Arterial Vascular Malformations Including Hemangiomas and Lymphangiomas

Updated: Feb 24, 2017
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Overview

Background

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

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]

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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.

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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.

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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]

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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. [18]

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. [19]

Vascular malformations include capillary and lymphatic malformations. Capillary malformations (ie, port-wine stains) occur in 3 per 1000 neonates. [20] 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 rate of lymphatic malformations is 1.2-2.8 per 1000 live births. [21] Approximately 50% of lymphatic malformations are apparent at birth; 90% appear before age 2 years. Most reports indicate an equal male-to-female distribution.

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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%. [22] 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.

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