Glioblastoma IDH wild-type

Case contributed by Dr Bruno Di Muzio



Patient Data

Age: 80 years
Gender: Male

CT Brain

Large right temporal mass associated with extensive surrounding hypodensity is demonstrated. Significant mass effect characterised by right uncal herniation, leftward midline shift of 6 mm, right cerebral sulcal effacement and partial effacement of the right lateral ventricle. Dilatation of the left lateral ventricle in keeping with hydrocephalus. No intracranial haemorrhage or collection.


MRI Brain

There is a large right temporal lobe mass with lobulated contours, surrounded by extensive areas of T2/FLAIR hypersignal and promoting a prominent mass effect characterised by uncal herniation, midline shift, right lateral ventricle effacement and right temporoparietal sulci effacement. The lesion has heterogeneous appearance with some small cystic areas and a probable extensive central necrotic area. There is a strong peripheral enhancement. 

On MRA images it is possible to spot the upward displacement of the right MCA. 


MICROSCOPIC DESCRIPTION: Sections show a hypercellular glial tumour composed of sheets of tumour cells containing abundant eosinophilic to clear cytoplasm, pleomorphic oval nuclei with vesicular chromatin and prominent nucleoli. There are extensive areas of tumour necrosis together with microvascular proliferation composed of multilayering of atypical cells around vascular lumina. There are up to 11 mitoses per 10 high-power fields.

Immunohistochemically tumour cells demonstrate the following profile:

  • GFAP Positive (strong)
  • Nestin Positive (high)
  • IDH-1 R132H Negative (not mutated)
  • ATRX Positive (not mutated)
  • MGMT Positive (promoter methylation unlikely)
  • p53 Positive
  • p16 (CDKN2A) Positive
  • Topoisomerase Approximately 20%

FINAL DIAGNOSIS:  IDH-1 wild-type Glioblastoma, WHO grade IV.

Case Discussion

The tumour was resected and confirmed as a glioblastoma (WHO grade IV) in keeping with the imaging features which were strongly suggestive for a high grade glioma. 

The immunohistochemical study has shown to be essential in better classifying and predicting CNS tumours behaviour. This case was considered to have a poor prognosis due to its IDH-1 negative (IDH1 negative = no mutation = 'wild type'), and though, two months later, the MRI follow-up showed disease progression involving all the splenium of the corpus callosum and contralateral extension. 

Note: Although this is tumour is entirely consistent with IDH wild-type molecular subtype, strictly speaking, to conclusively establish this, IDH would need to be sequenced to ensure that a non-IDH1 R132H mutation was present. In practice, an IDH1 R132H negative tumour in an elderly individual, particularly with unmethylated MGMT unmethylated 1 makes the possibility of this being IDH mutant remote, and sequencing is not felt to be necessary by many institutions. 

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Case information

rID: 39374
Published: 14th Sep 2015
Last edited: 22nd May 2017
Tag: rmh
Inclusion in quiz mode: Included

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