Neurooncology Flashcards
Where are the tumours of the CNS?
- Brain and coverings
- Spinal cord and coverings
- Pituitary gland
What are the tumours of the peripheral nervous system?
- Small nerves in any organ – usually neurofibromasof soft tissue or skin
- Large nerves: cranial and spinal nerve schwannomas (acoustic neuroma most common)
- Most are benign tumours
How do we classify CNS tumours?
By origin:
- PRIMARY Tumours that originated within the CNS
-
SECONDARY Metastases:
- 10x more frequent than primary tumours
- in adults (30% of patients with systemic
- cancer develop CNS mets)
How common are primary CNS tumours?
- responsible for 2% of cancers in ADULTS and 25% of cancers in CHILDREN and most common cause of cancer death
How are primary CNS tumours classified?
- Extra-axial (coverings):
- Tumours of bone, cranial soft tissue, meninges, nerves and metastatic deposits
- Intra-axial (parenchyma):
- Derived from normal cell populations of the CNS (glia, neurons, vessels, connective tissue)
- Derived from other cell types (metastases, lymphomas, germ cell tumours)
What are the interaxial and extraxial tumours?
- Extra-axial: malignant
- Meningothelial cells – meningioma
- Schwann cells – schwannoma
- Intra-axial: benign
- Astrocytes – astrocytoma
- Oligodendrocytes – oligodendroglioma
- Ependyma – ependymoma
- Neurons – neurocytoma
-
Embryonal cells – medulloblastoma
- Children
What are the aetiology of CNS tumours?
LARGELY UNKNOWN
•Only known environmental factor:
Radiotherapy to head and neck: meningiomas, rarely gliomas
•Genetic predisposition <5% of primary brain tumours
- Familiarity*
- Familial syndromes*
What are the familial CNS tumour syndromes?
Describe the signs and symptoms of CNS tumours?
- Signs & symptoms – often non-specific and subtly growing (can have a short history in aggressive lesions):
- Intracranial HTN → headache, vomiting, changed mental state
- Supratentorial → focal neurological deficits, seizures, personality change
- Subtentorial → cerebellar ataxia, long tract signs, cranial nerve palsies
What neuroimaging do we use for CNS tumours?
- CT scan / PET-CT (tracer compounds for hotspots)
- MRI scan (multiple types) MR-spectroscopy (metabolism), perfusion MRI, f-MRI
- Purpose of imaging:
- Assess tumour type Guide resection and biopsy
- Assess post-surgery Assess response to treatment
- Follow-up recurrence Progression
What is the management of CNS tumours?
(1) Surgery (maximal safe resection aims to obtain and extensive excision with minimal damage to the patient)
- Resectability is dependent on the location, site and number of lesions
- Craniotomy → debulking (subtotal and complete resections)
- Open biopsies → inoperable but approachable tumours
- Stereotactic biopsy → open biopsy not indicated
(2) Radiotherapy
* Used for… low and high-grade gliomas, metastases
(3) Chemotherapy
- Used for… high-grade gliomas (temozolomide)
- Biological agents (EGFR inhibitors, PD-1 inhibitors etc.)
How do we use histopathology and molecular pathology?
- To provide a definitive and complete diagnosis
- To guide treatment: predictive tests assays for target therapy
- To assess treatment response
Describe the WHO classification of CNS tumours.
What. are the different tumour types and their origins?
- Astrocytes
- Oligodendrocytes
- Ependyma
- Neurons
- Embryonal cells
- Meningothelial cells
- Schwann cells
Describe the use of grading ion CNS tumours?
- Grading stratifies tumours by their outcomes (it is rarely based on their genetic profile) and is based on a tumour’s natural history and does not consider the response to treatment, it GUIDES treatment
- Some tumours only have a few possible types and not all 4 (i.e. only 1 possible grade)
- Grading tells us… survival
- Grading does not tell us… therapy response, disease spread, cell of origin
Describe the 4 tier system of grading
What are the types of gliomas?
- Diffuse
- Circumscribed
What are diffuse gliomas?
What are circumscribed gliomas?
Much more stalble
Where are the mutations in glial tumours?
What is a pilocytic astrocytoma?
- Most common child brain tumour (20% CNS tumours <14yo)
- Common in neurofibromatosis I (NF1)
- MRI: cerebellar; well circumscribed, cystic, enhancing
-
Histopathology:
- Piloid (hairy) cell
- Rosenthal fibres and granular bodies
- Slow growing with low mitotic activity
- BRAF mutation present in 70% of cases
Rosenthal fibres - Pilocytic astrocytomas
Describe diffuse gliomas.
Describe diffuse astrocytomas.
(WHO grade II-IV):
- Patients 20-40yo
- Cerebral hemispheres (adults), cerebellum (children)
-
MRI: T1 hypointense, T2 hyperintense, non-enhancing lesion
- Low choline: creatinine ratio at MR-spectroscopy
- Low to moderate cellularity:
- Mitotic activity negligible/absent
- Vascular proliferation and necrosis absent
- IDH1/2 mutation present in >80% of cases (positive prognostic factor)
-
Progression: an astrocytoma (grade II-III) eventually will become a glioblastoma (grade IV)
- Over several years
Diffuse astrocytomas, IDH mutant
Progression: an astrocytoma (grade II-III) eventually will become a glioblastoma (grade IV)predict shorter time to progression
Describe glioblastoma multiform.
- Most patients >50yo
- MRI: heterogenous, enhancing post-contrast
- Cytology: high cellularity, high mitotic activity, microvascular proliferation (neoangiogenesis), necrosis
-
Histological criteria:
- Pathological blood vessels
- Blood vessel structural abnormalities (i.e. multi-layered vessels)
- Cellularity on inspection
- Genetics:
- 90% of cases of GBM occur de novo and have wildtype IDH = MOST COMMON primary brain cancer
- GBM, IDH wildtype
- 10% of cases of GBM occur secondary to astrocytoma (progression) and have the IDH mutation
- 90% of cases of GBM occur de novo and have wildtype IDH = MOST COMMON primary brain cancer
GBM, IDH mutant (positive prognostic factor)
High cellularity
Neoangiogenesis (microvascular proliferation)
Necrosis
GLIOBLASTOMA MULTIFORME
Describe meningiomas.
- 38% of primary CNS tumours
- Rare in patients < 40, incidence ↑ with age•
- Originate from meningothelial cells of the arachnoid mater.
Any site of craniospinal axis, can be multiple (NF2)
••MRI: extraxial, isodense, contrast-enhancing•
80% Grade 1: benign, recurrence <25%
20% Grade 2: atypical, recurrence 25-50
1% Grade 3: malignant, recurrence 50-90%
Psamomma bodies: calcification
MENINGIOMA
What is the histology of meningiomas?
Describe CNS metastases.
- Most frequent CNS tumour in adults (10x more than intrinsic tumours)
- Increasing incidence due to longer survival
- Often multiple
- Any tumour can potentially give CNS metastases, may be the first presentation of the disease
- Origin can be challenging to determine
- Most frequent tumours: lung, breast, melanoma
- Very poor prognosis
CNS metastases
- epithelial cells
Describe medulloblastomas.
- EMBRYONAL TUMOUR: originates from neuroepithelialcells/neuronal precursors of the cerebellum or dorsal brainstem•
- Rare (2 per 1,000,000 year), but second most common brain malignancy in children; also in young adults
- Outcome considerably improved with radio-chemotherapy and subtype stratification
- Very undifferentiated cells
- High grade
- Homer wright rosettes
- “Small blue round cell” tumour (i.e. it is a blastoma / of a primitive cell line – another = Wilm’s tumour)
- Expression of neuronal markers (very little differentiation) – i.e. synaptophysin
- Homer-Wright rosettes are a feature of primitive neuronal differentiation
MEDULOBLASTOMA
What are the 4 histological subtypes of meduloblastomas? What are the 3 molecular subtypes?
Describe the methylome profile.
- Most tumours have characteristic patterns of DNA methylation of CpG islands•
- The methylation signature is stable and reflects the tumour cell of origin or early transformed cells
→ Gives information on tumour type not progression/grade
•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 use of methylation classifiers?
Metastatic deposit
Pilocytic astrocytomas grade 1
Survival
IDH mutation
Metastatic carcinom
Pilocytic astrocytoma (WHO grade 1)
Glioblastoma (WHO grade 4)
