Glioblastoma with pseudoresponse (bevacizumab)

Case contributed by Assoc Prof Frank Gaillard

Presentation

Known glioblastoma, resected with tumor progression on Stupp protocol.

Patient Data

Age: 65 years

Pre-bevacizumab

MRI

Known glioblastoma in the white matter of the posterior left frontal and left parietal lobes demonstrates marked increase in the degree of related intra-axial enhancement compared to the previous study (not shown).

Patchy enhancement extends from the medial margin of the lesion into the splenium of the corpus callosum where it is associated with fairly low in ADC values, tumoral trace on spectroscopy and markedly increased relative cerebral blood volume.

The mass is surrounded by extensive vasogenic edema extending into the left frontal and left parietal white matter as well as the insula and posterior limb left internal capsule.

Conclusion: Progression of high-grade tumor.

8 weeks post-bevacizumab

MRI

The enhancing component of the left parietal tumor has reduced in size. The punctate foci of subependymal enhancement and the expansile T2 hyperintensity along the splenium of the corpus callosum are unchanged. The previously seen vasogenic edema surrounding the tumor has markedly improved.

The tumor again demonstrates a rim of low ADC values, with persistently elevated cerebral blood volume. MR spectroscopy again demonstrates markedly elevated choline within the enhancing tumor and moderately elevated choline in the non-enhancing T2 hyperintense region. Of note, there is also elevated choline in the regions that are no longer T2 hyperintense.

Small areas of blood product (intrinsic high T1 signal). 

Conclusion: The reduction of vasogenic edema and enhancement is likely due to bevacizumab-mediated change in blood-brain barrier permeability. The actual size of the viable tumor (based on the diffusion imaging, perfusion characteristics, and spectroscopy finding) has only modestly reduced. Overall, appearances are dominated by pseudoresponse.

Case Discussion

Histology

This histology is from the original resection (prior to the first study shown). 

ections show pieces of a moderately cellular diffusely infiltrating tumor. The tumor cells are enlarged and pleomorphic, with angulated nuclei, relatively fine chromatin and a central nucleolus. In some areas there appears to be some perinuclear clearing, while in other areas the tumor has a microcystic appearance. There are plentiful calcifications. Mitoses are not seen. There is no necrosis or microvascular proliferation.

  • GFAP: positive
  • OLIG2: positive
  • IDH1 R132H: negative (not mutated)
  • ATRX: positive (not mutated)
  • p53: mosaic (probably not mutated)
  • p16: positive
  • Ki67: 1-2%
  • BRAF V600E: negative
  • Synaptophysin: negative
  • NFP: negative
  • NeuN: negative I

Next-genereation sequencing

  • 1p/19q codeletion: Not detected
  • EGFRamplification: Not detected
  • IDH1codon 132: No pathogenic variant detected
  • IDH2codon 172: No pathogenic variant detected
  • BRAFcodon 600: No pathogenic variant detected
  • H3F3Acodons 27 and 34: No pathogenic variant detected
  • TERTpromoter Chr5:1295228 (C228T) and chr5:1295250 (C250T): PATHOGENIC VARIANT DETECTED

FINAL INTEGRATED DIAGNOSIS: Glioblastoma (IDH-wildtype).

Discussion

This case demonstrates the profound blood-brain-barrier reconstitution effects of bevacizumab that can result in a dramatic reduction in edema and enhancement without necessarily having an actual treatment effect on the tumor. This is best appreciated on rCBV and ADC. 

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