What is an embryonal tumour in the brain?
Embryonal brain tumours develop from cells left over from when the embryo was forming in the womb, but have remained in the brain after the child has been born. The cells should be harmless, but can sometimes become cancerous. Unfortunately they then have a tendency to spread via the cerebrospinal fluid (CSF) to other parts of the brain and spinal cord, which together form the central nervous system (CNS).
These tumours were previously called primitive neuro ectodermal tumours (PNETs), but as scientists have studied them in more detail they have noticed important differences that have led to new sub-types being identified and hence re-named. This is an important step forward that enables clinicians to adapt existing treatments to the individual patient’s risk, and researchers to explore new ways to tackle these challenging tumours.
How common are embryonal tumours?
Embryonal tumours represent 20% to 25% of primary paediatric central nervous system (CNS) tumours, with medulloblastoma accounting for the majority of these tumours. If medulloblastoma are considered separately, the incidence of non-medulloblastoma embryonal tumours drops to around 2% of paediatric brain tumours.
Embryonal tumours are up to ten times more likely to be diagnosed in a child under 9 years old than they are to be diagnosed in an adult.
What types of brain tumour are classified as embryonal tumours?
Embryonal tumours are grouped into a number of different tumour types, defined in the 2016 report by the World Health Organisation (WHO) entitled “Classification of Tumours of the Central Nervous System (CNS).”
All brain tumours are classified based on their characteristics identified by histology (how they look under a microscope), and by molecular profiling (information gained via genetic testing on a sample of the tumour removed during a biopsy).
Embryonal tumours include:
There are a number of different types of medulloblastoma, so we have covered this tumour type in detail on a separate page of our website.
Atypical teratoid / rhabdoid tumour (AT/RT)
AT/RT tumours are covered in detail on a separate page on our website.
Embryonal tumour with multilayered rosettes (ETMR), C19MC-altered
This embryonal tumour is identified by amplification (extra copies of a gene) on the C19MC region on chromosome 19 (19q13.42). It tends to be diagnosed primarily in children under 4 years old, but is so rare that no incidence statistics are available.
The category of C19MC-amplified embryonal tumours has only been recognised by the World Health Organisation (WHO) since 2016 and includes those previously known as embryonal tumours with abundant neuropil and true rosettes (ETANTR), ependymoblastoma and medulloepithelioma (MEPL).
The most common location is in the cerebral hemisphere (at the front of the brain), but they have also been found in the brainstem and spinal cord. The most common age of diagnosis is 2 to 3 years old.
ETMR is classified as grade 4, meaning that it is an aggressive form of brain tumour, with a prognosis of approximately 12 months despite treatment with surgery and radiotherapy.
Embryonal tumour with multi-layered rosettes (ETMR), NOS
“NOS” stands for “Not Otherwise Specified”. This category represents tumours that look like an embryonal tumour with multi-layered rosettes (ETMR) under a microscope, but lack the C-19MC amplification. The NOS designation thus represents tumours that need to be researched in more detail before further refinements in classification can be made.
Medulloepitheliomas can form anywhere in the brain, spinal cord, or nerves just outside the spinal column. They are aggressive, fast-growing tumours that occur most often in very young children.
Prognosis is poor for patients with medulloepithelioma, with 5-year survival rates ranging between 0% and 30%.
Neuroblastomas form in certain types of nerve cells (neuroblasts) left behind from a baby’s development in the womb. Neuroblastoma outside the CNS usually begins as a tumour in the abdomen that then spreads to other parts of the body. CNS Neuroblastomas can develop in the cerebral nerve tissue (at the front of the brain) or the layers of tissue that cover the brain and spinal cord (meninges).
Primary CNS neuroblastomas, meaning those that begin in the CNS, are extremely rare and so no definite prognosis is currently available, although they tend to be aggressive grade 4 tumours. If the tumour is large and has spread to other parts of the brain or spinal cord, the prognosis is poor. However if complete tumour removal is possible, and if the child is older than 3 years, including radiotherapy amongst the treatment options may improve the outlook.
CNS ganglioneuroblastomas contains elements of both malignant neuroblastoma and benign ganglioneuroma. Neuroblastomas, ganglioneuroblastomas and ganglioneuromas all develop from primordial neural crest cells that form the sympathetic nervous system, which triggers our “flight or fight” stress response to perceived dangers.
Pure ganglioneuromas are often discovered incidentally because they are so slow growing that they rarely cause symptoms, but in this case they are combined with elements of an aggressive neuroblastoma, which makes their behaviour hard to predict.
CNS embryonal tumour, NOS
“NOS” stands for “Not Otherwise Specified,” which means that there is insufficient information to assign a more specific code or category. In some instances this refers to tumours that have not been fully tested for relevant genetic markers, but can also include tumours that have been tested, but do not show the diagnostic genetic alterations commonly seen within this tumour type.
In other words, “NOS” does not define a specific type of tumour; rather it designates a group of lesions that cannot be classified into any of the more narrowly defined groups. An NOS designation thus represents tumours that need to be researched in more detail before additional refinements in classification can be made.
Are embryonal tumours benign or cancerous?
This depends upon the stage and type of the tumour. Most embryonal tumours tend to be classified as grade 4, the most aggressive form of brain cancer, but very occasionally they may be classified as benign or slow-growing (low grade).
What is the prognosis for embryonal tumours in the brain?
This is largely dependent on:
- Type and position of the tumour
- Type and level of tumour markers
- Whether or not it has spread (metastasised) by the time it has been diagnosed
- Whether or not it is newly diagnosed or has recurred after treatment
The prognosis for each type of embryonal tumour is included in the relevant section above, but overall survival rates for embryonal tumours (not including medulloblastoma) are generally poor, ranging from less than 5% to 50% of patients surviving more than 5 years from diagnosis.
What are the symptoms of embryonal tumours?
Signs and symptoms of embryonal tumours depend upon where the tumour has developed.
Common symptoms include
- Muscular weakness or partial paralysis of facial muscles
- Muscular weakness or partial paralysis on one side of the body
How is a embryonal 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. Patients with a suspected embryonal tumour may also be offered a lumbar puncture so that a sample of the cerebral spinal fluid (CSF) can be taken for analysis.
What causes an embryonal tumour in the brain or spine?
In most cases, the cause of an embryonal tumour is not known. However there are certain inherited diseases that increase the risk of developing this type of tumour, including Turcot syndrome, Rubinstein-Taybi syndrome, Nevoid basal cell carcinoma (Gorlin) syndrome, Li-Fraumeni syndrome and Faconi anemia.
Treatment options for embryonal tumours
Surgery is usually the first type of treatment offered to patients with embryonal tumours, followed by chemotherapy. Patients over 3 years old may also be offered radiotherapy.
Some patients with aggressive embryonal tumours may be offered high-dose chemotherapy with stem cell rescue. The first step in such treatment is to remove stem cells that are immature blood cells from the blood or bone marrow of the patient, which are then frozen and stored. The patient is then given high doses of chemotherapy to kill as many of the cancer cells as possible. Afterwards, the stem cells are thawed and returned to the patient via a blood transfusion, so that they can quickly restore the levels of healthy blood cells.
New treatments may be available to some patients in the context of clinical trials. These may include immunotherapy, novel combinations of existing chemotherapy drugs, and emerging drugs that target the specific genetic mutations of individual tumour types.
How will we find a cure for embryonal 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.
Scientists at our Research Centre in the University of Portsmouth are looking at repurposing drugs for a number of different types of brain tumours. They are also studying mitochondria, exploring ways to ‘shut down’ these ‘batteries’ that supply energy to the brain tumours.
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 cancer, which may have the potential to influence a wide range of brain tumours.
Pioneering research at our Brain Tumour Research Centre at Queen Mary University of London is focused on using GBM stem cells to help develop unique, patient-specific treatments. Their findings are expected to translate into other types of adult and paediatric brain tumours.
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.
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 embryonal brain tumours.