of hemangioma maturation spurred new hypotheses on the pathogenesis of IH.15,16 GLUT1 expression in absent in the normal cutaneous vasculature but is found in placental blood vessels as well as in other so-called barrier tissues such as the blood–brain barrier. This, together with other immunohistochemical markers shared by IH and ...