Brain tumours Flashcards
what brain tumours are associated with NF2?
acoustic schwannomas, ependymomas, meningiomas
what brain tumours are associated with NF1?
LGG
what brain tumours are associated with p53 mutations?
HGG
what is the characteristic mutation in DIPG
H3 K27M
what three chemotherapy regimens are used in LGG?
carboplatin/vincristine, vinblastine alone,
thioguanine, procarbazine, CCNU, and vincristine (TPCV)
abnormalities of what pathway are found in LGG?
MAPK
what is the most common abnormality found in LGG?
BRAF KIAA1549 fusion (found in 60%)
what are the high-grade gliomas?
GBM (IDH wt, IDH mutant)
Anaplastic astrocytoma
DIPG (H3K27M mutant)
what are the low grade gliomas?
diffuse astrocytoma
pilocytic astrocytoma
PXA
SEGA
Top 3 brain tumours in childhood
- gliomas
- medulloblastoma
- ependymoma
What condition predisposes to LGG? (name gene)
20% of patients with NF1 develop LGG (commonly OPG)
Gene: NF1 (17q11.2)
What does dabrafenib do?
BRAF inhibitor works in V600E mutated tumours
what does trametinib do?
MEK inhibitor works in KIAA1549 BRAF fusion
what tumour are patients with tuberous sclerosis predisposed to develop?
subependymal giant cell astrocytoma (SEGA)
what targeted treatment can you consider for SEGAs
sirolimus, everolimus (mTOR inhibitor)
what types of tumours do patients with LFS develop
Adrenocorticocarcinoma, HGG, sarcomas, choroid plexus carcinomas, medulloblastoma
what gene causes Gorlin syndrome?
PTCH1
aka nevoid basal cell carcinoma syndrome
increased risk of medulloblastoma (SHH-activated)
what conditions are due to mutations in APC
Familial adenomatous polyposis (gardner, turcot)
what is lynch syndrome
hereditary non-polyposis colorectal cancer (HNPCC), endometrial cancer, ovarian, stomach etc. Due to MMR
what germline mutations predispose to rhabdoid tumours
SMARCB1 (loss of INI1)
SMARCA4 (loss of BRG1)
six side effects of brain RT (early / late)
- fatigue
- rash
- cognitive impairment
- edema
- parotitis
- late: meningiomas, SMNs, endocrinopathies, cerebrovascular events, blindness , ototoxicity
most common locations of LGG
cerebellar, hemispheric, OPG
how do you stage a LGG
MRI brain (only do spine if there are concerning symptoms)
A LGG in cerebellum - what genetic aberration are you likely to find?
BRAF KIAA1549 fusion
74%) - less likely to be BRAF V600E (only 4% are in cerebellum
prognostic factors for LGG
- GTR
- location (optic nerve > optic pathway/chiasm)
- mets
- intracranial htn at presentation
- nf1 (better outcomes)
- BRAF KIAA1549 fusion (better)
- BRAF V600E mutation (more invasive)
chemo for LGG
carbo + vincristine
TPCV (thioguanine, procarbazine, CCNU, vincristine)
vinblastine monotherapy
three brain tumours that do not need biopsy
DIPG
NGGCT (secreting)
OPG (NF1)
tumours in what area can cause parinaud syndrome
tectum, pineal gland (midbrain) - caused by compression of the medial longitudinal fasiculus
what conditions increase the risk of HGG?
p53
APC mutations (FAP)
exposure to RT
prognostic factors for HGG
H3K27M (poor) IDH-1 mutant (favourable) Histology (AA better than GBM) H3 G34 mutations - intermediate prognosis, older cildren BRAF V600E (PXA-like) - favourable MYC-N amp - poor
Chemo for HGG
Lomustine (CCNU), vincristine, prednisone
how does DIPG present
short duration of symptoms, classic triad:
- long tract signs
- cranial nerve palsy
- ataxia
Treatment of craniopharyngioma
- Maximal surgery
- If GTR obtained; observe only
- If
What neuroendocrinopathies are seen with craniopharyngioma?
growth hormone deficiency (in 100%) amenorrhea DI adrenal insufficiency hypothyroidism
when do ATRTs present
Present in infancy, young children
75% in age < 3 yr of age
Most common malignant tumour in age <6m
how do you stage ATRT
MRI brain/spine, CSF, renal US (to look for synchronous renal rhabdoid if high suspicion for germline mutation)
what targeted therapy can be used to tumours with SMARCB1 mutations?
EZH2 inhibitors (tazemetostat)
treatment of ATRT
GTR
RT
High dose chemotherapy with alkylators followed by stem cell rescue
where do choroid plexus tumours present
usually lateral ventricles
which GCTs secrete AFP?
yolk sac tumours
which GCTs secrete b-HCG?
choriocarcinoma
types of NGGCT
choriocarcinoma yolk sac tumour teratoma embryonal carcinoma mixed
where does ependymoma most commonly present
posterior fossa - 55% infratentorial
genetic aberrations in supratentorial ependymoma
RELA positive (70% of supratentorial ependymomas), YAP1 fusion positive (young children, very good prognosis)
what are prognostic features in ependymoma
- gain of chr 1q (poor)
- YAP fusion (good)
- anaplastic
- extent of resection
RT in ependymoma
54 Gy - can be focal (no need for CSI unless multifocal tumour / disseminated disease)
what are the four histologic patterns in medulloblastoma
- classic
- medulloblastoma with extensive nodularity (MBEN)
- desmoplastic
- anaplastic
standard risk medullo
> 3 yrs
GTR < 1.5 cm3 residual
no metastasis
not anaplastic
high risk medullo
> 1.5cm3 residual disease
mets by spine MRI or lumbar CSF
diffusely anaplastic histology
medullo subgroups
Wnt-activated
Shh-activated
Group 3
Group 4
what type of medullo affects infants
Group 3 (most common) Shh-activated
Genetic aberrations in Wnt-activated medullo
beta-catenin (CTNNB1)
monosomy 6 (85%)
SMARCA4 (25%)
associated with germline APC mutations (rare, < 5%)
Genetic aberrations in Shh-activated medullo
PTCH1, SUFU
Can have Myc-n amplification
Genetic aberrations in group 3 medullo
can have myc-n amplification (15%)
SMARCA4 mutations (10%)
i17q
Often infants, metastatic at presentation
Genetic aberrations in group 4 medullo
can have myc-n amplification
i17q enriched
can have whole chr 11 loss (good prognosis)
what age group does better in Wnt-activated medullo?
< 16 yrs
which medullo subgroup is associated with p53 mutations
Shh-activated
treatment for SR medullo
GTR if possible
CSI with lower dose (23.4 Gy) with boost to posterior fossa + weekly VCR followed by maintenance cisplatin-based chemotherapy
treatment for HR medullo
GTR if possible
CSI with regular dose (36 Gy with boost to post fossa to 54 Gy) + weekly VCR followed by maintenance chemo (cisplat, VCR, cyclo)
other tumours with BRAF V600E mutation or KIAA1549 fusion
- melanomas (Spitzoid)
- papillary thyroid cancers
- acinar pancreatic carcinomas
- non-small‐cell lung cancers
- colorectal cancers
- papillary craniopharyngioma
what genetic aberration is seen in craniopharyngioma in children
activating mutations of beta-catenin
non-surgical options in craniopharyngioma management
- Radiotherapy
- Intracystic therapy - ie, Interferon-α 2a, bleomycin
- Cyst drainage (can be done via ommaya)
- Systemic interferon (generally for recurrent cranio)
