Glioblastoma IDH wild-type

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

Histology

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).

IMMUNOHISTOCHEMISTRY:

  • 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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