Neurooncology Flashcards by Georgia Leggett

What are the classifications of primary CNS tumours based on location?

EXTRA-AXIAL (COVERINGS):

Tumours of bone, cranial soft tissue, meninges, nerves

Majority BENIGN

INTRA-AXIAL (PARENCHYMA):

From normal cell populations of the CNS e.g. glia, neurons, neuroendocrine cells. Or from other cell types lymphomas, germ cell tumours.

INFILTRATIVE

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What are more common CNS tumours?

Non-malignant tumours are more common than malignant tumours

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What is the aetiology of CNS tumours?

Radiotherapy to head + neck: meningiomas, rarely gliomas.

Genetics: < 5% of primary brain tumours- Familial syndromes

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What is the chromosome and loci for NF1 and NF2?

NF1: 17q11

NF2: 22q12

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Give 5 familial CNS tumour syndromes

Neurofibromatosis 1: Neurofibroma, Astrocytoma

Neurofibromatosis 2: Schwannoma, Meningioma

Brain Tumour Polyposis: Malignant gliomas

Gorlin: Medulloblastoma

Von Hippel Lindau: Hemangioblastoma

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What are signs and symptoms of CNS tumours?

Intracranial HTN:

Headache + vomiting

Change in mental status

Supratentorial: (cerebral hemispheres)

Focal neurological deficit

Seizures

Personality changes (frontal lobe)

Infratentorial:

Cerebellar Ataxia

Long tract signs (motor descending, sensory ascending)

CN palsy

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What is the most common type of CNS tumour in adults?

Metastatic CNS tumour

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What is the most common type of CNS tumour in children?

Pilocytic astrocytoma

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What are the management options for CNS tumours?

SURGERY:

Max. safe resection with min. damage to patient

Gives best outcome (depends on age + performance status)

Resectability: location, size, no. lesions

RADIOTHERAPY:

Low + high-grade gliomas, mets, selected benign tumours

External fractionated RT, stereotactic radiosurgery

CHEMO:

High-grade gliomas (temozolomide) + lymphomas

Biological agents (EGFR inhibitors, PD-L1 inhibitors)

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What are the diagnostic and therapeutic objectives for CNS tumour surgery?

Craniotomy for debulking: Subtotal + complete resections (as much tumour as poss).

Open biopsy: Inoperable but approachable tumours (~1cm), usually representative.

Stereotactic biopsy: If open biopsy not indicated (~0.5cm tissue), tissue may be insufficient for dx.

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What is histopathology and molecular pathology of tissue biopsy used for in CNS tumours?

To provide a definitive + complete dx.

To guide tx: Predictive tests assays for target therapy.

To assess tx response.

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What is the WHO classification of CNS tumours based upon?

Tumour type: Putative cell of origin or lineage of differentiation.

Tumour grade: Aggressiveness.

Molecular profile: Most tumour types have molecular markers.

NO TNM STAGING

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What is tumour typing for CNS tumours?

Tumour type: Histological type

Defined by histological features

Tumour names derived from putative cell of origin

Histological type predicts tumour behaviour.

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What is the grading system in CNS tumours?

Attempt to stratify tumours by outcome i.e. degree of malignancy.

Based on morphological criteria of malignancy (proliferative activity, cell differentiation, necrosis) + increasingly on genetic profile.

Based on predicted natural clinical behaviour + does not consider response to tx: many pts with treated high-grade tumours have longer survival than expected according to grade.

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What are the 4 grades according to the WHO classification?

G1: Benign: long-term survival

G2: > 5y

G3: < 5y

G4: < 1y

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What are tumour grades used for?

To guide tx

Give 4 characteristics of diffuse gliomas. Name 2 diffuse gliomas.

Grades ≥ 2

Adults

Supratentorial

Malignant progression.

Astrocytomas (G 2-4)

Oligodendrogliomas (G 2-3)

Give 4 characteristic features of circumscribed gliomas. Name 3 examples.

Grades 1-2

Children

Often posterior fossa

Rare malignant transformation

Pilocytic astrocytoma (G1)

Subependymal giant cell astrocytoma (G1)

Ependymomas (usually circumscribed)

Which mutations are associated with diffuse gliomas?

IDH1/2 mutations (30%)

Describe the epidemiology and site of pilocytic astrocytomas.

Describe the features on MRI, histology, genetics.

Usually 1st + 2nd decade

Account for 20% of CNS tumours <14y

Often cerebellar, optic-hypothalamic, brainstem.

MRI: Well circumscribed, cystic, enhancing lesion.

Histology: Piloid “hairy” cell. Very often Rosenthal fibres.

Slow growing: Low mitotic activity

Genetic profile: BRAF mutation in 70%

What are the features of diffuse gliomas?

Usually 20-40y

Astrocytomas + Oligodendrogliomas

+/- Pathogenic point mutation in IDH1/2

IDH mutation A/W longer survival + better response to chemo + radiotherapy.

Describe the epidemiology and site of astrocytomas. Describe the features on MRI, histology, genetics.

20-40y

Cerebral hemispheres.

MRI: T1 hypointense, T2 hyperintense, non-enhancing lesion. Low choline/ creatinine ratio at MRSpec.

Histology: Low to moderate cellularity. Mitotic activity is low. No vascular proliferation/ necrosis.

Genetic profile: +/- Point mutation in IDH1/2.

What is the rule of progression in astrocytomas?

Progress from grade 2 to 3 to 4, typically in <10y

What is glioblastoma multiforme?

Most aggressive + most frequent glioma

Cerebral hemispheres affected

Incidence ↑ with age, most >50y

Median survival: 8m

What are signs on investigation for glioblastoma multiforme?

**MRI:** Heterogeneous, enhancing post-contrast. **Histology:** High cellularity + neoangiogenesis, necrosis. **Genetic profile:** IDH1 wildtype. Common mutations in TERT, PTEN, EGFR

What is this? What can be seen?

Glioblastoma multiforme High cellularity (normal brain tissue at top)

What is this? What can be seen?

Glioblastoma multiforme Neoangiogenesis (microvascular proliferation)

Describe the epidemiology of meningioma. From which cells do they arise? What is seen on MRI?

38% of primary CNS tumours. Rare in \< 40y Incidence ↑ with age. Originate from meningothelial cells of Arachnoid mater, at any site of craniospinal axis Can be multiple (NF2). **MRI:** Extraxial, isodense, contrast-enhancing.

What is the distribution of WHO grades for meningiomas?

**80% G1:** Benign, recurrence \< 25% **20% G2:** Atypical, recurrence 25-50% **1% G3:** Malignant, recurrence 50-90%

Why is subtyping and grading useful for meningiomas?

Grading = most useful predictor of recurrence. Mainly based on histology, recently molecular markers (ex TERT mutation, methylome) Complex histological assessment: proliferation, cell morphology, microscopic brain invasion. 15 morphological subtypes across 3 grades.

What are CNS metastases?

Most frequent CNS tumour in adults (10 x intrinsic tumours). Increasing incidence due to longer survival. Often multiple, located at grey/white matter junction +/- leptomeningeal disease. May be 1st presentation of the disease. Origin can be challenging to determine: immunohistochemical markers. Very poor prognosis.

What are the most common cancers to give rise to CNS metastases?

Any cancer can give CNS mets Most frequently: Lung ca Breast ca Melanoma Renal cell ca Can use antibodies to detect primary site.

What are medulloblastomas?

WHO Grade 4. **EMBRYONAL TUMOUR:** Originates from neuroepithelial cells/ neuronal precursors of the cerebellum or dorsal brainstem. RARE but 2nd most common brain malignancy in children + YA. Outcome considerably improved with radio-chemotherapy + subtype stratification.

Describe the epidemiology of CNS tumours

Mets 10x more frequent than primary Primary rare in adults, most common tumour in children Extra-axial tend to be benign Intra-axial infiltrate, tend to be malignant

Name the tumour based on the putative cell of origin Astrocytes Oligodendrocytes Ependyma Neurons Embryonal cells Meningothelial cells Schwann cells

Astrocytes: Astrocytoma Oligodendrocytes: Oligodendroglioma Ependyma: Ependymoma Neurons: Neurocytoma Embryonal cells: Medulloblastoma Meningothelial cells: Meningioma Schwann cells: Schwannoma, Neurofibroma

Describe tumours of the nervous system based on central or peripheral distribution

CNS: Brain + coverings, spinal cord + coverings, pituitary PNS: small nerves in any organ (neurofibromas of skin/ soft tissue) + large nerves (cranial + spinal nerve schwannomas) Most peripheral are benign

How is mitotic activity useful?

Determines grade Mitosis per 10 HPF \<4 = G1 4-20 = G2 \>20 = G3

What is the methylome profile?

Characteristic patterns of DNA methylation of CpG islands Epigenetic profile Stable signature, reflects cell of origin Helpful for atypical cases, rare entities, small biopsies, sub-typing