Glioblastoma IDH wild-type (with pseudoprogression)

Case contributed by Frank Gaillard



Patient Data

Age: 70 years
Gender: Male

MRI pre-operative


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 palisaded 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 coarsely 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 CNS grade 4). 


An 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 7 months post-surgery


Right frontal craniotomy. Underlying this is an enhancing 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. There is effacement of the frontal horn of the right lateral ventricle with subfalcine herniation and leftward midline shift of 4.5 mm. No hydrocephalus.

Cerebral blood volume is reduced throughout the right frontal lobe without any areas of focal elevation. Specifically, the enhancing component of the mass does not demonstrate high rCBV.

Only a thin rim of diffusion restriction surrounds the resection cavity, smaller than the enhancing component, which mostly demonstrates facilitated diffusion.

MR spectroscopy in the enhancing component of the mass is dominated by lipid and lactate peaks on an otherwise hypometabolic baseline.


Marked increase in the enhancing mass and FLAIR signal. Although there are areas of low ADC, that are concerning for viable high-grade tumor, the low cerebral blood volume and lack of choline elevation, large lipid and lactate peaks on spectroscopy suggest the dominant process, especially in the context of an MGMT methylated tumor, 7 months post-surgery, favor pseudoprogression as 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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