Brain tumors Flashcards
What is the differential diagnosis of a spine tumor (3)?
1) Low grade astrocytomas
2) Ependymomas
3) AA/GBM (much less commonly)
What is the differential diagnosis of a posterior fossa tumor (5)?
1) Pilocytic astrocytoma
2) Medulloblastoma
3) Ependymoma
4) ATRT
5) DIPG
How would you differentiate on imaging a brainstem diffuse midline glioma vs pilocytic astrocytoma?
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
Which brain tumors don’t need to be biopsied for Dx?
1) NG-GCT (if positive tumor markers)
2) Diffuse midline glioma H3K27M mutant, unless atypical features
Which brain tumors are usually not considered for radiation therapy?
1) Choroid plexus carcinoma
2) LGG, unless failure of other options
What is the common radiological appearance of pilocytic astrocytoma?
Most often cerebellar location (but can happen anywhere), contrast-enhancing, bright on T2, classically nodule with cyst
What targeted therapy could be considered if…
a) BRAF fusion
b) BRAF V600E mutation
a) MEK inhibitor e.g. trametinib
b) BRAF inhibitor
Staging: LGG and HGG
MRI of brain +/- spine
No metastatic potential outside the CNS
Prognosis of HGG
Anaplastic astrocytoma: 30% (GTR and adjuvant chemo)
GBM: EFS 18%
What is the OS for
a) Germinoma
b) NGGCT
a) Germinoma:
OS>90%
b) NGGCT
OS 70%
What is growing teratoma syndrome?
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
Germinoma: treatment
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)
Treatment: NGGCT
- 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
Epidemiology of GCT (CNS)
a) Histologic subtypes
b) Sex predominance
A) 60-70% Germinomas
30-40% NGGCT
b) Male prédominance in general
Pineal region: 15M:1F
Suprasellar region: slight female predominance
RF for brain tumors
- Ionizing radiation (meningioma, HGG, sarcoma)
- Immunosuppression (CNS lymphoma)
- Specific genetic conditions (differs for each brain tumors)
No proven environmental factor
Describe histologic features PA
- Rosenthal fibers
- Eosinophilic granular bodies
- GFAP (+)ve
- Low mitosis rate (MIB1 < 4%)
LGG: prognosis
OS: very good (>90%)
PFS: depends on the location; about 50% in unresectable lesions
Classical presentation of optic pathway glioma
- Visual loss
- Proptosis
- Optic nerve atrophy
Clinical course very variable, usually more indolent in NF1-OPG
OPG: treatment considerations
- 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
HGG: prognosis as per grade and degree of resection
Anaplastic astrocytoma: With GTR: 44% W/O GTR: 22% GBM: With GTR: 26% W/O GTR: 4%
ATRT: typical histology
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)
Prognostic factors: HGG
- WHO grade
- Gross total resection
- Biologic markers
(+)ve: PTEN, MGMT methylation, (-)ve: p53, endoglin, PARP positivity
MIB1 (mitosis rate)
DIPG: what treatment options are available in case of reprogression?
Only repeat radiation therapy have shown effect
What mutation is often encountered in craniopharyngioma?
Papillary subtype: BRAF v600E
Adamantinomatous: b-catenin
Craniopharyngioma: standard treatment for newly diagnosed CPG
- 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
ATRT: typical histology
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)
Epidemiology of ATRT
1-2% of childhood brain tumors
Male predominance, mostly in infants < 3 y.o.
WHO classification of choroid plexus tumors
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
Ependymomas: unfavorable prognostic factors (7), as per cancer.gov
- 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)
CP carcinoma: what is the standard treatment
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
CP tumors: prognosis
CPP: 80% at 5 y
CPC: 40% at 5 y
CPC: associated genetic abnormality
p53 mutation (Li-Fraumeni syndrome)
Ependymoma: typical imaging appearance
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
Ependymomas: unfavorable prognostic factors
- Younger age
- Higher proliferation rate (MIB1)
- Subtotal resection
- Controversial: anaplastic histology
- ?Subgroup A in posterior fossa ependymoma
Posterior fossa syndrome
- Incidence
- 4 symptoms
- Natural history
- Appears in 10-20% of pts following PF surgery
- Sx: mutism, ataxia, personnality changes, hypotonia, reduced oral intake
- Variable recovery over days to months
2 complications following posterior fossa neurosurgery
Aseptic meningitis
Posterior fossa syndrome (or cerebellar mutism)
Genetic syndromes associated with medulloblastoma (3)
- Gorlin syndrome (nevoid basal cell carcinoma synd)
- Li-Fraumeni syndrome
- Turcot syndrome
Medulloblastoma type WNT
- Histology?
- Molecular features?
- Prognosis?
- Mostly classic histology
- B-catenin, Turcot synd, monosomy 6
- Excellent prognosis
Medulloblastoma type SHH
- Affected populations?
- Histology?
- Molecular features?
- Prognosis?
- Infants, adults, occ children
- Desmoplastic, MBEN, classic, LCA
- PTCH11/SMO/SUFU, Gorlin synd, GLI2 amplification
- Ranges from fair to poor (if (+)ve TP53)
Medulloblastoma Group 3
- Affected populations?
- Histology
- Molecular features?
- Prognosis?
- Children, male predominance
- Classic, LCA (most LCA tumors are Group 3)
- i17q, MYC amplification
- Poor (very commonly metastatic)
Medulloblastoma Group 4
- Affected populations?
- Molecular features?
- Prognosis?
- Children, infants and adults to lesser extent
Male predominance - CKD6, MYCN amplification; i17q
- Intermediate (frequently metastatic)
Prognostic factors in craniopharyngioma
- Extent of surgical resection
- Focal radiation
- Size of tumors
- Presence of cystic components
Histological subtypes of medulloblastoma (4)
- Classic
- Desmoplastic/nodular
- MB with extensive nodularity
- Large cell anaplastic
Most predictive factor for recovery in posterior fossa tumor?
Initial level of severity
Prognosis for craniopharyngioma
OS > 90%
EFS 65%
Prognostic factors (5) for craniopharyngioma
- 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
Late effects of craniopharyngioma
- Neurocognitive, memory impairments
- Vision loss (commonly hemianopsia)
- Endocrinopathies
- Obesity
- Second malignancies
- Vascular disease, stroke
