Gliomas - KS

Question 1

Diffuse Astrocytoma (grade 2)
-Age
-Location

Answer 1

-Young adults (30s)
-Frontal lobes

Question 2

Diffuse Astrocytoma (grade 2)
-Molecular - Mutations (3)

Answer 2

-IDH1 (R132H) (90%)
-ATRX - Loss of expression
-TP53 - Strong nuclear p53 staining

Question 3

Pediatric Diffuse Astrocytoma (grade 2)
-Histology
-Location
-Molecular

Answer 3

-Same as adult diffuse astrocytoma
-Cerebrum (also Thalamus)
-MYB and BRAF mutations
*NO IDH1/2 or ATRX mutations!!

Question 4

IDH-wildtype VS. IDH-mutant:
-Age

Answer 4

WT - 60 y/o
Mutant - 45 y/o

Question 5

IDH-wildtype VS. IDH-mutant:
-TERT promoter mutations

Answer 5

WT - 70%
Mutant - 25%

Question 6

IDH-wildtype VS. IDH-mutant:
-ATRX mutation

Answer 6

-WT - Rare
-Mutant - 70%

Question 7

IDH-wildtype VS. IDH-mutant:
-EGFR amplifications

Answer 7

-WT - 35%
-Mutant - Rare

Question 8

IDH-wildtype VS. IDH-mutant:
-PTEN mutations

Answer 8

-WT - 25%
-Mutant- Rare

Question 9

MGMT promoter methylation status significance.

Answer 9

Response to alkylating chemotherapy agents

Question 10

Epithelioid Glioblastoma
-Age
-Mutations (2)
-Survival

Answer 10

-Young adults & Kids
-BRAF V600E; IDH-WT
-Short survival (6 months)

Question 11

Which IDH-WT GBM variant is often more circumscribed and has a somewhat better prognosis?

Answer 11

Giant Cell Glioblastoma

Question 12

Giant Cell Glioblastomas show a high rate of what mutation?

Answer 12

TP53

Question 13

Which molecular features are sufficient to call GMB, IDH-WT without histologic features? (3)

Answer 13

-TERT promoter mutation
-EGFR gene amplification
-+7/-10 chromosome copy number changes

Question 14

What molecular characteristic upgrades IDH-mutant Astrocytomas to a Grade 4?

Answer 14

CDKN2A/B homozygous deletion

Question 15

Diffuse Glioma, H3.3 G34-mutant:
-Age
-Location
-WHO Grade

Answer 15

-Kids and young adults
-Cerebral hemispheres
-Grade IV

Question 16

Does a Diffuse Glioma, H3.3 G34-mutant have an IDH mutation?

Answer 16

No - IDH-WT

Question 17

Diffuse Glioma, H3.3 G34-mutant:
-Primary mutation

Answer 17

Missense mutation
-Glycine for Arginine OR valine at position 34 of the Mature Histone H3.3 protein

Question 18

Diffuse Glioma, H3.3 G34-mutant:
-Other mutations (2)

Answer 18

-TP53 mutation
-ATRX mutation

Question 19

Diffuse midline glioma mutation

Answer 19

H3 K27M

*K27M mutation in the histone coding genes H3F3A or HIST1H3B/C

Question 20

Diffuse Midline Glioma (H3 K27M):
-Age
-Location
-Histology
-Grade

Answer 20

-Children»Adults
-Brainstem/Pons, Thalamus, Spinal cord
-Small and monomorphic typically
-WHO grade IV

Question 21

Tumor with very strong association with Tuberous Sclerosis?

Answer 21

Subependymal Giant Cell Astrocytoma (SEGA)

Question 22

SEGA:
-Growth
-Location
-Presentation
-Histology
-Grade

Answer 22

-Well-circumscribed
-Wall of lateral ventricles
-Seizures (~20 y/o)
-Histology:
- Gemistocytic Astrocytes w/ pink glassy cytoplasm
- Ganglion-like cells w/ prominent nucleoli
- Markedly pleomorphic
-WHO grade 1

Question 23

What is the most common glioma in children and adolescents?

Answer 23

Pilocytic astrocytoma (WHO grade 1)

Question 24

Pilocytic Astrocytoma:
-Mutation (pathway; 1&2 MC)

Answer 24

MAPK pathway gene alterations
- KIAA1549::BRAF gene fusions (~60%)
- NF1 mutation (10-15%; common with optic pathway tumors)

Question 25

Pilomyxoid Astrocytoma: -Age -Location -Histology (3)

Answer 25

-Infancy -Hypothalamic/Chiasmatic Region w/ propensity for CSF dissemination Histology: -Angiocentric arrangement -Lacks Rosenthal fibers & EBGs (typically) -Increased cellularity compared to PA

Question 26

Astrocytic tumor with large, pleomorphic, and frequently multinucleated spindled and lipidized cells

Answer 26

Pleomorphic Xanthoastrocytoma (PXA)

Question 27

PXA: -Histology (5)

Answer 27

-Dense Reticulin deposition -Intranuclear inclusions -Prominent Nucleoli -EGBs (numerous) -Neuronal differentiation (often)

Question 28

PXA: -Molecular (2)

Answer 28

-BRAF V600E (frequent) -Combo - BRAF V600E and CDKN2A/B homozygous deletion in majority of cases *NO IDH mutations

Question 29

PXA: -Age -Location -Grade

Answer 29

-Children & young adults -Superficially located in cerebral hemispheres (esp. in temporal lobe) w/ involvement of the Leptomeninges -WHO grade II

Question 30

Criteria for Dx of Anaplastic PXA (WHO grade 3).

Answer 30

>5 mitoses/10 HPF

Question 31

T/F: Anaplastic PXA show a LOWER frequency of BRAF V600E mutations.

Answer 31

True

Question 32

Oligodendrioglioma: -Molecular (2)

Answer 32

-IDH1/2 & 1p19q Co-Deletions -TERT promoter mutation (frequent) *No ATRX or p53 mutations

Question 33

Analplastic Oligodendroglioma (WHO grade 3) -Mitotic activity -Ki-67

Answer 33

- >= 6 mitoses/10 HPF (>=2.5 mitoses/mm2) - Ki67 > 5%

Question 34

Slow-growing, non-invasive glial tumor located in 3rd ventricle.

Answer 34

Chordoid Glioma (of the third ventricle) -Rare (<0.1% of primary brain tumors)

Question 35

Chordoid Glioma (of the third ventricle): -Histology (3)

Answer 35

-Clusters/cords of epithelioid tumor cells (GFAP+) -Mucinous stroma (variable) -Lymphoplasmacytic infiltrate

Question 36

Chordoid Glioma (of the third ventricle): -Age -Grade

Answer 36

-Adults -WHO grade 2

Question 37

Chordoid Glioma (of the third ventricle): -Mutation (gene)

Answer 37

recurrent p.D463H missense mutation in the PRKCA gene

Question 38

Diffuse glioma composed mainly of thin, cytologically bland, bipolar cells aggregating at least partly in perivascular spaces.

Answer 38

Angiocentric Glioma

Question 39

Angiocentric Glioma: -Location -Age -Grade

Answer 39

-Cerebral cortex primarily; also seen in brainstem -Children & Young adults (median age ~13) -WHO grade 1 (usually cured by excision)

Question 40

Angiocentric Glioma: -Mutation

Answer 40

MYB::QKI gene fusion (almost all)

Question 41

Astroblastoma: -Mutation -Age/Sex -Location

Answer 41

-MN1-alteration -3 months - 40 years (median: 15 years) -Strong FEMALE predominance -Cerebral Hemispheres (Frontal & Parietal >> Occipital & Temporal)