- Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden,
- Department of Neurosurgery, Bezmialem Vakif University Medical School, İstanbul, Turkey,
- Department of Oncology, Royal Berkshire NHS Foundation Trust, Reading, United Kingdom.
- Department of Neuropathology, Karolinska University Hospital, Stockholm, Sweden,
Department of Neuropathology, Karolinska University Hospital, Stockholm, Sweden,
DOI:10.25259/SNI_176_2019Copyright: © 2019 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Georges Sinclair, Yahya Al-saffar, Philippa Johnstone, Mustafa Aziz Hatiboglu, Alia Shamikh. A challenging case of concurrent multiple sclerosis and anaplastic astrocytoma. 23-Aug-2019;10:166
How to cite this URL: Georges Sinclair, Yahya Al-saffar, Philippa Johnstone, Mustafa Aziz Hatiboglu, Alia Shamikh. A challenging case of concurrent multiple sclerosis and anaplastic astrocytoma. 23-Aug-2019;10:166. Available from: http://surgicalneurologyint.com/surgicalint-articles/9591/
Background: Cases of gliomas coexisting with multiple sclerosis (MS) have been described over the past few decades. However, due to the complex clinical and radiological traits inherent to both entities, this concurrent phenomenon remains difficult to diagnose. Much has been debated about whether this coexistence is incidental or mirrors a poorly understood neoplastic phenomenon engaging glial cells in the regions of demyelination.
Case Description: We present the case of a 41-year-old patient diagnosed with a left-sided frontal contrast enhancing lesion initially assessed as a tumefactive MS. Despite systemic treatment, the patient gradually developed signs of mass effect, which led to decompressive surgery. The initial microscopic evaluation demonstrated the presence of MS and oligodendroglioma; the postoperative evolution proved complex due to a series of MS-relapses and tumor recurrence. An ulterior revaluation of the samples for the purpose of this report showed an MS-concurrent anaplastic astrocytoma. We describe all relevant clinical aspects of this case and review the medical literature for possible causal mechanisms.
Conclusion: Although cases of concurrent glioma and MS remain rare, we present a case illustrating this phenomenon and explore a number of theories behind a potential causal relationship.
Keywords: Anaplastic astrocytoma, Gamma knife radiosurgery, Magnetic resonance imaging, Multiple sclerosis, Oligodendroglioma, Tumefactive multiple sclerosis
Multiple sclerosis (MS) is a demyelinating disease with complex clinical and radiological features. Although 85% of MS-cases develop a clinically isolated syndrome involving the optic nerves, brainstem, or spinal cord,[
A 41-year-old female patient developed epileptic seizures in 2008. Further investigation with magnetic resonance imaging (MRI) revealed a glioma-suspect tumor within the boundaries of the left frontal lobe as well as multiple supratentorial MS-like lesions scattered in both hemispheres. The routine cerebrospinal fluid (CSF)-analysis showed evidence of MS-activity, while the complementary MR spectroscopy (MRS) study suggested the presence of a concurrent oligodendroglioma. The ensuing needle biopsy on the left frontal lobe lesion showed solely inflammatory signs of demyelination, suggesting an evolving tumefactive MS-plaque [
Re-evaluation (2017) of available samples from needle biopsy performed in 2008 (2 samples of <4 mm). (a) Hematoxylin and Eosin glial biopsy with a mild increase in astrocytes. (b) Inflammatory process dominated by foamy macrophages (confirmed by immunohistochemistry). (c+d) CD68 immunohistochemistry: presence of a large number of macrophages.
MS is a chronic inflammatory demyelinating disease with contentious evolution. MS-plaques are not uncommonly misdiagnosed as malignant processes, a phenomenon known as tumefactive MS; in fact, some groups have reported that up to 6% of all MS-cases are confused with other diseases, including primary brain neoplasms.[
Glioma: In the context of glial tumors (including astrocytomas), preoperative MRI-examinations may provide key data as to the plausible grade of malignancy.[ MS: Lesions are commonly found within the confinements of the posterior fossa, periventricular areas, spinal cord, and optic nerves. Dual-echo and fluid-attenuated inversion recovery (FLAIR) imaging reveal focal areas of hyperintensity while T1-weighted MRI (with Gd) help discerns between active and inactive MS-lesions, as enhancement results from an increase in blood-brain barrier permeability in areas of “active” inflammation.[
Glioma: In the context of glial tumors (including astrocytomas), preoperative MRI-examinations may provide key data as to the plausible grade of malignancy.[
MS: Lesions are commonly found within the confinements of the posterior fossa, periventricular areas, spinal cord, and optic nerves. Dual-echo and fluid-attenuated inversion recovery (FLAIR) imaging reveal focal areas of hyperintensity while T1-weighted MRI (with Gd) help discerns between active and inactive MS-lesions, as enhancement results from an increase in blood-brain barrier permeability in areas of “active” inflammation.[
CSF-analysis and MS
From a general perspective, the presence of demyelinating activity can be confirmed through CSF-analyses; common traits of MS-disease in CSF-analysis can be found in
MS: Histological characteristics of chronic MS lesions are well known to neuropathologists; however, diagnosing MS at early stages may prove complex, particularly in the context of needle biopsy where meager samples frequently represent small areas of a larger lesion. Although larger samples collected from “wider” surgical margins increase diagnostic accuracy, a complete microscopic interpretation of this type of lesion may prove difficult. In this aspect, key microscopic features of early MS lesions are described in Glial tumors: The revaluation made for the purpose of this article exposed the presence of a diffuse, infiltrating isocitrate dehydrogenase (IDH) 1-mutant AA [
MS: Histological characteristics of chronic MS lesions are well known to neuropathologists; however, diagnosing MS at early stages may prove complex, particularly in the context of needle biopsy where meager samples frequently represent small areas of a larger lesion. Although larger samples collected from “wider” surgical margins increase diagnostic accuracy, a complete microscopic interpretation of this type of lesion may prove difficult. In this aspect, key microscopic features of early MS lesions are described in
Glial tumors: The revaluation made for the purpose of this article exposed the presence of a diffuse, infiltrating isocitrate dehydrogenase (IDH) 1-mutant AA [
Re-evaluation (2017) of 25 mm sample collected from the second resection (November 2010). (a) Hematoxylin and Eosin glial biopsy with moderately increased atypical astrocytes with gemistocytic features and with few mitoses. (b) Smear from the same biopsy: moderate increase in astrocytes with variation in size and shape. (c) Glial fibrillary acidic protein immunohistochemistry: positive in glial cells with astrocytic features. (d) KI-67 proliferation index about 25%. Samples from the first resection were not made available.
Reports of concurrent MS and glial cell tumors can be traced back as early as 1912; however, despite significant advances in the field of neuro-diagnostics, the number of reported cases of coexistent MS and gliomas remains limited (<100 cases). This is probably due to the condition’s rareness and entangled histopathological characteristics, the repertoire of diagnostic tools used during disease evolution, and the degree of multidisciplinary experience. Despite the latter, our case has a striking resemblance to a number of reports.[
John Cunningham (JC)-virus
As previously described in this paper, different groups seem to share common thoughts concerning plausible environmental- modulated mechanisms and malignant transformation of glial cells during the process of remyelination; the role of the human polyoma JCV remains interesting in this context.[
Although cases of concurrent glioma and MS remain rare, their entangled evolution might pose a challenge in terms of diagnosis and treatment. Modern MRI-protocols are crucial in the diagnosis of MS and gliomas; however, further studies are warranted to overcome issues concerning MR-signal specificity, particularly in the face of a concurrent condition. In this context, microscopic evaluation remains largely dependent on reliable diagnostic markers and multidisciplinary expertise. At least, in theory, MS and CNS malignancies might synergistically concur through a set of shared micro-environmental and immune-modulated mechanisms. From that perspective, a casual origin cannot be fully ruled out. More studies on the subject are warranted and encouraged.
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
None of the authors has any conflicts of interest to disclose.
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