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Path - Histopath > neurooncology > Flashcards

neurooncology Flashcards

1
Q

what is the most common brain tumour in adults?

how common are cns tumours?

A

metastatic carcinoma - most common

glioblastoma IDH wildtype - 2nd most common

CNS tumours = rare

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2
Q

CLASSIFY CNS TUMOURS BY THEIR LOCATION

A

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

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3
Q

the following are which type of tumours;

Astrocytes - astrocytoma
 Oligodendrocytes - oligodendroglioma    ->       gliomas
 Ependyma – ependymoma
 Neurons - neurocytoma
 Embryonal cells – medulloblastoma
A

intra axial

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4
Q

the following are which type of tumours;

Meningothelial cells – meningioma
Schwann cells – schwannoma, neurofibroma

A

extra axial

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5
Q

WHAT IS THE AETIOLOGY OF CNS TUMOURS?

A

Irradiation to head and neck: meningiomas, rarely gliomas

Genetic predisposition <5%

Environmental factors
-eg ionising radiation / phones

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6
Q

which genes are involed in neurofibromatosis?

what is the inheritance pattern?

A

Neurofibromatosis 1 (17q11)

Neurofibromatosis 2 (22q12)

Autosomal dominant inheritance
Frequent de novo mutations

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7
Q

what signs and symptoms may you get with CNS tumour, in the following

Subtentorial, Supratentorial, Intracranial hypertension:

A

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

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8
Q

if there is a low grade cns tumour, or benign one, how can we treat it?

A

radiotherapy preferred over chemo - chemo reserved for high grade stuff.

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9
Q

The WHO CLASSIFICATION OF CNS TUMOURS (2016) involves which parameters?

A

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)

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10
Q

what are the WHO grades for tumours?

A

Grade I - benign - long-term survival
Grade II – more than 5 yrs
Grade III – less than 5 yrs
Grade IV – less than 1yr

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11
Q

characterise glial tumours in adults vs in children?

A

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

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12
Q

what is the most common glial tumour in kids?

A

Pilocytic astrocytoma (grade I)

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13
Q

what are the genetics involved in DIFFUSE GLIOMAS

(adults) ? what improves prognosis?

A

DIFFUSE GLIOMAS
IDH1/2 mutations (30%)*
Positive prognostic factor

*IDH = isocitrate dehydrogenase

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14
Q

what are the genetics involved in CIRCUMSCRIBED GLIOMAS (kids) ?

A

CIRCUMSCRIBED GLIOMAS
MAPK pathway mutations
(BRAF, NF1, FGFR1)

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15
Q

PILOCYTIC ASTROCYTOMA (WHO GRADE I) is usally seen in which age brackets?

A

1st and 2nd decade

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16
Q

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

A

PILOCYTIC ASTROCYTOMA - grade 1

20% of CNS tumours below 14 years

17
Q

List some clinical featurese of PILOCYTIC ASTROCYTOMA?

A

Often cerebellar, optic-hypothalamic, brainstem

Slowly growing: low mitotic activity

BRAF mutation (KIAA1549-BRAF fusion) in 70% of PA - believe its a duplication

18
Q

what are the clinical features, ivx findings and genetic associations of Diffuse Astrocytoma?

what gives good prognosis?

A

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

19
Q

what do astrocytomas progress to?

A

glioblastoma’s

20
Q

what is the Most aggressive and most frequent glioma?

A

GLIOBLASTOMA MULTIFORME (WHO GRADE IV)

MOST COMMON GLIOMA IN ADULTS

21
Q

what are the clinical features, ivx findings and genetic associations of Glioblastoma multiforme?

what gives good prognosis?

A

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

22
Q

_____ is a more powerful prognostic marker than grade for astrocytomas grade II and III

A

IDH mutation is a more powerful prognostic marker than grade for astrocytomas grade II and III

23
Q

which tumour has a hemispheric location ?

A

OLIGODENDROGLIOMA (WHO GRADE II – III)

24
Q

what are the clinical features, ivx findings and genetic associations of Oligodendroma?

what gives good prognosis?

A

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

25
Q

codeletion 1p/19q in oligodendroma is associated with? why?

A

better prognosis/survival

why; good response to chemo

26
Q

psamomma bodies may be seen in which CNS tumour ?

A

meningioma

27
Q

what are the grades of meningioma from most to least common?

what’s its grade based on?

A

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

28
Q

which tumours are most likely to cause brain mets?

A

lung ca, breast ca, melanoma, renal cell ca

29
Q

how does brain mets usually present?

A

Often multiple tumours,

located at grey/white matter junction (intra axial) and/or leptomeningeal disease (extra axial)

30
Q

how can we determine origin of a cns mets tumour?

A

immunohistochem - look for markers that we can identify as from a particular cell/organ

31
Q

what is the aetiology of medulloblastoma? epidemiology?

A

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

32
Q

A ‘Small round blue cell’ tumour: high grade, poorly differentiated is characteristic of

A

medulloblastoma

33
Q

what and how are the subtypes of medulloblastoma differentiated?

A

Molecular subtypes by transcriptome or methylome profiling: WNT-activated, SHH-activated, group 3, group 4

34
Q

what is the METHYLATION CLASSIFIER ? uses?

A

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

35
Q

true/false

medulloblastoma does not respond. to chemo/radiotherapy

A

false - it does, very well even

Path - Histopath (21 decks)

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