Neuro-oncology Flashcards by Emily Southall

What are primary CNS tumours

originated in CNS
most common (vs secondary) in children

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what are secondary CNS tumours

mets
10x more common than primary tumours
(30% of patients with systemic cancer develop CNS metastases)

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what are extra-axial CNS tumours (coverings)

Tumours of bone, cranial soft tissue, meninges, nerves

less malignant than intra-axial

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what are intra-axial CNS tumours (parenchyma)

from normal cell populations of the CNS - flia, neurons and neuroendocrine cells
form other cell types - lymphomas, germ cell tumours

more malignant - WHO grade 2-4 - Infiltrate the tissue of the brain – not encapsulated and they invade the brain tissue

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aetiology of CNS tumours

unknown
env - radiotherapy to head and neck -> meningioma (and rarely glioma)
genetic predisposition <5% primary - familial syndromes

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what are familial CNS tumour syndromes - with examples

Autosomal dominant inheritance with frequent de novo mutations

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signs and symptoms for CNS tumours

subtle in slow growing // short hx for malignant

intracranial HTN - SOL - headache, vomiting, change in mental status

supratentorial - focal neuro deficit, seizures, personality change (frontal lobe)

infratentorial - cerebellar ataxia, long tract signs (brain stem: motor/sensory tracts), cranial nerve palsy (ocular signs)

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imaging modalities used for CNS tumours

CT-scan
MR-scan – more usual in more chronic
MR-spectroscopy (metabolism)
Perfusion MRI
Functional MRI
PET-scan – more research looking for particular ligand binding

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Use of imaging in CNS tumours

Assess tumour type
Guide resection & biopsy
Assess post-surgery – have you taken all tumour
Assess response to treatments
Follow-up recurrence and progression

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mx for cns tumour - surgery

max safe resection with min damage to normal
need margin of normal - might be limited depending on where is in brain

resection - location, size, nymber of lesions

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mx of CNS tumours - radiotherapy

low and high grade glioma
metastases
some benign

external fractionated radiotherapy, stereotactic radiosurgery

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mx of cns tumours - chemo

high-grade gliomas (temozolomide – mixed effectiveness) and lymphomas

Biological agents (EGFR inhibitors, PD-L1 inhibitors, etc.)

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when is craniotomy used for CNS tumours

for debulking
may be sub-total or complete resections - depending where is
remove as much tumour as possible

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When is open biopsy used for CNS tumours

for inoperable but approachable tumours - 1cm of tissue

usually representative - able to make dx

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when is stereotactic biopsy used for CNS tumours

if open biopsy not indicated (about 0.5cm of tissue)
tissue may be insufficient esp if heterogenous - might not get definitive dx

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why do we need tissue dx of cns tumour

for:
* definitive and complete dx
* prognostic and predictive tests
* assessment of treatment response

Histopathology can make a decision while patient is on the table

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what is involved in the WHO classification of CNS tumours

Tumour type - Putative cell of origin or lineage of differentiation, based on histology, predicts tumour behaviour

Tumour grade – malignancy of the tumour- Tumour aggressiveness

Molecular profile - Most tumour types have molecular markers

cell of origin and name of tumour

Astrocytes – astrocytoma
Oligodendrocytes – oligodendroglioma
Ependyma – ependymoma
Neurons- neurocytoma
Embryonal cells – medulloblastoma
Meningothelial cells – meningioma
Schwann cells - schwannoma, neurofibroma

grading CNS tumours

startify tumours by outcome ie degree of malignancy
based on morphological criteria:
* proliferative activity (mitotic bodies – number = degree of proliferative activity),
* cell differentiation (wgich cells, are they vascular),
* necrosis (more necrosis = more malignant)

based on predicted natural clinical behaviour (ie doesnt include response to treatment so high grade may now live longer)

what are the WHO grades for CNS tumours

Grade 1 – benign – long-term survival
Grade 2 – more than 5 yrs
Grade 3 – less than 5 yrs
Grade 4 – less than 1 yr

Some tumour types have only one possible grade, but others have more than one and tjhey progress

Grades guide treatment – if grade 4 you can lengthen life but do you change the QOL

what are diffuse gliomas

infiltrate into the tissue
use structure of tissue eg perivascular, and grow under the meninges

grade >= 2
adults
supratentorial
malignant progressioon

astrocytomas grade 2-4
oligodendrogliomas grade 2-3

what are circumscribed gliomas

grades 1-2
children
posterior fossa
rare malignant transfromation

Pilocytic astrocytoma (grade 1)
Subependymal giant cell astrocytoma (grade1)
Ependymomas (usually) – lining of the ventricle, usually well circumscribed

what is a pilocystic adenoma

Who grade 1
intraparenchymal tumour
infra-tentoral, posterior fossa

usually 1st and 2nd decade of life - children
20% CNS tumours below 14 yrs - common
cerebellar, optic-hypothalamus, brainstem

BRAF mutation in 70%

MRI - well circumscribed, cystic, enhancing lesion

Pilocystic astrocytoma histology

Piloid “hairy” cells
Very often Rosenthal fibres – blue arrow
Slowly growing, low mitotic activity

Summarise diffuse gliomas

pts 20-40yrs Astrocytoma (IDH mutant) and Oligodendroglioma (IDH mutant) Pathogenic point mutation in the IDH1/2 gene IDH mutation -> longer survival and a better response to chemotherapy and radiotherapy

What is astrocytoma

WHO grade 2-4 pts 20-40yrs cerebral hemispheres point mutation - IDH1/2

Histology of astrocytoma

low to moderate cellularity Mitotic activity is low. No vascular proliferation or necrosis. IDH1 mutants can be detected Immunocytochemically – good prognosis progression to higher grades over time

summarise glioblastoma multiforme

who grade 4 Most aggressive and most frequent glioma incidence increase with age, most >50yrs median survival - 8mo

genetics of glioblastoma multiforme

IDH1 wildtype Common mutations in: TERT, PTEN, EGFR

Histology of glioblastoma multiforme

High cellularity Neoangiogenesis – overdeveloped Necrosis Not clean margin – tumour invading the tissue of the brain

what are meningiomas

WHO **grade 1-3** 38% primary CNS tumours rare less 40yrs - **increases with age** Originate from **meningothelial cells** of the **arachnoid mater** Any site of craniospinal axis, **can be multiple (NF2)** more accessible to neurosurgeons - **good surgery outcomes** MRI: **extraxial, iso-dense, contrast-enhancing, well circumscribed - not invading parenchyma**

grading of meningiomas

**80% Grade 1**: benign, recurrence less than 25% 20% Grade 2: atypical, recurrence 25-50% 1% Grade 3: malignant, recurrence 50-90% **grading is the most useful predictor of recurrence** mainly based on histology, recently molecular markers (**ex TERT mutation, methylome**) Complex histological assessment: proliferation, cell morphology, microscopic brain invasion, etc 15 morphological subtypes, 3 grades

how is mitotic activity used to determine grade

Hyperintense nuclear material Count them per high power field Grade depending on how many mitotic bodies find Mitosis per 10HPF (0.16mm2) <4 = grade 1 4-20 = grade 2 >20 = grade 3

why do you have to check the interface between meningoma and cortex

Most are sitting between tissue – but have to make sure not invading (even microinvasion)

summarise CNS mets

most common CNS tumour incidence increasing because of longer survival. Often multiple, located at grey/white matter junction and/or leptomeningeal disease can be 1st disease presentation - hard to know origin, use immunohistochem poor px because in the brain parenchyma

cancers that can give brain mets

any, but commonly: * lung ca, * breast ca, * melanoma, * renal cell ca

what is a medulloblastoma

WHO grade 4 embryonal tumour from neuroepithelial cells/neuronal precursors of the cerebellum or dorsal brainstem rare common type in children outcome improved with radio-chemo and subtype stratification

histology of medulloblastoma

High grade poorly differentiated Highly proliferated type of tumour 4 histological subtypes: classic, nodular/desmoplastic, extensive nodularity, large cell anaplastic 3 molecular subtypes by transcriptome or methylome profiling: WNT-activated, SHH-activated, nonWNT/nonSHH

what is teh methylome profile for CNS tumours

**Most tumours have characteristic patterns of DNA methylation of CpG islands** methylation signiture is stable - **reflect cell of origin - give info on tumour type** The DNA methylation status of a subset of CpG islands is assessed with DNA arrays and compared to a reference dataset (“Classifier”)

what is the methylome classifier

Helpful for atypical cases, rare entities, small biopsies, and subtyping: ex medulloblastoma subtypes, meningiomas… Not used for grade/progression or targeted therapy True molecular classification: does not consider the histology