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
Don’t know significance of TERT promoter status in conjunction with MGMT methylation as yet….
TERT telomerase reverse transcriptase gene..

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
Can use loss of expression of H2 K27Mme to confirm diagnosis- we have

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