Gliomas - KS Flashcards
Diffuse Astrocytoma (grade 2)
-Age
-Location
-Young adults (30s)
-Frontal lobes
Diffuse Astrocytoma (grade 2)
-Molecular - Mutations (3)
-IDH1 (R132H) (90%)
-ATRX - Loss of expression
-TP53 - Strong nuclear p53 staining
Pediatric Diffuse Astrocytoma (grade 2)
-Histology
-Location
-Molecular
-Same as adult diffuse astrocytoma
-Cerebrum (also Thalamus)
-MYB and BRAF mutations
*NO IDH1/2 or ATRX mutations!!
IDH-wildtype VS. IDH-mutant:
-Age
WT - 60 y/o
Mutant - 45 y/o
IDH-wildtype VS. IDH-mutant:
-TERT promoter mutations
WT - 70%
Mutant - 25%
IDH-wildtype VS. IDH-mutant:
-ATRX mutation
-WT - Rare
-Mutant - 70%
IDH-wildtype VS. IDH-mutant:
-EGFR amplifications
-WT - 35%
-Mutant - Rare
IDH-wildtype VS. IDH-mutant:
-PTEN mutations
-WT - 25%
-Mutant- Rare
MGMT promoter methylation status significance.
Response to alkylating chemotherapy agents
Epithelioid Glioblastoma
-Age
-Mutations (2)
-Survival
-Young adults & Kids
-BRAF V600E; IDH-WT
-Short survival (6 months)
Which IDH-WT GBM variant is often more circumscribed and has a somewhat better prognosis?
Giant Cell Glioblastoma
Giant Cell Glioblastomas show a high rate of what mutation?
TP53
Which molecular features are sufficient to call GMB, IDH-WT without histologic features? (3)
-TERT promoter mutation
-EGFR gene amplification
-+7/-10 chromosome copy number changes
What molecular characteristic upgrades IDH-mutant Astrocytomas to a Grade 4?
CDKN2A/B homozygous deletion
Diffuse Glioma, H3.3 G34-mutant:
-Age
-Location
-WHO Grade
-Kids and young adults
-Cerebral hemispheres
-Grade IV
Does a Diffuse Glioma, H3.3 G34-mutant have an IDH mutation?
No - IDH-WT
Diffuse Glioma, H3.3 G34-mutant:
-Primary mutation
Missense mutation
-Glycine for Arginine OR valine at position 34 of the Mature Histone H3.3 protein
Diffuse Glioma, H3.3 G34-mutant:
-Other mutations (2)
-TP53 mutation
-ATRX mutation
Diffuse midline glioma mutation
H3 K27M
*K27M mutation in the histone coding genes H3F3A or HIST1H3B/C
Diffuse Midline Glioma (H3 K27M):
-Age
-Location
-Histology
-Grade
-Children»Adults
-Brainstem/Pons, Thalamus, Spinal cord
-Small and monomorphic typically
-WHO grade IV
Tumor with very strong association with Tuberous Sclerosis?
Subependymal Giant Cell Astrocytoma (SEGA)
SEGA:
-Growth
-Location
-Presentation
-Histology
-Grade
-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
What is the most common glioma in children and adolescents?
Pilocytic astrocytoma (WHO grade 1)
Pilocytic Astrocytoma:
-Mutation (pathway; 1&2 MC)
MAPK pathway gene alterations
- KIAA1549::BRAF gene fusions (~60%)
- NF1 mutation (10-15%; common with optic pathway tumors)
Pilomyxoid Astrocytoma:
-Age
-Location
-Histology (3)
-Infancy
-Hypothalamic/Chiasmatic Region
w/ propensity for CSF dissemination
Histology:
-Angiocentric arrangement
-Lacks Rosenthal fibers & EBGs (typically)
-Increased cellularity compared to PA
Astrocytic tumor with large, pleomorphic, and frequently multinucleated spindled and lipidized cells
Pleomorphic Xanthoastrocytoma (PXA)
PXA:
-Histology (5)
-Dense Reticulin deposition
-Intranuclear inclusions
-Prominent Nucleoli
-EGBs (numerous)
-Neuronal differentiation (often)
PXA:
-Molecular (2)
-BRAF V600E (frequent)
-Combo - BRAF V600E and CDKN2A/B homozygous deletion in majority of cases
*NO IDH mutations
PXA:
-Age
-Location
-Grade
-Children & young adults
-Superficially located in cerebral hemispheres (esp. in temporal lobe) w/ involvement of the Leptomeninges
-WHO grade II
Criteria for Dx of Anaplastic PXA (WHO grade 3).
> 5 mitoses/10 HPF
T/F: Anaplastic PXA show a LOWER frequency of BRAF V600E mutations.
True
Oligodendrioglioma:
-Molecular (2)
-IDH1/2 & 1p19q Co-Deletions
-TERT promoter mutation (frequent)
*No ATRX or p53 mutations
Analplastic Oligodendroglioma (WHO grade 3)
-Mitotic activity
-Ki-67
- > = 6 mitoses/10 HPF (>=2.5 mitoses/mm2)
- Ki67 > 5%
Slow-growing, non-invasive glial tumor located in 3rd ventricle.
Chordoid Glioma (of the third ventricle)
-Rare (<0.1% of primary brain tumors)
Chordoid Glioma (of the third ventricle):
-Histology (3)
-Clusters/cords of epithelioid tumor cells (GFAP+)
-Mucinous stroma (variable)
-Lymphoplasmacytic infiltrate
Chordoid Glioma (of the third ventricle):
-Age
-Grade
-Adults
-WHO grade 2
Chordoid Glioma (of the third ventricle):
-Mutation (gene)
recurrent p.D463H missense mutation in the PRKCA gene
Diffuse glioma composed mainly of thin, cytologically bland, bipolar cells aggregating at least partly in perivascular spaces.
Angiocentric Glioma
Angiocentric Glioma:
-Location
-Age
-Grade
-Cerebral cortex primarily; also seen in brainstem
-Children & Young adults (median age ~13)
-WHO grade 1 (usually cured by excision)
Angiocentric Glioma:
-Mutation
MYB::QKI gene fusion (almost all)
Astroblastoma:
-Mutation
-Age/Sex
-Location
-MN1-alteration
-3 months - 40 years (median: 15 years)
-Strong FEMALE predominance
-Cerebral Hemispheres (Frontal & Parietal»_space; Occipital & Temporal)
