Brain tumors Flashcards
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
How do brain tumors present?
Asymptomatic Seizures Symtoms/signs of raised intracranial pressure Symptoms/signs of hydrocephalus Focal neurological deficit Endocrine disturbance Haemorrhage
How does raised ICP present?
- Headache (especially postural/ nocturnal/ early morning)
- Vomiting (especially children)
- Clouding of consciousness/ Coma
- Papilloedema
What is increased ICP characterised by?
oedema(generalized and local) and hydrocephalus- little room for expansion
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
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)
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
What is a result of brain herniation?
Vascular compression
–Anterior cerebral artery at falx
–Posterior cerebral artery at tentorium
–Brainstem Duret haemorrhage = death
Explain features of raised ICP
- Headache (especially postural/ nocturnal/ early morning)
- Vomiting (especially children)
- Clouding of consciousness/ Coma
- Papilloedema
Define hydrocephalus
Increase in CSF volume within the ventricular system
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
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
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
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
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
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
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
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
- Surgery – gross total resection (all except lymphoma & germinoma)
- +/- Radiotherapy (*Cognition)
- +/- 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.
