Glioblastoma IDH wild-type (multifocal)
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Confluent T2/FLAIR hyperintense signal affecting the corona radiata and the centrum semiovale of the cerebral hemispheres with involvement of the corpus callosum, the right frontal operculum, the thalami, particularly on the right, and the left internal capsule and cerebral peduncle (most easily seen on FLAIR). The cortex of the right frontal operculum is involved by high T2 signal and mildly expanded.
Embedded within the areas of abnormal T2 signal including the body of the corpus callosum, are a number of peripherally enhancing foci, arranged along crossing white matter tracts. Centrally these lesions demonstrate high T2 signal and non-enhancement.
Both the enhancing components and most of the high T2 signal component of this abnormality demonstrate reduced ADC values, lower than normal white matter.
Extensive bilateral confluent T2 hyperintense abnormalities in the cerebral hemisphere within which are multiple areas of contrast enhancement and probable cortical involvement almost certainly represent an adult-type diffuse glioma. The presence of low ADC values implies high cellularity and central non-enhancement in the enhancing lesions suggesting necrosis, both high-grade features. In this age group, IDH mutations in a high-grade diffuse glioma are rare and, therefore, this most likely represents a multifocal glioblastoma, IDH-wildtype (WHO CNS grade 5).
The patient went on to have a biopsy.
Paraffin sections show cores of a densely hypercellular astrocytic glioma. Tumor cells show marked nuclear and cellular pleomorphism. Scattered mitotic figures are identified. There are foci of microvascular proliferation with multi-layering of atypical cells around vessel lumena. There is also a small focus of necrosis.
- GFAP: positive
- Nestin: positive (high)
- IDH-1 R132H negative (wildtype - not mutated)
- ATRX: positive (not mutated)
- MGMT: negative (likely methylated)
- p53: positive
- p16: focally positive
- Topoisomerase labeling index: approximately 30%.
FINAL DIAGNOSIS: Multifocal glioblastoma, IDH-wildtype (WHO CNS Grade 4).
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.
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