Introduction

Embryonal tumours are a form of brain tumour, caused by the presence of leftover cells present in the earlier stage of embryonic development. These types of cells can also be called embryonic cells and they are mostly harmless, however in certain cases these cells can develop into cancer.¹ 

It is important to diagnose this condition as early as possible to improve treatment results, to personalise the treatment, prevent the progression of the disease and increase the possibility of survival for the affected persons.

Let’s take a look into embryonal tumours, and most importantly into the ways they can be diagnosed and treated.

Types of embryonal tumours

Embryonic tumours can be caused by cancerous cells that remain in the brain after birth. They are caused by a fast and uncontrolled growth of cells called embryonal cells. Embryonic tumours are mainly childhood cancers, with half of diagnoses being made in children younger than 10 years old.^2,12 

Tumours can be considered benign (non-cancerous), or malignant which leads to cancer. While benign tumours are known to grow in size, pressing on different parts of the brain, malignant tumours are bad anomalies which usually grow quickly and can spread not only in other parts of the brain but also around the body (in rare cases). This is known as metastasis, referred to as metastatic cancer. 

When growing or spreading the tumour can lead to damage, causing the part of the brain where the tumour is located to stop working the way it should, and in both cases can lead to serious consequences which should be treated.²

Embryonal tumours can be located in any part of the brain, including the cerebrum, brain stem or spinal cord. Types of tumours include:

• Medulloblastoma: this develops in a zone of the brain called the cerebellum and is most common in children
• Atypical teratoid/rhabdoid tumours, which are usually located in the cerebellum
• Embryonal tumour with multilayered rosettes or ETMRs, which originates in a zone called the cerebrum
• Central Nervous System (CNS) embryonal tumours NEC/NOS (not elsewhere classified/not otherwise specified) are brain tumours that have not been classified and cannot be put into other categories
• CNS tumours with BCOR internal tandem duplication: this tumour can develop anywhere between the brain or spinal cord
• CNS neuroblastomas, fox 2 activated, which develop in the nerve tissue of the cerebrum

Medulloblastoma 

Medulloblastoma is the most common type of embryonal tumour. This tumour forms in the cerebellum, a part of the brain with an important role in muscle movement and control of balance and posture. This type of tumour comprises about 20% of tumours occurring in the central nervous system (CNS) in patients younger than 18, and is commonly found in children aged between 3 and 8, most commonly in males.^2,7,13

CNS Neuroblastoma fox 2 activated 

Central nervous system (CNS) Neuroblastoma is a rare type of embryonal tumour that affects the nerve tissue of the cerebrum, the brain or the spinal cord. This type of tumour can be large and spread to the brain and spinal cord.¹⁴

Atypical teratoid/rhabdoid tumours

This is a rare form of embryonic tumour. It is the most common however in children younger than 12 months of age. It can affect the area of the cerebrum and cerebellum, but rarely the spinal cord.¹⁵ 

CNS embryonal tumours NEC/NOS

These types of tumours are excluded from the other categories of tumours and are also called central nervous system embryonal tumours, not otherwise specified (NOS) or not elsewhere classified (NEC). This type of tumour might have been rare or not known enough to meet any criteria.¹⁵ 

Embryonal tumour with multilayered rosettes

This is a rare and very aggressive tumour, with a survival rate of under 30% 5 years from diagnosis.

This type of tumour usually occurs in children younger than 2 years and It forms in the brain and spinal cord. This is a fast-growing and very malignant tumour.² 

CNS tumours with BCOR internal tandem duplication

This is a very rare tumour occurring mostly in children younger than 10, but which can occur also in older children and teens.

Most of these embryonal tumours in children can be malignant and can spread from the cerebrospinal fluid to other zones of the brain and to the spinal cord. After leukaemia, brain tumours are the most common form of cancer in children.²

Diagnosis of embryonal tumours

If you or a family member suspected you may be suffering from an embryonal form of tumour, your doctor will investigate different zones of your brain and spinal cord to exclude other conditions.

You will be asked about personal and family history and will undergo a neurological examination (physical exam checking vision, hearing and reflexes). Tests used to diagnose embryonal tumours include:

• MRI
• CT Scan
• Lumbar puncture
• A biopsy of the tumour

Clinical presentation

Symptoms of embryonal cancer can vary based on the type of tumour and the location on the body. Common symptoms include:

• Trouble with speech, balance, and coordination, or slow speech
• Headache in the morning, or headache that disappears after vomiting
• Weakness
• Weakness on the side of the face
• Sleepiness, change in energy levels
• Seizures
• Nausea or vomiting

In infants and children, this might also result in irritability and slow growth, bad appetite and slow development. In infants it can cause an increase in the infant’s head size.² 

It is important to note that many symptoms might not show until the tumour has grown bigger, but it is important to take note of any of the listed symptoms and check with your or your child’s doctor for the possible cause.²

Testing

MRI

Magnetic resonance imaging can be done on the spinal cord and brain. This procedure utilises radio waves to create a detailed image of the areas of the brain and spinal cord, with the help of an injected substance called gadolinium. Gadolinium can highlight the cancer cells, helping them appear brighter.² 

CT Scan

Computed tomography (CT) scans are connected to x-ray machines to make detailed pictures of internal organs. You might be asked to swallow or be injected with a dye to show organs and tissues clearly.² 

Lumbar puncture

This procedure can be used to collect cerebrospinal fluid. This substance is collected from the spinal columns by placing a needle between two bones in the spine. After collection, the sample is checked under the microscope for signs of tumoral cells, protein and glucose, as higher protein levels or lower glucose levels might highlight the presence of a tumour.² 

Biopsy

When a tumour is suspected, you might undergo a biopsy. A biopsy is carried out by removing part of the skull, by using a needle to remove a small sample of brain tissue. After the tissue is removed a pathologist will examine it for cancer cells under a microscope.²

Biomarker

A biomarker test is used to identify which processes happen in the body and can be used to understand the tumour, by predicting the rate of growth, detecting the type of tumour and estimating the patient's answer to treatment.^2,16 

Treatment approaches

Treatment is carried out taking into account factors such as tumour type or age. In children over 3 years of age it can also depend on the tumour risk.

An average-risk tumour can usually be completely or almost completely removed leaving only a small amount of tissue, if the tumour has not had the time to spread in the rest of the body.

A high-risk tumour may occur when the tumour was not removed and a part remains, and/or when the cancer spreads to other zones of the brain, body, or spinal cord. High-risk tumours have a higher chance of returning even after treatment.²

Usually, tumours are described using stages to describe the spread of the tumour, however in childhood embryonic tumours, there is no staging system. As treatment depends on the child’s age, younger children might receive different treatments than older children.² 

Surgery

Surgery might be the first treatment option proposed to the patient. A doctor, usually a neurosurgeon, will try to remove the tumour. Complete removal will depend on the position and size of the tumour. If the tumour is situated near important blood vessels or nerves, the doctor will most likely proceed with a partial removal, supplemented with additional radiotherapy and chemotherapy.

Radiation therapy

Radiotherapy uses radiation to kill cancer cells or stop their growth. In children, cancer might be treated with external beam radiation therapy which uses a machine to send radiation toward the area of the body affected by cancer.

Radiotherapy can affect development in younger children, especially if younger than 3 years old. In these cases, chemotherapy might help reduce the need for radiotherapy.^2,9

Chemotherapy

Chemotherapy uses a series of drugs to stop the progression of cancer by killing or stopping cancer cell growth. Just like radiotherapy, chemotherapy can be carried out alongside other treatments or on its own.

It can be ingested or given intravenously (by vein) so that it can spread from the bloodstream into the rest of the body. In some cases, drugs that can cross the brain barriers are used.² 

High-dose chemotherapy

In some cases, doctors might proceed with high doses of chemotherapy to kill cancerous cells. However, this treatment can destroy healthy cells. To replace the loss of healthy blood cells, a stem cell transplant can be used. Stem cells are immature blood cells removed from the patient's bone marrow, frozen, stored, and given back to the patients through infusion after chemotherapy.²

Targeted therapy

Targeted therapy is a procedure that uses drugs to block specific molecules, proteins or enzymes that help cancer growth and spread.² 

Clinical trials

Clinical trials are studies that develop new cures and treatments that give people with diseases the chance to try the latest new treatments or improved versions of existing treatments.

Clinical trial treatments may have unknown side effects as they are still being studied, however, for some patients, a clinical trial might be the best choice.^2,17

Side effects

There might be side effects after and during cancer treatment, during treatment, the patient might experience the side effects listed below:³

• Anaemia
• Appetite loss
• Bleeding and bruising (Thrombocytopenia)
• Constipation
• Delirium
• Diarrhoea
• Oedema (swelling)
• Fatigue
• Fertility issues
• Flu-like symptoms
• Hair loss (alopecia)
• Infection and neutropaenia
• Lymphoedema
• Memory or concentration problems
• Mouth and throat problems
• Nausea and vomiting
• Nerve problems (peripheral neuropathy)
• Organ-related inflammation and immunotherapy
• Pain
• Sexual health issues Skin and nail changes
• Sleep problems 
• Urinary and bladder problems

After treatment some side effects might continue for months or years. These symptoms are also called late effects and can include:

• Physical problems affecting growth and development
• Physical problems affecting the heart, thyroid, and hearing
• Mood swings, changes in feelings, thinking, learning and memory
• Secondary cancers, affecting different zones of the body such as the thyroid or other zones of the brain

After radiation therapy or surgery, children diagnosed with medulloblastoma might experience some changes, some of which might be tied to cerebellar mutism syndrome, including:

• Delayed speech
• Difficulty swallowing and eating
• Loss of muscle
• Mood swings and differences in personality
• Trouble with balance, walking and handwriting

Some late side effects can be treated and controlled.² 

Follow-up tests

Previous tests might be repeated, to monitor the progress of treatment and to check its effectiveness. Based on the results of these tests, doctors might decide whether to proceed with treatment or whether to stop.

After treatment, imaging tests such as MRI or CT scans will continue. These tests will highlight whether the tumour has returned or indicate the presence of abnormalities in the brain tissue.² 

Prognosis

Unfortunately, children diagnosed with embryonic tumours have a low survival rate, ranging from less than 5% to 50% of living patients after five years from treatment.¹²

Summary

In conclusion, embryonal tumours are serious but rare brain tumours that affect mainly young children under 10 years old. Because of the severity of this cancer, early detection and intervention are crucial to improve the success of treatment and increase the chances of survival.

Treatments have improved over the years, with new medical advancements in research and medical trials available as treatment options for patients, and additionally personalised treatment options available to fight embryonal tumours based on individual cases.

There are several risk factors associated with embryonal tumours, and it is important to be aware of them and seek immediate medical attention if any of the symptoms present themselves.

Summary of key points

• Embryonal tumours are a type of brain tumour caused by cells present during embryonic development before birth
• Early diagnosis is vital to personalise treatment and increase survival rates
• Embryonal tumours can be benign and grow in size or malignant, and spread reaching life-threatening levels
• At least 50% of patients affected by embryonal tumours are under 10, however, these tumours can affect young adults too
• Several treatment options are available, but the first step is almost always surgery
• Embryonal tumours are rare, but unfortunately children diagnosed with these tumours have a low survival rate