What are paediatric embryonal tumours?

Paediatric embryonal tumours are malignant tumours (cancer) found in the central nervous system.¹ The central nervous system (CNS) consists of the brain and spinal cord. 

As the name suggests, paediatric embryonal tumours derive from embryonal cells. These cells were part of the unborn child when it was an embryo (very early stage of development). Unlike the other embryonal cells, some of these embryonal cells did not become the parts of the body they were meant to become. Instead, they started forming paediatric embryonal tumours.² 

This article focuses on paediatric embryonal tumours occurring in babies and children. In general, embryonal tumours are seen more frequently in babies and children than they are in adults.¹

As cancers often do, paediatric embryonal tumours have a strong tendency to spread (disseminate), in this case throughout the CNS.³ This dissemination involves paediatric embryonal tumour cells reaching and trying to take hold in other parts of the CNS. If this is successful, this dissemination is called metastasis and results in the formation of a malignant tumour that is very similar to the original (primary) tumour but at a different location than the original. This new but similar malignant tumour would be called a secondary or metastatic tumour.

Types of paediatric embryonal tumours

There are several types of paediatric embryonal tumours. The three big categories of paediatric embryonal tumours are medulloblastoma, atypical teratoid rhabdoid tumour (ATRT), and embryonal tumours with multilayered rosettes (ETMR).⁴

Medulloblastoma

A medulloblastoma is a malignant tumour of the cerebellum which is a part of the brain towards the back of the skull. The function of the cerebellum is to control balance and movement. 

Medulloblastomas are the most common paediatric embryonal tumours. Unfortunately, one third of those plagued by a medulloblastoma do not survive. The two thirds who do survive often suffer from long-term consequences. These long-term afflictions include impaired mental abilities, endocrine disorders (having too many or too few hormones), and secondary malignant tumours.⁴

The World Health Organisation (WHO) distinguishes between 4 subtypes of medulloblastoma. The first two groups are called wingless (WNT) and sonic hedgehog (SHH). They are named after the signalling pathways which are very active in the respective medulloblastoma types.⁴ 

WNT medulloblastomas are the rarest type of medulloblastomas (roughly 10% of medulloblastomas), generally do not metastasize (spread), and have the best prognosis of all the medulloblastoma types.⁵ In contrast, about 30% of medulloblastomas are SHH medulloblastomas and their prognosis varies greatly. WNT and SHH medulloblastomas are associated with certain gene mutations commonly found in these medulloblastomas.⁴ 

The other two, simply called Group 3 and Group 4 medulloblastomas, do not have signalling pathways associated with them. Instead, there are simply some mutations in certain genes which are often found in Group 3 and 4 medulloblastomas.

Roughly 25% of medulloblastomas are Group 3 medulloblastomas and they carry the worst prognosis of all the medulloblastoma types. 

Group 4 is the most common type of medulloblastoma (about 35% of medulloblastomas). Despite their tendency to metastasize (spread), their prognosis is not as bad as it is for Group 3 medulloblastomas.⁴

Atypical teratoid rhabdoid tumour (ATRT)

Atypical teratoid rhabdoid tumours (ATRTs) are aggressive malignant tumours which mostly form in the cerebellum but can also be found in other parts of the CNS. ATRTs predominantly occur in babies and children who are assigned male at birth. They are most often found in babies and children who are under 3 years old. At the time of diagnosis, about 20% of the affected individuals have multiple ATRTs. Unfortunately, the prognosis is generally not good.⁴

ATRTs are characterised by either a dysfunctional SMARCB1 gene (common) or a dysfunctional SMARCA4 gene (rare).

These gene mutations impairing the SMARCB1 or the SMARCA4 gene are sometimes inherited from the biological parents. If that is the case, the affected baby or child has a cancer predisposition syndrome called rhabdoid tumour predisposition syndrome. This means they are born with these dysfunctional genes and are therefore very likely to develop ATRTs during their lifetime. It is advised that patients with ATRTs undergo genetic counselling and are subsequently checked for rhabdoid tumour predisposition syndrome.⁴

Embryonal tumours with multilayered rosettes (ETMR)

Embryonal tumours with multilayered rosettes (ETMR) are very aggressive malignant tumours. Unfortunately, patients with ETMR tend to survive for only about a year after diagnosis. ETMR are usually found in children under 4 and are more commonly seen in children which are assigned female at birth.⁴ 

ETMR are classified as PNETs (primitive neuro-ectodermal tumours).⁴ PNETs form from the external cells of an embryo.

ETMR are divided into three groups, namely embryonal tumours with abundant neuropil and true rosettes (ETANTR), medulloepithelioma (MEPL) and ependymoblastoma (EBL). Each one of them has a distinct appearance. All of them share characteristic genetic changes found on the 19th chromosome.⁴

Symptoms of paediatric embryonal tumours

Medulloblastoma

In babies and children with medulloblastoma(s), symptoms can include:⁵

• Headache
• Lethargy
• Nausea
• Vomiting
• Changes in behaviour
• Ataxia (lack of muscle control) 

Atypical teratoid rhabdoid tumour (ATRT)

ATRTs can cause:

• Nausea
• Vomiting
• Reduced balance
• Headache
• Drowsiness
• Decreased coordination

Embryonal tumours with multilayered rosettes (ETMR)

ETMR can result in the following symptoms:⁶

• Paresis (muscle weakness)
• Ataxia (lack of muscle control)
• Problems with vision
• Seizures
• Torticollis (neck muscles force the head into an awkward position)

Diagnosis of paediatric embryonal tumours

Medulloblastoma

Medulloblastomas show a characteristic appearance when imaged with CT (computer tomography) and/or MRI (magnetic resonance imaging).⁵

In order to determine what kind of medulloblastoma it is, the tumour will be examined after surgical removal. The removed tumour will serve as a sample to detect the specific gene mutations associated with the different types of medulloblastoma.⁴ 

Atypical teratoid rhabdoid tumour (ATRT)

An MRI scan will be used to detect a potential ATRT. Afterwards, a sample will be obtained either via a biopsy of the tumour or when the tumour is removed. If the tumour shows evidence of a dysfunctional SMARCB1 gene or a dysfunctional SMARCA4 gene, the tumour is confirmed to be an ATRT.⁴

Embryonal tumours with multilayered rosettes (ETMR)

An MRI scan of the tumour can already be indicative of an ETMR since it has a specific appearance in MRI images. Removal and subsequent examination of the tumour allows further confirmation of the ETMR diagnosis.⁷

ETMR often have a very typical appearance under the microscope. Additionally, detection of the characteristic genetic changes on chromosome 19 in the tumour also helps to confirm the ETMR diagnosis. The same thing applies to the detection of certain protein called LIN28A in the tumour.⁷

In the end, all of these things together (certain appearance on MRI images and under the microscope, chromosome 19 genetic alterations and the presence of LIN28A) establish the ETMR diagnosis.⁷

Treatment of paediatric embryonal tumours

Medulloblastoma

The standard therapies for medulloblastoma are surgery to remove as much of the tumour(s) as possible, followed by irradiation of the brain and spine (craniospinal radiotherapy) and/or chemotherapy.^1,3,4

Radiotherapy is not performed if the patient is younger than 3. Additionally, radiotherapy is avoided in general because it often causes long-term negative effects. If the patient is old enough and radiotherapy is absolutely necessary, it is attempted to lessen the long-term negative effects. This is done by using lower radiation doses or a different form of radiotherapy (e.g. radiotherapy using protons and electrons instead of X-rays and gamma rays).^3,4,8

Chemotherapy for medulloblastoma routinely involves using several chemotherapeutic drugs at once. If trying to avoid or reduce the radiotherapy dosage, the concentration of the chemotherapeutic drugs might be increased instead to make up for it.^1,4

Taking into account the medulloblastoma subtypes, a more targeted approach is being tested in research and clinical trials. An example of that would be the usage of drugs which target the WNT and SHH signalling pathways in WNT and SHH medulloblastomas, respectively.⁴

Atypical teratoid rhabdoid tumour (ATRT)

Treatment of ATRTs generally involves removal of the tumour(s) via surgery and subsequent chemotherapy.^1,4 

Craniospinal radiotherapy is used occasionally but is generally avoided. When it is put to use, applying radiotherapy of lower intensity can lessen the long-term negative effects of this treatment method.⁴

Experimental treatments for ATRTs are being looked into as well, with a plethora of different drugs being tested for their effectiveness.^1,4

Embryonal tumours with multilayered rosettes (ETMR)

ETMR are treated by a mix of surgical tumour removal and chemotherapy. Often, this combination is supplemented by radiotherapy. The radiotherapy is either restricted to the specific tumour location (focal) or it is used throughout the CNS (craniospinal).⁴

New treatment approaches for ETMR are being tested in research. These include drugs which target signalling pathways and proteins activated as a result of the characteristic genetic alterations on the 19th chromosome.^1,4

FAQs

What is the most common embryonal childhood tumour?

The most common paediatric embryonal tumours are medulloblastomas which are found in a part of the brain called the cerebellum. 

What is the survival rate for embryonal brain tumours?

The survival rate differs between the various types of embryonal brain tumours. Unfortunately, due to their aggressiveness and their tendency to spread, the survival rates tend to be poor for all the various types of embryonal brain tumours. 

At what age do embryonal brain tumours occur?

Embryonal brain tumours can occur at any age but a great many of them seem to manifest before the age of 4.

What causes embryonal tumours?

Embryonal tumours derive from embryonal cells and many of these embryonal tumours are associated with certain gene mutations. This suggests that these specific gene mutations are the reason some embryonal cells start forming tumours instead of healthy body cells.

Summary

Paediatric embryonal tumours are cancers of the brain and the spinal cord found in babies and children. They tend to spread throughout the CNS, forming new tumours in other locations of the CNS as a result. Paediatric embryonal tumours form from embryonal cells and most of them fall into three categories: medulloblastoma, atypical teratoid rhabdoid tumour (ATRT), or embryonal tumours with multilayered rosettes (ETMR). Each of them is associated with their own gene mutations and has their own characteristics.

Unfortunately, the survival rates tend to be equally poor among all of them. Symptoms of paediatric embryonal tumours include headaches, muscle weakness, nausea and seizures. The three general treatment methods are surgical tumour removal and subsequent chemotherapy sometimes combined with radiotherapy.