HistoPath - Neuro-oncology

Question 1

How are brain tumours classified (WHO)

Answer 1

Grade 1 - Extra-axial:
- Meningothelial cells – meningioma
- Schwann cells – schwannoma
Grade 2-4 Intra-axial (infiltrate the tissue of the brain):
- Astrocytes – astrocytoma
- Oligodendrocytes – oligodendroglioma
- Ependyma – ependymoma
- Neurons – neurocytoma
- Embryonal cells – medulloblastoma (Children)

Question 2

How are brain tumours graded

Answer 2

via histological criteria (proliferative activity, cell differentiation, necrosis)
Grade I = benign, long-term survival
Grade II = cause death in >5 years (long survival)
Grade III = cause death <5 years (short survival)
Grade IV = cause death <1-year (short survival)

Question 3

What are the risk factors for CNS tumours

Answer 3

Largely unknown
Radiation to head and neck → meningiomas, gliomas
Neurocarcinogens
Genetic predisposition (<5%):
- neurofibromatosis (AutDom)
- Tuberous sclerosis
- Brain tumour polyposis syndrome 1
- Gorlin syndrome
- Von Hippel Lindau

Question 4

What is the inheritance of neurofibromatosis and what CNS tumours does it predispose to

Answer 4

Neurofibromatosis 1 (17q11) → neurofibroma, astrocytoma
Neurofibromatosis 2 (22q12) → schwannoma, meningioma

Question 5

What are the signs and symptoms of a CNS tumour depending on where it is located

Answer 5

Intracranial: headache, vomiting, changed mental state
Supratentorial: focal neurological deficits, seizures, personality change
Subtentorial: cerebellar ataxia, long tract signs, cranial nerve palsies

Question 6

What investigations should be done for CNS tumours

Answer 6

CT/PET-CT
MRI:
- MR-spectroscopy (metabolism)
- Perfusion MRI
- Functional MRI

Question 7

What is the management for CNS tumours

Answer 7

1. Surgery
   - Craniotomy (debulking)
   - Open biopsy (inoperable but approachable tumour)
   - Stereotactic biopsy (if open biopsy is not indicated)
2. Radiotherapy (esp gliomas)
3. Chemotherapy (esp gliomas) - temozolamide

Question 8

What is the most common primary CNS tumour

Answer 8

Glial tumours (diffuse or circumscribed)
Circumscribed:
- Pilocytic astroctomas)
- SEGA
- Pleomorphic xanthoastrocytoma

Diffuse
- Diffuse astrocytoma
- Oligodendroma

Question 9

Describe diffuse glial tumours

Answer 9

High grade, malignant progression
Supratentorial
Adults 20-40yo
IDH1/2 mutation present 30% of cases (+ve prognostic factor)

Astrocytoma (grade 2-4)
Oligodendrogliomas (Grades 2-3)

Question 10

Describe circumscribed gliomas

Answer 10

Low grade, rarely malignant
Posterior fossa
Seen in children
BRAF mutationpresent in 50% of cases (MAPK pathway mutation)

Pilocytic astrocytoma (grade 1)
Ependymomas (usually)
Subependymal giant cell astrocytoma (Grade 1)
Pleomorphic xanthoastrocytoma (grade II)

Question 11

Describe pilocytic astrocytomas (epidemiology, associations, imaging appearance, histopathology)

Answer 11

Most common child brain tumour
Seen in NF1 and with BRAF mutatoins
MRI: cerebellar; well circumscribed, cystic, enhancing
Histopathology:
- Piloid (hairy) cell
- Rosenthal fibres and granular bodies
- Slow growing with low mitotic activity

Question 12

Describe diffuse astrocytomas (epidemiology, associations, imaging appearance, histopathology)

Answer 12

20-40yo
Cerebral hemispheres (adults), cerebellum (children)
IDH1/2 mutation in 80%
MRI: cerebral hemispheres, non-enhancing lesion, low choline:creatinine ratio
Histopathology: negligible/absent mitotic activity, vascular proliferation and necrosis absent

Will eventually become a glioblastoma

Question 13

Describe glioblastomas (epidemiology, associations, imaging appearance, histopathology, cytology)

Answer 13

> 50yo
90% de novo with wildtype IDH, 10% progress from astrocytomas
MRI: heterogenous, enhancing post-contrast
Cytology: high cellularity, high mitotic activity, microvascular proliferation, necrosis
Histo: pathological blood vessels, blood vessel structural abnormalities, cellularity

Question 14

Describe meningiomas (imaging appearance, histology)

Answer 14

Largely benign
MRI: extra-axial, isodense, contrast-enhancing
Histo: attaches to meninges, does not typically invade (displaces brain matter), globules seen

Question 15

How are meningiomas graded

Answer 15

Based on histology (mitotic activity, cell morphology and brain invasion) per 10 HPF

Grade I (80%)= benign, recurrence <25% | <4 mitotic activity

Grade II (20%)= atypical, recurrence 25-50% | 4-20 mitotic activity

Grade III (1%)= malignant, recurrence 50-90% | >20 mitotic activity

Question 16

What are the most frequent tumours to metastasise to the brain and where are they most commonly found

Answer 16

Mets = most frequent CNS tumour in adults)

Breast
Lung
Melanoma

Mets at the grey-white matter junction

Question 17

Describe medulloblastomas

Answer 17

Embyronal cell origin - neuroepithelial precursors of the cerebellum/dorsal brainstem
Cerebellum
2nd most common brain tumour in children

Question 18

What is the histology of medulloblastoma

Answer 18

“Small blue round cell” tumour (i.e. it is a blastoma/ of a primitive cell line)
Expression of neuronal markers (very little/poorly differentiation) – i.e. synaptophysin, GFAP, Ki67
Homer-Wright rosettes are a feature of primitive neuronal differentiation

Question 19

Which tumours do tuberous sclerosis and Von Hippel lindau predispose to

Answer 19

Tuberous sclerosis: haemartoma, SEGA (sub-ependymal giant cell astrocytoma)

Von Hippel lindau: haemangioblastoma

Question 20

Describe oligodendromas

Answer 20

20-40yo
MRI; no enhancement
Cytology: fried egg ells (lots of cytoplasma)
Histo: genetic mutation in 100%, esp IDH1/2 co-deletion 1p/19q→ good prognosis