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Diffuse gliomas
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What is the correct ‘integrated diagnosis‘ in the
following case?
Histology: Oligoastrocytoma
WHO grade: II
Molecular markers: IDH2 mutant, 1p19q codeleted, TERT
mutation, ATRX retained
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• A1. Oligodendroglioma, WHO grade II, IDH2 mutant and 1p19q codeleted
• A2. Oligoastrocytoma, WHO grade II, IDH2 mutant and 1p19q codeleted
• A3. Astrocytoma, WHO grade II, IDH2 mutant and 1p19q codeleted
• A4. Oligodendroglioma, WHO grade II, NOS
A1 is correct
Commonly used molecular techniques
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•
IDH
genes:
• Step 1: mutation-specific IDH1 R132H antibody
• Step 2: targeted IDH1/2 gene sequencing
•
Screening of all lower grade gliomas (II-III)
•
Screening of GBM, IV only in patients aged <55 years
• 1p 19q chromosomal arms:
• Multiplex ligation probe amplification
• Fluorescence in situ hybridization
•
MGMT
promoter methylation:
• Pyrosequencing
• Methylation-specific PCR
CAVE:Analytical test performance, interlab comparisons
Advanced molecular techniques
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• Gene-panel sequencing
• Exome/RNA sequencing
• DNA methylation array
• G-CIMP/IDH, copy numbers, MGMT
• CAVE:
• Quality control / data standardization
• DNA quality of FFPE tissues
Glioblastoma
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• Glioblastoma, IDH-wildtype (about 90% of cases)
• Glioblastoma, IDH-mutant (about 10% of cases) corresponds
closely to secondary glioblastoma
• Glioblastoma, NOS in cases without full IDH assessment
• Sequencing required for all patients > 55 years of age
Glioblastoma
Variant = Subtype of an entity of clinical utility
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• New variant: Epitheloid glioblastoma
• Stratifies into established diagnostic subsets upon molecular diagnosis
BRAF V600E
Louiset al,
Acta Neuropath 2016