Neurooncology Flashcards
What are the classifications of primary CNS tumours based on location?
EXTRA-AXIAL (COVERINGS):
Tumours of bone, cranial soft tissue, meninges, nerves
Majority BENIGN
INTRA-AXIAL (PARENCHYMA):
From normal cell populations of the CNS e.g. glia, neurons, neuroendocrine cells. Or from other cell types lymphomas, germ cell tumours.
INFILTRATIVE
What are more common CNS tumours?
Non-malignant tumours are more common than malignant tumours
What is the aetiology of CNS tumours?
Radiotherapy to head + neck: meningiomas, rarely gliomas.
Genetics: < 5% of primary brain tumours- Familial syndromes
What is the chromosome and loci for NF1 and NF2?
NF1: 17q11
NF2: 22q12
Give 5 familial CNS tumour syndromes
Neurofibromatosis 1: Neurofibroma, Astrocytoma
Neurofibromatosis 2: Schwannoma, Meningioma
Brain Tumour Polyposis: Malignant gliomas
Gorlin: Medulloblastoma
Von Hippel Lindau: Hemangioblastoma
What are signs and symptoms of CNS tumours?
Intracranial HTN:
Headache + vomiting
Change in mental status
Supratentorial: (cerebral hemispheres)
Focal neurological deficit
Seizures
Personality changes (frontal lobe)
Infratentorial:
Cerebellar Ataxia
Long tract signs (motor descending, sensory ascending)
CN 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 are the management options for CNS tumours?
SURGERY:
Max. safe resection with min. damage to patient
Gives best outcome (depends on age + performance status)
Resectability: location, size, no. lesions
RADIOTHERAPY:
Low + high-grade gliomas, mets, selected benign tumours
External fractionated RT, stereotactic radiosurgery
CHEMO:
High-grade gliomas (temozolomide) + lymphomas
Biological agents (EGFR inhibitors, PD-L1 inhibitors)
What are the diagnostic and therapeutic objectives for CNS tumour surgery?
Craniotomy for debulking: Subtotal + complete resections (as much tumour as poss).
Open biopsy: Inoperable but approachable tumours (~1cm), usually representative.
Stereotactic biopsy: If open biopsy not indicated (~0.5cm tissue), tissue may be insufficient for dx.
What is histopathology and molecular pathology of tissue biopsy used for in CNS tumours?
To provide a definitive + complete dx.
To guide tx: Predictive tests assays for target therapy.
To assess tx response.
What is the WHO classification of CNS tumours based upon?
Tumour type: Putative cell of origin or lineage of differentiation.
Tumour grade: Aggressiveness.
Molecular profile: Most tumour types have molecular markers.
NO TNM STAGING
What is tumour typing for CNS tumours?
Tumour type: Histological type
Defined by histological features
Tumour names derived from putative cell of origin
Histological type predicts tumour behaviour.
What is the grading system in CNS tumours?
Attempt to stratify tumours by outcome i.e. degree of malignancy.
Based on morphological criteria of malignancy (proliferative activity, cell differentiation, necrosis) + increasingly on genetic profile.
Based on predicted natural clinical behaviour + does not consider response to tx: 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?
G1: Benign: long-term survival
G2: > 5y
G3: < 5y
G4: < 1y
What are tumour grades used for?
To guide tx
Give 4 characteristics of diffuse gliomas. Name 2 diffuse gliomas.
Grades ≥ 2
Adults
Supratentorial
Malignant progression.
Astrocytomas (G 2-4)
Oligodendrogliomas (G 2-3)
Give 4 characteristic features of circumscribed gliomas. Name 3 examples.
Grades 1-2
Children
Often posterior fossa
Rare malignant transformation
Pilocytic astrocytoma (G1)
Subependymal giant cell astrocytoma (G1)
Ependymomas (usually circumscribed)
Which mutations are associated with diffuse gliomas?
IDH1/2 mutations (30%)
Describe the epidemiology and site of pilocytic astrocytomas.
Describe the features on MRI, histology, genetics.
Usually 1st + 2nd decade
Account for 20% of CNS tumours <14y
Often cerebellar, optic-hypothalamic, brainstem.
MRI: Well circumscribed, cystic, enhancing lesion.
Histology: Piloid “hairy” cell. Very often Rosenthal fibres.
Slow growing: Low mitotic activity
Genetic profile: BRAF mutation in 70%
What are the features of diffuse gliomas?
Usually 20-40y
Astrocytomas + Oligodendrogliomas
+/- Pathogenic point mutation in IDH1/2
IDH mutation A/W longer survival + better response to chemo + radiotherapy.
Describe the epidemiology and site of astrocytomas. Describe the features on MRI, histology, genetics.
20-40y
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/ necrosis.
Genetic profile: +/- Point mutation in IDH1/2.
What is the rule of progression in astrocytomas?
Progress from grade 2 to 3 to 4, typically in <10y
What is glioblastoma multiforme?
Most aggressive + most frequent glioma
Cerebral hemispheres affected
Incidence ↑ with age, most >50y
Median survival: 8m
What are signs on investigation for glioblastoma multiforme?
MRI: Heterogeneous, enhancing post-contrast.
Histology: High cellularity + neoangiogenesis, necrosis.
Genetic profile: IDH1 wildtype.
Common mutations in TERT, PTEN, EGFR
What is this? What can be seen?
Glioblastoma multiforme
High cellularity
(normal brain tissue at top)
What is this? What can be seen?
Glioblastoma multiforme
Neoangiogenesis (microvascular proliferation)
Describe the epidemiology of meningioma. From which cells do they arise? What is seen on MRI?
38% of primary CNS tumours.
Rare in < 40y
Incidence ↑ with age.
Originate from meningothelial cells of Arachnoid mater, at any site of craniospinal axis
Can be multiple (NF2).
MRI: Extraxial, isodense, contrast-enhancing.
What is the distribution of WHO grades for meningiomas?
80% G1: Benign, recurrence < 25%
20% G2: Atypical, recurrence 25-50%
1% G3: Malignant, recurrence 50-90%
Why is subtyping and grading useful for meningiomas?
Grading = most useful predictor of recurrence.
Mainly based on histology, recently molecular markers (ex TERT mutation, methylome)
Complex histological assessment: proliferation, cell morphology, microscopic brain invasion.
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 +/- leptomeningeal disease.
May be 1st 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 mets
Most frequently:
Lung ca
Breast ca
Melanoma
Renal cell ca
Can use antibodies to detect primary site.
What are medulloblastomas?
WHO Grade 4.
EMBRYONAL TUMOUR: Originates from neuroepithelial cells/ neuronal precursors of the cerebellum or dorsal brainstem.
RARE but 2nd most common brain malignancy in children + YA.
Outcome considerably improved with radio-chemotherapy + subtype stratification.
Describe the epidemiology of CNS tumours
Mets 10x more frequent than primary
Primary rare in adults, most common tumour in children
Extra-axial tend to be benign
Intra-axial infiltrate, tend to be malignant
Name the tumour based on the putative cell of origin
Astrocytes
Oligodendrocytes
Ependyma
Neurons
Embryonal cells
Meningothelial cells
Schwann cells
Astrocytes: Astrocytoma
Oligodendrocytes: Oligodendroglioma
Ependyma: Ependymoma
Neurons: Neurocytoma
Embryonal cells: Medulloblastoma
Meningothelial cells: Meningioma
Schwann cells: Schwannoma, Neurofibroma
Describe tumours of the nervous system based on central or peripheral distribution
CNS: Brain + coverings, spinal cord + coverings, pituitary
PNS: small nerves in any organ (neurofibromas of skin/ soft tissue) + large nerves (cranial + spinal nerve schwannomas)
Most peripheral are benign
How is mitotic activity useful?
Determines grade
Mitosis per 10 HPF
<4 = G1
4-20 = G2
>20 = G3
What is the methylome profile?
Characteristic patterns of DNA methylation of CpG islands
Epigenetic profile
Stable signature, reflects cell of origin
Helpful for atypical cases, rare entities, small biopsies, sub-typing
