Histo: Neuro-Oncology Flashcards
How much more common are secondary brain tumours than primary brain tumours?
10x more
In kids, primary CNS tumours are the most common
Describe the radiological classification of brain tumours.
- Extra-axial (coverings) - tumours of the bone, meninges and metastatic deposits
- Intra-axial (parenchyma) - derived from normal cell populations of the CNS (e.g. glia, neurones, vessels) or derived from other cell types (e.g. lymphomas, metastases)
List the different cell types within the CNS that can give rise to brain tumours.
Glial cells (most common)
* Astrocytes - astrocytomas (gliobastoma is a type of astrocytoma)
* Oligodendrocytes - oligodendroglioma
* Ependyma - Ependymoma
Neurons (rare)
* neuroblastoma
Meningothelial cells
* Meningioma
Embryonal cells
* Medulloblastoma
Schwann cells - schwannoma
Choroid plexus epithelium - carcinoma or papilloma
What is the most common genetic syndrome associated with brain tumours?
Neurofibromatosis
syndromes are responsible for <5% primary CNS tumours
What is the inheritance pattern of neurofibromatosis?
Autosomal dominant
Where are the genes that cause neurofibromatosis located?
- NF1 on chromsome 17
- NF2 on chromsome 22
List some manifestations of brain tumours that are:
- Supratentorial
- Infratentorial
-
Supratentorial - affecting cortex
- Focal neurological defect
- Seizures
- Personality changes - frontal lobe especially
-
Infratentorial - affecting cerebellum
- Cerebellar ataxia
- Contralateral long tract signs - hemiparesis, hemisensory loss
- Ipsilateral cranial nerve palsy
Above/below tentorium cerebelli
Raised ICP - headache, vomiting, altered mental status
Outline the management options for brain tumours.
- Surgery - aim for maximal safe resection with minimal damage to the patient. Debulking may be performed and biopsies may be taken.
- Radiotherapy - used for gliomas and metastases
- Chemotherapy - mainly for high-grade gliomas (temozolomide) and lymphomas
What is the WHO classification of brain tumours based on?
- Tumour type (cell of origin)
- Tumour grading (proliferation, cell differentiation, necrosis)
- Molecular markers
NOTE: metastases are not graded
Outline the meaning of the different WHO grades for brain tumours.
- Grade I = benign, long-term survival
- Grade II = death in > 5 years
- Grade III = death in < 5 years
- Grade IV = death in < 1 years
NOTE: grades I and II are low
Grades guide treatment of patients
Which brain tumours are staged?
None
Except medulloblastoma
What is the most common type of primary brain tumour?
Glial tumours
e.g. astrocytoma, ependydoma, oligodendroglioma
How are the types of glial tumours seen in children and adults different?
- Diffuse infiltration - mainly seen in adults, become more malignant with time, can either be astrocytomas or oligodendrogliomas
- Circumscribe gliomas - mainly seen in children, tend to be low-grade, rarely undergo malignant transformation
e.g. pilocytic astrocytoma
Which genetic mutations are associated with gliomas in adults and in children?
- Diffuse gliomas (adults) - IDH1/2
- Circumscribed gliomas (children) - MAPK (BRAF)
List some examples of circumscribe gliomas.
- Pilocytic astrocytoma (MOST COMMON)
- Pleiomorphic xanthoastrocytoma
- Subependymal giant cell astrocytoma
List some key features of pilocytic astrocytomas.
- Usually grade I
- Mainly occurs in children
- Associated with NF1
- Often cerebellar
- BRAF mutation in 70% of cases
What is the hallmark histological feature of pilocytic astrocytoma?
- Piloid (hairy) cell
- Often see Rosenthal fibres and granular bodies
- Slow-growing with low mitotic activity
List some key features of astrocytoma.
- Usually Grade II-IV
- Cerebral hemispheres are the most common site in adults
- Can progress to become a higher grade (malignant progression)
- IDH2 mutation in 80% of cases
- Mitotic activity and vascular proliferation is absent
What can astrocytomas eventually become?
Glioblastoma (after 5-7 years)
What is the most aggressive and most common type of glioblastoma
*Glioblastoma multiforme (stage IV)
List some key features of glioblastoma multiforme.
- Grade IV
- Most patients > 50 years
- High cellularity and high mitotic activity
- Microvascular proliferation and necrosis
What does glioblastoma multiforme tend to arise from?
90% arise de novo and have wildtype IDH
10% occur secondary to astrocytoma and have IDH mutation
List some key features of oligodendrogliomas.
- Grade II-III
- Tends to present with a long history of neurological signs (usually seizures)
- Slow-growing
- Better prognosis than astrocytoma (better response to chemotherapy and radiotherapy)
Slow, Seizures, Saved
What is a characteristic histological feature of oligodendroglioma?
Round cells with clear cytoplasm (friend egg)
Which gene mutations are associated with oligodendroglioma?
IDH1/2
Co-deletion of 1p/19q
What is the second most common primary intracranial tumour after gliomas?
Meningioma
List some key features of meningioma.
- Mainly low grade (I and II)
- Low recurrence afte surgery
- Can be multiple (e.g. in NF2)
- Can cause focal symptoms (e.g. seizures, compression)
Which histological feature of meningioma is important in determining grade?
Mitotic activity (number of mitoses per 10 high power fields)
- Grade 1: < 4
- Grade 2: 4-20
- Grade 3: > 20
NOTE: brain invasion is also an important thing to assess (presence of brain invasion makes it grade II)
How does grade of meningioma affect the management options?
Grade II and III requires radiotherapy as well as surgery
What is a medulloblastoma?
- Embryonal tumour originating from neuroepithelial precursors of the cerebellum and dorsal brainstem
- They are always found in the cerebellum
Describe the histological appearnce of medulloblastoma.
Small blue round cell tumour with expression of neuronal markers (very little differentiation)
NOTE: snaptophysin is an example of a neuronal marker
What histological feature is suggestive of partial neuronal differentiation?
Homer-Wright rosettes
Outline the molecular classification of medulloblastoma.
- WNT-associated
- SHH-associatd
- Non-WNT/non-SHH
Which tumours most commonly metastasise to the brain?
- Lung
- Breast
- Melanoma
- Renal Cell
Where in the brain do metastases tend to be found?
- At the grey-white matter junction and/or leptomeningeal
- This is because the cerebral blood vessels become smaller as they enter the white matter so neoplastic emboli get caught here
Most common CNS tumor
How can the DNA methylation of a CNS be useful
Gives information on tumour type, not on progression or grade
Good for very rare tumours
