Continuing Medical Education
Hemangiomas of infancy☆,☆☆,★,★★,♢

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Abstract

Hemangiomas of infancy are unique, benign, pediatric tumors of endothelial cells characterized by an initial phase of rapid proliferation, followed by slow involution, often leading to complete regression. Although most of these tumors are small and innocuous, some may be may be life- or function-threatening, or have associated structural congenital anomalies. Uncertainties regarding their diagnosis or management often prompt referral to a dermatologist. The pathogenesis of hemangiomas of infancy is not well understood, but recent findings suggest a unique vascular phenotype with dysregulated vascular homeostasis. This article reviews new information regarding the pathogenesis of these tumors and highlights the more worrisome presentations, including syndromic hemangiomas, that are likely to be problematic. In addition, management strategies and treatment options are discussed. (J Am Acad Dermatol 2003;48:477-93.) Learning objective: At the completion of this learning activity, participants should be able to describe the clinical features of hemangiomas of infancy and potential complications as well as to understand the strengths and limitations of various treatment options.

Section snippets

Epidemiology

HOI or their precursors can be identified in 1.1% to 2.6% of term neonates,5, 6 and their frequency is estimated to be as high as 10% to 12% within the first year of life.7, 8 They occur in children of all races, but may be less common in those of African or Asian descent. For unclear reasons, female neonates are more likely to be affected than male neonates at rates of 3 to 5:1.9 HOI are also more common in premature infants; increased prevalence correlates with both decreasing gestational age

Pathology and pathogenesis

On routine histology, proliferating HOI are composed of masses of plump, rapidly dividing endothelial cells with and without lumens. Multilamination of the basement membrane is also seen.1 As involution progresses, the vascular lumens dilate, endothelial cells flatten, and fibrous tissue is deposited, giving the hemangioma a lobular architecture. Fully involuted HOI contain few capillary-like feeding vessels and draining veins with flattened endothelium in a stroma of fibrofatty tissue,

Clinical features and natural history

The natural history of growth and regression of HOI was first described by Lister in 1938.38 These features have now been well characterized, but the enormous spectrum of severity, from tiny banal lesions to large and endangering ones, makes predictions of behavior and prognosis in individual patients difficult, especially in very young infants, in whom the most dramatic growth is likely to occur. The growth characteristics of HOI are often divided into phases: nascent, proliferating,

Sites of involvement

Although HOI may occur on any part of the body, they demonstrate a striking predilection for the head and neck region. In a large series, 60% of HOI occurred on the head and neck, followed by 25% on the trunk, and 15% on extremities.39 Furthermore, facial HOI seem to be nonrandomly distributed and occur in 2 morphologic forms. The majority are focal tumorlike lesions that tend to occur near lines of embryonic fusion. Less commonly, they involve a region of skin corresponding to a derivation

Worrisome presentations

Although the majority of HOI are localized and pose no immediate or long-term threat, a significant minority can cause serious morbidity. Early recognition of these problematic lesions, coupled with prompt intervention, may help to minimize future complications. Certainly, HOI in young infants warrant more attention as their growth pattern may be unpredictable. Also, HOI near ocular or periorificial locations are more likely to create complications. Finally, segmental HOI may be associated with

Differential diagnosis

Using the guidelines established by Finn, Mulliken, and Glowacki,39 more than 90% of vascular anomalies can be classified as hemangiomas or vascular malformations by history and physical examination alone. In a minority of cases, the diagnosis may be in question. A diverse group of conditions may mimic HOI (Table IV).

. Differential diagnosis of hemangioma of infancy

Other vascular anomalies and tumors
 Capillary malformation
 Venous malformation
 Lymphatic malformation
 Arteriovenous malformation
 NICH
 RICH
 

Imaging studies

Although many radiologists are unfamiliar with the use of imaging studies to differentiate HOI from vascular malformations or other soft-tissue tumors, several key reference have recently been published delineating characteristic radiologic findings.81, 82, 83 Noninvasive imaging studies such as Doppler ultrasound, computed tomography (CT), and MRI may be helpful in differentiating HOI from vascular malformations or other soft-tissue tumors. Invasive studies such as arteriography are best

Management and treatment

The management of HOI is controversial for several reasons.84 Perhaps foremost is the wide spectrum of clinical disease. This combined with the potential for rapid change in early infancy, can cause great difficulty in predicting which hemangiomas are innocuous and which will prove a real threat. In addition, randomized controlled trials or solid evidence-based studies of treatments and associated outcomes are sorely lacking. Some experts take an aggressive stance, favoring early intervention

Conclusions

HOI are common benign tumors of childhood, distinguished by their characteristic proliferation and involution. New findings regarding their pathogenesis, including newly described staining for GLUT1, point to a unique vascular phenotype rather than an overgrowth of the cutaneous vasculature. Dysregulation in vascular homeostasis may also help explain their development. HOI are extremely heterogeneous, and although most are relatively small and inconsequential, a significant minority may be

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    ☆

    Funding sources: None.

    ☆☆

    Conflict of interest: None identified.

    ★

    Reprints not available from authors.

    ★★

    Correspondence: Ilona J. Frieden, MD, Department of Dermatology, University of California, San Francisco, 1701 Divisadero St, 3rd Floor, San Francisco, CA 94143-0316. E-mail: [email protected].

    ♢

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    Copyright © 2003 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.