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a path 3 > HISTOPATH: Neuro-oncology > Flashcards

HISTOPATH: Neuro-oncology Flashcards

1
Q

How common are CNS tumours in children vs adults?

A

In adults make up 1-2% of all tumours

In children are the most common tumour type making up ~25% of all tumours

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2
Q

What is the histological classification for CNS tumours (based on cell of origin)?

A

Extra-axial:

  • Meningothelial cells – meningioma
  • Schwann cells – schwannoma

Intra-axial:

  • Astrocytes – astrocytoma
  • Oligodendrocytes – oligodendroglioma
  • Ependyma – ependymoma
  • Neurons – neurocytoma
  • Embryonal cells – medulloblastoma
    • Children
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3
Q

What is the aetiology of CNS tumours?

A
  • Radiation to head and neck: meningiomas, rarely gliomas N.B. mobile phone use does not increase risk
  • Neurocarcinogens
  • Genetic predisposition (<5% of primary brain tumours)
    • Neurofibromatosis is most common form
    • Autosomal dominant inheritance
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4
Q

What are the signs and symptoms of CNS tumours, in general and based on location?

A

Often non-specific and subtly growing (can have a short history in aggressive lesions):

  • Intracranial HTN –> headache, vomiting, changed mental state
  • Supratentorial –> focal neurological deficits, seizures, personality change
  • Subtentorial –> cerebellar ataxia, long tract signs, cranial nerve palsies
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5
Q

What are the neuroimaging studies used in CNS tumours?

A
  • CT scan / PET-CT (tracer compounds for hotspots)
  • MRI scan (multiple types) = MR-spectroscopy (metabolism), perfusion MRI, f-MRI
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6
Q

What are 5 purposes of imaging in CNS tumours?

A
  1. Assess tumour type
  2. Guide resection and biopsy
  3. Assess post-surgery
  4. Assess response to treatment
  5. Follow-up recurrence
  6. Progression
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7
Q

What are the management options for CNS tumours?

A
  1. Surgery (maximal safe resection aims to obtain and extensive excision with minimal damage to the patient)
    • Resectability is dependent on the location, site and number of lesions
    • Craniotomy = debulking (subtotal and complete resections)
    • Open biopsies = inoperable but approachable tumours
    • Stereotactic biopsy = open biopsy not indicated
  2. Radiotherapy
    • Used for… low and high-grade gliomas, metastases
  3. Chemotherapy
    • Used for… high-grade gliomas (temozolomide)
    1. Biological agents (EGFR inhibitors, PD-1 inhibitors etc.)
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8
Q

What categories does the WHO classification system for CNS tumours use?

A
  • Tumour type (cell of origin) = histological type, predicts behaviour (i.e. rate of spread)
  • Tumour grade (differentiation) - histological criteria (e.g. proliferative activity, cell differentiation, necrosis)
    • Grade I = benign, long-term survival - LOW grade, LONG survival - predicts survival
    • Grade II = cause death in >5 years - LOW grade, LONG survival
    • Grade III = cause death <5 years - HIGH grade, SHORT survival
    • Grade IV = cause death <1-year - HIGH grade, SHORT survival
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9
Q

IS staging used in WHO classification of CNS tumours?

A

No staging because typically no spread

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10
Q

What are 3 purposes of grading of CNS tumours?

A
  1. Stratifies tumours by their OUTCOMES (it is rarely based on their genetic profile)
  2. Grading is based on a tumour’s NATURAL HISTORY and does not consider the response to treatment, it GUIDES treatment
  3. Grading tells us… SURVIVAL

Grading does not tell us… therapy response, disease spread, cell of origin

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11
Q

Does grading of CNS tumours tell us about:

  1. Therapy response
  2. Disease spread
  3. Cell of origin
A

No for all

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12
Q

Which type of CNS tumour is the only one that is staged?

A

Medulloblastoma

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13
Q

Name 6 types of glial cells.

A
  • Astrocytes
  • Oligodendrocytes
  • Ependymal cells
  • Schwann cells
  • Microglia
  • Satellite cells
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14
Q

What is the most common primary type of CNS tumour?

A

Glial tumour

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15
Q

What are the types of glial tumours?

A
  1. Circumscribed gliomas
  2. Diffuse gliomas
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16
Q

What are the grades of circumscribed gliomas? Who is most affected? Does it transform?

A

Grade I-II

Children

Rare malignant transformation may occur

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17
Q

What are the types of circumscribed gliomas?

A
  1. Pilocytic astrocytoma (grade I) - most common
  2. Pleomorphic xanthoastrocytoma (grade II)
  3. Subependymal giant cell astrocytoma (grade I)
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18
Q

What genetics may be implicated in circumscribed gliomas?

A

BRAF mutation present in 50% of cases (MAPK pathway mutation)

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19
Q

What is the most common child brain tumour? What is its grade?

A

Pilocytic astrocytoma (WHO grade I)

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20
Q

What are these histological features present in pilocytic astrocytoma?

A

Histopathology:

  • Piloid (hairy) cell
  • Rosenthal fibres and granular bodies
  • Slowly growing with low mititic activity
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21
Q

What are the features of pilocytic astrocytoma on MRI?

A
  • Cerebellar
  • Well circumscribed
  • Cystic
  • Enhancing
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22
Q

What % of pilocytic astrocytomas are associated with BRAF mutation?

A

70% of cases

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23
Q

Name 2 types of diffuse gliomas.

A
  1. Diffuse astrocytoma (grades II-IV)
  2. Oligodendroglioma (grades II-III)
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24
Q

What are the general features of diffuse gliomas? (location, grades, age, malignancy) What genetic mutation are they associated with?

A
  • Grades II or higher
  • Adults
  • Supratentorial
  • Malignant progression
  • IDH1/2 mutation present in 30% of cases (positive prognostic factor)
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25
Q

In diffuse glioma, what is the importance of IDH1/2 mutation for prognosis?

A

It is a positive prognostic factor

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26
Q

What are the typical grades of diffuse astrocytoma? What age groups are affected ? Where does it usually occur in the brain?

A

WHO grade II-V

Patients 20-40yo

Cerebral hemispheres (adults), cerebellum (children)

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27
Q

What is seen on MRI/MR spectroscopy in diffuse astrocytoma?

A

MRI:

  • T1 hypointense,
  • T2 hyperintense,
  • non-enhancing lesion

Low choline: creatinine ratio at MR-spectroscopy

28
Q

What is the complication of astrocytomas if left untreated over several years?

A

An astrocytoma (grade II-III) eventually will become a glioblastoma (grade IV) over several years

29
Q

What are the histological features of diffuse astrocytoma?

A
  1. Low to moderate cellularity
  2. Mitotic activity negligible/absent
  3. Vascular proliferation and necrosis absent
30
Q

Who is most affected by glioblastoma multiforme (GBM)? What is the grade?

A

Most patients >50yrs

WHO grade IV

31
Q

What is seen on histology in GBM? What is seen in cytology on GBM?

A

MRI:

  • heterogenous enhancing post-contrast

Cytology:

  • high cellularity,
  • high mitotic activity,
  • microvascular proliferation (neoangiogenesis),
  • necrosis
32
Q
A

Metastatic deposit

33
Q
A

Pilocytic astrocytoma, WHO grade I

34
Q
A

Survival

35
Q
A

IDH1/2

36
Q
A

Metastatic

37
Q
A

Glioblastoma - option 1

38
Q
  • Meningioma (WHO I)
  • Medulloblastoma (WHO grade 4)
  • Glioblastoma (WHO grade 4)
  • Pilocytc astrocytoma (WHO grade I)
A

Pilocytic astrocytoma (WHO grade I) - common in chilren and usually in cerebellum

39
Q

Is a genetic mutation a common cause for GBM?

A

90% occur de novo with wildtype IDH

10% occur secondary to astrocytoma (progression) and have the IDH mutation (positive prognostic factor)

40
Q

What is the grade of oligodendrogliomas? When do they usually occur?

A

WHO grade II-III

Patients 20-40yrs

41
Q

Compared to astrocytomas, what is the prognosis with oligodendrogliomas? Why?

A

Better prognosis than astrocytomas

  • Slow growth –> amenable to resection
  • Better chemo- and radio-therapy response
42
Q

Which CNS tumour cytology is this? Why is it called fried eggs appearance?

A

Cytology: round cells with clear cytoplasm (“fried eggs”)

43
Q

What is seen on MRI in oligodendroglioma?

A

MRI: no/patchy contrast enhancement

MRI/MRSpec not predictive of transformation

44
Q
A
45
Q

What % of oligodendrogliomas are associated with IDH1/2 mutations? What other mutation occurs?

A

IDH1/2 mutation and co-deletion of 1p/19q present in ~100% of cases

Positive prognostic factor

46
Q

What is the 2nd most common CNS tumour?

A

Meningiomas

Usually occurs in adults >40yrs

47
Q

How do meningiomas appear on MRI?

A
  • Extra-axial,
  • Isodense,
  • Contrast-enhancing
48
Q

What does HPF stand for?

A

High power field

49
Q

What are the mitotic activities of grade I-III meningiomas?

A
  • I - <4 mitotic activity per 10 HPF
  • II - 4-20 mitotic activity per 10 HPF
  • III - >20 mitotic activity per HPF
50
Q

What grade are most meningiomas?

A
  • 80% grade I
  • 20% grade II
  • 1% grade III
51
Q

What is the histopathology of meningiomas?

A
  • Attaches to meninges but does not typically invade, just displaces brain matter
  • If they do invade, it is often a micro-invasion (as pictured)
  • Globules found on histopathology
52
Q

What is the most frequent cause of CNS tumours in adults?

A

CNS metastasis

53
Q

What are the features of CNS metastases?

A
  • Increasing in frequency due to longer survival
  • Often multiple
  • Origin may be difficult to determine and may be the first presentation of disease
54
Q

What are the most common origins of CNS metastases?(3)

A
  • Lung
  • Breast
  • Melanoma
55
Q

What is the prognosis of CNS metastases?

A

Very poor

56
Q

What is this type of CNS tumour growth called?

A

Pseudoinvasion along the Virchows-Robin space

57
Q

Where do CNS metastases usually grow and why?

A

Grey-white junction

  • Structure of cerebral blood vessels change here + become smaller as they enter the white matter
  • Therefore, neoplastic emboli tend to get stuck at this level and then start growing
58
Q

What grade are medulloblastomas?

A

Grade IV

59
Q

What is the cell origin of medulloblastoma? Where does it grow?

A

Embryonal origin - from the neuroepithelial precursors of the cerebellum/dorsal brainstem

Grows in the cerebellum

60
Q

Who is most affected by medulloblastomas?

A

Children - it is the 2nd most common brain tumour in children

Outcomes improved with radio-chemotherapy

61
Q

What is the histology of medulloblastomas?

A
  • “Small blue round cell” tumour (i.e. it is a blastoma* / of a primitive cell line)
  • Expression of neuronal markers (very little differentiation) – i.e. synaptophysin
  • Homer-Wright rosettes are a feature of primitive neuronal differentiation

Another blastoma is Wilm’s tumour.

62
Q

What type of tumour has this histology? What is the name given to this appearance?

A

Homer-Wright rosettes

Medulloblastoma

63
Q

What are the 4 groups of medulloblastomas?

A
  1. WNT-activated medulloblastoma
  2. SHH-activated “”
  3. Group 3 “”
  4. Group 4 “”
64
Q
  1. Seizure following 2 weeks of left arm and leg weakness
  2. MRI showing heterogeneous enhancing right frontal lesion, started on steroids
  3. Partial response to steroids with improved dexterity of the left arm and leg
  4. A tumour was partially resected

Answers:

  1. Glioblastoma (WHO grade IV)
  2. Oligodendroglioma (WHO grade II)
  3. Metastatic carcinoma
  4. Diffuse astrocytoma (WHO grade II)
A
65
Q
  1. 5-year-old boy
    1. Had headache and vomiting in the morning for 2 weeks
    2. Symptoms worsened and the vision became blurred
    3. Fundoscopic exam: papilledema
    4. MRI showing cystic cerebellar lesion à tumour was removed

Answers:

  1. Glioblastoma (WHO grade IV)
  2. Medulloblastoma (WHO grade IV)
  3. Oligodendroglioma (WHO grade II)
  4. Pilocytic astrocytoma (WHO grade I)
A
66
Q
  1. 45-year-old female
    1. History: pulmonary lobectomy
    2. 2 days of headache and vomiting
    3. Worsening headache
    4. CT: right frontoparietal SOL with minimal midline shift to the left
    5. DDx: primary tumour, metastasis, abscess

Answers:

  1. Glioblastoma (WHO grade IV)
  2. Astrocytoma (WHO grade II)
  3. Metastatic carcinoma
  4. Oligodendroglioma (WHO grade II)
A

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