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Neuropathology at Southmead

Neuropathology at Southmead. A brief update…. Dr Kathryn Urankar. New Consultant. cIMPACT. Group of world experts (outside of WHO) advice on difficult issues in brain tumours. New advice on issues that may affect treatment & prognosis.

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Neuropathology at Southmead

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  1. Neuropathology at Southmead A brief update…. Dr Kathryn Urankar

  2. New Consultant

  3. cIMPACT • Group of world experts (outside of WHO) advice on difficult issues in brain tumours. • New advice on issues that may affect treatment & prognosis. • Will probably be incorporated into new WHO (eventually) • Overall: Integrated histological & mutation grade SHOULD take priority over a strictly histological grade.

  4. IDH-wildtype astrocytic gliomas • Issue with IDH-W gliomas that despite appearing histologically as WHO grade II or III, appear to follow an aggressive clinical course resembling GBM, IDH-W. • Three particular molecular features impart a shorter patient survival compared with IDH-Mutant, WHO grade II/III astrocytomas. (1) EGFR amplification (high level gain) Or (2) Combined whole chromosome 7 gain and whole chromosome 10 loss (+7/-10) Or (3) TERT promoter mutations

  5. IDH-wildtype astrocytic gliomas • TERT promoter mutations: - are frequent in IDH-W GBMS - seen in association with EGFR or 7+/10- - are also characteristic of Oligos - and are found in other tumour types including PXA, GG, Ependymomas. • Large gene- some difficulties sequencing - in progress at Southmead

  6. Current Status • IDH-W WHO grade II/III will need further molecular testing • Bottom line in report if 1/3 molecular findings: ‘Diffuse Astrocytic Glioma, IDH-wildtype with molecular features of Glioblastoma’ • Supports clinical practice of recommending combined chemo & radiotherapy to patients with wildtype anaplastic astros if 1/3 of these molecular features identified.

  7. Other new ‘tools’ • DNA methylation arrays - send away to GOSH/UCL - robust means of characterising difficult tumours on basis of distinct methylation profiles. - IDH-W gliomas WHO II/III cluster on methylation arrays with IDH-W GBMS. • Brain tumour gene panels - in progress

  8. 1p19q • Do we need to do 1p19q on all gliomas? NO • cIMPACT guidelines: if ATRX or p53 mutation detected then 1p19q FISH not required • If ATRX lost = mutation in ATRX  astrocytic • p53= evidence of mutation with strong, extensive & positive staining for antibody

  9. Diffuse Midline Gliomas • Introduced into WHO classification CNS tumours in 2016 • Tumours with H3 K27M mutation regardless of histological appearance/grade. • Presence of mutation imparts poor prognosis • BUT H3 K27M mutation now detected in other tumours including pilocytic astrocytomas. • Recommendation for designation now: (i) Diffuse (ii) Midline (iii) Glioma (iv) H3 K27M mutant

  10. Pediatric WGS • From approx July 2019 • WGS for pediatric solid tumours incl. all pediatric brain tumours • Move to ‘standard of care’ testing • Will require fresh frozen tissue at operation. • Education/Protocols need to be established • Balance of tissue diagnosis vs molecular

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