Vascular lesions of the CNS can uncommonly be confused with neoplasms, both by the imaging appearance and clinical symptoms. In these cases, the role of the radiologist is to alert clinicians to the possibility of a vascular lesion and ensure proper imaging to avoid a potentially dangerous biopsy or a delay in appropriate management. Vascular lesions that are benign, ischemic, inflammatory, or iatrogenic in nature can all present with imaging features that simulate neoplasms. Our aim was to present a series of representative cases that highlight these lesions, with a discussion of imaging features to aid the correct diagnosis.
Learning Objective: Recognize imaging features of lesions that suggest a vascular rather than neoplastic etiology and the appropriate next steps for diagnosis.Keywords
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Despite continued advances in imaging, accurate differentiation between neoplastic and non-neoplastic masses of the CNS frequently poses a diagnostic challenge. Vascular lesions are among the more common lesions to simulate neoplasms on imaging and include both atypical presentations of common lesions and typical presentations of uncommon disorders. Differentiating vascular lesions from neoplastic lesions is particularly important for patient management and safety because biopsy of an aneurysm, infarction, or benign vascular malformation is unnecessary and potentially dangerous. Despite the occasional imaging overlap, many imaging features can aid in obtaining the correct diagnosis of a vascular lesion or guide recommendations for confirmatory vascular imaging. This article reviewed the overlapping imaging appearance of vascular lesions and neoplasms of the CNS and highlighted key clinical and imaging features that facilitate prospective diagnosis.
Aneurysms and pseudoaneurysms exhibit a variety of locations, sizes, and appearances on CT and MR imaging. They vary from each other in the degree of disruption of the 3 layers of the arterial wall or tunics (intima, media and/or muscularis, and adventitia) and the intervening internal and external elastic laminae present between each of the 3 tunics. Aneurysms are focal outpouchings of the arterial wall caused by structural weakening of a variety of causes, including congenital and environmental factors, which result in disruption of the internal elastic lamina and sometimes tunica media. Pseudoaneurysms are also focal outpouchings but are typically caused by vascular injury related to trauma, surgery, drug abuse, infection, or tumor invasion. They lack any of the normal arterial wall layers, with only tenuous and intermittent layers of adventitia, hemorrhage, clot, and fibrin that contains the aneurysmal contents. Aneurysms can be saccular or fusiform, with sizes that range from small (<1 cm) to large (1–2.5 cm) or giant (>2.5 cm). The aneurysm sac may be completely patent or may contain eccentric mural thrombus due to blood stasis. Clinically, patients with aneurysmal rupture and intracranial hemorrhage usually present with a severe headache, often described as the “worst headache of their life.” Patients with unruptured aneurysms may remain asymptomatic or may produce symptoms related to mass effect on adjacent structures. Large or giant intracranial aneurysms often present with neurologic symptoms related to mass effect simulating a tumor clinically including cranial nerve dysfunction (diplopia, tinnitus, vertigo), weakness, sensory disturbance, seizures, or pituitary endocrine dysfunction.1 Ischemic presentations can also occur, including transient ischemic attacks and cerebral infarctions, presumably secondary to distal thromboembolic disease from intra-aneurysmal thrombus.
Large aneurysms can mimic extra-axial neoplasms on imaging studies in a variety of locations. When growth is primarily intracranial, aneurysms can cause mass effect and edema within the adjacent brain parenchyma (Fig 1), similar to large extra-axial neoplasms.2,3 Aneurysms of the cavernous ICA (Fig 2) can expand the cavernous sinus and exert mass effect on the temporal lobe, similar to a cavernous sinus meningioma, schwannoma, and pituitary macroadenoma with cavernous sinus invasion or metastasis. Cavernous ICA aneurysms can also extend extracranially through defects in the skull base into the sphenoid sinus and cause expansile remodeling of the sinonasal cavity (Fig 3), which may simulate neoplasms of the skull base or sinonasal cavity, mucocele, or invasive pituitary macroadenoma. Cavernous or supraclinoid ICA aneurysms can also protrude into the sella, which could be confused for a Rathke cleft cyst or hemorrhagic pituitary adenoma. Petrous ICA aneurysms are much less common but, when present, can markedly expand the carotid canal (Fig 4) and may be confused for an expansile petrous apex lesion, such as cholesterol granuloma or dermoid or epidermoid cysts. Dermoid cysts that resembled thrombosed aneurysms have been reported, but an avascular pattern can be appreciated on angiographic studies.4,5 Large aneurysms of the anterior communicating artery can exert mass effect on the frontal lobes and protrude into the suprasellar cistern (Fig 1), similar to a meningioma or craniopharyngioma. Similarly, large aneurysms of posterior inferior cerebellar artery (Fig 5) may mimic hemorrhagic or densely cellular posterior fossa tumors, such as metastasis, hemangioblastoma, or meningioma.
Several CT imaging features are helpful in differentiating large aneurysms from extra-axial tumors. On bone windows, large aneurysms may produce smooth expansile bone remodeling of adjacent skull base structures (Figs 2F3–4). This feature is helpful in differentiating aneurysms from skull base neoplasms that more typically produce hyperostosis (meningioma) or permeative osseous changes (metastasis) but could simulate other slow-growing lesions, such as schwannoma, mucocele, or cholesterol granuloma. Large aneurysms frequently demonstrate rim or “egg-shell” calcification (Figs 1, 2), in contrast to many mineralizing neoplasms, such as meningioma, craniopharyngioma, or chondrosarcoma, that are characterized by central, irregular tumoral calcification or matrix.2,3 Nonthrombosed aneurysms are homogenously attenuated on CT, similar to intravascular blood. The thrombosed component often demonstrates heterogeneous attenuation on CT, which is frequently eccentric and may have a layered appearance (Figs 1, 2, 5). Such a layered and organized appearance of blood products would be atypical for neoplasm.
The MR imaging appearance of a partially thrombosed aneurysm is often very heterogeneous and could be confused with a hemorrhagic neoplasm; however, there are several features that are helpful in differentiating these entities. Pulsation artifacts in the phase-encoded direction are perhaps the most specific distinguishing feature between aneurysms and tumors (Figs 1, 2), although this is not always seen. Dark T2-weighted signal intensity within the lesion may correspond to a flow void within the lumen or blood products in the thrombosed component. This is helpful in differentiating aneurysms from most neoplasms that tend to exhibit intermediate-to-bright signal intensity on T2-weighted images. The thrombosed component of an aneurysm sac often demonstrates heterogeneous T1 bright and T2 dark signal intensity on MR imaging, which may appear eccentric or layered (Figs 1, 2, 3, 5). Steady-state free precession MR imaging techniques have been shown to improve delineation of aneurysm thrombus by increasing contrast between flowing blood and thrombus relative to T2-weighted images (Fig 2).6 Aneurysm thrombus contains blood breakdown products that frequently produce a pronounced magnetic susceptibility effect (Fig 1, 2), which could simulate a variety of extra-axial lesions that contain blood products. Restricted diffusion related to thrombus can also be seen within an aneurysm sac; however, this is typically heterogeneous, which differentiates it from other lesions such as epidermoid cyst, abscess, or densely cellular neoplasms, which demonstrate more homogeneous restricted diffusion.2,3
On gadolinium contrast-enhanced MR imaging, the enhancement pattern within an aneurysm sac is often confirmatory but could still occasionally be confused for a neoplasm. An aneurysm that is completely patent will enhance avidly and homogeneously, potentially simulating an avidly enhancing tumor such as meningioma. In these cases, thin section T1 postcontrast imaging is very helpful in delineating the relationship to the parent vessel, which can be overlooked on thicker section images. A partially thrombosed aneurysm often exhibits a heterogeneous appearance on T1 postcontrast images. The “target sign” with peripheral rim and central nodular enhancement has been described as a characteristic feature.7 The patent portion of the lumen enhances avidly but may have a variety of shapes, which range from round to serpiginous (Figs 1F2F3F4–5). The thrombosed component of the sac will often contain areas of intrinsically T1 bright thrombus and other areas of T1 dark nonenhancing thrombus. These may assume a layered concentric configuration that surrounds the aneurysm lumen (Figs 1F2–3, 5). This heterogeneous pattern of avid contrast enhancement admixed with intrinsic T1 bright signal intensity could potentially mimic craniopharyngioma or a skull base metastasis.2,3
On CTA or MRA, the patent portion of the aneurysm sac demonstrates continuity with the parent vessel (Figs 1F2F3F4–5), which usually confirms the diagnosis. Often, the patent lumen will course through the center of the thrombosed aneurysm sac in a serpiginous fashion, visible on CTA, MRA, and T1 postcontrast images (Figs 2, 4). On 3-dimensional time-of-flight MRA, there is a potential pitfall when imaging a partially thrombosed aneurysm. The luminal thrombus is often T1 hyperintense, which produces high signal intensity on MRA similar to that of flowing blood. Therefore, careful comparison of MRA source images with conventional MR imaging sequences, including thin section T1 postcontrast image, is often necessary to accurately determine the size of the patent lumen. Conventional DSA is often performed for diagnosis and/or treatment; however, this technique can only visualize the lumen and cannot directly visualize the thrombosed components of the aneurysm sac or accurately determine the wall thickness. Therefore, it is important to evaluate CT and MR imaging in conjunction with conventional angiography, if performed, to understand the true size of the aneurysm.
Stroke is a clinical diagnosis, often supported by a corresponding abnormality on brain imaging. The clinical diagnosis of ischemic stroke is often straightforward but can be inaccurate up to 30% of the time.8 The clinical presentation and imaging findings of ischemic stroke can occasionally overlap those of a brain tumor.8,9 Acute infarctions are easily diagnosed on MR imaging or serial CTs within the first few days after ictus; however, subacute infarctions are notorious for mimicking tumor or infection when patients present many days after ictus. Contrast enhancement and mass effect are frequently seen with subacute infarctions (Fig 6), which could simulate a high-grade glioma, metastasis, or encephalitis. Diffusion restriction within subacute infarctions is often heterogeneous and eventually pseudonormalizes, which could simulate the heterogeneous diffusion characteristics of a high-grade neoplasm. Hemorrhagic transformation, a common feature of subacute infarctions, could simulate hemorrhagic change within a neoplasm (Fig 6).
Several imaging features on MR imaging and CT are helpful in differentiating a subacute infarction from other contrast-enhancing lesions. Signal intensity abnormality that involves a single arterial distribution with characteristic wedge shape and sharp margins is often helpful in distinguishing between infarction and tumor. The contrast-enhancement pattern of subacute infarctions that involve cortical gray matter is frequently gyriform, which strongly favors a subacute infarction over neoplasm. Close attention to the artery that supplies the signal intensity abnormality is important as well. A loss of a flow void on MR imaging, a filling defect on CT or MR angiography, or a hyperattenuating thrombus in the artery on CT is strong evidence for arterial infarction. Diffusion restriction is usually homogenous and intense, with acute to early subacute infarctions but becomes more heterogeneous and eventually “pseudonormalizes” and reverses in the late subacute phase. By contrast, diffusion restriction in hypercellular neoplasms may be more mild and homogeneous in tumors that lack necrosis, such as lymphoma or meningioma, or markedly heterogeneous in the presence of a necrotic high-grade tumor, such as glioblastoma or metastasis.9
It is frequently difficult to distinguish multiple small subacute embolic infarctions from cerebral metastases. Subacute embolic infarctions are of variable sizes, often juxtacortical in location, and demonstrate contrast enhancement, variable restricted diffusion, and surrounding edema, all characteristics of metastases. Several features are helpful in differentiating small infarctions from metastases. Subacute embolic infarctions often have a more-curvilinear pattern of enhancement than parenchymal metastases and cause minimal surrounding edema relative to the size of the lesion. Metastases tend to be more rounded in shape, and the larger lesions often produce vasogenic edema disproportionate to the size of the lesion. Embolic infarctions are typically of slightly different ages, which leads to various patterns of DWI and ADC signal intensity within lesions. Restricted diffusion within metastases is less common, although can be seen when the primary tumor is densely cellular. When there is persistent diagnostic uncertainty, a follow-up MR imaging in 1–2 weeks is often sufficient to demonstrate early temporal evolution of embolic infarctions.
Cerebral venous sinus thrombosis may lead to hemorrhagic venous infarction, which can mimic cerebral neoplasm, inflammation, or encephalitis. Some of the more common presenting symptoms include headache, seizures, focal neurologic deficits, and impaired consciousness, which often develop over days or weeks.10 Occlusion of a dural venous sinus and/or cortical vein may produce vasogenic edema in the drainage territory of the occluded vessel. More-severe cases produce patchy or gyriform contrast enhancement, mass effect, and hemorrhage (Fig 7). DWI sequences may reveal variable signal intensity characteristics, with predominantly facilitated diffusion and some areas of restricted diffusion (Figs 7, 8), similar to many primary cerebral neoplasms. Susceptibility weighted or conventional T2* gradient recalled echo images may demonstrate foci of hemorrhage, which may be petechial and gyriform, or may form a space-occupying hematoma (Fig 7). These findings can overlap those of high-grade gliomas and metastases.10,11
Additional imaging findings can be helpful in differentiating venous infarction from tumor. Vasogenic edema that corresponds to a venous drainage territory is suggestive. For example, deep venous sinus thrombosis that involves the internal cerebral veins can produce an abnormality in the bilateral thalami and deep brain structures, although this can occasionally be asymmetric or unilateral (Fig 8). Transverse and sigmoid sinus occlusion can produce an abnormality both above and below the tentorium, including the temporal lobe and cerebellum (Fig 7). Small foci of petechial hemorrhage in a gyriform pattern are supportive of venous infarction. Facilitated diffusion with superimposed areas of restricted diffusion (Figs 7, 8), especially when involving the cortex, also supports venous infarction rather than primary glial tumors, which tend to occasionally spare the cortex. Close assessment of dural venous sinuses and cortical veins for flow voids is essential in obtaining an accurate diagnosis. Loss of flow void, with abnormally increased T1 and T2 signal intensity may be seen on MR imaging in venous sinus occlusion. High-resolution 3-dimensional gradient recalled echo contrast-enhanced T1-weighted images are also highly effective at detecting dural venous or cortical venous thrombus with high sensitivity and specificity comparable with MRV.12 A superficial cortical venous “cord” that produces a blooming susceptibility effect on iron-sensitive sequences that overlay the area of abnormality is highly suggestive of venous occlusion. Angiographic assessment with CTV or MRV usually confirms the venous occlusion.10,11
A dural arteriovenous fistula (DAVF) is a network of blood vessels in the wall of a dural venous sinus that shunts blood between dural arteries and dural venous sinuses, meningeal veins, or cortical veins. Multiple arteries that arise from the external carotid arteries and/or ICAs frequently supply a DAVF, although posterior circulation arteries can less commonly contribute an arterial supply. The etiology of these vascular malformations remains unclear. DAVFs have been linked to dural venous sinus thrombosis, trauma, and previous craniotomy but are often idiopathic. Patients present with a wide variety of symptoms related to the location and aggressiveness of the fistula. Those fistulas that involve the transverse and sigmoid sinuses, 2 of the most common locations for DAVFs, frequently cause pulsatile tinnitus. Cavernous sinus DAVF can cause pulsatile exophthalmos, chemosis, ophthalmoplegia, and decreased visual acuity. More aggressive fistulas can present with seizures, hemorrhage, and dementia.
Borden and Cognard classification schemes illustrate the key features associated with aggressive DAVF.13,14 Central to both classification schemes is the presence of cortical venous reflux or drainage, which portends a significantly higher rate of intracranial hemorrhage and mortality without treatment. van Dijk et al15 showed an annual mortality rate of 10.4% and hemorrhage rate of 8.1% in patients with cortical venous drainage. Aggressive DAVFs with cortical venous drainage can simulate a neoplasm on imaging when associated with parenchymal edema and mass effect. A correct diagnosis requires attention to imaging clues that are often subtle. On noncontrast CT, aggressive fistulas can present with parenchymal, low-attenuation, vasogenic edema, mass effect, and hemorrhage owing to severe venous hypertension and impaired venous drainage. Bone windows may reveal dilated skull base foramina, most commonly, the foramen spinosum, due to dilatation of the middle meningeal artery that supplies the fistula. Multiple transosseous vascular channels may be present in the calvaria adjacent to the fistula site, which transmit dilated arterial feeder branches of the external carotid artery. Hyperattenuating thrombus is occasionally identified in the involved dural venous sinus.
On MR imaging, severe venous hypertension that results from DAVF can cause a signal intensity abnormality within the brain parenchyma, including a vasogenic edema pattern on T2 and FLAIR, mass effect, hemorrhagic foci on SWI, and contrast enhancement (Figs 9F10–11). These findings are similar to those of venous infarction but can also be confused for a high-grade glial neoplasm or inflammatory lesion. Another diagnostic clue is the loss of flow void in the involved dural venous sinuses due to the presence of thrombus, which commonly coexists with DAVF. There frequently are multiple dilated corkscrew vessels adjacent to the lesion within the subarachnoid space or parenchyma (Figs 9, 10). SWI is particularly helpful in characterizing the vascular changes associated with DAVF.16 Hyperintensity within the involved dural venous sinus on SWI is often seen as a result of oxygenated, arterialized high flow within the sinus. Hyperintense signal intensity within the cortical veins has been shown to correlate with retrograde cortical venous drainage, which is an indication for treatment because of a higher risk of spontaneous intracranial hemorrhage if left untreated.17 In another published series, SWI venogram demonstrated dilated cerebral veins on the surface of the brain in all of the 14 patients with DAVF and cortical venous drainage.18
Angiographic imaging with MRA and CTA may show dilatation of arteries that supply the fistula and dilated veins that drain the fistula. Occlusion of the involved dural venous sinus is frequently seen on CTV and MRV. MRA without gadolinium by using a 3-dimensional time-of-flight technique is particularly sensitive to velocity of flow and can reveal abnormally high “arterialized” flow signal intensity within the involved dural venous sinus and draining cortical veins (Fig 10). Time-resolved dynamic MRA and CTA can directly demonstrate early venous drainage and retrograde venous flow. Catheter cerebral DSA is generally performed to assess the drainage pattern and to determine appropriate management. In summary, to increase sensitivity for recognizing DAVF on CT and MR imaging, one should appreciate the presence of abnormally dilated cortical venous structures in the vicinity of the lesion and carefully evaluate bone windows for enlarged skull base or transosseous arterial feeders. Careful evaluation should always be performed for dural venous sinus thrombus by noting the presence of arterialized venous flow signal intensity on MRA and assessing for parenchymal signal intensity changes related to venous hypertension.
Spinal DAVFs can frequently mimic spinal cord neoplasms and inflammatory lesions. The typical presentation is that of a middle-aged man (5th–6th decade, 5:1 male-to-female ratio) with progressive ascending sensory and motor symptoms, including paresthesias, sensory loss, gait dysfunction, and weakness.19 Spinal DAVFs are arteriovenous shunting lesions that result from an abnormal communication between a dural artery and the perimedullary venous system of the spinal cord.20 Altered arterial and venous hemodynamics produce venous hypertension and congestion, the pathophysiologic process responsible for the edema in the central spinal cord. Abnormal T2 hyperintense signal intensity in the spinal cord or lower brain stem is the most sensitive sign for a spinal DAVF.21 Additional findings, including cord enlargement and enhancement, are less frequently observed.21–23 Together, these findings can mimic a spinal cord tumor, such as an astrocytoma, ependymoma, or myelitis (Figs 11, 12).
The most helpful finding on MR imaging for distinguishing spinal DAVF from other spinal cord lesions is the presence of multiple dilated, intradural, perimedullary veins along the surface of the spinal cord. These manifest as flow voids on T2-weighted images20 (Figs 11, 12) but are often better appreciated as enhancing vessels on postcontrast images.19 However, enlarged vessels on the cord surface are absent in 50% of the cases.20,21 An additional finding that has been described is abnormally low T2 signal intensity in the cord periphery, which occurred in all 15 cases of spinal DAVF in 1 series.22 This was thought to be related to accumulation of deoxyhemoglobin in the peripheral pial capillaries due to venous hypertension.22
The cord edema caused by spinal DAVF usually has flame-shaped superior and inferior margins and most commonly involves the lower thoracic spinal cord and conus (Fig 12). Spinal DAVFs most commonly cause an ill-defined and patchy enhancement pattern within the cord (Fig 12), in contrast to the more focal nodular enhancement pattern frequently seen with primary spinal cord tumors.23 Conventional spinal angiography with DSA is typically required to confirm, localize, and eventually treat the fistula in a patient with aggressive imaging and clinical findings. Angiography studies can be lengthy and entail sequential injections of multiple spinal arteries on each side in search of the lesion. Preangiography spinal MRA is helpful to confirm dilatation of the perimedullary venous plexus, which can predict the side and level of the fistula, and has been shown to shorten procedure time and thus reduce radiation and contrast dosage for subsequent DSA.24
Cavernous malformations demonstrate a wide variety of appearances on CT and MR imaging, some of which can simulate aggressive neoplasms. Cavernous malformations, also referred to as cavernomas, are benign vascular hamartomas composed of a compact mass of sinusoidal-type vessels in apposition, without intervening normal brain parenchyma. Lesions can occur anywhere within the brain, brain stem, or spinal cord, or along the surface of the parenchyma or cranial or spinal nerve roots. These typically hemorrhage repeatedly in small amounts, with episodes separated in time by months or years. The annual hemorrhage rate is estimated to be <1% per year. The hemorrhagic event may be clinically silent, minor, or major. Most cavernous malformations are incidentally discovered on imaging studies. Lesions are most commonly isolated and sporadic but can also be multiple, as in patients with familial multiple cavernous malformation syndrome. When symptomatic, patients with cavernous malformations most commonly present with seizures or focal neurologic deficits due to acute hemorrhage; these are also common presentations for brain tumors.
The characteristic imaging appearance of cavernous malformations results from a combination of repeated intralesion hemorrhage and internal venous sinusoids. A complete hemosiderin rim on T2-weighted sequences is almost always present unless there has been recent hemorrhage within the lesion. Hemorrhage within the lesions often appears iso- to hyperintense on T1-weighted images. Zabramski et al25 classified cavernous malformations into 4 different categories based on the age of hemorrhage and size of the lesion. Type 1 Zabramski lesions contain subacute hemorrhage with methemoglobin products, characterized by increased T1 and variable T2 signal intensity (Fig 13). These lesions can cause a degree of surrounding brain edema, depending on the size of the lesion and amount of hemorrhage. Type 2 Zabramski lesions are referred to as the classic “popcorn” or “mulberry” lesion, characterized by mixed signal intensity on T1- and T2-weighted images, which reflect blood products of varying ages (Fig 14).
Due to their associated acute-to-subacute perilesional findings, the type 1 and type 2 Zabramski lesions are more likely to simulate neoplasms. Type 3 Zabramski lesions contain more chronic hemorrhagic products, which are hypointense on T1- and T2-weighted images. Type 4 Zabramski lesions are punctate microhemorrhages with or without blooming artifacts, which are easily visualized on T2*/gradient recalled echo sequences but are generally not visible on other sequences. Occasionally, cavernous malformations enlarge and become giant (>4–6 cm) (Fig 14). These lesions frequently present as multicystic lesions with rings of hemosiderin, which form a “bubbles of blood” appearance.26 Small fluid–fluid levels can be seen in some giant cavernous malformations.27 Calcifications are also frequently seen. Lesions with recent hemorrhage typically demonstrate a surrounding rim of vasogenic edema and mass effect. Contrast enhancement within a cavernous malformation is variable and usually minimal; however, large lesions can demonstrate avid heterogeneous contrast enhancement.28 Cavernous malformations tend to grow over time through repeated intralesion hemorrhage.28 Many of these features, including interval growth over time, contrast enhancement, hemorrhage, and surrounding brain edema can simulate a malignant brain neoplasm.
Several imaging features are helpful in differentiating a cavernous malformation from a malignant neoplasm. When a cavernous malformation presents acutely with hemorrhage, a follow-up MR imaging study in 2–3 months is often required to see the characteristic imaging features of cavernous malformation that may be obscured by hematoma in the acute phase. A complete hemosiderin rim seen after resolution of the acute hematoma is more characteristic of a benign hemorrhage or cavernous malformation than of a hemorrhagic neoplasm.26 In contrast to parenchymal hematomas of other causes, however, hemoglobin degradation products within cavernous malformations often do not follow a typical time course and may demonstrate T1 hyperintense methemoglobin for years. In addition, there often are imaging findings related to multiple previous hemorrhagic episodes that imply a chronic lesion rather than an aggressive neoplastic mass. SWI sequences may reveal extensive regional hemosiderosis related to previous episodes of hemorrhage leaking into the surrounding tissues or subarachnoid space (Fig 14). Similarly, T2 and FLAIR sequences may reveal encephalomalacia and volume loss adjacent to the lesion related to previous hemorrhage that had resolved (Fig 14).
Multiplicity of lesions is also a helpful diagnostic feature (Fig 14) and, when observed, should prompt consideration of genetic causes.28 Brain radiation is a risk factor associated with cavernous malformations and may be a helpful diagnostic clue.29 When multiple, many of the lesions are often small and only be visible on SWI images due to blooming susceptibility effects. However, these could also be confused for multifocal chronic microhemorrhages due to another cause, such as cerebral amyloid angiopathy (CAA), hypertension, or even cerebral metastases, unless larger lesions with characteristic imaging features are identified.
Another supportive diagnostic feature is the presence of an adjacent developmental venous anomaly.28,29 Developmental venous anomalies, also referred to as a venous angiomas, are dilated transcerebral veins that collect multiple radially oriented medullary veins or venous radicals.30 These are the most-common cerebral vascular malformation, with an incidence of approximately 3%.31 Developmental venous anomalies are commonly associated with other vascular malformations (13%–40%), most frequently a cavernous malformation (Fig 13).32 Developmental venous anomalies are rarely symptomatic and are typically diagnosed incidentally on CT and MR imaging by identifying an aberrant draining vein and prominent venous radicles. The venous radicles create the pathognomonic “caput medusae” appearance on postcontrast images.32 In the absence of contrast, T2*, gradient recalled echo, or SWI sequences often best visualize these structures. Parenchymal signal intensity abnormalities associated with developmental venous anomalies are infrequent in the experience of these authors, although they have been reported with variable incidence (28%–65%).31,33,34 The most common parenchymal abnormalities include locoregional atrophy, white matter signal intensity change, cavernous malformation, and calcification.31,33
Brain capillary telangiectasia (BCT) is a benign, low-flow vascular malformation characterized by clusters of enlarged, dilated capillaries interspersed with normal neural parenchyma. BCTs usually are incidental findings and rarely symptomatic. Described presenting symptoms include seizures, blurred vision, cranial nerve dysfunction, progressive spastic paraparesis, confusion, vertigo, tinnitus, dizziness, and headache.35,36 A meta-analysis revealed that 6% of the 203 patients with BCT were symptomatic.37 In another study, BCTs were attributed as the likely cause for 2 of 105 patients' presenting signs and/or symptoms (1.9%).35 The 2 patients who presented with seizures in this series had large BCTs (>1 cm) in the anterior temporal lobe and basal ganglia, respectively.35 Initial imaging and clinical findings were concerning for low-grade glial neoplasms due to the unusually large size and symptomatic presentation of the lesions.35 Imaging findings of BCT are frequently pathognomonic, especially when in the pons. The most common locations are the pons (78%) and the basal ganglia (11%) (Fig 15).37 Faint brushlike contrast enhancement and hypointensity on T2*/SWI images are virtually diagnostic.38 BCTs are occult on noncontrast CT and often demonstrate isointensity on T1, T2, and FLAIR, with no mass effect (Fig 15). In a meta-analysis of imaging features in BCT, all lesions enhanced after gadolinium, and all lesions were hypointense on gradient recalled echo, T2*, and SWI images.37 One-third of BCT lesions were hypointense on T1, and half were T2 hyperintense.37 Hemorrhage is exceedingly rare.37
When these lesions are found in locations other than the pons and/or have associated T2 hyperintensity (Fig 15), BCT could mimic a neoplasm (metastatic or primary), an inflammatory disorder, or a subacute infarction.36 Several key observations usually allow for an accurate distinction between a BCT and other lesions. The brushlike enhancement pattern, best appreciated on thin section T1 postcontrast images, can be helpful in differentiating from a neoplasm. The absence of mass effect and surrounding edema are also supportive features. The size of the lesion, best measured on contrast-enhanced sequences, is also an important consideration. Most of these lesions (>90%) measure <1 cm35,38 and few measure >3 cm. On SWI, additional vascular malformations may be found in up to 11% of patients with BCT.37 A draining collector vein best appreciated on SWI or thin section postcontrast images is present in approximately one-third and confirms the vascular nature of the lesion.37 Hypointense signal intensity on DWI has also been described as a helpful differentiating feature.38
Although rare, extra-axial cavernous hemangioma usually involves the cavernous sinus and is often difficult to distinguish from meningiomas and schwannomas, which are much more common in this location. Cavernous sinus hemangiomas are histologically very similar to cerebral cavernous malformations,39 although imaging features differ. These lesions are presumed to be present at birth; grow slowly throughout life; and are often large at presentation, with an average diameter of 4.3 cm.40 Patients present with symptoms related to mass effect on structures in and around the cavernous sinus, including headache, ophthalmoplegia, facial numbness or tingling, pituitary endocrine disorders (obesity, amenorrhea), and retroorbital pain.39–43 Patients are most commonly middle-aged women (7:1 female-to-male ratio). Symptoms are often exacerbated during pregnancy due to lesion growth, and there often is involution after pregnancy.
Imaging findings of cavernous sinus hemangioma can simulate more common neoplastic parasellar lesions, such as meningioma, schwannoma, chondroma, or chondrosarcoma, among others.40 However, it is important to differentiate an extra-axial cavernous hemangioma from these neoplasms before any planned surgical biopsy or decompression procedure. Extra-axial cavernous hemangiomas are known to profusely hemorrhage at the time of operation, and complete surgical excision is rare (16%).39 The surgical mortality rate due to intraoperative bleeding is as high as 25%.39 The risk of injury to nearby arteries, veins, and cranial nerves also increases morbidity. Unfortunately, the rate of misdiagnosis may be as high as 88%41 due to the imaging similarity to neoplasms and the rare incidence.
Knowledge of the existence of extra-axial cavernous hemangioma and its characteristic imaging features is essential to suggesting the diagnosis when appropriate. Noncontrast CT shows a smoothly marginated iso- to hyperattenuated cavernous sinus mass (Fig 16). The lesion rarely calcifies and can erode into the sella turcica and adjacent bony structures. Extra-axial cavernous hemangioma is usually dumbbell-shaped and surrounds but does not narrow the cavernous ICA.40 MR imaging shows T1 hypointensity and homogenous, and marked T2 hyperintense signal intensity (Fig 16). The T2 signal intensity is significantly brighter than most neoplastic tumors, especially meningioma, but not equal to that of cerebral spinal fluid. Postcontrast images reveal a characteristic enhancement pattern characterized by intense arterial phase enhancement that may be heterogeneous (Fig 16), with progressive homogeneous filling on more delayed sequences similar to hepatic hemangiomas.40 Some extra-axial cavernous hemangiomas demonstrate immediate homogenous enhancement similar to flash-filling hepatic hemangiomas.
Although dynamic contrast-enhanced brain imaging is not commonly performed, a comparison of multiplanar T1 postcontrast acquisitions acquired at progressively delayed time points during a routine imaging protocol may reveal progressive contrast filling of the lesions.40 A vascular arterial blush on DSA is observed in 80% of lesions.42 DWI may be helpful in differentiating an extra-axial cavernous hemangioma from a meningioma because extra-axial cavernous hemangioma is usually bright on ADC maps, whereas meningiomas usually show intermediate or dark signal intensity on ADC due to attenuated cell packing.39 An elevated choline peak on MR spectroscopy seen in meningiomas and metastases is not seen with extra-axial cavernous hemangioma. In patients with contraindications for IV contrast, a technetium Tc 99m pertechnetate brain scan or labeled red blood cell pool scintigraphy scan can also diagnose an extra-axial cavernous hemangioma.43
CAA is a common pathology in the elderly caused by amyloid deposition in the small arteries, arterioles, and capillaries along the cerebral cortex and leptomeninges.44 Although rarely occurring at age <50 years, CAA is common in the elderly population and has been found in up to 50% of people of age >90 years in autopsy studies.44 Clinically, CAA may present as a lobar parenchymal hemorrhage in an elderly patient who was normotensive and may cause up to 20% of primary intracranial hemorrhage in patients >60 years old.42,45 Imaging findings may include multiple lobar parenchymal hemorrhages of varying ages, subarachnoid hemorrhage, multiple subcortical microhemorrhages in a lobar distribution, superficial siderosis, white matter FLAIR hyperintensities (leukoaraiosis), and microinfarctions.46 Rarely, coexisting inflammation in patients with CAA can produce a steroid-responsive vasculitis or perivasculitis that may present with rapidly progressive dementia, focal neurologic deficit, headache, and/or seizures. This pathologic process has been referred to as amyloid-beta related inflammation and inflammatory CAA. On MR imaging, inflammatory CAA presents with patchy or confluent asymmetric T2/FLAIR hyperintensities, which involve the subcortical white matter and may exert mass effect (Fig 17).45,47,48
These lesions demonstrate facilitated diffusion (increased signal intensity on diffusion and ADC maps) due to vasogenic edema.47 Leptomeningeal contrast enhancement can occur (Fig 17), although some lesions show no enhancement.48 This constellation of findings, including multifocal masslike FLAIR hyperintensity with or without leptomeningeal enhancement can overlap with those of gliomatosis cerebri, venous infarctions, infection, and other inflammatory disorders. The most helpful imaging feature to indicate the diagnosis of inflammatory CAA is the presence of lobar microhemorrhages or hemosiderosis on SWI or gradient recalled echo, which are seen in patients with CAA (Fig 17). For this reason, SWI/gradient recalled echo should be considered in the imaging protocol of elderly patients who present with tumorlike lesions.49,50 In addition, leptomeningeal contrast enhancement when present would argue against gliomatosis cerebri or primary brain tumor but could be seen with metastatic disease, primary angiitis of the CNS (PACNS), venous infarctions, meningoencephalitis, among others. A normal N-acetylaspartate–to–creatinine ratio may help to distinguish tumefactive CAA from gliomas, which typically exhibit abnormally low N-acetylaspartate–to–creatinine ratios.51 Age is another important consideration, and inflammatory CAA should not be included in the differential diagnosis for patients of <40 years of age.49,50
PACNS is characterized by inflammation that involves the media and adventitia of small cerebral and leptomeningeal arteries and veins, with 3 main histologic patterns: granulomatous, lymphocytic, and necrotizing.49,50 Imaging features are protean and include multiple deep gray matter and subcortical white matter T2/FLAIR hyperintensities, with or without parenchymal infarctions or hemorrhages.49,50 Less commonly, PACNS may present on imaging as a masslike lesion that can be termed tumefactive PACNS. A large case series of tumefactive PACNS reported the most common presenting symptoms as headache (74%), focal neurologic deficit (64%), and diffuse neurologic deficit (50%).52 Seizures, nausea and vomiting, and constitutional symptoms were less frequent. Most cases of tumefactive PACNS demonstrate mass effect, surrounding edema, and contrast enhancement (Fig 18).50 The patterns of enhancement include multifocal masslike, subcortical, and leptomeningeal.50 PACNS can mimic both primary and secondary brain neoplasms, such as astrocytoma, lymphoma, gliomatosis cerebri, and metastases, but could also simulate an infectious meningoencephalitis or vasculitis of another cause (such as inflammatory CAA).
In part, due to the rarity of the disease, no reliable distinguishing imaging features of tumefactive PACNS have been reported. The criterion standard for diagnosing PACNS is often considered to be conventional angiography; however, classic angiographic findings of alternating areas of stenosis and dilatation are only seen in 25% of patients50,53 and the yield may be even lower for small-vessel vasculitis.52 On MR spectroscopy, the elevated choline-to-N-acetylaspartate ratio and lipid–lactate peaks have been described.50 Elevated glutamate and glutamine peaks have been identified in some patients54 but are not sensitive.50 No consistent findings on perfusion or diffusion have been described for tumefactive PACNS.50 On follow-up imaging, resolution of or decrease in size of the lesion can be an important clue for the diagnosis of PACNS, but the disease can have a recurrent course. Response to steroids or immunosuppressants is suggestive; however, other inflammatory processes and lymphoma are also sensitive to steroids. Unfortunately, current neuroimaging features do not reliably confirm the diagnosis and exclude malignancy, and biopsy is generally required for tumefactive PACNS before initiation of immunosuppressants.50
Behçet disease is a chronic, relapsing inflammatory perivasculitis disorder that affects many body systems, most frequently the skin. Incidence is greatest in the Middle East, Mediterranean basin, and Far East, and the disease is rare in North America and Europe.55 Approximately 10%–25% of patients have CNS involvement, termed neuro-Behçet disease. Only 5% of patients with Behçet disease present with neurologic symptoms at the time of initial presentation. CNS involvement usually occurs months or years after systemic disease. Reported neurologic symptoms include headache, pyramidal signs, dysarthria, cerebellar signs, changes in sensation, personality changes, and diplopia, among others.56 Steroids and other immunosuppressive agents are used in the treatment of neuro-Behçet disease.
Neuro-Behçet disease may manifest in a number of ways on neuroimaging. Neuro-Behçet disease findings can be broadly classified as parenchymal and nonparenchymal. Parenchymal manifestations are most common and are usually characterized by T2 hyperintensity and contrast enhancement caused by immune-mediated meningoencephalitis, which predominates in the brain stem (particularly cerebral peduncles and pons), thalamus, and basal ganglia (Fig 19).55,57 Nonparenchymal neuro-Behçet disease manifestations include venous sinus thrombosis, intracranial hypertension, aneurysm, arterial dissection, and arterial occlusion.57 A pseudotumoral form has been described and is associated with significant mass effect, T2 hyperintensity, and contrast enhancement. Most of these lesions are located between the internal capsule and the thalamus57,58 and can be confused with primary glial tumors, lymphoma, metastatic disease, or other inflammatory disorders.56,57 Another potential pitfall is that the lesions may demonstrate diffusion restriction, which could simulate an abscess or densely cellular neoplasm.59 A diagnosis of neuro-Behçet disease usually hinges on a good clinical history to elicit a diagnostic criterion for systemic Behçet disease (skin lesions, uveitis, genital ulcers, and oral ulcers). Neuro-Behçet disease can rarely occur before mucocutaneous manifestations, which can lead to significant diagnostic delay. An enhancing lesion at the characteristic midbrain–thalamus junction with concurrent venous sinus thrombosis (Fig 19) should raise suspicion of neuro-Behçet disease. A trial of steroids can be helpful to distinguish neuro-Behçet disease from some tumors, although some tumors, for example, lymphoma, also respond dramatically to steroids.
A variety of vascular lesions can simulate neoplastic tumors on neuroimaging studies, including both atypical appearances of common lesions and typical appearances of uncommon lesions. Knowledge of the imaging spectrum of these lesions with careful attention to subtle diagnostic clues and the appropriate diagnostic steps may help to improve a prospective diagnosis and facilitate appropriate patient management.
Presented as an educational exhibit poster at: Annual Meeting of the American Society of Neuroradiology, May 17–22, 2014; Montreal, Quebec, Canada.