Neoplastic

Question 1

From what cells does ecchordosis physaliphora originate? (this is the thing that looks like chordoma but b9)

Answer 1

Notochord rests

Question 2

GENE: papillary glioneuronal tumor

Answer 2

PRKCA (Chr 17)

PRKCA fusions are the hallmark, usually SLC44A1::PRKCA
(SLC is on chr 9)

Question 3

GENE: rosette-forming glioneuronal tumor

Answer 3

FGFR1 (chr 8)
FGFR1 hotspot mutation (FGFR1 p.N546 or p.K656) with either PIK3CA or PIK3R1 mutation
You can get NF1 mutations too but NOT SPECIFIC bc can also be seen in dysembryoplastic neuroepithelial tumour or pilocytic astrocytoma

Question 4

GENE: myxoid glioneuronal tumor

Answer 4

PDGFRA (chr 4)
p.K385L or p.K385I in extracellular ligand-binding domain

Question 5

GENE: diffuse leptomeningeal glioneuronal tumor

Answer 5

KIAA1549::BRAF fusion
(chr 7, spec 7q34; d/t tandem duplication)

del1p
(if no del1p, dx is “unlikely”)

if no KIAA::BRAF, then explore other less frequent MAPK alterations

Question 6

Prognostic genetic thing in diffuse leptomeningeal glioneuronal tumor

Answer 6

GAIN of chromosome 1q = POOR prognosis

Question 7

GENE: astroblastoma

Answer 7

MN1 fusion
(it’s now called astroblastoma, MN1 altered)
mostly in-frame fusions with BEND2 at Xp22.13 (MN1::BEND2)
Some also have CDKN2A homo del

Question 8

GENE: pleomorphic xanthoastrocytoma

Answer 8

BRAF p.V600E (on chr 7) (or other MAPK if not that one)
CDKN2A/B homo del (chr 9)

Question 9

Name 4 genes (families) that are in the MAPK pathway

Answer 9

1. BRAF (chr 7)
2. NTRK (1/2/3) (chr 1/9/15)
3. RAF1 (chr 3)
4. NF1 (chr 17)

Question 10

GENE: pilocytic astrocytoma

Answer 10

KIAA1549::BRAF (chr 7)
BRAF (chr 7)
NF1 (chr 17)

Question 11

GENE: angiocentric glioma

Answer 11

MYB (6q23.3)
Rearrangements (most commonly MYB::QKI fusion [QKI also on chr 6]) and/or copy number alterations (del or amp)

(ddx for MYB alterations should include “pediatric diffuse astrocytoma, MYB- or MYBL1-altered”)

Question 12

GENE: PLNTY

Answer 12

BRAF p.V600E mut (chr 7)
or
FGFR2 (chr 10) or FGFR3 (chr 4) fusions
(unique: FGFR2::CTNNA3)

others include FGFR2::SHTN1 (KIAA1589), FGFR2::INA, FGFR3::TACC3 but those aren’t specific

Question 13

GENE: pediatric diffuse astrocytoma, MYB- or MYBL1-altered

Answer 13

fusion btwn MYB (chr 6) or MYBL1 (chr 8) and either

PCDHGA1 (chr 5)
MMP16 (chr 8)
MAML2 (chr 11)
(usually NOT QKI, which is the angiocentric one)

Question 14

Why does the H3K27me3 methylation IHC work

Answer 14

Because when there’s a mutation, the H3 can’t encode the methyltransferase PRC2 (Ezh2) and that can’t put the methyl on, so it loses the methylation

Question 15

What is it about the PFA ependymomas that makes it lose H327me3 staining?

Answer 15

Overexpression of EZHIP, not bc an H3 mutation is present!
(they still have a bad prognosis!)

Question 16

GENES: infant-type hemispheric glioma

Answer 16

NTRK
ALK
ROS1
MET
Receptor tyrosine kinase fusions

Question 17

what is the most common molecular alteration a/w meningiomas? (any meningioma, not just subtypes)

Answer 17

22q loss/inactivation of NF2

Question 18

what molecular alterations are most commonly a/w angiomatous and microcystic meningiomas?

Answer 18

polysomy 5 & 20

Question 19

what is the most important prognostic cytogenetic alteration in meningiomas that are non-grade-1?

Answer 19

loss of 1p

Question 20

what is the molecular alteration you should immediately associate with grade 3 meningiomas?

Answer 20

CDKN2A/B homozygous inactivation
i.e. loss of 9p

Question 21

what syndrome is a/w polyostotic fibrous dysplasia?

Answer 21

McCune-Albright syndrome

Question 22

mut a/w sft

Answer 22

NAB2::STAT6 fusion

Question 23

what stain do you use for SFT?

Answer 23

STAT6 (nuclear+)

Question 24

what stain do you use for chordoma?

Answer 24

brachyury (nuclear+)

Question 25

what does poorly-differentiated chordoma have on IHC?

Answer 25

nuclear brachyury (just like regular chordoma)
LOSS of INI1 (same as AT/RT) bc this is the driver mutation in them actually (ugh)