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Infantile Hemangiomas Exhibit Neural Crest and Pericyte Markers

Spock, Christopher L. MD*; Tom, Laura K. MD*; Canadas, Karina MD*; Sue, Gloria R. MA*; Sawh-Martinez, Rajendra MD*; Maier, Cheryl L. MD; Pober, Jordan S. MD, PhD; Galan, Anjela MD; Schultz, Brent MD*; Waner, Milton MD§; Narayan, Deepak MD, FRCS*

doi: 10.1097/SAP.0000000000000080

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.

From the Departments of *Surgery, †Immunobiology, and ‡Dermatology, Yale University School of Medicine, New Haven, CT; and §Vascular Birthmarks Institute of New York, New York, NY.

Received April 21, 2013, and accepted for publication, after revision, November 10, 2013.

Conflicts of interest and sources of funding: Supported by the American Society of Maxillofacial Surgery, Plastic Surgery Educational Foundation, Ohse Research Award, NIH Grant R01-HL051014.

Presented at the International Society for the Study of Vascular Anomalies (2010), Plastic Surgery Research Council (2010), and American Association of Plastic Surgeons (2011).

Reprints: Deepak Narayan, MD, FRCS, Department of Surgery, Yale University School of Medicine, PO Box 208062, New Haven, CT 06520. E-mail:

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