In our practice, we often encounter patients referred to our care with a diagnosis of hemangioma mistaken for vascular malformation. These terms are often misused and misunderstood on a larger scale, which can strongly impact diagnosis and treatment. It is important for physicians to be able to distinguish vascular tumors such as hemangiomas from vascular malformations, because the lesions differ in their prognosis, morbidity, and management.
The current classification system accepted by the International Society for the Study of Vascular Anomalies (ISSVA) divides vascular lesions into two separate categories: vascular tumors and vascular malformations (See Table 1). Vascular tumors display endothelial hyperplasia and are generally characterized by a period of rapid growth followed by slower involution after birth, whereas vascular malformations exhibit flat endothelium and typically grow proportionally with the patient. Below, we will clarify the differences between vascular tumors and malformations as well as their appropriate diagnostic workup and management.
HEMANGIOMAS OF INFANCY
Of all vascular tumors, hemangiomas of infancy (HOI) are the most common in infants, with a prevalence of five to 10 percent. Infants with hemangiomas are more likely to be female (3:1 ratio), Caucasian, premature, have a low birth weight, and be the product of a multiple gestation.1 Chorionic villous sampling has also been implicated as a risk factor for hemangiomas. HOI's are typically not observed at birth, but subtle skin findings such as telangiectasias, red macules, or blanched spots can be seen in newborns as markers where the tumor will grow.2 HOI's are characterized by three phases: proliferative, involuting, and involuted. The initial proliferative phase in which the tumor grows to its maximum volume occurs during the first year of life, peaking between four and six months. After this steep growth phase, the tumor begins involuting. Involution involves subtle changes in color and an eventual decrease in tumor size to almost complete resolution. Roughly 50 percent of cases resolve by five years of age, 75 percent by seven years, and about 90 percent by nine years of age. However, in about 20 to 40 percent of patients, involuted hemangiomas can still leave permanent residual changes on the skin. These can range from mild atrophy to hypertrophic scars, especially if the tumor ulcerates.
The vast majority of hemangiomas present on the face and neck. Lesions on the trunk or extremities are less common. About 80 percent of cases occur as a single lesion, but when more than five lesions are present, internal organ involvement may be possible. The liver is the most commonly affected organ, with involvement of the lungs, intestine, and brain occurring to a lesser extent. Complications associated with large tumors and internal organ hemangiomatosis include hyperthyroidism and the development of high output cardiac failure. Large segmental hemangiomas can also be associated with structural anomalies, such as in PHACES syndrome. This syndrome is characterized by posterior fossa CNS anomalies, hemangiomas, arterial anomalies, coarctation of the aorta, cardiac defects, eye anomalies, and sternal defects.
Most HOIs are diagnosed clinically, but in complicated cases of large congenital lesions or hepatic compromise, ultrasonography with doppler studies is recommended. MRI may be indicated as well when the differentiation between hemangiomas and other vascular tumors or malformations is difficult to assess or when there is suspicion of internal organ involvement. Furthermore, MRI is necessary for PHACES evaluation or when extensive perineal hemangiomas are present.
The most common complication of infantile hemangiomas—in up to 13 percent of cases—is ulceration. Hemangiomas on the face, neck, and perineal region carry a higher risk for ulceration. Ulceration tends to occur during the proliferative phase and is more common in segmental hemangiomas. Once ulceration occurs, it increases the risk for infection, bleeding, and scarring and may result in severe pain.
Since treatment is focused on limiting the growth phase of the tumor to prevent ulceration, it is important to closely follow patients with HOIs during the first six months of life. The therapeutic approach varies depending on the size, location, complications, growth rate, and severity of the lesion. Small lesions on the face that may be prone to ulceration can initially be treated with high potency topical corticosteroids or intralesional corticosteroids. If these options fail or the lesion is very deforming and large, oral corticosteroids have traditionally been the mainstay of therapy. In about 30 percent of patients treated with systemic corticosteroids, notable shrinking of the lesion is observed. However, systemic corticosteroids have significant side effects including gastritis, immunosuppression, growth retardation, hypertension, and irritability. The dose ranges between 2-5mg/kg, and the duration of therapy can last from a few weeks up to several months.1,3
Other options that have been used for complicated cases or those that fail corticosteroids include interferon-a and vincristine. However, interferon is falling out of favor over concerns of spastic diplegia, which is reported in up to 20 percent of patients. Vincristine is usually reserved for cases of tufted hemangiomas and kaposiform hemangioendotheliomas associated with Kasabach-Merritt Phenomenon.3 Less common therapies for the prevention and treatment of ulcerated lesions include pulse dye lasers, topical antibacterial agents, and barrier creams.
Propanolol, a non-selective beta-blocker agent, is a novel therapy for infantile hemangiomas still in its early trial phase. Although this medication leads to quick involution of hemangiomas, its mechanism of action is not fully understood. It is thought that vasoconstriction, decreased expression of vascular growth factor genes, and induction of apoptosis may be involved.4 Important side effects of propranolol include hypotension and bradycardia, which can mask the physical signs of hypoglycemia. Thus, propranolol should be used with caution.
Although they are often mistaken for infantile hemangiomas, cutaneous vascular malformations occur less frequently and are seen in only 0.3 to 0.5 percent of the population.5 Although their pathogenesis is not fully understood, vascular malformations are thought to arise from errors in the process of normal vasculogenesis and angiogenesis.6 While vascular malformations can be associated with underlying anomalies and a variety of syndromes (see Table 2), this article will focus on the classification, presentation, and management of the main types of vascular malformations.
Vascular malformations are categorized according to their vascular components and flow characteristics. They may be composed of slow-flow capillary, venous, or lymphatic channels, fast-flow arterial channels, or a combination of these.7 Capillary malformations (CMs) of the skin, such as port-wine stains, are slow-flow vascular anomalies that affect three of 1,000 infants.7 These lesions are present at birth and typically arise sporadically, although familial cases have been reported.8 CMs may present as single or multiple pale pink macules or patches. They can be limited to small areas of the skin or involve an entire limb or portion of the face. Lesions on the head and neck may become darker, thicker, develop blebs, and even become hyperkeratotic over time, whereas CMs on the trunk and extremities can fade and lighten as the patient matures.7
Like CMs, venous malformations (VMs), are also slow-flow anomalies present at birth. VMs usually arise sporadically but can also occur via autosomal dominant inheritance. These lesions become more prominent with age and present as soft, compressible blue masses that swell with physical activity or when placed in dependent positions. They can be local or extensive, resulting in cosmetic and structural deformity. Complications associated with VMs include pain, swelling, pathologic fractures, phlebolith formation, bleeding diatheses, and functional impairment.9
In contrast, arteriovenous malformations (AVMs) are fast-flow vascular lesions made of arterial and venous anastomoses. Most commonly seen on the head and neck region,10 AVMs typically progress through four stages. Stage I (quiescent phase) occurs from birth until adolescence. During this time, the lesion is asymptomatic and clinically resembles a PWS or involuting hemangioma, but the presence of increased warmth, a bruit, or palpable thrill hints to the high-flow component of the lesion. Stage II (progressive phase) begins during adolescence and is characterized by enlargement and darkening of the lesion along with invasion of deeper structures. During stage III, deeper destruction may result in necrosis, ulceration, pain, hemorrhage, and lytic bone lesions. Finally, cardiac decompensation can occur in stage IV of large AVMs.
Another type of vascular malformation results from developmental anomalies of the lymphatic system. Three-fourths of these lymphatic malformations (LMs) are visible at birth, and the remainder present by two years of age.11 Macrocystic LMs typically occur on the neck or axilla as ill-defined subcutaneous masses that can expand over time. Large LMs can result in pain and tenderness along with structural and functional impairment. On the other hand, microcystic LMs tend to present as groups of thin-walled vesicles or hyperkeratotic papules localized to one area on the limbs, upper arms, or chest. These microcystic LMs are associated with clear fluid discharge and can cause thickening or swelling of the surrounding skin and subcutaneous tissue when deeper structures are involved.7
The diagnosis of vascular malformations is based on clinical appearance, but radiographic studies are required for confirmation. Ultrasound and Doppler can be useful in examining flow characteristics and distinguishing between no-flow LMs and slow-to-high-flow CMs, VMs, or AVMs. However, the gold standard is MRI, which can define the extent of the lesion and assess involvement of underlying structures. In addition, AVMs require angiography studies to help guide intra-arterial embolization.12
Management varies slightly between the types of malformations. CMs are best treated with flashlamp-pumped pulsed dye lasers,7 resulting in significant lightening of the lesion in 80 percent of cases.13 It is important to inform patients that complete disappearance of the lesion is rare, and that recurrence of the lesion three to four years after PDL may occur.14 Most physicians recommend PDL therapy early in childhood to diminish any psychological effects of a cosmetically disfiguring lesion.15 For VMs, obtain coagulation profiles prior to intervention. Moreover, most cases require a combination of sclerotherapy and surgical excision. Smaller lesions can be treated with sclerotherapy or excision alone, while extensive VMs on the trunk and limbs that involve muscles and joints are managed conservatively with compression garments. AVMs associated with extreme pain, ulceration, bleeding, or rapid enlargement are treated with preoperative embolization and surgical resection, while asymptomatic lesions are typically managed with continued observation. Finally, for symptomatic LMs, surgical resection is recommended for smaller, localized, well-defined lesions, while unresectable cases typically require sclerotherapy.
Because different types of vascular lesions can resemble each other clinically in the pediatric population, many physicians find them difficult to clinically diagnose and differentiate. Clinicians should be familiar with the classification of vascular lesions as either tumors or malformations and be able to recognize distinguishing characteristics of these disparate conditions. For more difficult cases, imaging can clinch the diagnosis by enabling visualization of the flow characteristics and extent of involvement of a vascular lesion. Fortunately, a variety of therapeutic options exists to effectively treat most hemangiomas and vascular malformations.