Brain tumors Flashcards by Marie Francis

Epidemiology of brain tumors

2% of all cancers
20% cancers >15 yrs 
leading cause of cancer related death in children as commonest solid tumour in children
Adults- supratentorial 
children-infratentorial

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How do brain tumors present?

Asymptomatic
Seizures
Symtoms/signs of raised intracranial pressure
Symptoms/signs of hydrocephalus
Focal neurological deficit 
Endocrine disturbance 
Haemorrhage

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How does raised ICP present?

Headache (especially postural/ nocturnal/ early morning)
Vomiting (especially children)
Clouding of consciousness/ Coma
Papilloedema

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What is increased ICP characterised by?

oedema(generalized and local) and hydrocephalus- little room for expansion

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Explain causes of localised and generalized oedema

oedema= excess fluid in brain
Two types
1.Vasogenic oedema = normal blood brain barrier disrupted -> increased vascular permeability -> fluid escapes from intravascular to intercellular compartments eg. trauma
2.Cytotoxic oedema = increase in intracellular fluid secondary to cellular (neuronal/ glial/ endothelial) injury eg. hypoxia/ischaemia

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Pathophysiology of abnormal water accumulation in brain

•Oedema (any cause)
Skull behaves as rigid box (infant skull will enlarge)
Brain compressed
Initial compensatory phase = CSF displaced to spinal compartment; blood volume reduced in cerebral veins
Swelling vascular compression vascular insufficiency exacerbates high ICP (cytotoxic oedema)

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Consequences of localised and generalised oedema

Consequences- cerebral herniation eg subfalcine herniation of cingulate gyrus, transtentorial herniation of medial part of temporal lobe, transforaminal herniation of cerebellar tonsil, cerebral fungus, upward herniation of cerebellum

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What is a result of brain herniation?

Vascular compression
–Anterior cerebral artery at falx
–Posterior cerebral artery at tentorium
–Brainstem Duret haemorrhage = death

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Explain features of raised ICP

Headache (especially postural/ nocturnal/ early morning)
Vomiting (especially children)
Clouding of consciousness/ Coma
Papilloedema

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Define hydrocephalus

Increase in CSF volume within the ventricular system

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What are the major sites of CSF block

foramen of Munro
third ventricle
aqueduct of sylvius
foramina of luschka and magendie
basal cistern/subarachanoid spaces

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Causes of hydrocephalus

Disturbance of CSF homeostasis (rare)
•CSF overproduction (choroid plexus tumour)
•Failure of CSF absorption (absence of Arachnoid granulations, various cranial dysplasias)

Interference with CSF flow (common)
•Neoplasm
•Malformation eg congenital stenosis, membrane at foramen of Monro, many more
•Infection- scarring
•Haemorrhage
•Gliosis, any cause eg stroke

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Neoplasms/ cysts commonly presenting with hydrocephalus

Posterior fossa tumour eg pilocytic astrocytoma, medulloblastoma
Pineal gland neoplasm
SEGA
Hypothalamic pilocytic astrocytoma
Central neurocytoma
Chordoid glioma of 3rd ventricle
Colloid cyst of 3rd ventricle

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Symptoms/ Signs of hydrocephalus

Infant: enlarging head, bulging fontanelle, vomiting, irritability, sleepiness, downward eyes (sunsetting)
Child: above + headache, blurred vision, poor balance, seizures
Adult: above + poor balance, memory loss, bladder control problems

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How do you classify brain tumours

primary -from cells originating in NS and its coverings– usually benign and malignant /potentially malignant
secondary - mets from elsewhere in body; 50% are solitary ; goes to brain but also meninges and vertebra

Primary
Cells within brain  - neurons, glial, blood vessels
Cranial nerves  -Schwann cells
Meninges
Pituitary gland
Pineal gland
Skull

Secondary
Metastasis

Meninges
-meningioma

neurons

gangliocytoma
ganglioglioma

glial cells (supporting cells ;; tumor of glial cells - glioma-many subtypes)

astrocytoma
oligodendroglioma
ependymoma

choroid plexus
-papilloma/carcinoma

primitive/precursor cells
-medulloblastoma/embryonal

nerve

schwannoma
neurofibroma

other
Pineocytoma
Pituitary adenoma
Embryological remnant cells
Craniopharyngioma

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What is the most common types of brain tumors?

Meningioma is the most common benign primary tumour.
Glioma is the most common malignant primary tumour.
- Glioblastoma (made up of abnormal astrocytic cells) is the most common glioma. grade 4

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What are some facts about brain tumors?

Primary brain tumours rarely metastasize

Prognosis is not solely related to grade
–Tumour site is very important
–Site impacts on resectability
–Site impacts on morbidity
i.e. A ‘benign’ or a ‘low grade’ tumour can kill

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Explain the WHO grade for gliomas

vs Burger system for astrocytic gliomas

Grade 1 - pilocytic astrocytoma; excellent prognosis 5 yr survival 95%
Burger system: pilocytic; curable

Grade 2- high grade features - median survival 10 yrs
burger system: low grade astrocytoma; 7-9 years survival

Grade 3- mitosis- median survival 3-5 yrs
burger system: anaplastric astrocytoma ; 2-3 years

Grade 4- vascular proliferation with or without necrosis - survival usually months- 5yrs <5%
burger system: glioblastoma multiforme; 14 months survival

What is the pathogenesis of brain tumours?

Unknown

Radiation

Immunosuppression – lymphoma

Hormonal – meningioma

Genetic - neurofibromatosis, Von Hippel-Lindau syndrome, Turcot’s syndrome

What are some familial tumour syndromes a/w brain tumours

neurofibroma- neurofibromatosis type 1

schwannoma- neurofibromatosis type 2

haemangioblastoma- Von hippel lindau disease

Subependymal giant cell astrocytoma- tuberous sclerosis

glioma/embryonal/chordoid plexus- li fraumeni syndrome

glioma- turcot syndrome

ATRT (Atypical teratoid rhabdoid tumor) - rhabdoid tumour predisposition syndrome

What are the most common ADULT primary tumors?

glioma 60%

astrocytic
oligodendroglioma
mixed O-A

meningioma 20%

pituitary, pineal 10%

nerve sheath tumours 5-8&

diverse rare tumours 10%

Describe low grade astrocytoma

15% astrocytomas

Peak age 30

Transform to higher grade

5 year survival with gross resection and radiotherapy is 70%

Describe glioblastoma multiforme(GBM)

Peak age 45-60

50% of astrocytomas

20% of primary brain tumours

Pathology - necrosis

What is the genetic mutation a/w the progression of astrocytic gliomas

low grade glioma- p53 mutation >65% , PDGFA, PDGFRalpha overexpression >60%

anaplastic astrocytoma- LOH chr 19 , Rb alterations

glioblastoma multiforme - LOH chr 10

from normal astrocyte to form GBM -> EGFR amplification (50%) , mutation , LOH chr 10 50%, loss of pTEN (80%) , PDGFB and PDGFRbeta

Describe oligodendroglial tumors

Vary from low grade to malignant. Usually occurs in the cerebrum. Grow slowly. Most common in middle-aged adults

Describe meningioma | tx?

Extra-axial Arise from cap cells of arachnoid Primarily a surgical disease Usually classified by location For residual or recurrent meningioma, use radiation and/or focused radiation

Describe vestibular schwannoma | tx?

Arise from vestibular branch of CN VIII Present with slowly progressive hearing loss Bilateral in NF2 Treated options surgery or stereotactic radiosurgery, observation

Describe pituitary adenomas | tx?

Non-functioning (present with visual symptoms, headache, hypopituitarism) Functioning: prolactin (galactorrhea, infertility) growth hormone (Acromegaly) ACTH (Cushing’s syndrome) Rarely pituitary apoplexy Treated with drugs, surgery, radiation

Describe primary CNS lymphoma | tx?

Most common in immune-suppressed persons (e.g. AIDS; organ transplant) Rate of PCNSL seems to be on the rise, irrespective of immune suppression Treated with biopsy and chemotherapy

List sources of mets to CNS

lung cancer >40% breast 40% renal cell 7% GI 6% melanoma 3% Undetermined 4%

Which parts of CNS affected by mets?

``` Brain spinal cord Leptomeninges Dura pituitary gland ``` mets to the brain greatly outnumber primary tumours

What are the most common childhood brain tumours

Astrocytoma Medulloblastoma Ependymoma

Describe cerebellar astrocytoma

Most common brain tumour in childhood usually benign, slow growing 90% cure 30% of paediatric posterior fossa tumours are astrocytomas. age group is 5 to 10 years

Describe medulloblastoma

This tumor usually arises in the cerebellar vermis. One of the most common brain tumors in children. It is a primitive neuroectodermal tumor. Extremely malignant characterised by the ability to seed along CSF pathways. Frequently they metastasise down the spinal axis.

Describe ependymoma

The tumor arises from cells that line the ventricles or the central canal of the spinal cord. Most common in children and young adults.

What is another tumor seen in children?

Diffuse brain stem tumor These tumours balloon the brain stem and infiltrate all layers. They are malignant tumours and have very poor prognosis. Cause cerebellar dysfunction, cranial nerve palsies and paresis..

What are some techniques used in diagnostic practice for brain tumours?

``` immunohistochemistry DNA sequencing fusion specific qPCR array comparative genomic hybridisation methylation molecular analysis/markers ```

What is the correlation between Molecular DNA and diagnosis and prognosis?

molecular information impacts the diagnosis and prognosis EG. BRAF gene fusion- 90% post fossa pilocytic astrocytoma H3 histone mut. - > WHO grade 4 (peds) ; dismal prognosis

What investigations can be performed in a suspected brain tumour?

History (symptoms, past history of cancer, rate of progression of symptoms, etc) Physical examination (neurological findings) Imaging – CT as screen but MRI is best CT chest/abdo/pelvis Functional imaging: fMRI PET ± CSF cytology

Treatment of brain tumours

1. Surgery – gross total resection (all except lymphoma & germinoma) 2. +/- Radiotherapy (*Cognition) 3. +/- Chemotherapy (BBB challenge)

How do you diagnose GBM? | Tx of GBM

Dx: histopathological/molecular Tx surgical resection Postoperative scan External beam radiotherapy 50-60Gy external beam RT Role of chemotherapy Concurrent chemoradiation with temozolomide is standard of care

What are the obstacles a/w chemotherapy?

Delivery/BBB: oral, IV, IT, intracavitary wafers Resistance (MGMT for alkylating agents) Genomic instability

List the surgical strategies and approaches for brain tumour resection

``` orbitozygomatic subtemporal pretrosal retrosigmoid supracerebellar-infratentorial suboccipital far lateral ``` transcallosal approach occipital transtentorial approach infratentorial supracerebellar approach

What can be used for tumour removal?

5 ala- optical imaging agent for use in people affected by high grade gliomas ; improves the removal of tumour tissue and delays worsening progression of the disease.