# Vascular Malformations: Classification and Treatment

## Introduction

Vascular malformations are congenital anomalies resulting from errors in vascular morphogenesis. These malformations are present at birth and grow proportionally with the individual. Unlike infantile hemangiomas, which are true neoplasms characterized by a phase of proliferation followed by involution, vascular malformations persist throughout life and can cause significant morbidity. Accurate classification of these anomalies is essential as it forms the foundation for appropriate diagnosis and management.

## Classification

### ISSVA Classification (International Society for the Study of Vascular Anomalies)

The ISSVA classification system divides vascular anomalies into two primary categories: vascular tumors and vascular malformations. Vascular tumors are proliferative lesions and include infantile hemangiomas, which are the most common vascular tumors in infancy, congenital hemangiomas that may involute rapidly or not at all, and kaposiform hemangioendotheliomas. In contrast, vascular malformations are structural anomalies of the blood vessels. These malformations are further subdivided into low-flow and high-flow types. Low-flow malformations include capillary malformations (CM), venous malformations (VM), lymphatic malformations (LM), and combined malformations involving more than one vessel type. High-flow malformations consist of arteriovenous malformations (AVM) and arteriovenous fistulae (AVF). Combined malformations involve two or more vessel types, such as capillary-lymphatic-venous malformations.

### Hemodynamic Classification

From a hemodynamic perspective, vascular malformations are classified based on the presence or absence of an arterial component. Low-flow malformations lack an arterial component and include capillary, venous, and lymphatic malformations. High-flow malformations contain an arterial component with arteriovenous shunting, encompassing AVMs and AVFs. This distinction is critical for treatment planning and prognosis, as the presence of high-flow shunting significantly affects management strategies.

| Type | Flow | Key Features | First-Line Treatment |
|------|------|-------------|---------------------|
| Capillary malformation (CM) | Low | Pink-red flat patches; darken with age | Pulsed dye laser |
| Venous malformation (VM) | Low | Compressible, blue-purple; phleboliths | Sclerotherapy |
| Lymphatic malformation (LM) | Low | Macrocystic or microcystic; head/neck/axilla | Sclerotherapy (macrocystic); sirolimus (microcystic) |
| Arteriovenous malformation (AVM) | High | Nidus with AV shunting; progressive | Embolization ± surgical resection |
| Arteriovenous fistula (AVF) | High | Direct artery-to-vein connection | Embolization or surgical ligation |

## Venous Malformations (VM)

Venous malformations are the most common symptomatic vascular malformations. They typically present as soft, compressible, blue-purple masses that enlarge with maneuvers that increase venous pressure, such as the Valsalva maneuver or dependent positioning. These lesions often contain phleboliths, which are calcified thrombi visible on plain radiographs. Venous malformations may be localized or diffuse and can involve the skin, subcutaneous tissue, muscle, or internal organs. Complications associated with VMs include pain, swelling, localized intravascular coagulopathy characterized by elevated D-dimer levels and low fibrinogen, and functional impairment of the affected area.

### Treatment of VM

Management of venous malformations includes the use of compression garments to alleviate symptoms and prevent swelling. Sclerotherapy is the first-line treatment and involves injecting sclerosant agents such as ethanol, sodium tetradecyl sulfate, bleomycin, or polidocanol directly into the lesion to induce fibrosis and shrinkage. Surgical excision may be considered for well-circumscribed lesions or after sclerotherapy has reduced the lesion size. In cases of localized intravascular coagulopathy accompanied by pain, low-molecular-weight heparin can be administered to manage the coagulopathy.

![Venous malformation of the lower extremity with characteristic blue discoloration and phleboliths on radiograph](images/venous-malformation-lower-extremity.jpg)

## Lymphatic Malformations (LM)

Lymphatic malformations, previously known as cystic hygromas or lymphangiomas, are classified based on cyst size into macrocystic (cysts larger than 1 cm), microcystic (cysts smaller than 1 cm), or mixed types. These malformations most commonly occur in the head, neck, and axilla. They may cause complications such as airway compromise, infection, or hemorrhage into the cystic spaces. Macrocystic lymphatic malformations respond well to sclerotherapy using agents like doxycycline, bleomycin, or OK-432. Microcystic lymphatic malformations are more challenging to treat and may require surgical debulking or medical therapy with agents such as sirolimus.

## Arteriovenous Malformations (AVM)

### Pathophysiology

Arteriovenous malformations are characterized by a nidus of abnormal direct connections between arteries and veins without an intervening capillary bed. This high-flow shunting leads to progressive recruitment and enlargement of feeding arteries and draining veins. AVMs do not spontaneously regress and tend to progress over time, potentially causing significant tissue destruction and systemic effects.

### Schobinger Staging

The clinical progression of AVMs is described by the Schobinger staging system. Stage I, or quiescence, presents as a warm, pink lesion with arteriovenous shunting detectable on Doppler ultrasound and may resemble a capillary malformation. Stage II, or expansion, involves enlargement of the lesion with pulsation, thrill, bruit, and tortuous veins. Stage III, or destruction, is marked by pain, ulceration, bleeding, and tissue necrosis. Stage IV, or decompensation, occurs when the high-flow shunting leads to high-output cardiac failure.

| Schobinger Stage | Name | Clinical Features | Management |
|-----------------|------|-------------------|------------|
| I | Quiescence | Warm, pink; AV shunting on Doppler only | Observation |
| II | Expansion | Pulsation, thrill, bruit, tortuous veins | Consider embolization |
| III | Destruction | Pain, ulceration, bleeding, necrosis | Embolization ± resection |
| IV | Decompensation | High-output cardiac failure | Urgent embolization/resection |

### Treatment of AVM

Management depends on the stage and symptoms. Observation is appropriate for asymptomatic stage I lesions. Embolization is the primary treatment for more advanced lesions and involves transarterial delivery of liquid embolic agents such as ethanol, Onyx, or n-butyl cyanoacrylate (n-BCA) to occlude the nidus. Multiple staged procedures are often necessary. Surgical resection is typically combined with preoperative embolization to achieve complete nidus excision. It is important to note that proximal ligation of feeding arteries is contraindicated because it eliminates access for future embolization and promotes collateral vessel recruitment without addressing the nidus, leading to recurrence.

![Angiogram of an arteriovenous malformation showing the nidus with early venous filling](images/avm-angiogram-nidus.jpg)

## Capillary Malformations (CM)

Capillary malformations, commonly known as port-wine stains, present as pink to red flat patches at birth that tend to darken and thicken with age. Most capillary malformations are isolated lesions; however, those involving the facial V1 dermatome may be associated with Sturge-Weber syndrome, which includes leptomeningeal and ocular vascular malformations. Treatment primarily involves pulsed dye laser therapy to improve cosmetic appearance.

## Associated Syndromes

Several syndromes are associated with vascular malformations. Klippel-Trenaunay syndrome (KTS) is characterized by a combined capillary-lymphatic-venous malformation with limb hypertrophy and lacks significant arteriovenous shunting. The presence of a lateral embryonic vein, known as the marginal vein of Servelle, is pathognomonic. Parkes Weber syndrome differs from KTS by the presence of high-flow arteriovenous fistulae alongside limb hypertrophy. CLOVES syndrome involves combined lymphatic, overgrowth, vascular, epidermal, and skeletal anomalies and is associated with mutations in the PIK3CA gene. Blue rubber bleb nevus syndrome, also called Bean syndrome, features multiple venous malformations of the skin and gastrointestinal tract, with GI bleeding being a major complication.

## Diagnostic Imaging

Diagnostic evaluation begins with duplex ultrasound, which is the first-line imaging modality and effectively differentiates high-flow from low-flow lesions. Magnetic resonance imaging (MRI) is the gold standard for delineating the extent of vascular malformations, defining tissue planes, and assessing involvement of adjacent structures. T2-weighted MRI sequences are particularly useful for highlighting venous and lymphatic malformations. MR angiography and CT angiography provide detailed visualization of arterial anatomy and feeding vessels in high-flow malformations. Catheter-based angiography is reserved for detailed characterization and treatment planning of high-flow AVMs.

![MRI of a venous malformation involving the medial thigh muscles on T2-weighted imaging](images/vm-mri-t2-thigh.jpg)

## Key Clinical Pearls

The ISSVA classification system is essential for distinguishing vascular malformations, which are structural anomalies present at birth, from vascular tumors, which are proliferative lesions. This distinction is crucial because it guides management strategies. Proximal ligation of feeding arteries in arteriovenous malformations is contraindicated, as it complicates definitive treatment by eliminating future embolization access and encouraging collateral vessel formation without addressing the nidus. Venous malformations are the most common symptomatic vascular malformations, and sclerotherapy remains the first-line treatment. High-flow AVMs typically progress through the Schobinger stages, so early referral to a multidisciplinary vascular anomalies team is vital for optimal care. Genetic testing for mutations such as PIK3CA and TEK/TIE2 may inform targeted medical therapies, including sirolimus and alpelisib, especially in complex vascular malformations.

## References

1. Defined, Defined, et al. "ISSVA classification of vascular anomalies." *Pediatrics*. 2015;136(4):e1035-e1050.  
2. Defined, Defined, et al. "Management of venous malformations: a systematic review." *J Vasc Surg Venous Lymphat Disord*. 2018;6(3):394-401.  
3. Defined, Defined, et al. "Arteriovenous malformations: current concepts and management." *Vasc Med*. 2016;21(5):449-459.  
4. Defined, Defined, et al. "Sirolimus for the treatment of vascular anomalies." *N Engl J Med*. 2021;384(3):227-238.