Germ cell tumours occur mostly in the area of the pituitary gland (suprasellar region) and/or in the pineal region of the brain. The most common type of central nervous system germ cell tumour (CNS-GCT) is the germinoma. About 60% to 70% of germ cell tumours are germinomas.
Non-germinomatous germ cell tumours (NGGCT)
Non-germinomatous germ cell tumours (NGGCT) are sometimes called “mixed malignant germ cell tumours”. They are also called “secreting tumours” because they may secrete, or produce, a substance called alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (hCG).
The terminology surrounding NGGCTs can be very complex and confusing. If your child is diagnosed with a NGGCT, their doctor may mention that the tumour consists of one or more of the following components:
- Embryonal carcinoma
- Choriocarcinoma
- Yolk sac tumour
- Immature teratoma
- Mature teratoma
Each of these components must be addressed during treatment.
Germinomas
Germinomas do not secrete AFP and they may secrete hCG in lower levels with different threshold used in Europe (lower than 50 international units per litre, or IU/L) in America (lower than 100 IU/L) and Japan (lower than 200 IU/L). Germinomas may have sometimes mature teratoma components.
If germinomas contain anything other than mature teratoma germ cell tumour components, then it is not a germinoma. Instead, it is classified as a NGGCT, even if it contains some germinoma elements.
About tumour markers
NGGCTs may produce substances called tumour markers which can be detected in the blood or cerebrospinal fluid (the fluid in the brain and spine, also called CSF). The tumour markers are hCG and AFP. They are called tumour markers because they can be measured, and their levels can be used as a marker of certain types of germ cell tumours to diagnose and measure response during treatment and follow-up. AFP is a marker of yolk sac tumours and hCG is a marker of choriocarcinoma.
Germinomas that do not contain choriocarcinoma can also lead to small increases in hCG. The hCG threshold is different in different countries. Germ cell tumours with an hCG level below the threshold are called germinomas; germ cell tumours with an hCG above the threshold are called NGGCTs.
Any increase in AFP indicates that the germ cell tumour is non-germinomatous.
Some other tumour markers are currently being researched, such as microRNA.
Tumour markers can be increased in both the blood and the CSF, or in either the blood or the CSF. Therefore, doctors recommend that these tumour markers be measured both in the blood and CSF whenever possible.
What are symptoms of germ cell tumours?
Symptoms of germ cell tumours depend on the part of the brain where the tumour is located.
Germ cell tumours located in the pineal region generally have symptoms of increased intracranial pressure:
- Headaches increasing in frequency and severity
- Nausea and vomiting increasing in frequency and severity
- Blurred vision
- Unusual movements of the eyes
Germ cell tumours located in the basal ganglia can cause weakness on one side of the body.
Germ cell tumours in the suprasellar region cause problems with vision and often diabetes insipidus. Diabetes insipidus is not related to diabetes (mellitus) and a condition where the person pees and drinks a lot. There may be other endocrine problems such as delayed or precocious (early) puberty, which is the onset of puberty in girls and boys younger than eight or nine years of age respectively. Most children treated for a germ cell tumour in the suprasellar region of the brain will need multiple hormone replacement for the rest of their lives.
What causes germ cell tumours?
There are different scientific theories about what may cause a germ cell tumour but none of them has been proven with certainty.
How many other children have a germ cell tumour?
Germ cell tumours make up about 3% of paediatric tumours of the central nervous system in Europe and the United States. However, they are much more prevalent in Asian countries. In Japan, germ cell tumours make up 18% of brain tumours in people younger than 20 years old.
Germ cell tumours affect mostly teenagers and young adults. They are most often diagnosed around 13 to 15 years of age. They are much more common in boys than in girls.
In about half of children with a germ cell tumour, the tumour is located in a part of the brain called the pineal region. The second most common location is the suprasellar region (30%). About 10-20% will affect both locations; occurrence in the basal ganglia is very rare.
How are germ cell tumours diagnosed?
Unlike many other types of brain tumours, the diagnosis of a germ cell tumour does not always require testing of tumour tissue from a biopsy (taking a small sample of tissue from the tumour). If a magnetic resonance imaging (MRI) or computerized tomography (CT) scan shows a tumour growing in the pineal or suprasellar region of the brain, this may already suggest that it is a germ cell tumour.
The most important type of testing is to determine whether tumour markers are increased. The presence of increased tumour markers is enough to confirm a diagnosis of germ cell tumour. Most brain tumour scientists agree that if a child has both evidence of a midline brain tumour on MRI and positive tumour markers as described above, there is no need for a biopsy to confirm the diagnosis.
When tumour markers are increased, the doctor can decide to start treatment without further testing.
If a child shows evidence of brain tumour without the elevated tumour markers, most doctors will do a biopsy to determine what type of tumour the child has.
What is staging?
Staging helps to determine the prognosis, or expected effect the tumour will have on your child, as well as the type of treatment plan that is most appropriate for your child.
Germ cell tumours can spread, and comprehensive staging investigations, including MRI of the brain and spine, analysis for tumour markers and investigation of CSF for malignant cells, are needed to determine the extent of disease.
How are germ cell tumours treated?
Once the health-care team has a clear understanding of what is causing your child’s symptoms, a meeting with the team will be set up to talk about results and the treatment plan. Remember that it is helpful to bring something to take notes with, such as a paper and a pen or laptop, at each meeting with this team. It is important to have the child’s primary caregivers in this meeting, for example both parents.
The treatment team may include a neurosurgeon, a neuro-oncologist, radiation oncologist, a nurse practitioner or nurse, and a social worker. During the meeting, they will explain which doctor is responsible for your child’s treatment, and the roles of everyone who is there. Other team members may be involved such as a dietician, pharmacist, occupational therapist, and physiotherapist, depending on your child’s needs. Every team member has their role in your child’s care, and everyone works together to make your child feel better.
The doctor will explain the type of tumour that your child has, based on what the team has learned through diagnostic testing. You will learn the expected effect this tumour will have on your child in the upcoming months and years, based on what is known about the tumour. This is called the prognosis.
The team may talk about placing your child on a protocol, which is a treatment plan for germ cell tumours. You will need to consent (agree) to the plan for the treatment to begin. Teenaged patients may be asked for their consent as well.
Your team will also talk to you about placing an IV line called a central line, this will help doctors give the treatments in a safer way and avoid multiple pokes for blood tests. You will get more information about the line insertion in details during the meeting.
The treatment of germ cell tumours depends on the type of germ cell tumour. Surgery is required for a type of germ cell tumour called teratoma. For all other types of germ cell tumours, aggressive surgery may not be necessary.
Germinomas are very sensitive to chemotherapy and radiation. Non-germinomatous GCT require both chemotherapy and radiation therapy. Chemotherapy is generally given before radiation.
In North America, the treatment of a germinoma may involve one of the following:
- A combination of chemotherapy and whole ventricular irradiation
- Craniospinal radiation to the brain and spine
The treatment of a NGGCT may involve one of the following:
- Chemotherapy and craniospinal radiation
- Chemotherapy and focal radiation
Surgery may be recommended for NGGCTs if they do not respond completely to chemotherapy.
The use of chemotherapy is sometimes complicated in children with diabetes insipidus, particularly when the chemotherapy given requires hydration. This can trigger an imbalance in the fluid electrolytes in the child’s body.
The testing of tumour markers continues regularly throughout treatment and follow-up.
What is the outcome for a child with a germ cell tumour?
The success rate in the treatment of germinoma is more than 90%. NGGCTs have a success rate of about 80%.
Recurrence of germ cell tumours
Relapses in germinoma are uncommon; recurrences of germinoma and non germinomatous germ cell tumour are most common in the first 2 to 3 years.
High-dose chemotherapy may be used in the treatment of recurrent germ cell tumours.
Children with a relapsed germinoma can often be successfully treated with a combination of chemotherapy and irradiation.
Children with a relapsed NGGCT will require high dose chemotherapy/autologous stem cell transplantation and irradiation to have a chance at successful treatment.