Infantile hemangiomas exhibit neural crest and pericyte markers.

Infantile hemangiomas (IHs) are the most common benign tumors of infancy and occur with greater than 60% prevalence on the head and neck. Despite their prevalence, little is known about the pathogenesis of this disease. Given the predilection of hemangioma incidence on the face and its nonrandom distribution on embryological fusion plates, we postulated that IHs are derived from pericytes of the neural crest. We performed an analysis on 15 specimens at various stages of the IH progression. Experiments performed included immunohistochemical staining, immunofluorescent staining, quantitative real-time polymerase chain reaction, and flow cytometry. We analyzed a number of cell markers using these methods, including cell markers for the neural crest, pericytes, endothelial cells, stem cells, and the placenta. We observed that neural crest markers such as NG2 and nestin were expressed in the hemangioma samples, in addition tomultiple pericytes markers including δ-like kinase, smooth muscle actin, calponin, and CD90. Stem cell markers such as c-myc, oct4, nanog, and sox2 were also more highly expressed in hemangioma samples compared to controls. Our work demonstrates that hemangiomas express pericyte, neural crest, and stem cell markers suggesting a possible pathogenetic mechanism.

Placental anomalies in children with infantile hemangioma.

Evaluation of the placenta provides some important insights into pathophysiologic changes that take place during the prenatal and intrapartum process. We investigated the pathogenic significance of placental features and their relationship to the development of infantile hemangioma in order to obtain a better understanding of its cause. Placental specimens were reviewed from 26 singleton pregnancies of women whose offspring weighed less than 1500 g. A group of 13 neonates who developed infantile hemangioma in the immediate neonate period were compared with 13 healthy preterm infants of comparable postconception age who had no infantile hemangioma. Pathologic placental changes were analyzed in both groups. Gross lesions with disturbance of the utero-placental circulation were found in all placentas from children who developed infantile hemangioma, including massive retroplacental hematoma in two infants, extensive ischemic infarction in seven, and large dilatated vascular communications, severe vasculitis, chorioamnionitis and funiculitis in four. Placental features included percentages greater than 25% of avascular villi, platelet and fibrin aggregates, and multifocal disease involving more than one histologic section. Examination of 13 placentas of low-birth-weight infants without infantile hemangioma only showed abnormal placentation in one and isolated villous dismaturity in two. The higher ratio of placental pathologic findings in patients with infantile hemangioma suggests that reduced placental oxygen diffusive conductance contributes to fetal hypoxic stress and that hypoxic/ischemic changes in the placenta could be related to infantile hemangioma development via vascular endothelial growth factor and placental growth factor expression, among others, within the villious vessels and throphoblasts.