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). [2]
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. [3, 4, 5]
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. [6]
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 have been subject to contentious debate. The surgeon must determine when excision would produce a more cosmetically acceptable result than conservative treatment would and must 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.
Given that there is histopathologic overlap between acral pseudolymphomatous angiokeratoma, T cell–rich angiomatoid polypoid pseudolymphoma of the skin, and other designations of some of these vascular proliferations with a rich and dense lymphoid infiltrate, these may be best viewed as representing a spectrum of vascular lesions with varying clinical presentations. [7]
Anatomy
Vascular tumors
Hemangiomas located on the trunk or face may be psychologically damaging when children approach school age. This must be considered in discussing early intervention for 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. [8] 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. [9]
During the involutional phase of hemangiomas, a subsequent decrease in angiogenic factors occurs, with a fivefold increase in endothelial cell apoptosis. [10] 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. [11] 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 lumina dilate, and fibrous tissue is deposited. 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. [12]
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. [13]
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. [14] 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. [15] (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. [16]
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. [17] 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. [18, 19]
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. [20] A mutation in exon 15 of TEK was delineated in one patient. [21]
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. [22]
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. [23]
Vascular malformations include capillary and lymphatic malformations. Capillary malformations (ie, port-wine stains) occur in 3 per 1000 neonates. [24] 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. [25] 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. [26]
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 recommended manner (see Treatment), 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%. [27] 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.
-
Fully developed vascular tumor on trunk of infant.
-
Large vascular tumor encompassing upper extremity and portions of trunk, clinically diagnosed.
-
Lower extremity port-wine stain in patient with Klippel-Trenaunay-Weber syndrome.
Tables
| Vascular Tumors | Vascular Malformations |
|---|---|
Benign vascular tumors Infantile hemangioma/hemangioma of infancy Congenital hemangioma
Tufted angioma Spindle-cell angioma Epithelioid angioma Pyogenic granuloma (lobular capillary hemangioma) Others Related lesions |
Simple vascular malformations Capillary malformation (CM)
Lymphatic malformation (LM)
Venous malformation (VM)
Arteriovenous malformation (AVM)
Arteriovenous fistula (AVF) (congenital)
|
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
Anomalies of
|
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. |
