CNS Tumours Flashcards
Why is a CNS tumour bad news?
- High and severe morbidity
- High mortality
- Severe effects of treatments
From what cell types can CNS tumours arise from (and how commonly)?
- Neurones - rarer, and are usually found in the paediatric population
- Glial cells (astrocyte, oligodendrocytes, etc) tumours are the most common
- Ependyma
- Choroid plexus epithelium
- Meninges
- Endothelium and pericytes
Why are CNS tumours particularly difficult to treat?
- One of the reasons CNS tumours are so difficult to treat is because of the blood brain barrier. It is unique to the CNS; found nearly everywhere in the brain (apart from a few regions in the midline).
- Resistance to chemotherapeutic agents
- Heterogeneity
- Diffusing nature of some brain tumours
- Invasiveness of local delivery into the brain
- Lack of efficacy through the systemic circulation
- Limitations attributable to medicines themselves
What makes up the BBB?
It is formed by tight junctions between endothelial cells; pericytes; and astrocyte processes. It ensures that the homeostasis within the brain is maintained.
How do tumours interact with the BBB?
Tumours can disrupt the BBB in a way that benefits them to aid in proliferation, but still proving difficult to deliver chemotherapy to. One of the main factors secreted by tumours VEGF stimulates neo-angiogenesis to the tumour.
Define primary and secondary brain tumour.
Primary tumours - any tumour that only occurs in the CNS. These are actually quite rare. Most are secondary.
Secondary tumours - metastases from other locations.
Name a few conditions that give a genetic predisposition to CNS tumour formation
The following is a group of syndromes where there is a genetic predisposition to CNS tumours: • Neurofibromatosis 2 (NF2) • Tuberous Sclerosis 1 (TS1) • Tuberous Sclerosis 2 (TS2) • Turcot’s syndrome (APC) • Li-Fraumeni (p53) • Cowden syndrome (PTEN) • Gorlin syndrome (PTCH1) • Von Hippel Lindau (VHL) However, most patients with a primary brain tumour, don't have these.
Describe how CNS tumours relate to co-morbitities e.g. MS incidence
- There is a possible association between CNS and non-CNS cancer – possible but not proven.
- Inverse association between neurodegenerative conditions (Alzheimer’s; ?Parkinson’s Disease) and CNS cancer. Possibly due to deposition of proteins which stop cell division.
- No clear association between neuroinflammatory conditions (mainly MS) and CNS cancer
- Lower risk of CNS cancer in patients with allergies – ?role of IgE (This is very important - it means that immunotherapy may work against brain tumours?)
- Possible role of viral infection (CMV & HHV6)
Describe the controversy of stem-cells in brain tumours
It may be that tumour stem cells derive directly from neural stem cells. Tumours that scientists believe derive from stem cells have the increased capacity to self-renew, differentiate and proliferate, and are more chemoresistant. Furthermore, one of the reasons chemotherapy fails is that within a tumour, there are cells with multiple and different mutations. So if a targeted drug selects one mutation, the other cells still survive.
What are the signs and symptoms of brain tumours in adults?
Signs and symptoms are not specific:
• Headache - highly unspecific. A typical headache from a tumour is a high pressure headache. Typically gets worse when patients are lying down, gets worse when coughing or sneezing. Usually worse in the morning, and better in the evening (due to increased venous and CSF discharge due to gravity).
• Weakness - depending where this is. Usually the weakness is more subtle and gradual than if it comes from a stroke. Stroke weaknesses are more acute.
• Clumsiness
• Difficulty walking (cerebellar tumours)
• Seizures
• Drowsiness
What are the signs and symptoms of brain tumours in children?
- Seizure not related to a high fever
- Staring, repetitive automatic movements
- Persistent vomiting without any known cause, nausea
- Progressive weakness or clumsiness; neck tilt, squint
- Walking, balance problems
- Precocious puberty; growth retardation
- Sleep apnoea
- Vision problems
- Headache, especially that wakes the child up at night or is early in the morning
- Pain, especially back pain, which should be taken seriously in a child
- Changes in personality, irritability, listlessness
- Excessive thirst, and excessive urination.
What types of neuroimaging do we do if a brain tumour is suspected?
- CT-Scan - good at showing mass. However, needs MRI scan for more detail. Often done first as you need radiologist permission for MRI.
- Physiological MRI and functional MRI
- MR Spectroscopy (metabolism) - useful as secondary technique when diagnosis is already established, to see how aggressive the tumour may be.
- PET-SCAN (traces compounds - research). With a glial tumour, there is often replication and metabolism happening beyond the borders of the tumour - which can only be showed on PET, rather than MRI. Very important.
Why is neuroimaging in brain tumours important?
Neuroimaging is important as it allows you to assess tumour type as well as to help in surgery (guiding resection and biopsies). Also important to assess the response to treatment and recurrences:
○ Efficacy of radio/chemotherapy
○ Monitory progression
○ Feasibility of re-invention.
Describe the treatment for brain tumours
There isn’t a magic pill to treat them. They tend to be needed to treat with surgery. This involved:
• Stereotactic biopsy – inoperable tumours (about 0.5cm tissue)
• Open biopsy – inoperable but approachable tumours (about 1cm)
• Craniotomy for debulking (as much as tissue as possible)
There is a known clear correlation between the amount of resection, and prognosis. However this is not usually curative, as we can’t usually reach/resect all areas. Therefore, post-operative treatment is important:
• Conventional fractionated radiotherapy
• Chemotherapy (mainly Temozolomide because we believe temozolomide can cross the BBB)
• Gamma knife
• Proton beam - proton beam stops at the tumour, it does not transverse the tumour (like the gamma knife does)
• Steroids (usually pre-op)
• Anti-angiogenic factors (Avastin)
• Drugs to control symptoms
Describe the grading and staging of brain tumours?
Note: There is no staging for CNS tumours (except for medulloblastomas) because CNS tumours do not metastasise (except for medulloblastomas, which can metastasise via CSF). Because there is no staging, we can only grade CNS tumours.
• The grading system used to be based histopathological criteria (essentially proliferative activity)
• Now a new classification where even the molecular pathology is considered as well as histopathology.
Why are individualised treatments for brain tumours important?
There is a paradigm shift from “magic bullets” treatments (giving regular chemotherapy) to “individualised treatment”. This is because CNS tumours, especially glioblastomas, are very heterogeneous, so we need “individualised treatments“. There is heterogeneity in:
• Intertumoural heterogeneity (same histotype but different genetics / molecular pathways)
• Intratumoural heterogeneity
• Heterogeneity of microenvironment
Why do we need molecular tests for CNS tumours?
- It allows for individualised therapy
- Identify treatment targets
- Increase our diagnostic accuracy
- Provide a more accurate grading
- Better predict outcomes
- Better predict response to treatment
- Understand mechanisms
What are the most common CNS tumours?
The most common are the diffuse astrocytic and oligodendrogliomas, and ependymal tumours.
Medulloblastomas are the most common type of CNS tumours in the paediatric population. Though they are classed as embryonal tumours, the cells are neuroblasts and so can also be thought of as neural tumours.
Of the non neural/glial tumours, meningiomas are the most common.
What are the different types of gliomas?
- Astrocytomas
- Ependymoma
- Oligodendroglioma
- Mixed Glioma (also called Oligoastrocytoma): These tumours usually contain a high proportion of more than one type of cell.
- Optic Glioma: These tumours may involve any part of the optic pathway, and they have the potential to spread along these pathways. Most of these tumours occur in children under the age of 10.
- Gliomatosis Cerebri: This is an uncommon brain tumour that features widespread glial tumour cells in the brain. This tumour is different from other gliomas because it is scattered and widespread, typically involving two or more lobes of the brain. It could be considered a “widespread low- grade glioma” because it does not have the malignant features seen in high-grade tumours.
List the different types of astrocytomas?
- Pilocytic astrocytoma
- Diffuse astrocytoma
- Anaplastic astrocytoma
- Subependymal Giant Cell astrocytoma
- Glioblastoma multiforme a.k.a astrocytoma grade I.V or glioblastoma.
List the different types of astrocytomas?
- Pilocytic astrocytoma
- Diffuse astrocytoma
- Anaplastic astrocytoma
- Subependymal Giant Cell astrocytoma
- Glioblastoma multiforme a.k.a astrocytoma grade I.V or glioblastoma.
Where would you find astrocytomas?
Astrocytomas can appear in various parts of the brain and nervous system, including the cerebellum, the central areas of the brain, the brainstem, and the spinal cord. Pilocytic astrocytomas are usually found in the cerebellum.
Describe the features of pilocytic astrocytomas
These grade I astrocytomas typically stay in the area where they started and do not spread. They are considered the “most benign” of all the astrocytomas. Two other, less well known grade I astrocytomas are cerebellar astrocytoma and desmoplastic infantile astrocytoma.
They usually have a large cyst, with a nodule and a wall. In unfortunate cases there is involvement of the brainstem making it untreatable. In those cases where you can resect it, the patient is usually cured. Although they are usually slow growing, these tumours can become very large.
Describe the features of diffuse astrocytomas
These grade II-III astrocytomas tend to invade surrounding tissue and grow at a relatively slow pace. There is widespread invasion of astrocytes into grey and white matter.
They tend to contain microcysts and mucous-like fluid. They are grouped by the appearance and behaviour of the cells for which they are named.
Describe the features of anaplastic astrocytomas
An anaplastic astrocytoma is a grade III tumour. These rare tumours require more aggressive treatment than benign pilocytic astrocytoma. These have projections, which make it impossible for the neurosurgeon to resect it all.
Tend to have tentacle-like projections that grow into surrounding tissue, making them difficult to completely remove during surgery.
Describe the features of Subependymal Giant Cell astrocytomas
Subependymal giant cell astrocytomas are ventricular tumours associated with tuberous sclerosis. Extremely rare, and associated with tuberous sclerosis.
