Neuro-Oncology Flashcards
How are CNS tumours classified?
Primary - tumours that originated within the CNS
Secondary (metastases) - 10 times more frequent than primary tumours in adults
What is the most common form of neurological tumour
Secondary metastases
What is the second most common cancer in children
CNS tumours
How common are CNS tumours in adults
1-2% of all cancers
How are CNS tumours classified by location (2)
Extra-axial (coverings) - tumours of bone, cranial soft tissue, meninges and nerves.
Intra-axial (parenchyma) - derived from the major normal cell populations of the CNS (glia, neurons, vessels, connective tissue)
OR
Derived from other cell types (metastases, lymphomas, germ cell tumours)
What are the cells of origin of primary CNS tumours (7)
Neurons. Astrocytes. Oligodendrocytes. Ependyma. Choroid plexus epithelium. Meningothelial cells. Embryonal cells.
What conditions have a genetic predisposition to CNS tumours (9)
Neurofibramatosis 1 Neurofibramatosis 2 Tuberous Sclerosis 1 Tuberous Sclerosis 2 Turcot's syndrome Li-Fraumeni Cowden syndrome Gorlin syndrome Von Hippel Lundau
What CNS tumours are associated with NF1 (2)
Neurofibroma
Pilocytic astrocytoma
What CNS tumours are associated with NF2 (2)
Schwannoma
Meningioma
What CNS tumours are associated with TS (2)
Hamartomas
Sega
What CNS tumours are associated with VHL
Hemangioblastoma
What is the only known environmental risk factor for CNS tumours
Ionising radiation
What are the signs of a supratentorial CNS tumour (5)
Focal neurological deficit Seizures Headache Change in mental status Personality changes
What are the signs of a subtentorial CNS tumour (2)
Cerebellar ataxia
Long tract signs
Cranial nerve palsy
What imaging is used to assess CNS tumours (6)
CT
MRI
MR-Spectroscopy
Perfusion MRI
Functional MRI
PET-Scan
What is the purpose of neuroimaging (5)
Assess tumour type Guide resection and biopsies Assess post-surgery Assess response to treatment Follow up recurrence and progression.
What are the management options for CNS tumours (3)
Surgery
Radiotherapy
Chemotherapy
What is the purpose of surgery for CNS tumours
Maximal safe resection aims to obtain an extensive excision with minimal damage to the patient
What determines the possibility of surgery for CNS tumours (3)
Age and performance status
Resectability: location, size, number of lesions
Histology (intraoperative diagnosis)
What are the types of radiotherapy available for CNS tumours (3)
Fractionated RT
Stereotactic radiosurgery
Whole brain
What are the indications for chemotherapy for CNS tumours
Mainly for high-grade gliomas (temozolomide)
What are the three main forms of neurosurgery (3)
Stereotactic biopsy - inoperable tumours (about 0.5cm tissue) - tissue may not be representative.
Open biopsy - inoperable but approachable tumours (about 1cm) - more accurate
Craniotomy for debulking (as much tissue as possible)
What is involved in the WHO classification of CNS tumours (2016) (4)
Tumour type - putative cell of origin
Tumour differentiation - grading
Tumour defined by genetic profile - integrated diagnosis
NO STAGING
What is the only CNS tumour that is staged
Medulloblastoma
How are tumours named (3)
One of three ways:
Descriptive - defined by histology
Names derives from putative cell of origin
Histological type
What is the point of grading a tumour
The grade is an attempt to stratify tumours by outcome - degree of malignancy
What is grading based on (2)
Histopathological criteria (proliferative activity, differentiation, necrosis) Based on natural history
How many grades does WHO define for CNS tumours
4
What are the grades for CNS tumours (4)
Grade 1 - long-term survival/cured
Grade 2 - cause death in more than 5 years
Grade 3 - cause death within 5 years
Grade 4 - cause death within 1 year
What is more accurate: tumour typing or tumour grading
Tumour typing
Grading is less accurate than typing - limited by size of biopsies
What is the most common primary CNS tumour
Glial
What are the most common adult glial tumours (2)
Astrocytoma (grades 2-4)
Oligodendroglioma (grades 2-3)
What is the most common glial CNS tumour presentation in adults
Diffuse infiltration (Grades >2)
What are the most common childhood glial tumours (4)
Pilocytic astrocytoma (grade 1)
Pleomorphic xantoastrocytoma
Subependymal astrocytoma
Ganglioglioma
What grades do childhood gliomas tend to be
Grades 1/2
What is the most common glial CNS tumour presentation in children
Compressive margins - rare malignant transformation
What mutation is present in diffuse gliomas
IDH mutations
What mutation is present in circumscribed gliomas
MAPK pathway mutations
What grade is a pilocytic astrocytoma
Grade 1
When do pilycytic astrocytomas tend to occur
Usually 1st and 2nd decade
20% of CNS tumours are below age 14
Where do pilocytic astrocytomas tend to occur (3)
Cerebellar
Optic-hypothalamic
Brain stem
How do pilocytic astrocytomas appear on MRI
Always contrast enhancement and circumscribed (never diffuse infiltration)
What is the hallmark of pilocytic astrocytoma (3)
Piliod ‘hairy’ cell
Very often Rosenthal fibres and granular bodies.
Slow growing: low mitotic activity
What mutation is associated with pilocytic astrocytomas
BRAF
When do diffuse astrocytomas tend to occur
Occur more commonly between 30-40 years
What grade are diffuse astrocytomas
Grade 2
How do diffuse astrocytomas appear on MRI/MRISpec (2)
`T1 hypointense, T2 hyperintense, non-enhancing lesion.
Low choline/creatinine ratio at MRSpec
What are the histological features of diffuse astrocytoma (3)
Low to moderate cellularity
Mitotic activity is negligible or absent
Vscular proliferation and necrosis are absent
What are the most common mutations in diffuse astrocytomas
IDH1/2
What grade is a glioblastoma multiforme
Grade 4
What age group are affected by glioblastoma multiforme
Most patients >50 years
What is the appearance of glioblastoma multiforme on MRI
T1 enhancing post-contrast
What are the histological features of glioblastoma multiforme (2)
High cellularity and high mitotic activity
Endothelial proliferation and/or necrosis
What is the natural history of glioblastoma multiforme (2)
90% are de novo GBM (IDH wildtype)
10% are secondary GBM (progression - IDH mutation)
What tumour can GBM progress from
Lower grade astrocytoma
What are two characteristics of large tumours (2)
Neoangiogenesis - new blood cell formation
Central necrosis.
What proportion of all brain tumours are oligodendrogliomas
5% of all primary CNS tumours
What grade are oligodendrogliomas
Grade 2-3
What age group do oligodendrogliomas affect
20-40 years
How do oligodendrogliomas present
With a long history of neurological signs (e.g. seizures)
What is seen on MRI of a oligodendroglioma
No or patchy contrast enhancement.
MRI and MRSpec are not predictive of transformation
What are the histological features of oligodendrogliomas
Round cells with clear cytoplasm (friend eggs)
What mutation is associated with oligodendroglioma
IDH1/2 + codeletion 1p/19q
What is the prognosis for oligodendroglioma (3)
Better prognosis than astrocytomas
Slow growth - resection is important
Better response to chem and radiotherapy.
What grade are meningiomas
Grade 1-3
80% Grade 1: benign, recurrence <25%
20% Grade 2: atypical, recurrence 25-50%
1% Grade 3: malignant, recurrence 50-90%
What proportion of primary CNS tumours are meningiomas
Second most common after gliomas.
25-30% of primary intracranial tumours
10% incidental in post-mortem
What age group are most affected by meningiomas
> 40 years
Where do meningiomas tend to occur
Any site of craniospinal axis
What are the symptoms of meningiomas
Focal signs (seizures, compression)
What is seen on MRI of a meningioma (3)
Extraaxial
Isodense
Contrast-enhancing
What is the most important factor in meningioma diagnosis and treatmetn
Most meningiomas are benign and slow-growing, so histology is crucial
What determines tumour grade (meningiomas)
Mitotic activity
Mitoses/10HPF: <4 = grade 1; 4-20 = grade 2; >20 = grade 3
What is crucial to determine (other than grade) in meningiomas
Brain invasion.
Interface between tumour and the cortex should be carefully examined.
Pseudoinvasion along the virchows-Robin space is possible
What grade are medulloblastomas
Grade 4
Where do medulloblastomas originate
Embryonal tumour - originate from neuroepithelial precursurs of the cerebellum/dorsal brianstem
What is the prevalence of medulloblastoma
It is a rare tumour (2/1,000,000/year), but it is the second most common brain tumour in children
What are the histological features of medulloblastoma
Small blue round cell tumour
What are the molecular classifications of medulloblastoma (3)
WNT-activated
SHH-activated
non-WNT/non-SHH
What radically improves outcome in medulloblastoma
Radio-chemotherapy
Where do medulloblastoma tend ot occur (2)
In children - vermis
Adults - hemispheric
What is the most frequent CNS tumour
CNS metastases
What are the most common tumours that give rise to CNS metastases (5)
Lung cancer Melanoma Breast cancer Renal cancer Colon cancer
What is the prognosis for brain metastases
Very poor
