Brain tumors

Question 1

What is the differential diagnosis of a spine tumor (3)?

Answer 1

1) Low grade astrocytomas
2) Ependymomas
3) AA/GBM (much less commonly)

Question 2

What is the differential diagnosis of a posterior fossa tumor (5)?

Answer 2

1) Pilocytic astrocytoma
2) Medulloblastoma
3) Ependymoma
4) ATRT
5) DIPG

Question 3

How would you differentiate on imaging a brainstem diffuse midline glioma vs pilocytic astrocytoma?

Answer 3

DIPG (diffuse midline glioma H3K27M mutant): diffuse, commonly but not always in the pons, encasing basilar artery
PA: exophytic, bright post-gad, can occur anywhere in the brainsteam

Question 4

Which brain tumors don’t need to be biopsied for Dx?

Answer 4

1) NG-GCT (if positive tumor markers)

2) Diffuse midline glioma H3K27M mutant, unless atypical features

Question 5

Which brain tumors are usually not considered for radiation therapy?

Answer 5

1) Choroid plexus carcinoma

2) LGG, unless failure of other options

Question 6

What is the common radiological appearance of pilocytic astrocytoma?

Answer 6

Most often cerebellar location (but can happen anywhere), contrast-enhancing, bright on T2, classically nodule with cyst

Question 7

What targeted therapy could be considered if…

a) BRAF fusion
b) BRAF V600E mutation

Answer 7

a) MEK inhibitor e.g. trametinib

b) BRAF inhibitor

Question 8

Staging: LGG and HGG

Answer 8

MRI of brain +/- spine

No metastatic potential outside the CNS

Question 9

Prognosis of HGG

Answer 9

Anaplastic astrocytoma: 30% (GTR and adjuvant chemo)

GBM: EFS 18%

Question 10

What is the OS for
a) Germinoma

b) NGGCT

Answer 10

a) Germinoma:
OS>90%

b) NGGCT
OS 70%

Question 11

What is growing teratoma syndrome?

Answer 11

Syndrome associated with NGGCT(pathology invariably mature teratoma)

Rapid radiological enlargement with progressive decrease of tumor markers

Treatment: surgical resection, ideally gross total extirpation followed by RT

Question 12

Germinoma: treatment

Answer 12

Localized:
Chemotherapy (carboplatin-etoposide, or ifosphamide-etoposide-carboplatin) followed by radiation (whole ventricular RT 24Gy with tumor boost 16Gy)
COG testing lower RT dose
In new trial

Metastatic:
Chemotherapy (carboplatin-etoposide, or ifosphamide-etoposide-carboplatin) followed by radiation (craniospinal RT with tumor boost)

Question 13

Treatment: NGGCT

Answer 13

• Chemotherapy (platinum based, for example ifos-carbo-etoposide)
  followed by
• RT: volume and dose debated; COG does CSI at 36Gy with tumor boost
• Surgical excision for mature teratoma and benign immature teratoma

Question 14

Epidemiology of GCT (CNS)
a) Histologic subtypes

b) Sex predominance

Answer 14

A) 60-70% Germinomas
30-40% NGGCT

b) Male prédominance in general
Pineal region: 15M:1F
Suprasellar region: slight female predominance

Question 15

RF for brain tumors

Answer 15

• Ionizing radiation (meningioma, HGG, sarcoma)
• Immunosuppression (CNS lymphoma)
• Specific genetic conditions (differs for each brain tumors)
  No proven environmental factor

Question 16

Describe histologic features PA

Answer 16

• Rosenthal fibers
• Eosinophilic granular bodies
• GFAP (+)ve
• Low mitosis rate (MIB1 < 4%)

Question 17

LGG: prognosis

Answer 17

OS: very good (>90%)
PFS: depends on the location; about 50% in unresectable lesions

Question 18

Classical presentation of optic pathway glioma

Answer 18

• Visual loss
• Proptosis
• Optic nerve atrophy
  Clinical course very variable, usually more indolent in NF1-OPG

Question 19

OPG: treatment considerations

Answer 19

• First line of treatment = chemotherapy
  re; risk associated with surgery
  VCR/carbo and TPCV have shown similar efficacy
• TPCV shouldn’t be used in NF1 patients re: risk of malignancies with alkylators

Question 20

HGG: prognosis as per grade and degree of resection

Answer 20

Anaplastic astrocytoma:
With GTR: 44%
W/O GTR: 22%
GBM:
With GTR: 26%
W/O GTR: 4%

Question 21

ATRT: typical histology

Answer 21

Eosinophilic nucleus, with prominent eosinophilic nucleoli, abundant cytoplasm, and eosinophilic globular cytoplasmic inclusion

Histology might be misleading (e.g. areas of small round blue cells), so diagnostic mostly based on loss of SMARCB1 (FISH or immunostaining)

Question 22

Prognostic factors: HGG

Answer 22

• WHO grade
• Gross total resection
• Biologic markers
  (+)ve: PTEN, MGMT methylation, (-)ve: p53, endoglin, PARP positivity
  MIB1 (mitosis rate)

Question 23

DIPG: what treatment options are available in case of reprogression?

Answer 23

Only repeat radiation therapy have shown effect

Question 24

What mutation is often encountered in craniopharyngioma?

Answer 24

Papillary subtype: BRAF v600E

Adamantinomatous: b-catenin

Question 25

Craniopharyngioma: standard treatment for newly diagnosed CPG

Answer 25

- Resection, total if possible - Radiation therapy if subtotal resection can be considered - Intracystic sclerosing agents (interferon, bleomycin) can be used as temporizing agents for the cystic part

Question 26

ATRT: typical histology

Answer 26

Eosinophilic nucelus, with prominent eosinophilic nucleoli, abundant cytoplasm, and eosinophilic globular cytoplasmic inclusion Histology might be misleading (e.g. areas of small round blue cells), so diagnostic mostly based on loss of SMARCB1 (FISH or immunostaining)

Question 27

Epidemiology of ATRT

Answer 27

1-2% of childhood brain tumors | Male predominance, mostly in infants < 3 y.o.

Question 28

WHO classification of choroid plexus tumors

Answer 28

WHO grade I = CP papilloma; closely resemble normal CP with low proliferation rate WHO grade II = atypical papilloma; CPP with increased mitotic activity WHO grade III = CP carcinoma; higher cell density, freq mitosis, high N/C ratio, necrosis, invasive appearance

Question 29

Ependymomas: unfavorable prognostic factors (7), as per cancer.gov

Answer 29

- Younger age - Higher proliferation rate (Ki67, MIB1) - Location: cranial < spinal (lower) < spinal (higher) - Subtotal resection - Anaplastic histology - Lower doses of radiation therapy (should be at least 54Gy) - Genomic expression profile (e.g. subgroup A in posterior fossa ependymoma)

Question 30

CP carcinoma: what is the standard treatment

Answer 30

Maximal surgical resection Usually with chemotherapy (re: mostly infants < 3 months); no SOC of care but multiagent chemo such as carboplatin-etoposide has shown good activity

Question 31

CP tumors: prognosis

Answer 31

CPP: 80% at 5 y CPC: 40% at 5 y

Question 32

CPC: associated genetic abnormality

Answer 32

p53 mutation (Li-Fraumeni syndrome)

Question 33

Ependymoma: typical imaging appearance

Answer 33

homogenously enhancing, well circumscribed solid mass, extending out of one of the foramina of Luschka or Magendie with obstructive HC; Classically wrap around brainstem or herniate trough the foramen magnum

Question 34

Ependymomas: unfavorable prognostic factors

Answer 34

- Younger age - Higher proliferation rate (MIB1) - Subtotal resection - Controversial: anaplastic histology - ?Subgroup A in posterior fossa ependymoma

Question 35

Posterior fossa syndrome - Incidence - 4 symptoms - Natural history

Answer 35

- Appears in 10-20% of pts following PF surgery - Sx: mutism, ataxia, personnality changes, hypotonia, reduced oral intake - Variable recovery over days to months

Question 36

2 complications following posterior fossa neurosurgery

Answer 36

Aseptic meningitis | Posterior fossa syndrome (or cerebellar mutism)

Question 37

Genetic syndromes associated with medulloblastoma (3)

Answer 37

- Gorlin syndrome (nevoid basal cell carcinoma synd) - Li-Fraumeni syndrome - Turcot syndrome

Question 38

Medulloblastoma type WNT - Histology? - Molecular features? - Prognosis?

Answer 38

- Mostly classic histology - B-catenin, Turcot synd, monosomy 6 - Excellent prognosis

Question 39

Medulloblastoma type SHH - Affected populations? - Histology? - Molecular features? - Prognosis?

Answer 39

- Infants, adults, occ children - Desmoplastic, MBEN, classic, LCA - PTCH11/SMO/SUFU, Gorlin synd, GLI2 amplification - Ranges from fair to poor (if (+)ve TP53)

Question 40

Medulloblastoma Group 3 - Affected populations? - Histology - Molecular features? - Prognosis?

Answer 40

- Children, male predominance - Classic, LCA (most LCA tumors are Group 3) - i17q, MYC amplification - Poor (very commonly metastatic)

Question 41

Medulloblastoma Group 4 - Affected populations? - Molecular features? - Prognosis?

Answer 41

- Children, infants and adults to lesser extent Male predominance - CKD6, MYCN amplification; i17q - Intermediate (frequently metastatic)

Question 42

Prognostic factors in craniopharyngioma

Answer 42

- Extent of surgical resection - Focal radiation - Size of tumors - Presence of cystic components

Question 43

Histological subtypes of medulloblastoma (4)

Answer 43

- Classic - Desmoplastic/nodular - MB with extensive nodularity - Large cell anaplastic

Question 44

Most predictive factor for recovery in posterior fossa tumor?

Answer 44

Initial level of severity

Question 45

Prognosis for craniopharyngioma

Answer 45

OS > 90% | EFS 65%

Question 46

Prognostic factors (5) for craniopharyngioma

Answer 46

- Resectability - Addition of radiation for subtotal resection (leads to comparable outcomes than GTR) - Age (better if older than 5 y.o.) - Subtype (adamantinous more locally aggressive) - Type: purely cystic seems better than mixed or solid lesions

Question 47

Late effects of craniopharyngioma

Answer 47

- Neurocognitive, memory impairments - Vision loss (commonly hemianopsia) - Endocrinopathies - Obesity - Second malignancies - Vascular disease, stroke