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Pathology > CNS > Flashcards

CNS Flashcards

1
Q

What type of brain tumour is an ependymoma (based on cell type)

A

A glioma

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2
Q

What distinguishes grade 4 astrocytoma and glioblastoma

A

Glioblastoma are IDH1 and IDH2 wildtype, associated with worse prognosis.

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3
Q

Low grade gliomas that ‘transform’ into higher grade are transforming from what to what

A

From a low grade IDH mutant glioma (ie astrocytoma) to a high grade IDH mutant grade IV astrocytoma.

Ie, they can’t get rid of the IDH mutation to become a glioblastoma

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4
Q

What are common genetic mutations of grade 4 glioblastoma, IDH wt

A

Gain of chromosome 7, loss of chromosome 10.
EGFR amplification
TERT promoter mutations

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5
Q

What is the pallisading pattern seen in glioblastoma

A

Serpentine areas of necrosis, surrounded by hypercellularity around the edges of the necrosis.
See picture Robbins pg 1295

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6
Q

Why do high grade gliomas demonstrate a ring of contrast enhancement on imaging

A

Because they produce abnormal blood vessels which are leaky (ie disrupted blood brain barrier

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7
Q

What is the function of MGMT

A

It is a DNA repair enzyme

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8
Q

Why does MGMT promoter methylation predict for better response to alkylation agents

A

Because MGMT is a key component to the repair of chemotherapy induced DNA modification.
Promoter methylation results in lower levels of MGMT, and therefore less repair of chemo induced DNA damage, and more tumour cell kill

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9
Q

What type of genetic alteration is involved with 1p/19q co-deletion

A

Whole arm deletion of chromosomes 1 and 19

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10
Q

What is the typical microscopic appearance of oligodendrogliomas

A

Fried egg appearance: Round nuclei with cleared cytoplasm causing halos.
Chicken wire vasculature: Thin walled capillaries (myxoid liposarcoma is the other with chicken wire)
Calcification

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11
Q

What is the molecular profile of a Oligodendroglioma, WHO grade 2 or 3

A

IDH mutant
Nuclear ATRX retained
1p/19q co-deleted

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12
Q

What is the molecular profile of an Astrocytoma WHO grade 2 or 3

A

IDH mutant
(Nuclear ATRX retained AND 1p/19q non-codeleted) OR Nuclear ATRX lost
CDKN2A/B retained
No necrosis or microvascular proliferation

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13
Q

What is the molecular profile of an Astrocytoma, WHO grade 4

A

IDH mutant
(Nuclear ATRX retained AND 1p/19q non-codeleted) OR Nuclear ATRX lost
CDKN2A/B homozygously deleted AND/OR necrosis/microvascular proliferation

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14
Q

What is the molecular profile of glioblastoma WHO grade 4

A

IDH1/2 wild type
Nuclear ATRX retained
H3.3 G34R/V wild type
Any of:
-necrosis
-microvascular proliferation
-TERT promoter methylation
-EGFR amplification
-chromosome 7 gain or 10 loss

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15
Q

What WHO grade are pilocytic astrocytoma. What is the relevance of tumour necrosis

A

WHO grade 1.
No relevance of tumour necrosis. Ie, doesn’t make it higher grade

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16
Q

What kind of glioma is commonly associated with NF2 mutation

A

Spinal ependymomas

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17
Q

Where do ependymomas usually arise

A

In proximity to the ependyma lined ventricles or central canal of spinal cord
Often different sites are associated with different driver mutations

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18
Q

Where do ependymomas typically arise in the first two decades of life

A

The 4th ventricle

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19
Q

Where do ependymomas typically arise in adults

A

Spinal cord, commonly associated with NF2 mutation

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20
Q

What is an example of a WHO grade I ependymoma

A

Subependymomas: usually small incidentally identified lesions growing under the ependymal layer in the 4th or lateral ventricles.

Excellent prognosis

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21
Q

What are the features that distinguish WHO grade 2 and 3 ependymomas

A

WHO grade 3: pallisading necrosis, increased cell density, high mitotic rates, microvascular proliferation

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22
Q

What are the key predictors of outcome for WHO grade 2-3 Ependymomas

A

Extent of resection
Molecular subtype
NOT WHO grade

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23
Q

What is a general term for higher grade gliomas

A

Diffuse gliomas

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24
Q

In gliomas which molecular markers are known to be homogenously expressed

A

IDH mutation
MGMT promoter methylation
1p/19q codeletion

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25
Q

What is the function of ATRX

A

Incompletely understood, but it is a regulator of gene expression very important for development

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26
Q

What is the initial testing that should be done on a diffuse glioma biopsy to check IDH status

A

Immunohistochemistry for IDH1 R132H protein. (Mutant protein product)

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27
Q

Under what circumstances can a WHO grade 4 glioma be classified at IDH wild type glioblastoma based on IHC for IDH1 R132H alone

A

Age >55
Histologically typical glioblastoma
No previous history of lower grade glioma
Non-midline location
ATRX nuclear expression retained

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28
Q

If IDH1 R132H IHC is negative and further testing is indicating, what testing should be performed

A

IDH1 and IDH2 DNA sequencing

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29
Q

What is an example of a neuronal brain tumour

A

Gangliogliomas. WHO grade 1

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30
Q

What is the most common embryonal brain tumour

A

Medulloblastoma. 20% of all paediatric brain tumours

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31
Q

Where are medulloblastomas located by definition, and what grade are they

A

Always cerebellum
WHO grade 4

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32
Q

Which two signalling pathways are frequently abnormal in medulloblastoma

A

Sonic hedgehog
WnT/B-catenin

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33
Q

What are some of the microscopic features of classical medulloblastoma

A

Small round blue cells
Synaptophysin IHC staining
Homer Wright rosettes
Abundant mitosis
High Ki-67

34
Q

What are the histological subtypes of medulloblastoma

A

Classical
Desmoplastic/nodular
Large cell/anaplastic

35
Q

What are risk factors for CNS lymphoma

A

Immunosuppression
Usually malignant B cells are infected by EBV

36
Q

Which layer of the meninges do meningiomas arise from

A

The arachnoid mater

37
Q

What type of genetic abnormality is common in meningiomas

A

Chromosomal loss, particularly part of 22
Higher grade meningiomas often have loss of several chromosomes

38
Q

What gene is most commonly mutated/lost in sporadic meningioma

A

NF2

39
Q

What are 4 types of WHO grade 1 meningioma

A

Psammomatous (psammoma bodies; see pg 1300)
Fibroblastic
Meningothelial
Transitional

40
Q

How is WHO grade 2 (atypical) meningioma defined

A

Require either 1 major criteria, or 3/5 minor criteria

Major criteria:
-increased mitotic index (>3 mitosis per 10 HPF)
-brain invasion (tongue like protrusions)

Minor criteria:
-increased cellularity
-small cells with high N:C ratios
-sheet-like growth
-spontaneous tumour-type necrosis
-macronucleoli

41
Q

What are the features of WHO grade 3 (anaplastic) meningiomas. What are examples

A

Markedly increased mitosis
Papillary and rhabdoid

42
Q

Is it possible to have an IDHwt grade 2 astrocytoma

A

Yes, there are some heterogenous other tumours that behave is much more indolent pattern than glioblastoma. Usually these arise in childhood rather than adults.

These need further molecular classification to figure out where they fit

43
Q

What are the criteria for grade 4 pathological features in glioma

A

Pseudo pallisading necrosis
OR
At least 3 of 4 MEAN criteria
high Mitotic index
Endothelial proliferation (ie microvascular proliferation)
nuclear Atypia
Necrosis

44
Q

Are there currently any treatment implications for EGFR amplification or mutation in glioblastoma

A

No. Phase 1/2 trials so far of tyrosine kinase inhibitors in glioblastoma have not shown any significant results. Likely due to significant heterogeneity in EGFR abnormality in glioblastoma

45
Q

What type of cell do vestibular schawannomas arise from.

A

Schwann cells (peripheral myelin sheath cells)

46
Q

What IHC marker is usually positive in vestibular schwannoma

A

S100

47
Q

What is the microscopic appearance of astrocytoma

A

Diffusely infiltrating tumour with oval to elongated nuclei. Variable cellular morphology

48
Q

What is the typical radiological appearance of oligodendroglioma

A

Well demarcated
Usually no contrast enhancement
Calcification commonly present

49
Q

What are the three main types of glial cells of the CNS, and what is their function

A

Oligodendrocytes: form myelin sheath. (Nerve conduction)
Astrocytes: blood brain barrier/regulate chemical environment
Ependymal cells: produce CSF

50
Q

What is the radiological appearance of glioblastoma

A

Infiltrative
Rim enhancing with contrast
May cross midline via corpus callosum
Vasogenic oedema.

51
Q

What are the important prognostic factors for a grade 2 glioma

A

Worse:
Age >40
Neurological deficit pre surgery
Size >6cm
Crossing midline
Astrocytoma
Extent of resection

52
Q

What are 4 examples of grade 1 gliomas

A

Pilocytic astrocytoma
Pleomorphic Xanthroastrocytoma
Subependymal giant cell astrocytoma
Ganglioglioma

53
Q

What are the key radiological/histological/mutation features of pilocytic astrocytoma

A

Enhancing on MRI
Often cystic
Commonly posterior fossa

Rosenthal fibres

BRAF driver mutations

54
Q

What are two key IHC markers for glial tumours

A

Olig2
GFAP

55
Q

In general, what are microscopic features associated with glial tumours

A

Fibrillary processes
“Naked nuclei”
Infiltrative growth into brain tissue (non glial tumours are usually well demarcated)
“Secondary structures”
Eosinophilic cytoplasm
Nuclear pleomorphism/hyperchromasia

56
Q

What are the differences in microscopic appearance between WHO grade 2 and 3 astrocytoma

A

A bit subjective overall

Grade 3: subjectively increased nuclear atypia (pleomorphism, coarse chromatin, multinucleation), increased hypercellularity
1 mitosis in biopsy sample, or multiple in resection sample (exact number not defined) = grade 3

57
Q

What is the histological appearance of glioma Roma

A

Biphasic: glial component and stromal component (spindle cells)
Similar clinical and prognostic characteristics to glioblastoma

58
Q

What are some microscopic features that distinguish grade 2 and grade 3 oligodendroglioma

A

Marked atypia
Increased mitotic activity
Microvascular proliferation
Necrosis

Progression from grade 2 to grade three thought to take approx 6 years

59
Q

What are the microscopic features of ependymoma

A

Uniform cells with speckled chromatin in fibrillary matrix: not really small round blue cell.
Perivascular pseudorosettes (perivascular anucleate zones)
Can also get true ependymal rosettes (cudoidal cells surrounding a central lumen)

60
Q

How are Ependymomas graded

A

WHO grade 2 or 3
Grade 2 is default. Grade 3 if dense cellularity and brisk mitotic activity

61
Q

What type of ependymoma typically arises in the spinal cord, and where specifically

A

Myxopapillary ependymoma, WHO grade 2

Arises at the conus medullaris, cauda equine and filum terminale

62
Q

What IHC stains are positive in medulloblastoma

A

Synaptophysin (not necessarily full range of neuroendocrine markers)
NeuN

63
Q

What are the microscopic features of meningioma in general

A

Oval nuclei, delicate chromatin
Frequent intranuclear pseudoinclusions
Abundant eosinophilic cytoplasm
Numerous whorls
Occasional psammoma bodies

64
Q

What is the common IHC findings of meningioma

A

Somatostatin receptor 2a (SSTR2A): most sensitive/specific
EMA, vimentin, PR.
S100 variable.

In keeping with somatostatin receptors being positive (with activation of Pi3K/Akt/mTOR pathways), there are trials assessing combined use of octreotide/everolimus. There is a phase 2 study supporting clinical benefit. Octreotide alone has demonstrated limited clinical benefit.

65
Q

What are two WHO grade 2 (atypical) subtypes of meningioma

A

Chordoid
Clear cell

66
Q

What are the two criteria that define grade 3 meningioma

A

Overtly malignant histology (resembling carcinoma, melanoma or sarcoma)
And/or
Markedly elevated mitotic rate >20/10 HPF

67
Q

What is the difference between solitary fibrous tumour and haemangiopericytoma, and what are the microscopic features of each

A

They are histological variations of the same entity

SFT: alternating hyper and hypo cellular areas with thick collagen bands

Haemangiopericytoma: high cellularity, rich network of reticulin fibres

Both: staghorn vessels: large open branching vessels.

IHC: STAT6 IHC (NAB2-STAT6 fusion)
CD34 and CD99+

68
Q

What are the grades of solitary fibrous tumour/haemangiopericytoma, and how does this affect treatment

A

Grade 1: solitary fibrous tumour. Considered benign: surgery only
Grade 2: haemangiopericytoma with <5 mitosis per 10 HPF
Grade 3: 5+ mitosis. Considered malignant and treated with surgery and radiation

69
Q

What mesenchymal CNS tumour resembles metastatic clear cell RCC

A

Haemangioblastoma
Both VHL associated with similar microscopic appearance, but different IHC profiles

70
Q

Where are CNS germ cell tumours most commonly located

A

Midline.
Usually arising from the 3rd ventricle and involving Pineal gland, hypothalamus, basal ganglia

71
Q

What is the microscopic appearance of pituitary adenoma

A

Variety of growth patterns, but overall similar to other neuroendocrine tumours, eg papillary, diffuse, trabecular
Monomorphic neuroendocrine cells.
Might get perivascular orientation (ie rosettes)

72
Q

What IHC is useful for pituitary adenoma

A

NE markers: synaptophysin, chromogranin
S100 negative
IHC panel for hormone secretion to determine cell type (usually still stain in non-functioning tumours)
-GH, prolactin, TSH-B, ACTH, FSH-B, LH-B, alpha subunit.

73
Q

What is the most common functioning pituitary adenoma

A

Prolactinoma
Presents with amenorrhea, galactorrhoea in females, sexual dysfunction and mass effect in males

74
Q

How is pituitary carcinoma defined

A

Defined by the presence of metastasis with a primary pituitary adenoma present.
IHC mostly resembles pituitary adenoma, but associated with more mitosis, higher Ki67

75
Q

What is craniopharyngioma

A

Benign epithelial CNS tumours derived from rathkes pouch.
In differential diagnosis for a suprasellar tumour

76
Q

What are differentials for a sellar region tumour

A

Benign:
Pituitary adenoma
Craniopharyngioma (1st and 5th decades)
Rathkes cleft cyst
Xanthogranuloma
Epidermoid cyst
Meningioma

Malignant:
Pituitary blastoma
Germ cell tumour
Metastasis
Glioma

77
Q

What is the usual CT appearance of meningioma

A

Well circumscribed
Homogenously enhancing
-moderate-intense enhancement with with contrast
Dural tail= linear thickening and enhancement adjacent to extra-axial mass

78
Q

What is the typical MRI appearance of meningioma

A

T1 isointense to grey matter
T2 hyper intense to grey matter
Intensely enhancing with gadolinium
Oedema uncommon

79
Q

Describe the Simpson grading system for meningioma

A

Estimates risk of recurrence based on degree of resection. Recurrence risk approx 10x Simpson grade

0- GTR + dural attachment and bone plus stripping of 2-4cm of dura
1- GTR with resection of dural attachement and abnormal bone
2- GTR with coagulation of dural attachment
3- GTR without resection or coagulation of dural attachment
4- STR
5- biopsy only

80
Q

In simple terms what are the recurrence rates for each grade of meningioma following GTR

A

Grade 1: up to a quarter
Grade 2: quarter to half
Grade 3: more that half

Pathology (16 decks)

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