CNS Flashcards
medulloblastoma subgroups, epi, associated mutations, px
WNT (10%): CTNNB1, monosomy 6, DDX3X, APC
- best px, >90%
SHH (30%): PTCH1, PTCH2, SMO, SUFU, TP53
- 75% desmoplastic/nodular (TP53 WT) - OS 80%
- LC/A OS <50%
Group 3 (25%): i17q, MYCN amp (15%)
- worst px, 50-70% (worse with MYCN)
Group 4 (40%): i17q, MYCN amp, CDK6 amp
- 75%
medulloblastoma histo subgropus
classic
desmoplastic/nodular
extensive nodularity (MBEN)
large cell/anaplastic
Medulloblastoma staging
post op MR brain/spine
CSF 14d post op
M0: none
M1: CSF +
M2: gross nodular seeding subarachnoid
M3: gross nodular seeding spinal subarachnoid
M4: extraneural mets
Medulloblastoma risk stratification and associated px
Average: M0, <1.5 cm2 residual, undifferentiated histo, >3yo
- 5yDFS >80%
High
- 5yOS 40-6%
- <3yo except MBEN which ash excellent px
craniopharyngioma px factors
extent of resection (goal GTR)
younger age
craniopharyngioma tx
Controversial
maximal safe resection
- high perioperative M+M
STR -> RT
Omira reservoir (cyst drainage)
intracystic decompression and chemo (interferon alpha, bleo)
peglyated interferon alpha
BRAFi
CNS tumors dx without biopsy
DIPG: imaging expansile pons
NSGCT: bHCG/AFP
Optic pathway glioma in NF1
Pilocytic astrocyoma mutations
BRAF-KIAA1549 fusion (60-80%
BRAF V600E (10-15%)
CNS GCT tumor markers
Choriocarcinoma: bHCG
NGGCT: bHCG, AFP
embryonal carc or yolk sac: AFP
syncytiotrophoblastic germinoma: bHCG
pure germinoma or mature teratoma: negative all
CNS germinoma 2nd look indications
residual disease (>1.5cm)
progressive disease w normal tumor markers
CNS germinoma vs NGGCT tx, px
Germinoma:
- biopsy
- chemo x4 (carbo/etop)
- +- 2nd look
- response based RT, minimum whole ventricular
NGGCT:
- optional biopsy (nonsecreting)
- chemo x6
- CSI if no viable tumor
- HDC + ASCT if viable tumor
Germinoma 5yDFS >90%
NGGCT: EFS 80-90%
ependymoma px factors
Poor:
- <GTR
- no RT
- younger age
- PF-A 1q gain
- 6q loss
- anaplastic histo
- PF-A and RELA
ependymoma grading
grade I: subependymoma; rare in children
grade I: myxopapillary
grade II: papillary, clear cell, tancytic
grade II-III: RELA fusion, anaplastic
CNS elevated bHCG DDx
syncytiotrophoblastic germinoma
choriocarcinoma
mixed GCT
NGGCT (with AFP)
immature teratoma
CNS elevated AFP DDx
NGGCT (w bHCG)
embryonal carcinoma
yolk sac tumor
mixed GCT
immature teratoma
midline posterior fossa mass DDx
medulloblastoma (more likely group 3 or 4)
DIPG
glioma
CNS GCT
NF1 optic pathway glioma mutation and tx
BRAF V600E
vinblastine
carbo/VCR
MEK inhibitor (trametinib)
BRAF inhibitor (vemurafenib)
if not NF1:
TPCV: thio, procarbazine, CCNU, VCR
Ependymoma mutations and tx
PF-A: 1q gain, 6q loss
Supratentorial: RELA fusion, YAP1 fusion
GTR –> RT (focal 59.4 Gy)
Medulloblastoma px by subgroup
1) WNT: >90%
2) SHH: 80% if desmoplastic/nodula, <50% if LC/A
3) Group 4: 75%
4) Group 3: 50-70%
Medulloblastoma tx (incl RT doses)
GTR
adj RT
- CSI 23.4 Gy (if mets 36 Gy)
- involved field boost to 54 Gy
adj chemo: VCR, carbo, cyclo, etop, cisplat, MTX
DIPG imaging findings
midline
>50% of pons
hyperdense
MR hyperintense (dark T1, bright T2)
DIPG mutation if biopsied
H3K27M mutation (80-90%
H3K27me3
DIPG tx and px
palliative RT: focal 54Gy
symptomatic CS
median survival 10 mo
posterior fossa syndrome features
onset 1-3d post op, peak 2w
mutism (transient)
emotional lability
hypotonia
oropharyngeal dysfxn
dysphagia
CN palsies
RT S/E acute, subacute, late
acute: fatigue, N/V, skin/hair, h/a
subacute: somnolence, pseudoprogression, edema
late
- brain necrosis
- SMN: glioma, meningioma, 4-5% at 10y
cognitive
- ototox
- cerebrovascular disease
- endo: GH defic, delayed puberty
- infertility
HGG mutations
H3K27 mutation
adolescents: IDH1 mutation
CNS tumor epi
Astrocytoma 40-50%
medullo 20%
ependymoma 10%
HGG 10%
craniopharyngioma 5-10%
choroid plexus 1-2%
ATRT 1-2%
GCT 1-3%
cerebral hemisphere tumor DDx
glioma
meningioma
ETMR (previously PNET)
anaplastic astrocytoma
pineal tumor DDx
GCT (until proven otherwise)
pineoblastoma
astrocytoma
sellar/suprasellar tumor DDx
craniopharyngioma
GCT
optic glioma
cerebellar tumor DDx
medullo
ependymoma
cerebellar astrocytoma (JPA)
brain stem tumor DDx
medullo
JPA
ETMR (previously PNET)
infant posterior fossa tumor DDx
medullo
DIPG
LGG
Ependymoma
ATRT
ventricular tumor DDx
CPP
CPC
neurocytoma
spinal cord tumor DDx
astrocytoma
ependymoma
extradural: NBl, ewing, neurofibroma
NF2 CNS tumors
acoustic schwannoma (bilat)
meningioma
ependymoma
LFS CNS tumors
medullo
GBM
HGG
FAP (Turcot) CNS tumors
medullo (WNT)
GBM
HGG
PNET
Gorlin CNS tumors
desmoplastic medullo
meningioma
BCC
T21 and Klinefelter CNS tumors
germinoma
DICER-1 CNS tumor
pineoblastoma
ATRT px factors
poor
<3yo
infratentorial
disseminated
germline mutation (SMARCB1)
myxopapillary ependymoma features and tx
WHO Grade 1
classically at conus
GTR + RT
define parinaud syndrome, and DDx
bilateral upgaze palsy
convergence nystagmus
light near dissociation
lid retraction (Collier sign)
GCT (germinoma)
choriocarcinoma
immature teratoma
LGG path and DDx
WHO I-II
lack of aggressive features
pilocytic astrocytoma
SEGA
ganglioglioma
oligodendroglioma
DNET (dysembryoplastic neuroepithelial tumor)
DIG (desmoplastic infantile ganglioglioma)
LGG locations
cerebellum (15-25%)
cerebral (10-15%)
deep midline (10-15%)
optic pathway (5%)
brainstem (2-4%)
LGG staging
MR head/spine
Biopsy - not if NF-1
(no CSF)
no metastatic potential
LGG genetics and targeted tx
BRAF-KIAA1549 fusion
BRAF V600E
MEK or BRAF inhibitor
LGG tx, px
GTR
STR –>
weekly vinblastine
carbo/VCR
MEK/BRAF inhibitor
NF1: observation
SEGA: mTOR
GTR 5yPFS >90%
HGG tx
resection
focal RT
+- chemo - ?VCR/carbo
Ependymoma tx
GTR
RT - focal or CSI if CSF+
NF1 OPG epi
NF-1: 15-20% have LGG
OPG: 70% have NF-1
Diencephalic syndrome
diencephalon location
typically young children
happy FTT
hyperkinesis
macrocephaly
neuro: visual field defect, endocrine dysfxn, behaviour change, h/a
2yo with 4 mo of FTT NYD. Recent vomiting and nystagmus. MRI reveals large hypothalamic mass with associated hydrocephalus. Syndrome?
Diencephalic syndrome
List high grade gliomas
anaplastic astrocytoma
anaplastic oligodendroglioma
GBM
mixed glial tumors
DIPG
pleomorphic xanthoastrocytoma
LGG vs HGG locations
LGG: 20% cerebellar; hemispheric, optic pathway, brainstem
HGG: hemispheric, midline
HGG predispositions
GBM: NF-1, LFS, Turcot
Anaplastic astrocytoma: NF-1, LFS, Turcot, TS
Hx RT
GBM imaging
thick irregular margin
necrotic core
+- hemorrhage
Craniopharyngioma imaging
sellar/suprasellar
rim calcifications
cystic
enhancing
ATRT histopathology
SRBC
loss of INI-1 (SMARCB1)
Germline SMARCB1 mutation 35% (80% <1yo)
EMRT epi, tx, px
presentation ~3yo
2/3 supratentorial
1/2 mets
max safe resection
CSI
HD chemo w ASCT
very poor - 5yOS 15-35%
ATRT epi, ix
median age 1y (2/3 <3yo)
anywhere in brain
30% mets (including kidney, skin, liver)
MR brain and spine
CSF
AUS
ATRT tx, px
GTR
+-2nd look
chemo
+-HD chemo w ASCT
RT (CSI if disseminated)
4yEFS 37%, OS 43%
pineoblastoma location, presentation, genetics, px
supratentorial
hydrocephalus, Parinaud
RB1, DICER1 germline
OS 50-60%
choroid plexus tumor location
75% lateral ventricle
15% 4th ventricle
10% 3rd ventricle
CPP vs CPC grade, tx
CPP: grade I
aCPP: grade II
CPC: grade III-IV (20-40%)
CPP: Sx (GTR alone)
aCPP: Sx -> chemo
CPC:
- Sx
- +-2nd look
- chemo (ICE)
- +- RT if <CR
GCT location + presentation, mets?
50% pineal (Parinaud syndrome)
40% suprasellar (DI, altered puberty, visual defect)
mets 30%
Ependymoma location, mets
anywhere
70% infratentorial
30% supratentorial
rare spinal
10-15% mets
Ependymoma px factors
poor:
subtotal resection
PF-A +1q
-6q
younger
anaplastic
less/no RT
Ependymoma tx, px
GTR
focal RT (CSI if disseminated)
EFS 60-80%
- PF-A worse (PFS 33% OS 70%)
- PF-B better (PFS 63% OS 100%)
- YAP1 better (PFS 66%, OS 100%)
- RELA worse (PFS 30% OS 75%
DIPG presentation
triad
- long tract signs
- contralateral CN palsy
- ataxia
neuro GCT px
Good risk >90%
- germinoma, mature teratoma
int px 70%
poor risk 40%
- choriocarcinoma, yolk sac, embryonal
which CNS tumors need CSF for staging
MEGA:
- Medullo
- Ependymoma
- GCT
- ATRT
summarize ependymoma
10% peds CNS
infant PF, old supratentorial
mets 10-15%
PF-A, PF-B, RELA, YAP1
GTR -> focal RT (CSI if CNS+)
px 60-80%
Poor px: PF-A, YAP1, +1q, -6p
choroid plexus imaging
nonobstructive hydrocephalus
cauliflower appearance
++ enhancement
CPC genetics
25-45% TP53
