Clinical - Tumours of the CNS

Question 1

CNS tumours require an integrated diagnosis. What 3 aspects does this include?

Answer 1

1. Histology
2. WHO - Grade
3. Genetic

Question 2

What % of lung cancers spread to the brain?

Answer 2

20%

Question 3

What is a glioma?

Answer 3

Glioma is a type of tumor that begins in the glial (supportive) cells that surround nerve cells and help them function.

Question 4

What is a meningioma?

Answer 4

A meningioma is a tumor that forms on membranes that cover the brain and spinal cord just inside the skull (meninges)

Question 5

What is a blastoma?

Answer 5

A blastoma is a type of cancer caused by malignancies in precursor cells, which are commonly referred to as blasts

Question 6

What is a medulloblastoma?

Answer 6

Medulloblastoma is the most common type of cancerous brain tumor in children - most commonly starts in the cerebellum.

Question 7

There are 4 major types of glial cells in the CNS?

Answer 7

1. Astrocytes
2. Oligodendrocytes
3. Ependymal cells and choroid plexus cells
4. Microglia

Question 8

Function of astrocytes?

Answer 8

• Support and protection
• Bridge blood to the neurones, providing nutrition
• Also metabolise the nutrients so that they are suitable for the neurones.

Question 9

Function of oligodendrocytes?

Answer 9

myelin production

Question 10

Function of microglia?

Answer 10

• 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

Question 11

What are ependymal cells?

Answer 11

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.

Question 12

Function of ependymal cells and choroid plexus cells?

Answer 12

Produce CSF

Question 13

What is the GFAP stain in histology? What is it useful for?

Answer 13

• 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

Question 14

Histology of CNS tumours. What is the criteria?

Answer 14

• 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

Question 15

CNS tumours can be graded 1-4 (WHO). Describe each grade

Answer 15

• 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

Question 16

Molecular genetic ring:

Answer 16

• 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

Question 17

What are Schwann cells?

Answer 17

Schwann cells are a type of glial cells of the peripheral nervous system that help form the myelin sheath around the nerve fibers.

Question 18

What is a Schwannoma?

Answer 18

• Tumour of Schwann cells
• Benign but difficult to remove
• Usually just grade 1
• Mitosis is normally not seen

Question 19

Which tumours would require oncology?

Answer 19

• 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)

Question 20

Presentation of brain tumours?

Answer 20

• Pressure symptoms: headache, confusion, reduced conscious level, nausea and vomiting
• Seizures (50%)
• Focal symptoms due to location (e.g. weakness, dysphasia)

Question 21

Why are seizures more common in low grade tumours?

Answer 21

As some electrical activity is occurring

Question 22

When would a scan be ordered when a patient presents with potential brain tumour symptoms?

Answer 22

Scan ordered if someone presents with a headache and neurological sign/symptoms

Question 23

Where is language processed in the brain?

Answer 23

Usually located in the left (dominant) hemisphere of the brain, specifically in two areas:

1. Broca’s area (associated with speech production and articulation)
2. Wernicke’s area (associated with comprehension).

Question 24

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?

Answer 24

• 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

Question 25

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?

Answer 25

* 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

Question 26

A 50 year old company director becomes withdrawn, apathetic and bad-tempered - then develops headaches and vomiting. Where is the lesion?

Answer 26

* **Frontal** lobe; involved in higher order functioning e.g. personality, behaviour, planning, timekeeping * Pressure symptoms

Question 27

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?

Answer 27

* **Parietal** lobe; sensory loss, dyspraxia, inattention * Pressure symptoms

Question 28

Which lobe of the brain is involved in higher order functioning e.g. personality, behaviour, planning, timekeeping?

Answer 28

Frontal lobe

Question 29

What is radiotherapy?

Answer 29

* 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.

Question 30

What are xrays? How are they effective against cancer?

Answer 30

* 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)

Question 31

What is external beam radiotherapy?

Answer 31

* 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

Question 32

Typical radiotherapy regime?

Answer 32

* Small doses built up over several weeks * Often 5 days on, 2 days off to allow for cellular repair of normal tissue

Question 33

What is proton radiotherapy?

Answer 33

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

Question 34

Why is proton therapy often preferred in children where whole body dose can be needed OR if near sensitive normal tissue?

Answer 34

* 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.

Question 35

What are the acute side effects of cranial radiotherapy?

Answer 35

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

Question 36

What are the immediate side effects of cranial radiotherapy (within a few weeks/few months)?

Answer 36

* Somnolence syndrome (severe tiredness) and exacerbation of existing neurological symptoms * Due to short term demyelination of neurones * Self-limiting

Question 37

What is somnolence syndrome?

Answer 37

* 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.

Question 38

What are the late effects (several months to years after RT)?

Answer 38

Damage to sensitive structures e.g. lens (cataracts), pituitary (hypopituitarism), cerebral hemispheres (memory loss) Shield these from the radiation as much as possible.

Question 39

For a high grade glioma (3/4), when would radiotherapy not be carried out?

Answer 39

If elderly or poor PS, patient may die of brain tumour within 3 months before recovering from side-effects, therefore not recommended

Question 40

For a high grade glioma (3/4), when would radiotherapy be carried out?

Answer 40

If young and fit and can live for several years, RT recommended

Question 41

Median survival of grade 1-4 gliomas?

Answer 41

* 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)

Question 42

What are 5 common cancers that can cause brain metastases?

Answer 42

breast, bowel, lung, prostate, kidney

Question 43

What is gamma knife treatment?

Answer 43

highly targeted radiation after pinning the patient into place