Glioblastoma IDH wild-type

Case contributed by A.Prof Frank Gaillard


3 generalized tonic clonic seizures

Patient Data

Age: 25 years
Gender: Male

Selected FLAIR and T1 C+ images demonstrate a small region of high T2 involving the cortex and subcortical white matter of the precuneus, without contrast enhancement. This was felt to most likely be a low grade glioma, or potentially a region of focal cortical dysplasia. Follow-up imaging was organised. 


4 months later

Selected FLAIR and T1 C+ images demonstrate surprisingly fast growth with faint punctate enhancement now visible. Findings are suspicious for progression to a higher grade.

The patient was reviewed as an outpatient a few weeks later. Given the fairly rapid growth, the decision was made to biopsy this lesion and a stereotaxis scan was organised. 


1 month later still

Selected FLAIR and T1 C+ images from stereotaxis scans for operative planning demonstrate still further growth and increase in enhancement. 



Paraffin sections show multiple fragments of a densely  hypercellular tumour. Tumour cells have pleomorphic round, oval and  angulated hyperchromatic nuclei with fibrillary processes. Moderate  numbers of mitotic figures are identified (8 in 20 high power  fields). Foci of microvascular proliferation with multilayering of  atypical cells around vessel lumena are noted and there are scattered  foci of palisaded necrosis. There is patchy microcalcification.


  • GFAP: positive
  • Nestin: positive (high)
  • IDH-1 R132H: negative (not mutated)
  • ATRX: positive (not mutated)
  • p53: positive
  • p16 CDKN2A: positive
  • MGMT: positive (likely unmethylated)

Topoisomerase labelling index:  Approximately 40%.

DIAGNOSIS: Glioblastoma (WHO Grade IV)

Case Discussion

This case illustrates the difficulty conventional imaging has in distinguishing a low-grade tumour with indolent biological behaviour from early imaging of a more aggressive tumour. In this case were a biopsy to have been performed at the time of the first scan it would almost certainly have demonstrated a diffuse low-grade glioma. At that stage, however, it would have been IDH negative, which would have been predictive of aggressive behaviour. 

Although the very aggressive behaviour is entirely consistent with IDH wild-type molecular subtype, as is MGMT being unmethylated 1, to conclusively establish this IDH would need to be sequenced to ensure that a non-IDH1 R132H mutation was present. This is particularly relevant in young patients. 



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Case information

rID: 43877
Published: 27th Mar 2016
Last edited: 21st May 2017
Inclusion in quiz mode: Excluded

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