Venous Malformations

Fig. 45.1
Venous malformation, neck. a Intramuscular VM composed of large, irregular, thin-walled channels. A phlebolith is indicated by arrows. b The channels vary in size and are arranged back to back with scant intervening stroma. c Abnormal venous channels with flat endothelium and thin, variably muscular walls
A215095_1_En_45_Fig2_HTML.jpg
Fig. 45.2
Venous malformation, maxillary bone. a Portion of maxillary bone with intraosseous VM associated with osteolysis (asterisks). Arrows indicate teeth and arrowheads indicate residual trabeculae of bone. b Cluster of intramedullary, thin-walled venous channels of variable size. c Back to back, thin-walled venous channels with flat endothelium and luminal red blood cells

Key Points

  • VM is particularly problematic because it can expand, especially during adolescence, and often recurs after treatment.
  • The majority of patients who present with asymptomatic lesions ultimately will require intervention.
  • VMs should be treated in a vascular anomalies center by a multidisciplinary team.

Biology and Epidemiology

VMs arise from an error in vascular morphogenesis, which results in dilated, thin walled channels of variable size and mural thickness [1]. VM is sporadic and solitary in 90 % of patients; 10 % have multifocal, familial lesions (GVM: 8.0 % or CMVM: 2.0 %) [4, 5].

Pathophysiology

  • The mechanism for VM enlargement is unknown. Atypical structural characteristics of the vein may predispose the lesion to distention causing stagnation, thrombus, pain, deformation, and/or obstruction [2].
  • Neovascularization may be involved in VM progression. Hypoxia-inducible factor (HIF), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and endothelial proliferation are upregulated in cerebral VMs [79].
  • Lesions progress 2.6 times more often in adolescence compared to childhood, indicating that pubertal hormones may be involved in the pathogenesis of VM [2].

Molecular/Genetic Pathology

  • Sporadic VMs arise from abnormal vasculogenesis; approximately one-half of lesions have a somatic mutation in the endothelial tyrosine kinase receptor TIE2 [4, 5]. Angiopoetins, the ligands for TIE2, are involved with vascular stabilization; the mutation alters endothelial–pericyte contact affecting venous development [5, 10].
  • GVM is an autosomal dominant condition with abnormal smooth muscle-like glomus cells along the ectatic veins; it is caused by a mutation in the glomulin gene [11, 12].
  • CMVM is an autosomal dominant disorder produced by a mutation in the TIE2 receptor [10].
  • CCM is an autosomal dominant condition that results from mutations in CCM1/KRIT1, CCM2, and CCM3 genes [1315].

Incidence and Prevalence

  • VMs are the most common vascular malformation treated in a vascular anomalies center, comprising 36.8 % of referrals [16].

Age Distribution

  • VM is present at birth, but may not become obvious until childhood or adolescence [2].

Sex Predilection

  • Men and women are affected equally.

Risk Factors

  • The offspring of patients with GVM, CMVM, or CCM have a 50 % risk of inheriting the condition [1115].
  • Progesterone-only oral contraceptives are recommended because estrogen has more potent proangiogenic activity than progesterone [6, 1720].
  • Pregnant women do not have an increased risk of VM expansion and thus pregnancy is not contraindicated [2]. Nevertheless, women with significant lesions should be cautioned about possible worsening of symptoms during pregnancy.

Relationships to Other Disease States, Syndromes

  • Blue rubber bleb nevus syndrome (BRBNS) is a rare condition with multiple VMs in the skin, soft tissue, and gastrointestinal tract [21].
  • Diffuse phlebectasia of Bockenheimer is an extensive extremity VM that affects the skin, subcutaneous tissue, muscle, and bone [22].
  • Kippel-Trénaunay syndrome (KTS) is an eponym used to describe capillary-lymphatic-venous malformation (CLVM) of an overgrown extremity.
  • Sinus pericranii is a soft tissue/cutaneous VM of the scalp or face that has a transcranial communication with the dural venous system.

Presentation

Symptoms

  • Bleeding
    • Head/neck VM may present with mucosal bleeding.
    • BRBNS can cause gastrointestinal bleeding and chronic anemia.
  • Distortion/obstruction of anatomical structures
    • Head/neck VM may compromise airway or orbital function.
  • Pain
    • Caused by thrombosis and phlebolith formation.
    • VM of muscle may result in fibrosis and contractures.
    • GVMs are typically more painful than sporadic VM.
  • Thrombosis
    • Large VMs are likely to have venous pooling and are predisposed to localized intravascular coagulopathy (LIC) causing thrombosis and pain [23].
    • Phlebectasia that communicates with the deep venous system is at risk of thrombosis and pulmonary embolism [6].

Differential Diagnosis

Arteriovenous malformation (AVM)
Capillary malformation (CM)
Congenital hemangioma (CH)
Infantile hemangioma (IH)
Kaposiform hemangioendothelioma (KHE)
Lymphatic malformation (LM)

Diagnosis and Evaluation

Physical Examination

Venous Malformation

Approximately 90 % of VMs are diagnosed by history and physical examination [24, 25]. VMs can be small and well localized, or involve multiple tissue planes and important structures. Almost all lesions involve the mucosa, skin, and/or subcutaneous tissue; 50 % also affect deeper structures (e.g., muscle, bone, joints, viscera) [4]. The primary differential diagnosis is LM.
  • Findings:
    • VMs are blue, soft, and compressible; dependent positioning may enlarge the lesion.
    • VMs are usually > 5 cm (56 %) and solitary (99 %), they are located on the extremities (48.3 %), head/neck (30.3 %), trunk (16.6 %), or viscera (4.8 %) [16].
    • VMs are slow-flow lesions; hand-held Doppler excludes fast-flow vascular anomalies (e.g., AVM, hemangioma) [6].

Glomuvenous Malformation

Patients with a family history of VM should be evaluated for GVM. This condition is autosomal dominant, and individuals are counseled about the risk of transmitting the gene to their offspring [6]. Patients are also predisposed to develop new lesions [4, 12].
  • Findings:
    • Confined to the skin and subcutaneous tissue. Lesions are usually < 5 cm, and multiple (70 %) [4].
    • Involve the extremities (76 %), trunk (14 %), or head/neck (10 %) [4].
    • More painful than VM, especially on palpation [12].

Cutaneomucosal-Venous Malformation

Patients with a family history of similar lesions should be examined for CMVM. Individuals are counseled about the autosomal dominant inheritance pattern of this condition.
  • Findings:
    • Lesions are small (76 % < 5 cm), multiple (73 %), and located on the head/neck (50 %), extremity (37 %), or trunk (13 %) [4].
    • Unlike GVM, CMVM is not painful on palpation [4].

Laboratory Data

  • Large VMs are at risk for blood stagnation and subsequent coagulation.
    • Plasma D-dimers and fibrin split products may be elevated [26].
    • Antithrombin, fibrinogen, and factors V, VIII, and XIII can be low [26].
    • Prothrombin and partial thromboplastin time are normal [26].

Imaging Evaluation

Imaging is usually performed for large or deep VMs. Small, superficial lesions typically do not require radiographical work-up.

Ultrasonography (US)

US can be performed without sedation and demonstrates compressible, anechoic-hypoechoic spaces with septations [27]. Phleboliths are hyperchoic and cause acoustic shadowing [28].

Computed Tomography (CT)

CT may be indicated if there is bony involvement [6].

Magnetic Resonance Imaging (MRI)

MRI is usually obtained for large, deep, or problematic lesions to (1) confirm the diagnosis, (2) define the extent of the malformation, and (3) plan treatment [6]. VMs are hyperintense on T2-weighted images; phleboliths are hypointense [6]. VMs enhance following gadolinium administration [29].

Venography

Venography is not required for diagnostic confirmation, but is often performed during sclerotherapy .

Pathology

Histopathological diagnosis of VM is rarely necessary, but may be indicated if imaging is equivocal. Histopathologically, VMs show abnormal, thin-walled venous channels with irregular layers of smooth muscle (see Figs. 45.1 and 45.2) [1]. Vessels frequently have thrombi or phleboliths in their lumens (see Fig. 45.1a) [1]. GVMs are characterized by abnormal venous channels surrounded by characteristic cuboidal myoid “glomus” cells (see Fig. 45.3) [1].

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Dec 28, 2016 | Posted by in PEDIATRICS | Comments Off on Venous Malformations

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