Glioblastoma IDH wild-type

Case contributed by Bruno Di Muzio


Delirium of unclear cause. Fever.

Patient Data

Age: 60 years
Gender: Female

CT Brain


Mltiple peripherally enhancing lesions with central hypodensity in the right frontal lobe. The largest lesions measures 2.9 x 2.2 x 1.7cm with multiple smaller lesions superiorly. Significant surrounding vasogenic edema. There is effacement of the frontal horn of the right lateral ventricle, subfalcine herniation and right-to-left midline shift of 13mm at the level of the septum pellucidum. No tonsillar or uncal herniation. The left ventricle is not dilated

No other areas of abnormal contrast enhancement. Mastoid air cells and paranasal sinuses are clear.

Conclusion: Multiple peripherally enhancing lesions in the right frontal lobe resulting in significant mass effect. In the setting of fever, the findings are suspicious for cerebral abscesses. The differential includes metastatic lesions and a primary brain tumor. MRI is recommended to further evaluate.

MRI Brain


Technique: Multiplanar, multisequence imaging has been obtained through the brain including pre and post contrast sequences, MR perfusion and MR spectroscopy.

Findings: Within the right frontal lobe, there is a cluster of multiple adjacent peripherally enhancing lesions which together measure 3.4 x 3.5 x 4.0cm (cc x trans x AP). This is surrounded by a large amount of FLAIR hyperintensity which extends across the genu of the corpus callosum into the left frontal lobe, and involves the right internal capsule, lentiform nucleus and thalamus. The signal abnormality and enhancement involve the right frontal cortex as well as white matter. Within the right frontal lobe just superior to the sylvian fissure, there is a separate 10 mm nodule of enhancement. There is a large amount of mass effect, characterized by right frontal cortical sulcal effacement, compression of the right lateral and third ventricles and 11 mm of right to left shift and subfalcine herniation. There is a slight dilatation of the left lateral ventricle consistent with early hydrocephalus. Within the right frontal lobe, there is mild diffusion restriction and increased CBV. Spectroscopy demonstrates increased choline, decreased NAA and a lactate/lipid peak. The paranasal sinuses are clear.

Conclusion: Findings are strongly favored to represent a high-grade glioma, although abscess and metastasis are much less likely differentials.

Case Discussion

This case brings some of the difficulties that sometimes we found when reporting brain CTs in the emergency department. The patient came with a clinical history of fevers and delirium, making infection a favorable diagnosis. MRI Brain with advanced sequences (Spectroscopy and Perfusion) helped to narrow and spot a most certain diagnosis. 

Biopsy was performed and confirmed a glioblastoma


MICROSCOPIC DESCRIPTION: Paraffin sections show extensive replacement of white matter by a densely hypercellular glial tumor. This is composed predominantly of fibrillary and gemistocytic astrocytes which show moderate nuclear and cellular pleomorphism. In addition, there is a minor oligodendroglial component. Frequent mitotic figures are identified. There is prominent microvascular proliferation with multilayering of atypical cell around vascular lumens. Several areas of palisaded necrosis are also noted. These incorporate thin-walled necrotic and thrombosed blood vessels. Tumor extensively involves cerebral cortex and there is prominent peri-neuronal, perivascular and sub-pial secondary structuring. The features are of glioblastoma multiforme with a minor oligodendroglioma component (WHO Grade IV).


  • GFAP positive in tumor and reactive astrocytes; negative in oligodendroglial cells
  • NogoA positive in tumor oligodendrocytes
  • Nestin positive (high)
  • IDH-1 R132H negative (not mutated)
  • MGMT negative (likely methylated)
  • p53 negative
  • p16 negative

Topoisomerase labeling index: Approximately 20%

DIAGNOSIS: Glioblastoma multiforme with a minor oligodendroglioma component (WHO Grade IV).

Note: 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.

This is particularly relevant in this setting as there is a component that appears oligodendroglial, and MGMT is methylated. It is, therefore, possible that if a non-R132H mutation was identified, and 1p19q was co-deleted, then this would represent an anaplastic oligodendroglioma rather than a GBM. 

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