Practice EssentialsInfantile hemangiomas are benign vascular neoplasms that have a characteristic clinical course marked by early proliferation and followed by spontaneous involution. Hemangiomas are the most common tumors of infancy and usually are medically insignificant.
Essential update: Timolol maleate safe and effective for infantile hemangiomas
Timolol maleate appears to be a safe and effective treatment for infants with small, nonulcerated, superficial infantile hemangiomas on nonmucosal surfaces, according to a recent randomized, double-blind, placebo-controlled trial. Of the 32 infants (aged 5-24 weeks) with superficial infantile hemangiomas who completed the study, 15 of them were treated with a drop of timolol maleate 0.5% gel gently rubbed in twice daily for 24 weeks. The other patients received a similarly applied placebo.[1, 2]
A significantly higher proportion of treated hemangiomas were found to have decreased in size by more than 5% when reviewed at weeks 20 and 24, as compared to lesions in the placebo group.
Safety was assessed by measuring blood pressure and heart rate before and after application of the gel or placebo, and no significant variation in these measurements were found between the 2 groups over the course of the study.
Signs and symptoms
Infantile hemangiomas may be cutaneous or extracutaneous. Frequency of cutaneous hemangiomas at particular sites is as follows:
Head and neck - 60% Trunk - 25% Extremities - 15%
Sites of extracutaneous hemangiomas include the following:
Liver Gastrointestinal tract Larynx Central nervous system Pancreas Gallbladder Thymus Spleen Lymph nodes
Lung Urinary bladder Adrenal glands
Cutaneous hemangiomas progress sequentially through the following stages:
Blanching of the involved skin Occasionally (especially with lip and buttock lesions), a shallow ulceration Fine telangiectasias A red or crimson macule or papule, often surrounded by a faint halo of vascular
blanchingFeatures are as follows:
Usual maximum size 0.5-5 cm Range from the size of a pinhead to greater than 20 cm in diameter Most remain well circumscribed and focal A minority are segmental in nature and more extensive
Infantile hemangiomas characteristically exhibit early rapid growth followed by slow involution, as follows[3, 4, 5, 6] Rapid growth during the neonatal period (birth to 4 wk)
The hemangioma becomes elevated and dome shaped, lobulated, plaquelike, tumoral, or any combination of these morphologies
The most growth occurs during the first 4-6 months of life Proliferation slows considerably between 6-12 months of life Complete involution in 50% of infantile hemangiomas by age 5 years and 70%
by age 7 years Complete involution may take an additional 3-5 years in the remainder
See Clinical Presentation for more detail.
Diagnosis
Skin biopsy can be performed if the diagnosis is in question after a thorough history and physical examination. Infantile hemangiomas uniformly stain positively for glucose transporter 1 (GLUT-1) during both the proliferation and the involution phases.
The following laboratory studies have been investigated as possible markers of hemangioma proliferation and differentiation[7, 8] :
Serum and urinary vascular endothelial growth factor (VEGF) Urinary beta-fibroblast growth factor Urinary matrix metalloproteinases (MMPs)
Magnetic resonance imaging (MRI) has the following uses:
Delineate the location and extent of cutaneous and extracutaneous hemangiomas
Differentiate proliferating hemangiomas from other high-flow vascular lesions (eg, arteriovenous malformations)
Features of ultrasonography:
Can help differentiate hemangiomas from other deep dermal or subcutaneous structures, (eg, cysts, lymph nodes)
Cannot fully evaluate the magnitude and extent of the hemangioma High vessel density (>5 vessels/cm2) and high peak arterial Doppler shift (>2
kHz) are sensitive and specific for infantile hemangiomas, as compared with other soft tissue masses[9]
See Workup for more detail.
Management
The vast majority of infantile hemangiomas do not require any medical or surgical intervention.[10] Treatment options for clinically significant hemangiomas include the following:
Laser surgery Surgical excision Medication
Features of laser surgery:
Flashlamp-pumped pulsed-dye laser most widely used Pulsed-dye laser surgery effective for treating ulcerated hemangiomas and thin
superficial hemangiomas Lasers used especially on areas likely to result in significant functional or
psychological impact (eg, fingers, eyes, lips, nasal tip, ears, face)[11, 12]
Many ulcerated hemangiomas respond with decreased pain (sometimes as early as a few days after the initial treatment), rapid reepithelialization, and hastened involution
Laser treatments generally performed every 2-4 weeks until complete healing results
Scarring or residual skin changes may occur Laser treatment may worsen ulceration, particularly of deep or combined
superficial and deep lesionsFeatures of surgical excision:
Not uncommonly used for correction of cutaneous defects from involuted hemangiomas[13]
Specially trained surgeons needed for surgical excision of proliferating hemangiomas because of the risk of hemorrhage and damage to vital structures
Early excision may save life, preserve vision, or eliminate a cosmetically disfiguring lesion
Features of pharmacologic treatment:
No treatments of infantile hemangiomas are approved by the US Food and Drug Administration
Corticosteroids can slow the growth and decrease the size of proliferating infantile hemangiomas
Oral corticosteroids preferred over intralesional injection Propranolol has become the treatment of choice for disfiguring or functionally
significant hemangiomas[14] ; an expert panel recently developed provisional recommendations for the use of propranolol in complicated infantile hemangioma[15, 16]
See Treatment and Medication for more details.
Image library
This proliferating superficial infantile hemangioma on the trunk required no therapy.
PathophysiologyInfantile hemangiomas are composed of proliferating, plump endothelial cells. Early in proliferation, the cells are in disarray, but, with time, they form vascular spaces and channels replete with blood cells (see image below).
Histopathology of a proliferating infantile hemangioma with plump endothelial cells in the dermis.These benign-appearing endothelial cells produce limited basement membrane structures. Hemangiomas assume a lobular architecture as proliferation slows and ends. Mast cells appear to affect this process and are implicated in the promotion of feeding arterioles and veins that supply each lobule. They also have been found in high concentrations during involution.
Takahashi hypothesized that during the third trimester of fetal development, immature endothelial cells coexist with immature pericytes, which maintain their proliferative capacity for a limited period during postnatal life.[14] Angiogenic peptides, such as beta-fibroblast growth factor, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen, induce proliferation of these immature cells, resulting in the development of the hemangioma. As the endothelial cells differentiate, an influx of mast cells, various myeloid cells, and tissue inhibitors of metalloproteinases (TIMPs) occurs.[17] TIMPs, along with interferon and transforming growth factor produced by the mast cells, terminate the endothelial cell proliferation and passively induce involution by senescence of endothelial cells.
United States
Infantile hemangiomas occur in approximately 1-2% and 10% of white infants at birth and at age 1 year, respectively.[5, 6] African American and Japanese infants have a similar incidence of 1-2% at birth; however, there are no studies regarding the incidence at age 1 year (the actual incidence since the majority are not present at birth) in other nonwhite populations.[6, 18] The incidence of infantile hemangiomas is approximately 22-30% of preterm infants with birthweight less than 1 kg; for preterm infants with birthweight greater than 1.5 kg,[19] the incidence is the same as for term infants. An increased incidence is recognized in infants from multiple gestations.
The incidence is increased with older maternal age, maternal placenta previa, and preeclampsia.[20] Some, but not all, surveys have demonstrated increased incidence in infants born to mothers who have undergone prenatal chorionic villus sampling.
Mortality/Morbidity
Most infantile hemangiomas are benign and do not cause any morbidity or mortality. Occasionally, they may impinge on vital structures and interfere with breathing, vision, eating, or hearing. Ulceration of certain areas (eg, diaper area, neck, mucosal surfaces) is not uncommon. Excessive bleeding is infrequent and rarely, if ever, life threatening. In the past, infantile hemangiomas were confused with other vascular neoplasms, particularly kaposiform hemangioendothelioma andtufted angiomas, which can incite a consumptive coagulopathy that may be life threatening. This is referred to as Kasabach-Merritt phenomenon (KMP). It is now generally accepted that infantile hemangiomas are rarely, if ever, responsible for KMP.[21, 22]
Large cutaneous or visceral hemangiomas (particularly liver) can result in high-output cardiac failure resulting from increased vascular flow. Permanent significant structural abnormalities may result, particularly when facial structures are involved. The highest risk appears to be with involvement of the nasal tip, lips, and ears.[23]Segmental hemangiomas, which cover a particular section or area of skin, may be markers for underlying malformations or developmental anomalies of the heart, blood vessels, or nervous system (PHACE and PELVIS syndromes [see below] and lumbosacral hemangiomas) and, depending on the severity of the associated anomaly, can result in increased morbidity or mortality.[24, 25]
PHACE syndrome (see image below) is posterior fossa structural brain abnormalities (Dandy-Walker malformation and various forms of hypoplasia); hemangiomas of the face, head, and neck (segmental, >5 cm in diameter); arterial lesions (especially carotid, cerebral, and vertebral); cardiac anomalies (coarctation of the aorta in addition to many other structural anomalies); eye abnormalities; and, rarely, associated midline ventral defects such as sternal cleft or supraumbilical raphe). A consensus statement with detailed diagnostic criteria for both PHACE and possible PHACE syndromes was published in 2009.[26]
Segmental infantile hemangioma in a female infant with PHACE syndrome involving the posterior neck and right forehead associated with an absent right vertebral artery and a laryngeal hemangioma.PELVIS syndrome (see image below) is perineal hemangioma with any of the following: external genital malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and/or skin tags.
Segmental infantile hemangioma with minimal or arrested growth of the bilateral buttocks and posterior thigh in this male infant with PELVIS syndrome (complicated by cutaneous ulceration, hypospadias, anal stenosis, intraspinal lipoma with tethered cord). The white material is a barrier diaper cream.Race
Hemangiomas occur most commonly in white infants, with an incidence rate 10-12 times that of black and Asian infants.
Sex
Females are affected more often than males by a ratio of 3:1. This disparity is higher (9:1) in those infants with large cervicofacial segmental hemangiomas associated with PHACE syndrome.
Age
Thirty percent of infantile hemangiomas are present at birth, and 70% of them initially appear in the first several weeks of life.
Vascular Anomalies: Review & Current Therapy
Samuel M. Lam, M.D.*, and Edwin F. Williams III, M.D.***Clinical Instructor, Division of Otolaryngology, Department of Surgery,Albany Medical College, Albany, New YorkStratton Veteran Affairs Medical Center, Albany, New York**Clinical Associate Professor, Division of Otolaryngology, Department of Surgery,Albany Medical College, Albany, New YorkChief of Division, Facial Plastic & Reconstructive Surgery,Albany Medical College, Albany, New YorkMedical Director, Williams Center for Facial Plastic Surgery,Latham, New York
Abstract Congenital vascular anomalies have been the subject of much controversy and confusion over the years. Since 1982, hemangiomas and vascular malformations have been recognized as distinct diseases that exhibit unique properties and behavior that demand an appropriately tailored treatment plan. This article will briefly review the characteristics of these vascular anomalies, including epidemiology, classification, and clinical presentation and then focus on the current therapeutic options that are available. The past decade has witnessed a revolution in the understanding and treatment of vascular lesions, marked by more advanced laser therapy, earlier intervention, and an increased sensitivity to the psychosocial dynamics of the disease. Key Words: Hemangiomas, Vascular Malformations, Current Therapy
Introduction
Much confusion and controversy have shrouded the classification and treatment of benign, congenital vascular anomalies. Hemangiomas and vascular malformations share the common attribute that they exhibit an abnormal abundance of blood vessels. Beyond this similarity, these vascular lesions differ fundamentally in histology and physiology. Early practitioners failed to distinguish between these two types of vascular anomalies, leading to inappropriate and at times harmful care of afflicted children. In 1982, Mulliken and Glowacki’s seminal treatise proposed that hemangiomas and vascular malformations represent unique disease processes, with the former constituting a true neoplasm by virtue of an increased endothelial turnover.1 The past decade has witnessed a revolution of thought and practice in the treatment of congenital vascular diseases and seen a further refinement of the concepts originally developed by Mulliken and Glowacki. A better understanding of the natural history of hemangiomas has resulted in a more effective treatment algorithm that may in turn diminish the damaging psychological repercussions of the disease on the child and family.2 Genetic loci **3,4, related syndromes5,6 , and cellular markers7have also been discovered that have shed new light on the clinical behavior of these vascular anomalies. Laser technology continues to evolve and can now achieve outstanding results with minimal morbidity. A host of therapeutic modalities has been introduced– including interferon therapy8-10 and interventional-radiology techniques**11 – that has met with varying success in the treatment of these disparate vascular disorders.
In order to provide a meaningful review of hemangiomas and vascular malformations, the article will be divided equally into respective sections on these two types of vascular anomalies.
Hemangiomas
Epidemiology
Hemangiomas are the most common neoplasm of infancy and childhood, with an estimated prevalence of 1-3% of all neonates 12,13 and 10% of infants by 1 year of age.14,15 Most hemangiomas arise in the head and neck region (60%), and 20% of patients may suffer from more than one lesion.16 Prematurity is a well-identified risk factor, especially in those neonates that fall below 1500 grams in weight.17 A predilection for the female sex has also been reported, with a ratio of 3 to 1.18 Most hemangiomas tend to arise de novo without an antecedent family history, but a few studies have determined an autosomal-dominant pattern of inheritance in a select group of patients.18 Chorionic villus sampling has also been found to predispose one’s progeny to the development of a hemangioma.19
Classification
Prior to the work of Mulliken and Glowacki, terminology that described hemangioma types was mired in inconsistency and confusion. A plethora of words abounded to describe various hemangioma morphologies that at times overlapped with descriptions of vascular malformations, such as “strawberry nevus” and “cavernous hemangioma”. These ill-defined terms have been largely replaced by a systematic nomenclature that seeks to delineate the anatomic dimensions of the lesion. Hemangiomas that arise only on the surface of the skin and immediate subjacent tissue may be accurately referred to as superficial (formerly known as capillary). Conversely, a lesion that is situated only in the deeper subcutaneous tissue may be considered a deep hemangioma (formerly known as cavernous). If both superficial and deep components are present, then the hemangioma may be categorized as compound or mixed. Field hemangiomas represent multiple hemangiomas that rapidly enlarge and coalesce into a more singular entity. Visceral hemangiomas are derived within the internal organs, like the liver, colon, and brain. Diffuse neonatal hemangiomatosis refers to a highly lethal condition in which the newborn is covered with hundreds of hemangiomas that may involve the viscera as well, leading eventually to cardiac failure and ultimately to death within weeks.20 Hemangiomas
may also be part of a syndrome known as PHACE(S) (Posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities [and sternal clefting and supraumbilical raphae]).21
Clinical Presentation
At birth, a child may exhibit various manifestations of the incipient hemangioma, including an erythematous macule, a telangiectatic mark, a faded area, or no identifiable lesion at all. Although most hemangiomas are present within the first month of life, it is rare that they are recognizable as such at the time of birth. Superficial hemangiomas are bright red and non-compressible and may assume a raised or flat contour. Deep hemangiomas are situated in the subcutaneous tissue and may be well below the skin so that a raised mound provides the only clue to the underlying lesion. At times, a bluish hue may be visible through the skin as a hint of a deep hemangioma that approaches more closely to the skin’s surface. In addition, telangiectasias or prominent veins may pepper the skin overlying a deep hemangioma.The natural history of hemangiomas is characterized by a marked proliferative phase during the first few months of life that usually is sustained to the end of the first year but rarely persists beyond that time. During this period, the hemangioma may risk ulceration or frank hemorrhage, the former condition may lead to infection and scarring and the latter may usually cease with simple application of pressure. The greatest concern with rapid growth of the hemangioma lies in its obstructive potential: in the subglottic airway resulting in stridor or further compromise, situated near the eye leading to amblyopia, or in the external auditory canal causing a conductive hearing loss. The psychological impact of the expanding hemangioma should not be underestimated and may cause considerable alarm in parents, leading them to seek medical counsel during this time. After the first year of life, the hemangioma may begin to involute slowly or remain stable and only then slowly diminish in size over the next several years. If the hemangioma should resolve slowly (a late involuter), then the child may suffer considerable psychological damage during the school years and still be left with a marked cosmetic deformity. The classification of hemangiomas into early and late involuting types has shaped a newer treatment algorithm that will be discussed in the following section.
Current Therapy
Since the work of Lister, management of hemangiomas has been plagued with the prevailing dictum of benign neglect.22 Many practitioners have advocated no therapy at all with the prescription that all hemangiomas will ultimately resolve. Recent studies have determined that late-involuting hemangiomas only incompletely regress and leave behind an often-significant residuum.23,24 Neonates and infants may remain unaware of their disfiguring condition, but children 3 years and older are subjected to a burgeoning self-identity and the attendant social stigma that “being different” bears.25,26 A policy of watchful waiting in a slowly involuting hemangioma may prove detrimental to a child’s psyche and may lead to ostracism from his peers.Williams et al. have proposed a new treatment strategy based on the proliferative and involuting characteristics of a hemangioma in order to treat select patients on a timely basis and to preclude the potential psychological sequelae of a longstanding hemangioma.2 A proliferative hemangioma that risks ulceration or bleeding or that is rapidly expanding in a cosmetically sensitive area is a candidate for early intervention. Pulse-dye laser therapy with adjunctive intralesional steroid application has proven to be effective to retard the rate of growth. A trial of oral steroids may be mandated for a hemangioma that shows signs of impending obstruction, e.g., by encroaching on the airway or vision. Most hemangiomas begin to involute early, albeit slowly, and should be left to regress spontaneously. However, a hemangioma that tends toward late involution should receive therapy so as to remove the disease that would most likely fail to involute completely and that would impair the child’s favorable psychosocial maturation. At this stage, surgical debulking with adjunctive laser therapy is the preferred method of intervention, as steroids have no beneficial role during the involutional phase.It should be emphasized at this point that most hemangiomas do not require therapy, and only a select minority coincide with the enumerated criteria for intervention. Parents suffer significant psychological distress from the presence of a vascular birthmark.27 However, the timing and rationale for intervention should never be dictated by parental coercion, as this injudicious policy would do a disservice to both the child and insurance carrier, or other third-party payer, to whom the physician is responsible. Throughout the history of hemangioma management, many therapeutic options have been advocated or tried with mixed success. Compression therapy was hitherto popular when few options were available at the time.28,29,30 However, some authors still rely on this low-risk method of treatment. Cryosurgery was popular in the past but has lost some of its charm.31 Many therapeutic modalities that carry a high morbidity profile were also once in vogue, including embolization,
sclerosis, chemotherapy, and irradiation.32,33 Embolization of visceral hemangiomas34 and intralesional chemotherapy35 for refractory cases have still shown some clinical utility. Interferon therapy may also prove helpful in life-threatening or recalcitrant cases.8-10 but has been associated with neurotoxicity, including spastic diplegia36, and should be used with great caution. The cornerstones of effective therapy for hemangioma today principally involve steroid, laser, and surgery.
Steroid TherapySystemic steroid therapy has been a reliable method of treatment for over 30 years37, but no controlled, prospective studies have been undertaken to evaluate the efficacy, proper dosing, duration of therapy, or tapering regimen. Steroid therapy, whether systemic (oral and intravenous) or local (intralesional and topical), is only effective during the proliferative phase of hemangioma development and should be used to treat a rapidly proliferating hemangioma in a cosmetically sensitive area that risks imminent ulceration or bleeding or that may lead to obstruction, e.g., near the eye or in the airway. Usually a rapidly proliferating hemangioma that may ulcerate or hemorrhage may be treated with the pulse-dye laser and with concomitant intralesional kenalog injection. However, if an obstructive potential exists, then oral steroids may be necessary.A meta-analysis of systemic steroid therapy determined a response rate of 84% in 10 original case series that met inclusion and exclusion criteria (viz., treatment of a problematic hemangioma, child less than 2 years old, greater than 5 cases, no other simultaneous treatments, proper follow-up, and sufficient data).**38 The study concluded that administration of higher doses of prednisone (>3 mg/kg/day) resulted in a higher response rate (94%) but a concomitantly higher side-effect profile and that lesser doses (<2mg/kg/day) showed less response, fewer adverse effects and greater rebound rate (70%). Patients underwent a mean 2-month period of therapy and were maintained on oral steroids until cessation of growth or actual regression was evident. Tapering schedules were not delineated in most case series and varied considerably in the reported studies. In conclusion, oral steroid therapy (2-3 mg/kg/day) can be effective in a select group of hemangioma patients who have obstructive or recalcitrant lesions and who demonstrate a response to steroids.
Laser Therapy The introduction of the pulse-dye laser has proved to be nothing short of miraculous for the treatment of vascular lesions and has almost entirely replaced
the argon laser. A large series (617 hemangiomas) treated with the pulse-dye laser demonstrated a 96.6% arrest in further growth after a mean of 2.5 treatments (13.8% complete remission, 14.9% significant regression, 67.9% discontinuation of growth).**39 During rapid proliferation, hemangiomas may require several sessions of laser therapy divided 6 to 8 weeks apart in order to retard the growth rate. As mentioned, intralesional steroid therapy may be a beneficial adjunct at the time of laser administration. The indication for laser therapy would include a rapidly proliferating lesion that may ulcerate, bleed, or obstruct. The pulse-dye laser really only targets the superficial component of the hemangioma. The ND:Yag and argon lasers have been applied interstitially for the treatment of deeper hemangiomas40, but we strongly advise caution as the risk of scar formation may be considerable. During the involutional period, the laser may remove residual dermal ectasias and telangiectasias, tighten the loosened skin overlying the hemangioma, and serve as a useful adjunct post-surgery to address the aforementioned residual deformities. Unlike late-involuting hemangiomas, early involuters should be permitted to regress naturally and not be subjected to unnecessary therapy. The carbon-dioxide (CO2) laser may play a useful role in the treatment of laryngeal hemangiomas that encroach on the airway but should be used conservatively to avoid tracheal stenosis.41 Because the risk of scarring is high for large or circumferential lesions, tracheotomy and systemic steroid therapy may be beneficial in certain cases.*42 Tracheotomy and systemic steroid therapy clearly have their own attendant risks and limitations, including delayed speech and swallowing problems for the former and the many well-known side effects of the latter. The physician is urged to apply clinical judgment when deciding on a particular course of therapy.
Surgery Surgery remains a reliable technique of debulking hemangiomas in a rapid and definitive manner. During the proliferative phase, hemangiomas rarely require surgical intervention except to alleviate obstructive lesions that fail more conservative measures. Generally, surgery plays a more useful role during the involutional phase to remove the unsightly residuum that may remain. A key surgical concept is removal of the bulk of disease but leaving a small (10%) remainder of the lesion behind to accommodate for any further regression that the lesion may undergo in the future. Usually 6-8 weeks after surgery, the patient may benefit from pulse-dye laser therapy to remove any superficial dermal ectasias or discolorations that are still present. By approaching the involuted hemangiomas conservatively, the surgeon may avoid larger, unnecessary incisions and prevent a
depression due to over-resection. Most residual hemangiomas may be removed in a straight-forward fashion. However, infrequently the surgeon may require tissue expanders or serial excisions to resect larger residual deformities that encompass a greater cutaneous surface. Although tissue expanders have been described with success in the literature43, we believe that children tend not to tolerate these devices well psychologically or physically and may be better served with serial excisions for larger, more difficult hemangiomas.
Kasabach-Merritt Syndrome Before concluding this section, we must address the current thinking of the Kasabach-Merritt syndrome, which is characterized by thrombocytopenic coagulopathy. This phenomenon has been recently found not to be associated with true hemangiomas but with two distinct vascular tumors known as the kaposiform hemangioendothelioma and tufted angioma44. These unique lesions exhibit a violaceous tone and nodular pattern, but each has its own particular histopathologic features. Kasabach-Merritt carries a high mortality rate, and treatment is often inadequate and inconsistent, relying on multimodality therapy of cytotoxic agents such as vincristine, cyclophosphamide, systemic prednisone, and interferon alfa.45
Vascular Malformations
Epidemiology, Classification & Clinical Presentation
Vascular malformations (VMs) arise from an error in morphogenesis of any combination of the following vascular networks: arterial, venous, capillary, and lymphatic. Unlike hemangiomas, these vascular anomalies are present at birth and grow proportionally to the size of the child and do not exhibit any tendency to involute spontaneously. Hormonal factors, such as puberty or pregnancy, may influence the growth of these vascular lesions, causing acceleration in size during these periods. Direct trauma or infection may also trigger a rapid expansion. The predominant vessel type (arterial, venous, capillary or lymphatic) dictates the flow (slow or fast) and thereby the physical attributes of the lesion. Fast-flow malformations usually have an arterial component and exhibit a propensity to expand, to achieve large volumes, and to pulsate. Slow-flow lesions encompass capillary, venous and lymphatic types and behave according to the primary vessel present.By far the most common of the VMs, capillary malformations (port-wine stains [PWS]) occur in an estimated 3 children per 1000 births, with approximately 80%
occurring in the head and neck region and with an equal sex distribution.46 PWS manifests as a flat lesion with a red to pink hue which may lighten during the first year but then tends to darken throughout life turning a deeper shade of red or blue and may even become thicker or more nodular as the individual matures.47 Two related syndromes have been linked with PWS: Sturge-Weber and Klippel-Trenaunay. Sturge-Weber, or encephalotrigeminal angiomatosis, refers to a PWS that is distributed in the first trigeminal division (V1), with or without V2 or V3 involvement, and with central nervous system (CNS) abnormalities. CNS defects include cerebral atrophy, leptomeningeal angiomas, and cortical calcifications that may lead to seizures, mental retardation and hemiparesis. Magnetic resonance imaging (MRI) should be conducted after 6 months of age to screen the high-risk neonate, who, by our experience, usually has V1 involvement that circumscribes the eyelid and often V2 extension as well. In addition, ocular examinations should be undertaken to determine whether glaucoma is present with the syndrome. Klippel-Trenaunay syndrome, or angio-osteohypertrophy, is characterized by a PWS that usually involves a unilateral, lower extremity marked by hypertrophy, varicose veins, lymphedema and phleboliths. 48
Venous malformations are characterized by a dark blue hue and may be situated in the skin, subcutaneous tissue, or mucosa. They tend to be compressible and may have nodular areas that constitute phleboliths scattered throughout. Lymphatic malformations, formerly known as lymphangiomas, typically arise in the head and neck. They may be deeply infiltrative above the hyoid and more circumscribed in nature below the hyoid. Arteriovenous malformations are principally found in the cephalic region and show signs of rapid arterial flow, including warmth and the presence of a bruit or thrill. One of the most dreaded complications that may occur with this fast-flow lesion is high-output cardiac failure.
Current Therapy
Vascular malformations represent a dissimilar group of disorders that mandate a treatment plan predicated on the vessel type(s) and related clinical manifestation. Port wine stains represent the most common form of VM, and the extent of literature concerning PWS is commensurate to its prevalence. Accordingly, most of the current treatment options that will be discussed focus on management of PWS.Capillary Malformations (Port Wine Stains)
Prior to the introduction of laser therapy, the only method of treatment for PWS was simply cosmetic camouflage. Initially, the argon laser showed promise in the treatment of vascular diseases, but the incidence of scarring and the advent of the pulse-dye laser have largely relegated the argon to historical interest. Now with the pulse-dye laser that selectively targets the vascular chromophore in PWS, patients have found a new hope in minimizing their deformity with little morbidity. However, patients should be properly informed that their lesion will fade but not completely vanish with the pulse-dye laser. Numerous studies have documented the proven reliability of the pulse-dye laser in treating PWS.*49,50 Some studies have investigated the role of a 532-nm KTP laser in the treatment of resistant PWS and found clinical efficacy**51, but scarring has been reported with this laser type.**51,52 Intense pulsed light has also proven to be highly effective and safe for the treatment of PWS according to one study.53 The authors recommend discretion in the use of lasers other than the pulse dye, which is a proven and safe gold standard of therapy. Recent studies have emphasized the psychological aspect as much as the efficacy of treatment.54,55,56,57 Most studies have demonstrated the ostracizing effects of the PWS and the benefit of intervention to the psychological welfare of the afflicted individual. One small study contended that the patients in the series (n=9) revealed no subjective benefit to treatment despite objective physical improvement.55 As the child matures, he/she not only confronts the psychosocial trauma of bearing the unsightly mark but also may develop a lesion that is more difficult to treat as age and hormonal factors darken and thicken the PWS. For all these reasons, it is imperative to institute early laser therapy to counteract the detrimental psychological and physical forces and to continue therapy based on the responsiveness to the treatment and the tolerance and desire of the patient and family to undergo further cycles of therapy.
Other Vascular Malformations
A comprehensive review of all the options that are available to cope with vascular malformations lies beyond the scope of discussion. The mainstay of therapy for other types of vascular malformations remains complete surgical extirpation. Incomplete attempts only make future surgery both necessary and more difficult and can foil any successful pre-embolization efforts. Embolization for arteriovenous malformations should be seriously considered in order to minimize intraoperative blood loss as well as the extent and complexity of
surgery.**11 Patients should be counseled on the morbidity of embolization and surgery against that of no intervention and should weigh the options intelligently.
Conclusions
Many advances have been made in the understanding and treatment of vascular anomalies, including improved laser therapy, knowledge of disease biophysiology, and sensitivity to the psychological repercussions on the child and family. This progress has informed the timing and technique with which care givers have therapeutically intervened. More active and earlier therapy has been administered to a select minority of hemangioma patients who demonstrate a rapidly proliferating hemangioma in a cosmetically sensitive area or that risks ulceration and hemorrhage or who show a late- involuting lesion that may not completely resolve and only serve to worsen the child’s psychosocial integration. Port wine stains have been successfully treated with the pulse-dye laser and those afflicted with these lesions have been the favored subject of much psychological analysis. Advances in all fronts are expected in the management of vascular anomalies and should alleviate the considerable burden of disease carried by the child and family alike.
Hemangioma Newsline
Providing Medical Information for the Diagnosis and Treatment of Vascular Birthmarks
HEMANGIOMAS
Hemangioma is the most common benign tumor of infants. They are usually apparent at birth but become evident within the first two weeks.Hemangiomas occur in 5-10 % of all children and three times more often in females then males.Hemangiomas occurs more often in Caucasian infants then in African American infants.They occur more often in premature infants.Hemangioma will grow for the first 8-12 months of life.Growth can be prolific and may appear to change daily.Hemangiomas will begin to regress or involute around 12 months of age. This process may take up to 10-12 years leaving residual scarring.
HEMANGIOMA TYPES;
SUPERFICIAL- located in the upper layers of the skin
MIXED- located in the upper and lower layers of the skin or internal organs
DEEP- located in deep tissue layers, muscle or internal organs.
70 % of all Hemangiomas occur on the head and neck but they may occur anywhere including the internal organs like, the brain, liver, lungs, kidneys and GI tract.
VASCULAR MALFORMATIONS
Vascular Malformations are always present at birth but may not be evident until later on in life.Vascular Malformations enlarge as the child grows without a prolific growth period. Growth may not occur until adulthood.Vascular Malformations do not regress or involute spontaneously.
Vascular Malformations are often misdiagnosed as Hemangioma.Vascular Malformations usually cannot be totally eradicated.
TYPES:
Capillary - Port Wine Stain
Venous - frequently mislabeled a cavernous hemangioma
Arteriovenous - usually involves internal organs, the most difficult to manage
Lymphatic - abnormalities of the lymphatic vessels and are usually apparent at birth, difficult to manage
Mixed - a combination of the above, may involve fast and slow flow vessels and shunting of blood flow
TREATMENT OPTIONS
Hemangioma and Vascular Malformations are treated differently.Hemangioma - early diagnosis and evaluation of growth give best treatment options including steroid, laser, alpha-interferon, surgical excision.Vascular Malformation - options include laser, surgical excision, embolization, scelerotherapy, and radiation
Evaluation of both Hemangioma and Vascular Malformations is essential for diagnosis and treatment,
Hemangioma Newsline has a complete list of multi-specialty clinics located in the United States specializing in Vascular Birthmarks.
RELATED SYNDROMES
Kasabach Merritt Syndrome
Klippel Trenaunay Syndrome
Parkes Webber Syndrome
Sturge Webber Syndrome
Hemorrahagic Telangiectasia
Von Hippel - Lindau
Most vascular anomalies are recognized with various imaging modalities. Radiography, ultrasonography (US), CT, or MRI is usually performed to confirm the suspected diagnosis, to determine the extent of the vascular anomaly and to search for associated abnormalities. Vascular anomalies are grouped into hemangiomas and vascular malformations.[1, 2]
Examples of vascular anomalies are shown in the images below:
Vascular anomalies. Infantile hemangioma. Coronal contrast-enhanced T1-weighted image shows the classic MRI appearance of infantile hemangioma. A well-rounded homogeneously enhancing cervical mass is associated with high-flow vessels (signal voids) in and around the mass. Most of these lesions require no additional testing for
diagnosis. Vascular anomalies. Kaposiform hemangioendothelioma (KHE). Axial T2-weighted MRI obtained through the face shows an extensive soft-tissue abnormality in the right facial area that involves the adjacent osseous structures and extends
into the oropharyngeal structures; it results in significant airway narrowing.Vascular anomalies. Arteriovenous malformation (AVM). Contrast-enhanced magnetic resonance angiogram (MRA) shows a nidus and early draining veins in the forearm.
Vascular anomalies. Venous malformation (VM). Axial CT image of the pelvis shows a mass that contains multiple phleboliths. Although CT is not the imaging modality of choice for VMs; however, phleboliths and osseous changes, in some cases, are best
appreciated on CT scans. Vascular anomalies. Lymphatic malformation (LM). Axial T2-weighted MRI shows an extensive soft-tissue abnormality involving the neck, face, and oropharyngeal structures. The lesion has inhomogeneous hyperintense signal and causes significant airway compression.Misclassifications or incorrect diagnoses are common and are usually due to the limited experience of the clinicians or radiologists involved in the diagnosis and management of vascular malformations. Use of an inappropriate imaging modality (eg, CT instead of MRI) and poor image quality can also contribute to this clinical dilemma.
The most common misdiagnosis or misconception is the use of the term hemangioma to mean venous malformations (VMs). This misconception can easily lead to incorrect triaging and mistreatment. For example, patients are
commonly treated with steroids because the interpretation of a hemangioma lesion on the imaging study (eg, MRI).
Another common diagnostic dilemma is arteriovenous malformation (AVM). Often, the malformation is called an AVM although all clinical and radiologic findings are characteristic of a low-flow vascular anomaly (eg, VM). Therefore, recognizing a vascular malformation and appropriately classifying the malformation is essential for optimal patient care and requires solid knowledge and experience.
