Neuro Oncology Diagnosis

Diagnosing Oligodendrogliomas

• Proliferation markers like Ki-67 (MIB1) and clinical/neuroradiological features (e.g. rapid symptomatic growth and contrast enhancement) may provide additional information in borderline cases.
• Homozygous deletion involving the CDKN2A and/or CDKN2B locus is found in a small subset (~30%) of oligodendrogliomas.
• Immunohistochemical detection of IDH1 p.R132H expression and preserved nuclear ATRX expression is not sufficient to diagnose an IDH-mutant and 1p/19q-codeleted oligodendroglioma, even with classic histology.

Molecular Characteristics

• Most IDH-mutant and 1p/19q-codeleted oligodendrogliomas carry TERT promoter mutations.
• Detection of a TERT promoter mutation in an IDH-mutant glioma is not sufficient for an oligodendroglioma diagnosis, as rare cases are TERT-wildtype.
• TERT promoter mutations are also observed in a subset of 1p/19q-intact IDH-mutant astrocytomas.

DNA Methylation Array Analysis

• DNA methylation array analysis reveals a diagnostic molecular profile by combining the detection of an oligodendroglioma-associated methylation signature and 1p/19q codeletion.

Pathogenesis

• The cell (or cells) of origin of IDH-mutant and 1p/19q-codeleted oligodendroglioma remains unknown.

Imaging

• IDH-mutant and 1p/19q-codeleted oligodendrogliomas usually appear on CT as hypodense or isodense mass lesions that are typically located in the cortex and subcortical white matter.
• Calcifications are commonly seen, but they are not diagnostic; some tumours show intratumoural haemorrhages and/or areas of cystic degeneration.
• MRI typically shows a T1-hypointense and T2-hyperintense mass with indistinct tumour margins.
• Gadolinium contrast enhancement can be detected in ~70% of CNS WHO grade 3 oligodendrogliomas, where it is associated with microvascular proliferation and less favourable prognosis.

Diagnostic Features of IDH-Mutant and 1p/19q-Codeleted Oligodendrogliomas

• Ki-67 (MIB1) and clinical/neuroradiological features may provide additional information in borderline cases
• Homozygous deletion of CDKN2A and/or CDKN2B locus is found in a small subset (~30%) of cases
• IDH1 p.R132H expression and preserved nuclear ATRX expression are not sufficient for diagnosis without 1p/19q codeletion
• 1p/19q analysis is critical for accurate molecular diagnosis in IDH-mutant gliomas with preserved nuclear ATRX expression
• Most IDH-mutant and 1p/19q-codeleted oligodendrogliomas carry TERT promoter mutations
• Detection of TERT promoter mutation is not sufficient for oligodendroglioma diagnosis, as rare cases are TERT-wildtype

Imaging Features

• IDH-mutant and 1p/19q-codeleted oligodendrogliomas typically appear as hypodense or isodense mass lesions on CT
• Calcifications are commonly seen, but not diagnostic
• MRI typically shows a T1-hypointense and T2-hyperintense mass with indistinct tumour margins
• Gadolinium contrast enhancement is detected in ~70% of CNS WHO grade 3 oligodendrogliomas, associated with microvascular proliferation and less favourable prognosis
• IDH-mutant and 1p/19q-codeleted oligodendrogliomas show higher microvascularity and higher vascular heterogeneity than IDH-mutant diffuse astrocytomas

Additional Diagnostic Techniques

• Magnetic resonance spectroscopy and radiomics can identify differences between 1p/19q-codeleted and 1p/19q-intact low-grade diffuse gliomas, but have limited sensitivity and specificity
• Demonstration of elevated 2-hydroxyglutarate levels by magnetic resonance spectroscopy is a new means of non-invasively detecting IDH-mutant gliomas
• PET imaging may allow the distinction between CNS WHO grade 2 and 3 IDH-mutant gliomas, but reported series tend to be small and unvalidated

Spread of Oligodendrogliomas

• IDH-mutant and 1p/19q-codeleted oligodendrogliomas characteristically extend into adjacent brain in a diffuse manner
• They occasionally have a gliomatosis cerebri pattern
• Distant leptomeningeal spread may occur in some patients, especially in late-stage disease
• Rare cases of extracranial metastases of oligodendrogliomas, mostly CNS WHO grade 3, have been reported