Histo: Neuro-Oncology Flashcards
How much more common are secondary brain tumours than primary brain tumours?
Brain metastases are 10x more common that primary tumours
Describe the locational classification of brain tumours.
Extra-axial (coverings):
* bone
* meninges
* nerves
* cranial soft tissue
Intra-axial (parenchyma): derived from normal cell populations of the CNS (e.g. glia, neurones, neuroendocrine, vessels) or derived from other cell types (e.g. lymphomas, germ cell tumours)
List the different cell types within the CNS that can give rise to brain tumours.
- Neurones
- Astrocytes
- Oligodendrocytes
- Ependyma
- Choroid plexus epithelium
- Meningothelial cells
- Embryonal cells
What is the aetiology of CNS tumours
Largely unknown
* Environmental: radiation associated with meningioma
* Genetic predispostion: familial CNS tumour syndromes
What is the most common genetic syndrome associated with brain tumours?
Neurofibromatosis
What is the inheritance pattern of neurofibromatosis?
Autosomal dominant
Where are the genes that cause neurofibromatosis located?
- NF1 = 17q11
- NF2 = 22q12
What tumours are associated with following Familial CNS Tumour Syndromes:
* NF1
* NF2
* Brain Tumour polyposis syndrome 1
* Gorlin syndrome
* Von Hippel Lindau syndrome
- NF1 - neurofibroma, astrocytoma
- NF2 - bilateral vestibular schwanoma, meningioma
- BTP1 - malignant glioma
- Gorlin syndrome - medulloblastoma
- VHL - haemangioblastoma
AD inheritance
What are some common signs of CNS tumours
Raised ICP:
* Headache (worse in morning, coughing, lying down)
* Vomiting
* Altered mental status
List some manifestations of brain tumours that are:
- Supratentorial
- Subtentorial
Supratentorial
* Focal neurological deficit
* Seizures
* Personality changes
Subtentorial
* Cerebellar ataxia
* Long tract signs (e.g. hyperreflexia)
* Cranial nerve palsies
What are some neuroimaging modalties
- CT
- MRI
- MR spectroscopy - assess tumour metabolic activity
- Perfusion MRI
- fMRI
- PET
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 and lymphomas
What is the role of histopathology and molecular pathology
- Definitive diagnosis
- Prognostic tests
- Assessement of treatment response
What is the WHO classification of brain tumours based on?
- Tumour type (cell of origin)
- Tumour grade (aggressiveness/degree of malignancy)
- Molecular profile - most tumour types have specific molecular markers
NOTE: metastases are not graded
What are some criteria that tumour grade is based on?
- Mitotic activity
- Degree of cell and tissue differentiation
- Degree of necrosis
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
GRADE GUIDES Mx
Which brain tumours are staged?
None
Except medulloblastoma
What is the most common type of primary brain tumour?
Glial tumours, specifically astrocytoma
How are the types of glial tumours seen in children and adults different?
Diffuse gliomas
* Mainly seen in adults
* Supratentorial
* Malignant progression
* Astrocytomas, oligodendrogliomas
Circumscribe gliomas
* Mainly seen in children
* Posterior fossa
* Rarely undergo malignant transformation
* Astrocytomas, ependymomas
Which genetic mutations are associated with gliomas in adults and in children?
- Diffuse infiltration (adults) - IDH1/2
- Circumscribed gliomas (children) - MAPK (BRAF)
List some examples of circumscribe gliomas.
- Pilocytic astrocytoma (MOST COMMON)
- Ependymoma
- Subependymal giant cell astrocytoma
List some key features of pilocytic astrocytomas (WHO grade 1)
- Mainly occurs in children (1st and 2nd decade of life)
- Associated with NF1
- Often located cerebellar, optic hypothalamus, or brainstem
- 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 (WHO grade 2, 3, and 4)
- Usually affects adults 20-40 years old
- Cerebral hemispheres are the most common site in adults
- Can progress to become a higher grade (malignant progression)
- IDH1/2 mutation in 80% of cases
Describe the histology of astrocytoma (WHO grade 2, 3, and 4)
- Low cellularity and mitotic activity
- No vascular proliferation or necrosis
- IDH mutants can be detected with immunocytochemistry
What can astrocytomas eventually become?
Glioblastoma (after 5-7 years)
What is the most aggressive form of astrocytoma
Glioblastoma multiforme (WHO stage 4)
List some key features of glioblastoma multiforme.
- Grade IV
- Most patients > 50 years
- Affects cerebral hemispheres
- most freq glioma
- median survival 8months
Describe the histology of GBM
- High cellularity and high mitotic activity
- Neoangiogeneis
- 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
What is the second most common primary intracranial tumour after gliomas?
Meningioma
List some key features of meningioma.
- Mainly low grade (I and II)
- Rare in patients <40, incidence increases with age
- Can be multiple (e.g. in NF2)
80% - grade 1 (benign)
20% - grade 2 (atypical)
1% - grade 3 (malignant)
What cell type does meningioma originate from
Meningioepithelial cells of arachnoid mater
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
Describe the role of methylome profiling
- Most tumours have characteristic DNA methylation patterns of CpG islands
- This methylation signatures is stable and can be used to identify the tumour cell origin
Which tumours most commonly metastasise to the brain?
- Lung
- Breast
- Melanoma
- Renal cell
How can the origin of brain metastases be identified
Immunohistochemistry
Where in the brain do metastases tend to be found?
- At the grey-white junction
- This is because the cerebral blood vessels become smaller as they enter the white matter so neoplastic emboli get caught here
What mutation is associated with a better prognosis?
IDH mutation
found in IDH mutant diffuse gliomas
Useful predictor of recurrence in meningiomas?
Tumour grade
based on:
* histology
* molecular markers
