Glioblastoma IDH wild-type

Case contributed by RMH Neuropathology
Diagnosis certain


Patient referred do a left frontal brain tumor.

Patient Data

Age: 60 years
Gender: Male

CT Brain


Technique: Pre and post contrast volumetric acquisition through the brain. 

Findings: There is a heterogeneous cortical-subcortical mass in the left frontal lobe showing intense peripheral enhancement and central areas of hypoattenuation (necrosis). It promotes local mass effect with adjacent vasogenic edema and local sulci effacement. No midline shift. The ventricular system is normal and in keeping with the expected for the age group. The remainder brain is unremarkable.

Conclusion: Left frontal tumor which may correspond to a high-grade glioma, metastasis is a less likely differential diagnosis to be considered. Further assessment with brain MRI is advised. 

MRI Brain


A left frontal mass with irregular peripheral enhancement and heterogeneous internal signal extends to the cortex of the left middle frontal gyrus. There is a small volume of surrounding non-enhancing T2 hyperintensity. Within the lesion there are foci of signal dropout demonstrate susceptibility blooming artefact on T2* weighted sequence, compatible with blood product or calcification.

Although the presence of blood product or calcification complicates the assessment of diffusion-weighted and diffusion imaging, there is low ADC associate with the enhancing periphery of the tumor and probable increased cerebral blood volume (CBV) along the inferior margin.

Spectroscopy trace performed immediately medial to the enhancing margin of the mass demonstrates choline elevation and NAA reduction without significant lactate peak, however voxels straddling the enhancing margin and the necrotic center demonstrates more pronounced choline elevation and NAA reduction with a lactate peak.

The mass causes mild local sulcal effacement with minimal distortion of the left lateral ventricle and no midline shift. No hydrocephalus.

Conclusion: Appearance suggests a glial tumor, high grade favored based on spectroscopy findings and enhancement pattern.


MICROSCOPIC DESCRIPTION: Paraffin sections show fragments of a densely hypercellular glial tumor. This is composed predominantly of moderately pleomorphic fibrillary astrocytes arranged in diffuse sheets. A small component of gemistocytic cells is noted. There are moderate numbers of mitotic figures. Foci of microvascular proliferation with multilayering of atypical cells around vessel lumena are also noted and there is prominent pallisading and confluent necrosis. Several of the latter areas incorporate thin-walled necrotic blood vessels. The features are of glioblastoma multiforme (WHO Grade IV).


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

Topoisomerase labeling index: Approximately 35%

DIAGNOSIS: IDH-1 wild-type glioblastoma multiforme (WHO Grade IV) 

Case Discussion

This case shows a glioblastoma with a poor prognosis based on its immunohistochemistry panel. 

Although this is tumor is entirely consistent with an IDH wild-type glioblastoma, immunohistochemical IDH1 R132H negativity does not categorically exclude a non-IDH1 R132H mutation. To be absolutely certain one would need to perform IDH sequencing. 

In this age-group and with MGMT being unmethylated, the likelihood of such a mutation is remote. 


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