Vascular anomalies is a broad term used to encompass congenital errors in vascular development. This comprises a large group of separate entities including all vessel types, locales, and sizes, as well as syndromic presentations. In the day-to-day setting, these lesions can be frustrating for patients and their families, adversely affecting quality of life.
The clinical presentation of vascular anomalies is varied and may be particularly troublesome, requiring unique considerations in management. These can include life-threatening risks such as airway compromise, congestive heart failure and severe bleeding.1-4 There are also functional risks involving the eyes, lips, ears and nose, which can affect vision, speech, feeding and hygiene.5,6 Although the majority of vascular anomalies are benign, some can present with sequelae of ulceration or leaking, leading to chronic infections.
As a group, these lesions carry a varied amount of morbidity, but just as important is their psychosocial effect on patients. All in all, swift recognition and appropriate multidisciplinary management become paramount in treating this group of diseases.
The initial description of a vascular anomaly, namely the arteriovenous malformation, is credited to Dr. William Hunter who described the “particular species of aneurysm” in 1761.7 Since then, nonspecific and nondescript terms applied to vascular anomalies have grown, unfortunately without concrete pathologic or imaging characteristics. An example of these antiquated and misleading terms is listed in Table 1. Standardizing classification and characterization of these lesions was needed to facilitate proper diagnosis and subsequent treatment.
The seminal paper introducing a method to classify vascular anomalies based on histopathological and clinical characteristic-based classification was published by Mulliken and Glowacki in 1982,8 and has since been cited over 4300 times. Mulliken and Glowackis’ observations led them to separate vascular anomalies into two main categories: tumors and malformations. The former is characterized by vasoproliferative activity and the second by a congenital lesion that grows in proportion with the patient. This classification system has been refined over the years with adoption by the International Society for the Study of Vascular Anomalies (ISSVA),9 but the core principle remains the same.
Numerous subsequent publications have been released through a myriad of journals across multiple disciplines, yet the wastebasket use of hemangioma to describe all vascular anomalies persists. Although true hemangiomas are a type of vascular anomaly, most vascular anomalies, particularly malformations, cannot be described by hemangioma. For example, the suffix “-oma” alone implies neoplasia, which is often not the case. Lacking specificity, it can generate confusion, misdiagnosis and inadequate or improper management.
A multidisciplinary approach has largely become standard of care with dedicated clinics for the diagnosis and treatment of vascular anomalies.10-12 These clinics have proven vital given the range of pathology presented and treatments offered. These clinics also provide continuity of care with re-evaluation of disease progression and management of comorbidities over the patient’s lifetime. At our institution, this team consists of hematology, diagnostic and interventional radiology, plastic surgery and otolaryngology, and meets monthly to discuss and coordinate each patient’s care.
For many of these anomalies, an initial history and physical examination can often lead to a diagnosis without the need for diagnostic imaging. That said, in a modern practice environment, it is recommended that these lesions be imaged, most often with MRI and ultrasound. Less often, CT can be used to troubleshoot the angioarchitecture of complex lesions, evaluating bony involvement or used for logistical purposes in which MRI may not be feasible or is contraindicated.
The term hemangioma should be reserved for true neoplasms characterized by proliferative tissue. Most hemangiomas are diagnosed clinically, although nonsuperficial or complex hemangiomas may require imaging, which can detail the extent of disease and clarify the diagnosis. The infrequent biopsy may also be necessary in lesions that exhibit more aggressive characteristics, discussed later in this article.
Most vascular anomalies are true hemangiomas, 14 which are split into two types: infantile and congenital. Both exhibit similar imaging characteristics but are distinct entities differentiated by clinical history and immunohistochemistry, specifically the expression of the GLUT-1 glucose transport protein. Only infantile type hemangiomas express GLUT-1.13,14
Infantile hemangiomas represent the most common head and neck vascular anomaly and tumor in infants with a preponderance for the head and neck.6,15 Incidence is relatively high, identified in up to 2.6% of term infants, with 10% to 12% presenting by 1 year of age. There is a female predilection in addition to being more common in low birth weight and Caucasian patients.15-17 Reportedly, there is also increased incidence of infantile hemangiomas correlating with chorionic villus sampling at 9 to12 weeks’ gestation.
Clinically, these lesions present as lumps/bumps palpated by a parent, which may not be visually obvious. They exhibit progression through four phases: nascent, proliferative, involutional and involuted. Classically, infantile hemangiomas are not visualized at birth, although premonitory or precursor patches of skin discoloration may be identified by the scrutinizing physician in up to 50% of patients.15
Depending on the depth and character of the lesion, the proliferative phase may be detected as early as a few weeks of age.18 Most pronounced growth occurs during 3 to 6 months of age, with a minority continuing to grow beyond 1 year. After a period of quiescence, involution takes place lasting 5 to 6 years.2 Hemangiomas reach involution at a classically described rate of 50% by 5 years and 70% by 7 years.
In the evaluation of infantile hemangioma, ultrasound is often an ideal first choice. On ultrasound, hyperechoic and/or hypoechoic lesions are seen demonstrating uniformly scattered punctate vascularity, which are high velocity/low resistance on Doppler interrogation11,19 (Figure 1). Involuted lesions generally demonstrate an isoechoic appearance and may not be distinguishable from surrounding soft tissue.20
MR findings typically demonstrate a well-circumscribed lesion with nonaggressive features. Hemangiomas generally exhibit increased T2 and intermediate T1 intensity with strong enhancement on postcontrast sequences. Classically, flow voids depicting faster flow vessels are present21,22 and there should be no adjacent soft-tissue edema (Figure 2).
Infantile hemangiomas are predominantly self-limiting in that nearly all involute without complication. Medical intervention is warranted in approximately 10% to 20% of cases where lesions generate complications including high output heart failure, airway compromise, vision impairment, ulceration, or facial lesions whose unabated growth can lead to more permanent disfigurement.
First line medical therapy includes weight-based dosing of propranolol,18 followed by the addition of corticosteroids and/or vincristine in resistant lesions. Lesions responding poorly to medical therapy or with significant comorbidities (eg, Kasabach Merritt syndrome with high output cardiac failure) are candidates for either surgery, endovascular embolization, or a combination of both coordinated with input from the multidisciplinary team.
Finally, in select cases where there are residual remnants of fibrofatty tissue after complete lesion involution, surgical resection may be warranted or elected.
The distinction between congenital and infantile hemangiomas is based on two main features. Congenital hemangiomas are fully formed at birth having completed their proliferative phase. Secondly, they do not express GLUT-1 on immunohistochemical staining. Two forms of congenital hemangiomas exist: noninvoluting congenital hemangiomas (NICH) and rapidly involuting congenital hemangiomas (RICH).8,22,23
As their names suggest, NICHs do not involute, whereas RICHs usually involute by 14 months of age.24 As is the case with infantile hemangiomas, uncomplicated congenital hemangiomas are well identified clinically. Nonetheless, ubiquitous availability of imaging allows for easily accessible assistance in generating a more complete diagnosis, especially determining the extent of deeper lesions.20 In some instances, a biopsy may be performed to confirm diagnosis.
Imaging of congenital hemangiomas is similar in approach and appearance to that of infantile hemangiomas. They are generally well-circumscribed masses with variable echogenicity and high vessel density. Where they differ from infantile hemangiomas is gray-scale visibility of tubular vessels, echogenic heterogeneity, and the occasional calcification (RICH > NICH). Also, NICH lesions may demonstrate increased vascular velocities compared with RICH and involuting infantile hemangiomas.14,24
The MR imaging characteristics of NICH and RICH are also similar to that of infantile hemangiomas although congenital hemangiomas may present with ill-defined margins. Adjacent fat-stranding may also be present, more commonly with NICH. Soft-tissue masses with low vessel density, adjacent edema or high resistive indices should prompt further interrogation to rule out other soft-tissue tumors22,25 (Figure 3). Aggressive features such as infiltration or bony involvement should raise suspicion for kaposiform hemangioendothelioma.26 Additional differentials are listed in Table 2.
RICH lesions require no treatment given their self-limiting rapid involution, although sequelae such as remnant excess cutaneous tissue or discoloration may require cosmetic correction. Smaller NICH lesions are generally treated conservatively while larger lesions require laser therapy and/or surgical resection. In very large lesions, endovascular embolization prior to resection may have a role.
To reiterate, vascular malformations represent a morphogenic abnormality of various vessels present at birth. They are nonproliferative and demonstrate normal cellular turnover, growing in proportion to the child and may not be distinctly visible at birth. Although they maintain a nonmitotic “mature” endothelium, they can still grow in response to trauma (iatrogenic or otherwise), hormonal changes, or infection.
Vascular malformations are subdivided initially by the dominant vessel type (eg, venous, capillary, lymphatic, arterial) or a combination thereof with further subdivision based on flow velocity. In theory, these lesions can have overlapping characteristics manifesting as a gradient of lesions that may require a balance of therapies including: intralesional or interstitial sclerotherapy, surgical resection, laser therapy and chemotherapy. From a treatment perspective, we will focus on the classic subtypes.
These slow-flow vascular anomaly malformations are generally restricted to usually involve the capillaries of the superficial dermal layers and present as discolored macules or patches. Prior antiquated terminology included terms like angel’s kiss, stork bite or salmon patch (nevus simplex) or port-wine stain (nevus flammeus). They occur in approximately 0.3% of infants27 and are usually noticed at birth, although initially they may be dismissed as erythema or bruising from birth trauma. Single or multiple lesions may be present as small patches and involve a portion of the face or an entire limb. Facial involvement may herald additional syndromic associations and, for this reason, children with craniofacial involvement should undergo additional workup in the form of a brain MRI (or, less preferred, CT). This specifically pertains to capillary malformations in the trigeminal nerve distribution, which is highly associated with anomalies of the ipsilateral leptomeninges, ie, Sturge-Weber syndrome.11
Craniofacial capillary malformations are diagnosed on a clinical basis and often require no imaging outside of excluding associated syndromic disease. Sonographic features are nonspecific. MR imaging may demonstrate skin thickening or abnormality of the subcutaneous tissue, if anything.22,25 The primary treatment option of capillary malformations is laser therapy, initially pulsed-dye laser (PDL), given the superficial involvement.27
Congenital venous malformations are characterized by a collection of abnormal, ectatic veins with irregular channels present at birth. The smooth muscle layer is discontinuous and thin, resulting in inability of veins to constrict normally after distention from increased volume. Associated absence of valves aggravates swelling, and dysplastic veins become progressively enlarged. Stagnation of blood leads to further thrombosis, swelling and pain. Chronic thrombi calcify forming phleboliths, which are pathognomonic for venous malformations.10,12
Detection is usually early in superficial lesions with dermal involvement showing varying levels of bluish discoloration. Deeper lesions (ie, intraosseous, intramuscular) may not be identified until later in life when significant swelling or pain manifests. Characteristic enlargement with heavy activity, Valsalva, or crying, as well as dependent position can often assist with clinical diagnosis. Rapid enlargement may also occur with trauma, hemorrhage, or hormonal influences (ie, puberty, pregnancy). Superficial lesions are compressible without audible bruit or pulsatility and may have palpable phleboliths within them.
Venous malformations are most commonly described as cystic, dysplastic or spongiform in morphology. In practice, they are a combination of these characteristics with associated, usually dysplastic, narrow draining vessels,28 which eventually often communicate with the normal venous system.
As with most vascular anomalies, initial evaluation with ultrasound and MR imaging are the mainstays. Ultrasound allows for evaluation of flow velocity, compressibility, and visualization of thrombus/phleboliths but is limited to relatively superficial areas (Figure 4). Multiple-region MRI can also demonstrate secondary characteristics of flow velocities such as fluid-fluid levels (hematocrit effect) and phleboliths (signal voids) but adds the ability for large field-of-view imaging, evaluating the deeper extent and multiplicity of lesions.11,21,28 It should be mentioned that phleboliths can be detected radiographically and are usually pathognomonic for venous malformations.
Gray-scale sonography typically shows a compressible hypoechoic lesion, which can be well circumscribed, but are more often ill-defined or infiltrative. Mobile internal echoes can be visualized sonographically with compression maneuvers while tourniquets can engorge lesions. Tubular structures may be visualized in larger malformations consistent with ectatic veins.
Venous malformations are hyperintense on fluid-sensitive MR sequences. Well-circumscribed hypointense T1 and T2 foci would represent phleboliths. Fluid-fluid levels are also visualized representing a hematocrit effect. Venous malformations are generally considered to enhance diffusely.22,25,29 In our practice, however, we have found enhancement to be variable, including minimal enhancement, enhancement with layering, and avid enhancement (Figure 5). Reporting on venous malformations should include lesion size and extent, tissue compartments involved, flow velocities if any, compressibility, and presence of phleboliths.
Venography is often performed during the treatment of venous malformations. This is facilitated by direct ultrasound-guided puncture of anechoic spaces followed by fluoroscopy with contrast injection (Figure 6). Venography depicts the individual morphology – cystic, lobulated or dysplastic – of each component within the venous malformation and identifies any prominent drainage of the malformation, which is necessary in guiding therapy.
Treatment depends on the location and extent of the venous malformation. Multiple options exist including compression, laser therapy, surgery and sclerotherapy, or a combination.5,29
Local compression may be of benefit in isolated locations such as extremities. However, unlike extremities, compression garments cannot be practically applied to venous malformations in the head and neck. Surgical excision is reserved for accessible and localized lesions; otherwise, these anomalies are managed most often with sclerotherapy.
With sclerotherapy, patient and family expectations must be tempered during the initial consultation, especially in extensive lesions involving large areas and multiple components. The goal of sclerotherapy is not curative, but rather management of the disease for reducing the comorbidities, which range from pain to disfigurement. It is often unclear initially how many treatments will be required, ranging from a single therapy to numerous repeat sessions over several years. This depends not only on disease extent but on variables such as patient satisfaction with cosmesis, pain and relapsing disease as the child grows, and external forces such as trauma or infection.
Sclerotherapy begins with contrast venography to depict lesion size and draining veins, and to assess deep veins and sclerosant volume needed (Figures 8, 9). The goal of sclerotherapy is localized destruction of endothelial lining, inflammation, and thrombosis of the malformation. Most commonly used sclerosants include 98% ethanol, 1% or 3% sodium tetradecyl sulphate foam, doxycycline, Ethibloc, polidocanol and bleomycin. Ethanol and sodium tetradecyl sulphate are generally considered the most common, effective and available sclerosants. Manual compression may be used to reduce outflow during treatment. In scenarios where there is “rapid” or significant outflow, coils or glue can be used to occlude outflow prior to sclerosant injection. Coils can also be utilized to protect nontarget veins. Complications of sclerotherapy include systemic toxicity of sclerosant, nontarget embolization, temporary nerve injury, fibrosis and skin necrosis in superficial lesions.
Lymphatic malformations represent vascular anomalies proceeding from disorganized lymphangiogenesis and are estimated to account for approximately 6% of all benign childhood head and neck lesions.21 Similar to venous malformations, lymphatic malformations are characterized by cystic spaces lined by “mature” endothelial cells, which do not exhibit neoplasia.8 Larger lymphatic malformations are still often referred to by old terminology such as cystic hygromas or lymphangiomas, which should be discouraged. These lesions may be visualized in utero, as early as the second trimester and are present at birth. Between 65% and 75% are diagnosed at the time of birth – as they are not always visible on physical examination – and 80% to 90% by 2 years of age. They can present at any age with sudden onset rapid growth from incidental trauma, infection (eg, upper respiratory) or hormonal change (puberty, pregnancy, etc.), which is often disconcerting to parents and some primary care physicians.
Lymphatic malformations have a greater propensity to insinuate between soft tissues as well as a greater likelihood of demonstrating communication between cystic spaces compared with venous malformations. Lymphatic malformations are characterized as either microcystic (< 1 cm), macrocystic (≥ 1 cm), or a combination of both. This classification helps determine treatment plans.
Lymphatic malformations are very slow flow structures, which is well depicted on imaging, particularly ultrasound. Macrocysts are usually well-defined, loculated fluid collections, which can have few internal septae (Figure 8). They are hypoechoic or anechoic in character, although debris or hemorrhage can be seen within. Microcystic morphology is hyperechoic in character due to the closely packed cysts/septae (Figure 9A), which demonstrate increased vascularity.
On MRI, lymphatic malformations are septated cystic structures usually following fluid signal (high T2/low T1) internally, the caveat being that proteinaceous or hemorrhagic content can increase the T1 signal. Increased confidence in identifying the presence of enhancement can be aided by performing subtraction images (subtracting the unenhanced from the enhanced T1-weighted images in postprocessing). When present, septations may demonstrate enhancement, while there should be no enhancement of the cystic components. This is an important distinction in differentiating lymphatic from venous malformations and translates to CT imaging. With CT, cystic spaces are low attenuation with usually thin walls. The exception is infection, which generates thickening of the cyst walls and adjacent inflammatory changes.21,22,25
Conventional angiographic imaging is key in the treatment of macrocystic lymphatic malformations. Although diagnostic value is relatively limited, morphology and presence of draining vessels/venous can aid in developing a more complete diagnosis, especially with complex or combined venous and lymphatic malformations.
Regarding management, the large majority of lymphatic malformations should not be treated conservatively as there is only an approximately 3% chance of spontaneous regression.30 Conservative therapy is, therefore, a relatively poor option as there is progression of disease with susceptibility for infection, ulceration, bleeding and sequelae of mass effect (eg, airway compromise). Sclerotherapy is generally the first-line treatment for macrocysts with high long-term success rates and low rates of complication. Microcystic lesions can also be treated with sclerosant injection under ultrasound guidance, most commonly using a doxycycline emulsion (Figure 9B) and, alternatively, bleomycin.
In well-circumscribed smaller and superficial lesions, surgical resection may be considered. Staged surgical debulking in conjunction with sclerotherapy may be effective in massive or life-threatening lesions. However, surgical involvement can lead to complication of macrocysts requiring a significant increase in efforts for subsequent percutaneous therapy. For extensive disease, as in diffuse superficial microcystic disease where sclerotherapy or surgical debulking is not feasible, pharmacotherapy may be considered. Specifically, sirolimus has shown promise.31 This echoes the need for the involvement of a multispecialty team familiar with the natural history and management of the disease.
Arteriovenous malformations (AVMs) are the prototypical congenital high-flow vascular malformations. AVMs typically have a central nidus with feeding artery/arteries and draining vein(s) meeting at a central location. There is no intervening capillary bed between the arterial and venous components generating variable amounts of shunting.4,8 Like other vascular malformations, arteriovenous malformations are structural abnormalities with normal mature endothelial lining. The most common locations are intracranial followed by extracranial head and neck.32
Superficial lesions present as a mass, which can be pulsatile and warm on palpation. Deeper lesions tend to manifest later in life as areas of pain. Skin discoloration is noted in most patients presenting with superficial, extracranial AVMs as infants, whereas less than 50% of postpubertal patients exhibit skin discoloration.32 Bruits may also be heard on auscultation. Deeper lesions tend to manifest later in life and can present due to pain. Generally, AVMs do not exhibit rapid growth but, like other vascular malformations, growth can be triggered by trauma, surgical/endovascular intervention and hormonal changes (pregnancy/puberty). The natural history is progression of the disease with growth and recruitment of additional vasculature increasing the complexity of the lesion. Untreated lesions can have an aggressive clinical course including life-threatening bleeding, ischemia, ulceration, high-output heart failure and significant pain.
AVMs are typically a tangle of intertwining vessels best demonstrated with conventional angiography or MR/CT angiography. There is a soft-tissue component interdigitating the hypertrophied vessels, which has been shown to have angiogenic effects. Initial MR or contrast-enhanced CT assist in obtaining the overall picture and are paramount for planning treatment. Ultrasound may be the first modality used for superficial lesions on initial presentation demonstrating an overall hypoechoic mass. Doppler shows a low resistance pattern in feeding arteries and arterial waveforms in draining veins (arterialization). Aliasing or turbulence is seen in the nidus, and abnormal pulsatility is present in draining veins.4,11
Similar to other malformations, CT and MR are excellent for demonstrating extent of lesion including intramuscular and intraosseous involvement. Depiction of multiple hypertrophied arteries and dilated veins associated with the lesion and their relation are necessary for classification and treatment planning. MR exhibits flow voids on T1 and T2 sequences and an overall lack of identifiable soft-tissue components (Figure 10). Presence of a soft-tissue mass should prompt consideration for neoplasm such as sarcoma. Temporal imaging with or without contrast enhancement is helpful to separate arteries from veins in complex lesions.11 Time-resolved MRA techniques are especially helpful (TRICKS – GE Healthcare and TWIST – Siemens Healthineers). Finally, traditional angiography exhibits the highest image and temporal resolution facilitating visualization of early draining veins (Figure 11). Angiography also allows for concurrent intervention minimizing the number of examinations.
Small, asymptomatic lesions may be conservatively managed initially with observation and repeat imaging. However, the expected natural course is progression toward expansion of the lesion with associated sequelae of pain, bleeding, ulceration, etc.
Symptomatic lesions are treated most commonly with endovascular therapy, classically a transluminal intra-arterial approach with coil or glue embolization as well as absolute ethanol (Figure 11). Particles are usually not a recommended embolic agent as shunting will likely result in a nontarget injury. An almost expected progression of arterial recruitment often complicates subsequent treatments; therefore, a more comprehensive initial embolic therapy from combined arterial and venous approaches is critical. Postembolization surgical intervention may also be combined in certain accessible lesions.
Complex lesions require a multidisciplinary team with diagnostic and interventional radiology, plastic surgery and/or vascular surgery. Each lesion is unique, requiring a combination of therapy and follow-up. There is a high recurrence rate in the long term.5
Vascular anomalies are a group of life-altering and life-long diseases with far-reaching physical and psychosocial consequences. Understanding the basic presentation, pathology and imaging characteristics allows for accurate diagnosis with swift and appropriate treatment. Multidisciplinary teams are an essential component in improving the long-term outlook for this patient population, significantly improving quality of care and prognosis.
Beydoun T, Eghbal A, Holmes WN. Vascular Anomalies: Basics of Imaging and Treatment. J Am Osteopath Coll Radiol. 2021;10(3):5-14.