neurooncology Flashcards
what is the most common brain tumour in adults?
how common are cns tumours?
metastatic carcinoma - most common
glioblastoma IDH wildtype - 2nd most common
CNS tumours = rare
CLASSIFY CNS TUMOURS BY THEIR LOCATION
EXTRA-AXIAL (COVERINGS)
Tumours of bone, cranial soft tissue, meninges, nerves
INTRA-AXIAL (PARENCHYMA);
Derived from the normal cell populations of the CNS glia, neurons, vessels, connective tissue..
Derived from other cells types lymphomas, germ cell tumours
the following are which type of tumours;
Astrocytes - astrocytoma Oligodendrocytes - oligodendroglioma -> gliomas Ependyma – ependymoma Neurons - neurocytoma Embryonal cells – medulloblastoma
intra axial
the following are which type of tumours;
Meningothelial cells – meningioma
Schwann cells – schwannoma, neurofibroma
extra axial
WHAT IS THE AETIOLOGY OF CNS TUMOURS?
Irradiation to head and neck: meningiomas, rarely gliomas
Genetic predisposition <5%
Environmental factors
-eg ionising radiation / phones
which genes are involed in neurofibromatosis?
what is the inheritance pattern?
Neurofibromatosis 1 (17q11)
Neurofibromatosis 2 (22q12)
Autosomal dominant inheritance
Frequent de novo mutations
what signs and symptoms may you get with CNS tumour, in the following
Subtentorial, Supratentorial, Intracranial hypertension:
Intracranial hypertension:
Headache, vomiting
Change in mental status
Subtentorial:
Cerebellar Ataxia
Long tract signs: spasticity,hyperreflexia, and abnormalreflexessuch as Babinski
Cranial nerve palsy
Supratentorial:
Focal neurological deficit
Seizures
Personality changes
if there is a low grade cns tumour, or benign one, how can we treat it?
radiotherapy preferred over chemo - chemo reserved for high grade stuff.
The WHO CLASSIFICATION OF CNS TUMOURS (2016) involves which parameters?
Tumour type: histologically (putative cell of origin or lineage of differentiation)
Tumour grade: tumour aggressiveness. tells us about SURVIVAL
Incorporation of genetic profile
No staging (TNM)
what are the WHO grades for tumours?
Grade I - benign - long-term survival
Grade II – more than 5 yrs
Grade III – less than 5 yrs
Grade IV – less than 1yr
characterise glial tumours in adults vs in children?
Adults - the gliomas tend to be of high grades (2+) and have high risk of malignant progression
Diffuse gliomas
Astrocytomas (grades II-IV)
Oligodendrogliomas (grades II-III)
Kids -
the gliomas and astrocytomas are of low grade (1-2), low risk progression
Circumscribed gliomas
what is the most common glial tumour in kids?
Pilocytic astrocytoma (grade I)
what are the genetics involved in DIFFUSE GLIOMAS
(adults) ? what improves prognosis?
DIFFUSE GLIOMAS
IDH1/2 mutations (30%)*
Positive prognostic factor
*IDH = isocitrate dehydrogenase
what are the genetics involved in CIRCUMSCRIBED GLIOMAS (kids) ?
CIRCUMSCRIBED GLIOMAS
MAPK pathway mutations
(BRAF, NF1, FGFR1)
PILOCYTIC ASTROCYTOMA (WHO GRADE I) is usally seen in which age brackets?
1st and 2nd decade
A CNS tumour is described as follows, what tumour is it?
MRI - Well circumscribed, cystic, enhancing lesion
Hallmark on histology:
piloid glial “hairy” cell. Very often see Rosenthal fibres
PILOCYTIC ASTROCYTOMA - grade 1
20% of CNS tumours below 14 years
List some clinical featurese of PILOCYTIC ASTROCYTOMA?
Often cerebellar, optic-hypothalamic, brainstem
Slowly growing: low mitotic activity
BRAF mutation (KIAA1549-BRAF fusion) in 70% of PA - believe its a duplication
what are the clinical features, ivx findings and genetic associations of Diffuse Astrocytoma?
what gives good prognosis?
Patients usually 20-40 years
Cerebral hemispheres
MRI: T1 hypointense, T2 hyperintense, non-enhancing lesion.
Low choline / creatinine ratio at MRSpec.
Low to moderate cellularity
Mitotic activity is low
No vascular proliferation and necrosis
Point mutation in IDH1/2: in >80% of cases
IDH mutation gives better prognosis
what do astrocytomas progress to?
glioblastoma’s
what is the Most aggressive and most frequent glioma?
GLIOBLASTOMA MULTIFORME (WHO GRADE IV)
MOST COMMON GLIOMA IN ADULTS
what are the clinical features, ivx findings and genetic associations of Glioblastoma multiforme?
what gives good prognosis?
Age: Most patients >50 years
Area; Cerebral hemispheres
MRI: heterogeneous, enhancing post-contrast
High cellularity and high mitotic activity,
microvascular proliferation - new vessel formation, necrosis
note; wants to look similar to diffuse astrocytoma but clear signs of malignant potential here.
90% de novo GBM
GBM, IDH wildtype
10% secondary GBM (progression)
GBM, IDH mutant
Prognosis:
IDH mutation is associated with longer survival and a better response to rtherapy
_____ is a more powerful prognostic marker than grade for astrocytomas grade II and III
IDH mutation is a more powerful prognostic marker than grade for astrocytomas grade II and III
which tumour has a hemispheric location ?
OLIGODENDROGLIOMA (WHO GRADE II – III)
what are the clinical features, ivx findings and genetic associations of Oligodendroma?
what gives good prognosis?
Patients usually 20-40 years, hemispheric location
Presents with long history of neurological signs – seizure
Round cells with clear cytoplasm (“fried eggs”)
Point mutation in IDH1/2 + codeletion 1p/19q: 100%
Better prognosis than astrocytomas Slow growth, more circumscribed – resection is important Better response to chemo and radiotherapy
MRI: no or patchy contrast enhancement; MRI and MRSpec are not predictive of transformation
codeletion 1p/19q in oligodendroma is associated with? why?
better prognosis/survival
why; good response to chemo
psamomma bodies may be seen in which CNS tumour ?
meningioma
what are the grades of meningioma from most to least common?
what’s its grade based on?
80% Grade I: benign, recurrence <25%
20% Grade II: atypical, recurrence 25-50%
1% Grade III: malignant, recurrence 50-90%
based on histology only :
MITOTIC ACTIVITY - crucial
Microscopic brain invasion - Pseudoinvasion along
the Virchows-Robin space
which tumours are most likely to cause brain mets?
lung ca, breast ca, melanoma, renal cell ca
how does brain mets usually present?
Often multiple tumours,
located at grey/white matter junction (intra axial) and/or leptomeningeal disease (extra axial)
how can we determine origin of a cns mets tumour?
immunohistochem - look for markers that we can identify as from a particular cell/organ
what is the aetiology of medulloblastoma? epidemiology?
EMBRYONAL TUMOUR: originates from neuroepithelial precursors of the cerebellum/dorsal brainstem
second most common brain tumour in children (after pilocytic astrocytoma); also in young adults
A ‘Small round blue cell’ tumour: high grade, poorly differentiated is characteristic of
medulloblastoma
what and how are the subtypes of medulloblastoma differentiated?
Molecular subtypes by transcriptome or methylome profiling: WNT-activated, SHH-activated, group 3, group 4
what is the METHYLATION CLASSIFIER ? uses?
considers EPIGENETIC PROFILE of tumours
Looks at DNA methylation pattern of cpg islands in the tumour to help identify the tumour
Useful for atypical cases, small biopsies, and subtyping:
medulloblastoma subtypes, meningiomas
true/false
medulloblastoma does not respond. to chemo/radiotherapy
false - it does, very well even
