Neuronal and Mixed Neuronal-glial Tumours
40% of all cancers spread to the brain
What is a neuronal or mixed neuronal-glial (glioneuronal) tumour?
A neuronal tumour contains abnormal neurones. Neurones are responsible for all the neurological functions of the brain, so their main role is to carry information throughout the brain and central nervous system.
Mixed neuronal-glial tumours, sometimes referred to as glioneuronal tumours, are a mixture of neuronal and glioma brain tumours. They therefore contain abnormal neurones plus elements of one or more type of glioma brain tumour such as astrocytoma, oligodendroglioma and ganglioglioma.
Neuronal and mixed neuronal-glial tumours are usually low-grade (slow growing) tumours with an excellent long-term prognosis. Almost all of them are associated with epilepsy that rarely responds to drug treatment, but the seizures can often be cured once
the tumour is wholly or partly removed using neurosurgery.
What types of neuronal or mixed neuronal-glial brain tumours are there?
This large group includes the following types of tumour:
Dysembryoplastic neuroepithelial tumour (DNET)
DNETs are the most common type of mixed neuronal-glial tumours.
- Grade 1 low-grade (slow growing) tumour.
- Only very rarely transforms to a more aggressive grade.
- Can occur anywhere in the central nervous system (brain and spine) but over 65% cases are in the temporal lobe, and around 20% cases in the frontal lobe of the brain.
- In up to 80% cases, DNET brain tumours are associated with abnormal development of the cortex area of the brain, which is the outermost part of the brain responsible for thought processes that define the human personality such as perception, reasoning, memory and language.
- In some cases, an association with a developmental disorder called Noonan syndrome has been reported. This can be established using genetic testing.
- Usually causes longstanding, treatment resistant partial seizures that begin in childhood (before the age of 20).
- Treatment for DNETs is usually neurosurgery, which can often stop the seizures and results in an excellent prognosis of potential cure.
Gangliogliomas are the second most common form of mixed neuronal-glial tumours are are covered in detail on our web page dedicated to this tumour type.
- Grade 1 low-grade (slow growing) neuronal tumour.
- Gangliocytomas are formed of large, abnormal mature neurones.
- They differ from gangliogliomas because they don’t contain any abnormal glial cells, so are not classified as a type of mixed glioma.
- Primarily diagnosed in children.
- Frequently cause epilepsy that tends not to respond well to drugs.
- Treatment for gangliocytoma is usually neurosurgery, which can often stop the seizures and results in an excellent prognosis of potential cure.
Dysplastic cerebellar gangliocytoma (Lhermittte-Duclos disease)
- A rare condition characterised by a particular form of the low-grade neuronal tumour gangliocytoma (described above) that occurs in the cerebellar cortex of the brain; an area that controls purposeful movements such as being able to grasp things and pick them up.
- Other features of Lhermitte-Duclos disease may include an enlarged brain, extra fingers or toes, partial gigantism and/or a large tongue (macroglossia).
- Lhermitte-Duclos disease is sometimes found to be part of a condition called Cowden's syndrome, which increases the risk of several forms of cancer. The cause of these diseases is unknown.
- Lhermitte-Duclos disease typically presents in adults aged 30 to 40 years, although it has been encountered at all ages.
- The genetics of childhood-onset dysplastic cerebellar gangliocytoma (Lhermittte-Duclos disease) appears to be different to the adult onset form, so in future it is likely that different personalised treatments will be available for different age groups.
Desmoplastic infantile astrocytoma and ganglioglioma
Previously classified as two different types of tumour, desmoplastic infantile astrocytoma and desmoplastic infantile ganglioglioma are considered so similar that they were grouped together by the World Health Organisation (WHO) in 2016. However, more recent laboratory and data processing techniques have identified some distinct genetic mutations between these two tumours, which may lead to the development of individualised treatments in the future.
- Grade 1 low-grade (slow growing) mixed neuronal-glial tumour.
- Abnormal cells within these tumours may resemble those that usually form the meninges (layers of cells that surround the brain, just below the skull), combined with astrocytes (a type of glial cell that supports neurones) as well as abnormal neurones.
- Tumours contain both solid and cystic (fluid filled) areas.
- Usually appear in children under 2 years old, but very occasionally in adults.
- The most common symptom is a rapidly increasing head circumference, noticed over timeframes varying between 5 days and 3 months.
- This is one of the few mixed neuronal-glial tumours that rarely cause seizures.
- Surgery would be the first line of treatment, and if all of the tumour can be removed, this can result in a cure. If some of the tumour is unable to be removed, chemotherapy and/or radiotherapy may then be offered.
Papillary glioneuronal tumour
Originally considered to be a type of ganglioglioma, a papillary glioneural tumour has been recognised as a distinct mixed neuronal-glial tumour by the World Health Organisation since 2007.
- Usually a grade 1 low-grade (slow growing) tumour.
- Occasionally these tumours can behave more aggressively.
- Tumours contain abnormal glial (astrocytic) and neuronal cells.
- They contain both solid and cystic (fluid filled) areas, and often areas of calcification (a build-up of calcium).
- Most papillary glioneuronal tumours have been reported in patients aged between 11 and 41 years old, but can appear at any age.
- If they can be completely removed, a cure can be achieved.
- Radiotherapy and chemotherapy may be offered if some areas of tumour are unable to be removed using neurosurgery alone.
Rosette-forming glioneuronal tumour (RGNT)
- A grade 1 low-grade (slow growing) tumour.
- RGNTs consist of 2 types of abnormal cells: neuronal cells that form shapes resembling rosettes, and astrocyte cells that resemble those found in a type of paediatric tumour called a pilocytic astrocytoma.
- Can be a solid tumour or one that contains cysts (fluid filled sacs).
- Calcification (a build-up of calcium) is seen in around 25% tumours.
- 60% of these tumours appear on the midline of the brain and involve the fourth ventricle (one of the fluid-filled areas in the centre of the brain) and/or the aqueduct of Sylvius. The aqueduct of Sylvius is a canal between the third and fourth ventricles in the brain that carries the cerebral spinal fluid (CSF) between the ventricles and the central canal of the spinal cord.
- Unfortunately these tumours often invade surrounding tissues within the brain, sometimes including the pineal region.
- Mainly diagnosed in younger people, though the average age at diagnosis is 30 years old.
- If the tumour appears in a position that allows for complete removal using neurosurgery, a cure is possible without the need for any further treatment.
Diffuse leptomeningeal glioneuronal tumour
- This is a new category of brain tumour introduced by the World Health Organisation (WHO) in 2016.
- Grade 1 or 2 low-grade (slow growing) tumours.
- Most commonly diagnosed in young people under the age of 18, but can also be found in adults.
- Often cause hydrocephalus (a build-up of cerebral spinal fluid in the brain) and hence headaches or seizures.
- Reported survival times vary widely, because this relatively new classification may have historically included tumours now categorised differently.
- Severity of hydrocephalus influences the prognosis, with hydrocephalus that is hard to treat sometimes shortening the lifespan as well as the quality of life of the patient.
- Their diffuse nature means that they spread amongst healthy brain tissue and hence are difficult to remove completely using neurosurgery. Radiotherapy and/or chemotherapy is likely to be offered after neurosurgery.
Neurocytomas are classified as grade 2 (low-grade) tumours and consist of abnormal neuronal cells, often with cysts (sacs filled with cerebral spinal fluid). The first line of treatment would be neurosurgery, which often results in a cure if the tumour can be completely removed. If any tumour remains behind then this is likely to be followed by radiotherapy and/or chemotherapy.
All neurocytomas are very similar but are divided into a number of different types:
Intraventricular or central neurocytoma
- The most common form of neurocytoma
- Usually located centrally within the ventricles (fluid filled spaces of the brain) and in these cases referred to as a central neurocytoma.
Extraventricular neurocytoma (EVN)
- Extraventricular means that these tumours are found outside the ventricles of the brain.
- Occur anywhere within the brain or spinal cord, but often appear in the cerebral hemispheres of the brain and in such cases was previously known as a cerebral neurocytoma, The right cerebral hemisphere controls the muscles on the left side of the body, and the left cerebral hemisphere controls the muscles on the right side of the body.
- Primarily found in children and young adults, and rarely in elderly patients.
- A type of extraventricular neurocytoma that involves ganglion cells as well as neuronal cells. Ganglion cells are found in neurons that are partly outside the central nervous system (brain and spinal cord), and therefore form connections between the central and peripheral nervous systems. For example, there is a ganglion cell layer in the retina at the back of the eye containing neurons that carry information from the eyes to the brain.
These tumours are also known as neurolipocytomas and are partly named after the place in which they occur, which is the cerebellum. The cerebellum is found at the back and bottom of the brain, and helps to control voluntary actions such as movement, co-ordination, balance and speech.
- Grade 2 low-grade (slow growing) tumours.
- Formed of abnormal neuronal cells, they also feature a build-up of fats (lipids) inside the tumour cells.
- Very rare, but tend to be recorded in middle-aged adults.
- Neurosurgery alone can result in a cure for some patients, whilst for others radiotherapy and/or chemotherapy may also be offered.
- Due to the complex nature of the area in which they occur not all tumours can be successfully removed and so the overall 5 years survival rate is approximately 50%, though cases of people surviving for more than 18 years are also recorded in the literature.
Paragangliomas are sometimes called glomus tumours and can be found in various locations throughout the body. Those within the head and neck are referred to as parasympathetic paragangliomas because they influence the parasympathetic nervous system, sometimes known as the “rest and digest” part of the nervous system that balances the “fight or flight” sympathetic nervous system stress response.
- Formed of abnormal paraganglia cells, which are clusters of neuroendocrine cells left over from the formation of the embryo that secrete the stress hormones adrenalin and noradrenalin (also referred to as epinephrine and norepinephrine). Paraganglia cells are found throughout the body, particularly around the adrenal glands and various blood vessels and nerves, including some in the head and neck. Paraganglia cells interact closely with the autonomic nervous system, which affects functions such as breathing and heart rate.
- Parasympathetic paragangliomas rarely secrete adrenalin or noradrenalin, but cause symptoms because they take up space in the head and hence impact upon brain function.
- They can be hereditary, and are associated with genetic conditions such as von Hippel-Lindau syndrome, neurofibromatosis type 1, multiple endocrine neoplasia types 2A and 2B, and Carney-Stratakis syndrome. All can be confirmed using genetic testing, and patients with these conditions would receive extra support in addition to their neuro-oncology team.
- Treatment is likely to include neurosurgery and/or radiotherapy.
- Unfortunately paragangliomas may metastasise (spread) to other locations in the body and this will influence the prognosis, which varies widely between individuals.
Are neuronal and mixed neuronal-glial tumours benign or cancerous?
The majority of these tumours are low-grade, slow growing tumours. Those that can be completely removed using neurosurgery would be considered to be benign, although sometimes the symptoms that these low-grade tumours can cause are challenging and hence the term benign may not feel appropriate.
Only very rarely do these tumours present in aggressive, high-grade forms of cancer.
What is the prognosis for neuronal or mixed neuronal-glial tumours?
Neuronal and mixed neuronal-glial tumours are usually low-grade (slow growing) tumours with an excellent long-term prognosis, as many of them can be completely removed during a neurosurgical operation.
Unfortunately, those that cannot be completely removed using neurosurgery may have a worse impact on quality of life, and a worse prognosis. Due to their rarity, many of the tumours within this group do not have an average prognosis available and each
patient will be treated as an individual.
What are the symptoms of a neuronal or mixed neuronal-glial tumour?
The symptoms will depend upon exactly where the tumour is in the brain, and hence which parts of brain function are affected. Symptoms are likely to include one of more of the following:
- Regular vomiting
- High blood pressure
- Visual disturbances
- Headaches, often worse after lying down
- Nerves in the face being affected: so a lopsided smile or a drooping eyelid
- Problems with speaking
- Personality changes
- Confusion, such as not understanding what others are saying
- Ataxia, meaning a lack of voluntary control of muscles. This can take the form of weakness or paralysis on one side of the body, perhaps in one arm for example, or difficulty with walking.
How is a neuronal or mixed neuronal-glial tumour diagnosed?
The most reliable way to diagnose any kind of brain tumour is initially by an MRI scan and then by taking a biopsy (a small sample of the tumour, removed during neurosurgery) for analysis in a laboratory.
How common are neuronal or mixed neuronal-glial tumours?
For children, neuronal and mixed neuronal-glial tumours represent about 10% of all tumours of the central nervous system (brain and spine).
Occasionally these tumours may also be diagnosed in adults, but this is more unusual and no reliable statistics for such cases are available.
What causes a neuronal or mixed neuronal-glial tumour?
The cause of most neuronal or mixed neuronal-glial tumours is not known, so unfortunately there are no proven ways to prevent them from occurring.
Some tumours may be associated with conditions such as Neurofibromatosis 1, Noonan syndrome, Lhermitte-Duclos disease and Cowden's syndrome, all of which can be confirmed using genetic tests. Patients would then be offered specialist care in addition to that provided by their neuro-oncology team.
Treatment options for neuronal or mixed neuronal-glial brain tumours
The first type of treatment offered to patients with neuronal or mixed neuronal-glial brain tumours would be neurosurgery, and in many cases a complete resection (removal) of the tumour that results in a cure can be achieved.
If some of the tumour is unable to be removed using neurosurgery, chemotherapy or radiotherapy may also be offered.
There are many researchers looking for a cure for brain tumours, so new treatments may be available to some patients in the context of clinical trials.
To potentially participate in other types of research, please click here.
How will we find a cure for neuronal and mixed neuronal-glial brain tumours?
Research we are funding across all of our dedicated Research Centres will help lead towards finding a cure for a wide range of brain tumours.
Pioneering research at our Brain Tumour Research Centre at Queen Mary University of London is focused on using glioblastoma multiforme (GBM) stem cells to help develop unique, patient-specific treatments. GBMs are the most aggressive type of glioma brain tumour in adults and it is hoped that discoveries will translate into other types of adult and paediatric gliomas.
Our team at the University of Plymouth Low-Grade Brain Tumour Research Centre are researching a number of molecular pathways that influence immune system function, tumour metabolism and tumour growth in a range of low-grade brain tumours in children and adults. This includes how gliomas begin, and how they transform from low-grade to high-grade.
The team of research and clinical experts in our Research Centre at Imperial College, London are studying the way in which the ketogenic diet works in brain tumours including gliomas. Their work on drugs that reduce levels of arginine, an amino acid in the blood, may also have the potential to influence a wide range of brain tumours.
We also fund BRAIN UK at Southampton University, the country’s only national tissue bank registry providing crucial access to brain tumour samples for researchers from all clinical neuroscience centres in the UK, effectively covering about 90% of the UK population, and an essential component in the fight to find a cure for all types of brain tumours.
Page last updated in October 2019.