British Journal of Radiology (2004) 77, 153-156
© 2004 British Institute of Radiology
doi: 10.1259/bjr/26682607
Monophasic, solitary tumefactive demyelinating lesion: neuroimaging features and neuropathological diagnosis
H M Tan, FRCR
1
L L Chan, FRCR
1
K L Chuah, FRCPA
2
N S S Goh, MBBS (Singapore)
2 and
K K Tang, FRCS
3
Departments of 1 Diagnostic Radiology, 2 Pathology and 3 Neurosurgery, Singapore General Hospital, Outram Road, Singapore 168609
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Abstract
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The characteristic clinicoradiological findings of multiple sclerosis and acute disseminated encephalomyelitis (ADEM), demonstrating a recurrent progressive course in the former and monophasicity in the latter associated with multiple discrete white matter lesions with variable enhancement on MRI, are not a diagnostic challenge. On the other hand, the less typical radiological presentation of a solitary tumefactive demyelinating lesion mimics a neoplasm, and often necessitates a biopsy. Nonetheless, histopathological examination is an imperfect gold standard and the recognition of certain imaging features may facilitate the correct diagnosis.
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Introduction
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The spectrum of primary demyelinating diseases, of which multiple sclerosis is most common, is often made on clinical grounds. Histological confirmation is uncommon except when atypical clinical or radiological features are present. Tumefactive demyelination, as the name implies, poses a diagnostic challenge as it simulates a neoplasm on imaging, and especially so in a clinically monophasic and solitary lesion [1]. We highlight in our report how radiological features aided in the diagnosis of a case of acute tumefactive demyelination, and discuss potential histopathological pitfalls of demyelinating lesions.
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Case report
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A previously well 30-year-old right-handed Chinese male factory worker presented with subacute onset of right-sided weakness and numbness over 6 week's duration. Neurological examination confirmed a mild right hemiparesis and neuropsychological examination further revealed a clinical tetrad of right–left disorientation, finger agnosia, agraphia and acalculia, constituting Gerstmann's syndrome. There was no language disturbance, or history of preceding viral prodrome or immunization. A CT scan of the brain showed a hypodense lesion without significant enhancement or mass effect in the superior left parietal subcortical white matter (Figure 1
). MRI revealed a 3 cm rounded, well-defined T1 hypointense, T2 hyperintense mass with an incomplete rim of enhancement in the post-contrast scans (Figure 2). No other similar mass lesion or focal signal change was visualized. There was no encroachment into the grey matter. Given the large size of the mass, it was observed that the accompanying oedema was disproportionately mild. Despite its mass-like appearance, the rim enhancement and relative little perilesional oedema were thought to favour a demyelinating lesion over a low grade glioma. Progressive multifocal leucoencephalopathy (PML) was unlikely as the patient was not immunocompromised. HIV serology was also negative. Other negative blood test results included absent autoimmune markers and normal erythrocyte sedimentation rate (ESR) value.
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Figure 1. Contrast-enhanced CT reveals a hypodense lesion in the left parietal subcortical white matter, showing no significant mass effect or enhancement.
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Figure 2. (a, b, c) MRI shows high T2, low T1 signal white matter lesion with patchy rim enhancement. The lesion is solitary. Linear high T2 signal in the left periventricular white matter represent a prominent perivascular space on the T2 weighted scan.
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Despite the radiological features favouring a tumefactive demyelinating lesion, both the patient and the surgeon favoured stereotactic biopsy for the purpose of obtaining a histological confirmation. The choice of MR spectroscopy was also offered to the patient at this juncture but he opted for biopsy as he felt that histological confirmation would be definitive. The pre-biopsy surgical planning contrast-enhanced MRI scan was performed 8 days later. Interval increase in rim enhancement was noted in this scan (Figure 3). The patient underwent uneventful stereotactic biopsy of the mass. The lesion was reported to be an astrocytoma on histology. However, the patient declined surgery.
At 2 months follow-up, repeat MRI was performed and this time the patient agreed to undergo proton MR spectroscopy. The lesion demonstrated an interval decrease in overall mass effect and resolution of enhancement at its inferior edge (Figure 4). Proton MR spectroscopy (Figure 5) demonstrated a reduced N-acetyl aspartate (NAA) peak and no significant elevation of the choline peak relative to the creatine peak; the latter feature being against a mitotic lesion. A lumbar puncture revealed normal cerebrospinal fluid (CSF) cytology, biochemistry and absence of oligoclonal bands. Evoked potential studies performed were also normal.
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Figure 5. Proton MR spectroscopy showing reduced NAA peak, but no significant elevation of the choline peak.
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In view of the both the imaging and MR spectroscopy findings, a second expert histological opinion was sought. The final histopathological report confirmed a demyelinating process. There was myelin loss associated with relative preservation of axons. Immunoperoxidase for neurofilaments showed disruption of white matter tracts with relative preservation of neurofibrils whereas Luxol fast blue stain revealed dissolution of myelin in the affected areas (Figures 6 and 7). There were no giant astrocytic changes or oligodendroglial inclusions to suggest PML. At last follow up, the patient had not suffered a relapse.
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Figure 6. Haematoxylin and eosin stained sections of brain biopsy showing bizarre astrocytes simulating neoplastic process (original magnification x 200).
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Figure 7. The presence of foamy macrophages betray the diagnosis of a demyelinating disorder on histology (Haematoxylin and eosin, original magnification x 100).
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Discussion
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Multiple sclerosis is the most common demyelinating disease of the central nervous system affecting young adults [2]. The diagnosis is often a clinical one, with evidence of white matter lesions disseminated in time and space. Classically there is a remitting and relapsing course, or sometimes less typically gradual neurological deterioration. Evoked potentials, elevated CSF gamma globulin with oligoclonal bands and MRI facilitate the diagnosis [3]. It has been quoted that oligoclonal bands are present in only around 65% of patients with multiple sclerosis when a standard commercial assay is used [4]. Conversely, acute disseminated encephalomyelitis (ADEM) is a monophasic inflammatory demyelinating disease, usually preceded by a systemic viral infection or vaccination, and more commonly found in children and some tropical countries. The diagnosis is only made with a typical clinical presentation. MRI, electrophysiology and CSF analysis may corroborate the diagnosis.
MRI is especially helpful in providing imaging evidence of disease multifocality and also as a means of monitoring disease activity over time. Occasionally, both multiple sclerosis and ADEM may present as a mass lesion that clinically and radiologically is indistinguishable from a brain tumour.
The classic radiological appearance of multiple sclerosis is that of multiple sharply demarcated plaques. These plaques are found in the white matter, typically in the periventricular areas, and also in the septocallosal interface, juxtacortical and infratentorial locations. Contrast enhancement occurs in acute rather than chronic plaques.
Large (2 cm or more) tumefactive demyelinating plaques with mass-like features, although not classical, is a recognised finding in multiple sclerosis [5]. These lesions have been described to be generally well-demarcated, hypodense on CT, and of high T2 signal and relatively low signal on T1 signal on MRI. The lesions are notably found in the white matter. Contrast enhancement, mostly of the rim-enhancement type, is more common in the tumefactive variant than in the standard multiple sclerosis plaque [5]. A helpful diagnostic feature is multiplicity of lesions, often with one of the lesions in a typical periventricular or infratentorial location. However, caution needs to be exercised as gliomas can also develop in patients with multiple sclerosis [6]. The relative lack of mass effect or vasogenic oedema given the size of the lesions is also often a clue to the diagnosis [5].
The MRI lesions of ADEM are variable, and range from small to large size, with solid or ring enhancement, and predominantly affecting white but also grey matter. In the majority, the lesions are multifocal and asymmetric in distribution [7].
The diagnosis in this patient initially eluded us due to the monophasic clinical history, preliminary histology report, and negative evoked potentials and CSF findings, which all pointed to a neoplastic entity. The radiological presentation of a solitary mass-like lesion was also disconcerting and worrisome for tumour. However its location in the white matter, disparity between size and adjacent oedema, and short interval changes in enhancement pattern favoured tumefactive demyelination as the diagnosis. The MR spectroscopic findings of reduced NAA without corresponding elevation of choline peak relative to creatine peak also supported the radiological diagnosis. In astrocytomas, the NAA levels are also low reflecting a decrease in population of normal neurons and their metabolism. However, solid portions of the tumour are generally high in both choline and lactate levels due to low clearance of these metabolites [8]. Retrospectively if the MR spectroscopy were not skipped in the first instance, the stereotactic biopsy could have been avoided.
On histology, tumefactive demyelinating lesions may be associated with florid and cytologically atypical astrogliosis in which mitotic figures can be identified. Biopsy of the gliotic margin may therefore be misinterpreted as the edge of a glioma, especially in the context of limited tissue sampling from a stereotactic biopsy. Occasionally, some astrocytes may also show peculiar parcellation of nuclear material, simulating atypical mitosis. These features may lead the unwary to a misdiagnosis of gliomas such as astrocytomas or rarely oligodendrogliomas. However, careful observation of orderly spacing of the reactive astrocytes and recognition of the presence of macrophages should prompt the consideration of a demyelinating process leading to the performance of neurohistochemical and relevant immunohistochemical stains [9–12]. Although the morbidity rate of a stereotactic biopsy is relatively low at 3.5% and mortality rate of 0.7% [13], it is not without risks. Thus, recognition of the imaging features of a tumefactive demyelinating lesion would potentially save the patient a biopsy.
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Conclusion
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Monophasic, solitary tumefactive demyelinating lesions can be mistaken for a primary neoplasm and this case report illustrates how the radiological features including MR spectroscopy findings can aid the diagnosis in spite of potential histological pitfalls.
Received for publication June 17, 2002.
Revision received April 29, 2003.
Accepted for publication May 19, 2003.
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Abstract
Introduction
