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YEAR 5: Histopathology PM > Histo: Neuro-Oncology > Flashcards

Histo: Neuro-Oncology Flashcards

1
Q

How much more common are secondary brain tumours than primary brain tumours?

A

Brain metastases are 10x more common that primary tumours

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2
Q

Describe the locational classification of brain tumours.

A

Extra-axial (coverings):

  • bone
  • meninges
  • nerves
  • cranial soft tissue

Intra-axial (parenchyma):

  • Derived from normal cell populations of the CNS (e.g. glia, neurones, neuroendocrine, vessels)
  • Derived from other cell types (e.g. lymphomas, germ cell tumours)
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3
Q

List the different cell types within the CNS that can give rise to brain tumours.

A
  • Neurones
  • Astrocytes
  • Oligodendrocytes
  • Ependyma
  • Choroid plexus epithelium
  • Meningothelial cells
  • Embryonal cells
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4
Q

What is the aetiology of CNS tumours

A

Largely unknown

  • Environmental: radiation associated with meningioma
  • Genetic predispostion: familial CNS tumour syndromes
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5
Q

What is the most common genetic syndrome associated with brain tumours?

A

Neurofibromatosis

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6
Q

What is the inheritance pattern of neurofibromatosis?

A

Autosomal dominant

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7
Q

Where are the genes that cause neurofibromatosis located?

A
  • NF1 = 17q11
  • NF2 = 22q12
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8
Q

What tumours are associated with following Familial CNS Tumour Syndromes:

  • NF1
  • NF2
  • Brain Tumour polyposis syndrome 1
  • Gorlin syndrome
  • Von Hippel Lindau syndrome
A
  • NF1 - neurofibroma, astrocytoma
  • NF2 - bilateral vestibular schwanoma, meningioma
  • BTP1 - malignant glioma
  • Gorlin syndrome - medulloblastoma
  • VHL - haemangioblastoma

AD inheritance

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9
Q

What are some common signs of CNS tumours

A

Raised ICP:

  • Headache (worse in morning, coughing, lying down)
  • Vomiting
  • Altered mental status
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10
Q

List some manifestations of brain tumours that are:

  1. Supratentorial
  2. Subtentorial
A

Supratentorial

  • Focal neurological deficit
  • Seizures
  • Personality changes

Subtentorial

  • Cerebellar ataxia
  • Long tract signs (e.g. hyperreflexia)
  • Cranial nerve palsies
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11
Q

What are some neuroimaging modalties

A
  • CT
  • MRI
  • MR spectroscopy - assess tumour metabolic activity
  • Perfusion MRI
  • fMRI
  • PET
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12
Q

Outline the management options for brain tumours.

A

Surgery - aim for maximal safe resection with minimal damage to the patient. Debulking may be performed and biopsies may be taken.

Radiotherapy - used for gliomas and metastases

Chemotherapy - mainly for high-grade gliomas and lymphomas

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13
Q

What is the role of histopathology and molecular pathology

A
  • Definitive diagnosis
  • Prognostic tests
  • Assessement of treatment response
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14
Q

What is the WHO classification of brain tumours based on?

A
  • Tumour type (cell of origin)
  • Tumour grade (aggressiveness/degree of malignancy)
  • Molecular profile - most tumour types have specific molecular markers

NOTE: metastases are not graded

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15
Q

What are some criteria that tumour grade is based on?

A
  • Mitotic activity
  • Degree of cell and tissue differentiation
  • Degree of necrosis
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16
Q

Outline the meaning of the different WHO grades for brain tumours.

A
  • Grade I = benign, long-term survival
  • Grade II = death in > 5 years
  • Grade III = death in < 5 years
  • Grade IV = death in < 1 years

NOTE: grades I and II are low

GRADE GUIDES Mx

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17
Q

Which brain tumours are staged?

A

None

Except medulloblastoma

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18
Q

What is the most common type of primary brain tumour?

A

Glial tumours, specifically astrocytoma

19
Q

How are the types of glial tumours seen in children and adults different?

A

Diffuse gliomas

  • Mainly seen in adults
  • Supratentorial
  • Malignant progression
  • Astrocytomas, oligodendrogliomas

Circumscribe gliomas

  • Mainly seen in children
  • Posterior fossa
  • Rarely undergo malignant transformation
  • Astrocytomas, ependymomas
20
Q

Which genetic mutations are associated with gliomas in adults and in children?

A
  • Diffuse infiltration (adults) - IDH1/2
  • Circumscribed gliomas (children) - MAPK (BRAF)
21
Q

List some examples of circumscribe gliomas.

A
  • Pilocytic astrocytoma (MOST COMMON)
  • Ependymoma
  • Subependymal giant cell astrocytoma
22
Q

List some key features of pilocytic astrocytomas (WHO grade 1)

A
  • Mainly occurs in children (1st and 2nd decade of life)
  • Associated with NF1
  • Often located cerebellar, optic hypothalamus, or brainstem
  • BRAF mutation in 70% of cases
23
Q

What is the hallmark histological feature of pilocytic astrocytoma?

A
  • Piloid (hairy) cell
  • Often see Rosenthal fibres and granular bodies
  • Slow-growing with low mitotic activity
24
Q

List some key features of astrocytoma (WHO grade 2, 3, and 4)

A
  • Usually affects adults 20-40 years old
  • Cerebral hemispheres are the most common site in adults
  • Can progress to become a higher grade (malignant progression)
  • IDH1/2 mutation in 80% of cases
25
Q

Describe the histology of astrocytoma (WHO grade 2, 3, and 4)

A
  • Low cellularity and mitotic activity
  • No vascular proliferation or necrosis
  • IDH mutants can be detected with immunocytochemistry
26
Q

What can astrocytomas eventually become?

A

Glioblastoma (after 5-7 years)
Grade IV astrocytoma

27
Q

What is the most aggressive form of astrocytoma

A

Glioblastoma multiforme (WHO stage 4)

28
Q

List some key features of glioblastoma multiforme.

A
  • Grade IV
  • Most patients > 50 years
  • Affects cerebral hemispheres
  • most freq glioma
  • median survival 8months
29
Q

Describe the histology of GBM

A
  • High cellularity and high mitotic activity
  • Neoangiogeneis
  • Necrosis
30
Q

What does glioblastoma multiforme tend to arise from?

A

90% arise de novo and have wildtype IDH

10% occur secondary to astrocytoma and have IDH mutation

31
Q

What is the second most common primary intracranial tumour after gliomas?

A

Meningioma

32
Q

List some key features of meningioma.

A
  • Mainly low grade (I and II)
  • Rare in patients <40, incidence increases with age
  • Can be multiple (e.g. in NF2)

80% - grade 1 (benign)
20% - grade 2 (atypical)
1% - grade 3 (malignant)

33
Q

What cell type does meningioma originate from

A

Meningioepithelial cells of arachnoid mater

34
Q

Which histological feature of meningioma is important in determining grade?

A

Mitotic activity (number of mitoses per 10 high power fields)

  • Grade 1: < 4
  • Grade 2: 4-20
  • Grade 3: > 20

NOTE: brain invasion is also an important thing to assess (presence of brain invasion makes it grade II)

35
Q

How does grade of meningioma affect the management options?

A

Grade II and III requires radiotherapy as well as surgery

36
Q

What is a medulloblastoma?

A
  • Embryonal tumour originating from neuroepithelial precursors of the cerebellum and dorsal brainstem
  • They are always found in the cerebellum
37
Q

Describe the histological appearnce of medulloblastoma.

A

Small blue round cell tumour with expression of neuronal markers (very little differentiation)

NOTE: snaptophysin is an example of a neuronal marker

38
Q

Describe the role of methylome profiling

A
  • Most tumours have characteristic DNA methylation patterns of CpG islands
  • This methylation signatures is stable and can be used to identify the tumour cell origin
39
Q

Which tumours most commonly metastasise to the brain?

A
  • Lung
  • Breast
  • Melanoma
  • Renal cell
40
Q

How can the origin of brain metastases be identified

A

Immunohistochemistry

41
Q

Where in the brain do metastases tend to be found?

A
  • At the grey-white junction
  • This is because the cerebral blood vessels become smaller as they enter the white matter so neoplastic emboli get caught here
42
Q

What mutation is associated with a better prognosis?

A

IDH mutation

found in IDH mutant diffuse gliomas

43
Q

Useful predictor of recurrence in meningiomas?

A

Tumour grade

based on:

  • histology
  • molecular markers

YEAR 5: Histopathology PM (20 decks)

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