Glioblastoma IDH wild-type (multifocal)

Discussion:

Although the presence of three discrete enhancing lesions would make one naturally think of metastases, there are a few features that enable you to make the diagnosis of GBM pre-operatively with confidence. 

  1. the three lesions are in a line, along crossing white matter tracts
  2. the middle lesion is within the corpus callosum, a very unusual location for a metastasis

The patient went on to have a craniotomy and resection of the right sided lesion, confirming that this does indeed represent a GBM. 

Histology

MICROSCOPIC DESCRIPTION:

Paraffin sections show fragments of a densely hypercellular astrocytic glioma. Tumor cells show moderate nuclear and cellular pleomorphism. Frequent mitotic figures are identified as well as foci of microvascular proliferation. There is also confluent and palisaded necrosis. Some areas of necrosis incorporate thin-walled necrotic and thrombosed blood vessels. The features are of glioblastoma multiforme (WHO grade IV). Neither oligodendroglioma or primitive neuroectodermal tumor components are identified.

IMMUNOHISTOCHEMISTRY:

  • GFAP positive
  • Nestin positive
  • IDH-1 R132H negative (not mutated)
  • MGMT negative (likely unmethylated)
  • p53 positive
  • p16 negative
  • Topoisomerase labeling index: Approximately 15%

FINAL DIAGNOSIS:

Glioblastoma (WHO Grade IV)

 

Note: As the three foci of enhancement are along a dominant white matter tract, even if definite T2 bridging signal abnormality could not be identified (in this case there is definite bridging T2 signal change), it should still be considered multifocal rather than multicentric disease. 

Note: Although this tumor is entirely consistent with IDH wild-type molecular subtype, strictly speaking, to conclusively establish this, IDH would need to be sequenced to ensure that a non-IDH1 R132H mutation was present. In practice, an IDH1 R132H negative tumor in an individual over 55-years-of-age makes the possibility of this being IDH mutant remote (<1%), and sequencing is not felt to be necessary by many institutions, and not recommended by the WHO classification of CNS tumors (2016). 

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