and Emir Q. Haxhija2
Department of Plastic Surgery and Burns, Institute for Mother and Child Health Care of Republic Serbia, University of Belgrade, New Belgrade, Serbia
Department of Pediatric and Adolescent Surgery, Medical University Graz, Graz, Austria
A biological classification of vascular anomalies introduced in 1982 clearly separates two major categories of vascular anomalies, tumors and malformations [1–3]. Vascular tumors (mostly hemangiomas) are characterized by endothelial cell proliferation, and vascular malformations are inborn defects in vascular morphogenesis and rarely involute and grow in proportion to the child [1–4]. Infantile hemangiomas (IHs) have unique characteristics, consisting of a proliferating, involuting, and involuted phase [1–8]. The term hemangioma is often wrongly used to describe all types of vascular anomalies .
Infantile hemangiomas (IHs) are the most common benign, soft tissue tumors of infancy which affect between 4 and 5% of Caucasian infants [1, 3, 5]. The incidence is 22–30% in preterm infants who weigh less than 1000 g [2–4]. The risk factors for IHs are also transcervical chorionic villus sampling, older maternal age, and multiple gestation pregnancy . There is a familial history in about 12% of cases [1, 5]. IHs have female predomination 3–4:1 and mostly involve the head and neck (up to 60%), and they are solitary in 80% [1–3, 5].
The pathogenesis of IHs is still unknown [1, 5]. Angiogenic and vasculogenic factors are known as intrinsic (within the IH) and extrinsic factors (tissue hypoxia and developmental field disturbances) [1, 3, 5]. There is a theory that IHs develop from the clonal expansion of circulating endothelial progenitor cells (EPCs), resulting in de novo formation of new blood vessels (vasculogenesis) [1, 2].
Hemangioma-derived endothelial progenitor cells (HemEPCs) share similarities with placental endothelium (glucose transporter protein GLUT1, Lewis Y antigen, merosin, type III iodothyronine deiodinase); there is increased incidence of IH in association with chorionic villus sampling, placenta previa, and preeclampsia; and it has been postulated that the precursor cell for IH might have embolized from the placenta [1–3, 5, 6]. Hypoxia-induced factors (vascular endothelial growth factor, VEGF-A; matrix metalloproteinases, MMP-9) produced by endothelial cells may stimulate circulating (HemEPCs) recruitment to the growing tumor [1, 2, 5]. The mechanism for IH involution is unknown; apoptosis begins before 1 year of age and peaks at 24 months [2, 5].
13.4 Clinical Features
IHs usually appear within the first 2–4 weeks of life [1–3, 5, 9]. Defined (mark-out) anatomical area of hemangioma is noted at birth as telangiectatic or macular red stain, barely visible pale area, or an ecchymotic spot [2, 3, 7]. By 5 months of age, nearly 80% of final size of IH is achieved [1, 5, 7]. IHs are classified on the basis of their soft tissue depth into superficial (red surface, without subcutaneous component), deep (under the skin surface, they appear later and grow longer compared to superficial IHs), and mixed (growth pattern that is intermediate between superficial and deep) (Fig. 13.1a–c) [1, 3–5, 7]. There is a specific subtype of superficial IH named abortive IHs with arrested growth phase .
Infantile hemangioma: (a) superficial; (b) deep; (c) mixed
Clinical appearance of IHs allows differentiation between focal (most common), multifocal, indeterminate, and segmental, depending on their morphology, extent, or distribution (Fig. 13.2a–c) [1, 3, 8, 9]. Focal IH arises from a single focal point, while segmental hemangioma tends to involve a larger area of the skin [1, 7–9]. Lesions between these two groups are considered indeterminate, and focal lesions occurring in more than one anatomical site are multifocal [1, 9]. Segmental IHs have more tendencies to be accompanied with other anomalies and have higher risk for complications [1, 3, 5, 8–10]. If there are more than five cutaneous hemangiomas, the child is at risk for harboring visceral, particularly intrahepatic, hemangiomas [1, 10–13].
Infantile hemangioma: (a) focal; (b) segmental; (c) multifocal; (d) intermediary
IHs have a life cycle going through proliferation (during 5–9 months of life), plateau phase, and involution (starting from 12 months of life lasting up until 5–10 years of age) (Fig. 13.3a–c) [1–5, 7, 9]. Proliferation phase is characterized by growth of hemangioma, its elevation with surrounding pallor, and dilatation of veins [1–3, 8]. If the tumor proliferates in the lower dermis and subcutis, the lesion may not be visible until 3–4 months of age, and the overlying skin may be bluish [1, 5].
Infantile hemangioma: (a) proliferative phase; (b) involutive phase
Approximately 24% of patients with IH experience some complication [1, 5]. Ulceration occurs in 5–21% of all cutaneous hemangiomas, leading to pain, bleeding, and infection (Fig. 13.4a–f) [1, 2, 5, 6]. Superficial and segmental hemangiomas are at higher risk, as well as hemangioma with periorbital, neck, perianal/perineal, and intertriginous localization [1, 2, 5, 9]. Treatment of ulceration includes daily application of nonadherent dressings, hydrocolloid dressing, topical antimicrobials, becaplermin gel, pulsed-dye laser (PDL), excision, and propranolol [1, 2, 5].
Complication of hemangioma: (a) ulceration; (b) visual obstruction; (c) ulcerated hemangioma of urogenital region; (d) feeding problems; (e and f) airway obstruction
Bleeding from IH is rare, it stops spontaneously or with minimal pressure, and rarely it is necessary to place a mattress suture to control a local bleeding site [1, 2, 5]. Feeding impairment occurs in infants with IHs involving perioral or airway region .
Airway IHs can occur in a presence or absence of cutaneous hemangioma, and it can cause respiratory failure [1, 2, 5]. In case of beard distribution of hemangioma or bilateral involvement of lower facial segment, there is higher association of airway involvement [1, 5, 14]. Treatment of airway hemangioma is multidisciplinary, propranolol is first-line therapy, and tracheostomy is needed in emergent or resistant cases [1, 5, 14].
Child with periorbital hemangioma is in higher risk for amblyopia, and in that case evaluation of an ophthalmologist is needed [1, 2, 5]. Propranolol and surgery (in acute cases) are treatment options for periocular IHs [1, 5].
Lip hemangioma often causes distortion and ulceration of lips during proliferative phase [1, 15]. Reconstruction of the lip is indicated (usually when the growth of hemangioma ceased) [1, 5, 15, 16].
Nasal tip hemangiomas are known to cause both cosmetic and functional problem (by displacing lower lateral nasal cartilage and distorting nasal tip) [1, 2, 16, 17]. Only the hemangiomas that do not respond to propranolol, or if there is excess of the skin left, should be treated surgically [1, 16–18]. Congestive heart failure and hypothyroidism are connected as complication with large IHs and with diffuse or multifocal hepatic IHs [1, 5, 12].
13.6 Congenital Hemangiomas
Congenital hemangiomas (CHs) are less common and they are fully present at birth (Fig. 13.5a, b) [1–3]. There are three types of congenital hemangioma: noninvoluting congenital hemangioma (NICH), rapidly involuting congenital hemangioma (RICH), and partially involuting CH . They have the same sex ratio, and they are negative for GLUT1 immunostaining [1–4]. NICH grows proportionately to the child and remains unchanged [1–3]. RICH goes through a rapid regression phase and may be completely gone by the time the child is 12–18 months old [1, 3].
Congenital hemangioma: (a) noninvoluting congenital hemangioma; (b) rapid involuting congenital hemangioma
A small subgroup of children with IHs exhibits additional associated structural anomalies like in the syndrome called PHACES (posterior fossa malformations, hemangioma, arterial anomalies, cardiovascular anomalies, eye abnormalities, and sternal clefting) [1–3, 5, 6, 8, 10, 13]. LUMBAR syndrome includes lower body IH, urogenital anomalies and ulceration, myelopathy, bony deformities, anorectal malformations, and arterial anomalies and renal anomalies (Fig. 13.6a–d) [3, 5, 6].
PHACES syndrome: (a) beginning of the treatment with corticosteroids; (b) the result 4–5 years after treatment; (c) magnetic resonance imaging revealing intracranial anomaly; (d) LUMBAR syndrome
13.8 Patient Evaluation
The diagnosis of IH is possible in most cases by correlating history and physical examination [1–5]. Histologic diagnosis is gold standard, and immunohistochemically positive staining of endothelial cells in IH tumor specimens with GLUT1 presented in all stages differentiates IH from other vascular tumors and malformations [1–5, 18]. In case of deep subcutaneous, intramuscular or visceral lesions, or when there are associated anomalies, radiological evaluation is indicated including ultrasonography (US) (gray scale or color Doppler), computerized tomography (CT), and magnetic resonance imaging (MRI) with contrast, which is the gold standard diagnostic procedure for hemangioma [1, 2, 4].