Neuro-oncology Flashcards
What are the two main classifications of CNS tumors based on their origins?
- Primary - tumors that originated within the CNS
- Secondary (metastases) - 10x more frequent than primary tumors in adults (30% of patients with systemic cancer)
What are the classification of CNS tumors based on their location?
- Extra-axial (coverings)
- Tumors of bone, cranial soft tissue, meninges, nerves, metastatic deposits
- Intra-axial (parenchymal)
- Derived from the normal cell populations of the CNS (glia, neurons, vessels, connective tissue..)
- Derived from other cells types (mets, lymphomas, germ cell tumors)
Describe the classficiation of CNS tumors based on histology
PUTATIVE CELL OF ORIGIN/ DIFFERENTIATION
- Neurons
- Astrocytes - astrocytomas
- Oligodendrocytes - oligodendrogliomas
- Ependyma
- Choroid plexus epithelium
- Meningothelial cells - meningiomas
- Embryonal cells
What are the possible etiologof CNS tumors?
LARGELY UNKNOWN
- Radiation to head and neck: meningiomas, rarely gliomas
- Neurocarcinogens?
- Genetic predisposition <5% of primary brain tumours
Familiarity
Familial syndromes
Which genetic conditions can cause a predisposition to CNS tumors developing?
- Neurofibromatosis 1 (17q11) - neurofibroma, pilocytic astrocytoma
- Neurofibrmatosis 2 (22q12) - schwannoma, meningioma
- Tuberous sclerosis 1 (9q34) - harmatomas, sega
- Von Hippel Lindau (3q25) - hemangioblastoma
What are the general signs and symptoms of a brain tumor as well as:
- Supratentorial
- Subtentorial
Signs and symptoms are not specific they include:
- Headache
- Vomiting
- Change in mental status
Can be subtle in slow growing tumors, and a short history in aggressive tumors. Non neoplastic lesions can mimic CNS cancer
- Supraentorial (The supratentorial region contains the cerebrum)
- Focal neurological deficit
- Seizures
- Personality changes
- Subtenorial (beneath the tentorium of the cerebellum)
- Cerebellar ataxia
- Long tract signs
- Cranial nerve palsy
- What are the main modes of neuroimaging?
- What do they show?
- CT Scan and MRI scan - MRI scan being the first choice as MRI is better at assessing soft tissue changes
2.
Assess tumour type
Guide resection and biopsy
Assess post-surgery
Assess response to treatment
Follow up recurrence and progression
What are the managements for brain tumors?
A. SURGERY
Maximal safe resection aims to obtain an extensive excision
with minimal damage to the patient
Age and performance status
Resectability: location, size, number of lesions
B. RADIOTHERAPY
Low and high-grade gliomas, metastases
External fractionated RT, stereotactic radiosurgery, whole brain
C. CHEMOTHERAPY
Mainly for high-grade gliomas (temozolomide)
Biological agents (EGFR inhibitors, PD-1 inhibitors etc)
CNS tumors do not use TNM to stage. How are CNS tumors graded?
Grade I - benign - long-term survival
Grade II - cause death in more than 5 yrs
Grade III - cause death within 5 yrs
Grade IV - cause death within 1yr
Grade 1 and 2 are low grade, grade 3 and 4 are high grade
What is the most common primary CNS tumor?
Glial tumors
Describe the different glial tumors
- Diffuse infiltration
- Circumscribed gliomas
- Diffuse infiltration - grades ≥ II
- adults
- malignant progression
Astrocytomas (grades II-IV)
Oligodendrogliomas (grades II-III) - Circumscribed gliomas - grades I-II
- children
- rare malignant transformation
Pilocytic astrocytoma (grade I)
Pleomorphic xanthoastrocytoma (grade II)
Subependymal giant cell astrocytoma (grade I)
What are the underlying genetic abnormalities of the following glial tumors:
- Diffuse gliomas
- Circumscribed gliomas
- Diffuse gliomas
- IDH/2 Mutations
- Positive prognostic factor
- Circuscribed gliomas
* MAPK pathway mutations (BRAF)
Pilocytic astrocytoma
- What is the epidemiology?
- What does it look like on MRI?
- Where do they occur?
- Hallmarks
- Mutations
- Usually 1st and 2nd decade - 20% of CNS tumours below 14 years. Common in NF1
- MRI: well circumscribed, cystic, enhancing lesion
- Often cerebellar, optic-hypothalamic, brainstem
- Hallmark: piloid “hairy” cell. Very often Rosenthal fibres and granular bodies Slowly growing: low mitotic activity
- BRAF mutation (KIAA1549-BRAF fusion) in 70% of PA
Pic: Rosenthal fibers
Diffuse astrocytoma: Grade II
- What is the epidemiology?
- What does it look like on MRI?
- Where do they occur?
- Mutations
- Patients usually 20-40 years
- MRI: T1 hypointense, T2 hyperintense, non-enhancing lesion.
Low choline / creatinine ratio at MRSpec. - Cerebral hemispheres most common site. Progression to higher grade is the rule - astrocytomas become eventually glioblastomas (5-7 years)
Low to moderate cellularity
Mitotic activity is negligible or absent
Vascular proliferation and necrosis are absent
- Mutation of IDH1/2: in >80% of cases
Glioblastoma multiforme (grade IV)
- What is the epidemiology?
- What does it look like on MRI?
- Activity?
- Genetic mutations
- Most patients >50 years
- MRI: heterogeneous, enhancing post-contrast
- High cellularity and high mitotic activity
microvascular proliferation, necrosis
- 90% de novo GBM - IDH widtype
10% secondary GBM (Progression from a lower grade astrocytoma) - IDH mutant
Oligodendroglioma (grade I-III)
- Epidemiology
- Signs
- What does it look like on MRI?
- Hall mark signs
- Mutations
- 5% of all primary brain tumours. Patients usually 20-40 years
- Presents with long history of neurological signs – seizure
- MRI: no or patchy contrast enhancement; MRI and MRSpec are not predictive of transformation
- Round cells with clear cytoplasm (“fried eggs”) - see pic
- Mutation of IDH1/2 + codeletion 1p/19q: almost 100%
Note: Better prognosis than astrocytomas. Slow growing - resection is important. Better response to chemo and radiotherapy
What is the most common brain tumor in adults?
- Glioblastoma, IDH wildtype
- Meningioma
- Metastatic carcinoma
- Astrocytoma, IDH mutant
- Metastatic carcinoma
What is the most frequent CNS tumor in children?
- Meningioma
- Pilocytic astrocytoma
- Medulloblastoma
- Astrocytoma, IDH mutant
- Pilocytic astrocytoma
What is the major change in the last (2016) CNS tumour classification ?
- Changes in grading system
- Changes in staging system
- Incorporation of genetic profile
- Addition of new histological types
- incorporation of genetic profile
What does tumour grade tell us?
- Therapy response
- Survival
- Cell of origin
- Disease spread
- Survival
Meningioma (grade I-III)
- Epidemiology
- Site
- Symptoms
- What does it look like on MRI?
- 25-30% primary intracranial tumours – second after gliomas
Rare in patients < 40 - Any site of craniospinal axis, can be multiple (NF2)
- Focal symptoms (seizures, compression)
- MRI: extraxial, isodense, contrast-enhancing - Attached to the epidura
- 80% Grade I: benign, recurrence <25% - majority are benign and slowly growing
- 20% Grade II: atypical, recurrence 25-50%
- 1% Grade III: malignant, recurrence 50-90%
Why is knowing mitotic activity important?
Crucial in determining grade - higher mitotic activity indicates faster growing tumor and high mortality
Medulloblastoma - grade IV
- Type of CNS tumor
- Epidemiology
- Hallmarks
- Molecular classifications
- EMBRYONAL TUMOUR: originates from neuroepithelial precursors of the cerebellum/dorsal brainstem
- Rare (2 per 1,000,000 year), but second most common brain tumour in children
- “Small blue round cell tumour” (see pic), Homer-Wright rosettes (see pic)with expression of neuronal markers
- Molecular classification: WNT-activated, SHH-activated,
non-WNT/non-SHH
**Outcome considerably improved with radio-chemotherapy
CNS mets
- Epidemiology
- Origin
- Prognosis
- Most frequent CNS tumour in adults (10 x intrinsic tumours)
Increasing incidence due to longer survival. Often multiple - Any tumour can potentially give CNS metastases, may be the first presentation of the disease
Most frequent tumours are: lung ca, breast ca, melanoma, colorectal ca, renal ca. Origin can be challenging to determine - Very poor prognosis
Pic - mets - at grey-white junction
45 year old female
History: pulmonary lobectomy
2 days of headache and vomiting
Worsening headache
CT: right frontoparietal SOL with minimal midline shift to the left
Dd: primary tumour, metastasis, abscess
What is the diagnosis?
- Glioblastoma (WHO grade IV)
- Astrocytoma (WHO grade II)
- Abscess
- Metastasis
- Metastasis
70 year old male
Seizure following 2 weeks of left arm and leg weakness
MRI showing heterogeneous enhancing right frontal lesion, started on steroids
Partial response to steroids with improved dexterity of the left arm and leg
A tumour was partially resected
What is the diagnosis?
- Glioblastoma (WHO grade IV)
- Meningioma (WHO grade II)
- Metastasis
- Astrocytoma (WHO grade II)
- Glioblastoma (WHO grade IV)
5 year old boy
Had headache and vomiting in the morning for 2 weeks
Symptoms worsened and the vision became blurred
Fundoscopic exam: papilledema
MRI showing cystic cerebellar lesion
A tumour was removed - NOT VERY cellular
What is the diagnosis?
- Medulloblastoma (WHO grade IV)
- Meningioma (WHO grade I)
- Oligodendroglioma (WHO grade II)
- Pilocytic astrocytoma (WHO grade I)
- Pilocytic astrocytoma (WHO grade 1)
