Clinical - Tumours of the CNS Flashcards
CNS tumours require an integrated diagnosis. What 3 aspects does this include?
- Histology
- WHO - Grade
- Genetic
What % of lung cancers spread to the brain?
20%
What is a glioma?
Glioma is a type of tumor that begins in the glial (supportive) cells that surround nerve cells and help them function.
What is a meningioma?
A meningioma is a tumor that forms on membranes that cover the brain and spinal cord just inside the skull (meninges)
What is a blastoma?
A blastoma is a type of cancer caused by malignancies in precursor cells, which are commonly referred to as blasts
What is a medulloblastoma?
Medulloblastoma is the most common type of cancerous brain tumor in children - most commonly starts in the cerebellum.
There are 4 major types of glial cells in the CNS?
- Astrocytes
- Oligodendrocytes
- Ependymal cells and choroid plexus cells
- Microglia
Function of astrocytes?
- Support and protection
- Bridge blood to the neurones, providing nutrition
- Also metabolise the nutrients so that they are suitable for the neurones.
Function of oligodendrocytes?
myelin production
Function of microglia?
- As the resident macrophage cells, they act as the first and main form of active immune defense in the central nervous system (CNS).
- Come from mesoderm
What are ependymal cells?
The cell type lining the brain ventricles. As non-neuronal cells in the brain and derived from neuroectoderm, they are clearly defined as a subtype of glial cells.
Function of ependymal cells and choroid plexus cells?
Produce CSF
What is the GFAP stain in histology? What is it useful for?
- Done to determine whether cells contain glial fibrillary acidic protein, a protein secreted by a normal astrocyte
- It is useful for determining whether a tumour is of glial origin
Histology of CNS tumours. What is the criteria?
- mitosis: for cell division
- vascular endothelial proliferation: more blood vessels to supply growing tumour
- necrosis: tumour necrosis factor secreted by tumour to remove competition, kill the environment
-
dedifferentiation: Cell dedifferentiation is the process by which cells grow reversely from a partially or terminally differentiated stage to a less differentiated stage
- loss of functional brain cells to promote growth
CNS tumours can be graded 1-4 (WHO). Describe each grade
- 1: benign, no recurrence, no/very slow progression
- 2: low grade, progression to 3 (astrocytoma 6-7year)
- 3: high grade, rapid progression (astrocytoma 2-3years)
- 4: aggressive
Molecular genetic ring:
- Inner ring –> driver of mutation
- IDH is the most common, leading to uncontrolled cell division
- Middle ring –> additional mutations
- With time, additional mutations in the middle ring will occur. These affect the survival of the cell e.g. EGFR
- Outer ring –> histological diagnosis
- Determines the prognosis
- H3G34R with ATRX and GBM lead to poor prognosis, for example
What are Schwann cells?
Schwann cells are a type of glial cells of the peripheral nervous system that help form the myelin sheath around the nerve fibers.
What is a Schwannoma?
- Tumour of Schwann cells
- Benign but difficult to remove
- Usually just grade 1
- Mitosis is normally not seen
Which tumours would require oncology?
- High grade glioma, especially glioblastoma.
- Without treatment, outcome after surgery is poor.
- Low grade glioma.
- Significant cause of morbidity and disability, often not surgically curable
- Benign tumours (meningiomas, pituitary adenomas, schwannomas) – still affected by radiotherapy and chemotherapy due to loss of blood supply
- Paediatric (e.g. medulloblastoma, germ cell, ependymoma)
Presentation of brain tumours?
- Pressure symptoms: headache, confusion, reduced conscious level, nausea and vomiting
- Seizures (50%)
- Focal symptoms due to location (e.g. weakness, dysphasia)
Why are seizures more common in low grade tumours?
As some electrical activity is occurring
When would a scan be ordered when a patient presents with potential brain tumour symptoms?
Scan ordered if someone presents with a headache and neurological sign/symptoms
Where is language processed in the brain?
Usually located in the left (dominant) hemisphere of the brain, specifically in two areas:
- Broca’s area (associated with speech production and articulation)
- Wernicke’s area (associated with comprehension).
A 40 year old right handed plumber presents to A & E after a fit and has a 2 week history of gradually increasing numbness and weakness of right side. Where is the lesion?
- Lesion likely to be in left hemisphere of brain
- Motor and sensory symptoms; involving both sides of central sulcus (frontal and parietal lobes –> left fronto-parietal region
A 30 year old mother can’t make her children understand what she is trying to say. She seems to understand what is said to her. She is right-handed. Where is the lesion?
- Broca’s area affected in left hemisphere (associated with speech production and articulation) –> left temporo-frontal region
- Expressive dysphasia –> difficulty expressing what you want to say
A 50 year old company director becomes withdrawn, apathetic and bad-tempered - then develops headaches and vomiting. Where is the lesion?
- Frontal lobe; involved in higher order functioning e.g. personality, behaviour, planning, timekeeping
- Pressure symptoms
A 55 year old lady can’t dress herself properly, has numbness down one side and develops headaches. Which lobe of the brain is likely to be affected?
- Parietal lobe; sensory loss, dyspraxia, inattention
- Pressure symptoms
Which lobe of the brain is involved in higher order functioning e.g. personality, behaviour, planning, timekeeping?
Frontal lobe
What is radiotherapy?
- Use of X-rays to treat tumours. Carefully controlled high energy X-ray beams are focused on the tumour
- Beams travel through the skin to the tumour.
What are xrays? How are they effective against cancer?
- X-rays deliver photons, produced by naturally occurring radioactive decay
- Cause disruption of atomic/molecular structure, including DNA
- Affects tumour cells because they are under mitotic stress.
- They will be ineffective at repairing damage to DNA due to X-rays.
- Specific damage is DNA base damage, single strand breaks and double strand breaks (thought to be the most significant)
What is external beam radiotherapy?
- External beam radiotherapy is given from a radiotherapy machine outside the body.
- High energy X-ray beams to penetrate tissue
- Linear accelerator
- Beams designed to target tumour and avoid normal tissue
Typical radiotherapy regime?
- Small doses built up over several weeks
- Often 5 days on, 2 days off to allow for cellular repair of normal tissue
What is proton radiotherapy?
Proton beam therapy is a type of radiotherapy that uses a beam of high energy protons rather than photons (high energy x-rays) to treat specific types cancer
Why is proton therapy often preferred in children where whole body dose can be needed OR if near sensitive normal tissue?
- A proton beam delivers some radiation to healthy tissue in reaching the tumour but very little radiation beyond the edge of the tumour being treated.
- I.e. No dose beyond end of beam: dose goes into tumour and then stops, does not leave
- More specific dose delivery, spares normal tissue
- In an older person, low dose to normal brain tissue may not have a significant effect.
What are the acute side effects of cranial radiotherapy?
First few weeks after RT:
- Cerebral oedema causing raised intracranial pressure and exacerbation or pre-RT neurological symptoms, less common
- Hair loss
- Scalp/ear erythema
What are the immediate side effects of cranial radiotherapy (within a few weeks/few months)?
- Somnolence syndrome (severe tiredness) and exacerbation of existing neurological symptoms
- Due to short term demyelination of neurones
- Self-limiting
What is somnolence syndrome?
- Somnolence syndrome is a collection of symptoms consisting of drowsiness, lethargy and fatigue (hypersomnia)
- It is linked to receiving radiation therapy to the head.
- The symptoms of somnolence syndrome usually happen 3 to 12 weeks after radiation therapy ends.
What are the late effects (several months to years after RT)?
Damage to sensitive structures e.g. lens (cataracts), pituitary (hypopituitarism), cerebral hemispheres (memory loss)
Shield these from the radiation as much as possible.
For a high grade glioma (3/4), when would radiotherapy not be carried out?
If elderly or poor PS, patient may die of brain tumour within 3 months before recovering from side-effects, therefore not recommended
For a high grade glioma (3/4), when would radiotherapy be carried out?
If young and fit and can live for several years, RT recommended
Median survival of grade 1-4 gliomas?
- Grade 1: many years (cured if complete resection)
- Grade 2: 5-12 years
- Grade 3: 2-4 years
- Grade 4: 6-18 months (depending on prognostic factors)
What are 5 common cancers that can cause brain metastases?
breast, bowel, lung, prostate, kidney
What is gamma knife treatment?
highly targeted radiation after pinning the patient into place
