Oligodendroglioma

Oligodendrogliomas are intracranial tumours that account for 5-25% of all gliomas and 5-10% of all primary intracranial neoplasms.

They are characterised by IDH mutation and 1p19q codeletion and can be a WHO CNS grade 2 or 3. 

On imaging, oligodendrogliomas commonly present as masses involving the cortex or subcortical white matter, with low attenuation on CT, hypointense compared to grey matter on T1 and hyperintense compared to grey matter on T2-weighted MRI images. The attenuation or signal can be eventually heterogeneous due to calcification, cystic degeneration and haemorrhage.

Terminology

Historically, oligodendrogliomas have been defined on purely histological grounds. As of 2016, however, with the update to the WHO classification of CNS tumours the diagnosis of oligodendroglioma is made by identifying a diffuse infiltrating glioma with IDH mutation and 1p19q codeletion ⁹. This was a very significant change, as the tumours previously diagnosed as oligodendrogliomas on the grounds of histology, and those currently diagnosed on the basis of the molecular markers are not identical, with somewhat different imaging features. As such it is essential when reading about gliomas to ascertain which definition is being used. As a general rule, anything written before 2016 will use histology alone. 

The reliance on molecular markers is, however, not foolproof. Sometimes molecular markers are unavailable (in many countries or regional centres) or sometimes equivocal. In such instances, the diagnosis reverts to histological features alone, and are termed not otherwise specified (NOS) ⁹. 

In the 5th edition (2021) of the WHO classification of CNS tumours, the term "anaplastic" has been removed, and tumours are merely graded as 2 or 3 ¹¹. 

Note, oligoastrocytomas are no longer recognised as a distinct entity. The coexistance of neoplastic astrocytoma and oligodendrocgliomaoligodendroglioma (when molecularly defined) in the one tumour is considered extremely rare.More commonly, the term is used to denote tumours that appear histologically to have both astrocytic and oligodendroglial components but that who cannot be fully molecularly characterised (thus oligoastrocytoma NOS) ¹¹. 

Epidemiology

Oligodendroglioma is considered the third most common glioma accounting for 2%–5% of primary brain tumours and 5%–18% of all glial neoplasms ⁸. 

Oligodendrogliomas are usually tumours of middle-aged adults, occurring most commonly in the 4^th and 5^th decades of life, somewhat older for grade 3 tumours ^10,11. There is a slight male predilection (M:F 1.3:1) ¹⁰. 

They are rare in children ^10,11.

Clinical presentation

Due to frequent cortical involvement, oligodendrogliomas most commonly (two-thirds of patients) present with seizures ⁹. Otherwise, the clinical presentation is non-specific with symptoms related to increased intracranial pressure and focal neurological deficits being common. 

Pathology 

Location

The vast majority of oligodendrogliomas arise in the cerebral hemispheres, with brainstem, cerebellum and spinal cord being distinctly uncommon ⁹. 

Macroscopic appearance

Historically, oligodendrogliomas were considered well-circumscribed, gelatinous, grey masses, and this remains true of histologically defined oligodendrogliomas NOS.

Molecularly defined IDH-mutant and 1p19q co-deleted oligodendrogliomas, however, appear to be a slightly different group of tumours and recent studies suggest that in fact they have poorly defined borders ¹⁰.

Oligodendrogliomas are often calcified (70-90% of histological oligodendrogliomas: one of the most frequently calcifying tumours) and also frequently demonstrate focal haemorrhage ⁹. Cystic change is also quite common. Slow growing cortical tumours can often expand a gyrus and eventually remodel the skull. 

Microscopic appearance and classification

Histological features are only one aspect of the diagnosis of oligodendroglioma and to formally make the diagnosis, a tumour must be shown to have both IDH-mutation and 1p19q co-deletion (see Terminology section above). 

Neoplastic oligodendrocytes appear as regular cells with spherical nuclei containing finely granular chromatin surrounded by a halo of cytoplasm "fried egg" appearance under the light microscope. Typically there is a delicate network of anastomosing capillaries giving it a so-called "chicken wire" appearance ⁶. These tumours are slowly growing.

Grade 3 oligodendrogliomas (formerly known as anaplastic oligodendrogliomas) demonstrate increased cellular density, increased mitotic activity, microvascular proliferation and necrosis. Nuclear anaplasia is also common.

Importantly, and unlike astrocytomas, oligodendrogliomas with necrosis and microvascular proliferation are considered only WHO grade 3 and not grade 4 tumours ⁹. 

Molecular markers

By definition oligodendrogliomas should demonstrate ^11,12:

1. IDH mutation (either IDH1 or IDH2)

2. 1p19q codeletion

Additionally, a number of other mutations are commonly encountered in oligodendrogliomas ¹²:

• TERT promoter mutation

• CIC mutation

• FUBP1 mutation

• NOTCH1 mutations

Radiographic features

CT

Non-contrast CT

Tumours are of mixed density (hypodense to isodense). High-attenuation areas within the tumour are likely from calcification (70-90% of oligodendrogliomas are calcified) or, less commonly, haemorrhage. Calcification can be located centrally, peripherally or can be ribbon-like ⁴. The overlying skull may show pressure remodelling.

Post-contrast CT

Approximately 50% of oligodendrogliomas enhance: the degree of enhancement is extremely variable, ranging from no enhancement to strikingly vivid enhancement.

MRI

The MRI appearances also vary depending on whether a histological diagnosis or a molecular definition is used.

Oligodendrogliomas NOS, or those tumours that histologically show oligodendroglial features but are 1p/19q intact show more homogeneous signal on T1 and T2 images and have sharper borders than 'true' oligodendroglioma, those with 1p/19q co-deletion ¹⁰. In fact, a lesion being well-circumscribed homogeneously T1 hypoattenuating with high T2 signal and T2/FLAIR mismatch without calcification is predictive of not having 1p19q codeletion ¹⁰. 

Calcification and haemorrhage are difficult to distinguish on MR, appearing as areas of signal loss on T2* sequences, although the phase component of SWI may help. Peritumoral vasogenic oedema is minimal in grade 2 tumours.

• T1: typically hypointense 

• T2: typically hyperintense (except calcified areas)

• GRE/SWI: calcium can be seen as areas of "blooming"

• T1 C+ (Gd): contrast enhancement is common but it is not a reliable indicator of tumour grade, with only 50% of oligodendrogliomas enhancing to a variable degree, and usually heterogeneously

• DWI

  • typically no diffusion restriction

  • DWI can be used to help differentiate oligodendrogliomas (generally lower grade) from astrocytomas (generally higher grade); astrocytomas have higher ADC values probably because of their lower cellularity and greater hyaluronan proportion ⁵.

• MR perfusion (PWI)

  • ​increased vascularity "chicken wire" network of vascularity results in elevated relative cerebral blood volume (rCBV)

  • older literature ¹ suggested that this was useful in predicting histological grade of tumour, however, how this relates to modern classification systems based on molecular markers is unclear

PET

¹¹C-Methionine studies can be used to differentiate oligodendrogliomas from anaplastic oligodendrogliomas. FDG uptake of oligodendrogliomas is similar to normal white matter. FDG uptake of anaplastic oligodendrogliomas is similar to normal grey matter.

Treatment and prognosis

As mentioned earlier response to radiochemotherapy and hence prognosis depends significantly on the presence or absence of 1p19q gene deletion ^2,7. 

Treatment is surgical, with adjuvant radiotherapy and chemotherapy. Although they are macroscopically well delineated, infiltration is present at their margins and local recurrence is common.

Survival statistics are primarily available for histologically defined oligodendrogliomas and tend to demonstrate 10 year-survival of approximately 50% ⁹. 

Differential diagnosis

General imaging differential considerations include:

• astrocytoma: ​difficult to separate from oligodendrogliomas with certainty but some features are helpful

  • astrocytomas are more common

  • T2/FLAIR mismatch sign favours astrocytoma

  • well-defined margins favour astrocytomas

  • calcification strongly favours oligodendroglioma

• ganglioglioma

• pleomorphic xanthoastrocytoma (PXA)

• CAPNON: entirely calcified