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TABLE OF CONTENTS

[INFECTIONS]=20 [DEMYELINATION]=20 [VASCULAR=20 DISORDERS] [AMYLOIDOSIS]=20 [NONINFECTIOUS=20 INFLAMMATORY...] [IATROGENIC=20 CONDITIONS] [REFERENCES]=20 [TABLES] [FIGURES]

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=A9=20 Copyright by College of American Pathologists 2009=20

Archives of Pathology and Laboratory = Medicine:=20 Vol. 133, No. 1, pp. 101=96123.

Intracranial Lesions Mimicking Neoplasms

Clare H. Cunliffe, MD; Ingeborg Fischer, MD; David Monoky, = MD; Meng=20 Law, MD, MBBS, FRACR; Carolyn Revercomb, MD; Susan Elrich, MD; Michael = Jered=20 Kopp, BA; David Zagzag, MD, PhD

From the Department of Pathology, Division of Neuropathology = (Drs=20 Cunliffe, Fischer, and Zagzag) and Department of Radiology, = Division of=20 Neuroradiology (Dr Monoky), New York University Medical Center, = New York;=20 the Departments of Radiology and Neurosurgery, Mount Sinai Medical = Center,=20 New York, NY (Dr Law); the Office of the Chief Medical Examiner,=20 Washington, DC (Dr Revercomb); the Department of Neurology, Yale=20 University Hospital, New Haven, Conn (Dr Elrich); and the Stern = School of=20 Business, New York University, New York (Mr=20 Kopp)

Accepted July 25, 2008


3D""=20 Context.=97A=20 broad spectrum of nonneoplastic conditions can mimic a brain tumor, = both=20 clinically and radiologically. In this review we consider these, = taking into=20 consideration the following etiologic categories: infection, = demyelination,=20 vascular diseases, noninfectious inflammatory disorders, and = iatrogenic=20 conditions. We give an overview of such diseases, which represent a=20 potential pitfall for pathologists and other clinicians involved in = patient=20 care, and present selected cases from each category.

3D""Objective.=97To illustrate the = radiologic and=20 pathologic features of nontumoral intracranial lesions that can = clinically=20 and radiologically mimic neoplasia.

3D""Data Sources.=97Case-derived material = and literature=20 review.

3D""Conclusions.=97A variety of = nonneoplastic lesions=20 can present clinically and radiologically as primary or metastatic = central=20 nervous system tumors and result in surgical biopsy or resection of = the=20 lesion. In such situations, the pathologist has an important role to = play in=20 correctly determining the nature of these lesions. Awareness of the = entities=20 that can present in this way will assist the pathologist in the = correct=20 diagnosis of these lesions.

3D""A broad spectrum of nonneoplastic conditions can=20 radiologically and clinically mimic an intracranial neoplasm.

3D""In this review, we have compiled a unique series = of cases=20 that presented both clinically and radiologically as intracranial mass = lesions.=20 Tumor was initially considered in each of the cases. However, pathology = revealed=20 a variety of nonneoplastic etiologies, including demyelinating disease, = vascular=20 disease, inflammation, and infection, as well as posttreatment effects. = Although=20 tumor is often the most likely diagnostic consideration in a patient = presenting=20 with a contrast-enhancing mass lesion within the brain parenchyma with=20 surrounding edema and mass effect, that is not always the case. Not = uncommonly,=20 there can be significant overlap in the radiologic presentation between=20 neoplastic and nonneoplastic diseases. Both neoplastic and nonneoplastic = diseases can produce abnormal contrast enhancement, mass effect, and=20 perilesional edema on both computed tomography (CT) and magnetic = resonance=20 imaging (MRI). Occasionally, some of these nonneoplastic etiologies may = produce=20 signs and symptoms mimicking tumoral disease clinically.1=20 As such, these situations may offer a diagnostic challenge to both the = clinician=20 and radiologist, and often these patients undergo biopsy. In most cases, = the=20 pathologist can readily differentiate between neoplasia and = nonneoplastic=20 imitators. However, because the benign nature of some pseudoneoplastic = lesions=20 may not be immediately apparent on pathologic examination, it behooves = the=20 pathologist to be aware of their existence.

3D""The purpose of this case series is to alert = pathologists,=20 radiologists, and other clinicians involved in the care of = neurooncologic=20 patients to consider nonneoplastic etiologies in the differential = diagnosis of=20 both intra-axial and extra-axial mass lesions.

3D""Tumor-mimicking conditions from several etiologic = categories=20 are presented in tabular form, including infection and inflammation,=20 demyelinating disease, vascular disease, and posttreatment conditions, = with=20 accompanying illustrations and discussion of the current and pertinent=20 literature. Case examples of each condition discussed are described in = the Table= =20 3D""=20.


INFECTIONS Return=20 to TOC

Case Example 1: Aspergilloma

3D""The radiologic finding of erosion of the skull = base by this=20 mass lesion may have contributed to its interpretation as a destructive=20 neoplasm, with the differential diagnosis including chondrosarcoma, = metastatic=20 lesion, osteosarcoma, and meningioma.

3D""However, the histology in this case ruled out a = diagnosis of=20 neoplasm. Based on the hematoxylin-eosin morphology of a granulomatous = process,=20 a diagnosis of tuberculosis came to mind. Special stains for = microorganisms=20 solved this differential diagnostic dilemma, highlighting fungal hyphae = with the=20 characteristic acute angle branching of Aspergillus species. In retrospect, the = history of=20 otitis media and mastoidectomy in this patient pointed toward an = infectious=20 process, even in the absence of predisposing factors such as = immunosuppression=20 or diabetes. Even though most commonly occurring as an opportunistic = infection,=20 aspergilloma is well described in immunocompetent patients, especially = in the=20 context of local infection of the ear or paranasal sinuses.1,2

3D""The increase in fungal central nervous system = (CNS) disease=20 seen by neurosurgeons and neuropathologists can be attributed to the = increasing=20 numbers of immunocompromised patients, which is due to wide use of=20 immunosuppressive drugs such as steroids, large elderly and diabetic=20 populations, and increasing numbers of long-term survivors of human=20 immunodeficiency virus infection due to antiretroviral treatment.3,4=20 The presentation can be very variable, so a high index of suspicion is = required=20 in patients with a history of immunosuppression.

3D""Intracranial fungal infection has been described = following a=20 surgical intervention, often with fatal outcome,5=20 Aspergillus species being the most = commonly=20 reported organism in these cases. Typically, cerebral aspergillosis = results from=20 hematogenous spread of the organism, or alternatively by direct = extension from=20 an adjacent focus of infection. Central nervous system Aspergillus infections can present = either as an=20 abscess or as cerebral infarcts but only rarely as meningitis.6=20 Aspergilloma may also present as an extra-axial mass with extension into = the=20 brain parenchyma. Kim et al7=20 described a case of extra-axial Aspergillus flavus granuloma involving = the left=20 middle and posterior cranial fossa, extending into the skull base and = adjacent=20 cerebellar parenchyma. Of note, the patient was an immunocompetent = 34-year-old=20 man with no other significant history. Radiologically, the mass was = hypointense=20 on T1-weighted MRI and exhibited irregular contrast enhancement. In the = case=20 series by Dubey et al,4=20 patients with intracranial fungal granuloma most commonly presented with = headache, followed by vomiting, proptosis, and visual disturbances. = Other=20 presentations could include cranial nerve palsies and symptoms/signs of = elevated=20 intracranial pressure and meningismus.8=20 The granulomas were most frequently seen in the frontal lobe, although a = classic=20 location of aspergillomas is in a basal cranial location, where it is = thought to=20 arise from an infectious focus in the paranasal sinuses.9=20 In the 40 cases described by Dubey et al,4=20 aspergilloma was the most frequent organism found (25, 63%), followed by = mucormycosis (7, 18%), cryptococcoma (3), Cladosporium (3), Bipolaris hawaiiensis (1), and Candida species (1). There was a 63% = mortality=20 rate in these patients, mostly due to meningoencephalitis.

3D""Radiologically, fungal granulomas present as = enhancing=20 masses.9=20 Adjacent to the dura, they can simulate meningiomas, even producing a = dural tail=20 sign.3=20 On CT scan, they may be associated with paranasal sinusitis and small = areas of=20 bony destruction.4=20 Their MRI appearances can vary somewhat depending on the organism = involved.=20 Aspergillomas tend to demonstrate intermediate signal intensity = surrounded by=20 perilesional edema on T2.4=20 However, cryptococcomas have low T2-weighted signal intensity in = contrast to the=20 surrounding hyperintense cerebral edema. Other fungal infections such as = histoplasmosis can also simulate brain tumors radiologically.9

Case Example 2: Pituitary Cryptococcoma

3D""In immunosuppressed individuals, cryptococcal = infections=20 typically produce a diffuse meningitis, and infiltration of the = perivascular=20 Virchow-Robin spaces by the organism can result in the formation of = small=20 intraparenchymal gelatinous pseudocysts, with a minimal or absent = inflammatory=20 response. In immunocompetent hosts, a chronic granulomatous reaction = surrounds=20 the organisms and there is neovascular growth around the granulomas, = producing=20 contrast enhancement similar to that of primary or secondary brain = tumors.10,11=20 Cryptococcomas may be seen in individuals with a predisposition to = fungal=20 infections, which may not be evident on initial inquiry, and may require = more=20 detailed history and workup to identify conditions such as diabetes or=20 sarcoidosis.12=20 Cryptococcomas are most commonly found in the cerebellum, brainstem, = basal=20 ganglia, or temporoparietal lobes. Distinguishing them from tumors and = abscesses=20 due to other organisms can be challenging because there is no = distinctive=20 radiologic feature that is unique to cryptococcomas. Typically, = cryptococcal=20 disease presents on MRI as T2 hyperintense cystic lesions within the = bilateral=20 basal ganglia with variable enhancement and surrounding edema. They also = often=20 tend to insinuate in dilated Virchow-Robin perivascular spaces. = Enhancing=20 cryptococcomas often do not show restricted diffusion on = diffusion-weighted=20 imaging (DWI),9=20 low signal intensity on T1-weighted imaging, and low9=20 or high intensity12=20 on T2 imaging, with uniform or ring enhancement. They may also have mild = surrounding edema and focal calcification within them.12=20 Cryptococcomas may rarely involve the parasellar or pituitary region. Yu = et al13=20 described a case of parasellar cryptococcoma occurring in an = immunocompetent=20 patient. The radiologic features of the lesion were similar to a = pituitary=20 adenoma, showing uniform contrast enhancement, with low signal on = T1-weighted=20 imaging and high signal on T2 imaging. The contrast enhancement of the = meninges=20 adjacent to the cryptococcoma helped in differentiating it from an=20 adenoma.

Case Example 3: Whipple Disease

3D""Whipple disease is a chronic inflammatory = disorder that=20 involves multiple organ systems, typically the gastrointestinal tract = and=20 musculoskeletal system.14=20 The causative agent is a soil-borne gram-positive bacillus Tropheryma whippelii. The classic = presentation=20 includes fever, steatorrhea, weight loss, skin pigmentation, = lymphadenopathy,=20 and recurrent arthritis.14,15=20 The walls of the intestine and lymph nodes are found to contain = accumulations of=20 foamy macrophages containing the characteristic periodic = acid-Schiff=96positive=20 organisms. The CNS is involved in 6% to 43% of patients with Whipple = disease,15=20 but isolated CNS disease is very rare, with only 14 cases described in = the=20 literature.14,15=20 Radiologically, the lesions are predominantly hyperintense on = T2-weighted=20 magnetic resonance (MR) images and may show homogeneous or ring = enhancement.15=20 They can be surrounded by variable perilesional edema. Generally = speaking,=20 patients presenting with primary CNS Whipple disease can be divided into = 2=20 groups. First, those with multiple lesions may exhibit a plethora of = neurologic=20 symptoms and signs, including seizures, ataxia, supranuclear vertical = gaze=20 palsy, headaches, papilledema, hemiplegia, syndrome of inappropriate=20 antidiuretic hormone, and fever. Interestingly, some patients may = develop=20 oligoclonal bands in the cerebrospinal fluid similar to those found in = multiple=20 sclerosis, cerebral lupus, human immunodeficiency virus infection, and=20 sarcoidosis.14=20 Those with focal mass lesions have symptoms referable to the site = involved. The=20 patient described by Lohr et al15=20 had an isolated frontal mass in the white matter, which had MRI features = suggestive of a low-grade glioma. It was T2 hyperintense, was slightly=20 hypointense on T1-weighted images, and had subtle ring enhancement = without=20 perilesional edema. As in our patient, the presentation included = behavioral=20 changes and aggressiveness. Following resection of the mass, the = characteristic=20 perivascular foamy macrophages containing periodic = acid-Schiff=96positive,=20 diastase-resistant rod-shaped organisms were seen. There was marked = associated=20 gliosis.

3D""Other cases of solitary CNS Whipple disease have = also=20 involved the frontoparietal regions, and in one of these, there was = associated=20 destruction of the calvarium adjacent to the lesion.16=20 In cases of multifocal disease, the lesions have mostly occurred in the = cortical=20 or subcortical grey matter, involving mainly the temporal lobes and = thalamus.15=20 Although the clinical presentation and radiologic findings in = intracranial=20 Whipple disease can closely mimic those of a low-grade glioma, the = histologic=20 picture of perivascular foamy histiocytes should prompt the pathologist = to look=20 for the periodic acid-Schiff=96positive intracellular organisms and = arrive at the=20 correct diagnosis.

Case Examples 4 and 5: Bacterial Abscess

3D""Differentiating between pyogenic brain abscesses = and=20 centrally necrotic intra-axial tumors can often be challenging = radiologically,=20 because both commonly demonstrate ring enhancement and perilesional = edema. A=20 helpful finding on MRI examination is the presence of a hypointense = capsule on=20 T2-weighted images, which is not usually seen in tumors.9=20 Diffusion weighted imaging is a well-known and valuable radiologic tool = in these=20 cases: brain abscesses typically show markedly hyperintense signal = changes on=20 DWI, whereas the appearance of high-grade gliomas varies from slightly=20 hyperintense to hypointense signal.17=20 The apparent diffusion coefficient reveals reduced values in brain = abscesses.=20 These findings are, however, not entirely specific, because a centrally = reduced=20 apparent diffusion coefficient has been also reported in neoplastic = lesions.18

Case Example 6: Nocardiosis

3D""Brain abscess due to Nocardia species is a rare condition, = and although=20 it can occur in patients with an intact immune system, it is usually = seen among=20 immunocompromised patients.6=20 It can be confused with intracranial tumors radiologically.19=20 Ozturk et al20=20 described a case of nocardial brain abscess occurring in a renal = transplant=20 recipient on an immunosuppressive drug regimen. Kilincer et al19=20 described a further 2 cases of nocardial brain abscess, one of whom was = a=20 39-year-old woman with systemic lupus erythematosus who developed a left = frontoparietal abscess, and the other was a 43-year-old man with=20 glomerulonephritis treated with corticosteroids who developed a = ring-enhancing=20 multiloculated abscess in the left cerebellar hemisphere, with an = additional 2=20 small supratentorial lesions. Both underwent treatment with long-term=20 antibiotics and evacuation of the abscess. Histologically, nocardiosis = appears=20 as a necrotic lesion with acute inflammation. The organism is weakly = acid-fast=20 with the Fite stain, having a beaded, filamentous appearance, and also = is=20 highlighted by the Gomori methenamine silver stain.

Case Example 7: Tuberculoma

3D""Intracranial tuberculomas may exhibit nodular or = ringlike=20 enhancement on MRI similar to a primary or metastatic brain tumor.10=20 When present, areas of caseation can correlate with isointense or mixed=20 intensity areas seen within the mass on T1-weighted images. The = surrounding=20 collagenous fibrosis corresponds to the slightly hyperintense rim. The = MRI=20 appearance of tuberculomas varies according to the age of the lesion. On = T2-weighted imaging, immature tuberculomas appear as multiple small = areas of=20 isointensity or hypointensity surrounded by hyperintense edema. Mature=20 tuberculomas are heterogeneously hypointense or isointense throughout = the=20 lesion, with ring enhancement seen on postcontrast T1-weighted images. = Clues to=20 the granulomatous nature of the lesion are its conglomerate and = ring-enhancing=20 MRI appearance. A =93targetlike=94 appearance with central = calcification,=20 perilesional edema, and peripheral enhancement on CT scan has been = described,=20 although is not always present.10=20 Magnetic resonance spectroscopy (MRS) is typically inconclusive and does = not=20 help distinguish the condition from a neoplasm. Diffusion-weighted = imaging is=20 usually hyperintense.9=20 Fortunately, if biopsy or excision is performed, the histologic = appearance of=20 tuberculoma is characteristic, with granulomatous inflammation, = caseation,=20 calcification, and surrounding gliosis. If only the edge of the lesion = is=20 biopsied, it is important for the pathologist to distinguish this = reactive=20 gliosis from a glial neoplasm.

Case Example 8: Progressive Multifocal=20 Leukoencephalopathy

3D""Typically, patients with progressive multifocal=20 leukoencephalopathy (PML) present with weakness, hemianopia or = quadrantanopia,=20 and cognitive abnormalities.21=20 On imaging, PML lesions typically present as large, multifocal, = subcortical=20 white matter lesions without mass effect. They are most commonly found = in the=20 parietal lobe white matter,22=20 but they can also be seen in the occipital lobe, corpus callosum, and = thalamus.=20 Typically, PML does not enhance, although lesions may demonstrate mild=20 peripheral or scalloped areas of enhancement, often associated with=20 reconstitution of the patient's immune response. In some cases there may = be low=20 density or T2 hyperintense cystlike areas within PML lesions.21=20 These may represent areas of necrosis within the lesion. The lesions may = typically show no or faint contrast enhancement. In the series of = Thurnher et=20 al,21=20 a third of the patients with PML lesions had significant mass effect = with=20 compression of the ipsilateral lateral ventricle, which is in contrast = to the=20 typical lack of mass effect described in the literature. Therefore, = necrotic=20 white matter lesions in acquired immunodeficiency syndrome patients,=20 particularly with peripheral scalloping, should be considered highly = suggestive=20 of PML rather than a necrotizing tumor, and the pathologist should be on = the=20 alert for the accompanying histologic appearance. On microscopic = examination of=20 the biopsy or resection, the PML lesions exhibit demyelination and = contain=20 enlarged oligodendrocytes with hyperchromatic nuclei, some of which may = contain=20 eosinophilic intranuclear inclusions, and enlarged astrocytes with = bizarre=20 nuclei.23=20 Immunohistochemistry for the JC viral capsid protein may also be = performed as=20 confirmation.23

Case Example 9: Neurocysticercosis

3D""Neurocysticercosis develops when the larval form = of the=20 tapeworm Taenia solium encysts in the brain = inciting a=20 surrounding inflammatory and granulomatous response.

3D""It is the most common cause of acquired seizures = worldwide=20 and is increasingly seen in the United States, particularly in the = immigrant=20 community.24=20 Although epilepsy is the most common presenting symptom, other = manifestations=20 include severe episodic headache,25=20 meningitis, obstructive hydrocephalus if the cyst is near a ventricle or = the=20 subarachnoid space, and cognitive problems.10,24=20 Radiologic diagnosis is often straightforward, although the appearance = varies=20 depending on the life cycle stage of the parasite and the age of the = lesion. The=20 lesion can appear as a single or multiple enhancing cysts with = calcification,=20 the latter representing dead larvae or nodular calcified stage.1,10=20 When the larvae are invading the brain, they appear as small = nonenhancing=20 edematous lesions, later forming small enhancing nodules.10=20 As the lesions become cystic and the larvae start to die, surrounding = edema=20 develops due to the inflammatory response to the cyst contents, and = there is=20 ring enhancement due to the formation of granulation tissue and a thick = capsule.=20 On DWI, the cysts have a similar signal intensity to cerebrospinal = fluid, unlike=20 pyogenic abscesses.9=20 Usually the lesions are less than 20 mm in diameter.10=20 A helpful finding is the identification of a scolex (larval body) within = the=20 cyst.9=20 The scolex is typically hyperintense on T1-weighted sequences.10=20 Solitary lesions can be difficult to distinguish from a neoplasm owing = to the=20 surrounding edema and the cyst enhancement.9=20 It may even mimic a glioblastoma multiforme radiologically.26

3D""In these cases, it is helpful to correlate the = findings with=20 other clinical data such as cerebrospinal fluid immunology for T solium antibody titers. = Pathologically, the=20 presence of a fibrous cystic structure with granulomatous inflammation = should=20 prompt a search for an infectious etiology. In patients originating from = endemic=20 areas such as South America, Africa, and Asia, a careful search for the=20 characteristic larval forms and scolices should be made.


DEMYELINATION Return=20 to TOC

Case Examples 10 and 11: Demyelination

3D""Masslike features or a so-called tumefactive = appearance of=20 demyelinating plaques are well described in the literature. Multiple = sclerosis,=20 and other primarily demyelinating diseases, such as myelinoclastic = diffuse=20 sclerosis (Schilder disease) and acute disseminated encephalomyelitis = can=20 manifest as tumefactive lesions. Differentiating between demyelinating = lesions=20 and brain tumors, such as gliomas, in the presence of solitary lesions = can be=20 difficult and problematic.

3D""As in case 10, a peripherally enhancing lesion = with a=20 butterfly configuration occurring in a 57-year-old man with acute onset = of=20 symptoms almost automatically triggers a suspected diagnosis of = glioblastoma.=20 However, on closer examination of the images, the incomplete ring and = peripheral=20 contrast enhancement as seen in this case should give rise to suspicion = and=20 perhaps prevent a premature conclusion. This condition is a = =93classic=94 mimic of=20 high-grade glioma, and recently, the characteristic horseshoe-shaped = contrast=20 enhancement on MRI has been described. Additional radiologic tools, = including MR=20 perfusion imaging or MRS can further aid in arriving at the correct = diagnosis,=20 thus avoiding a surgical biopsy.27,28=20 Features that favor a demyelinating lesion include a relative lack of = mass=20 effect and vasogenic edema.10=20 In radiologic parlance, the =93open ring sign=94 is contrast enhancement = shaped as=20 an open ring or a crescent in the white matter. It is often present in = large=20 contrast-enhancing demyelinative lesions and is more likely to be = associated=20 with these than with neoplasms or infections.29=20 In demyelination, the incomplete ring of enhancement may have = ill-defined=20 margins.30=20 Differentiation between a solitary demyelinating lesion and a glioma can = be very=20 challenging radiologically.10,30,31=20 Therefore, if the presentation and imaging findings remain inconclusive = and a=20 histologic diagnosis is necessary, the pathologist has to keep this = condition in=20 the differential diagnosis, because erroneous diagnoses of high-grade = glioma=20 have been reported many times in the medical literature, even though the = distinguishing features are also well documented.32=20 When demyelinative lesions have a marked inflammatory component, they = may be=20 confused with a primary CNS lymphoma. The more gliotic lesions are more = apt to=20 be confused with high-grade astrocytomas, however. If one is unfamiliar = with the=20 characteristic appearance of Creutzfeldt astrocytes seen in = demyelination, the=20 possibility of substantial astrocytic pleomorphism, and the occurrence = of=20 mitotic figures in demyelinative lesions, they may be misinterpreted as=20 high-grade glioma.33


VASCULAR DISORDERS Return=20 to TOC

Case Example 12: Infarct

3D""Instances in which infarcts mimic high-grade = gliomas due to=20 contrast enhancement and mass effect are documented in the literature.34,35=20 To distinguish a cerebrovascular accident from a neoplasm, repeat = imaging=20 studies after a short interval or advanced techniques such as MR = perfusion may=20 also be helpful.34,36=20 In most cases, diagnosis of ischemic stroke/infarction is not = problematic. The=20 characteristic clinical history of a sudden onset of neurologic symptoms = and=20 signs, in combination with the typical radiologic findings, including=20 diffusion-restriction, T2/fluid-attenuated inversion recovery = hyperintense=20 signal, mass effect, and possible gyral enhancement pattern together in = a=20 typical vascular distribution, usually leads to the correct diagnosis.9=20 Confounding diagnostic features in ischemic infarction that are more = suggestive=20 of a brain tumor include an atypical presentation, such as a slow = evolution of=20 neurologic symptoms,10=20 and a poorly defined cerebral lesion on imaging with associated mass = effect,=20 radiologically simulating glioma.9,10=20 A subacute infarction can show irregular contrast enhancement and mimic=20 high-grade glioma. Some infarcts can also exhibit ring enhancement, = strongly=20 resembling that of glioblastoma.34=20 An understanding of the cerebral arterial vasculature is essential in = arriving=20 at a correct diagnosis.10=20 Diffusion weighted imaging is a helpful modality for distinguishing = between=20 these 2 conditions,10=20 particularly when the clinical history is obscure, and in the acute or = early=20 subacute phase of an ischemic stroke.9=20 In late subacute to chronic infarctions, however, restricted diffusion = may not=20 be evident thus making DWI less useful in making the distinction between = tumor=20 and an infarct.9=20 In this case, short-term follow-up imaging may be necessary to document = the=20 evolution of the lesion.10

Case Example 13: Vasculitis

3D""The clinical presentation and imaging findings in = this case=20 do not provide unequivocal evidence to arrive at the correct diagnosis. = The=20 sudden focal neurologic deficit and the ring enhancement of the deep = white=20 matter lesion prompted the preoperative diagnosis of high-grade glioma. = There=20 were no findings in the patient's preoperative evaluation consistent = with an=20 inflammatory process: there were no systemic symptoms and her laboratory = values=20 including an erythrocyte sedimentation rate and a white blood cell count = were=20 within reference range. Indeed, there are relatively few cases of this = condition=20 reported in the literature, especially presenting as a solitary=20 contrast-enhancing mass. Further imaging studies (perfusion-weighted = MRI,=20 angiography) may be valuable, but it has been suggested that a = stereotactic=20 biopsy should become the gold standard in the management of these cases, = even=20 though the diagnostic yield is reportedly low.37,38=20 Beh=E7et disease has been reported to produce a solitary masslike lesion = in the=20 hemisphere, with low attenuation on T1-weighted MRI, and extensive=20 hyperintensity on fluid attenuated inversion recovery.39,40=20 However, this scenario is very rare, as Beh=E7et disease usually = presents as=20 multiple T2 hyperintense lesions.39=20 Magnetic resonance spectroscopy can be of assistance in distinguishing a = vasculitic lesion from a neoplasm. Panchal et al41=20 reported a case of lymphocytic vasculitis presenting as multifocal = tumorlike=20 lesions within the right cerebral hemisphere, which were enhancing on=20 postgadolinium T1-weighted MR, with associated massive vasogenic edema = involving=20 the whole hemisphere. Radiologically, the lesions mimicked a multifocal = glioma.=20 However, the MRS pattern was more consistent with an inflammatory = process (no=20 elevated choline peak, marked elevation of glutamate/glutamine = metabolites)=20 rather than an aggressive neoplasm. The diagnosis was confirmed by = craniotomy=20 and excisional biopsy.


AMYLOIDOSIS Return=20 to TOC

Case Examples 14i and 14ii: Amyloidoma

3D""After the initial clinical and radiologic workup, = the lesion=20 in case 14i was thought to be a schwannoma of the fifth nerve, which = would fit=20 the imaging features and presentation. A meningioma was also considered, = because=20 the lesion showed a highly suggestive =93dural tail sign=94 on imaging. = The absence=20 of any evidence of systemic disease associated with the deposition of = amyloid in=20 this case made this a very difficult diagnosis.

3D""Nonetheless, several such lesions in this = location with=20 similar presentation and imaging findings have been reported. = Interestingly, the=20 deposits were histochemically composed of λ protein, as in the = present case.42=96= 44

3D""The most frequent presentation of intracranial = amyloid is as=20 cerebral amyloid angiopathy, or as deposits within the senile plaques of = Alzheimer disease. Amyloidoma is seen much less frequently. Amyloid = presenting=20 clinically and radiologically as an intracranial tumor is rare. Amyloid=20 presenting as a tumorlike mass has been reported in the cerebral = hemispheres in=20 patients ranging in age from 28 to 60 years, including the temporal45,46=20 and occipital lobes,46,47=20 and also the cerebellopontine angle.43=20 Typically, they appear as supratentorial white matter masses that are = high=20 density on nonenhanced CT scan, with little to no mass effect.48=20 They can extend up to the walls of the lateral ventricle and have fine,=20 irregular enhancing margins. Central nervous system amyloid can also = present as=20 multiple contrast-enhancing lesions in the hemispheres.49

3D""Other locations have included the Gasserian = ganglion43=20 manifesting clinically as trigeminal neuropathy, which had a signal = intensity=20 similar to cortex on T1-weighted imaging, heterogeneous signal intensity = on T2=20 imaging, with marked uniform enhancement on postcontrast T1 imaging. The = mass=20 was thought to be a meningioma or schwannoma preoperatively. The sella50=20 and choroid plexus are other known sites. Ragel et al47=20 described a 59-year-old man with a 6-month history of confusion and = headaches;=20 MRI revealed a left parietooccipital lesion extending to the splenium of = the=20 corpus callosum. The mass had MRI and MRS features of a high-grade = glioma, with=20 a stellate hyperintense rim on T2-weighted imaging, and elevated choline = peak on=20 MRS. Biopsy findings were those of amyloidoma, with amorphous = congophilic=20 deposits and apple green birefringence. Findings not consistent with = high-grade=20 glioma were the lack of peritumoral edema and minimal mass effect. = Another=20 article45=20 described a right temporal lobe mass in a 51-year-old woman presenting = with=20 hearing loss and recurrent right-sided otitis media. The MRI and CT = findings=20 were suspicious for glioma, and stereotactic biopsy with intraoperative = squash=20 preparation followed by routine histology and electron microscopy = revealed=20 amyloidoma.

3D""Cerebral amyloid angiopathy can also mimic glioma = radiologically and clinically. Safriel et al46=20 reported 2 patients with MR findings suggestive of low-grade glioma. The = first=20 case was a 49-year-old man with a tumefactive mass in the = occipitotemporal lobe=20 without enhancement or restricted diffusion and unremarkable spectra. = Biopsy and=20 histopathology revealed cerebral amyloid angiopathy with angiitis. The = second=20 case was a 71-year-old woman with an ill-defined infiltrative = nonenhancing mass,=20 without restricted diffusion, within the right occipital and parietal = lobes, and=20 unremarkable MRS findings. Biopsy revealed cerebral amyloid angiopathy. = Cerebral=20 amyloid angiopathy may also present as a mass within the brain. Osumi et = al51=20 describe a 59-year-old woman presenting with a large right = temporoparietal lobe=20 mass lesion, which was white matter based, and was nonenhancing, = nonhemorrhagic,=20 and low attenuation on MRI examination. A diagnosis of low-grade glioma = was=20 considered. Biopsy was nondiagnostic, revealing only gliosis. Subtotal = resection=20 of the right temporal lobe was then performed, and histology showed = congophilic=20 vascular mural deposits of amyloid, with diffuse white matter gliosis = and edema.=20 There was no evidence of tumor.


NONINFECTIOUS INFLAMMATORY CONDITIONS Return=20 to TOC

Case Example 15: Castleman Disease

3D""Castleman disease, also known as angiofollicular = lymph node=20 hyperplasia, occurs in 2 forms. Most cases are the hyaline-vascular = type, as in=20 our case, with the typical histologic finding of hyalinized follicular = centers=20 with a radial penetrating vessels and prominent interfollicular = capillary=20 proliferation. The plasma cell type represents only 5% to 10% of cases, = and is=20 characterized by large lymphoid follicles separated by sheets of mature = plasma=20 cells and less stromal vascularization.52,53=20 Localized forms of the disease are generally asymptomatic, while the = generalized=20 form may present with fever, weight loss, anemia, polyneuropathy, = organomegaly,=20 and monoclonal proteinemia, thus resembling a paraneoplastic syndrome.=20 Intracranial Castleman disease is very rare, with 13 cases described in = the=20 literature, and in this locality it may mimic a neoplasm, in particular = a=20 meningioma. Previously described locations include the hemisphere = convexities=20 and adjacent to the falx. As expected with the predominantly cortical = location=20 of the lesion, patients presented most commonly with seizures, and focal = signs=20 such as right hand clumsiness,53=20 left hemiparesis, and incoherent speech.52=20 By CT imaging, the lesions were homogeneously enhancing with = perilesional=20 edema.52=20 Some demonstrated dural enhancement by MRI, mimicking a meningioma.53=20 Angiography of these intracranial cases revealed no vascular blush, in = contrast=20 to other sites where there is typically a homogeneous capillary blush = from=20 neovascularization.52=20 Although most cases occur in adults, there is a single report in an = 8-year-old=20 girl.54=20 The child presented with sudden onset of partial motor seizures and a = left=20 posterior parietal, partially mineralized, contrast-enhancing meningeal=20 mass.

3D""The treatment of choice for localized Castleman = disease is=20 gross total resection of the lesion, after which total and complete = recovery is=20 the rule52,54=20 including resolution of the systemic manifestations of the disorder. In = summary,=20 although it is a rare entity in the CNS, Castleman disease should be = considered=20 in the differential diagnosis of intracranial meningeal tumors.

Case Example 16: Rosai-Dorfman Disease

3D""Sinus histiocytosis with massive lymphadenopathy, = or=20 Rosai-Dorfman disease, was first described in 1969.55=20 It typically presents in children and young adults, and has a mean age = of onset=20 of 20.6 years, with bilateral, painless cervical lymphadenopathy. Some = patients=20 also have systemic symptoms such as elevated sedimentation rate, fever,=20 leukocytosis, and polyclonal hypergammaglobulinemia.55=20 Extranodal involvement also occurs in more than 40% of patients, = particularly in=20 the paranasal sinuses, orbit, skin, and upper respiratory tract.56=20 Central nervous system involvement is less common, being found in 22% of = patients, and isolated CNS disease is rarer still. Disease of the CNS = typically=20 manifests itself in the epidural or subdural compartments,56=20 but a suprasellar location has been reported.55=20 Patients presenting with or developing cranial involvement have a mean = age of=20 34.9 years, with a male predominance. Some of the usual presentations of = intracranial disease include seizures, headache, cranial nerve deficits, = hemiparesis, and dysphasia.55=20 Imaging reveals single or multiple meningeal-based masses, which are = enhancing,=20 with variable surrounding edema, and can appear identical to a = meningioma on CT=20 and MRI scan.55,57,58=20 Associated lytic lesions may be seen in the skull.56=20 On surgical resection, the lesion may also grossly be indistinguishable = from a=20 meningioma, and so diagnosis will rest with histology. Fortunately,=20 differentiation of sinus histiocytosis with massive lymphadenopathy from = meningioma presents no difficulty in most cases, with the possible = exception of=20 the lymphoplasmocyte-rich variant of meningioma.57

3D""Helpful histologic features include the = characteristic=20 pale-staining histiocytes with delicate nuclear membranes, exhibiting=20 emperipolesis, that is, intact lymphocytes, neutrophils, and plasma = cells within=20 the cytoplasm. There may also be erythrophagocytosis and perivascular=20 collections of plasma cells.56=20 Immunohistochemistry is helpful in demonstrating the characteristic S100 = protein, CD68, and factor XIIIa=96positive histiocytes, which unlike = those in=20 Langerhans cell histiocytosis, are negative for CD1a.57

3D""Because there are as yet only a few reports of = intracranial=20 Rosai-Dorfman disease, the ideal treatment for this condition is so far=20 undefined. Surgery has been the treatment of choice.55=20 Adjunctive therapy has included chemotherapy, irradiation, and steroids. = So far,=20 no deaths from intracranial sinus histiocytosis with massive = lymphadenopathy=20 have been reported, and patients who underwent complete resections had = no=20 recurrences.55=20 The effectiveness of steroids in this condition has been described. = McPherson et=20 al59=20 reported a 53-year-old male patient with multiple skull base lesions who = underwent craniotomy for 1 lesion and experienced marked resolution of = the=20 remaining lesions following corticosteroid administration.

3D""Another systemic histiocytic disease that can = involve the CNS=20 and produce lesions mimicking a primary brain tumor is Erdheim-Chester=20 disease.

3D""The disease is a non=96Langerhans cell = histiocytosis and=20 usually affects middle-aged adults, producing osteosclerotic and=20 lipogranulomatous lesions of the long bones and retroperitoneal and = pulmonary=20 fibrosis.60=20 When there is neurologic involvement, it typically manifests itself as=20 hypothalamic/pituitary dysfunction.61=20 A solitary left temporoparietal cortical lesion has been described in a=20 previously healthy 26-year-old patient who experienced recent onset of=20 seizures.62=20 The lesion was solitary, well-demarcated and homogeneously enhancing on = MRI=20 examination. It had minimal surrounding edema and no mass effect. = Positron=20 emission tomography scan suggested a low-grade neoplasm, such as = astrocytoma or=20 pleomorphic xanthoastrocytoma. Intraoperative squash preparations and = frozen=20 sections revealed many multinucleate cells with a background of = fibrillary=20 astrocytes, and a diagnosis of glial neoplasm was made. On permanent = histology,=20 clusters of xanthomatous histiocytic cells were evident, many of which = were=20 multinucleate with a wreathlike nuclear arrangement, surrounded by dense = gliosis. The histiocytic cells were KP-1 (CD68) immunopositive and = negative for=20 CD1a and S100 (in contrast to those seen in Rosai-Dorfman disease or = Langerhans=20 cell histiocytosis).

Case Example 17: Inflammatory Pseudotumor

3D""Inflammatory pseudotumors, also known as = inflammatory=20 myofibroblastic tumors, may involve any organ system.63=20 In the CNS, it most commonly produces a dural-based/meningeal mass, = although it=20 may be intraparenchymal or may occasionally arise from the choroid = plexus,=20 producing a hyperdense intraventricular mass on CT imaging.3=20 Shah and McClain64=20 described a form of inflammatory pseudotumor (plasma cell granuloma) = involving=20 the cavernous sinus and middle cranial fossa in a 14-year-old girl. On = MRI, it=20 was seen to extend into the pterygopalatine and infratemporal fossae = producing=20 thickening of the right lateral tentorium and edema of the right = temporal lobe.=20 Typically, inflammatory pseudotumor is hypointense on T1-weighted images = and=20 markedly hypointense on T2. Because of its polymorphous histologic = appearance,=20 ranging from hypocellular connective tissue containing scattered mixed=20 mononuclear inflammatory cells to a proliferation of plump fibroblastic = cells=20 with a prominent inflammatory component, it may potentially be confused = with a=20 lymphoplasmacyte-rich meningioma or even a fibroblastic meningioma. The=20 radiologic appearance of a dural-based mass may further mislead the = pathologist.=20 The demographics of patients with the 2 lesions are different, however, = with=20 most inflammatory pseudotumors (73%) occurring in those younger than 40 = years.10=20 There is a distinct male predominance,10=20 and most cases in the CNS are solitary (82%). Intraparenchymal = heterogeneously=20 enhancing inflammatory pseudotumors may mimic a malignant brain = neoplasm.63


IATROGENIC CONDITIONS Return=20 to TOC

Case Example 18: Radiation Necrosis

3D""Distinguishing between radiation necrosis and = glioma=20 recurrence can be difficult.65=20 In cases of high-grade glioma, both are likely to be present at the same = time,=20 but in these cases the challenge is to determine whether one or the = other is=20 predominant because this may affect treatment planning. Increased = contrast=20 enhancement secondary to irradiation may be seen within a variable time = frame=20 after administration of radiotherapy. These changes may be seen as soon = as 2 to=20 4 months after the treatment and may improve over time.9=20 Additionally, delayed radiation necrosis should be considered when = patients=20 present with a new enhancing lesion, particularly in the irradiation = field,=20 months or years after the end of treatment.9=20 Obviously, obtaining an accurate clinical history is important in these = cases.=20 Diffusion weighted imaging, which shows a spotty hypointense lesion in = the=20 irradiation field, is suggestive of radiation necrosis.66=20 Radiation necrosis shares some major MRI features with recurrent glioma, = including contrast enhancement, vasogenic edema, and mass effect.67=20 However, some additional features that may favor radiation necrosis = include=20 conversion from no enhancement to enhancement and remote new = enhancement, new=20 periventricular enhancement, and =93Swiss cheese=94 enhancement.68=20 In 1 study, MRI findings which favored recurrent tumor included = involvement of=20 the corpus callosum with subependymal spread, corpus callosal = involvement with=20 crossing of the midline and multifocal lesions, and the combination of = corpus=20 callosal involvement with subependymal spread and multiple lesions.65=20 Of note, the authors found that these combinations of MRI findings = rather than=20 individual features were statistically significant. However, in many = cases, the=20 definitive diagnosis of radiation necrosis versus recurrent tumor rests = with=20 surgery and biopsy.


References Return=20 to TOC

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50. Mori H, Mori S, = Saitoh Y,=20 Moriwaki K, Iida S, Matsumoto K. Growth hormone-producing pituitary = adenoma with=20 crystal-like amyloid immunohistochemically positive for growth hormone.=20 Cancer 1985;55:96=96102.

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67. Castel=20 JC, Caille JM. Imaging of irradiated brain tumours: value of magnetic = resonance=20 imaging. J Neuroradiol 1989;16:81=96132.

68. Kumar AJ, Leeds NE, Fuller = GN. et al.=20 Malignant gliomas: MR imaging spectrum of radiation therapy- and=20 chemotherapy-induced necrosis of the brain after treatment. = Radiology=20 2000;217:377=96384.



Tables Return=20 to TOC


3D""=20Illustrative Case Examples With = Corresponding Clinical History, Imaging Findings, Histology, and Final=20 Pathologic Diagnosis*

3D""=20


3D""=20Extended

3D""=20


3D""=20Continued

3D""=20


3D""=20Extended=20 (Continued)

3D""=20

Figures Return=20 to TOC

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 1.3D""=20A,=20 Coronal T1-weighted magnetic resonance imaging demonstrating a centrally = hypointense lesion (arrow) within the left temporal bone with irregular = contrast=20 enhancement. B, Granulomatous inflammation (hematoxylin-eosin, original=20 magnification =D7200). Inset, Multinucleate giant cells = (hematoxylin-eosin,=20 original magnification =D7400). C, Fungal hyphae with acute angle = branching=20 (Gomori methenamine silver stain, original magnification =D7400). = Pathologic=20 diagnosis: aspergilloma

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 2.3D""=20A,=20 Coronal T1-weighted magnetic resonance imaging (MRI) demonstrating a = centrally=20 hypointense intrasellar mass (arrow) with a thin rim of peripheral = enhancement.=20 B, Axial T1-weighted MRI demonstrating a low signal intensity mass = (arrow)=20 within the sella with thin peripheral enhancement and a thin enhancing=20 septation. C, Necrotic basophilic material containing small- to = medium-sized=20 oval yeast forms (hematoxylin-eosin, original magnification =D7200). D, = Organisms=20 are strongly periodic acid=96Schiff positive (original magnification = =D7400). Inset,=20 Capsule of organism is weakly mucicarmine positive (original = magnification=20 =D7400). E, Organisms are strongly labeled by Gomori methenamine silver = stain=20 (original magnification =D7400). Pathologic diagnosis:=20 cryptococcoma

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 3.3D""=20A,=20 Axial fluid-attenuated inversion recovery magnetic resonance imaging = (MRI)=20 demonstrating bilateral hyperintense temporal lobe lesions (arrows), = left=20 greater than right, involving cortex and subjacent white matter. B, = Axial=20 T1-weighted postcontrast MRI demonstrating bilateral hypointense = temporal lobe=20 lesions (arrows) with peripheral enhancement and some prominent = surrounding=20 vessels. C, Perivascular lymphohistiocytic inflammatory infiltrate=20 (hematoxylin-eosin, original magnification =D7200). D, Macrophages with = pale=20 eosinophilic, foamy cytoplasm (hematoxylin-eosin, original magnification = =D7400).=20 E, Brightly periodic acid-Schiff=96positive intracellular organisms = within=20 macrophages (original magnification =D7400). Pathologic diagnosis: = Whipple=20 disease

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 4.3D""=20A,=20 Axial postcontrast T1-weighted magnetic resonance imaging (MRI) = demonstrating a=20 peripherally enhancing lesion (arrow) within right frontal lobe, with = cortical=20 extension. B, Axial T2-weighted MRI demonstrating marked T2 hyperintense = perilesional edema (arrow) typical for a bacterial infection. C, Abscess = containing dense collections of neutrophils (hematoxylin-eosin, original = magnification =D7200). D, Edge of abscess is composed of a = fibroinflammatory=20 capsule (hematoxylin-eosin, original magnification =D7200). Pathologic = diagnosis:=20 bacterial abscess

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 5.3D""=20A,=20 Axial postcontrast T1-weighted magnetic resonance imaging (MRI) = demonstrating a=20 left thalamic ring=96enhancing lesion (arrow). B, Axial T2-weighted MRI=20 demonstrating a well-circumscribed T2 hyperintense left thalamic lesion = (arrow)=20 with peripheral T2 hypointense rim. C, Neutrophilic abscess with = collections of=20 basophilic organisms (hematoxylin-eosin, original magnification =D7400). = D,=20 Organisms are gram-positive cocci (Brown-Hopps Gram stain, original=20 magnification =D71000). Pathologic diagnosis: bacterial=20 abscess

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 6.3D""=20A,=20 Axial postcontrast T1-weighted magnetic resonance imaging demonstrates a = ring-enhancing lesion (arrow) within the left parietal white matter with = central=20 hypointensity and surrounding edema. B, Axial diffusion-weighted = imaging. The=20 lesion (arrow) demonstrates hyperintensity on diffusion imaging. C, = Gliotic=20 brain tissue with mixed inflammatory infiltrate (hematoxylin-eosin, = original=20 magnification =D7200). D, Center of lesion contains neutrophilic abscess = (hematoxylin-eosin, original magnification =D7200). E, Tissue Gram stain = reveals=20 fine, filamentous gram-positive bacteria within abscess (arrow) = (Brown-Hopps=20 Gram stain, original magnification =D71000). Pathologic diagnosis:=20 nocardiosis

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 7.3D""=20A,=20 Axial postcontrast T1-weighted magnetic resonance imaging (MRI) scan=20 demonstrating a right basal ganglia lesion (arrow) with irregular = peripheral=20 enhancement with midline shift and surrounding edema. B, Axial = T2-weighted MRI=20 demonstrating heterogeneous signal intensity with central areas of low = T2 signal=20 and marked surrounding edema. C, Gliosis and chronic inflammation=20 (hematoxylin-eosin, original magnification =D7200). D, Granuloma with = surrounding=20 intense chronic inflammatory infiltrate (hematoxylin-eosin, original=20 magnification =D7200). E, Rare pink-stained acid-fast bacilli within the = lesion=20 (arrow) (Kinyoun acid-fast stain, original magnification =D71000). = Pathologic=20 diagnosis: tuberculoma

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 8.3D""=20A,=20 Axial postcontrast T1-weighted magnetic resonance imaging (MRI) = revealing=20 hypointense, nonenhancing lesion within the right middle cerebellar = peduncle=20 (arrow). B, Axial T2-weighted MRI demonstrating T2 hyperintense lesion = within=20 the right middle cerebellar peduncle (arrow). C, White matter pallor = with mild=20 chronic inflammation and enlarged, hyperchromatic oligodendroglial = nuclei=20 (hematoxylin-eosin, original magnification =D7400). D, Enlarged, bizarre = astrocytes, with collections of foamy histiocytes (hematoxylin-eosin, = original=20 magnification =D7400). E, Enlarged progressive multifocal=20 leukoencephalopathy-infected cells are MIB1 (Ki-67) immunopositive = (original=20 magnification =D7400). Pathologic diagnosis: progressive multifocal=20 leukoencephalopathy

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 9.3D""=20A,=20 Axial postcontrast T1-weighted magnetic resonance imaging (MRI) = demonstrates=20 suprasellar heterogeneous peripherally ring-enhancing lesion (arrow) = near the=20 anterior communicating artery. B, Axial T2-weighted MRI demonstrates a = T2=20 hypointense rounded suprasellar lesion (arrow). C, Thick-walled vessel = with=20 adjacent mixed chronic inflammatory infiltrate (hematoxylin-eosin, = original=20 magnification =D7100). Inset, The infiltrate contains numerous = eosinophils. D,=20 Degenerated eosinophilic capsule of cysticercus, with serrated surface=20 (hematoxylin-eosin, original magnification =D7200). Pathologic = diagnosis:=20 cysticercosis

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 10.3D""=20A,=20 Axial T2-weighted magnetic resonance imaging (MRI) demonstrating a = hyperintense=20 bifrontal butterfly-shaped lesion (arrow) extending across the genu of = the=20 corpus callosum. B, Axial postcontrast T1-weighted MRI demonstrates = peripheral=20 enhancement surrounding the lesion, in the form of an open ring (arrow), = an=20 imaging sign suggestive of a tumefactive demyelinating lesion. C, = Extensive=20 white matter vacuolation with preservation of the overlying cortex=20 (hematoxylin-eosin, original magnification =D740). D, Perivascular = chronic=20 inflammation with surrounding lipid-laden macrophages and gliosis=20 (hematoxylin-eosin, original magnification =D7400). E, Relative = preservation of=20 axons (stained black) in areas of demyelination (Bielschowsky stain, = original=20 magnification =D7200). Pathologic diagnosis: tumefactive demyelinating=20 lesion

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 11.3D""=20A,=20 2004 postcontrast T1-weighted axial magnetic resonance imaging (MRI)=20 demonstrating a right frontal heterogeneously enhancing mass (arrow) = with=20 surrounding edema and mass effect. B, 2004 biopsy, with perivascular = chronic=20 inflammation and abundant foamy macrophages (Luxol fast blue and=20 hematoxylin-eosin, original magnification =D7200). C, 2007 postcontrast=20 T1-weighted axial MRI demonstrating a homogeneously enhancing = subcortical lesion=20 (arrow) in the left inferior parietal lobe. D, 2007 biopsy, with = monotonous=20 lymphocytic infiltrate and numerous apoptotic bodies (hematoxylin-eosin, = original magnification =D7200). E, 2007 biopsy, infiltrate is composed = of CD20=20 (L26) immunopositive B cells (original magnification =D7200). Pathologic = diagnosis: demyelinating disease and central nervous system=20 lymphoma

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 12.3D""=20A,=20 Axial postcontrast T1-weighted magnetic resonance imaging demonstrating = abnormal=20 gyriform enhancement involving the bilateral paramedian cerebellar = hemispheres,=20 left greater than right (arrow), with mass effect and edema. B, Axial=20 diffusion-weighted imaging demonstrates gyriform hyperintensity of the=20 cerebellar folia (arrow), mimicking the appearance of Lhermitte-Duclos = disease.=20 C, Sharply demarcated area of cortical necrosis at right of field, = extending to=20 underlying white matter (hematoxylin-eosin, original magnification = =D712). D,=20 Eosinophilic, demarcated area of cortical necrosis seen at right of = field=20 (hematoxylin-eosin, original magnification =D7200). E, Numerous KP-1=20 immunopositive macrophages and microglia within infarct (original = magnification=20 =D7400). Pathologic diagnosis: subacute = infarct

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 13.3D""=20A,=20 Axial postcontrast T1-weighted magnetic resonance imaging (MRI) reveals = a=20 centrally hypointense deep left parietal lobe mass lesion (arrow) with a = thickened, irregular enhancing rim. B, Axial T2-weighted MRI = demonstrates a=20 rounded T2 hypointense left parietal lesion (arrow) with marked = surrounding=20 edema. C, Prominent perivascular inflammatory infiltrate = (hematoxylin-eosin,=20 original magnification =D7100). D, Fibrinoid necrosis of vessel wall=20 (hematoxylin-eosin, original magnification =D7400). E, The fibrinoid = necrosis is=20 highlighted bright red by an azocarmine stain (original magnification = =D7400). F,=20 Perivascular histiocytes within the infiltrate are immunopositive for = CD68=20 (KP-1) (original magnification =D7200). G, Perivascular B cells are = highlighted by=20 the CD20 immunostain (original magnification =D7400). H, Perivascular T = cells are=20 highlighted by the CD3 immunostain (original magnification =D7400). = Pathologic=20 diagnosis: vasculitis

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 14.3D""=20A,=20 Axial postcontrast T1-weighted magnetic resonance imaging (MRI) = demonstrating a=20 mildly hypointense mass (arrow) centered at left Meckel cave at the = expected=20 location of the trigeminal/gasserian ganglion. B, Homogeneous = eosinophilic=20 deposits are present within lesion (hematoxylin-eosin, original = magnification=20 =D7100). C, The deposits are stained orange-red (Congo red stain, = original=20 magnification =D7100). Inset, Deposits demonstrate apple green = birefringence under=20 polarized light (Congo red stain and polarized light, original = magnification=20 =D7100). D and inset, Electron microscopy reveals haphazard arrangement = of 6-μm=20 fibrils, typical for amyloid. E, Axial computed tomography bone window = shows a=20 hyperdense biconvex-shaped lesion involving the right frontoparietal = calvarium=20 causing mass effect on the right cerebral hemisphere. F, Congophilic = deposits=20 have apple green birefringence (Congo red stain and polarized light, = original=20 magnification =D7400). Pathologic diagnosis:=20 amyloidoma

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 15.3D""=20A,=20 Axial fluid-attentuated inversion recovery magnetic resonance imaging = (MRI)=20 demonstrates increased signal intensity bifrontally on either side of = the falx=20 (arrow). B, Axial postcontrast T1-weighted MRI shows contrast-enhancing = lesion=20 (arrow) along the falx and frontal dura bilaterally. C, A dense = lymphocytic=20 infiltrate surrounds hyalinized central vessel (hematoxylin-eosin, = original=20 magnification =D7400). D, The lymphocytic infiltrate is predominantly B = cells=20 (CD20 immunostain, original magnification =D7400). E, There is a minor = population=20 of T cells (CD3 immunostain, original magnification =D7400). Pathologic = diagnosis:=20 Castleman disease, hyaline-vascular type

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 16.3D""=20A,=20 Sagittal postcontrast T1 magnetic resonance imaging shows a = trilobed-enhancing=20 central skull base lesion with involvement of the sella and suprasella = cistern.=20 B, The resected lesion contains a dense diffuse mixed inflammatory = infiltrate=20 (hematoxylin-eosin, original magnification =D7100). C, Within the = infiltrate,=20 there are numerous pale-staining histiocytes and plasma cells=20 (hematoxylin-eosin, original magnification =D7400). Pathologic = diagnosis:=20 Rosai-Dorfman disease

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 17.3D""=20A,=20 Axial postcontrast T1-weighted magnetic resonance imaging (MRI) = demonstrating a=20 homogeneously enhancing left cerebellar mass (lower arrow) with = perilesional=20 edema and a second right pontine=96enhancing nodule (upper arrow). B, = Sagittal=20 postcontrast T1-weighted MRI again reveals the cerebellar lesion (lower = arrow)=20 with additional enhancing lesions (upper arrows) within the corpus = callosum,=20 posterior cingulate gyrus, anterior thalamus, and suprasellar region. C, = The=20 lesion consists of a dense mixed inflammatory infiltrate = (hematoxylin-eosin,=20 original magnification =D7400). D, Histiocytes are present within the = infiltrate=20 (CD68 immunostain, original magnification =D7400). E, The B-cell = component of the=20 infiltrate is highlighted by the CD20 immunostain (original = magnification =D7400).=20 F, Scattered rare T cells are present within the infiltrate (CD3 = immunostain,=20 original magnification =D7400). Pathologic diagnosis: inflammatory=20 pseudotumor

3D""=20
Click on thumbnail for full-sized = image.


3D""=20Figure 18.3D""=20A,=20 Axial postcontrast T1-weighted magnetic resonance imaging (MRI) = demonstrates a=20 well-circumscribed mass (arrow) within the left posterior = parietooccipital=20 region with thin peripheral enhancement. B, Axial T2-weighted MRI = reveals a=20 hyperintense partially cystic lesion (arrow) with an internal = fluid-fluid level.=20 C, There is parenchymal necrosis with hemosiderin deposits and dilated = vascular=20 channels (hematoxylin-eosin, original magnification =D7200). D, Necrosis = and=20 hemosiderin deposits (hematoxylin-eosin, original magnification =D7400). = Pathologic diagnosis: radiation necrosis

3D""The authors have no relevant financial = interest in=20 the products or companies described in this article.

3D""Reprints: Clare H. Cunliffe, = MD, Department=20 of Pathology, Division of Neuropathology, Mount Sinai School of = Medicine, One=20 Gustave L. Levy Place, New York, NY 10029 (E-mail: clare@drcunliffe.com)



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