Neurooncology Flashcards
What are the classifications of primary CNS tumours based on location?
EXTRA-AXIAL (COVERINGS):
Tumours of bone, cranial soft tissue, meninges, nerves
INTRA-AXIAL (PARENCHYMA):
Derived from the normal cell populations of the CNS e.g. glia, neurons, neuroendocrine cells. Derived from other cells types lymphomas, germ cell tumours.
What are more common CNS tumours?
Non-malignant tumours are more common than malignant tumours
What is the aetiology of CNS tumours?
Only known environmental factor is radiotherapy to head and neck: meningiomas, rarely gliomas.
Genetic predisposition <5% of primary brain tumours
- Familiarity
- Familial syndromes
What is the chromosome and loci for NF1?
17q11
What is the chromosome and loci for NF2?
22q12
What are other genetic risk factors for CNS tumours and their chromosomes and loci?
Schwannomatosis (22q11)
Tuberous Sclerosis 1 (9q34) and 2 (16p13)
Brain tumour polyposis syndrome 1 (PMS2 7p22, MSH6 2p16) and 2 (APC 5q21)
Li-Fraumeni (p53 17p13)
Cowden syndrome (PTEN,10q23.3)
Gorlin syndrome (PTCH1, 9q31)
Von Hippel Lindau (3p25)
Rhabdoid tumour predisposition (SMARCB1, 22q11)
What do different CNS tumour syndromes result in?
NF1: Neurofibroma, pilocytic astrocytoma
NF2: Schwannoma, meningioma
BTP, Li-Fraumeni: Malignant gliomas
Gorlin: Medulloblastoma
VHL: Hemangioblastoma
What are signs and symptoms of CNS tumours?
Intracranial hypertension:
- Headache, vomiting
- Change in mental status
Supratentorial:
- Focal neurological deficit
- Seizures
- Personality changes
Subtentorial:
- Cerebellar Ataxia
- Long tract signs
- Cranial nerve palsy
What is the most common type of CNS tumour in adults?
Metastatic CNS tumour
What is the most common type of CNS tumour in children?
Pilocytic astrocytoma
What is the management for CNS tumours?
SURGERY:
- Maximal safe resection with minimal damage to the patient
- Gives best outcome
- Age and performance status
- Resectability: location, size, number of lesions
RADIOTHERAPY:
- Low and high-grade gliomas, metastases, selected benign tumours
- External fractionated RT, stereotactic radiosurgery
CHEMOTHERAPY:
- Mainly for high-grade gliomas (temozolomide) and lymphomas
- Biological agents (EGFR inhibitors, PD-L1 inhibitors etc)
What are the diagnostic and therapeutic objectives for CNS tumours?
Craniotomy for debulking: Subtotal and complete resections (as much tumour as possible).
Open biopsy: Inoperable but approachable tumours (about 1cm) – usually representative.
Stereotactic biopsy: If open biopsy not indicated (about 0.5cm tissue) – tissue may be insufficient.
What is histopathology and molecular pathology used for in CNS tumours?
To provide a definitive and complete diagnosis.
To guide treatment: Predictive tests assays for target therapy.
To assess treatment response.
What is the WHO classification of CNS tumours?
Tumour type: Putative cell of origin or lineage of differentiation.
Tumour grade: Tumour aggressiveness.
Molecular profile: Expanded compared to previous 4th edition (genetics, methylome), most tumour types have molecular markers.
NO TNM STAGING
What is tumour typing for CNS tumours?
Tumour type: Histological type
Tumour defined by histological features
Tumour names often derive from putative cell of origin or differentiation
Histological type predicts tumour behaviour.
What is grading in CNS tumours?
The grading system is an attempt to stratify tumours by outcome and degree of malignancy.
It is based on morphological criteria of malignancy (proliferative activity, cell differentiation, necrosis) and increasingly on genetic profile.
It is based on predicted natural clinical behaviour and does not consider response to treatment: many pts with treated high-grade tumours have longer survival than expected according to grade.
What are the 4 grades according to the WHO classification?
Grade 1: Benign - long-term survival
Grade 2: More than 5 yrs
Grade 3: Less than 5 yrs
Grade 4: Less than 1yr
What are tumour grades used for?
To guide treatment
What are diffuse gliomas?
Grades ≥ 2
Adults, supratentorial; malignant progression.
- Astrocytomas (grades 2-4)
- Oligodendrogliomas (grades 2-3)
What are circumscribed gliomas?
Grades 1-2
Children, often posterior fossa, rare malignant transformation.
- Pilocytic astrocytoma (grade 1)
- Pleomorphic xanthoastrocytoma (grade 2)
- Subependymal giant cell astrocytoma (grade 1)
- Ependymomas (usually)
Which mutations are associated with diffuse gliomas?
IDH1/2 mutations (30%)
H3 mutations (1%)
Which mutations are associated with circumscribed gliomas?
MAPK pathway mutations (BRAF, NF1, FGFR1)
What are pilocytic astrocytomas?
Usually 1st and 2nd decade - 20% of CNS tumours below 14 years.
Often cerebellar, optic-hypothalamic, brainstem.
MRI: Well circumscribed, cystic, enhancing lesion.
Histology: Piloid “hairy” cell. Very often Rosenthal fibres.
Slowly growing: Low mitotic activity
Genetic profile: BRAF mutation (KIAA1549-BRAF fusion) in 70% of PA
What are the features of diffuse IDH mutation tumours?
Patients usually 20-40 years.
Pathogenic point mutation in the IDH1/2 gene.
IDH mutation is associated with longer survival and a better response to chemotherapy and radiotherapy.
What are the features of astrocytomas?
Young adults 20-40, cerebral hemispheres.
MRI: T1 hypointense, T2 hyperintense, non-enhancing lesion. Low choline/creatinine ratio at MRSpec.
Histology: Low to moderate cellularity. Mitotic activity is low. No vascular proliferation and necrosis.
Genetic profile: Point mutation in IDH1/2.
What is the rule of progression in astrocytomas?
Astrocytoma grade 2 to grade 3 to grade 4, typically in <10 years.
Certain genetic alterations predict shorter time to progression.
What is glioblastoma multiforme?
Most aggressive and most frequent glioma; incidence ↑ with age.
Median survival: 8 months (2012-17).
What are signs on investigation for glioblastoma multiforme?
Most patients >50 years, cerebral hemispheres.
MRI: Heterogeneous, enhancing post-contrast.
Histology: High cellularity and high mitotic activity, microvascular proliferation, necrosis.
Genetic profile: IDH1 wildtype.
Common mutations in TERT, PTEN, EGFR and EGFR ampl.
What is this?
Glioblastoma multiforme
High cellularity
What is this?
Glioblastoma multiforme
Neoangiogenesis (microvascular proliferation)
What is a meningioma?
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.
What is the distribution of WHO grades for meningiomas?
80% Grade 1: Benign, recurrence <25%
20% Grade 2: Atypical, recurrence 25-50%
1% Grade 3: Malignant, recurrence 50-90%
What is this?
Meningioma
Psammoma bodies: calcifications
Why is subtyping and grading useful for meningiomas?
Grading is the most useful predictor of recurrence. It is mainly based on histology, recently molecular markers (ex TERT mutation, methylome)
Complex histological assessment: proliferation, cell morphology, microscopic brain invasion.
There are 15 morphological subtypes across 3 grades.
What are CNS metastases?
Most frequent CNS tumour in adults (10 x intrinsic tumours). Increasing incidence due to longer survival.
Often multiple, located at grey/white matter junction and/or leptomeningeal disease. May be the first presentation of the disease.
Origin can be challenging to determine: immunohistochemical markers.
Very poor prognosis.
What are the most common cancers to give rise to CNS metastases?
Any cancer can give CNS metastasis, but most frequent tumours are:
- Lung ca
- Breast ca
- Melanoma
- Renal cell ca
What are medulloblastomas?
WHO Grade 4.
EMBRYONAL TUMOUR: Originates from neuroepithelial cells/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.
