20.06.21 CNS Tumours

Question 1

What are CNS tumours

Answer 1

• Central nervous system tumours
• Involve brain and/or spinal cord.
• most common types= gliomas and meningiomas (combined= 70% of CNS tumours)

Question 2

How common are CNS tumours in children (<15 yrs)

Answer 2

• Second most common

- 25%

Question 3

Are CNS/ brain tumours sub grouped into benign/ malignant

Answer 3

-No as significant morbidity/mortality is due to growth and adverse effects of “space occupying lesions” of “benign” brain tumours.

Question 4

How are CNS tumours grouped

Answer 4

• Grade 1 and 2= slow growing, relatively contained, unlike to spread. Difficult to culture.
• Grade 3 and 4= fast growing, cannot be treated by surgery alone, need radio/chemotherapies

Question 5

Two main cell types in CNS

Answer 5

Neurons and glial cells

Question 6

What are the major glial types

Answer 6

• Astrocytes: control potassium levels in extracellular space, roles in CNS development
• oligodendrocytes: responsible for formation of myelin sheath around nerve fibres.

Question 7

Review of medulloblastoma

Answer 7

• Paediatric noninvasive, rapidly growing primary brain tumour. Can spread through cerebrospinal fluid, metastasising to other locations of brain.
• 30% cases die within 2 years.
• Survivors suffer long term side effects due to treatment.
• 17p loss and 17q gain are most frequent cytogenetic abnormalities. Isochromosome 17q seen in 30-50% tumours.
• Pathways disrupted= WNT (due to TNNB1 mutations), SHH (due to PTCH1, SMO, SUFU mutations), Photoreceptor/ GABAergic

Question 8

What are CNS gliomas

Answer 8

• Tumors involving glial cells.
• Account for >70% brain neoplasms
• e.g. oligodendroglioma and glioblastoma

Question 9

Review of oligodendroglioma

Answer 9

• Better prognosis and response to treatment than other glioma subtypes
• Loss of 1p and 19q seen in 80% cases. Predicts increased chemosensitivity and better prognosis. Helps confirm diagnosis.
• Detected by FISH or SNP array, PCR

Question 10

Review of glioblastoma

Answer 10

• Most common primary brain tumour (50% of all primary brain gliomas, 12-15% of all brain tumours)
• Usually seen in adults
• Very poor prognosis
• Common genetic findings: gain of 7p11.2 (EGFR- activates RAS pathway), 9p21.3 loss (CDKN2A- tumour suppressor), 10q23.31 (PTEN- tumour suppressor), inactivation of IDH1/2

Question 11

Which 3 genes are commonly hypermethylated in glioblastoma

Answer 11

1. MGMT- associated with TP53 mutations, better survival rate, due to more sensitivity to alkylating drugs. Prognostic test for glioma.
2. GATA6- associated with better survival rate
3. CASP8- associated with worse outcome.