Diagnosis of Vascular Anomalies in Patients with Skin of Color

J Clin Aesthet Dermatol. 2024;17(10):54–62.

by Marta E. Taye, MD*; Jay Shah, MD*; Elizabeth V. Seiverling, MD; and Leslie P. Lawley, MD

*Drs. Taye and Shah share co-first authorship of this article.

Drs. Taye and Lawley with the Department of Dermatology, Emory University School of Medicine in Atlanta, Georgia. Drs. Shah and Lawley are with the Vascular Anomalies Clinic at Children’s Healthcare of Atlanta in Atlanta, Georgia. Dr. Shah is also with the Department of Radiology and Imaging Services at Children’s Healthcare of Atlanta and Emory University School of Medicine and at the Children’s Pediatric Institute in Atlanta, Georgia. Dr. Seiverling is with the Department of Dermatology at the University of Pittsburgh School of Medicine in Pittsburgh, Pennsylvania.

FUNDING: No funding was provided for this article.

DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article.

ABSTRACT: Vascular anomalies can be broadly classified as vascular tumors or vascular malformations, depending on the degree of endothelial involvement. These lesions can be subtle and challenging to diagnose in individuals with darker skin tones, which can lead to a delay in treatment. Improving diagnostic accuracy of these lesions may prevent progression and potential adverse outcomes when left untreated. Here, we present a review of common vascular anomalies with a focus on diagnostic considerations in individuals with skin of color.

Keywords. vascular malformation, vascular tumor, hemangioma, capillary malformation, melanin

Introduction

Vascular anomalies arise from aberrant vascular morphogenesis.¹ The International Society for the Study of Vascular Anomalies (ISSVA) presents a classification scheme in which these lesions are characterized based on biologic and genetic properties.² The two primary categories include vascular tumors (VT) and vascular malformations (VM). VTs are often characterized as vessels with increased endothelial proliferation whereas VMs have a relatively quiescent, or slow growing, endothelium. Recent studies have elucidated the genetic mutations attributed to certain vascular anomalies associated with overgrowth syndromes and are shedding light on pathogenesis.^3,4 The diagnosis of vascular anomalies is based on clinical exam often in conjunction with radiographic imaging, yet diagnosis can be challenging in individuals with darker skin tones due to difficulty in discerning red and blue coloration, especially with transient color changes that may occur in certain vascular anomalies due to situational changes (ie, increased intracranial pressure, crying, illness). 

There is a lack of educational resources on vascular anomalies in SOC populations. Racial and ethnic disparities within the field of dermatology have been documented and include increased rates of hospitalization and worse outcomes for common skin conditions among underrepresented groups.⁵ To date there has not been a comprehensive review of vascular anomalies in skin of color (SOC) patients (defined as individuals with African, Asian, Hispanic/Latinx, Native Indian, and/or Pacific Islander ancestry) despite their prevalence across racial and ethnic minority groups. A cross-sectional study of 352 patients at a single vascular anomaly center demonstrated that over 37 percent of pediatric patients identified as non-White and over 17 percent as Hispanic/Latino, with no observed differences in vascular malformation type by race.⁶ Better recognition of vascular anomalies in this population can improve rates of diagnosis and avoid potential adverse health outcomes with delayed treatment. The aim of this review is to summarize unique clinical characteristics of vascular anomalies in SOC populations to improve diagnostic accuracy among underrepresented groups. 

Recognizing vascular anomalies in SOC patients requires an understanding of how these lesions appear in neonates with darker skin and evolve with the growth of the child. Skin matures during embryogenesis which concludes by 34 weeks of gestation; however, melanin continues to be produced in response to ultraviolet (UV) radiation exposure during infancy.⁷ Melanin production primarily occurs over the first two years of life, and in conjunction with other physiologic factors such as skin thickness and hemoglobin concentration, produces an individual’s natural skin tone. In early infancy, vascular birthmarks may appear more red or blue. As melanin concentration in the skin increases, the red and blue tones are less noticeable under skin pigment and present more hyperpigmented.  

Diagnosing vascular anomalies in darker skin can be challenging due to their subtle presentation.⁸ Dermoscopy can aid in the visualization of vasculature and differentiate from pigmented nonvascular lesions. Clinical photography can serve as a tool to track the evolution of vascular anomalies. To optimally image darker skin tones, a light-toned or plain background and natural lighting or light-emitting diode (LED) light sources are best to minimize the casting of yellow and blue hues.⁹

Occasionally, visual inspection and radiographic imaging may not be sufficient for determining a diagnosis and we recommend clinicians retain a high degree of suspicion based on the data available. The differential diagnosis for vascular growths in SOC populations is broad and includes pigmentary lesions (congenital melanocytic nevus, café au lait macule, pigmentary mosaicism, etc.), traumatic purpura, sarcoma, among others. Dermoscopy serves as a valuable tool in differentiating melanocytic growths from vascular growths in the pediatric population.^8,10 At times, biopsy may be necessary to distinguish between sarcoma and vascular tumors including congenital hemangioma and kaposiform hemangioendothelioma. In the setting of a vascular anomaly, overgrowth syndromes (ie, PIK3CA-related overgrowth spectrum (PROS), Parkes-Weber syndrome, etc.) should be considered in the proper clinical context. This review will highlight the distinct clinical features of vascular anomalies in darker skin types and provide corresponding visual examples.

Benign vascular tumors. Infantile hemangioma. Infantile hemangiomas (IH) are the most common benign tumor of childhood, and have been shown to be most prevalent in infants who are female, delivered pre-term, and of White non-Hispanic race/ethnicity.¹¹ A multicenter study of 1,722 IH patients found that the percentage of the study population identifying as White Hispanic, Asian, and Black, was 13 percent, 11 percent, and 4 percent, respectively.¹² One proposed hypothesis for the lower prevalence of IH in darker skin individuals is thought to be due to the protective factor of fibromodulin, an angiogenic protein secreted by melanocytes.¹³ The increased secretion of fibromodulin in individuals with more melanin (ie, darker skin) may serve as a key regulator against the development of angiogenesis-dependent diseases.¹³ 

IHs are classified according to their depth (superficial, deep, mixed) and distribution (localized, indeterminate, segmental, multifocal) (Figures 1–4).² Superficial IH are the most common subtype and present as a brightly erythematous patch or plaque typically on the head or neck.¹⁴ In darker skin tones, superficial IH may appear as brightly erythematous or dull, deep red papules or plaques (Figures 5­–6). Dermoscopy of IH demonstrates red lacunae sometimes separated by white septae (Figure 7).¹⁵ Deep IH may be more difficult to distinguish in SOC patients as the typically described blue coloration may be masked or appear slightly hyperpigmented (Figure 8).  

The diagnosis of IH rarely requires radiographic imaging as history and physical exam are often sufficient. Occasionally, ultrasound is utilized to confirm the diagnosis of a deep IH and assess degree of vascularity. Deep IH appear as well-defined, homogenous masses with high-flow on Doppler ultrasound.¹⁶ Complications of IHs can arise in approximately 10 to 15 percent of patients, with ulceration being the most common (Figure 9).¹² Lesions with ulceration present greater risk for pain, bacterial infection, scarring, and destruction of localized tissue.¹² Although IHs are less prevalent in SOC populations, a multicenter retrospective review of 1,722 patients found that Black patients had over two times greater odds of ulceration compared to non-Hispanic White patients.¹² While the etiology of this difference is not clear, it is thought to be a combination of difficulty recognizing IH in darker skin and limitations in access to specialty care, among other factors.¹² Similarly, a nationwide study of 10,495 hospitalized IH cases found that Black infants were older at presentation (1.8 years vs. 1.0 years) and had longer lengths of stay (16.4 vs. 13.8 days) compared to White infants.¹⁷ Cases of complicated IH require prompt recognition and treatment to reduce the likelihood of functional defects and permanent disfigurement. 

Congenital hemangioma. Congenital hemangiomas (CH) are rare vascular tumors that proliferate in utero and are fully formed at the time of birth.¹⁸ CH are classified based on their clinical course: rapidly involuting congenital hemangioma (RICH), partially involuting congenital hemangiomas (PICH), and non-involuting congenital hemangiomas (NICH).² In darker skin tones, the localized soft tissue mass of CH may be darker red-purple or even appear more brown in color with faint overlying telangiectasias (Figures 10–11). On dermoscopy, PICH demonstrates large irregular linear vessels and NICH demonstrates red dots, globules, and lacunae.¹⁵ 

Demographic incidence of CH in SOC is limited; however, a single site retrospective study of 592 vascular anomaly patients in China reported CH comprised three percent of vascular tumors.¹⁹ Diagnosis of CH can be made by clinical examination. Ultrasound demonstrates high flow vasculature with heterogeneous hyperechoic masses.²⁰ The most common early complications of CH are ulceration and bleeding due to high flow vasculature, which in large CHs may lead to hemodynamic complications.¹⁸

Pyogenic granuloma. Pyogenic granulomas (PG, also referred to as lobular capillary hemangioma) are small, red, friable papules commonly on the acral skin or craniofacial region and often present with bleeding or ulceration.²¹ In SOC, PG may present a more deep red exophytic papule (Figure 12) and may have a surrounding hyperpigmented, scaly collarette in contrast to the glistening bright red papule that is often observed in lighter phototypes. Dermoscopy of PG commonly demonstrates a homogenous red center with a white collarette and in some SOC patients a surrounding ring of pigmentation (Figure 13).¹⁵ 

Although the exact incidence of PG in SOC is not known, a retrospective study of 74 pediatric oral PG biopsies found the racial/ethnic distribution to be 58 percent White, 26 percent Black, and 16 percent Hispanic.²² Radiographic imaging is often not necessary as the diagnosis can be made clinically. Lesions may bleed and crust, leading to a shrunken appearance; however, a recurrence rate of about 16 percent has been reported.²¹  

Borderline vascular tumors. Kaposiform hemangioendothelioma. Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor with varying cutaneous features including blue-red papules, nodules, and plaques commonly located on the extremities.²³ In darker skin, KHE may appear deep red or brown in color (Figure 14). Given its low prevalence (one study estimates 678 KHE cases in the United States), there is limited reporting of KHE incidence in SOC populations.²⁴ A recent study of 338 KHE patients in China demonstrates the heterogeneity in clinical presentation, even within a homogenous population.²³ KHE is thought to exist on a spectrum of disease with tufted angioma (TA), which presents as red or violaceous nodules or papules (Figures 15–16). Kasabach-Merritt phenomenon (KMP), a severe complication of KHE observed in 46 percent of the Chinese patient cohort, presents with life-threatening thrombocytopenia and hypofibrinogenemia.^23,24 MRI is useful in determining the extent of KHE given its multiplanar involvement and poorly defined margins.²⁴

Vascular malformations. Capillary malformation. Capillary malformations (CM) are vascular malformations recognized by the dilation of capillaries and venules.¹ CM is an umbrella term used to describe various distinct lesions including nevus simplex (also known as “salmon patch”), cutaneous and/or mucosal CM (also known as “port-wine birthmark”), capillary malformation–arteriovenous malformation (CM-AVM), and telangiectasia, among others.² 

Nevus simplex is the most common among these, presenting as a pale pink to bright red patch with ill-defined borders that fade over time.¹ The incidence of nevus simplex has been reported as high as 78 percent in Hispanic, 76 percent in Asian, and 68 percent in Black populations.²⁵  

In contrast to nevus simplex, the excess vessels in cutaneous and/or mucosal CM are well-demarcated and persist over time.¹ In approximately 90 percent of cutaneous and/or mucosal CM cases, there is an associated somatic activating mutation of GNAQ, leading to a disruption in the growth of vascular endothelial cells^.4 Genetic sequencing of Chinese patients found GNAQ mutations in 83 percent of cutaneous and/or mucosal CM and 86 percent of CM with overgrowth patients; however, data in other SOC populations is limited.²⁶ GNAQ mutations have also been implicated in phakomatosis pigmentovascularis (PPV), a congenital syndrome affecting neural crest derivatives such as melanocytes.²⁷ PPV presents as the co-existence of a cutaneous vascular malformation (CM) with extensive dermal melanocytosis (Figure 17).²⁷ 

In SOC populations, CM may have a deep red or even hyperpigmented color and are less well-defined (Figures 18–19). In all patients, the intensity of color may vary with change in temperature, patient positioning or activity (ie, crying, Valsalva, or other instances of increased intracranial pressure). In PPV, the variation in CM coloration due to these transient changes may assist in diagnosis despite potential masking by dermal melanosis. A recently published case series highlighted the potential for misdiagnosis of CM in darker skin types given the subtlety of the pigmentary changes and similarity to pigmentary lesions such as a café au lait macule.²⁸ In darker skin, telangiectasias may be more subtle, requiring a greater degree of clinical suspicion. Dermoscopy can aid in visualization of capillaries, distinguishing CM from hyperpigmentation (Figure 20).²⁸

Venous malformation. Venous malformations (VM) present at birth as a soft, compressible blue patch or mass.²⁹ These lesions are typically small (<5 cm) but can increase in size through puberty and infiltrate surrounding soft tissue and bone.²⁹ Diagnosis is often made using physical exam and ultrasound imaging which demonstrates slow-flow vasculature within subcutaneous soft tissue, dilated channels, and sponge-like collection of vessels.^16,29 In SOC, the blue hue of VM may be less apparent and may appear skin colored to hyperpigmented (Figures 21–22). The dermoscopy features of VM include blue-red lacunae and structureless areas.¹⁵ The compressibility and increase in size with dependent positioning can aid in diagnosis when findings are not clinically apparent. 

A study of 144 VM patients at one vascular anomaly center reported the demographic distribution as 20 percent Hispanic, 13 percent Black, 2 percent Asian, and 1 percent American Indian/Alaskan Native.⁶ At a single center in southeast China, VM comprise 41 percent of all diagnosed vascular malformations.¹⁹ 

Lymphatic malformation. Lymphatic malformations (LM) are dilated lymphatic channels classified as microcystic, macrocystic, or mixed type.² Lymphatic malformations present as a flesh-colored smooth mass filled with lymphatic fluid ranging in clear to serosanguinous in appearance.¹ Darker skin types may exhibit translucent papules, erythematous, skin-toned or hyperpigmented papules and plaques (Figures 23–24). Inflammatory reactions including pain, swelling, and infection are common complications of LM.¹ Diagnosis is often clinical, although ultrasound may be used to diagnose a mass under normal appearing skin, demonstrating well-defined collections of cysts and stroma.²⁹ In a cross-sectional study of 112 patients with at a Southern United States vascular anomaly center, 17 percent were Hispanic, 14 percent were Black, two percent were Asian, and one percent were American Indian/Alaskan Native.⁶

Arteriovenous malformation. Arteriovenous malformations (AVM) are malformed vessels that result in fast-flow arteriovenous shunting.²⁹ In SOC, cutaneous findings can include a deep red to violaceous ill-defined patch, plaque or nodule with pulsation, thrill or bruits (Figure 25). These lesions progress over time and have a potential risk for cardiac overload.¹ AVM can be congenital, iatrogenic, combined with other anomalies, or representing a genetic disorder, often resulting from somatic mutations in MAP2K1.^2,30 In early stages, AVM may resemble capillary malformations with erythematous to brown patches.¹ Imaging is helpful in diagnosis, with angiography demonstrating tortuous arteries and venous drainage.³⁰ There is limited demographic data on the incidence of cutaneous AVM in SOC populations. 

Combined vascular malformations. Combined lesions consist of at least two vascular malformations including simple malformations and malformations of major named vessels.² Examples of these lesions include capillary-arteriovenous malformation and mixed capillary-venous malformation (Figure 26).² Additionally, eponymous disorders appear often in the literature and include such disorders as CLOVES syndrome (LM, VM, CM/AVM, lipomatous overgrowth) and Klippel-Trénaunay syndrome (KTS) (CM, LM, VM, overgrowth) which share many features with combined vascular malformations.² A recently published case report highlights the delayed diagnosis of KTS in an individual of African descent which has in part been attributed to the subtlety of the CM in darkly pigmented skin.³¹ 

New access to genetic evaluation continues to shape how these disorders are interconnected, often sharing the same genetic cause. A study on 14 Japanese patients with KTS found PIK3CA mutations in 86 percent, along with a previously unreported Q546K mutation in 21 percent of participants.³ Sequencing in 4 Chinese patients with CLOVES found a PIK3CA somatic mutation in all patients.²⁶ While our understanding of the genetic association of these conditions is continuing to expand, the inherent complexity of these malformations requires long-term interdisciplinary management.

Conclusion

Vascular anomalies encompass a broad range of cutaneous diseases that can be challenging to differentiate in SOC populations. This review provides information on the important clinical distinctions of vascular anomalies to help guide clinicians caring for these patients. 

Acknowledgements

We thank our multidisciplinary partners and providers at Children’s Healthcare of Atlanta and Emory for all of the continued collaboration in the care of these patients. We would like to thank Rachel Swerdlin, NP, and Alyssa Kesselman, NP, for providing media support in completing this review.

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