Clinical features

Venous malformation (VM) results from an error in vascular morphogenesis; veins are dilated with thin walls and abnormal smooth muscle. Consequently, lesions expand, flow stagnates, and clotting occurs. Although a VM is present at birth, it may not become evident until childhood or adolescence when it has grown large enough to cause a visible deformity or symptoms. Lesions are blue, soft, and compressible; hard calcified phleboliths may be palpable. VMs may range from small localized skin lesions to diffuse malformations involving multiple tissue planes and vital structures.

VMs are typically sporadic and solitary in 90% of patients; 50% of patients have a somatic mutation in the endothelial receptor TIE2. Angiopoietins, the ligands for TIE2, are involved in angiogenesis; the mutation uncouples endothelial cells and pericytes altering venous development. Sporadic VMs are usually larger than 5 cm (56%); single (99%); and located on the head/neck (47%), extremities (40%), or trunk (13%). Almost all lesions involve the skin, mucosa, or subcutaneous tissue; 50% of the lesions also affect deeper structures (ie, muscle, bone, joints, viscera).

Approximately 10% of patients with VM have multifocal familial lesions, either glomuvenous malformation (GVM) (8.0%) or cutaneomucosal VM (CMVM) (2.0%). GVM is an autosomal dominant condition with abnormal smooth muscle–like glomus cells along the ectatic veins and is caused by a loss-of-function mutation in the glomulin gene. Lesions are typically multiple (70%), small (two-thirds are <5 cm), and located in the skin and subcutaneous tissue. GVM involves the extremities (76%), trunk (14%), or head/neck (10%). GVM is more painful than typical VM, especially on palpation. It is reported that 17% of patients develop new lesions over time. CMVMs are small multifocal mucocutaneous anomalies caused by a gain-of-function mutation in the TIE2 receptor. The condition is autosomal dominant and less common than GVM. Lesions are small (76% of the lesions are <5 cm); multiple (73%); and located on the head/neck (50%), extremity (37%), or trunk (13%). Unlike GVMs, CMVMs are not painful on palpation. Cerebral cavernous malformation (CCM) is a rare familial disorder with VM involving the brain and spinal cord; patients may also have hyperkeratotic skin lesions. The disorder results from mutations in CCM1/KRIT1, CCM2, and CCM3 genes, and patients are at risk for developing new intracranial malformations and hemorrhage.

Blue rubber bleb nevus syndrome (BRBNS) is a rare condition with multiple small (<2 cm) VMs involving the skin, soft tissue, and gastrointestinal tract. Morbidity is primarily associated with gastrointestinal bleeding requiring long-term blood transfusions. Diffuse phlebectasia of Bockenheimer is an eponym occasionally used for an extensive extremity VM involving the skin, subcutaneous tissue, muscle, and bone. Sinus pericranii is a venous anomaly of the scalp or face with transcalvarial communication with the dural sinus. Verrucous hemangioma (VH) most closely resembles a hyperkeratotic VM (verrucous VM), although some histologic features are similar to an involuted infantile hemangioma. Lesions range from 2 to 8 cm and are located on an extremity (91%) or the trunk (9%). VH involves the skin and subcutis, becomes more hyperkeratotic over time, and is frequently associated with bleeding. VMs may also be a part of a combined malformation, particularly lymphatic, because lymphatics arise from veins embryologically. Phlebectasia, a distinct venous anomaly, has 3 major forms: (1) sporadic (also called congenital varicosity), (2) associated with lymphatic malformation (LM), and (3) syndromic (eg, Klippel-Trénaunay syndrome).

Complications of VMs depend on the extent and location of the anomaly. Lesions often cause psychosocial morbidity because of their appearance. Patients can have pain and swelling from dependent positioning or secondary to thrombosis and phlebolith formation. Head and neck VMs may present with mucosal bleeding or progressive distortion, leading to airway or orbital compromise. Extremity VMs can cause leg length discrepancy, hypoplasia due to disuse atrophy, pathologic fracture, hemarthrosis, and degenerative arthritis. VMs of muscle may result in fibrosis and subsequent pain and disability. Patients with phlebectasia, particularly when it communicates with the deep venous system through large perforators, are at risk for thrombosis and pulmonary embolism. Gastrointestinal VMs can cause bleeding and chronic anemia. Stagnation within a large VM results in a localized intravascular coagulopathy (LIC) and thromboses. A VM is especially problematic because it is progressive; it enlarges over time, particularly during adolescence; and often reexpands after treatment. Consequently, most patients who present with asymptomatic lesions will ultimately require intervention.