Port-Wine Birthmarks
Lance W. Chapman
Kristen M. Kelly
BACKGROUND
Vascular anomalies encompass 2 broad categories: vascular tumors and vascular malformations.1 Adopted in 1996 by the International Society for the Study of Vascular Anomalies (ISSVA), this nomenclature allows for the distinction between those vascular lesions with increased endothelial cell turnover and vascular proliferation (vascular tumors) and vascular lesions with a more latent endothelium and abnormal vascular structure (vascular malformations).2
In 2014, the ISSVA updated the Classification of Vascular Anomalies to reflect the additional disease types that have been identified over the previous decade.3 Vascular malformations, which in 1996 were classified as either simple or combined, have been further divided by 2014 ISSVA (Table 3.2.1).
This chapter will focus on capillary vascular malformations know as port-wine birthmarks (PWBs). These lesions were previously known as port wine stains (PWS), but this terminology is no longer preferred because of potential negative connotations.
PRESENTATION
PWBs present at birth as a pink or light red patch. The head and neck region is a common area of presentation; however, they can occur anywhere on the body. Facial PWBs may occur in a dermatomal-type distribution, including the V1 ophthalmic region, V2 maxillary region, and V3 mandibular region. Central facial PWBs also occur. Rather than corresponding to areas of trigeminal innervation, these identified
patterns support the association with somatic mosaicism, which was described by Happle and Assim in 2001.8 PWBs do not follow the lines of Blaschko but rather are mostly localized or segmental in distribution. Multifocal and widespread PWBs do occur but are less common.
patterns support the association with somatic mosaicism, which was described by Happle and Assim in 2001.8 PWBs do not follow the lines of Blaschko but rather are mostly localized or segmental in distribution. Multifocal and widespread PWBs do occur but are less common.
TABLE 3.2.1 Vascular Anomalies per the 2014 ISSVA Classification | ||
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PWBs tend to grow proportionally with the growth of the child and also thicken over time. The color progressively darkens, and by adulthood there may be a purple-red hue, along with tissue hypertrophy and nodularity (Figure 3.2.1). In a study by Klapman et al,9 of 173 patients with PWBs, thickening was observed in 11% (median age 32 years), nodularity in 24% (median age of 44 years), with 6% having both hypertrophy and nodularity (median 45 years). In another study by Geronemus et al,10 the mean age of hypertrophy was determined to be 37 years and 65% of PWB lesions had either hypertrophied or become nodular by the fifth decade.
Treatment of PWBs should not be viewed from purely a cosmetic perspective. Soft-tissue overgrowth can lead to functional impairment, particularly of the lip. Enlargement of the lips and gums can result in gingival bleeding and lip incompetence. Deeper structural changes can also occur, particularly with overgrowth of the maxilla and surrounding facial bones. This can cause the affected patient to develop a permanent open-bite. Furthermore, several studies have demonstrated that personality development can be severely impacted in patients with PWBs. The negative reaction of others to a “marked” patient can have significant psychological effects.11,12,13
 FIGURE 3.2.1 Hypertrophic and nodular port-wine birthmark. |
DIAGNOSIS
Clinical Diagnosis
Diagnosis of PWB is generally made clinically. However, additional testing may be useful when associated syndromes are considered (see later discussion). In newborns, PWBs may sometimes be mistaken as infantile hemangiomas. Clinical course (infantile hemangiomas generally grow rapidly during the first few months followed by stabilization and then slow involution) as well as distribution and lesional characteristics (PWBs are generally flat, although there may be tissue hypertrophy, whereas infantile hemangiomas may start as flat but in many cases become raised) can help distinguish these 2 diagnoses.
Histopathology
CMs are characterized by ectatic papillary dermal capillaries and postcapillary venules in the upper reticular dermis and increased vessel density with no apparent proliferation of vessels. The ectatic vessels are lined by flat, benign-appearing endothelial cells, similar to normal dermal blood vessels, with similar immunohistochemical staining for endothelial antigens, such as fibronectin, von Willebrand factor, and collagenous basement membrane proteins. The cell cycle rate of the endothelial cells is similar to that of normal vessels,
as demonstrated by the lack of mitoses and of tritiated thymidine uptake. A mean vessel depth of 0.46 mm has been reported for CMs, suggesting that most of the vessels are superficial. Immunohistochemical studies reveal a significantly decreased density of perivascular nervous tissue in lesional skin associated with progressive vascular dilatation.14 On confocal microscopy, nerve density and blood vessel diameter are inversely correlated with the lowest nerve density exhibiting the highest blood vessel density and the poorest response to laser intervention.15 The expression of endothelial cell mitogen vascular endothelial growth factor (VEGF)-A and of its receptor VEGF-R2 are significantly increased in CM tissue as compared with control skin.16
as demonstrated by the lack of mitoses and of tritiated thymidine uptake. A mean vessel depth of 0.46 mm has been reported for CMs, suggesting that most of the vessels are superficial. Immunohistochemical studies reveal a significantly decreased density of perivascular nervous tissue in lesional skin associated with progressive vascular dilatation.14 On confocal microscopy, nerve density and blood vessel diameter are inversely correlated with the lowest nerve density exhibiting the highest blood vessel density and the poorest response to laser intervention.15 The expression of endothelial cell mitogen vascular endothelial growth factor (VEGF)-A and of its receptor VEGF-R2 are significantly increased in CM tissue as compared with control skin.16
Subtypes
Sturge-Weber Syndrome
A number of syndromes are associated with PWB (Table 3.2.2). Sturge-Weber syndrome (SWS) is the presence of 2 of the 3 following conditions: facial PWB and ocular and brain anomalies. Such anomalies may cause the patient to develop glaucoma, seizures, and developmental delay. Patients with SWS may have a PWB that affects a V1-type distribution, but there may be extension into the lower face or extensive ipsilateral or bilateral involvement (Figure 3.2.1). A recent prospective study performed by Dutkiewicz et al17 demonstrated that certain PWB distribution patterns, specifically hemifacial, are associated with a high risk for SWS.
Klippel-Trenaunay Syndrome
Another syndromic association of PWBs is Klippel-Trenaunay syndrome (KTS). KTS involves a PWB (or more specifically a capillary-venous malformation or capillary-lymphatic-venous malformation) on an extremity. KTS can be associated with concomitant limb hypertrophy, lipomatosis, lymphedema, and gastrointestinal vascular lesions that may bleed.
TABLE 3.2.2 Syndromic Associations and Characteristics | ||||||||||||||||||||
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Parkes Weber Syndrome
Parkes Weber syndrome has an underlying arteriovenous fistulae (AVFs), which can cause limb overgrowth, with an overlying PWB (CMs) and can also be associated with lymphatic abnormalities. The prognosis of Parkes Weber syndrome is more guarded given the lytic bone lesions and cardiac failure that often develops after puberty.18,19 Parkes Weber syndrome is associated with RASA1 mutations, which are inherited in an autosomal domination fashion.20 Other RASA1-related disorders involve multiple and
small CMs on the face and limbs, with about 30% of individuals with concomitant arteriovenous malformations (AVMs) and/or AVFs,20 which are generally symptomatic early in life.
small CMs on the face and limbs, with about 30% of individuals with concomitant arteriovenous malformations (AVMs) and/or AVFs,20 which are generally symptomatic early in life.
Proteus Syndrome
PWBs can also be associated with Proteus syndrome. This disorder involves a mosaic activating mutation in the AKT1 gene, which ultimately transcribes a protein that regulates cellular growth.21 This syndrome often phenotypically demonstrates disfiguring, asymmetric, disproportionate overgrowth with concomitant orthopedic consequences.
CLOVES Syndrome
CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular anomalies, Epidermal nevi and Scoliosis/other Skeletal abnormalities) can also be associated with PWBs; however, unlike the other syndromic associations, the vascular lesions in CLOVES syndrome can be varied.
CLAPO syndrome (CMs, Lymphatic malformations, Asymmetry and Partial Overgrowth of the face and extremities) and Macrocephaly-CM (usually with reticulated or confluent PWBs) are also syndromic associations with PWBs.
Cobb Syndrome
Cobb syndrome is a very rare sporadic disease with AVMs involving cutaneous, intraspinal, and vertebral regions. What makes this syndrome unique to the aforementioned syndromes is that, although there are often red vascular patches (often on the nape of the neck) that mimic a PWB, these are actually stage 1 AVMs. Neurologic manifestations frequently develop from AVM expansion on the spinal cord, sometimes resulting in bladder dysfunction and paraplegia.22
Differential Diagnosis
Vascular tumors
Other vascular malformations
Telangiectasia
Cutis marmorata telangiectatica congenita (CMTC)
Nevus simplex/salmon patch/“stork bite”/“angel kiss”
Lymphatic malformations (LMs)
Venous malformations (VMs)
Differential Diagnosis Evaluation
In evaluating a presumed PWB, distribution is important. For a typical segmental PWB involving V1 type or central distribution, a workup including neurologic examination, ophthalmologic examination, and, in many cases, magnetic resonance brain imaging should be performed to evaluate for possible SWS.23 To ensure optimal care, it is important to work with neurologists and ophthalmologists with expertise in SWS, if this diagnosis is likely. Consultation with experienced neurologists and neuroradiologists is also useful to assure that the time and ordering of imaging is optimal. Patients with SWS require at least annual ophthalmologic examinations and, if there is neurologic involvement, close follow-up with a neurologist.
For PWBs affecting the lower face, close follow-up monitoring for maxillary overgrowth, dental problems, and gingival hypertrophy is important.
Extremity lesions should be monitored for limb overgrowth, and imaging may be useful to rule out involvement of deep vasculature.
Any atypical PWBs should be evaluated by an expert and other diagnoses considered, including other types of malformations. Again, imaging may be useful to make a definitive diagnosis.
Lesions characteristic of RASA1 malformations should be referred to a geneticist.
PATHOGENESIS
Vascular malformations encompass a wide array of disorders that involve altered blood vessels or lymphatic channels. Therefore, it is believed that any mutation or dysfunction in any of the processes that signal for migration, differentiation, maturation, and cell survival of vascular anatomy can ultimately cause vascular malformations.23,24,25
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