Arterial Vascular Malformations Including Hemangiomas and Lymphangiomas 

Updated: Jun 10, 2020
Author: Robert A Schwartz, MD, MPH; Chief Editor: Mary C Mancini, MD, PhD, MMM 

Overview

Practice Essentials

Vascular malformations result from abnormal-sized vascular structures or an abnormal number of vascular structures. These malformations usually manifest as cutaneous birthmarks and have had a number of classifications, producing an array of confusing terms.

The evaluation and treatment of common vascular malformations, particularly hemangiomas and lymphangiomas, are discussed in this article. The widely accepted Mulliken and Glowacki classification system is used, and attempts are made to sort out the nomenclature that has been used over the years.[1]  In this system, vascular abnormalities are divided into two broad categories, vascular tumors (hemangiomas) and vascular malformations (see Classification). 

When evaluating a patient with these types of malformations, one must also consider syndromes associated with vascular malformations, such as  Klippel-Trenaunay-Weber syndrome and Sturge-Weber syndrome.[2, 3, 4]

Other uncommon forms of vascular malformations have been reported. For example, PHACE syndrome (OMIM 606519) is a neurocutaneous syndrome that associates large, plaquelike, segmental hemangiomas of the face, with one or more of the following: posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral developmental defects, specifically sternal defects, or supraumbilical raphe. In a prospective cohort study of 1096 children with hemangiomas, 25 children met the criteria for PHACE, representing 20% of infants with segmental facial hemangiomas.[5]

The indications and value of the various interventions are also discussed (see Treatment).

In patients with vascular tumors, watchful waiting is now the accepted first step in the management of nonproblematic hemangiomas. Medical treatment is the first-line approach to treating potentially destructive lesions.

The technique and timing for surgical resection of hemangiomas has been a topic of contentious debate. The surgeon must determine when excision would produce a more cosmetically acceptable result than conservative treatment would andmust choose a technique that leads to the best possible outcome. Depending on the location of the lesion, surgical resection may be the initial treatment of choice.

Most capillary malformations are currently treated with an argon laser or a flashlamp-pumped pulsed dye laser (PDL).

Most surgeons agree that surgical excision of lymphangiomas is the treatment of choice in patients with localized disease. Management of diffuse lymphatic disease has historically been surgical.

Anatomy

Vascular tumors

Hemangiomas located on the trunk or face may be psychologically damaging when children approach school age. This must be considered when discussing early intervention in these lesions. Lesions of the eye, ear, or larynx warrant early intervention because they may affect proper development of these organs or compromise the airway. Lesions involving the orbit should be properly evaluated by an ophthalmologist. In cases involving the larynx, the first priority is ensuring a secure airway.

Capillary malformations

Capillary malformations are frequently located on the face, where they often present a psychological problem.

Lymphatic malformations

In most series, the head and neck are the most common sites for lymphatic malformations, followed by the trunk, axilla, and extremities. In the head, the oral cavity and face area are the most common sites. In the neck, the posterior triangle is reportedly the most common site. However, many series have reported no difference between the anterior and posterior triangles. Right-side lesions seem to predominate. Laryngeal involvement is not uncommon. Cases of diffuse disease may occur, encompassing large portions of the body.

Pathophysiology

Hemangiomas are the result of abnormal changes in angiogenesis that allow the overproliferation of vascular entities. Several authors have elucidated the complex interplay of angiogenic and angiostatic forces involved in normal and pathologic processes.[6] However, fetal vascular development remains poorly understood. Many of the angiogenic markers (ie, fibroblast growth factor [FGF], vascular endothelial growth factor [VEGF], E-selectin, type IV collagenase) are increased during the proliferative phase.[7]

During the involutional phase of hemangiomas, a subsequent decrease in angiogenic factors occurs, with a fivefold increase in endothelial cell apoptosis.[8] These alterations in angiogenic factors may account for the increased vascular proliferation that occurs in hemangiomas. Mesenchymal progenitor cells may be key to infantile hemangioma development.[9] These hemangiomas may be caused by an abnormal or delayed differentiation of mesodermal progenitor cells into the disorganized mass of blood vessels.

Microscopic hemangioma tissue reveals proliferating endothelial cells. During involution, endothelial cells flatten, the vessel lumens dilate, and fibrous tissue is deposited. Recent studies have also discovered hemangioma-specific antigens not found in normal skin. These include GLUT1, merosin, and Lewis Y antigen.

Capillary malformations (port-wine stains) are groups of tortuous blood vessels located in the upper layers of the dermis. One study revealed that these lesions have decreased innervation in perivascular regions, which generates the hypothesis that the lesions are secondary to impaired vascular tone.[10]

Lymphangiomas are collections of lymph vessels filled with serous fluid. Their histology ranges from capillary-sized vessels to macroscopic fluid-filled vessels. Lymphatic malformations can be associated with gross anatomic deformities with severe involvement of the surrounding structures on the face or extremities.

Research has begun to reveal some of the cell signals that may be involved in the formation of lymphangiomas. For example, VEGF-C has been found to be adequate in causing lymphatic hyperplasia. Evaluation of VEGF-C and VEGF receptor (VEGFR)-3 in a series of lymphangiomas has suggested that superficial lymphangiomas likely represent peripheral lymphatic dilatation.[11]

Verrucous hemangiomas, a rare form of vascular malformation, were analyzed on the basis of 74 cases and found to be usually located on the extremities, mostly as solitary or multiple hyperkeratotic plaques or nodules with various diameters.[12] They represent a vascular malformation with an incomplete lymphatic immunophenotype.

Etiology

Vascular tumors (hemangiomas) are believed to result from developmental errors that occur at 4-10 weeks' gestation. Most cases are sporadic; however, they are occasionally inherited in an autosomal dominant fashion with moderate-to-high rates of penetrance.[13] (See Pathophysiology.) The anatomic location of infantile hemangiomas may be a result of variant anatomy of arterial supply during embryo fetal development, producing temporary regional tissue hypoxia and encouraging the proliferation of hemangioma stem cells.[14]

Capillary malformations are generally considered to be sporadic lesions; however, pedigrees of autosomal dominant inheritance have been reported. Port-wine stains are also associated with Klippel-Trenaunay-Weber and Sturge-Weber syndromes. Mutations in the RASA1 gene may underlie the capillary malformation–arteriovenous malformation syndrome. A novel mutation in RASA1 has been reported to cause capillary malformation and limb enlargement.[15] An extensive degree of phenotypic heterogeneity may be associated with deleterious mutations in RASA1.

The exact cause of lymphangioma formation is unknown, but most cases are believed to be sporadic. The formation of lymphangiomas may reflect a failure of lymph ducts to connect with the venous system during embryogenesis, abnormal sequestration of lymphatic structures, or both. Ongoing research has elucidated some of the vascular growth factors that may be involved in formation of lymphatic malformations (eg, VEGF-C and flt-4). Cases secondary to trauma and infection have also been reported. Vulvar lymphangioma circumscriptum may be a result of pelvic lymphatic obstruction, linked in some patients to rectal adenocarcinoma, cervical carcinoma, or endometrial carcinoma.[16]

The blue rubber bleb nevus syndrome is a rare disorder with many cutaneous and internal venous malformations, especially of the gastrointestinal (GI) tract. Soblet et al identified somatic mutations in TEK, the gene encoding TIE2, in 15 of 17 people with this syndrome.[17]  A mutation in exon 15 of TEK was delineated in one patient.[18]

Epidemiology

Vascular tumors (ie, hemangiomas) are the most common tumors in infants. They are apparent in 1-2.6% of neonates at birth across all races, according to one series.[19]

Approximately 30% of hemangiomas are recognized in the newborn nursery. Prevalence is increased in preterm infants weighing less than 1000 g and in white children younger than 1 year. The male-to-female ratio is 3:1.[20]

Vascular malformations include capillary and lymphatic malformations. Capillary malformations (ie, port-wine stains) occur in 3 per 1000 neonates.[21] They are the most common type of vascular malformations. The lesions are present in neonates and darken during adolescence and middle age. The sex distribution is equal.

The incidence of lymphatic malformations is 1.2-2.8 per 1000 live births.[22] Approximately 50% of lymphatic malformations are apparent at birth; 90% appear before age 2 years. Most reports indicate an equal male-to-female distribution. There is a predilection for the head and neck.[23]

Prognosis

Vascular tumors

As mentioned earlier, approximately 75% of hemangiomas of infancy involute without intervention. Involution is usually complete by age 7-10 years. Ulceration secondary to infection or trauma increases the risk of residual scarring. A large facial lesion is also more likely to leave an unacceptable scar. Patients with significant residual scarring may choose to undergo a surgical procedure.

If systemic glucocorticoids are used in the manner stated above, efficacy rates of 84% have been reported. Side effects during and after treatment have also been previously mentioned. All treatments listed above are used primarily for troublesome situations or cases where scarring after involution is considered unacceptable. Studies to date have been unable to prove a significant change in outcome with earlier intervention versus watchful waiting.

Capillary malformations

The pulsed dye laser (PDL) has vastly enhanced the treatment efficacy of cutaneous capillary malformations. Laser wavelengths that are specific for the lesion result in a lesser degree of damage to the surrounding tissues, minimizing the risk of hypopigmentation. In one series, 15.3% of patients treated with the PDL experienced more than 90% lesional resolution, and 65.3% of patients had lightening from 50% to 90%.[24] Poor response was observed in 17.8% of patients, and no response was noted in 1.2%.

Lymphatic malformations

Complete surgical resection of localized disease has proved to be extremely effective. Recurrence rates are low if complete removal of cystic epithelium is achieved.

Patients and parents undergoing surgical resection of diffuse disease should be aware that despite intervention, diffuse lymphatic disease entails lifelong morbidity. An essential component of care in these children should involve a child psychiatrist to cope with this stressful situation.

 

Presentation

History and Physical Examination

Hemangiomas are most commonly located on the head and neck (59%), followed by the trunk (24%), lower extremities (10%), and upper extremities (7%).[25] Most are less than 2 cm in diameter, but some can cover large portions of the body (see the images below).

Fully developed vascular tumor on trunk of infant. Fully developed vascular tumor on trunk of infant.
Large vascular tumor encompassing upper extremity Large vascular tumor encompassing upper extremity and portions of trunk, clinically diagnosed.

Typical presenting symptoms occur superficially, and the appearance can range from a hypopigmented macule to a bruiselike macule.[26] The course of these lesions includes a proliferative postnatal growth phase that lasts for 3-9 months, with a gradual involution that occurs over 2-6 years. Involution is usually complete by age 7-10 years. Only 50% of patients have completely normal-appearing skin at this time.

Recognizing atypical presentations and subclassifications of hemangiomas is critical for prognostic and treatment purposes. A congenital hemangioma is a lesion that is fully developed at birth. Deep hemangiomas have a blue discoloration because of their proliferation in the dermis and subcutaneous tissues. Multiple hemangiomas, often referred to as hemangiomatosis, appear as multiple smaller lesions. Pseudoclubbing may be the first sign of an underlying subungual hemangioma.[27]

When evaluating hemangiomas, a family history should be elicited. Although most are sporadic, infantile hemangiomas may be the result of an autosomal dominant trait. One study suggests that the formation of hemangiomas may be associated with mutational events that result in a loss of heterozygosity at a specific locus on chromosome 5.[28] Mutations in genes responsible for regulation of vascular development, such as FGF-4, PDGF-b, and a tyrosine-kinase gene, have been linked to familial forms of hemangioma.[29]

Because hemangiomas may be a part of a syndromic complex, query about other symptoms that may be associated with Klippel-Trenaunay-Weber or Sturge-Weber syndromes. The triad of Klippel-Trenaunay-Weber syndrome symptoms includes vascular tumors of the limbs, trunk, or perineum; varicose veins; and bony and/or soft tissue hypertrophy of the extremities.[2] (See the image below.)

Lower extremity port-wine stain in patient with Kl Lower extremity port-wine stain in patient with Klippel-Trenaunay-Weber syndrome.

The presenting symptom in patients with Sturge-Weber syndrome is often a facial lesion, most commonly a nevus flammeus located in the V1-V2 dermatomes. Other findings include a history of epileptic seizures, hemiplegia, visual field defects, and glaucoma.[3]

Most lymphangiomas are clinically apparent at birth, and almost all are apparent by age 2 years. Most appear as soft doughy masses that are located in the head and neck region, and most have no associated symptoms. Clinical manifestations are dependent on the flow of lymph within the channels of the lesion. Lymphangiomas may manifest as lymphedema, and larger lesions can involve the skeletal system and cause gross disfigurement. Large malformations in the neck or mediastinum can compromise the airway, leading to stridor, dysphonia, or dyspnea.

Lymphangiomas have also been found in patients with Turner syndrome, Klinefelter syndrome, and Noonan syndrome. Sometimes, a lymphoma may require distinction for lymphangiomalike Kaposi sarcoma in the skin or oral mucosa.[30]  On dermoscopic examination, lymphangiomas may show yellow lacunae surrounded by pale septa and reddish to bluish lacunae.[31]

Infantile hemangioma precursors, or those without a proliferative phase, may have dermoscopic features of red round globular vessels, red commalike vessels, and red linear vessels, allowing their distinction from a port-wine stain.[32] Early white discoloration of infantile hemangioma portends ulceration, whereas a lack of substantial white discoloration early in infancy reflects a low risk of it.[33]

Classification

Vascular tumors and malformations have often been described using a classification system based on morphologic characteristics. This practice has given rise to countless names that are interchangeably used, often befuddling medical professionals.

In 1982, Mulliken and Glowacki proposed a biologic classification of vascular tumors and malformations that has since gained wide acceptance.[1] This system correlates histologic features with historical and physical findings to provide a simplified classification of vascular lesions. The system has been modified slightly over the years to incorporate new information. Mulliken and Glowacki used the following criteria to separate vascular malformations into two broad categories:

  • Vascular tumors, also known as hemangiomas - These tumors exhibit endothelial hyperplasia; approximately 30% are visible at birth, and the remaining 70% appear in children aged 2-4 years; postnatal growth is rapid, and involution is slow; in 1996, the International Society for the Study of Vascular Anomalies (ISSVA) added the rapidly involuting congenital hemangioma, noninvoluting congenital hemangioma, kaposiform hemangioendothelioma, tufted angioma, and pyogenic granuloma to the list of vascular tumors
  • Vascular malformations - These are subdivided into high-flow (arterial, arteriovenous) malformations and slow-flow (venous, capillary, lymphatic) malformations; they exhibit normal endothelial turnover; approximately 90% are recognized at birth, and the lesions increase in size as the child grows

The 1996 classification system adopted by the ISSVA was based on Mulliken and Glowacki’s biologic study but also further distinguished vascular malformations according to hemodynamics and predominant anomalous channels. In May 2018, the ISSVA issued a revised classification of vascular anomalies (see Table 1 below).[34]

Table 1. ISSVA Classification of Vascular Anomalies (May 2018 Revision) (Open Table in a new window)

Vascular Tumors Vascular Malformations

Benign vascular tumors

Infantile hemangioma/hemangioma of infancy

Congenital hemangioma

  • Rapidly involuting (RICH)
  • Noninvoluting (NICH)
  • Partially involuting (PICH)

Tufted angioma

Spindle-cell angioma

Epithelioid angioma

Pyogenic granuloma (lobular capillary hemangioma)

Others

Related lesions

Simple vascular malformations

Capillary malformation (CM)

  • Nevus simplex/salmon patch, "angel kiss," "stork bite"
  • Cutaneous/mucosal CM (port-wine stain)
  • Reticulate CM
  • CM of CM-AVM (arteriovenous malformation)
  • Cutis marmorata telangiectatica congenita (CMTC)
  • Others
  • Telangiectasia (hereditary hemorrhagic telangiectasia [HHT], others)

Lymphatic malformation (LM)

  • Common (cystic) LM (macrocystic, microcystic, mixed cystic)
  • Generalized lymphatic anomaly (GLA) (kaposiform lymphangiomatosis [KLA])
  • LM in Gorham-Stout disease
  • Channel-type LM
  • "Acquired" progressive lymphatic anomaly (acquired progressive "lymphangioma")
  • Primary lymphedema
  • Others

Venous malformation (VM)

  • Common VM
  • Familial VM cutaneomucosal (VMCM)
  • Blue rubber bleb nevus (Bean) syndrome VM
  • Glomuvenous malformation (GVM)
  • Cerebral cavernous malformation (CCM)
  • Familial intraosseous vascular malformation (VMOS)
  • Verrucous venous malformation (formerly verrucous hemangioma)
  • Others

Arteriovenous malformation (AVM)

  • Sporadic
  • In HHT
  • In CM-AVM
  • Others

Arteriovenous fistula (AVF) (congenital)

  • Sporadic
  • In HHT
  • In CM-AVM
  • Others

Locally aggressive or borderline vascular tumors

Kaposiform hemangioendothelioma

Retiform hemangioendothelioma

Papillary intralymphatic angioendothelioma (PILA), Dabska tumor

Composite hemangioendothelioma

Pseudomyogenic hemangioendothelioma

Polymorphous hemangioendothelioma

Hemangioendothelioma not otherwise specified

Kaposi sarcoma

Others

Combined vascular malformations

CM + VM = CVM

CM + LM = CLM

CM + AVM = CAVM

LM + VM = LVM

CM + LM + VM = CLVM

CM + LM + AVM = CLAVM

CM + VM + AVM = CVAVM

CM + LM + VM + AVM = CLVAVM

Malignant vascular tumors

Angiosarcoma

Epithelioid hemangioendothelioma

Others

Anomalies of major named vessels (channel-type or truncal vascular malformations)

Affecting

  • Lymphatics
  • Veins
  • Arteries

Anomalies of

  • Origin
  • Course
  • Number
  • Length
  • Diameter
  • Valves
  • Communication (AVF)
  • Persistence (of embryonal vessel)
 

Vascular malformations associated with other anomalies

Klippel-Trenaunay syndrome

Parkes Weber syndrome

Servelle-Martorell syndrome

Sturge-Weber syndrome

Limb CM + congenital nonprogressive limb overgrowth

Maffucci syndrome

Macrocephaly-CM

Microcephaly-CM

CLOVES syndrome

Proteus syndrome

Bannayan-Riley-Ruvalcaba syndrome

CLAPO syndrome

C=capillary, V=venous, L=lymphatic, A=arterial, M=malformation, F=fistula.  

There are a number of vascular malformations with specific clinical and radiologic characteristics in the lower limbs, including the following[35] :

  • Klippel-Trénaunay syndrome
  • Port-wine stain with or without hypertrophy
  • Cutis marmorata telangiectatica congenita
  • Macrocephaly-capillary malformation
  • Parkes Weber syndrome
  • Stewart-Bluefarb syndrome
  • Venous malformation
  • Glomuvenous malformation
  • Lymphatic malformation

Extensive vascular malformations may be complex and associated with underlying disease or systemic anomalies.[36]

Capillary and lymphatic malformations are the focus of this article and are used as models for vascular malformations.

The fading macular stain (ie, stork bite, salmon patch, nevus flammeus) is a common lesion that is often grouped with capillary malformations because of their similar appearance. The terms used to describe fading macular stains have often been used interchangeably with those for port-wine stains. This usage is incorrect, because fading macular stains are not permanent anomalies and hence are not true vascular malformations. Fading macular stains are discussed only briefly because they should be included in the differential diagnosis of port-wine stains.

Complications

Vascular tumors

In some cases, hemangiomas can be life-threatening or severely problematic, interfering with eating, breathing, seeing, hearing, and speaking. These cases require immediate and aggressive intervention because delayed treatment can lead to improper development of these organ systems.

The most common sequela of untreated problematic vascular tumors is amblyopia secondary to lesions of the upper eyelid. Such cases should be immediately evaluated by an ophthalmologist. Hemangiomas located on internal organs can be dangerous because they are difficult to detect. Furthermore, by the time they are detected, the infant often requires aggressive treatment. Despite intervention, internal hemangiomas are still associated with a high mortality.

Infants who have hemangiomatosis (ie, multiple smaller hemangiomas) may also have internal lesions. Visceral hemangiomas occur in the liver, intestines, airway, and brain. If an infant has more than three clinically apparent hemangiomas, ultrasonography of the entire body should be performed to rule out internal lesions. In rare cases, a brain tumor (eg, an astrocytoma) may be evident in Klippel-Trenaunay-Weber syndrome.[37]

Other suspicious findings include the following:

  • Jaundice, which may be a sign of liver hemangiomas
  • Bloody stools, which may be a sign of gastrointestinal hemangiomas
  • Stridor or dyspnea, which may be a sign of airway hemangiomas

Capillary malformations

Patients with port-wine stains should be evaluated and monitored for a larger syndromic entity.

Hemangiomas that are part of the Klippel-Trenaunay-Weber syndrome can be located on the lungs, spleen, liver, bladder, or colon. Visceral involvement can often lead to substantial morbidity in the form of internal hemorrhage.

The recognized components of Sturge-Weber syndrome can appear at various points in the patient's life. Neurologic findings are evident within the first 2 years of life, often manifesting as seizures. In addition, patients can exhibit hemiparesis, visual field defects, or lower intelligence quotient (IQ) scores. Ocular defects, such as glaucoma or ocular hemangiomas, can lead to visual loss or retinal detachment that requires prompt evaluation and treatment.

Lymphatic malformations

Complications of lymphangiomas depend on the location and extent of disease.

Diffuse cervicofacial disease can result in mandibulomaxillary hypertrophy because of direct invasion of the bone and growth of the malformation within the bone. A secure airway is also essential in these patients; a tracheostomy may be required to avoid acute respiratory problems.

Lymphangiomas often swell with the onset of general viral infection or remote bacterial infection. This typically resolves with the resolution of the infection. Occasionally, lymphangiomas can become infected, and intravenous (IV) antibiotic treatment is required. Primary lymphangioma circumscriptum of the vulva may be evident as verrucous plaques.[38]

Collision of vascular and pigmentary anomalies

Occasionally, a vascular anomaly with be seen in association between congenital melanocytic nevi and infantile hemangiomas.[39] For example, a Spitz nevus may arise in direct contiguity to a glomuvenous malformation, or phakomatosis pigmentovascularis may be seen in association with congenital melanocytic nevus.

Patietns with Klippel-Trenaunay syndrome have an enhanced obstetric risk if pregnancy ensues, with the choice of anesthesia for a possible cesarean delivery an important consideration.[40]

 

DDx

Diagnostic Considerations

A giant aggressive angiomyxoma is benign but can be locally aggressive.[41] It may be evident in the vulva, perineal region, buttocks, or pelvis in women in their 30s and 40s.

 

Workup

Laboratory Studies

The diagnosis of vascular tumors and malformations is usually made solely on the basis of the history and physical examination. No laboratory studies are specifically useful in this setting.

Imaging Studies

Magnetic resonance imaging (MRI) provides precise localization of the lesion. It is performed to detect the presence or absence of associated nervous system abnormalities. Furthermore, because vascular tumors have a distinct appearance on MRI, it is used in the diagnosis of atypical lesions.

Ultrasonography (US) with color flow is cost-effective; however, it is operator-dependent and does not accurately depict the relation of the lesion to other anatomic structures.

Intracranial vascular anomalies are present in more than two thirds of patients with a periorbital lymphatic malformation and potentially require treatment.[42] Imaging of patients with orbital lymphatic malformation should include the brain as well as the orbit.

Antenatal diagnosis of an intracranial, rapidly involuting congenital hemangioma by means of prenatal imaging has been described.[43]

Enhanced noninvasive diagnosis of acquired lymphangiectasias using dermoscopy and reflectance confocal microscopy to demonstrate diagnostic features may avoid the need for a tissue specimen.[44]

Procedures

Biopsy is performed if malignancy is suspected.

 

Treatment

Approach Considerations

Vascular tumors and malformations are rather unsightly lesions that often occur in children. Parents of these children often (understandably) pressure physicians to deliver definitive medical or surgical treatment. However, the acknowledgment of the natural involution of vascular tumors (hemangiomas) in the mid-20th century changed the way in which these lesions are managed.

Medical and surgical treatments of vascular tumors are discussed below, and the way in which the involutional phase fits into the treatment plan is explained. However, there is less of a consensus regarding the management of vascular malformations (lymphangiomas), especially in patients with diffuse disease.

In patients with vascular tumors, watchful waiting is now the accepted first step in the management of nonproblematic hemangiomas because 75% of these lesions involute, leaving a minimal residual scar. Medical treatment is the first-line approach to treating potentially destructive lesions and is discussed in detail below.

The technique and timing for surgical resection of hemangiomas has been a topic of contentious debate. Because in most cases these lesions involute without intervention, the surgeon must identify situations in which excision would produce a more cosmetically acceptable result than conservative treatment would. The surgeon must also choose a technique that leads to the best possible outcome (see Surgical Therapy). Depending on the location of the lesion, surgical resection may be the initial treatment of choice.

In the past, capillary malformations were managed by using various treatment modalities, including electrocauterization and cryosurgery. However, these methods have fallen out of favor because of their poor efficacy and the degree of scarring that they cause. Today, most of these lesions are treated with an argon laser or a flashlamp-pumped pulsed dye laser (PDL).

Most surgeons agree that surgical excision of lymphangiomas is the treatment of choice in patients with localized disease. Studies have been performed to correlate the depth of the excision with the rate of recurrence. In addition, new medical treatments are being developed, with encouraging results.

Management of diffuse lymphatic disease has historically been surgical. Although techniques have improved over the years, treatment still involves multiple procedures with substantial morbidity.

A small dose of sirolimus proved lifesaving in a patient with blue rubber bleb syndrome.[18]

Future and controversies

To develop more effective medical treatments for vascular tumors, studies are needed to clarify the pathogenic mechanism behind the formation of sporadic hemangiomas. Cases of autosomal dominant inheritance suggest a genetic predisposition to some hemangiomas. Identification of these genetic alterations may shed light on the pathogenesis behind sporadic cases.

Because some vascular malformations spontaneously regress, evidence suggests that conservative treatment or a period of watchful waiting may be beneficial in cases in which disease is not life-threatening. The efficacy of OK-432 has been well documented for the treatment of localized lymphangioma in Japan; studies are under way in the United States.[45] A better understanding of the pathogenesis behind lymphangioma is needed to develop newer and more efficacious medical treatments.

Medical Therapy

Vascular tumors

Approximately 75% of hemangiomas involute without intervention and are in anatomically benign locations; thus, they are a cosmetic issue. Therefore, parents must be educated about their child's condition, and the typical course of these lesions must be explained to them. In this manner, the physician can avoid hastily instituting medical therapy that may lead to a less desirable outcome. Regular follow-up visits should be scheduled to monitor the course of the lesion and to provide continuous reassurance to the parents.

The synthesis of informational advances in functional and phenotypic effects may enable the use of animal models to test less-invasive, targeted, perhaps locally administered, biologic therapies.[46]

Medical intervention is indicated if hemangiomas are located in areas that hinder normal development, interfere with important life processes, or cause severe pain. Such locations include the eye, nose, and airways. Current practices include the following:

  • Systemic glucocorticoids are the first-line therapy for lesions that are life threatening or cause severe deformity [47] ; efficacy rates have been reported at 84% with prednisone equivalent doses of 2.9 mg/kg if administered during the proliferative phase
  • The beta blocker propranolol is a promising an oral agent for first-line systemic therapy of infantile hemangiomas [48] ; it can produce a dramatic and rapid response, though serious consideration of the risks and benefits of its use must be considered [49, 50] ; the topical beta-blocker timolol lotion may also be strikingly effective, [51]  but premature and low-birthweight infants must be watched for signs of bradycardia, hypotension, apnea, and hypothermia [52]
  • Triamcinolone is indicated for smaller hemangiomas; intralesional injections administered every 4-6 weeks have been shown to result in faster rates of involution in 30% of patients
  • Interferon alfa-2a is used for life-threatening or deforming lesions that do not respond to glucocorticoid therapy [53] ; it is subcutaneously administered at a dose of 1-3 million U/m 2 of body surface area
  • Flashlamp-pumped PDL is indicated for superficial residual lesions that remain after involution, though it is not effective on deep hemangiomas; some studies have shown no advantage to early laser intervention versus conservative treatment, but one study suggests possible benefit [54]
  • Local wound care is shown to alleviate pain and infection in ulcerated lesions [55] ; wet compresses can be used to debride the ulcer in conjunction with topical mupirocin, bacitracin, or metronidazole
  • Ethanol sclerotherapy for venous malformation has been utilized [56]

Capillary malformations

First-line treatment of capillary malformations involves use of the flashlamp-pumped PDL or the argon laser.

The PDL is the treatment of choice in infants and children. Treatment involves a brief pulse that is relatively specific for the lesion, compared with that from the argon laser. This results in a lesser degree of damage to the surrounding tissues, minimizing the hypopigmentation often associated with treatment.

In one series, 15.3% of patients treated with the PDL experienced more than 90% lesional resolution, and 65.3% of patients had lightening from 50% to 90%. Poor response was observed in 17.8% of patients and no response in 1.2%.[24]

The 577-nm 0.36-ms PDL has proven to be efficacious in light-colored stains and is more effective in younger than in older children. The 585-nm PDL was developed and became popular in the mid-1990s because one study demonstrated an improved response in deeper lesions. With the use of the 585-nm 0.45-ms PDL, some authors report the highest degree of blanching in pink lesions, whereas others find a lower degree of lightening in pink lesions than in red ones.

Some authors report better results with fewer treatments in infants and young children, whereas others do not find significantly better results in the youngest age groups. Most studies report a more favorable response in lesions on the face or neck and on the torso, but one study did not find any significant difference in the required number of treatments for different body locations.

The argon laser is currently used in adults with darker or raised port-wine stains. This is because of the hypopigmentation and textural changes that are often the result of treatment.

Lymphatic malformations

For localized lymphatic malformations, various pharmacologic agents have been used around the world to treat lymphangioma. Some of the agents used in sclerotic therapy include boiling water, tetracycline, bleomycin, and cyclophosphamide.[57] None of the treatments has been completely effective. Sclerotherapy may also be of value in venous malformations, acquired digital arteriovenous malformations, and hemangiomas.[58]

Special considerations should be taken with lymphatic malformations on the tongue or glottis. Malformations on the tongue (formerly known as lymphangioma circumscriptum) should be managed with laser resurfacing. If these lesions are large enough to interfere with respiration, tongue reduction surgery should be performed. Malformations on the glottis should be treated with carbon dioxide laser and debulking therapy with aggressive airway management.

Aspiration of lymphangiomas has been used in the past but has largely fallen out of favor because of the high rate of recurrence. However, it can still be useful to manage life-threatening lymphangiomas that are in need of immediate reduction.

Management of diffuse disease is usually surgical (see below), though cyclophosphamide may be a good choice for life-threatening diffuse neonatal hemangiomatosis that is unresponsive to corticosteroids.[59] However, an essential component of care in children with diffuse disease should involve a child psychiatrist because management of diffuse disease often entails lifelong morbidity.

Surgical Therapy

Indications

Vascular tumors

Surgical excision of vascular tumors (hemangiomas) is controversial because most lesions involute with little intervention (75%). Generally, surgery is indicated if the procedure is expected to leave a scar that is more cosmetically acceptable than a scar due to medical therapy or following involution. Furthermore, in the following few specific situations, surgical intervention is considered inevitable:

  • If an abnormal scar or excess tissue is present after natural involution
  • If lesions are ulcerated and bleed excessively or are associated with pain
  • If lesions interfere with the development or activities necessary for life (eg, lesions of the eye, ear, or larynx)

Capillary malformations

Surgical management of port-wine stains has largely fallen out of favor with the advent of laser treatment. Surgical methods have included dermabrasion, electrocauterization, and cryosurgery.

Lymphatic malformations

For therapeutic purposes, lymphangiomas are often divided into localized and diffuse disease. In localized disease, a period of watchful waiting is appropriate if the lesion is not immediately compromising life functions. However, fewer than 15% of lesions regress spontaneously. Some surgeons believe that if the lesion has not spontaneously regressed by age 5 years, surgical intervention is warranted; others believe that excision should be performed sooner to avoid complications of lymphangioma (eg, infection).[60] Infection can be a severe sequela of lymphangiomas.

At present, most surgeons agree that complete excision is the preferred treatment for localized lymphangiomas, depending on the accessibility of the lesion. However, the close quarters of the head and neck give rise to a tedious dissection that often results in sacrifice of vital structures and significant postoperative impairment. In these cases, it may be best to avoid surgery and pursue an alternative therapy. Partial excision is frequently possible and is an acceptable alternative to complete excision, particularly if surgical resection would require removal of vital structures.

Management of diffuse lymphatic disease is a complex multistaged treatment associated with high complication rates. Patients and parents must be informed that management may be a lifelong endeavor and that significant morbidity may occur. Some studies report the use of nonsurgical therapy with special drugs that may promote regression of complex lymphangiomas. However, this treatment is not yet approved by the US Food and Drug Administration (FDA).

Contraindications

Vascular tumors

No absolute contraindications for surgical resection of hemangiomas have been recognized. However, in cases of nontroubling vascular tumors, the surgeon should thoroughly discuss the alternatives before proceeding.

Capillary malformations

No absolute contraindications for laser surgery have been identified in patients with capillary malformations. The physician should assess the risk of complications. For example, the 585-nm PDL can damage choroidal and retinal vasculature if the patient is not wearing the appropriate protective eyewear. In addition, the possibility of damage to surrounding structures and tissues must be evaluated.

Lymphatic malformations

No absolute contraindications for surgery have been identified in the treatment of lymphangiomas. Surgical treatment of diffuse lymphatic disease is a complex multistaged treatment that has high complication rates. Patients and parents must be informed that management may be a lifelong endeavor and that significant morbidity may occur.

Vascular tumors

When resecting hemangiomas, the surgeon must decide whether the result of surgical intervention would be more cosmetically acceptable than that of medical treatment or watchful waiting. In addition, the timing of resection should be considered because facial deformities can have a psychological impact on children, especially when they enter the school years. Some surgeons, however, advocate postponing excision until after the involution phase of hemangiomas.

Mulliken et al studied the outcome of surgical resection of hemangiomas involving a circular excision with purse-string closure compared with that involving a standard lenticular incision.[61] A line of excision was drawn to include the area affected by hemangiomatous infiltration and any fibrofatty residuum. In involuted lesions, this included all areas that were atrophic, scarred, pigmented, or otherwise deemed irreversibly scarred.

The marked area was then excised to the depths of the subcutaneous tissue, and the circular incision was drawn together with a single 4-0 or 5-0 purse-string suture.[61] When the suture was tightened, ridges of skin were created at the newly formed wound margin. If a small opening remained at the center of the purse-string, a gauze wick was placed inside, and the wound was dressed.

The skin ridges leveled off over the course of several weeks, and after several months of scar remodeling, the physician and parents decided whether to accept the result or have the patient undergo a second procedure.[61]

The study concluded that after a circular incision with purse-string closure, the mean scar area was 15% of the original area.[61] The study also concluded that the mean scar length with circular excision would be 72% shorter than with lenticular excision. The results did not vary significantly among the phases in which the procedure was performed or between the techniques used in a second procedure (circular or lenticular). To date, no other excision and closure technique produces a smaller scar.

Lymphatic malformations

As stated above, surgical excision is the treatment of choice for localized lymphangioma if anatomically possible. Of the various surgical techniques that have been explored over the years, total removal of the tumor, leaving behind no cystic epithelium, has been the most reliable procedure.

In one study, total resection led to no recurrences following the procedure. This is compared with recurrences in six of seven patients if excision of only protruding cystic epithelium was performed.[62] Another option for lymphangioma circumscriptum may be treatment with fractional carbon dioxide laser ablation.[63]

The surgical management of diffuse disease is often a complex and lifelong endeavor that is accompanied by substantial morbidity. Patients and parents must be aware of this before surgery is undertaken so that the high likelihood of complications can be factored into the initial decisions in management.

The first step in managing diffuse cervicofacial disease is to ensure an adequate airway and adequate feeding; this often requires tracheotomy and possibly gastrostomy.

The next task is to divide the patient into anatomic zones and then try to manage those zones as individual areas of localized disease until a given zone is completely disease-free. Failure to excise a diseased area completely predisposes to a high recurrence rate of in that area. Approaching the divided components of the total malformation from the top down is also advisable, if possible, to avoid lymphatic swelling at more proximal locations.

Children with diffuse cervicofacial disease also frequently require maxillomandibular reconstruction because of overgrowth of the facial bones. Depending on the severity of the disease and the extent of infiltration into local structures, these additional procedures can draw out an already lengthy treatment process.

Long-Term Monitoring

Vascular tumors

Regular follow-up care is an integral part of the management of hemangiomas to monitor the natural history of the lesion and to provide ongoing comfort to the patient's parents. The physician should also monitor for potential adverse effects of treatment, including the following:

  • With local glucocorticoid treatment, a case of retrobulbar hematoma with subsequent blindness has been reported
  • With systemic glucocorticoid treatment, adrenal suppression and other common adverse effects of systemic steroid therapy may occur
  • With interferon alfa-2a administration, adverse effects include transient fever, neutropenia, and elevated liver function test results; several cases of spastic diplegia (some permanent) have also been reported in infants after treatment
  • Laser therapy may produce hypopigmented lesions

If the patient has undergone surgical excision, the physician and the parents should decide whether the results of the excision are acceptable or whether a second excision and closure should be performed.

Capillary malformations

Patients who received laser treatment for capillary malformations should be monitored for recurrence and for the adverse effects of laser therapy. The argon laser can result in hypopigmented lesions and textural changes in the skin. Although both of these outcomes are factored into the decision to use the argon laser, the physician and the patient should come to a consensus on an acceptable result after treatment. Recurrence can occur up to several years after treatment.

Lymphatic malformations

Patients who undergo excision of a localized lymphangioma should simply be monitored for recurrence. Individuals treated for diffuse disease are often lifelong patients and should receive regular follow-up. The support of a child therapist may be useful to help manage the psychosocial impact of the disease and treatment.