The term vasculitis refers to inflammation of blood vessels. There are various classification schemes for noninfectious vasculitis, based on the sizes of the blood vessels typically involved and the pathology of the lesions (Table 13-1). Takayasu disease is the most important large vessel vasculitis in children. Kawasaki disease, polyarteritis nodosa, and primary central nervous system (CNS) vasculitis of childhood are vasculitides that primarily involve mediumsize vessels. Examples of small vessel vasculitis include Henoch-Schönlein purpura, Wegener granulomatosis, Churg-Strauss syndrome, and microscopic polyangiitis. There is considerable variation in the organ systems most prominently affected by the various vasculitides. Constitutional symptoms, fever, and skin lesions are common with these disorders.¹

Takayasu Arteritis (Occlusive Thromboarthropathy)

Takayasu arteritis (Takayasu disease) is a rare idiopathic chronic inflammatory arteritis that causes thrombosis, stenosis, dilation, and aneurysm formation in the pulmonary arteries, aorta, and major aortic branch vessels. Although the pathogenesis is incompletely understood, Takayasu arteritis apparently is an autoimmune process. There is granulomatous inflammation of the involved vessel, a result of the deposition of autoimmune complexes in areas of vessel wall permeability. The inflammation damages the adventitia and media, and leads to subsequent reactive proliferation of the intima and adventitia. Ultimately, there is progression to concentric mural thickening and calcification; all layers of the arterial wall are involved. The aortic arch and its branches are the most common locations of symptomatic disease in patients with Takayasu arteritis. Other potential sites of involvement include the descending thoracic aorta, abdominal aorta, renal arteries, and splanchnic arteries.²

The clinical manifestations of Takayasu arteritis are predominantly caused by vascular stenoses. Symptomatic aneurysms can also occur. The clinical onset of Takayasu arteritis in children is usually during the second decade of life; 90% of patients are younger than 30 years at the time of presentation. The onset may be insidious or, less commonly, fulminant. Potential early symptoms in children include dyspnea and hemoptysis. Hypertension is common, usually as a result of renovascular stenosis. Carotid artery involvement can result in syncope or other neurological symptoms. Aortic regurgitation can occur in patients with a dilated aortic root. Patients with Takayasu arteritis are at risk for osteoporosis, either as a complication of the disease or as a side effect of therapy. Takayasu arteritis most often occurs in young adult women. This disorder is most prevalent in individuals of Asian descent.³

CT is useful for demonstrating mural thickening and calcification within the aorta, pulmonary arteries, and major aortic branch vessels in patients with Takayasu arteritis. The thickened vascular wall may enhance prominently with IV contrast. MR can show mural thickening and adherent thrombi, but visualization of calcifications is poor with this technique. As with CT, prominent contrast enhancement is often present within the thickened aortic wall; this is an indicator of active disease. The inflamed aortic wall is hyperintense on fat-suppressed T2-weighted sequences during the active stage of the disease (Figure 13-1). The most common angiographic finding in patients with Takayasu arteritis is the presence of one or more long stenotic vascular lesions and/or large vessel occlusions (Figure 13-2). There may be vessel wall irregularity and poststenotic dilation. Ectatic vessels or true aneurysms are present in a substantial minority of patients. Doppler sonography shows elevated flow velocity at the site of a stenosis and dampened velocity distally. An aortic aneurysm in a patient with Takayasu arteritis usually has a visibly thickened wall on cross-sectional imaging with CT or MR.^4–7

Polyarteritis Nodosa

Polyarteritis nodosa is an idiopathic focal segmental necrotizing vasculitis. The necrotizing vasculitis results in aneurysm or pseudoaneurysm formation, typically at the bifurcation of a medium-sized artery. The most commonly affected vessels are the renal and mesenteric arteries. The vascular pathology can lead to ischemia or hemorrhage that is detectable with cross-sectional imaging examinations. Affected organs include the kidneys, liver, spleen, pancreas, and intestine. Angiography shows multiple small aneurysms at bifurcations and small vessel irregularity.^8,9

Idiopathic Infantile Arterial Calcification

Idiopathic infantile arterial calcification is a rare autosomal recessive disorder in which there is deposition of calcium (hydroxyapatite) in the elastic fibers of the walls of large- and medium-size systemic and pulmonary arteries. Associated intimal proliferation leads to vessel narrowing. The descending aorta and the coronary arteries are the most common areas of clinically significant involvement. There is typically little or no involvement of intracranial vessels. Many affected patients die during the first few months of life because of cardiac failure, although the clinical severity of disease is variable and medical intervention can alter the course. Fetal involvement can lead to nonimmune hydrops and polyhydramnios. Infants with this disorder may exhibit manifestations of myocardial ischemia, hypertension, visceral infarction, periarticular swelling, developmental delay, and seizures.¹⁰

Potential prenatal sonographic findings of idiopathic infantile arterial calcification include polyhydramnios, pericardial fluid, and echogenic calcifications in the walls of the coronary arteries, aorta, and pulmonary arteries. In infancy, radiographs may show calcifications in vessel walls and periarticular soft tissues. On CT, axial images of the aorta sometimes demonstrate a target pattern caused by hypoattenuating thickened intima between the contrast-enhanced lumen and the calcified media. Intimal plaques are often visible on sonography. MR angiography is useful for characterization of stenoses.^11–13

Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF-1) is a multisystem disorder in which there are dysplasias of mesodermal and neuroectodermal tissues. Vascular involvement is uncommon, but can lead to serious clinical alterations. Potential vascular manifestations of NF-1 include arterial stenoses and aneurysms. Common sites of involvement are the renal arteries, splanchnic vessels, abdominal aorta, central cerebral arteries, coronary arteries, and subclavian arteries. Approximately 1% of individuals with NF-1 have hypertension as a result of coarctation of the aorta, pheochromocytoma, or renal artery stenosis. Renal artery stenosis is the most common vascular lesion in patients with NF-1.

There are two basic categories of vascular stenosis in NF-1.¹⁴ The first consists of encasement of larger vessels such as the aorta, carotid arteries, and main renal arteries by neurofibromatous or ganglioneurofibromatous tissue. This abnormal perivascular tissue can elicit intimal proliferation, thinning of the media, and fragmentation of elastic tissue, with progression to a stenosis or aneurysm. The second type of vascular lesion in NF-1 is a small vessel mesodermal dysplasia that causes vascular stenoses. In the kidneys, multiple small intrarenal branches may be involved. Visceral stenoses are usually, but not invariably, accompanied by aortic narrowing. This has the appearance of long smoothly tapered narrowing of the abdominal aorta.

Arterial Fibrous Dysplasia

Arterial fibrous dysplasia (fibromuscular dysplasia) is a developmental abnormality of the fibrous, muscular, and elastic tissues of the involved vessel. Pathological classification is according to the predominantly affected layers: intimal fibroplasia, medial fibroplasia, perimedial fibroplasia, medial hyperplasia, and adventitial dysplasia. The renal arteries are the most common sites of arterial fibrous dysplasia, although there occasionally is concomitant involvement of other vessels (e.g., the aortic arch, extremity arteries, or splanchnic arteries). Chapter 52 has additional discussion of vascular fibrous dysplasia.

Arterial Tortuosity Syndrome

Arterial tortuosity syndrome is a rare autosomal recessive disorder in which elongation, tortuosity, stenoses, and aneurysms occur in large and medium-size arteries. Vascular dissection and pulmonary artery stenosis are common. Patients with this disorder have mutations in the SLC2A10 gene, which encodes for the facilitative glucose transporter 10 (GLUT10).^15,16

Moyamoya

Moyamoya disease is an idiopathic vasculopathy of central intracranial arteries. Progressive narrowing of cerebral vessels leads to various neurological complications. There is secondary enlargement of numerous collateral vessels in the central aspect of the brain. Moyamoya syndrome refers to similar cerebrovascular alterations occurring in association with a systemic disease or known insult, such as sickle cell disease, NF-1, cranial irradiation, PHACES (posterior fossa malformations, facial hemangiomas, arterial anomalies, cardiac anomalies and aortic coarctation, eye anomalies, and sternal clefting and/or supraumbilical raphe) syndrome, or Down syndrome. Chapter 20 has additional discussion of moyamoya.

Median Arcuate Ligament Syndrome

Median arcuate ligament syndrome refers to stenosis of the celiac artery as a result of extrinsic compression of the vessel by the median arcuate ligament of the diaphragmatic crura. With time, fibrosis of the vessel wall leads to an intrinsic stenosis. Most individuals with imaging evidence of celiac artery narrowing are asymptomatic. Symptomatic patients may suffer weight loss and report postprandial abdominal pain, nausea, or diarrhea. The nonspecific nature of the symptoms is frequently problematic in the management of these patients. Median arcuate ligament syndrome is more common in females than males.

Imaging studies of median arcuate ligament syndrome demonstrate inferior deviation and narrowing of the proximal aspect of the celiac artery, best demonstrated on sagittal images in the plane of the aorta (Figure 13-3). There is exacerbation of the stenosis during expiration. Doppler sonography shows elevation of the flow velocity at the site of stenosis during expiration and normalization during inspiration. There is dampened systolic flow distal to a moderate-to-severe narrowing (Figure 13-4). With severe involvement, flow through the celiac artery ceases during expiration. Normalization of the vessel caliber and flow characteristics during deep inspiration militates against significant fibrotic stenosis, suggesting that a simple median arcuate ligament release procedure would likely be effective in improving flow. In some patients, there is enlargement of the gastroduodenal artery as a collateral pathway. End-expiratory inferior deviation and narrowing of the celiac artery has been reported to be common in asymptomatic adults undergoing MR studies for unrelated indications.^17–20

Marfan Syndrome

Marfan syndrome is a generalized connective tissue disease that primarily involves elastic tissue. This is an autosomal dominant condition with high penetrance, predominantly caused by mutations in the fibrillin-1 (FBN1) gene. These patients lack normal fibrillin, a glycoprotein that is the main constituent of the microfibrils of the extracellular matrix. Fibrillin is crucial for normal elastin function. The cardiovascular manifestations of this disorder are predominantly a result of a lack of normal tensile strength of the supporting tissue of the aorta and other major blood vessels as well as the cardiac valves. Abnormal tissue growth factor signaling is an additional pathogenic factor.

Potential cardiovascular manifestations of Marfan syndrome include aortic valve disease, aortic root dilation, aortic aneurysm, aortic dissection, mitral valve prolapse, and pulmonary artery dilation (Table 13-2). About half of individuals with Marfan syndrome have clinical evidence of cardiovascular disease during childhood or adolescence. The most common finding is a murmur caused by mitral regurgitation. Aortic regurgitation can also occur, but is more common in adults. Aortic regurgitation in infants with Marfan syndrome is predominantly restricted to males. Chapter 57 has additional discussion of the genetic and clinical factors of Marfan syndrome.^21–24

Histological examination of the ascending aorta in patients with Marfan syndrome shows disruption and disorganization of the elastic media, with separation of fibers by mucoid material. Aortic involvement usually begins in the sinuses of Valsalva (Figure 13-5). There is progressive dilation of the ascending aorta. Small linear tears occur in the intima immediately above the aortic valve. These usually heal spontaneously, but there is a potential for progression to a dissecting aneurysm. Dilation of the aortic root causes aortic valve regurgitation. There also can be thinning or fenestration of the aortic valve leaflets. Mitral valve abnormalities are common in these patients, leading to regurgitation. The combination of aortic and mitral valve disease can precipitate marked left ventricular volume overload. Involvement of a coronary artery ostium in a patient with an aortic dissection can lead to myocardial infarction. Potential fatal cardiovascular complications in individuals with Marfan syndrome include severe valvar incompetence, aortic dissection, and rupture of an aortic aneurysm. Conduction abnormalities and severe ventricular dysrhythmias can occur.

Chest radiographs of individuals with Marfan syndrome often show a narrow anteroposterior diameter of the thorax. Scoliosis and pectus excavatum are common. Sinus of Valsalva dilation is usually not visible on standard radiographs. Dilation of the ascending aorta sometimes results in fullness that obliterates the retrosternal airspace on the lateral view. Increasing dilation of the arch leads to fullness of the upper right-heart border on the frontal projection. Aneurysmal dilation and tortuosity can also produce radiographic fullness of the remainder of the arch and/or the descending aorta (Figure 13-6). The presence of cardiomegaly suggests substantial aortic insufficiency.

Abnormalities of the aorta in patients with Marfan syndrome are effectively detected and characterized with MR or dynamic contrast-enhanced CT (Figure 13-7). Annuloaortic ectasia has a characteristic appearance. There is loss of visualization of the normal sinotubular ridge. The aortic root (annulus, sinuses of Valsalva, and sinotubular junction) and proximal ascending aorta are dilated. There usually is abrupt change to normal caliber proximal to the upper aspect of the arch. Surgical therapy is generally indicated when the sinus of Valsalva aneurysm is equal to or greater than 5.5 cm in diameter (≥5.0 cm in a child) or when the diameter is at least twice that of the uninvolved distal portion of the thoracic aorta. Aneurysms can also occur in any other portion of the thoracoabdominal aorta (Figure 13-8). Concomitant involvement of major branch vessels is common.²⁵

Sinus of Valsalva aneurysms and mitral valve disease with a floppy valve are frequent findings on echocardiography and angiocardiography in patients with Marfan syndrome. Prolapse most often involves the mitral valve, but aortic or tricuspid prolapse can occur as well. There is usually aortic arch dilation, although severe aortic lesions often do not occur until later in life. Echocardiography allows monitoring of aortic and pulmonary artery calibers and cardiac valve function. Marfan syndrome patients sometimes develop an interatrial septal aneurysm.^26,27

Electrocardiographically gated cardiac CT and MR are useful for evaluating aortic valve function in selected patients with Marfan syndrome. Because of dilation of the sinus of Valsalva, the cusps of the aortic valve appear tethered on midsystolic-phase images, rather than having normal arched configurations. There is a triangular coaptation defect on end-diastolic images, resulting in valvular insufficiency.

An aortic dissection results from an intimal tear that allows blood to enter the medial layer of the aorta. The possibility of an aortic dissection should be considered when sequential chest radiographs show progressive enlargement of the aorta. Characteristic features of dissection on CT and MR are an intimal flap and a false lumen (Figures 13-9, 13-10, and 13-11). However, one or both of these findings are often absent despite the presence of dissection. Important secondary findings of dissection on cross-sectional imaging evaluations include mediastinal or pericardial hematoma, clot in the false lumen, and ischemia in organs supplied by branch arteries.

The most common surgical treatment for an aneurysm of the aortic root in a Marfan syndrome patient is insertion of a composite valve graft (prosthetic valve with a synthetic graft). In some institutions, the native aortic valve is left in place. An aortic root homograft with a valve can also be used; this procedure is most often carried out in the setting of prosthetic valve endocarditis and aortic root inflammatory destruction. Pseudoaneurysm formation is an important potential complication following aortic root surgery. The pseudoaneurysm most often occurs at the anastomotic site. MR demonstrates a localized area adjacent to the graft that has a signal void on spin-echo MRI because of flowing blood. Cine gradient-recalled echo MR shows bright signal because of flowing blood within the cavity of the pseudoaneurysm. An infectious pseudoaneurysm can occur in the presence of endocarditis; this has a similar appearance to that of a noninfected pseudoaneurysm. Extraluminal fluid collections that do not have features of flowing blood on MR include abscess and hematoma.^28–31

Ehlers-Danlos Syndrome

Ehlers-Danlos syndrome encompasses a heterogeneous group of connective tissue disorders that result in deficient integrity of the supporting structures of the body. Common features of these disorders include hyperextensible skin, hypermobile joints, easy bruisability, and dystrophic scarring. Patients with the vascular type (type IV) of EhlersDanlos syndrome are at risk for catastrophic bleeding from weakened major arteries. Vascular Ehlers-Danlos syndrome is an autosomal dominant disorder that is caused by heterozygous mutations of the COL3A1 gene encoding for type III procollagen. The major consequence of the procollagen abnormality is excessive tissue fragility.

Patients with deficient or abnormal procollagen III are prone to various vascular lesions, including catastrophic vessel rupture. The typical clinical features include thin translucent skin (80% of patients); excessive bruising; a thin “pinched” nose and prominent eyes (30% of patients); joint hypermobility; spontaneous rupture of the bowel; transient intestinal obstruction; obstetrical complications; and manifestations of arterial fragility. The prevalence of vascular Ehlers-Danlos syndrome is 1 per 25,000 livebirths. The long-term prognosis is poor; approximately 80% of these patients develop a life-threatening complication by age 40 years.^32,33

The most common vascular consequences of vascular Ehlers-Danlos syndrome are vessel ruptures and solid organ infarcts within the abdomen, thorax, and brain. Vascular ruptures are often spontaneous or follow minor trauma or interventional procedures. Vascular rupture can occur in vessels without a preexisting aneurysm or dissection. On imaging evaluation, most patients with vascular Ehlers-Danlos syndrome have vascular lesions at multiple sites. Aneurysms are most common, followed by dissections and vascular ectasia. The most common sites are the abdominal visceral arteries, iliac arteries, aorta, and the lower extremity, carotid, vertebral, subclavian, pulmonary, and cerebral arteries. Noninvasive vascular imaging techniques are preferable for these patients because of the elevated risk for complications with arterial puncture and catheterization.

Loeys-Dietz syndrome

Loeys-Dietz syndrome is a rare disorder characterized by arterial tortuosity, aneurysms, and hypertelorism. Bifid uvula or cleft palate can occur. Scoliosis and foot deformities are common. This autosomal dominant disorder is a result of mutations in transforming growth factor (TGF)-β receptors I (TGFBR1) and II (TGFBR2) genes. Individuals with Loeys-Dietz syndrome have a high risk for aortic dissection or aortic rupture. Some patients have findings that overlap those of vascular Ehlers-Danlos syndrome or Marfan syndrome. The intracranial vessels are tortuous, and intracranial aneurysms can develop. Carotid or vertebrobasilar dissections can also lead to central nervous system symptoms.^34,35

Aneurysms of the aorta are rare in children. These lesions are most often associated with Marfan syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome, Turner syndrome, Noonan syndrome, bicuspid aortic valve, Takayasu arteritis, bacterial endocarditis, or repaired aortic coarctation. Trauma and infection can also lead to large vessel aneurysms. Mycotic aneurysm of the aorta is a potential complication of an indwelling arterial catheter in the newborn. The ductus arteriosus is a potential site of a congenital aneurysm. Aneurysmal dilation of the pulmonary artery can occur in association with pulmonary hypertension or in neonates with tetralogy of Fallot and absence of the pulmonary valve. Multiple large pulmonary artery aneurysms can occur in children with Behçet syndrome. Aneurysms and pseudoaneurysms of small and mid-size vessels in children are most often mycotic, traumatic, or related to a systemic vasculitis.

In the abdomen and pelvis, aneurysms can occur in the aorta, mesenteric vessels, renal arteries, or small branch vessels within an organ (Table 13-3). Aneurysms of the main renal artery can occur in children with NF-1, infectious arteritis, renal artery stenosis, or Kawasaki disease. Vasculitis is the most common cause of small vessel renal aneurysms. Aneurysms of the cerebral vasculature are most often congenital, mycotic, or traumatic.

Mycotic pulmonary artery pseudoaneurysm is a rare lesion that is usually associated with lung infection. The most common cause is erosion from adjacent cavitary tuberculosis; this is termed a Rasmussen aneurysm. This lesion can also develop adjacent to a pyogenic lung abscess or in patients with aspergillosis. Noninfectious causes of pulmonary pseudoaneurysm include trauma, iatrogenic (e.g., thoracostomy tube or angioplasty), vasculitis, and neoplasm. The radiographic appearance of a pulmonary artery pseudoaneurysm is that of a round or lobulated lung mass.

Diagnostic imaging techniques for the detection and characterization of aneurysms include sonography, CT, MR, and conventional angiography (Figure 13-12). Transcatheter angiography is usually required for accurate characterization of small vessel aneurysms. Noninvasive techniques are usually sufficient for evaluation of aneurysms of large and mid-size vessels. On MR, gradient-echo pulse sequences complement standard spin-echo images by demonstrating the blood flow characteristics in the region of the lesion. CT angiography also demonstrates the flow characteristics, thrombus within the lesion, and effects on adjacent structures (Figure 13-13). Sonography provides similar information for accessible lesions (Figure 13-14). Sonography is particularly helpful for characterization of posttraumatic pseudoaneurysms in the extremities; pulsed Doppler examination typically shows to-and-fro blood flow within the neck of the lesion.³⁶

Patients with Marfan syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome, Turner syndrome (Table 13-4), systemic lupus erythematosus, and aortitis are susceptible to the development of aortic dissection, particularly in conjunction with hypertension. Dissection can also occur following blunt trauma to the chest or abdomen (see “Vascular Trauma” below). Dissection is a potential complication of cardiac surgical procedures. Clinical manifestations of acute dissection include chest pain, back pain, hypotension, loss of pulses, mesenteric ischemia, and hypertension. Cardiac tamponade can occur as a consequence of the accumulation of blood in the pericardial space.^37,38

The initiating event of an aortic dissection is a tear within the intima, leading to separation of the layers of the aortic wall and the formation of 2 lumina, 1 true and 1 false. There is propagation of the dissection from the site of the tear; distal propagation is most common. Blood from the false lumen can reenter the true lumen at any point along the course of the dissection. The most common sites of origin of dissections are the proximal aspect of the ascending aorta and the distal arch just beyond to the origin of the left subclavian artery. According to the Stanford classification, dissections involving the ascending aorta are type A (regardless of the distal extent) and all others are type B.

Techniques for the diagnosis and characterization of aortic dissection include CT, MR, transesophageal echocardiography, and conventional angiography. Catheter aortography is rarely required because of the availability of highly sensitive and specific noninvasive imaging techniques. Potential findings on standard radiographs include mediastinal widening, cardiac silhouette enlargement, and a double contour of the aortic arch. Thrombus is occasionally present in the false lumen, producing high attenuation on unenhanced CT images and high signal intensity on T1-weighted MR sequences. The most important finding on contrast-enhanced CT and MRI is the presence of a thin intimal flap that separates the true lumen from the false lumen (see Figures 13-9 and 13-11). There are sometimes thin linear residual ribbons of media within the false lumen; that is, the “cobweb sign.” There are often varying flow characteristics in the true and false lumens (see Figure 13-10). The false lumen frequently compresses the true lumen. Potential complications of aortic dissection include branch-vessel obstruction and rupture into the pericardium, the left pleural space, or the mediastinum.^39,40

The nomenclature and classification of congenital vascular and lymphatic lesions has undergone considerable evolution. In 1982, Mulliken and Glowacki proposed the most widely accepted and most clinically useful system.⁴¹

They developed a biological classification system that separates vascular anomalies into 2 major categories: vascular neoplasms and vascular malformations. Vascular neoplasms, such as hemangioma, are characterized by cellular proliferation, cellular hyperplasia, and rapid growth; the suffix “-oma” should only be used for lesions with these characteristics. In contradistinction, vascular malformations are nonproliferating lesions caused by dysmorphogenesis.^42–44

The development of blood vessels occurs by 2 general mechanisms: vasculogenesis and angiogenesis. Vasculogenesis is the formation of new blood vessels by differentiation of precursor mesenchymal cells into endothelial cells. As opposed to this in situ formation of new blood vessels, angiogenesis is the formation of capillaries as extensions from preexisting blood vessels. As the endothelial lining of developing blood vessels matures, smooth muscle cell precursors migrate to form the muscular layers of the blood vessel walls. Vessel differentiation leads to the formation of veins, arteries, and capillaries. The lymphatic system develops as an extension from the embryonic venous system. Vascular malformations are congenital lesions that result from developmental errors at 1 or more stages of vasculogenesis and/or angiogenesis.^45,46

Vascular malformations tend to grow commensurately with the patient. When greater expansion occurs, it is because of enlargement of the blood-filled components rather than because of cellular proliferation. Vascular malformations can be subclassified according to the predominant vascular component and the hemodynamic features. Arteriovenous malformations and arteriovenous fistulae are high-flow malformations. Capillary malformations and venous malformations are slow-flow vascular malformations. Lymphatic malformations (previously termed lymphangiomas) are also slow-flow lesions. Mixed lesions can occur, and the terminology can be adapted to indicate the predominant components, such as “lymphaticovenous malformation” or “capillary-venous malformation.” All of the congenital vascular malformations can be considered variations of a single embryological anomaly, with categorization based on the pattern of embryological differentiation. In some patients, vascular malformations or vascular neoplasms occur in conjunction with additional developmental abnormalities (Table 13-5). Angiodysplasias are syndromes in which vascular malformations occur in association with specific patterns of involvement of adjacent structures (e.g., limb hypertrophy).

Vascular malformations can be categorized with imaging studies into 2 main types: high flow and low flow. High-flow lesions contain substantial arterial components (e.g., an arteriovenous malformation). Low-flow lesions have little or no arterial component (e.g., a venous malformation). MR is the most useful imaging technique for demonstrating the location of a vascular lesion and for detecting involvement of adjacent structures. This can be supplemented with MR angiography or MR venography to ascertain the flow characteristics. The simplest technique to evaluate the nature of blood flow within these lesions, however, is Doppler sonography. Blood flow velocity is accurately determined with sonography, and the compressibility of vessels and cysts can be evaluated. Angiography remains the gold standard technique for the imaging evaluation of vascular malformations. However, noninvasive techniques have largely supplanted angiography as a primary diagnostic technique for this indication. Angiography serves an important role during catheter-directed therapeutic interventions.⁴⁷

Hemangioma

Infantile Hemangioma

Infantile hemangioma is a benign developmental neoplasm composed of fibrous connective tissue and multiple vascular channels that are lined with a single layer of endothelium. Infantile hemangioma is the most common vascular tumor. The overall prevalence in infants is greater than 4%. Twenty percent of patients have multifocal lesions. At least one infantile hemangioma is present in approximately 10% of white infants by 1 year of age. There is an association with prematurity, low birth weight, female gender, and chorionic villus sampling. The female-to-male ratio is 2.5-4:1.⁴⁶

Infantile hemangioma is a complex mixture of cell types, including endothelial cells, pericytes, dendritic cells, and mast cells. Infantile hemangiomas undergo characteristic growth patterns, consisting of an initial phase of proliferation and rapid growth during the first year of life and subsequent slow involution over the next several years. During the proliferating phase, there is endothelial hyperplasia and the lesion contains a large number of mast cells. Elevated levels of the angiogenic proteins basic fibroblast growth factor and vascular endothelial growth factor are detectable within proliferating hemangiomas. The endothelial cells of a proliferating hemangioma express proteins that are also present in the placenta, including GLUT1. GLUT1 is an important histochemical marker for infantile hemangioma. Histological evaluation of involuting hemangiomas shows evidence of endothelial apoptosis, diminished angiogenesis, decreased size, fibrosis, and fat deposition. The tissue inhibitor metalloproteinase, which suppresses new blood vessel formation, appears to be involved in involution. Infantile hemangioma is distinct from noninvoluting vascular tumors in adults and older children that are sometimes labeled as hemangiomas because of clinical and/or histological similarities (e.g., cavernous hemangioma).^41,45,46,48

Although infantile hemangioma is a developmental lesion, it often is not identifiable at birth. Approximately one-third of patients present in the perinatal period with a pale cutaneous spot, a macular stain, or a pseudoecchymosis. The mass itself first becomes apparent sometime over the next few weeks or months, as the lesion enlarges. Nearly all patients present during the first year of life. Enlargement of the lesion (the proliferation stage) occurs for at least several months before the onset of regression. Small hemangiomas usually grow rapidly for a few weeks to a few months. Larger hemangiomas tend to grow for a longer period; rarely, there is continued growth during the second year of life. The involution stage varies from months to years. After involution, there is a variably sized end-stage fibrofatty residuum.

Classic infantile hemangioma is absent or quite small at birth. There are unusual instances of true “congenital” hemangiomas, with initiation of the proliferation phase during fetal life and the presence of a fully developed tumor at birth. These variants include rapidly involuting congenital hemangioma (RICH) and noninvoluting congenital hemangioma (NICH) (discussed in subsequent sections).⁴⁹

Infantile hemangiomas can arise in nearly any location throughout the body, with the skin representing the most common site. Approximately 60% of infantile hemangiomas occur in the head and neck region. Potential deeper sites of origin include the liver, trachea, orbit, and GI tract. Hemangiomas with a cutaneous component are readily diagnosed clinically. The lesion is red, raised, and irregular. Deeper lesions may have normal overlying skin, although the presence of skin hemangiomas elsewhere is a clue to the diagnosis. Cutaneous lesions can ulcerate and bleed. The size, location, and hemodynamic effects of the lesion determine the potential complications. Orbital hemangiomas can cause proptosis and visual disturbance. Approximately 30% of facial hemangiomas lead to childhood facial disfigurement. Subglottic hemangiomas cause stridor and hoarseness. Extensive hepatic hemangiomas can cause high-output cardiac failure in young infants.

A variety of developmental anomalies can occur in association with infantile hemangiomas. Head and neck hemangiomas (most commonly segmental hemangiomas of the face) sometimes occur in association with other anomalies as part of the PHACES syndrome. PHACES syndrome includes posterior fossa malformations, hemangiomas, arterial anomalies, cardiac anomalies and aortic coarctation, eye abnormalities, and a sternal cleft or suprapubic raphe. The hemangiomas in PHACES syndrome patients tend to be large, plaque-like lesions of the face. The appearance can be mistaken for the port-wine stain that occurs with Sturge-Weber syndrome. The potential posterior fossa malformations in children with PHACES syndrome include cerebellar hypoplasia, Dandy-Walker malformation, and cerebellar cortical dysplasia with features of polymicrogyria (Figure 13-15). Arterial anomalies that can occur in these children include unilateral or bilateral carotid artery aplasia or hypoplasia, kinking or tortuosity of the carotid arteries, vertebral artery hypoplasia, and persistence of the trigeminal artery (Figure 13-16). The eye lesions include glaucoma, cataracts, microphthalmos, optic nerve hypoplasia, and exophthalmos caused by an orbital hemangioma. PHACES syndrome may represent a phakomatosis with a broad phenotypic spectrum. A developmental field defect that occurs during early gestation is postulated. The female-to-male ratio for patients with PHACES syndrome is 9:1.^50–52

Many infantile hemangiomas do not require diagnostic imaging evaluation. Imaging studies are useful, however, to establish the diagnosis of a deep hemangioma or to delineate involvement of adjacent structures. Sonography, CT, MRI, angiography, and scintigraphy all provide characterizing information; imaging modality selection is based on the specific patient circumstance. In general, imaging of the spinal cord is indicated when there is a cutaneous hemangioma adjacent to the spine. Imaging of the liver and brain may be appropriate for children with multiple (5 or more) cutaneous hemangiomas.

Sonography shows an infantile hemangioma as a solid mass. Although large lesions insinuate along adjacent structures, the margins are usually relatively well circumscribed with both small and large hemangiomas. Doppler examination during the proliferation phase shows venous flow within the lesion, as well as high-velocity low-resistance arterial flow. There can be pulsatile flow in draining veins as a result of arteriovenous shunting. Color Doppler images show prominent perfusion during the proliferation phase, even if individual vessels are too small to be visualized on standard images (Figure 13-17). The vascularity of the lesion progressively diminishes during the involuting phase. A large high-flow hemangioma of the liver is sometimes detectable with prenatal sonography; initiation of maternal corticosteroid therapy may diminish the hemodynamic consequences for the neonate.^53,54

The solid nature of an infantile hemangioma can also be documented with CT. The lesion has similar attenuation characteristics as normal muscle on unenhanced images. Prominent contrast enhancement is typical. Some hemangiomas have a very homogeneous high-attenuation appearance on contrast-enhanced images, whereas others appear more heterogeneous. Some, but not all, have prominent vessels coursing through the mass. In areas such as the face, CT is useful for evaluating bony expansion adjacent to the mass.

For many children with a suspected infantile hemangioma, MR is the most useful and comprehensive imaging technique. The degree of involvement of adjacent soft-tissue structures is well documented by MR. Fat-suppressed T2-weighted images often provide the greatest differentiation from adjacent normal structures. A proliferating hemangioma is visualized as a solid, lobulated tumor that produces moderately high signal intensity on T2-weighted images, and is roughly isointense to other soft-tissue structures on T1-weighted images. Some hemangiomas have prominent vascular flow voids within the tumor matrix (Figure 13-18). The major arteries and veins adjacent to the lesion are usually normal. A large lesion in the proliferation phase sometimes has enlarged feeding arteries and draining veins (Figure 13-19). As with CT, contrast enhancement is usually intense, but varies somewhat between patients. During the involution phase, the increasing fibrous and fatty composition of the lesion results in a relative increase in signal intensity on T1-weighted images; the mass often appears heterogeneous on T2-weighted images. Vascular structures diminish in prominence during involution. In any infant with a plaque-like facial hemangioma, the examination should include cross-sectional MRI of the brain as well as MR angiography of the neck and head to asses for associated lesions.

Scintigraphy with radionuclide-labeled red blood cells (blood pool imaging) can be used as a confirmatory test for the diagnosis of infantile hemangioma. The vascular nature of the lesion is indicated on this study by rapid, intense, and persistent accumulation of labeled red cells.

Although only rarely indicated as a primary diagnostic study for patients with a suspected infantile hemangioma, angiography is an essential tool for endovascular therapeutic procedures. During the proliferating phase, an infantile hemangioma appears as a lobular mass with intense, persistent staining (Figure 13-20). The mass sometimes has the appearance of multiple lobules that are separated by ill-defined zones of diminished vascularity. The supplying arteries are usually only minimally enlarged, as are the draining veins. Angiographic evidence of arteriovenous shunting is lacking with most of these lesions.

Most infantile hemangiomas do not require specific therapy. Parents need to be reassured that the initial increase in size during the proliferation phase is to be expected, and that eventual spontaneous reduction will occur. Pulsed-dye laser therapy can be used to treat lesions with substantial ulceration. Medical, surgical, or endovascular therapies are sometimes indicated to treat hemangiomas that are associated with obstruction or distortion of an important structure, or those rare lesions that cause sufficient shunting to produce heart failure. The most commonly used medical therapy is intralesional or systemic corticosteroids. Interferon-α therapy is a second-line medical option, but carries the risk of spastic diplegia as a complication (occurring in approximately 5% of patients). Systemic vincristine therapy is also effective. Some hemangiomas are in locations that are amenable to surgical resection or debulking. Transcatheter particulate embolotherapy is effective in reducing the vascularity of a high-flow hemangioma that is causing cardiac failure. Embolization is also an option for reducing the size a hemangioma that is interfering with the function of an important adjacent structure; intraarterial injection of corticosteroid can be performed as part of the procedure.⁵⁵

The distinction between a hemangioma and a venous malformation or lymphatic malformation is usually straightforward on cross-sectional imaging studies, as a hemangioma is a solid mass without cysts or large blood-filled spaces. Infantile vascular neoplasms with features that sometimes overlap those of infantile hemangioma include kaposiform hemangioendothelioma, tufted angioma, and hemangiopericytoma. Malignant neoplasms occasionally have imaging features that overlap those of hemangioma. Biopsy is required for children with clinical or imaging features suggesting an aggressive lesion.

Rapidly Involuting Congenital Hemangioma

RICH is a recently recognized vascular lesion in which the tumor is fully developed at birth and undergoes rapid involution. This is distinct to the pattern of infantile hemangioma, in which there is increase in size for at least the first several months of life, prior to spontaneous regression. Involution of RICH progresses rapidly over the early months of life, and complete resolution occurs at less than 1 year of age in most patients. Physical examination demonstrates a firm mass or plaque that is red or purple with a pale or blanched halo. A surface telangiectasia may be present. After involution, some patients have residual soft-tissue atrophy. A large RICH can cause high-output cardiac failure.

The pathological features of RICH are distinct from those of infantile hemangioma. Histological examination shows lobules of capillaries within a densely fibrotic stroma that contains hemosiderin deposits. There is focal lobular thrombosis and sclerosis. Multiple thin-walled vessels are usually present. Intermingling of the neovasculature with normal tissue elements (as occurs with infantile hemangioma) is lacking. Also distinctive from infantile hemangioma is a lack of immunoreactivity for GLUT1 and LeY.^56,57

Sonographic examination of RICH shows a well-circumscribed mass that is predominantly located in the subcutaneous fat. The lesion is diffusely vascular. A mixture of vessels with arterial and venous flow characteristics is typical. The echo character varies between patients. The lesion enhances intensely on CT and MR (see Figure 26-35 in Chapter 26). There is marked hyperintensity on T2-weighted MR sequences. Fat-suppressed T2-weighted images provide optimal differentiation from adjacent soft tissues. The mass may appear homogeneous or somewhat heterogeneous on MR images. With a large mass, there are usually prominent flow voids because of dilated draining veins. The flow voids predominate along the peripheral aspect of the lesion. The flow voids tend to be much larger than those associated with infantile hemangioma.^57,58

Angiography of RICH shows heterogeneous parenchymal staining, large and irregular feeding arteries in a disorganized pattern, arterial aneurysms, direct arteriovenous shunts, and intravascular thrombi. Large draining veins predominate at the periphery of the lesion. The angiographic appearance sometimes mimics that of an arteriovenous malformation or a congenital infantile fibrosarcoma.⁵⁹

Noninvoluting Congenital Hemangioma

NICH refers to a rare cutaneous vascular lesion that, unlike classic infantile hemangioma or RICH, does not regress spontaneously. This lesion may represent a variant of RICH. A NICH is a solitary cutaneous lesion that usually measures a few to several centimeters in diameter. The lesion is clinically evident at birth, and continues to grow approximately in proportion to the adjacent normal structures. Histological examination shows lobular collections of small thin-walled vessels and a large central vessel. Doppler ultrasound demonstrates high-velocity flow. The mass usually appears homogeneous on cross-sectional imaging studies, and undergoes prominent uniform enhancement. The imaging features of NICH generally do not allow distinction from classic hemangioma of infancy.⁶⁰

Kaposiform Hemangioendothelioma

Kaposiform hemangioendothelioma is a rare benign vascular tumor that is distinct from infantile hemangioma and has no association with Kaposi sarcoma. The lesion is characterized histologically by the presence of infiltrating nodules and sheets of spindle cells. This aggressive benign neoplasm often undergoes rapid enlargement. The cutaneous component is clinically obvious, with marked edema, induration, and purpura. There is a poorly defined ecchymotic margin. The lesion is often painful. Kaposiform hemangioendothelioma is a lesion of infancy, with the diagnosis made at birth in approximately half of patients. Unlike infantile hemangioma, kaposiform hemangioendothelioma does not have a gender predilection. Common sites of involvement include the extremities, head and neck region, mediastinum, retroperitoneum, and pelvis. Kaposiform hemangioendothelioma is often (at least 50% of patients) complicated by Kasabach-Merritt syndrome (as is tufted angioma). This potentially life-threatening thrombocytopenia results from platelet trapping within the vascular tumor. The architectural features of these lesions cause turbulent blood flow and platelet activation.^52,61–63

MRI is the most useful imaging technique for infants with kaposiform hemangioendothelioma. This aggressive vascular neoplasm has poorly defined, infiltrative margins. Fibrosis, blood products, and vessels result in a heterogeneous character (Figure 13-21). Signal voids as a result of hemosiderin deposits are common. The majority of the lesion is moderately hyperintense on T2-weighted images. There is diffuse contrast enhancement of the mass. Erosion of adjacent bony structures can occur; this is best demonstrated with CT. Imaging studies performed after therapeutic interventions typically show diminished size of the mass, but there are usually residual enhancing foci of viable tumor. The aggressive growth characteristics of kaposiform hemangioendothelioma sometimes result in imaging features that overlap those of a malignancy.⁶⁴

Because of the large and aggressive nature of kaposiform hemangioendothelioma, therapy is almost always required. Variable clinical results have been achieved in treating these patients with systemic corticosteroids, interferon-α, and systemic chemotherapy. Radiation therapy has also been utilized for some patients. Spontaneous regression is not a feature of this tumor. Metastasis does not occur.^65,66

Kaposiform hemangioendothelioma complicated by Kasabach-Merritt syndrome is fatal in nearly 1 in 4 patients. Heparinization is contraindicated for these children, as it can lead to accelerated tumor growth and subcutaneous hemorrhage. Platelet infusion can also precipitate rapid expansion of the mass. Treatment of children with Kasabach-Merritt syndrome generally consists of supportive care and immediate institution of therapies aimed at diminishing the size of the tumor. Transcatheter embolization is helpful for some patients.^63,67,68

Tufted Angioma

Tufted angioma is a rare cutaneous vascular tumor that is characterized clinically by slowly spreading erythematous macules and plaques, sometimes including nodular formations. The name is derived from the histological appearance, which includes small circumscribed angiomatous tufts and lobules scattered in the dermis. Tufted angioma is predominantly a lesion of children. The tumor is visible at birth in some patients. The neck and upper trunk are the most common sites of involvement. Slow extension into the adjacent skin is typical. Extensive lesions can cause Kasabach-Merritt syndrome. Because this is a cutaneous lesion, diagnostic imaging studies are generally not required. Tufted angioma is sometimes termed angioblastoma of Nakagawa.^69–71

Hemangiopericytoma

Hemangiopericytoma is a rare soft-tissue neoplasm that arises from endothelial pericytes. In keeping with the vascular origin, this tumor can arise anywhere in the body. Some hemangiopericytomas have malignant characteristics. Hemangiopericytomas arising in children younger than 1 year of age typically follow a more benign clinical course than those arising in older children or adults. Histological examination shows endothelial proliferation within these lesions. Approximately one-third of hemangiopericytomas in children are congenital. Congenital hemangiopericytoma may undergo a phase of rapid initial growth in the young infant; spontaneous regression similar to that of infantile hemangioma occasionally occurs.⁷²

The imaging appearance of hemangiopericytoma is that of a well-circumscribed soft-tissue mass. Calcifications are occasionally present. Although any portion of the body can be involved, the most common locations are the thigh and the pelvic retroperitoneum. The congenital variety often arises within the subcutaneous tissues. These aggressive lesions sometimes cause erosion of adjacent bone. There is marked contrast enhancement on CT and MR. Conventional angiography shows a dense tumor stain and small vessel arteriovenous shunting.⁷³

Arteriovenous Malformation

Arteriovenous malformations are congenital high-flow vascular anomalies. Abnormal connections between arteries and veins are present within the “nidus” of the lesion, which consists of a tangle of small, tortuous, dysplastic vessels. There are dilated arteries extending into the nidus and dilated veins draining from the nidus, but the enlargement of these vessels is secondary to the shunting at the nidus. Even though they are congenital lesions, arteriovenous malformations can present at any age during childhood; some do not become apparent until adulthood. Potential presenting symptoms include cutaneous changes, a palpable mass, pain, or manifestations of effects on adjacent structures. Superficial lesions can ulcerate or bleed. Arteriovenous malformations in the extremities cause hemodynamic alterations that sometimes lead to soft tissue and osseous overgrowth. Arteriovenous malformations tend to slowly increase in size with time. Sudden enlargement can be triggered by pregnancy, puberty, hormonal therapy, trauma, or surgery.⁴⁶