Oligodendroglioma

Oligodendrogliomas are intracranial tumours that account for 5-25% of all gliomas and 5-10% of all primary intracranial neoplasms. They are identified on histological grounds and now require 1p19q codeletion.

On imaging, these tumours commonly present as a round or oval sharply marginated mass 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.

Epidemiology

These are usually tumours of middle-aged adults, occurring most commonly in the 4^th and 5^th decades of life. 

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

Clinical presentation

Due to frequent cortical involvement, they most commonly present with seizures.

Pathology 

Gross appearance

Generally, oligodendrogliomas are well-circumscribed, gelatinous, grey masses. They are usually calcified (70-90%: one of the most frequently calcifying tumours), less often with focal haemorrhage. 20% of these tumours are cystic, and they can often expand a gyrus and remodel the skull. They can occur essentially anywhere, including intraventricularly where they are difficult to distinguish from central neurocytomas on light microscopy.

Microscopic appearance and classification

It is essential to appreciate that as of the 2016 update to the WHO classification of CNS tumours, to formally make the diagnosis of oligodendroglioma, a tumour must be shown to have 1p19q co-deletion. If molecular testing is unavailable or is equivocal, then the fall back is histology, and the diagnosis should then be oligodendroglioma NOS (not otherwise specified). 

Oligodendroglioma (WHO grade II/low grade)

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 contains a delicate network of anastomosing capillaries giving it a so-called "chicken wire" appearance ⁶. These tumours are slowly growing.

Anaplastic oligodendroglioma (WHO grade III/high grade)

Increased cellular density, mitotic activity, microvascular proliferation and necrosis.  Nuclear anaplasia is also common.

Anaplastic oligodendrogliomas make up 20-50% of all oligodendrogliomas.

Note: When necrosis is present in an anaplastic tumour, then they are no longer considered WHO Grade IV tumours unless an astrocytic (1p19q intact) component is also present ⁹. 

Oligoastrocytoma

Oligoastrocytomas, a tumour of mixed oligodendroglioma and astrocytoma cell populations have historically been variably reported depending on local practice. As of the 2016 update to the WHO classification of CNS tumours, to make the diagnosis genomic evidence of both astrocytic and oligodendroglial components will be required to make the diagnosis, and as such, they are likely to become rare ⁹.  

Molecular genetics and subclassification

• 1p/19q chromosome loss: excellent response to radiation and chemotherapy
• 1p/19q chromosome intact: refractory to radiation and chemotherapy ^2,7

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 they can be ribbon-like ⁴. The overlying skull may show pressure erosion.

Post-contrast CT

50% of oligodendrogliomas enhance: degree of enhancement is extremely variable (no enhancement to striking).

MRI

Tumours in which 1p/19q is intact show more homogenous signal on T1 and T2 images and have sharper borders than tumours with 1p/19q deletions. Calcification and haemorrhage are difficult to distinguish on MR. Peritumoral vasogenic oedema is minimal.

• T1: typically hypointense 
• T2: typically hyperintense (except calcified areas)
• T2*: calcium 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: increased vascularity "chicken wire" network of vascularity results in elevated relative cerebral blood volume (rCBV) of grade II vs grade III on PWI; PWI has a sensitivity of 95% and PPV or 87% for distinguishing grade II from grade III oligodendrogliomas ¹; a threshold of 1.75, rCBV above this threshold demonstrate more rapid tumour progression ¹

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 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. Five years survival rate is approximately 50-75%.

Differential diagnosis

General imaging differential considerations include:

• astrocytoma
• ganglioglioma
• dysembryoplastic neuroepithelial tumour (DNET)
• pleomorphic xanthoastrocytoma (PXA)
• cerebritis/herpes simplex (HSV) encephalitis
• cerebral ischaemia/infarction
• cerebral arteriovenous malformation (AVM)