Are You Confident of the Diagnosis?

What you should be alert for in the history

Hemangiomas are benign vascular neoplasms. They are both the most common vascular tumor and the most common tumor of infancy. Classically, a parent will present with an infant who appeared normal at birth but subsequently developed a cutaneous lesion within the first days to months of life. Cutaneous hemangiomas may be associated with visceral hemangiomas and, though rare, the clinician should be alert for any associated systemic symptoms such as respiratory or cardiovascular difficulty that may indicate visceral involement.

Characteristic findings on physical examination

Hemangiomas commonly first appear as red, bluish, or telangiectatic macules or patches. They often begin subtly and can be mistaken for bruising or trauma. They are most often solitary and may vary widely in size, from pinpoint to multi-centimeter. While they can occur anywhere on the skin, mucous membranes, or internal organs, they are most often found on the head and neck.

Hemangiomas can be classified as superficial, deep, or combined based on the level of skin involvement. The most common form is the superficial hemangioma (also referred to as a strawberry or capillary hemangioma), which presents as a raised bright red papule, nodule, or plaque (Figure 1). Purely deep hemangiomas (also referred to as subcutaneous or cavernous hemangiomas) are least common and appear as soft skin-colored masses with a bluish hue and occasional overlying telangiectasias (Figure 2). Combined hemangiomas contain both superficial and deep components and are also common (Figure 3).

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Figure 1.

Superficial hemangioma of the ear.

Figure 2.

Deep hemangioma of the nasal tip.

Figure 3.

Combined hemangioma of the elbow (involuting stage).

Hemangiomas can be further classified into localized and segmental types. Localized hemangiomas tend to be smaller and spatially-contained compared with segmental forms, which display a plaque-like geographic distribution often covering an anatomic region.

Hemangiomas follow a typical clinical course that helps differentiate them from other vascular lesions. Presenting a few days to months after birth, hemangiomas subsequently undergo a period of rapid growth for the first several months of life. Hemangiomas often feel warm and firmer during the early proliferative phase and show temperature-dependent color change, but they are usually not painful unless ulcerated.

By 5 months of age, 80% of hemangiomas have either slowed or stopped growing. However, larger and/or deep hemangiomas, especially in certain locations such as the parotid, may continue to grow for up to 12 months or longer. A spontaneous involution phase follows, which typically begins after one year and may last a variable number of years. A central color change from bright red to dark red-violet to gray heralds the beginning of involution with superficial hemangiomas. Deep hemangiomas become smaller, softer, and cooler to the touch.

Though all hemangiomas involute, some may leave permanent residual scarring, atrophy, discolorations, or telangiectasias. The potential and significance of such changes varies by lesion type, size, and location.

Expected results of diagnostic studies

In the vast majority of cases, the diagnosis of hemangioma can be made clinically based on characteristic history and clinical features. However, purely deep hemangiomas can sometimes be more difficult to diagnose and may require further studies. Physical examination should include a careful examination of the skin and mucous membranes. In infants with multiple (5 or more) hemangiomas, it is important to palpate the liver carefully, listen for an abdominal bruit, and be alert for signs of high output heart failure such as bounding pulses, wide pulse pressure, and a third heart sound that may indicate hepatic involvement.

When the diagnosis of hemangioma is in question, further studies may be indicated. An ultrasound with Doppler is the most cost-effective initial study. A high vessel density of more than 5 vessels/cm2 and high flow patterns exceeding 2kHz support the diagnosis of a hemangioma (Figure 4). Magnetic resonance imaging (MRI) is regarded as the best technique to evaluate lesion extent and characteristically shows a densely lobulated mass with isointensity to muscle on T1-weighted images and hyperintensity on T2-weighted sequence, with central and peripheral high-flow vessels (Figure 5).

Figure 4.

Doppler ultrasound showing heterogenous hypoechoic lesion with prominent vasculature (increased vascular flow), consistent with a hemangioma.

Figure 5.

Top left: T1-weighted image; Top right: T1-weighted image postcontrast. Bottom left and right: T2-weighted images showing hyperintensity and multiple flow voids.

CT demonstrates a well-circumscribed lesion with homogenous enhancement without calcification or fat stranding. Though tissue biopsy is rarely needed, it should be strongly considered if there is any concern for malignancy, since even the best imaging cannot definitively distinguish a benign from malignant vascular tumor.

The histopathology of a hemangioma demonstrates large masses of rapidly dividing endothelial cells with variable lumens and multi-laminations of the basement membrane. The glucose transporter variant GLUT-1 is uniquely expressed in both proliferating and involuting hemangiomas and is an important diagnostic marker (Figure 6, Figure 7).

Figure 6.

H&E showing vascular proliferation with vessel lumina lined by plump endothelial cells.

Figure 7.

GLUT-1 staining of endothelial cells.

Elevated urinary basic fibroblast growth factor (bFGF) levels and serum concentrations of endothelial growth factor (VEGF) have been proposed as diagnostic markers of hemangiomas but are rarely utilized in clinical practice.

In infants less than 6 months of age with 5 or more hemangiomas, a liver ultrasound is indicated. Of note, however, symptomatic liver hemangiomas are rare and thus the presence of liver hemangiomas alone rarely necessitates treatment. Dependent on history and physical examination, basic laboratory testing that may be considered to exclude the possibility of systemic involvement includes a complete blood count, liver function panel, and fecal occult blood test.

Diagnosis confirmation

While relatively uncommon compared with hemangiomas, a number of other vascular tumors and malformations may mimic hemangiomas and create diagnostic confusion.

So-called “congenital” hemangiomas exist in two forms: the rapidly involuting congenital hemangioma (RICH) and non-involuting congenital hemangioma (NICH). Both are distinguished from infantile hemangiomas by being fully formed at birth and by negative staining for GLUT-1 on histopathology.

Tufted angiomas and Kaposiform hemangioendotheliomas can be congenital or present in infancy or early childhood. Tufted angiomas most often present as firm, nodular, tender, erythematous to violaceous plaques. Increased sweating and/or hair growth over the tumor has been reported. Kaposiform hemangioendotheliomas tend to be larger and more infiltrative, sometimes extending over the chest or limb. Violaceous discoloration is often indicative of underlying Kasabach-Merritt phenomenon.

Both tufted angiomas and kaposiform hemangioendotheliomas have distinct histopathologic and MRI features from hemangiomas. Some overlap between these two tumors can also be seen, as many experts feel they represent a spectrum of the same entity.

Pyogenic granulomas present as solitary red, rapidly growing papules or nodules with a collarette of scale. They are acquired lesions, generally presenting in early to mid-childhood, and often exhibit recurrent bleeding as a result of minor trauma.

Capillary malformations (port-wine stains) are present at birth as pale pink to red, well defined patches. Unlike hemangiomas, they demonstrate no dynamic change (proliferation or ulceration) during infancy.

Venous malformations are also congenital, though they may not manifest and become noticeable until later in infancy or childhood. They are distinguished from hemangiomas by a deep dark-blue color and compressibility. Lesions enlarge with dependent positions, crying, or physical activity. Venous malformations do not involute and are characterized by slow, gradual expansion over time. Episodic pain, most commonly with morning wakening or heavy activity, is also characteristic. Physical examination and imaging can help distinguish and characterize the extent of venous malfornations.

Glomangiomas, a variant of venous malformations, are congenital or acquired. They may be solitary or multiple, tender, and can be inherited in an autosomal dominant manner.

Lymphatic malformations, like venous malformations, are congenital and are generally apparent at birth. They present as firm, flesh-colored masses that may demonstrate an overlying stain or pinpoint flesh-colored to violaceous papules. They can demonstrate rapid enlargement with infection or trauma.

Arteriovenous malformations often present in infancy but may initially be quite subtle, sometimes mimicking capillary malformations. Over time, arteriovenous malformations can be associated with soft tissue fullness, warmth, and characteristic pulsatility. Advanced lesions can be associated with ulceration and pain. Patterns on Doppler ultrasound and magnetic resonance angiogram can mimic hemangiomas (particularly deep and hepatic hemangiomas), thus they are best distinguished by an experienced radiologist. Definitive diagnosis may require conventional arteriography.

Other vascular malformations to consider include multifocal lymphangioendotheliomatosis with thrombocytopenia, spindle cell hemangioma, blue rubber bleb nevus syndrome, Klippel-Trenaunay syndrome and hereditary hemorrhagic telangiectasia. The diagnoses are best distinguished by unique history and clinical characteristics.

Other benign tumors that may resemble hemangiomas include pilomatricoma, juvenile xanthogranuloma, infantile myofibroma, infantile hemangiopericytoma, solitary reticulohistiocytoma, lipoblastoma, sacral lipoma, encephalocele/meningocele, heterotropic brain tissue, dermoid cyst, plexiform neurofibroma, and Spitz nevus. Clinical characteristics and/or imaging can generally differentiate the majority of these lesions.

Malignant tumors that mimic hemangiomas are rare but important to remember. Such tumors include infantile fibrosarcoma, rhabdomyosarcoma, and rarely, dermatofibrosarcoma protuberans and giant cell fibroblastoma. Imaging can aid in differentiating these malignancies but biopsy should be performed if history, physical, and imaging studies cannot clearly make a diagnosis.

Who is at Risk for Developing this Disease?

Hemangiomas occur in 1.1% to 2.6% of term neonates, 12.7% of preterm infants, and 15.6% of very low-birth-weight infants (below 1500g). They may affect all children but are most commonly found in Caucasian infants and less commonly in African and Asian races. Females are affected more than males and have a higher risk of developing segmental hemangiomas. Increased incidence has been associated with advanced maternal age, premature births, multiple gestations, placenta previa, and preeclampsia.

The most significant associated risk factor is low birth weight. There has been a reported association between hemangiomas and chorionic villus sampling, but there is no conclusive evidence of a causal relationship. The majority of hemangiomas occur sporadically.

What is the Cause of the Disease?

The etiology and pathogenesis of hemangiomas is not yet entirely understood. Evidence suggests that hemangiomas are clonal proliferations of endothelial cells that develop during vasculogenesis. This abnormal proliferation of endothelial cells appears to result from an imbalance in vasculogenic factors. Hemangiomas have been shown to exhibit unregulated expression of markers such as GLUT-1, VEGF, bFGF, intercellular adhesion molecule-3 (ICAM-3), E-selectin, insulin-like growth factor-2 (IGF-2), merosin, FcRII, Lewis Y antigen, CD83, CD15, CD32, and hypoxia-inducible factor-alpha (HIF-1alpha), and downregulation of others, such as CD146.

Three main hypotheses currently exist to explain hemangioma development: intrinsic activation of VEGF signaling, formation of hemangioma tumor cells from placental cell emboli, and development of hemangiomas from endothelial progenitor cells or stem cells.

Systemic Implications and Complications

While the majority of hemangiomas resolve without complications and require no intervention, clinicans should be aware of the potential associated morbidities. Early recognition of high-risk hemangiomas is key to minimizing potential complications. Both morphology and location are important factors in determining when a hemangioma is high risk.

Ulceration is the most common hemangioma complication. Hemangiomas are prone to ulceration when they are large, segmental, in the rapidly proliferating stage (generally within the first 3 to 4 months), or located in areas prone to trauma or friction, such as the diaper area, scalp, or back. Ulceration may result in secondary complications of pain, bleeding, infection, and scarring or disfigurement. First-line management includes wound care, with additional pain control and antibiotic therapy when indicated. Pulsed-dye laser is a commonly employed adjunctive therapy to improve pain and healing.

Disfigurement is also a relatively common hemangioma complication, which can range from minor to life-altering. Large segmental hemangiomas of the face are of particular concern, in addition to superficial and raised localized lesions, especially when involving the vermillion border of the lip, nose, or ear pinna. As noted above, ulceration also invariably leads to scarring.

Functional organ compromise is an additional hemangioma complication. The best-recognized scenario is when a hemangioma is periorbital and compromises the visual axis. Potential risks include amblyopia, astigmatism, exophthalmos, ptosis, proptosis, and strabismus. Infants with at-risk periorbital hemangiomas should be evaluated promptly by an experienced ophthalmologist.

Less well recognized is the association between segmental hemangiomas located in a “beard” or cervicomandibular distribution (eg, preauricular region, chin, lower lip and/or anterior neck) and concomitant airway hemangioma. Infants with hemangiomas in this distribution should be monitored closely for signs of airway distress, including the gradual onset of croup-like cough, stridor, or hoarseness, especially in the first 3 to 4 months of life. Infants who develop concerning clinical signs should be evaluated promptly by an experienced otolaryngologist, who will generally use direct laryngoscopy to evaluate the airway.

Infants with large segmental facial hemangiomas, including those in a “beard” distribution, are at high risk for PHACE(S) syndrome: Posterior fossa malformations, large facial Hemangiomas, Arterial anomalies, Coarctation of the aorta and cardiac defects, Eye abnormalities, and less commonly, Sternal defects (Figure 8). The syndrome is considered primarily vascular, with the vast majority of affected children having cerebrovascular and/or cardiovascular anomalies. All infants with facial segmental hemangiomas should undergo screening with MRI and MRA imaging of the head and neck, cardiac imaging to include the aortic arch, and an ophthalmologic evaluation.

Figure 8.

Large segmental facial hemangioma in a patient with PHACES syndrome.

Diagnostic criteria for PHACE(S) syndrome were recently proposed and should be referred to once the evaluation has been completed. The most commonly associated morbidities of PHACE(S) are neurologic, ranging from rare acute ischemic stroke to neurocognitive.

Hemangiomas of the lumbosacral skin, particularly when segmental, midline, ulcerated and/or associated with a second high-risk birth anomaly in the same location, such as aplasia cutis or a lipoma, should be evaluated for potential spinal dysraphism with MRI. PELVIS syndrome has been proposed to describe this constellation of findings: perineal hemangioma, external genitalia malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag. As MRI may not detect tethered spinal cords in infants younger than 3 months, repeat imaging may be indicated if spinal cord abnormalities are strongly suspected. Of note, ultrasound is not an appropriate screening tool for spinal dysraphism at any age.

Multiple (5 or more) hemangiomas can be associated with visceral hemangiomas, though of note, visceral hemangiomas involute just like their cutaneous counterparts, and symptomatic visceral hemangiomatosis is rare. While a number of organs can be affected, the liver is the most common, and therefore liver ultrasound is generally recommended in infants less than 6 months who present with multiple hemangiomas. Importantly, treatment is not required for asymptomatic hepatic hemangiomas as the majority remain asymptomatic.

Large hepatic hemangiomas have been rarely associated with hypothyroidism, although consumptive hypothyroidism due to the presence of type 3 deiodiinase, produced by the hemangiomas, has been reported in large cutaneous infantile hemangiomas. Due to the irreversible morbidity of hypothyroidism in children, routine thyroid screening has been advocated in all children with very large hepatic hemangiomas.

Treatment Options

Table I. Hemangioma treatment options

Table I.
Medical Treatment Surgical Procedures Physical Modalities
Non-adherent dressings
Hydrogen peroxide soaks
Becaplermin gel
Excisional surgery Pulsed-dye laser
Intralesional: Corticosteroids    

Optimal Therapeutic Approach for this Disease

As most hemangiomas resolve without complications, intervention is often not required. Decisons regarding therapy depend on hemangioma size, morphology, and location, as well as the potential for complications, patient age, and stage of the hemangiomas at the time of evaluation. Treatment risks and benefits must be carefully weighed and individualized for each patient.

When a hemangioma ulcerates, therapy is primarily directed at appropriate wound care, which includes gentle cleansing, application of thick, bland emollients or topical antibiotics and nonadherent dressings when possible, and pain control. If crusting is present, removal with dilute hydrogen peroxide soaks as needed or more frequent application of emollients may be required to promote re-epithelialization and prevent bacterial superinfection.

Systemic antibiotics may be considered when signs of infection such as purulent drainage are noted; a swab bacterial culture should be obtained prior to initiating therapy. For perineal hemangiomas, the addition of metronidazole gel or cream once daily along with mupirocin ointment daily may be effective.

Second-line treatments include becaplermin gel, a topical platelet-derived growth factor that has been reported to hasten resolution of ulcers, and/or pulsed-dye laser therapy, which can help with both pain relief and healing of the ulcer. Parents must be informed of the black box warning issued by the FDA due to reports of increased incidence of cancer-related deaths in adults treated with becaplermin gel for leg ulcers; however, there have been no reports of increased incidence of cancer in the pediatric population treated for ulcerated hemangiomas.

Suggested laser settings are 10mm spot size when appropriate (to minimize the number of pulses, and therefore, pain), low fluence such as 5 to 6 joules/cm2, and 0.45 to 1.5ms pulse duration. Laser treatments can be repeated every 1 to 2 weeks; however, improvement is often adequate after the first or second treatment.

In some cases, surgical excision should be considered if the infant is not responding to first- or second-line management and the patient is deemed an appropriate candidate. Lastly, particularly for rapidly proliferating hemangiomas, treatment of the proliferation with systemic therapy (corticosteroids or propranolol) can be an effective adjunct for ulceration.

Small superficial, relatively low-risk hemangiomas may improve with application of topical therapies such as corticosteroids once daily, imiquimod nightly, or topical timolol 0.5% gel twice daily over several months; however, deep hemangiomas will respond minimally, if at all, to such agents. Of note, imiquimod can be irritating and occasionally result in erosions or ulceration.

Intralesional corticosteroids are another option to minimize proliferation of relatively small, localized hemangiomas. Triamcinolone at 10mg/mL concentration injected with a maximum dose of 1 to 2mg/kg at 3- to 6-week intervals is the optimal dosage. This is generally utilized for at-risk periorbital or nasal tip hemangiomas but should be administered by an experienced clinician due to potentially serious side effects, especially in the periocular location such as lid necrosis, dyspigmentation, and central retinal artery occlusion.

The risk of central retinal artery occlusion is thought to be due to high injection pressures causing embolization of steroid suspension particles into the ocular circulation, thereby resulting in occlusion from retrograde arterial flow. A slower injection of less volume may lessen this risk.

Hemangiomas that are at-risk for functional or significant cosmetic impairment, and are thus potentially life-threatening or altering, require systemic treatment. While there is no FDA-approved systemic treatment for hemangiomas, options include systemic corticosteroids, propranolol, and chemotherapeutic agents such as vincristine and alpha-interferon. Systemic corticosteroids, which have been used to treat hemangiomas since the 1960s, are most effective at stabilizing growth when used early during the proliferative phase at a dose of 2 to 3mg/kg/day of prednisolone.

While families need to be counseled on the potential side effects of systemic corticosteroid use, including linear growth delay, gastrointestinal upset, irritability, adrenal suppression, and immunosuppression, most infants tolerate therapy well without serious health impairment. Once the proliferative phase is complete, the steroids can be slowly tapered off.

Oral propranolol, at a dose of 1 to 3mg/kg divided into two to three doses daily, has shown great promise in the treatment of high-risk hemangiomas. Protocols for initiation vary between practitioners and institutions, but may include EKG, CXR, or echocardiogram, baseline vital signs, and inpatient or outpatient initiation. Evaluation for PHACE syndrome in infants with large facial hemangiomas is important prior to initiation to assess for compromised vasculature that could be impacted by propranolol therapy. Infants on propranolol should be followed for potential side effects including hypoglycemia, hypotension, bradycardia, nightmares, bronchospasm, and hypokalemia.

To minimize the risk of hypoglycemia, propranolol should be held during illness or surgical procedures — when the infant is most likely to be feeding poorly or in a fasting state. Propranolol therapy is usually continued until about 12 to 18 months of age. Discontinuing treatment prior to this time commonly results in rebound growth.

For severely compromised hemangiomas that fail to respond to systemic corticosteroids and/or propranolol, referral to a hematologist/oncologist for administration of vincristine at a dose of 1 to 1.5mg/m2 weekly can be considered. However, vincristine is administered via intravenous infusion, generally weekly in the hospital setting, and is associated with additional risks including neuropathy and immunosuppression. Recombinant interferon alpha 2a and 2b is no longer widely used, primarily due to serious neurologic complications such as spastic diplegia, which can remain permanent in treated infants.

Flash lamp pulsed-dye laser (PDL) at 585 to 595nm is a treatment modality that is most often utilized, as noted above, for ulcerated hemangiomas, or involuting or involuted hemangiomas with residual erythema/telangiectasias. Initial settings vary based on location and skin type but can range from a 7 or 10mm spot size, pulse duration of 0.45 or 1.5ms, and fluence of 6 to 12 joules/cm2. Post-treatment purpura is expected to resolve within 1 to 3 weeks. If a good response is achieved, PDL treatment may be repeated every 6 to 12 weeks, and fluence may be increased at subsequent visits by increments of 0.5 to 1 joule/cm2.

The number of treatments required for adequate cosmesis is highly variable but, in general, patients experience the most improvement within the first 5 to 7 sessions.

Excisonal surgery may be considered for severely or chronically ulcerated hemangiomas and for lesions that are likely to have poor aesthetic outcome with excessive fibrofatty tissue or scarring after involution. Appropriateness and timing of surgery depends on numerous factors including size and location and potential for early complications and disfigurement. Due to psychosocial factors, most surgical interventions are completed before school age; however, elective surgery is not generally recommended before 6 months of age since the risk of general anesthesia is higher in this age group.

Patient Management

After the initial visit, follow-up is determined based on size and location of the lesion, potential for complications, therapeutic need, and caregivers’ level of comfort. Even if no treatment is indicated, follow-up may still be frequent during the proliferative phase and then lessened to every 6 to 12 months or longer during involution. Pre-school age (3 to 4 years), before school starting, is often an ideal time to reassess children and discuss any potential need for further interventions. For patients who are undergoing therapeutic interventions, follow-up every 1 to 2 months is often necessary to assess response and side effects, adjust dosing of medications based on weight gain, and answer caregivers’ questions.

Unusual Clinical Scenarios to Consider in Patient Management

Periorbital hemangiomas with the greatest risk of visual compromise include those around the upper eyelid and/or behind the eye. Regular eye examinations by an ophthalmologist, particularly during the proliferative phase, are essential. Therapeutic intervention is indicated if visual impairment is imminent. Ophthalmologists may also recommend patching of the unaffected eye if amblyopia is present.

Symptomatic airway hemangiomas require a multidisciplinary approach that may include systemic therapy with either oral corticosteroids (3 to 5 mg/kg/day) or propranolol, in conjunction with laryngoscopy and excisional surgery, laser surgery and/or intralesional corticosteroids administered by an experienced otolaryngologist. Infants with combined cutaneous facial and airway hemangiomas should be evaluated for PHACE syndrome.

Large segmental hemangiomas that cover an extremity are at higher risk for ulceration and limb atrophy or hypertrophy, though functional compromise is rare. Rarely, such hemangiomas may have regionally associated visceral or vascular anomalies.

Exophytic, pedunculated hemangiomas often leave redundant fibrofatty tissue even after complete involution, and thus early surgical intervention in this setting may be reasonable. A so-called “purse string” closure is often utilized to minimize the redundant scar.

During the proliferative phase, nasal tip hemangiomas may lead to cartilage destruction, fibrofatty replacement, and a bulbous appearance of the nose, referred to as “Cyrano” nose. For larger hemangiomas, early intervention with systemic or intralesional therapy should thus be considered. Involuted, disfiguring lesions in an older child should be referred to an experienced surgeon for evaluation.

What is the Evidence?

Metry, DW, Hebert, AA. “Benign cutaneous vascular tumors of infancy: when to worry, what to do”. Arch Dermatol. vol. 136. 2000. pp. 905-14. (A review of the world literature that discusses the diagnosis and management of complicated hemangiomas including cervicofacial, periorbital, lumbosacral, parotid, PHACE syndome, diffuse neonatal hemangiomatosis, Kaposiform hemangioendothelioma and tufted angioma.)

Frieden, IJ, Rogers, M, Garzon, MC. “Conditions masquerading as infantile hemangiomas: Part 1”. Australas J Dermatol. vol. 50. 2009. pp. 77-97. (This article reviews the extensive differential diagnosis of infantile hemangiomas including other vascular anomalies, benign growths, and malignancies.)

Bruckner, AL, Frieden, IJ. “Hemangiomas of infancy”. J Am Acad Dermatol. vol. 48. 2003. pp. 477-93. (A comprehensive review of the epidemiology, pathology, pathogenesis, clinical features, sites of involvement, complications, differential diagnosis, workup, management and treatment of infantile hemangiomas. This article highlights new information regarding the pathogenesis of hemangiomas and highlights the more worrisome presentations, including syndromic hemangiomas.)

Jinnin, M, Ishihara, T, Boyce, E, Olsen, BR. “Recent progress in studies of hemangiomas”. J Dermatol. vol. 37. 2010. pp. 283-98. (An important article that reviews recent studies and new hypotheses on the pathogenesis of hemangiomas. Discusses detailed mechanisms of activated VEGF signaling in tumor cells, attempts to identify their origin and characterize multipotent stem cells that can give rise to infantile hemangiomas to improve understanding and treatment of this vascular tumor.)

Frieden, IJ, Eichenfield, LF, Esterly, NB, Geronemus, R, Mallory, SB. “Guidelines of care for hemangiomas of infancy. American Academy of Dermatology Guidelines/Outcomes Comimittee”. J Am Acad Dermatol. vol. 37. 1997. pp. 631-7. (A comprehensive review of infantile hemangiomas, reviewing the standard of care for diagnosis and management.)

Maguiness, SM, Frieden, IJ. “Current management of infantile hemangiomas”. Semin Cut Med Surg. vol. 29. 2010. pp. 106-14. (A comprehensive review of current treatment options for infantile hemangiomas.)

Burns, AJ, Navarro, JA. “Role of laser therapy in pediatric patients”. Plast Reconstr Surg. vol. 124. 2009. pp. 82e-92e. (A review of laser treatment options for skin lesions in pediatric patients.)

Metry, D, Heyer, G, Hess, C, Garzon, M, Haggstrom, A, Frommelt, P. “PHACE Syndrome Research Conference. Consensus Statement on Diagnostic Criteria for PHACE Syndrome”. Pediatrics. vol. 124. 2009. pp. 1447-56. (A summary of current research findings providing the most up-to-date consensus on the diagnosis of PHACE syndrome.)

Amir, J, Metzker, A, Krikler, R, Reisner, SH. “Strawberry hemangioma in preterm infants”. Pediatr Dermatol. vol. 3. 1986. pp. 331-2. (A retrospective study of the prevalence of hemangiomas in preterm infants at a medical center in Israel over a 7-year period.)

Girard, C, Bigorre, M, Guillot, B, Bessis, D. “PELVIS Syndrome”. Arch Dermatol. vol. 142. 2006. pp. 884-8. (A retrospective study defining a new syndrome for findings associated with large perineal hemangiomas.)

Egbert, JE, Paul, S, Engel, WK, Summers, CG. “High injection pressure during intralesional injection of corticosteroids into capillary hemangiomas”. Arch Ophthalmol. vol. 119. 2001. pp. 677-83. (A study investigating high injection pressure during intralesional injection of corticosteroids into periocular capillary hemangiomas as a mechanism for the complication of ocular embolization with permanent vision loss.)