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Glioblastoma IDH wild-type (with progression)

Case contributed by Frank Gaillard
Diagnosis certain

Presentation

Right sided weakness.

Patient Data

Age: Adult
Gender: Male

Pre-operative MRI

mri

Selected axial pre-operative images demonstrating a left sided mass with peripheral enhancement. 

The patient went on to have a resection, followed by Stupp protocol

Histology

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. 

IMMUNOHISTOCHEMISTRY:

  • 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%

FINAL DIAGNOSIS: 

IDH-1 wild type glioblastoma (WHO Grade IV)

MRI 24 hours post-op

mri

Selected images obtained the day after surgery demonstrate near-complete resection of the enhancing component, with intrinsic high T1 material within the resection cavity consistent with blood product. At most a small amount of enhancing tissue remains anteriorly. 

MRI 2 months post resection

mri

Selected FLAIR and T1 C+ images obtained at 8 weeks post surgery, during Stupp protocol, demonstrate some enhancement, which was new compared to immediate post op scan. At this stage it was not certain if this represented residual postoperative enhancement, tumor progression, or less likely early pseudoprogression. 

MRI 7 mth post surgery

mri

MRI obtained 7 months post resection, 3-4 months following the end of radiotherapy, demonstrates significant increase in enhancement. There are a number of features that suggest that this, despite the timing and presence of MGMT methylation, represents tumor progression: 

  • ADC values are low, particularly anteriorly where they are much lower than normal brain, suggesting high cellularity
  • CBV is elevated, compared to normal white matter
  • MRS demonstrates a high choline and preserved NAA peak

Interestingly much of the change seen posteriorly may actually represent treatment effect. 

Case Discussion

Determining true tumor progression vs pseudoprogression can be challenging, and emphasis should be placed on ADC, CBV and MRS above morphological features. This tumor has continued to grow. 

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