The cooccurrence of multiple sclerosis (MS) and oligodendroglioma is very rare. We present a 43-year-old male patient with the diagnosis of MS lasting for 14 years who developed seizures and right hemiparesis; cerebral MRI revealed an already known extensive lesion, previously misdiagnosed as tumefactive demyelinating lesion. Cerebral biopsy leads to oligodendroglioma diagnosis, successfully treated with radiotherapy. The diagnosis of a brain tumor in a MS patient is challenging. The atypical clinical and radiological features are the key for accurate diagnosis. In such cases, a brain tumor has to be kept in mind no matter how rare this association is.
The global risk of cancer among patients with multiple sclerosis (MS) seems to be lower than in general population with a reported incidence of 1.75% [
Reported cases of MS and pure oligodendroglioma cooccurrence.
Author | Age at MS onset | Age at tumor diagnosis | MS course | Tumor clinical presentation | MRI main features (other than typical MS findings) | Histopathology | |
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Khan et al. [ |
43 | 51 | RRMS | No symptoms (suspicion based on routine MRI) | 3 cm enhancing lesion involving both white and gray matter in the right parietal lobe* | Monomorphic neoplasm composed of oligodendrocytes, GFAP positive, and CD68 negative | |
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Green et al. [ |
Case |
34 | 50 | RRMS | No symptoms (suspicion based on routine MRI) | Nonenhancing mass lesion involving white matter in the right temporoparietal area, with some sulcal effacement of the overlying cortex* | Microcystic low grade oligodendroglioma |
Case |
44? | 44? | N/A | Seizures and monocular inferior left scotoma | Right temporal lobe lesion with some mass effect* | Grade 2 oligodendroglioma | |
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Giordana et al. [ |
34 | 42 | PPMS | N/A | Bilateral frontal lesion, involving anterior |
Unclear grade oligodendroglioma, not contiguous with MS lesions | |
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Rao et al. [ |
N/A | 65 | N/A | N/A | Diffuse lesion (right > left) across |
Oligodendroglioma with spotty calcification, ring lesions, contiguous with MS plaques | |
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Barnard and Jellinek [ |
28 | 43 | RR/SC MS | N/A | Mass lesion at the right temporal lobe | “Polymorphic” oligodendroglioma with mitotic figures and central necrosis | |
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de la Lama et al. [ |
26 | 37 | RRMS | Seizures | Large subcortical lesion at the right frontal lobe, poorly enhancing, causing mass effect and midline shifting to the left* | Tumoural proliferation with homogeneous nuclei and clear cytoplasms, not contiguous with MS plaques—grade C oligodendroglioma (Smith classification) |
*Enlargement from previously known lesion in routine MRI.
N/A: not available; RRMS: relapsing-remitting multiple sclerosis; SC: secondary progressive.
Oligodendroglioma accounts for approximately 2.5% of all primary brain tumours and 5-6% of all gliomas [
A 43-year-old male patient is followed in our MS clinic since 1994 with the diagnosis of clinical definite relapsing-remitting MS. The clinical presentation was a grade 4 paraparesis with no other symptoms; the initial MRI showed typical lesions for MS and cerebrospinal fluid analysis revealed positive oligoclonal bands. Interferon beta 1-b was started as treatment in 2003 with clinical efficacy and the patient had a full recovery of the paraparesis. In 2003 a routine brain MRI revealed a new extensive subcortical and deeper white matter lesion localized in the left frontal lobe, which is noncontrast-enhancing, suggesting a tumefactive demyelinating lesion (Figure
Cerebral MRI (2003): large left frontal lobe lesion (arrow) suggesting a tumefactive demyelinating lesion.
Cerebral MRI (2008): (a) large lesion in the left frontal lobe (large arrow). (b) Subtle contrast-enhancement (small arrow) and mass effect, suggesting an infiltrative lesion from glial series.
Histological examination. (a) Hematoxylin/Eosin coloration, with ×20 magnification, reveals moderately cellular neoplasm, consisting of cells with round nuclei and perinuclear light halo. (b) GFAP coloration, with ×40 magnification, reveals focal immunoreactivity of neoplastic cells (GFAP positive, CD68 negative cells).
The diagnosis of a brain tumor in a MS patient is challenging, due to several reasons that include the fact that new neurological symptoms in MS patients are easily attributed to a relapse of the disease and the MRI lesions, even if suspicious, are commonly diagnosed or confused as a tumefactive form of MS. Also the cooccurrence of two neurological diseases in the same patient is uncommon, particularly oligodendroglioma and MS. In fact, several years before the tumor suspect, routine MRI revealed an atypical new extensive lesion, similar to others reported cases [
Radiological red flags for MS, that is, atypical MRI features, include size of >2 cm, mass effect, perilesional oedema, and/or atypical enhancement (such as complete ring or heterogeneity), but they may occur in both tumefactive demyelinating lesions (TDL) and malignancies. In comparison with tumor, mass effect and oedema in MS are proportionally minor relative to plaque size [
It is worth noting that oligodendroglioma is a tumor derived from the glial cell involved in myelin production and hence in the MS physiopathology. In this sense, a causal association between oligodendroglioma and MS has been already proposed [
The cause-effect hypothesis is also based on the temporal sequence: tumor usually occurs many years (average of 15 years) after MS onset. On the other hand, these tumors tend to be multicentric. From gliomas occurring in MS patients, nearly 30 percent are multicentric or diffusely infiltrative, against 2.5 to 5 percent of gliomas unassociated with MS [
The role of long-term exposure of MS patients to first line immunomodulatory drugs (interferon-beta and GA) remains controversial. There is one report of intracranial neoplasm (medulloblastoma) in a MS patient taking GA [
However, as the reported cases are so exceptional, the association between oligodendroglioma and MS could be explained merely by coincidence.
As far as we know from the literature review, this is the 8th reported case of pure oligodendroglioma and MS cooccurrence. The atypical clinical and radiological features in MS patients are the key for accurate diagnosis. If a pseudotumoral form of MS is diagnosed, a careful clinical and radiological follow-up is required. In such cases, a brain tumor has to be kept in mind no matter how rare this association is. The lesion biopsy is the only accurate method for definitive diagnosis and should be used as soon as new atypical lesions appear.
The authors declare that there is no conflict of interests regarding the publication of this paper.