Brain tumours Flashcards by Reena Pabari

what brain tumours are associated with NF2?

acoustic schwannomas, ependymomas, meningiomas

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what brain tumours are associated with NF1?

LGG

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what brain tumours are associated with p53 mutations?

HGG

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what is the characteristic mutation in DIPG

H3 K27M

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what three chemotherapy regimens are used in LGG?

carboplatin/vincristine, vinblastine alone,

thioguanine, procarbazine, CCNU, and vincristine (TPCV)

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abnormalities of what pathway are found in LGG?

MAPK

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what is the most common abnormality found in LGG?

BRAF KIAA1549 fusion (found in 60%)

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what are the high-grade gliomas?

GBM (IDH wt, IDH mutant)
Anaplastic astrocytoma
DIPG (H3K27M mutant)

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what are the low grade gliomas?

diffuse astrocytoma
pilocytic astrocytoma
PXA
SEGA

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Top 3 brain tumours in childhood

gliomas
medulloblastoma
ependymoma

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What condition predisposes to LGG? (name gene)

20% of patients with NF1 develop LGG (commonly OPG)

Gene: NF1 (17q11.2)

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What does dabrafenib do?

BRAF inhibitor works in V600E mutated tumours

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what does trametinib do?

MEK inhibitor works in KIAA1549 BRAF fusion

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what tumour are patients with tuberous sclerosis predisposed to develop?

subependymal giant cell astrocytoma (SEGA)

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what targeted treatment can you consider for SEGAs

sirolimus, everolimus (mTOR inhibitor)

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what types of tumours do patients with LFS develop

Adrenocorticocarcinoma, HGG, sarcomas, choroid plexus carcinomas, medulloblastoma

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what gene causes Gorlin syndrome?

PTCH1
aka nevoid basal cell carcinoma syndrome
increased risk of medulloblastoma (SHH-activated)

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what conditions are due to mutations in APC

Familial adenomatous polyposis (gardner, turcot)

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what is lynch syndrome

hereditary non-polyposis colorectal cancer (HNPCC), endometrial cancer, ovarian, stomach etc. Due to MMR

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what germline mutations predispose to rhabdoid tumours

SMARCB1 (loss of INI1)

SMARCA4 (loss of BRG1)

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six side effects of brain RT (early / late)

fatigue
rash
cognitive impairment
edema
parotitis
late: meningiomas, SMNs, endocrinopathies, cerebrovascular events, blindness , ototoxicity

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most common locations of LGG

cerebellar, hemispheric, OPG

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how do you stage a LGG

MRI brain (only do spine if there are concerning symptoms)

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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

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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)