Glioblastoma IDH wild-type (with pseudoprogression)

Case contributed by Assoc Prof Frank Gaillard



Patient Data

Age: 70 years
Gender: Male

There is am intraaxial peripherally enhancing mass in the peripheral right middle frontal gyrus. There is surrounding abnormal hyperintensity in the surrounding right frontal white matter consistent with vasogenic edema. Blooming on gradient echo sequence indicate the presence of blood products within the mass. Diffusion weighted imaging sequences difficult to interpret any presence of blood products.

A second smaller focus of enhancement is present anterior and medial to the larger lesion.

Previous right posterior cerebral artery territory infarct.

Conclusion: Two closely related enhancing intra-axial masses in the right frontal lobe either represent hemorrhagic metastases or a hemorrhagic high grade glial tumor (GBM). 

The patient went on to have a resection. 


MICROSCOPIC DESCRIPTION: Sections show a hypercellular tumor composed of sheets of tumor cells with extensive areas of pallisaded tumor necrosis. There is focal microvascular proliferation with multilayering of atypical cells around vessel lumena. Tumor cells contain abundant eosinophilic cytoplasm, oval angulated nuclei with coarse granular chromatin and small nucleoli. Frequent mitoses are observed.


  • GFAP Positive
  • Nestin Positive (high)
  • IDH-1 R132H Negative (not mutated)
  • ATRX Positive (not mutated)
  • MGMT Negative (likely methylated)
  • p53 Positive
  • p16 CDKN2A Positive
  • Topoisomerase labeling index: Approximately 20%.

The features are of glioblastoma, IDH wildtype (WHO grade IV). 


Immediate post-op scan (not shown) demonstrated complete resection of the enhancing component. The patient went on to receive routine Stupp protocol (radiotherapy and temozolomide). 

Follow up scanning (not shown) showed a small amount of developing enhancement at ~10 weeks post surgery. 

MRI brain 7 months post surgery


Right frontal craniotomy. Underlying this is a right enhancing frontal mass with marked increase of surrounding FLAIR hyperintensity, which crosses the midline at the genu of the corpus callosum and extends to the posterior frontal lobe. Effacement of the frontal horn of the right lateral ventricle with subfalcine herniation and leftward midline shift of 4.5 mm. No hydrocephalus.

Mild diffusion restriction surrounds the resection cavity. On MR spectroscopy in the enhancing component of the mass there is increased lactate with depressed choline, creatine, and NAA. Minimal cerebral blood volume on perfusion imaging some of which may be the result of susceptibility effect from blood product.

Conclusion: Marked increase in the enhancing mass and FLAIR signal. Advanced imaging gives somewhat conflicting results, with the low ADC and the mass effect suggesting progressive high-grade disease, but the lack of significant choline elevation and large lactate peak on spectroscopy favoring radiation necrosis. This is further supported by low CBV although interpretation of this is complicated by blood product.

Overall appearances in the context of a MGMT methylated tumor, 7 months post surgery, favor pseudoprogression being the dominant process. 

The patient proceeded to re-resection. 


MICROSCOPIC DESCRIPTION: The sections show small areas with features of high grade astrocytoma. These show dense hypercellularity, marked nuclear and cytoplasmic pleopmorphism, multilayering of atypical cells around microvessel lumena and areas of necrosis. No immunostaining for MGMT is seen in tumor cell nuclei. Topoisomerase labeling index: Approximately 10%

The majority of the specimen, however, shows florid reactive gliosis and neovascularization (not hyperplastic microvascular proliferation as seen in tumor) and areas of infarct-like necrosis (bottom left corner). Nuclear MGMT staining is preserved in these areas (note the tumor was methylated, thus this is suggestive or normal cells) and the features are most consistent with post irradiation/post-chemotherapy effect.

DIAGNOSIS: Recurrent glioblastoma IDH-1 wild type with florid reactive changes most consistent with post-irradiation/post-chemotherapy effect.

Case Discussion

This case illustrates the importance of remembering that favoring pseudoprogression does not mean that no tumor will be present if biopsied, but rather that the apparent growth (i.e. progression) is due to treatment effect rather than true tumor growth. 

The importance of this is that it will determine whether management should change (e.g. shift into second line salvage therapy) or push on. Prognostically pseudoprogression is probably desirable reflecting pronounced treatment effect. This is further supported by the fact that it is seen more frequently in tumors that are MGMT methylated. 

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