B7-058 Brain Tumors 2 Flashcards by Felicia Jones

adult-type diffuse gliomas [3]

astrocytoma
oilgodendroglioma
glioblastoma

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you can only grade CNS tumors using

and you should write out what when assigning grade?

arabic numerals 1, 2, 3, 4

“CNS WHO Grade”

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most important first step in grading gliomas is determining […] type

IDH

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lower grade and better prognosis gliomas have […]

IDH mutations

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vast majority of IDH mutations in gliomas will have a point mutation at

R132H

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gene encoding cytosolic nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase

IDH

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IDH mutation in diffuse glioma is associated with [better/worse] prognosis

better

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IDH mutations in diffuse gliomas are associated with […] age of onset

younger

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how do we test for IDH mutations?

immunostain for IDH1-R132H

(most common mutation)

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If immunostain for IDH1-R132H is negative but diffuse glioma is strongly suspected, what is the next best test?

Next Generation Sequencing (NGS)

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discovers “non-canonical” IDH mutations

Next Generation Sequencing (NGS)

(mutations other than R132H)

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IDH immunostain takes […] days, NGS takes […] days

1-2
10-14

(cannot continue work up until IDH status is known)

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high incidence in diffuse astrocytomas

lower incidence in oligodendrogliomas, oligoastrocytomas, and glioblastomas

ATRX mutation

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[…] expression is mutually exclusive with 1p/19p co-deletions

ATRX

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ATRX expression is mutually exclusive with […] co-deletions

1p/19p

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if you have a […] mutation you are very likely to have a diffuse astrocytoma

if you do not, you are very unlikely to have diffuse astrocytoma

ATXR

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when IDH mutation is present, the immunostain is […]

positive (tissue turns brown)

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when ATRX mutation is present, the immunostain is […]

negative (loose stain)

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interpret the result of this ATRX immunostain

not mutated

retained expression

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interpret the result of this ATRX immunostain

mutated

loss of expression
very likely diffuse astrocytoma

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ATRX mutations are associated with IDH mutations and […] mutations

p53

(usually tested for with p53 immunostain, but more conclusively with NGS)

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IDH mutant
tp53 mutant
ATRX mutant

molecular signature of […]

diffuse astrocytoma

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poor prognostic factor in IDH mutant astrocytomas

homozygous deletion of CDKN2A/B

(automatically makes it CNS WHO grade 4)

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presence of […] mutation automatically makes a IDH-mutant astrocytoma CNS WHO grade 4

homozygous deletion of CDKN2A/B

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how to test for deletion of CDKN2A/B? [3]

NGS FISH **CMA** (what KU uses)

a technique used to detect the presence or absence of specific gene sequences

FISH

used to detect chromosomal alterations

FISH

very expensive, very comprehensive test used to analyze genomic copy number variation that can detect very small deletions and duplications

CMA (basically the entire genome)

turn around time for CMA

14 days

essential for both grade and prognosis of diffuse astrocytoma

CMA for CDKN2A/B

what mutations are required for diagnosis of oligodendrogliomas? [2]

IDH mutations 1p/19p co-deletions

tests for 1p/19p co-deletions [2]

**FISH** CMA if FISH doesnt pick it up

IDH mutation 1p/19p co-deletions molecular signature of [...]

oligodendroglioma

molecular signatures of IDH wildtype gliomas [3]

EGFR amplification whole chromosome 7 gain and 10 loss (+7/-10) TERT promoter mutation (only need 1 to classify as WHO grade 4)

[...] confers a better prognosis for IDH wildtype gliomas

MGMT methylation

MGMT is associated with long survival in patients treated with [...]

alkylating agents (temozolomide)

why is MGMT methylation considered a good prognostic indicator for IDH wildtype gliomas?

silences the gene so there is no DNA repair so, the tumor cells are more sensitive to DNA damage from alkylating agents

how do you test for MGMT methylation?

PCR analysis

are CNS gliomas staged?

no grade

first step in molecular classification of gliomas

IDH status

common, highly malignant primary brain tumor with less than one year median survival

glioblastoma

grade 4 astrocytoma is called

glioblastoma

"butterfly" glioma

glioblastoma (can cross corpus callosum resulting in this shape)

glioblastoma is associated with [...] amplification

EGFR

astrocyte origin GFAP+

glioblastoma

pseudo-palisading pleomorphic tumor cells central necrosis microvascular proliferation

glioblastoma

relatively rare, slow growing primary brain tumor often calcified

oligodrendroglioma

"fried egg" cells (round nuclei with clear cytoplasm) "chicken wire" capillary pattern

oligodrendroglioma

ring enhancing lesion with edema butterfly lesion crossing the midling

glioblastoma

criteria to make a histologic diagnosis a high grade glioma or glioblastoma

3 of the following: Atypia Mitoses Endothelial proliferation Necrosis AMEN mneumonic

hypercellularity dense cells

example of atypia

what is circled?

mitotic figures

what are these?

vessels (endothelial proliferation)

what is this showing?

pseudo palisading necrosis (viable cells on edge)

in patients above [...] the likelihood of finding an IDH mutation that is not IDH1-R132 drops significantly

what type of testing is typically done for young patients with high grade gliomas without IDH mutation?

NGS (under 55ish)

what is the prognostic marker for high grade IDH wildtype gliomas?

MGMT methylation = good no methylation= bad

what grades of IDH mutant astrocytomas are possible?

2, 3, 4

mitoses in astrocytoma automatically makes it grade

astrocytoma with just atypia and negative FISH and CMA is grade

astrocytoma with atypia mitoses, necrosis and/or MVP

what grades can oligodendroglioma be

2, 3

calcifications perinuclear haloes "fried egg" chicken wire vasculature

oligodendroglioma

artefact of fixation, only seen on FFPE tissue

perinuclear haloes "fried egg" oligodendroglioma

first thing you do on any diffuse glioma

IDH stain

oligodendroglioma with no mitoses, no MVP, no necrosis is grade

oligodendroglioma with mitoses OR MVP OR necrosis is grade

infiltrative mid-line high grade glioma with predominantly astrocytic differentiation

diffuse midline glioma H3 K27 altered

must have K27M mutation or alteration in H3 K27

diffuse midline glioma H3 K27 altered

diffuse midline glioma H3 K27 altered is grade

4 automatically

H3 K27M immunostain positive

diffuse midline glioma H3 K27 altered

rosettes or pseudorosettes GFAP+

ependymoma

myxopapillary ependymoma

ependymoma occurring in the **extramedullary sacral** area

myxopapillary ependymoma

by definition, myxopapillary ependymoma are grade

2 (no grade 1)

circumscribed tumor arising in cerebellum occurs in children

pilocytic astrocytoma

arises in cerebellum and cerebral midline, optic pathways, hypothalamus, and brainstem

pilocytic astrocytoma

cyst with mural nodule biphasic compact bipolar cells looser multipolar cells with microcysts

pilocytic astrocytoma

BRAF-KIAA1549

pilocytic astrocytoma

patients with NF1 generally have [...] pilocytic astrocytomas

optic pathway

by definition, pilocytic astrocytoma is grade

high grade small round blue cell tumors presenting mainly in childhood

medulloblastoma

medulloblastoma is grade

4 automatically

an embryonal neuroepithelial tumor arising in the cerebellum or dorsal brain stem

medulloblastoma

most common primary brain tumor in childhood

pilocytic astrocytoma

often found in the posterior fossa of children

pilocytic astrocytoma

often found in the posterior fossa of adults

hemangioblastoma

bipolar neoplastic cells with hairlike projections microcysts rosenthal fibers

pilocytic astrocytoma

most common malignant brain tumor in childhood

medulloblastoma

can compress the 4th ventricle causing noncommunicating hydrocephalus, headaches, and papilledema can involve the cerebellar vermis causing ataxia

medulloblastoma

Homer-Wright rosettes (small blue cells surround central area of neurophil)

medulloblastoma

most commonly found in the 4th ventricle can cause hydrocephalus

ependymoma

characteristic perivascular pseudorosettes rod-shaped blepharoplasts found near the nucleus

ependymoma

diffuse midline glioma, H3 K27M altered is automatically grade

defined molecularly by co-deletions of chromosomes 1p and 19q AND mutation in IDH1/2

oligodendrogliomas

histologic finding associated with long standing gliosis, slow growing astrocytic tumors, and walled off infarcts

rosenthal fibers

what is this?

pseudopalisading necrosis

glioblastomas are grade [...] astrocytomas

enhancing on imaging is usually associated with [...] grade gliomas

high

partially solid and cystic tumor of the cerebellum that contains many rosenthal fibers in children

pilocytic astrocytoma

[...] are only seen in oligodendrogliomas and are an artefact of formalin fixation

halos (do not see halos on frozen tissue or fresh)