A 32-year-old man presents with right lower extremity edema, pain, lipodermatosclerosis, and history of recurrent right ankle ulcers. Physical examination demonstrates port-wine stains overlying his right upper and lower extremity, as well as the right hemithorax and abdomen (Figure 17-1). He states that these lesions have been present since birth. A clear asymmetry of his lower extremity is also noted with the right leg being larger than the left. Some soft tissue masses are also present, mainly in his lower extremity with an overlying cutaneous bluish discoloration. A duplex ultrasound documents a heterogeneous network of hypoechoic vessels with monophasic flow patterns and an incompetent great saphenous vein that is feeding many of the dilated venous structures. The deep venous system is normal and intact.

T2-weighted hyperintense magnetic resonance imaging or magnetic resonance angiography (MRI or MRA) demonstrates low-flow lesions mostly in his upper and right lower extremities (Figure 17-1) with osteomuscular hypertrophy of the right leg. The iliac veins and inferior vena cava are normal and patent.

A diagnosis of the unique vascular malformation, Klippel-Trenaunay syndrome (KTS), is made. The treatment plan is to eliminate the great saphenous vein using thermal ablation, and to treat the remainder of the venous malformations with ultrasound-guided foam sclerotherapy in multiple sessions.

Congenital vascular anomalies are a unique group of vascular disorders whose treatment remains a significant challenge. The groundbreaking work of Mulliken and Glowacky in characterizing vascular anomalies provides the definition of vascular malformations as “diffuse or localized embryologically developed errors of vascular morphogenesis leading to true structural anomalies.”¹ It is critical to understand that with this classification and definition, hemangiomas are considered vascular tumors, as they exhibit a different clinical appearance and biologic behavior. For this reason, vascular malformations and hemangiomas will be discussed separately here.

Hemangiomas are the most common pediatric vascular tumor, and as such represent a proliferative disorder in contrast to vascular malformations, which are nonproliferative.

Epidemiology

They are congenital and occur in 7% to 10% of children, and 30% are evident at birth, while the remainder appears within the first 4 weeks of life. The female:male ratio is typically 5:1.²

Etiology and Pathophysiology

The etiology is unknown. Recently, overexpression of the notch signaling pathway has been associated with the progression of hemangioma stem cells into hemangioma endothelial cells. Abnormal vascular endothelial growth factor (VEGF) production has also been observed.² Increased estrogen levels have been found in children with hemangiomas. In contrast to vascular malformations, hemangioma cells express the GLUT1 gene, an erythrocyte-type glucose transporter protein.^2,3

More recently it was hypothesized that hemangiomas may be derived from a stem cell arrested in an early stage of vascular development, as demonstrated by the expression of an immature immunophenotype (Prox-1, SLC, VEGFR-3, CD31, CD34) in tumor cells of infantile hemangioma. This immature immunophenotype tends to fade during the regression of the tumor.³

Histopathology

There are two histologic types of infantile hemangioma. The capillary variant is nonvascular with a spongy appearance, while the cavernous type is characterized by large vessels with thin walls of lined, flat endothelial cells.²

Clinical Presentation and Differential Diagnosis

In contrast to vascular malformations, hemangiomas are benign tumors whose biologic behavior includes a growth phase, a static phase, and then an involutive phase. They commonly affect the head and neck region, while the extremities are less commonly involved (upper extremities are involved in 15% of cases).²

Hemangiomas may appear as bright red, raised, or flat patches (Figure 17-2). Deeper lesions may have healthy overlying skin with a bluish discoloration. Hemangiomas are usually warm to touch, firm to palpation, and swell when the child is upset. Ulceration occurs in about 30% of patients.^2,4

Diagnosis

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  MR is the most common imaging modality.^2,5

  
  
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  On MRI, hemangiomas appear as T2 hyperintense, well- circumscribed lesions with some heterogeneity due to feeding and draining vessels.⁵

Management

As the overwhelming majority of hemangiomas involute spontaneously within the first 7 years of life, the initial approach is observation. It has been reported that 50% of hemangiomas involute by age 5 and 70% by age 7.²

Persistent or symptomatic lesions have been treated by oral, systemic, and intralesional steroids with mixed success.² Leaute-Labreze et al. initially reported the effectiveness of oral propranolol for treatment of infantile hemangioma.⁶ More recently, a large multicenter retrospective study conducted on 71 patients treated with oral propranolol (1 mg/kg/12 h) documented regression of the tumor over a 32-week treatment period regardless of gender, age at the initiation of treatment, location, ulceration, and depth.^7,8

Propranol is currently the treatment of choice in patients requiring medical therapy. Pulsed dye lasers in ulcerated lesions are associated with decreased pain and shorter healing time.² Intralesional bleomycin has also been utilized. Common complications are local hyperpigmentation and pulmonary fibrosis.²

Surgical treatment is recommended in patients with involvement and impairment of vital structures. In a review of 85 patients over 25 years, surgical excision with clean margins has reduced recurrence rates with the majority of patients reporting excellent function with no impairment.²

Kasabach-Merritt syndrome (KMS) was originally described as a life-threatening and localized consumption coagulopathy with thrombocytopenia and microangiopathic anemia, associated with a lesion initially called “capillary hemangioma with extensive purpura.”⁷ Current opinion indicates that KMS is rarely an epiphenomenon of infantile hemangioma, but is more commonly associated with the kaposiform hemangioendothelioma, an aggressive, rare pediatric vascular tumor.⁷

Vascular malformations are congenital nonproliferative vascular disorders, usually evident at birth, although some may present at a later age.

Epidemiology

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  Their incidence has been reported to be 1.5% of the general population with no gender predilection.^4,9

  
  
• 
  

  Venous malformations are the most common type. In a recent series, the ratio of venous to arteriovenous malformations was 4:1.⁴

  
  
• 
  

  Frequently vascular malformations are mixed and associated with developmental anomalies as in the KTS or the Parkes Weber syndrome, in which case they have shown familiarity and an autosomal pattern of inheritance.⁴

Classification

Several classification schemes for vascular malformations have been proposed over the years.

In 1996 the International Society for the Study of Vascular Anomalies (ISSVA), based on the initial work of Mulliken and Glowacki, implemented the previous Hamburg classification and approved a classification system in which vascular malformations were divided on the basis of the cellular kinetics, anatomy, and clinical behavior in two major categories: high-flow (HFVMs) and low-flow vascular malformations (LFVMs) (Figure 17-3).^4,9 HFVMs are vascular malformations that involve arterial vessels, often with abnormal connections to the venous system, while LFVMs involve only venous or lymphatic channels. The distinction is critically important to the management of patients as the treatment of LFVM and HFVM differs. LFVMs are further subdivided into venous, capillary, lymphatic, and mixed subtypes.