Oligodendrogliomas are defined as IDH mutant and 1p 19q codeletion grade II tumours by the World Health Organization Classification of Tumors of the Central Nervous System 2016 1).
Variants at 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR and subsequent validation SNP genotyping, we identified seven low-frequency SNPs at 8q24.21 that were strongly associated with glioma risk (P=1×10(-25) to 1×10(-14)). The most strongly associated SNP, rs55705857, remained highly significant after individual adjustment for the other top six SNPs and two previously published SNPs. After stratifying by histological and tumor genetic subtype, the most significant associations of rs55705857 were with oligodendroglial tumors and gliomas with mutant IDH1 or IDH2 (odds ratio (OR)=5.1, P=1.1×10(-31) and OR=4.8, P=6.6×10(-22), respectively). Strong associations were observed for astrocytomas with mutated IDH1 or IDH2 (grades 2-4) (OR=5.16-6.66, P=4.7×10(-12) to 2.2×10(-8)) but not for astrocytomas with wild-type IDH1 and IDH2 (smallest P=0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA 2).
Findings suggest a possible participation of rs891835, rs6470745, and rs55705857 as risk factors to develop glioma 3).
Tumor DNA may approximate genotype at the rs55705857 locus. Hummel et al., confirmed this locus confers an increased risk of all cancers and especially of oligodendroglioma. No increased cancer or brain tumor risk is seen in family members of individuals without the high-risk G allele 4).
Some studies have linked oligodendroglioma with a viral cause. A 2009 Oxford Neurosymposium study illustrated a 69% correlation between NJDS gene mutation and the tumor initiation shown by Kevin Smith. A single case report has linked oligodendroglioma to irradiation of pituitary adenoma.
For nearly a century, the diagnosis and grading of oligodendrogliomas and oligoastrocytomas has been based on histopathology alone.The first glioma-associated molecular signature was found with complete chromosome 1p and 19q codeletion being particularly common in histologically classic oligodendrogliomas. Subsequently, this codeletion appeared to not only carry diagnostic, but also prognostic and predictive information, the latter aspect only recently resolved after carefully constructed clinical trials with very long follow-up times. More recently described biomarkers, including the non-balanced translocation leading to 1p/19q codeletion, promoter hypermethylation of the MGMT gene, mutations of the IDH1 or IDH2 gene, and mutations of FUBP1 (on 1p) or CIC (on 19q), have greatly enhanced our understanding of oligodendroglioma biology, although their diagnostic, prognostic, and predictive roles are less clear. It has therefore been suggested that complete 1p/19q codeletion be required for the diagnosis of 'canonical oligodendroglioma'. This transition to an integrated morphological and molecular diagnosis may result in the disappearance of oligoastrocytoma as an entity, but brings new challenges as well. For instance it needs to be sorted out how (histopathological) criteria for grading of 'canonical oligodendrogliomas' should be adapted, how pediatric oligodendrogliomas (known to lack codeletions) should be defined, which platforms and cut-off levels should ideally be used for demonstration of particular molecular aberrations, and how the diagnosis of oligodendroglioma should be made in centers/countries where molecular diagnostics is not available. Meanwhile, smart integration of morphological and molecular information will lead to recognition of biologically much more uniform groups within the spectrum of diffuse gliomas and thereby facilitate tailored treatments for individual patients 5).
The classic presentation of ODG: a patient with seizures for many years prior to the diagnosis which would be made when they later present with an apoplectic event due to peritumoral intracerebral hemorrhage. This scenario is less common with the proliferation of CT & MRI scans.
In anywhere from fifty to eighty percent of cases, the first symptom of oligodendroglioma is the onset of seizure activity. They occur mainly in the frontal lobe. Headaches combined with increased intracranial pressure are also a common symptom of oligodendroglioma. Depending on the location of the tumor, any neurological deficit can be induced, from visual loss, motor weakness and cognitive decline.
In rare cases, without conclusive data on IDH mutation and 1p/19q codeletion status, tumours are classified as oligodendroglioma, not otherwise specified. The diagnosis of oligoastrocytoma is discouraged in the new WHO classification, which states that only exceptional cases that cannot be conclusively tested for IDH mutation and 1p/19q codeletion that show a mixed oligoastrocytic histology can still be classified as oligoastrocytoma, not otherwise specified 6).
A 83-year-old man with an 11-year history of lentigo maligna melanoma who presented with impaired balance and cognitive slowing and was found to have rapid progression of a previously known indolent right frontal brain mass. Pathologic examination of the tumor after resection revealed the presence of both malignant melanoma and an oligodendroglioma WHO grade II. To the best of our knowledge, this is the first reported case of malignant melanoma metastasizing to an oligodendroglioma that has been confirmed by immunohistochemistry and genetic analysis 7).