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Diagnosis and Management of Infantile Hemangioma David H CLINICAL REPORT Guidance for the Clinician in Rendering Pediatric Care Diagnosis and Management of Infantile Hemangioma David H. Darrow, MD, DDS, Arin K. Greene, MD, Anthony J. Mancini, MD, Amy J. Nopper, MD, the SECTION ON DERMATOLOGY, SECTION ON OTOLARYNGOLOGY–HEAD AND NECK SURGERY, and SECTION ON PLASTIC SURGERY abstract Infantile hemangiomas (IHs) are the most common tumors of childhood. Unlike other tumors, they have the unique ability to involute after proliferation, often leading primary care providers to assume they will resolve without intervention or consequence. Unfortunately, a subset of IHs rapidly develop complications, resulting in pain, functional impairment, or permanent disfigurement. As a result, the primary clinician has the task of determining which lesions require early consultation with a specialist. Although several recent reviews have been published, this clinical report is the first based on input from individuals representing the many specialties involved in the treatment of IH. Its purpose is to update the pediatric community regarding recent discoveries in IH pathogenesis, treatment, and clinical associations and This document is copyrighted and is property of the American to provide a basis for clinical decision-making in the management of IH. Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication. NOMENCLATURE Clinical reports from the American Academy of Pediatrics benefit from The nomenclature and classification of vascular tumors and expertise and resources of liaisons and internal (American Academy malformations have evolved from clinical descriptions (“strawberry of Pediatrics) and external reviewers. However, clinical reports from the American Academy of Pediatrics may not reflect the views of the birthmark,”“salmon patch,”“cavernous hemangioma,” and “port wine liaisons or the organizations or government agencies that they stain”) to terminology based on their cellular features, natural history, and represent. clinical behavior. Originally described by Mulliken and Glowacki in 1982, The guidance in this report does not indicate an exclusive course of fi treatment or serve as a standard of medical care. Variations, taking the most current and widely accepted classi cation of vascular anomalies into account individual circumstances, may be appropriate. is that adopted by the International Society for the Study of Vascular 1 All clinical reports from the American Academy of Pediatrics Anomalies (Table 1). This system includes infantile hemangioma (IH) automatically expire 5 years after publication unless reaffirmed, among the vascular neoplasms, which are lesions characterized by revised, or retired at or before that time. abnormal proliferation of endothelial cells and aberrant blood vessel www.pediatrics.org/cgi/doi/10.1542/peds.2015-2485 architecture. In contrast, vascular malformations are structural anomalies DOI: 10.1542/peds.2015-2485 and inborn errors of vascular morphogenesis. PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Although IH is the most common neoplasm, this group also includes such Copyright © 2015 by the American Academy of Pediatrics tumors as congenital hemangiomas, pyogenic granulomas, tufted angiomas (TAs), and several types of hemangioendothelioma. Congenital FINANCIAL DISCLOSURE: The authors have indicated they do not have a financial relationship relevant to this article to disclose. hemangiomas are biologically and behaviorally distinct from IH. As fl POTENTIAL CONFLICT OF INTEREST: The authors have indicated they re ected in the name, congenital hemangiomas are present and fully have no potential conflicts of interest to disclose. formed at birth; they do not exhibit the postnatal proliferative phase FROM THE AMERICAN ACADEMYDownloaded OF PEDIATRICS from http://pediatrics.aappublications.org/ by guest on MarchPEDIATRICS 29, 2018 Volume 136, number 4, October 2015 characteristic of IH. The 2 variants are It is a reactive proliferating vascular and may grow slowly over the course the noninvoluting congenital lesion that is classified as a vascular of months to years, grow rapidly, hemangioma (NICH), which remains neoplasm (Table 1). This common spontaneously regress, or remain stable without growth or acquired vascular lesion of the skin dormant for years.14–16 Unlike KHE involution,2,3 and the rapidly and mucous membranes primarily and TA, IHs are not associated with involuting congenital hemangioma affects infants and children and is thrombocytopenia or coagulopathy. (RICH), which undergoes a rapid frequently misdiagnosed as IH. Vascular malformations are fi involution phase beginning in the rst Approximately 12% occur in infancy, congenital lesions, but some may 4 fi year of life (Fig 1). RICHs, in some and 42% present during the rst 5 become clinically apparent only later 10 cases, have been associated with years of life. Pyogenic granulomas in life, presumably because of slowly thrombocytopenia but with milder are most commonly located on the progressive ectasia resulting from and more transient coagulopathy head and neck, rapidly enlarge to intraluminal flow. They exhibit than that seen in Kasabach-Merritt a median size of 6.5 mm, frequently a normal rate of endothelial cell phenomenon (KMP; see discussion develop a pedunculated base, and, turnover throughout their natural that follows); rarely, they can be with erosion, are prone to bleeding history but expand as the patient fi 10 associated with congestive heart that is dif cult to control (Fig 2). grows. Vascular malformations do not 5,6 failure. Some RICHs show Pyogenic granulomas are seen with involute, and their growth may be incomplete involution, and it is higher frequency within the skin influenced by trauma, infection, and possible that RICH and NICH lie at containing capillary malformations. hormonal changes. Classification is opposite ends of the same clinical Two other distinct benign vascular based on the predominant vessel 7,8 spectrum. Both subtypes of neoplasms, kaposiform type: capillary or venulocapillary, congenital hemangioma were initially hemangioendothelioma (KHE) and venous, lymphatic, arterial, or believed to be variants of IH that TA, have been confused with IH. KHE mixed.17 As with vascular neoplasms, exhibited prenatal growth until North presents primarily in infancy but with the nomenclature of vascular 9 et al showed that, unlike IH, neither a far wider age range than IH, which malformations has led to great lesion expresses glucose transporter is usually apparent in the first month confusion. Capillary or protein isoform 1 (GLUT1). of life. KHE is considered a locally venulocapillary malformations have Pyogenic granuloma, also known as aggressive neoplasm that typically had numerous alternative lobular capillary hemangioma, is appears as a deep, soft tissue mass. designations, the most common being neither pyogenic nor granulomatous. This lesion has been associated with “port wine stain” and “nevus KMP,11 a potentially life-threatening flammeus.” Venous malformations consumptive coagulopathy have often been mistaken for IH, TABLE 1 Classification of Cutaneous characterized by severe platelet Vascular Anomalies, 2014 trapping. Before KHE was described Vascular malformations in the early 1990s, KMP was Venous malformations erroneously thought to occur in Lymphatic malformations association with IH. Capillary malformations Arteriovenous malformations and fistulae Histopathologically, KHE shows Mixed (combined) malformations infiltrating sheets of slender, GLUT1- Vascular tumors negative endothelial cells lining Benign slitlike capillaries.12 TAs are benign Infantile hemangioma (IH) vascular tumors that occur in infants, Congenital hemangioma (rapidly involuting [RICH]; non-involuting [NICH]) children, or young adults and are Lobulated capillary hemangiomas (LCH) usually located on the neck or the (pyogenic granuloma)* upper part of the thorax.13 Their Tufted angioma (TA) clinical appearance is variable and Others includes erythematous to violaceous Locally aggressive Kaposiform hemangioendothelioma (KHE) patches, plaques, and nodules. Kaposi sarcoma Histopathologically, TA shows well- Others defined tufts of capillaries in the Malignant dermis that lack cellular atypia or Angiosarcoma GLUT1 positivity and, like KHE, is Others FIGURE 1 associated with increased lymphatic Adapted from the International Society for the Study of RICH is fully formed at birth (A) and then Vascular Anomalies, 2014, ref 1 (issva.org/classification). vessels and a predisposition to KMP. involutes, mostly during the first year of life. B, *Reactive proliferating vascular lesion Both tumors behave unpredictably The same lesion seen at 8 months of age. PEDIATRICS Volume 136, number 4, OctoberDownloaded 2015 from http://pediatrics.aappublications.org/ by guest on March 29, 2018 e1061 termed “cavernous hemangiomas” years, especially predating the among female infants; however, and “venous hemangiomas” in the distinction between IH and the although older data suggest female- literature (Fig 3A). Lymphatic congenital hemangiomas. to-male ratios ranging from 3:1 to 5:1, malformations, which are subdivided “Hemangioma” has also been more recent studies suggest a range into microcystic and macrocystic
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