Astrocytoma, IDH-mutant - grade 4

Case contributed by Ana Brusic
Diagnosis certain


12 months of headache, single episode of syncope

Patient Data

Age: 30 years
Gender: Female

A large intraparenchymal mass with prominent T2/FLAIR mismatch as well as central areas of presumed necrosis with surrounding irregular enhancement is surrounded by peritumoral edema and significant non-enhancing tumor. The mass is centered upon the splenium of the corpus callosum. Foci of increased CBV is present particularly in the enhancing components. ADC values are generally facilitated. No spectroscopy has been performed.


Features are almost certainly those of high-grade diffuse adult-type glioma. In this age group, an IDH mutation is likely, even in the setting of necrosis, and the presence of T2/FLAIR mismatch in the non-enhancing components makes an oligodendroglioma unlikely. As such, an astrocytoma, IDH-mutant WHO CNS5 grade 4 is considered most likely.

Case Discussion

The patient went on to have a biopsy. 


Sections show fragments of a moderately cellular tumor. The tumor cells have enlarged, hyperchromatic and angulated nuclei and are set in a fibrillary and somewhat myxoid background. There are scattered cells with large quantities of eosinophilic cytoplasm. Mitotic figures are not obvious but there are a few small foci of microvascular proliferation and also a small focus of necrosis.


  • GFAP: positive
  • OLIG2: positive
  • IDH1 R132H:  positive (mutated)
  • ATRX: negative (mutated)
  • p53: mosaic (probably not mutated)
  • p16 CDKN2A: negative (probably lost)
  • Ki67: low (<5%) 

FINAL DIAGNOSIS: Astrocytoma, IDH-mutant (WHO CNS grade 4).


The initial histology report did not identify any necrosis of definite microvascular proliferation. As a result of further discussion at a multidisciplinary meeting, other specimens were reviewed confirming the presence of necrosis on histology. 

In this instance, the presence of necrosis is almost certain on the basis of imaging and therefore ideally grading should reflect this. 

Grade 4 was also suggested by the probable deletion of CDKN2A. 

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