Abstract
Infantile hemangioma (IH), also known as hemangioma of infancy, is the most common soft tissue tumor of childhood. IH demonstrate significant clinical heterogeneity in their presentation, ranging from small self-limiting lesions to bulky tumors that impart significant morbidity. IH can present as superficial, deep, or mixed lesions depending on the depth of soft tissue involvement (Drolet et al, N Engl J Med 341: 173–181, 1999; Haggstrom et al, Pediatrics 117:698–703, 2006). Most lesions are superficial, presenting as bright red papules or plaques which are typically round and involve the superficial dermis, while deep lesions have a more bluish hue; mixed lesions have characteristics of both. The morphological pattern of IH tends to be localized or segmental (Haggstrom et al, Pediatrics 117:698–703, 2006; Chiller et al, Arch Dermatol 138: 1567–1576, 2002). Localized lesions tend to be discrete ovoid or rounded lesions, while segmental lesions, which impart higher risk of complications, tend to involve a broad region and are more geometric in shape.
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References
**Drolet BA, Esterly NB, Frieden IJ. Hemangiomas in children. N Engl J Med. 1999;341:173–81.
*Haggstrom AN, Lammer EJ, Schneider RA, Marcucio R, Frieden IJ. Patterns of infantile hemangiomas: new clues to hemangioma pathogenesis and embryonic facial development. Pediatrics. 2006;117:698–703.
*Chiller KG, Passaro D, Frieden IJ. Hemangiomas of infancy: clinical characteristics, morphologic subtypes, and their relationship to race, ethnicity, and sex. Arch Dermatol. 2002;138:1567–76.
**Munden A, et al. Prospective study of infantile haemangiomas: incidence, clinical characteristics and association with placental anomalies. Br J Dermatol. 2014;170:907–13.
*Waner M, et al. The nonrandom distribution of facial hemangiomas. Arch Dermatol. 2003;139:869–75.
*Costa VA, et al. Social impact of facial infantile hemangiomas in preteen children. JAMA Otolaryngol Head Neck Surg. 2016;142:13–9.
*Metry DW, Hawrot A, Altman C, Frieden IJ. Association of solitary, segmental hemangiomas of the skin with visceral hemangiomatosis. Arch Dermatol. 2004;140:591–6.
*Sie KC, Tampakopoulou DA. Hemangiomas and vascular malformations of the airway. Otolaryngol Clin N Am. 2000;33:209–20.
*Orlow SJ, Isakoff MS, Blei F. Increased risk of symptomatic hemangiomas of the airway in association with cutaneous hemangiomas in a “beard” distribution. J Pediatr. 1997;131:643–6.
**Metry DW, et al. A prospective study of PHACE syndrome in infantile hemangiomas: demographic features, clinical findings, and complications. Am J Med Genet A. 2006;140:975–86.
*Uihlein LC, Liang MG, Mulliken JB. Pathogenesis of infantile hemangiomas. Pediatr Ann. 2012;41:1–6.
*Boye E, et al. Clonality and altered behavior of endothelial cells from hemangiomas. J Clin Invest. 2001;107:745–52.
*Khan ZA, et al. Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice. J Clin Invest. 2008;118:2592–9.
***Greenberger S, Bischoff J. Pathogenesis of infantile haemangioma. Br J Dermatol. 2013;169:12–9.
*Kleiman A, Keats EC, Chan NG, Khan ZA. Evolution of hemangioma endothelium. Exp Mol Pathol. 2012;93:264–72.
*Xu D, et al. Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model. J Hematol Oncol. 2011;4:54.
**Harbi S, et al. Infantile hemangioma originates from a dysregulated but not fully transformed multipotent stem cell. Sci Rep. 2016;6:35811.
***North PE, Waner M, Mizeracki A, Mihm MC Jr. GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas. Hum Pathol. 2000;31:11–22.
**Barnes CM, et al. Evidence by molecular profiling for a placental origin of infantile hemangioma. Proc Natl Acad Sci U S A. 2005;102:19097–102.
*Itinteang T, et al. A placental chorionic villous mesenchymal core cellular origin for infantile haemangioma. J Clin Pathol. 2011;64:870–4.
**Strub GM, et al. Endothelial and circulating C19MC microRNAs are biomarkers of infantile hemangioma. JCI Insight. 2016;1:e88856.
*Noguer-Dance M, et al. The primate-specific microRNA gene cluster (C19MC) is imprinted in the placenta. Hum Mol Genet. 2010;19:3566–82.
*Luo SS, et al. Human villous trophoblasts express and secrete placenta-specific microRNAs into maternal circulation via exosomes. Biol Reprod. 2009;81:717–29.
**Burton BK, Schulz CJ, Angle B, Burd LI. An increased incidence of haemangiomas in infants born following chorionic villus sampling (CVS). Prenat Diagn. 1995;15:209–14.
*Drolet BA, Frieden IJ. Characteristics of infantile hemangiomas as clues to pathogenesis: does hypoxia connect the dots? Arch Dermatol. 2010;146:1295–9.
*Colonna V, Resta L, Napoli A, Bonifazi E. Placental hypoxia and neonatal haemangioma: clinical and histological observations. Br J Dermatol. 2010;162:208–9.
*Mihm MC Jr, Nelson JS. Hypothesis: the metastatic niche theory can elucidate infantile hemangioma development. J Cutan Pathol. 2010;37(Suppl 1):83–7.
*Gonzalez-Crussi F, Reyes-Mugica M. Cellular hemangiomas (“hemangioendotheliomas”) in infants. Light microscopic, immunohistochemical, and ultrastructural observations. Am J Surg Pathol. 1991;15:769–78.
*Nguyen VA, Furhapter C, Romani N, Weber F, Sepp N. Infantile hemangioma is a proliferation of beta 4-negative endothelial cells adjacent to HLA-DR-positive cells with dendritic cell morphology. Hum Pathol. 2004;35:739–44.
***North PE, et al. A unique microvascular phenotype shared by juvenile hemangiomas and human placenta. Arch Dermatol. 2001;137:559–70.
*Huang SA, et al. Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas. N Engl J Med. 2000;343:185–9.
*Huang SA, Dorfman DM, Genest DR, Salvatore D, Larsen PR. Type 3 iodothyronine deiodinase is highly expressed in the human uteroplacental unit and in fetal epithelium. J Clin Endocrinol Metab. 2003;88:1384–8.
*Ritter MR, et al. Identifying potential regulators of infantile hemangioma progression through large-scale expression analysis: a possible role for the immune system and indoleamine 2,3 dioxygenase (IDO) during involution. Lymphat Res Biol. 2003;1:291–9.
*Ligam P, Manuelpillai U, Wallace EM, Walker D. Localisation of indoleamine 2,3-dioxygenase and kynurenine hydroxylase in the human placenta and decidua: implications for role of the kynurenine pathway in pregnancy. Placenta. 2005;26:498–504.
*Ritter MR, Dorrell MI, Edmonds J, Friedlander SF, Friedlander M. Insulin-like growth factor 2 and potential regulators of hemangioma growth and involution identified by large-scale expression analysis. Proc Natl Acad Sci U S A. 2002;99:7455–60.
*Thomsen BM, et al. Patterns in expression of insulin-like growth factor-II and of proliferative activity in the normal human first and third trimester placenta demonstrated by non-isotopic in situ hybridization and immunohistochemical staining for MIB-1. Placenta. 1997;18:145–54.
**Huang L, Nakayama H, Klagsbrun M, Mulliken JB, Bischoff J. Glucose transporter 1-positive endothelial cells in infantile hemangioma exhibit features of facultative stem cells. Stem Cells. 2015;33:133–45.
**Haggstrom AN, et al. Prospective study of infantile hemangiomas: demographic, prenatal, and perinatal characteristics. J Pediatr. 2007;150:291–4.
*Grimmer JF, et al. Familial clustering of hemangiomas. Arch Otolaryngol Head Neck Surg. 2011;137:757–60.
*Chang LC, et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics. 2008;122:360–7.
*Brandling-Bennett HA, et al. Infantile hemangiomas with unusually prolonged growth phase: a case series. Arch Dermatol. 2008;144:1632–7.
**Haggstrom AN, et al. Prospective study of infantile hemangiomas: clinical characteristics predicting complications and treatment. Pediatrics. 2006;118:882–7.
**Holland KE, Drolet BA. Infantile hemangioma. Pediatr Clin N Am. 2010;57:1069–83.
*Stockman A, Boralevi F, Taieb A, Leaute-Labreze C. SACRAL syndrome: spinal dysraphism, anogenital, cutaneous, renal and urologic anomalies, associated with an angioma of lumbosacral localization. Dermatology. 2007;214:40–5.
*Garin EH, Araya CE. Treatment of systemic hypertension in children and adolescents. Curr Opin Pediatr. 2009;21:600–4.
***Leaute-Labreze C, et al. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008;358:2649–51.
**Sans V, et al. Propranolol for severe infantile hemangiomas: follow-up report. Pediatrics. 2009;124:e423–31.
*Price CJ, et al. Propranolol vs corticosteroids for infantile hemangiomas: a multicenter retrospective analysis. Arch Dermatol. 2011;147:1371–6.
*Bertrand J, et al. Propranolol versus prednisone in the treatment of infantile hemangiomas: a retrospective comparative study. Pediatr Dermatol. 2011;28:649–54.
*Hogeling M, Adams S, Wargon O. A randomized controlled trial of propranolol for infantile hemangiomas. Pediatrics. 2011;128:e259–66.
**Leaute-Labreze C, et al. Double-blind randomized pilot trial evaluating the efficacy of oral propranolol on infantile haemangiomas in infants < 4 months of age. Br J Dermatol. 2013;169:181–3.
***Leaute-Labreze C, et al. A randomized, controlled trial of oral propranolol in infantile hemangioma. N Engl J Med. 2015;372:735–46.
*Li LL, et al. Propranolol in the treatment of infantile hemangiomas: a meta-analysis in Chinese patients. Pediatr Dermatol. 2015;32:e210–4.
*Liu X, Qu X, Zheng J, Zhang L. Effectiveness and safety of oral propranolol versus other treatments for infantile hemangiomas: a meta-analysis. PLoS One. 2015;10:e0138100.
*Lou Y, et al. The effectiveness of propranolol in treating infantile haemangiomas: a meta-analysis including 35 studies. Br J Clin Pharmacol. 2014;78:44–57.
*Chinnadurai S, et al. Pharmacologic interventions for infantile hemangioma: a meta-analysis. Pediatrics. 2016;e20153896:137.
**Marqueling AL, Oza V, Frieden IJ, Puttgen KB. Propranolol and infantile hemangiomas four years later: a systematic review. Pediatr Dermatol. 2013;30:182–91.
*Ji Y, Chen S, Xu C, Li L, Xiang B. The use of propranolol in the treatment of infantile haemangiomas: an update on potential mechanisms of action. Br J Dermatol. 2015;172:24–32.
*Greenberger S, Bischoff J. Infantile hemangioma-mechanism(s) of drug action on a vascular tumor. Cold Spring Harb Perspect Med. 2011;1:a006460.
**Cushing SL, Boucek RJ, Manning SC, Sidbury R, Perkins JA. Initial experience with a multidisciplinary strategy for initiation of propranolol therapy for infantile hemangiomas. Otolaryngol Head Neck Surg: Off J Am Acad Otolaryngol-Head Neck Surg. 2011;144:78–84.
*de Graaf M, et al. Adverse effects of propranolol when used in the treatment of hemangiomas: a case series of 28 infants. J Am Acad Dermatol. 2011;65:320–7.
***Drolet BA, et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics. 2013;131:128–40.
***Hoeger PH, et al. Treatment of infantile haemangiomas: recommendations of a European expert group. Eur J Pediatr. 2015;174:855–65.
*Malik MA, Menon P, Rao KL, Samujh R. Effect of propranolol vs prednisolone vs propranolol with prednisolone in the management of infantile hemangioma: a randomized controlled study. J Pediatr Surg. 2013;48:2453–9.
*Enjolras O, Riche MC, Merland JJ, Escande JP. Management of alarming hemangiomas in infancy: a review of 25 cases. Pediatrics. 1990;85:491–8.
*Bennett ML, Fleischer AB Jr, Chamlin SL, Frieden IJ. Oral corticosteroid use is effective for cutaneous hemangiomas: an evidence-based evaluation. Arch Dermatol. 2001;137:1208–13.
*Boon LM, Enjolras O, Mulliken JB. Congenital hemangioma: evidence of accelerated involution. J Pediatr. 1996;128:329–35.
*Boon LM, MacDonald DM, Mulliken JB. Complications of systemic corticosteroid therapy for problematic hemangioma. Plast Reconstr Surg. 1999;104:1616–23.
*Rossler J, Wehl G, Niemeyer CM. Evaluating systemic prednisone therapy for proliferating haemangioma in infancy. Eur J Pediatr. 2008;167:813–5.
*Barrio VR, Drolet BA. Treatment of hemangiomas of infancy. Dermatol Ther. 2005;18:151–9.
*Tay YK, Tan SK. Treatment of infantile hemangiomas with the 595-nm pulsed dye laser using different pulse widths in an Asian population. Lasers Surg Med. 2012;44:93–6.
*Nakagawa H, Tan OT, Parrish JA. Ultrastructural changes in human skin after exposure to a pulsed laser. J Invest Dermatol. 1985;84:396–400.
*Shen L, et al. Pulsed dye laser therapy for infantile hemangiomas: a systemic review and meta-analysis. QJM. 2015;108:473–80.
*Rizzo C, et al. Outcomes of childhood hemangiomas treated with the pulsed-dye laser with dynamic cooling: a retrospective chart analysis. Dermatol Surg: Off Publ Am Soc Dermatol Surg. 2009;35:1947–54.
*Scheepers JH, Quaba AA. Does the pulsed tunable dye laser have a role in the management of infantile hemangiomas? Observations based on 3 years’ experience. Plast Reconstr Surg. 1995;95:305–12.
*Poetke M, Philipp C, Berlien HP. Flashlamp-pumped pulsed dye laser for hemangiomas in infancy: treatment of superficial vs mixed hemangiomas. Arch Dermatol. 2000;136:628–32.
*Ehsani AH, et al. Combination therapy of infantile hemangioma with pulsed dye laser with topical propranolol: a randomized clinical trial. Arch Iran Med. 2014;17:657–60.
*Ezekowitz RA, Mulliken JB, Folkman J. Interferon alfa-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med. 1992;326:1456–63.
*Fawcett SL, Grant I, Hall PN, Kelsall AW, Nicholson JC. Vincristine as a treatment for a large haemangioma threatening vital functions. Br J Plast Surg. 2004;57:168–71.
*Jimenez-Hernandez E, et al. Treatment with interferon-alpha-2b in children with life-threatening hemangiomas. Dermatol Surg: Off Publ Am Soc Dermatol Surg. 2008;34:640–7.
*Michaud AP, Bauman NM, Burke DK, Manaligod JM, Smith RJ. Spastic diplegia and other motor disturbances in infants receiving interferon-alpha. Laryngoscope. 2004;114:1231–6.
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Strub, G., Sidbury, R., Bauman, N. (2018). Vascular Tumors: Infantile Hemangioma. In: Perkins, J., Balakrishnan, K. (eds) Evidence-Based Management of Head and Neck Vascular Anomalies. Springer, Cham. https://doi.org/10.1007/978-3-319-92306-2_6
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