Child's Nervous System

, Volume 26, Issue 10, pp 1417–1433

Update on pediatric extracranial vascular anomalies of the head and neck

Authors

    • Department of Dermatology, Division of Pediatric DermatologyThe Johns Hopkins Hospital
  • Monica Pearl
    • Department of Radiology, Division of Interventional NeuroradiologyThe Johns Hopkins Hospital
  • Aylin Tekes
    • Department of Radiology, Division of Pediatric RadiologyThe Johns Hopkins Hospital
  • Sally E. Mitchell
    • Department of Radiology, Division of Interventional RadiologyThe Johns Hopkins Hospital
Special Annual Issue

DOI: 10.1007/s00381-010-1202-2

Cite this article as:
Puttgen, K.B., Pearl, M., Tekes, A. et al. Childs Nerv Syst (2010) 26: 1417. doi:10.1007/s00381-010-1202-2

Abstract

Purpose

Vascular anomalies most frequently present at birth or in early childhood, and the craniofacial region is the most common site of involvement. A long history of misleading nomenclature born of confusion about the presentation and natural history of various vascular anomalies has made appropriate diagnosis difficult. The present article emphasizes the importance of clarity of nomenclature for proper diagnosis, both clinically and radiographically, to guide appropriate therapy. In addition, updates on clinical concepts, imaging, and treatment strategies will be discussed. Pediatric vascular anomalies can be divided into two broad categories: vascular tumors and vascular malformations. This biologic classification is based on differences in natural history, cellular turnover, and histology. An updated classification was introduced in 1996 by the International Society for the Study of Vascular Anomalies (ISSVA) to include infantile hemangioma variants, other benign vascular tumors, and combined lesions. Widespread confusion propagated throughout the literature and in clinical practice stems from the continued improper use of many of the terms used to describe vascular tumors and malformations ignoring their pathophysiology. This leads to errors in diagnosis and the dissemination of misinformation to patients and clinicians. Certain terms should be abandoned for more appropriate terms. The clinical presentation usually identifies what general type of vascular anomaly is present, either vascular tumor or vascular malformation. Imaging provides crucial information about the initial diagnosis and aids in follow-up.

Conclusions

Adoption and use of uniform nomenclature in the ISSVA classification system is the first vital step in correct diagnosis and treatment of often complicated vascular tumors and vascular malformations. A multidisciplinary team approach is necessary to provide optimal care for patients, and the necessity for specialists in all areas to communicate using standardized terminology cannot be overemphasized.

Keywords

Vascular anomalyHemangiomaVenous malformationArteriovenous malformationCapillary malformation

Introduction

Vascular anomalies most frequently present at birth or in early childhood, and the craniofacial region is the most common site of involvement [1]. A long history of misleading nomenclature born of confusion about the presentation and natural history of various vascular anomalies has made appropriate diagnosis difficult and has, in the past, limited discussion and understanding among physicians in different specialties. The term “hemangioma” is emblematic of the convoluted history of nomenclature, as it has been used to describe vascular lesions in varied locations, with varied behavior and varied implications for management. The present article emphasizes the importance of clarity of nomenclature for proper diagnosis, both clinically and radiographically, to guide appropriate therapy. In addition, updates on clinical concepts, imaging, and treatment strategies will be discussed.

Pediatric vascular anomalies can be divided into two broad categories: vascular tumors and vascular malformations. This biologic classification is based on differences in natural history, cellular turnover, and histology, first highlighted by Mulliken and Glowacki in 1982 [2]. An updated classification was introduced in 1996 by the International Society for the Study of Vascular Anomalies (ISSVA) to include infantile hemangioma (IH) variants, other benign vascular tumors, and combined lesions [3] (Table 1). Vascular tumors include IH, congenital hemangiomas including non-involuting and rapidly involuting variants dubbed non-involuting congenital hemangiomas (NICH) and rapidly involuting congenital hemangiomas (RICH), respectively, as well as kaposiform hemangioendotheliomas and tufted angiomas. Vascular malformations can be further subdivided into low-flow lesions (capillary, lymphatic, and venous malformations) and high-flow lesions (arteriovenous malformations (AVMs) and arteriovenous fistulae). Mixed lesions are common.
Table 1

Classification of Vascular Anomalies (simplified and adapted from the ISSVA 1996 classification)

Vascular tumors

Vascular malformations

Infantile hemangioma (IH)

 

Low-flow

 
 

Superficial

 

Capillary

 

Deep

 

Venous

 

Mixed

 

Lymphatic

Congenital hemangioma

RICH (Rapidly involuting congenital hemangioma)

High-flow

AVM

 

NICH (Noninvoluting congenital hemangioma)

 

AVF

Kaposiform hemangioendothelioma

±Kasabach–Merritt phenomenon

Combined

Capillary-lymphatic-venous (Klippel-Trenaunay)

Tufted angioma

±Kasabach–Merritt phenomenon

 

Capillary-venous (mild cases of Klippel-Trenaunay)

Pyogenic granuloma

  

Capillary-venous with arteriovenous shunting (Parkes-Weber syndrome)

Spindle cell hemangioendothelioma

  

Capillary-arteriovenous malformation (CM-AVM)

More rare hemangioendotheliomas (e.g.—Dabska tumor, lymphangioendotheliomatosis)

  

Arteriovenous malformation-lymphatic malformation (AVM-LM)

Widespread confusion propagated throughout the literature and in clinical practice stems from the continued improper use of many of the terms used to describe vascular tumors and malformations ignoring their pathophysiology. This leads to errors in diagnosis and the dissemination of misinformation to patients and clinicians. Certain terms should be abandoned for more appropriate terms (Tables 2 and 3).
Table 2

Nomenclature

Vascular tumors

Vascular malformations

Misleading term

Appropriate term

Misleading term

Appropriate term

Strawberry hemangioma

Infantile hemangioma

Port-wine stain

Capillary malformation

Capillary hemangioma

Infantile hemangioma

Lymphangioma

Microcystic lymphatic malformation

Cavernous hemangioma

Venous malformation

Cystic hygroma

Macrocystic lymphatic malformation at neck

 

Deep hemangioma

  
 

Mixed hemangioma

  
Table 3

Imaging features of vascular anomalies

Vascular anomaly

Flow

US

CT

MRI

Key feature(s)

Vascular tumor

Vascular malformation

     

Infantile Hemangioma

 

High

Variable echogenicity, high vessel density, high flow, low resistance, little/no AV shunting

Intensely staining lobular soft tissue mass

T1 isointense, T2 hyperintense, homogeneously enhancing soft tissue mass. Flow voids in and around lesion

Soft tissue mass. No phleboliths

Capillary malformation

Low

   

Clinical diagnosis

 

Lymphatic malformation

Low

Macrocystic: cystic mass, no flow, internal debris/fluid levels

Poorly circumscribed low attenuation mass, wall enhancement

T2 hyperintense, minimal/peripheral enhancement

None/minimal enhancement

Microcystic: hyperechoic, no flow

Fluid levels

 

Venous malformation

Low

Compressible, mixed echogenicity; low/no flow

Phleboliths, contrast enhancement

T2 hyperintense, patchy/avid enhancement

Enhancement, phleboliths

 

Arteriovenous malformation

High

Multiple hypoechoic vascular channels, no soft tissue mass; arterialized venous waveform

Dilated feeding arteries, rapid contrast shunting, enlarged draining veins

Multiple enlarged flow voids, no soft tissue mass

No soft-tissue mass; pulsatile venous flow

The clinical presentation usually identifies what general type of vascular anomaly is present, either vascular tumor or vascular malformation. Imaging provides crucial information about the initial diagnosis and aids in follow-up. Each imaging study should be tailored to provide important details such as size, location, anatomic extent, presence or absence of phleboliths, vascular anatomy, and proximity to vital structures. This is not only essential for interventional and surgical planning but also enables classification based on the ISSVA system. Utilizing more than one imaging modality may be necessary to obtain all necessary information.

A combination of imaging modalities is useful in the evaluation of vascular anomalies. Ultrasound with Doppler imaging is often the initial imaging modality sought for evaluation of vascular anomalies in pediatric patients because of its portability, accessibility, lack of ionizing radiation, and limited need for sedation. The interrogation of superficial and small vascular lesions, which may be inconspicuous on MRI, is well performed with ultrasound. Gray scale imaging defines the extent and compressibility of the lesion and determines whether a lesion is cystic or solid. Spectral and color Doppler are used to identify flow characteristics [4] and to differentiate arterial from venous flow. Disadvantages include operator dependence and limited ability to display the full extent of very large lesions.

MRI plays a major role because of its superior soft-tissue contrast and multiplanar capabilities. At our institution, the standard protocol for the evaluation of vascular anomalies of the head and neck includes tri-planar T2 with fat saturation, pre- and post-contrast axial T1, and post-contrast coronal and sagittal T1 weighted images with fat saturation. The MRI examination is tailored to the area of interest and special imaging techniques may be added to a particular study to answer the clinical question. We combine MRI with MRA and prefer to use time-resolved MRA, which enables evaluation of the vascular supply almost analogous to conventional X-ray angiography. Time-resolved MRA can be performed using 2D or 3D MRA acquisitions. 3D MRA is used to dynamically assess the vascular supply and define the arterial feeders and venous drainage of a vascular anomaly and to assess the normal arterial and venous anatomy, which helps guide the treatment plan, as well as monitor the effects of treatment.

CT plays a minor role in the evaluation of pediatric vascular anomalies, as most information may be obtained with ultrasound and MRI without the risk of ionizing radiation. It is, however, useful in cases where assessment of osseous involvement is crucial (sinus, skull base, cranium, mandible [5].)

Angiography is performed to confirm the diagnosis of a vascular lesion and to guide treatment. It remains the gold standard for diagnosis of high-flow vascular lesions [6] and reflects histopathology. It is also useful in the evaluation of atypical lesions to exclude a high-flow (AVM/AVF) component.

Vascular tumors

Infantile hemangioma

IH are the most common tumors of infancy, appearing in as many as 10% of Caucasian infants by 1 year of age [7], with more than double this incidence in preterm infants weighing less than 1,000 g [8]. Recent data suggest that low birth weight is the single most important predictor of IH, with the risk of IH increasing by 40% for every 500 g decrease in birth weight [9]. Additional risk factors for IH include prematurity, female sex, Caucasian ethnicity, multiple gestation pregnancy, advanced maternal age, and placental abnormalities including placenta previa [10]. Most hemangiomas appear in the first 6 weeks of life. They follow a triphasic pattern of evolution, characterized by proliferation, plateau and involution. In the first 2 months of life, nearly all IH double in size, and most IH reach 80% of their maximum size between 3 and 5 months of age [11]. It is important to realize that complete involution does not necessarily indicate complete resolution, as up to 40% of IH will leave residual textural changes and scarring characterized by fibrofatty residuum.

The head and neck regions are involved most frequently (60% of cases), followed by the trunk (25% of cases), and extremities (15% of cases [12, 13].) Morphologically, IH can be subdivided into superficial, deep and mixed (containing both superficial and deep components) lesions. Further, they should be designated as focal (those which appear to arise from a single point), segmental (those occupying an apparent developmental unit), and indeterminate (those which likely occupy a “sub-segmental” distribution). Segmental and deep IH are known to have a longer proliferative phase. Segmental IH are postulated to arise from embryonic developmental units or placodes, though their exact origin is not fully discerned. They do not follow nerve root distribution, nor do they follow Blaschko’s lines, which are developmental embryonic cleavage lines recognized in many disorders of the skin.

The concept of segmental IH is most important as it pertains to PHACE syndrome, which is a combination of posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta, and eye abnormalities. Sternal cleft and supraumbilical raphe can also be seen, and the disorder is sometimes referred to as PHACES. Diagnosis requires the presence of a facial segmental IH and one extracutaneous anomaly [14]. Typical IH have a female to male ratio of 2 to 3 to 1 in most series; in contrast, PHACE has a striking female to male ratio of 9 to 1. Because of associated anomalies, patients suspected of having PHACE syndrome are most likely to require imaging. Mapping of common patterns and morphologic appearance of IH on the face has helped to categorize IH into higher risk and lower risk categories [15]. Those infants with frontotemporal and frontonasal IH (segments 1 and 4) have a higher correlation with structural cerebral and cerebrovascular anomalies, while those with mandibular (segment 3) or “beard” distribution IH are at higher risk for ventral and cardiac defects, along with airway IH [16]. Segment 2, which corresponds to the maxillary face, appears to be a lower risk segment for IH involvement.

Neurologic sequelae of PHACE are the most ominous and the most common associated finding and can present as structural anomalies of the brain and cerebral vasculature or as progressive stenoses or occlusions of cerebral arteries. Both moya-moya like vasculopathy and arterial ischemic strokes have been reported [17, 18]. There has been one report of PHACE associated with sinus pericranii and agenesis of the corpus callosum [19]. There are also several reports of intracranial hemangiomas, most diagnosed based on imaging findings, and one recent report of four infants suggesting that location in the internal auditory canal or cerebellopontine angle may be a more common location for these extra-axial enhancing lesions, and can be associated with PHACE [20]. The largest series of IH involving the neuraxis of 15 patients, reported eight patients with intracranial IH, six with intraspinal IH, and one patient with IH in both locations [21]. According to Pascual-Castroviejo, the most common arterial anomalies in PHACE are persistence of the trigeminal artery, hypoplasia or agenesis of one carotid or vertebral artery. Persistence of embryonic vascularization has also been reported [22].

At our institution, we prefer to initiate imaging in asymptomatic infants with transcranial Doppler ultrasound in infants younger than 6 months of age and echocardiography. MRI/MRA is pursued if the study is either abnormal or suboptimal. All infants suspected of PHACE receive MRI/MRA after 6 months of age.

The majority of IH do not require medical or surgical intervention, but a significant subset prove to be problematic either because of size, location, ulceration, associated anomalies (as with PHACE syndrome), or a combination of these factors. Ulceration is the most common complication. Large IH, those on the face, and segmental IH are significantly more likely to require treatment [23].

Imaging is not required for the majority of IH but can be useful to confirm the suspected diagnosis in atypical lesions and for deep lesions to determine their extent and to exclude atypical vascular tumors (suspected kaposiform hemangioendothelioma), soft-tissue malignancies, and vascular malformations or to exclude associated anomalies with PHACE syndrome. It is also important for preoperative planning in many cases in the head and neck. Imaging hallmarks include a homogeneous, solid, parenchymal mass with increased vascularity, and less frequently high-flow vascular supply and drainage [24].

The evolutionary phase of the hemangioma (proliferation, plateau, or regression) determines the imaging features. During the proliferative phase, ultrasound shows a well-circumscribed mass with variable echogenicity. Increased color flow, high Doppler shift, and low resistance represent the arterial feeder within the infantile hemangioma. Unlike congenital forms, arteriovenous shunting is not observed [4] (Fig. 1). During regression, the number of vessels and size of the lesion decrease, but the high-frequency Doppler shifts may remain stable [24].
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Fig. 1

Infantile hemangioma. Ultrasound of IH in the proliferative phase: a Well-circumscribed mass with variable echogenicity. b Arterial flow: high vessel density (>5 vessels/cm2), and high Doppler shift (>2 kHz), are observed with low resistance. Note the absence of arteriovenous shunting

The characteristic MRI findings during the proliferative and plateau phases (Fig. 2) include a focal, lobulated, soft-tissue mass that is isointense to muscle on T1-weighted imaging, hyperintense on T2-weighted imaging with avid, homogeneous enhancement [25]. Multiple enlarged, high-flow vessels are present in the lesion and are seen as flow voids on spin-echo sequences [6]. CT findings include a homogeneous mass with intense, persistent enhancement, usually in a lobular pattern [4]. During regression, decreased vascularity and enhancement is seen on MRI with progressive fibrofatty replacement of the tumor. Phleboliths and calcification are not features of infantile hemangioma [6].
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Fig. 2

Infantile hemangioma. MRI findings (a) and clinical image (b) of IH during the proliferative and plateau phases. a MRI shows a focal, well-circumscribed, lobulated, hyperintense on T2-weighted imaging. Note the diffuse, avid, and homogenous enhancement on post-contrast T1-weighted image

Conventional angiography is rarely needed for the diagnosis of hemangioma but is performed prior to embolization for associated spontaneous hemorrhage or congestive cardiac failure resistant to medical treatment. Angiographic features include a well-circumscribed, lobular mass with an intense, staining parenchymal component (Fig. 3). An arborizing branch pattern is typical, with smaller branches originating perpendicular to the main pedicle. Prominent draining veins may be present. Less intense tissue staining is seen during regression [26].
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Fig. 3

Infantile hemangioma: Lateral view and 3D rendering from left maxillary artery angiography show a well-circumscribed, lobular mass with an intense, staining parenchymal component

If treatment is necessary, the vast majority of IH are treated medically during the proliferative phase and often into the plateau and early involutional phases, depending on lesion location, size, and associated complications. The de facto standard of care for several decades has been high dose (generally 2 to 3 mg/kg/day) corticosteroids. Interferon-α was considered the second line therapy, for those patients who experienced severe side effects from high dose corticosteroids, until reports surfaced in the 1990s showing sometimes irreversible spastic diplegia in up to 20% of treated infants, with increased risk in those infants under 12 months of age (i.e., those most likely to receive such treatment.) Vincristine subsequently became the second line therapy [2729].

Since publication of a small series of patients in July 2008 who showed dramatic response to treatment with propranolol [30], a nonselective beta-blocker, there has been a dramatic paradigm shift at many institutions and among physicians who care for these patients. Case reports and small case series continue to be published echoing the apparent efficacy and safety of propranolol over traditional therapies [3138].However, it is important to note that randomized controlled trials are currently lacking, though enrollment is currently underway for two such multicenter trials (clinicaltrials.gov). Despite the lack of randomized trial data, we currently advocate the use of propranolol as first-line monotherapy in the vast majority of IH patients, after a thorough discussion of risks and benefits of therapy. At our institution, in collaboration with pediatric cardiology, we admit patients for 48 hours to obtain baseline electrocardiogram and specialty consultation if necessary. Propranolol is initiated at 1 mg/kg/day divided every 8 hours and increased to the goal dose of 2 mg/kg/day starting with the fourth dose until the sixth dose. Patients are monitored closely for changes in blood pressure, heart rate and blood glucose. Most infants require therapy for approximately 6 months or until maximum clinical benefit is achieved and proliferative phase has ended.

Treatment of infantile hemangiomas beyond medical treatment includes percutaneous or endolesional laser [39], embolization, percutaneous injection of medications or sclerosants, and surgery. These treatments are often utilized in an effort to debulk large lesions, treat lesions that interfere with function, encourage early involution, and treat complicated hemangiomas not responding adequately to medical therapy.

Location is an important factor in treatment for IH located near the eye or on the nose. Those that obstruct vision require treatment urgently as pharmacological [40] intervention or surgical removal [41], so that visual development is not impeded. IH located on the tip of the nose may affect nasal growth and also may require more urgent treatment [42].

Airway hemangiomas are also a location requiring careful attention and possible early treatment [43, 44].

Ulceration of an IH may result in bleeding. Very rarely, this bleeding can be severe, requiring blood transfusion. This complication may require embolization or surgery for control [45]. In summary, treatment of hemangiomas beyond medical therapy is varied depending on a variety of complicating issues such as size, location, and ulceration. However, with the advent of propranolol therapy looking very promising with few side effects, we may see a shift in hemangioma therapy as the clinical trial results develop.

Congenital hemangiomas

Congenital hemangiomas are subdivided into NICH [46] and RICH [47] variants. These are both significantly rarer than IH. Both present fully formed at birth with little or, more often, no postnatal growth, and can often be seen on prenatal ultrasound as early as 12 weeks gestation [47] (Fig. 4). Postnatal growth is reported in NICH, but clinically little or no growth after birth is the rule for both NICH and RICH, making definitive diagnosis difficult in the neonatal period. Unlike IH, RICH are equally common in male and female infants, while NICH are reported to be slightly more common in males. Both variants are distinct from IH, most notably in that they lack staining for GLUT-1, which is a defining characteristic for IH [48]. Clinically, RICH and NICH appear similar, often presenting as violaceous gray tumors with prominent overlying veins or telangiectases which extend beyond the periphery of the lesion. Many have a lighter or bluish halo on the surrounding skin. In practice, RICH and NICH are often only able to be fully distinguished in retrospect, as the former involutes by 12 months of age, and the latter involutes either partially or not at all and requires surgical excision. RICH, too, can leave significant textural change necessitating reconstructive surgery after involution. In certain cases, lesions that initially behave as RICH will involute to a point and then stabilize, mimicking NICH [49, 50]. RICH may reach maximum size in the last weeks of the third trimester and have already begun involution at the time of birth. In rare instances, RICH has been reported to be associated with high output heart failure, sometimes requiring embolization of shunts. A relatively short-lived thrombocytopenia secondary to localized intravascular coagulation, not to be confused with Kasabach Merritt phenomenonon, may also occur [51].
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Fig. 4

Rapidly involuting congenital hemangioma: Fetal ultrasound with 3D reconstruction (a) and clinical presentation of RICH at birth (b). Note apparent onset of involution prior to birth

Congenital hemangiomas are similar in imaging appearance to infantile hemangiomas except that congenital hemangiomas may show arteriovenous shunting and arteriovenous fistulae more often than the infantile forms (Fig. 5). RICH may also exhibit aneurysms, cysts, or calcifications [46, 49]. Ultimately, they are differentiated based on the natural history of the lesion.
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Fig. 5

NICH. AP (a) and lateral (b) views from a left external carotid artery injection show multiple angiographic blushes involving the left superior and inferior lips, left cheek, areas around the left maxillary artery, and infraorbital regions. Note the arborizing branching pattern and the early venous drainage suggestive of a high flow lesion. c Magnified view shows a well-circumscribed, lobular mass with a dense, staining parenchymal component

Kaposiform hemangioendothelioma

Kaposiform hemangioendothelioma (KHE) are rare vascular tumors which typically present in the first 2 to 3 years of life and can be congenital. They are rare in the head and neck, with only nine cases reported in the literature [52]. They can be locally aggressive but are not believed to metastasize. Aside from local destruction, the most common and potentially life-threatening complication is the Kasabach–Merritt phenomenon, characterized by a severe coagulopathy thought to be due to platelet trapping within the tumor. It is important to note that Kasabach–Merritt phenomenon occurs in KHE and in tufted angioma (thought by some to be a milder variant of KHE) but does not occur in IH. KHE has also been reported to cause hemothorax [53]. Clinically, KHE may be cutaneous or deep seated, often in the retroperitoneum or mediastinum. Cutaneous lesions are infiltrative bluish red plaques or nodules, and deeper soft tissue KHE may present only as masses with induration. Regression does not typically occur, and surgical resection is the treatment of choice for KHE if feasible. Medical therapy is disappointing, and corticosteroids, interferon-α 2A, vincristine, or a combination of vincristine, cyclophosphamide, actinomycin D, and methotrexate have been used [54] in addition to radiation therapy. Embolization has also been reported as a part of a multiple modality therapeutic approach. We have recently had modest success in the treatment of a biopsy proven nonlife-threatening KHE on the arm with propranolol, with decrease in size and softening, though without full involution.

MRI demonstrates ill-defined tumor borders with nodules and subcutaneous stranding. KHE are heterogeneously hyperintense on T2 weighted fat-suppressed images and isointense on T1weighted images and enhanced inhomogeneously [55].

Vascular malformations

Low-flow lesions

Venous malformation

Venous malformations (VMs) are the most common type of vascular malformation and present as soft, compressible, blue or blue purple lesions. Many present with a segmental appearance. Most VM are sporadic, but there are multiple reports of autosomal dominantly inherited VM, which can often be multiple. In the head and neck, VMs are especially problematic because of the propensity to involve deeper structures including muscle, orbit, and underlying bones. Patients often give a history of swelling when the head is in a dependent position, which can be tender or painful. Facial deformity is common and slowly progressive over the life of the patient. Difficulties with feeding, sleep apnea, bite deformities, and enophthalmia can occur depending on the location and extent of the lesion. Extensive cephalic VMs can be associated with intracranial vascular malformations.

Venous malformations are seen as compressible, mixed echogenicity lesions with either low flow, pure monophasic flow, or no flow on ultrasound. If a biphasic component to the vascular flow pattern is noted, a mixed vascular malformation should be considered (capillary-venous or lymphatic-capillary-venous malformation [56]). CT demonstrates lesion extent, phleboliths, and slow, peripheral contrast enhancement [4].

MRI is the best imaging modality to define lesion extent, depicting their infiltrative nature and violation of tissue planes. Variable signal intensity may be present on T1 and T2 weighted sequences due to the presence of hemorrhage and thrombosis, but venous malformations most often are intermediate signal intensity on T1 and hyperintense on T2 [57].Characteristic features of venous malformations include a lobulated mass with internal serpiginous vessels, rounded signal voids representing phleboliths, and variable contrast enhancement (Fig. 6). Contrast enhancement is a key feature of venous malformations distinguishing them from other nonenhancing cystic malformations including lymphatic malformations, branchial cleft cysts, foregut duplication cysts and thyroglossal duct cysts [6]. Intraosseous involvement may be apparent as focal areas of cortical thinning with increased trabeculae [58]. Fluid levels may be present, but this is a rare occurrence [25] and more characteristic of lymphatic malformations. High-flow and flow-related enhancement are atypical features of true venous malformations [6].
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Fig. 6

Venous malformation. Angiogram: a lateral scout film shows multiple calcified phleboliths in the more superficial component of the venous malformation. b Lateral right external carotid artery angiography shows the typical avascular appearance of a venous malformation. A small superiorly oriented branch of the facial artery is seen with a direct fistulous connection to a small vein within the deeper component of the mass. c Delayed phase shows puddling of contrast within the venous channels, as would be expected after direct venous puncture. d MRI: Large, invasive, lobular, T2 bright mass with avid enhancement is noted to involve the right maxillary sinus and right inferior orbit, with extension into the right nasal cavity and anterior nasopharynx. Multiple round hypointense foci represents the pheboliths. Post-contrast T1-weighted image shows a small serpiginous vessel coursing medial to the phebolith which may represent the level of shunting documented on the angiogram

Angiography is rarely needed for the diagnosis but may be necessary when other noninvasive imaging studies are indeterminate or when associated anomalies such as sinus pericranii or small AVF are present (Fig. 6). The angiogram may show puddling of contrast material within sinusoidal spaces and abnormal veins [6], but findings are generally normal. Direct intralesional puncture and injection of contrast better illustrates the characteristic features of the lesion: tortuous, dilated venous channels [26].

Imaging findings may change over time, either spontaneously or from treatment related thrombosis or developing phleboliths. Treated venous malformations usually show a reduction in size, but residual signal abnormality and T2 hyperintensity are common in large, diffuse lesions. Patchy T2 hypointense areas are also common, representing blood clots and possibly fibrotic change from sclerotherapy. Ultrasound features of a sclerosed venous malformation include mixed echogenicity and acoustic shadowing.

Treatment of venous malformations was primarily surgical resection [59] in the past, with evolution more recently to primary percutaneous sclerotherapy. The decision for surgical resection is often dependent on location of VM, the tissue planes involved, and depth of tissue involvement.

Location of the venous malformation is important in the decision to treat and in determining the best treatment modality. For example, venous malformations of the orbit are unique. There is little room for swelling which occurs post-sclerotherapy. Surgical resection with or without preoperative cyanoacrylate glue embolization may be a good way to safely remove these [6064]. If vision is not affected, there may be a decision not to treat. In the airway, treatment of venous malformations with visually guided percutaneous sclerotherapy has been described, though laser therapy has proven effective in the hands of the otolaryngologist [65]. Venous malformations located outside but near the airway may require prolonged intubation or tracheostomy to protect the airway after sclerotherapy.

Percutaneous sclerotherapy involves accessing and monitoring injection of the lesion using ultrasound and fluoroscopic guidance [5]. MRI guidance has also been described [66].

Sclerotherapy agents for percutaneous therapy are varied, a result of availability differences in different countries, and also a result of an effort to find the best agent for the most effective treatment with the fewest complications and the lowest recurrence rate. Ethanol has been considered the most potent sclerosing agent, with the lowest recurrence rate. However, it must be used with great care by experienced physicians to avoid extravasation or transmural egress which can result in damage to tissues outside the venous malformation. In addition, the dose total should not exceed 1 ml/kg, and the volume administered should be given in small increments over time (0.1 ml/kg every 5 min) to avoid overwhelming the cardiovascular system with large volumes. Sotradecol 3% has been utilized for sclerotherapy of VMs, and foaming of sotradecol with ethiodol has been reported to improve results possibly due to less layering of agent with improved VM endothelial surface contact [67].

Complications of sclerotherapy for VMs include neuropathy which is usually transient, skin necrosis usually related to direct skin involvement by the VM, swelling, muscle contracture if extensively treating intramuscular VM [5]. Hemoglobinuria can result from hemolysis [68, 69]. Cardiovascular collapse has been a significant concern [70], especially with ethanol, though it is very rare, and in our opinion may be able to be avoided by very small volumes of sclerosant over time so as not to overwhelm the cardiovascular system [71].

Other treatments include percutaneous laser [72, 73], intralesional laser [74], and percutaneous radiofrequency ablation [75].

In general, treatment of venous malformations requires a multidisciplinary team. Often, treatments need to be combined for most effective therapy. The individual patient’s venous malformation characteristics, the presence of fibro-fatty tissue compared to vascular tissue, the tissue planes involved, and the degree of connection to the normal venous system are among many factors to be considered in determining the safest, most effective treatment. Results vary from series to series, and probably reflect the complexity of venous malformations and the variety of treatments and sclerosing agents in use [5, 68, 69].

Capillary malformations

Capillary malformations, known in traditional nomenclature as port wine stains, are limited to the superficial layers of the skin but can slowly progress over years to become thickened, nodular, and disfiguring. They occur in three in 1,000 newborns. Most importantly, depending on location, CM can suggest underlying associated syndromes including Sturge–Weber syndrome (SWS), Klippel–Trenaunay syndrome or Parkes–Weber syndrome, or underlying spinal dysraphism. Discussion here will be limited to facial CM as Klippel Trenaunay and Parkes–Weber syndrome generally affect the lower limbs.

SWS is characterized by facial CM and ipsilateral ocular and leptomeningeal anomalies. Up to a quarter of infants with CM in the distribution of the segment, one of the trigeminal nerves (V1) is reported to have neurologic and/or ocular involvement typical of SWS [76]. CM in the V2 and V3 distribution are less commonly associated with SWS, but appropriate workup should be performed. The disorder is sporadic with an unknown etiology, but involved tissues are all derived from the neural crest. Glaucoma and choroidal vascular malformation may be present in the affected eye. The majority of neurologic involvement occurs in the occipital region, consisting of a capillary-venous malformation. Seizures, hemiparesis or hemiplegia, migraines, developmental delay, and behavioral difficulties occur. Referral to dermatology (for pulsed dye laser therapy of the CM), ophthalmology, and neurology, in addition to imaging for evaluation of possible underlying abnormalities, should be performed in patients at risk.

Lymphatic malformation

The pathogenesis of lymphatic malformations is thought to be a developmental defect during embryonic lymphangiogenesis. One theory states that segmented buds of lymphatic tissue become sequestered from the normal lymphatic system [77], and cause malformations, which can be microcystic, macrocystic, or combined. They occur with equal frequency in males and females. The vast majority of LMs are superficial, with cutaneous and mucous membrane involvement, but approximately 10% involve the viscera. Macrocystic LMs most frequently involve the neck, lateral chest, and axilla. Ultrasound is often able to document large LMs as early as the fourth month of gestation, and in this setting, LMs can be associated with Down, Turner, or Noonan syndrome. Clinically, a large soft compressible, sometimes translucent mass is evident under the skin surface. Hemorrhage into a cyst of an LM can result in dramatic changes in lesion size, and the swelling is often tender, firm and ecchymotic. Infection is a common complication and can result in dramatic fluctuation in size as well. Purely microcystic LM are commonly encountered in clinical practice and typically present as a plaque with clear or hemorrhagic coalescing vesicles. There is typically a deeper component than is appreciable on clinical examination and attempts at excision almost uniformly result in recurrence, even after all visible evidence of the LM is removed. Bleeding, oozing, infection and pain can often complicate the clinical picture. Mixed microcystic and macrocystic LMs are common, especially in the head and neck region. On the face, large LM often results in maxillary and mandibular deformities. Tongue involvement and parapharyngeal extension can threaten the airway, especially with expansion from hemorrhage into the malformation or in the setting of infection. Massive cervicofacial LMs (Fig. 7) are severely function threatening and ultimately life threatening in most cases. The recently described CLAPO syndrome was proposed by Lopez-Gutierrez and Lupunzina to explain the association they noted in six patients with lower lip CM, face and neck LM, facial and limb asymmetry, and partial or generalized overgrowth. This syndrome in essence constitutes a mixed capillary-lymphatic-venous malformation with asymmetric overgrowth [78].
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Fig. 7

Macrocystic cervicofacial lymphatic malformation. a MRI findings: large cystic mass that extends from the soft tissues of the orbits to deep soft tissues of the neck. The mass is very large and infiltrative in nature. There are multiple T2 bright, large cysts of various different sizes. Note the bright signal on precontrast T1 that represents hemorrhage. Post-contrast T1-weighted image reveals enhancement of the cyst walls. Relatively, homogeneously enhancing areas in between large cysts may represent the enhancing wall of the microcysts. b Clinical presentation

Although rarely performed, lymphatic malformations appear as avascular lesions on angiography. A prominent capillary blush may be seen in those lesions associated with bleeding [26]. Imaging of lymphatic malformations may identify an unsuspected deep component or an infiltrative nature, as they may not be confined to a single anatomic compartment [79]. Imaging also provides valuable information to narrow a broad differential diagnosis of cystic lesions in the neck, which includes branchial cleft cyst, thyroglossal duct cyst, and foregut duplication cysts.

The subtype of lymphatic malformation determines the imaging features, although they are often combined lesions with both macrocystic and microcystic components within the same lesion. Macrocystic lesions appear on ultrasound as multilocular cystic masses without flow except in variably thickened septa. Internal debris or fluid levels from hemorrhage are characteristic but not required for the diagnosis. Microcystic lymphatic malformations are hyperechoic on ultrasound due to the numerous interfaces encountered by the ultrasound beam and show no flow in the lesion on Doppler imaging. The CT appearance of a lymphatic malformation is of a poorly circumscribed, multiloculated, low-attenuation mass with wall enhancement [4]. Higher attenuation lesions can be seen in the presence of infection or hemorrhage [79].

Macrocystic lymphatic malformations have clearly defined cysts and septa on MRI (Fig. 7). The cysts are T1 hypointense and T2 hyperintense with or without fluid levels. Fluid levels are thought to be secondary to hemorrhage and/or proteinaceous content, and presence of fluid-fluid levels is neither pathognomonic nor mandatory for diagnosis. Microcystic lymphatic malformations also appear as T1 hypointense and T2 hyperintense areas, but discrete cysts are very difficult to identify given the microcystic size. Hence, a microcystic component of a LM may be confused with other vascular malformations such as a venous malformation, especially in post-contrast images [6]. The walls and septations of the cysts, not the cystic spaces themselves, may enhance which is an important feature in differentiating them from venous malformations. Increased enhancement may be seen after treatment (surgical or intralesional injection), in mixed lymphatic-venous malformations [58], or especially in the setting of infection or inflammation [5]. High-flow vascular flow voids and flow related enhancement are not features of lymphatic malformations [6].

Treatment of lymphatic malformations depends on the size of the malformation, the extent, the number of tissue layers involved, the location of the malformation, and the symptoms. Lymphatic malformations in the skin or mucosa may be treated with laser therapy [80] to decrease the clear or blood-tinged drainage of the skin cysts. Deeper lesions that cannot be reached by laser have been treated with a variety of treatments, including intralesional laser [39, 81], radiofrequency ablation [82, 83], surgery [84], and a variety of sclerotherapy agents [8590]. In addition, treatments are often combined for improved outcome. The goals of any therapy are to debulk the large lesions, reduce lymph leakage or bleeding, and to prevent recurrence.

Surgical resection has been the standard treatment for many years. Complications of surgery include damage to surrounding nerves and blood vessels, recurrence due to incomplete resection, and scarring [91]. This has led to more recent interest in sclerotherapy as a primary treatment for some lymphatic malformations. Choice of a sclerotherapy agent is often more dependent on specialist preference, international availability, or trends in treatment than on a clear, obvious advantage of one agent over another. There are no prospective randomized trials comparing various agents.

OK-432 has received a great deal of focus in the otolaryngology literature [90]. The largest trial to date prospectively randomized patients over a 6-year period, into immediate and delayed treatment groups, the latter of whom were observed for spontaneous resolution. Patients underwent four injections, 8 weeks apart. Results demonstrated complete or substantial response in 94% of patients with macrocystic LM, and 63% of patients with mixed macrocystic-microcystic LM. Spontaneous resolution was rare, occurring in fewer than 2% of patients. Recurrence rate was 9% over a mean follow-up of 2.9 years. Patients did experience a post treatment inflammatory response that peaked within a few days and resolved over the next 2 weeks. Because OK-432 is lyophilized low-virulence group A Streptococcus pyogenes incubated with penicillin, patients must be screened for penicillin allergy. A review of the literature for OK-432 reviewed 111 patients from 10 centers, demonstrating an excellent response in 88%, good response in 8%, poor response in 4%, with recurrence of 5% [86]. However, OK-432 is not available for clinical use in the USA outside of the otolaryngology trials.

Ethanol has been a useful agent for sclerotherapy for many years. It is a potent sclerosing agent that denudes the endothelium by causing rapid cellular dehydration and precipitation of protoplasm. Ethanol is effective in sclerosing lymphatic malformations, though concerns for safety have been raised in a retrospective analysis of LM treatment with various agents [92]. In one report, ethanol has been used following sotradecol injection and aspiration with the theory that the sotradecol increases endothelial permeability to ethanol [87]. Limitations on volume that can be injected (<1 ml/kg) limit the use of ethanol in large cysts in young patients.

Doxycycline has been effective also in LM sclerotherapy, with concentration of 10 mg/ml and maximum dose of 20 mg/kg. A retrospective review of 60 doxycycline sclerotherapy procedures in 41 patients [88], demonstrated a complete/excellent response in macrocysts and combined lesions, and a good response in microcysts. Single or intermittent injections of relatively large volumes were safe with no dental staining. There was one major complication of Horner’s syndrome, and exposure of nerves to doxycycline must be avoided. Doxycycline has been recommended by some for primary treatment in LM, with excellent safety and efficacy [85].

In general, LM sclerotherapy effectiveness is less dependent on the agent used, in our opinion, and is more related to the operator’s ultrasound skills, ability to access the cysts, and to the use of catheters when possible for good drainage of the cysts pre- and post-sclerotherapy. The results of most sclerotherapy series confirm that the larger cysts have the best results. However, even microcysts can be treated percutaneously, with the only limitation being the ability to find and access these microcysts. In addition, once a microcystic LM is accessed and confirmed with contrast, others enlarge through the connections between cysts, improving the ability to access even more microcysts.

Mixed lesions

Mixed lesions are common among vascular malformations, and can involve any combination of capillary, lymphatic, and venous components. The imaging characteristics represent a combination of the findings described in each respective section above.

High-flow lesions

AVM

AVMs of the head and neck are the most aggressive of all the vascular malformations and can lead to dramatic deformity, functional impairment, and possible mortality. They are high-flow lesions characterized by direct connections between arteries and veins without an intervening capillary bed. The majority are congenital and noted at birth, with smaller percentages noted during childhood or in adult life. Among head and neck AVMs, nearly 70% involve the midface. The cheek, ear, nose, and forehead are common sites of involvement [93]. Invasion of the underlying bone is commonly seen and complicates therapy. A clinical staging system describes the progression of these lesions as follows: Stage I AVMs—quiescent, clinically warm pink-blue macules; Stage II—expansion pulsations, thrills, or bruits; Stage III—destruction of surrounding tissues, pain, ulceration and/or hemorrhage; Stage IV—congestive heart failure secondary to decompensation from overwhelming growth. Puberty, pregnancy, and trauma are all known to result in increased growth and progression.

Recent work has elucidated that RASA1 gene mutations cause the autosomally dominantly inherited capillary malformation-arteriovenous malformation (CM-AVM) syndrome (OMIM #608354.) Clinically, these patients present with small, randomly arranged, multifocal CMs ranging in size from 1 to 15 cm, described as pink, red, brown or gray, often with a surrounding white halo; these unique CMs are thought to be pathognomonic. In a recent report of 42 RASA1 mutations in 44 families, a third of patients presented with high flow vascular malformations, which presented as intracranial, extracranial, or peripheral lesions in different patients, suggesting a high degree of heterogeneity in the presentation. Neural tumors similar to those seen in neurofibromatosis types 1 and 2 are also reported in CM-AVM patients, suggesting that neurologic evaluation may be necessary in these patients [94].

Gray-scale imaging features of AVM include a heterogeneous lesion with multiple hypoechoic vascular channels [24] without a well-defined soft tissue mass. High flow, low-resistance arteries and an arterialized waveform in enlarged draining veins [4, 95] are characteristic features. The pulsatile venous flow is always present in AVMs, contrary to hemangiomas [4].

Contrast enhanced CT of AVMs shows numerous enlarged feeding arteries with rapid contrast shunting into enlarged draining veins without significant tissue enhancement usually present within a normal capillary network [96]. MRI characteristics are dilated feeding and draining vessels without a discrete soft-tissue mass [25]. The high-flow vessels appear as flow voids on spin-echo imaging, which may be interspersed with small punctate areas of high signal intensity due to hemorrhage and thrombosis [97], with corresponding hyperintensity on flow-enhanced gradient echo sequences. [6] The absence of a discrete soft tissue mass differentiates an AVM from an infantile hemangioma [79] (Fig. 8).
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Fig. 8

Multiple sequential images from a right occipital artery injection show hypertrophied right occipital artery feeders to a large right pinna and facial AVM with rapid venous shunting across a large nidus

Angiography is essential for treatment planning to determine the extent of the AVM, evaluate the flow dynamics, and to precisely define the vascular anatomy. Classic angiographic features are multiple hypertrophied feeding arteries rapidly shunting into enlarged draining veins across a nidus [6, 26] (Fig. 8).

Treatment of extracranial arteriovenous malformations of the head and neck requires a decision concerning whether the AVM is to be treated surgically with preoperative embolization, or whether the AVM is to be treated by embolization alone [98]. Preoperative embolization for facial AVMs is usually done at our institution using cyanoacrylate glue to fill the malformation [99]. Treatment by embolization alone requires extreme precision for occlusion of only the nidus, or arteriovenous shunts, while sparing normal nutrient arteries. Also, the agent for treatment by embolization alone varies in the literature, though ethanol has been considered the most potent sclerosant for permanently occluding AVMs [98]. In our opinion, particulate embolization of AVMs is not appropriate due lack of accuracy in sizing particles to the AVM shunts, with tendency to cross the malformation to the lungs.

Extracranial AVMs also differ from intracranial AVMs in that the venous side of the AVM can be occluded, and indeed, is often a very safe and effective way to occlude extracranial AVMs. The other significant issue in head and neck AVM embolization is to be knowledgeable of the connections between the external and internal carotid vessels, which require great care to avoid complications [100].

Specific sites of involvement, such as ear [101103], tongue [104, 105], mandible or maxilla [106], may require specific techniques for optimal treatment. Each patient must be evaluated individually by a multidisciplinary team to determine appropriate management.

Extracranial arteriovenous malformations are difficult to cure, with a tendency to recruit new feeders [93]. These patients require long-term follow-up and management.

The key to embolization treatment of AVMs, in an effort to prevent collateral recruitment, is to find the actual congenital shunting site or sites between artery and vein, and to focus on occluding only the shunts, whether these are direct shunts or a tangle of malformed vessels (nidus). Once the shunts are occluded, the AVM arterial feeders will close down. This is easier with fewer shunts, and much more difficult with more numerous shunts, unless the shunting is into a single draining vein or venous aneurysm, when the venous approach may be used. It is important to avoid occluding arteries proximally, which will only occlude access to the nidus and allow recruitment of collateral flow.

Summary

Adoption and use of uniform nomenclature in the ISSVA classification system is the first vital step in correct diagnosis and treatment of often complicated vascular tumors and vascular malformations. A multidisciplinary team approach is necessary to provide optimal care for patients, and the necessity for specialists in all areas to communicate using standardized terminology cannot be overemphasized. Dermatologists, radiologists, interventional radiologists, surgeons, hematologist/oncologists, pathologists, and neurologists all contribute valuable input to the care of patients with vascular anomalies. The clinical presentation of each vascular anomaly dictates the appropriate workup, and knowledge of imaging findings is critical to interventional and operative planning. As knowledge of the molecular and genetic basis of disease expands, our classification system will need to evolve to reflect such advances. Treatment remains difficult and cures for many malformations remains elusive, but as our understanding of the pathogenesis of vascular anomalies improves, so will our ability to offer improved therapies and outcomes for patients.

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© Springer-Verlag 2010