Germ cell tumours (GCTs) are cancers that develop from germ cells, the biological cells that develop into gametes (reproductive cells), such as the ovum and sperm. They are typically found in the gonads (organs that produce gametes, including the testicles and ovaries), most often in children under the age of 15. For more information on gonadal GCTs, please refer to the Rare Cancers Australia Ovarian Cancer (Germ-Cell) page and/or the Testicular Cancer page.
In rare cases, GCTs can develop in places outside of the gonads, and are known as extragonadal GCTs. Extragonadal GCTs most commonly occur in the brain, the mediastinum (space between the lungs that holds many important structures, including the heart, trachea, and oesophagus), the retroperitoneum (a space located behind the abdomen that contains many important bodily structures such as the kidneys), and the sacrococcygeal region (the area where the sacrum and coccyx sections of the spine are connected).
This page will focus on GCTs that occur in the brain, also known as intracranial GCTs. Much like other extragonadal GCTs, intracranial GCTs tend to develop in the midline structures of the brain, such as the pineal gland and the suprasellar region (the area between the top of the pituitary gland and the bottom of the hypothalamus that holds cerebral spinal fluid (CSF)).
The brain is a complex organ that is responsible for controlling all functions of the body. It has five main portions: the cerebrum, cerebellum, brainstem, pituitary gland, and hypothalamus. The cerebrum is the biggest part of the brain, and consists of the frontal, parietal, temporal, and occipital lobes. This part of the brain is responsible for voluntary movement, intelligence, and memory. The cerebellum is a small part of the brain located at the back of the head, and regulates posture and balance. At the centre of the brain is the pineal gland, which is a small, pea-shaped organ in the centre of the brain that is responsible for the production and secretion of melatonin (also known as the sleep hormone). The brainstem is a small, stalk-like structure towards the bottom of the brain that connects the brain to the spinal cord. It regulates many vital bodily processes, such as swallowing, breathing, and heart rate. The pituitary gland is a pea sized organ located behind the eyes, and is responsible for the production and secretion of hormones in the body. The hypothalamus is located deep within the brain, and has many important functions, such as producing and secreting different hormones, regulating temperature, and controlling appetite.
Intracranial GCTs are more common in males, and tend to be diagnosed before the age of 20. However, anyone can develop this disease.
Types of Intracranial Germ-Cell Tumours
There are several types of intracranial GCTs, which are categorised by the types of cells the cancer originates from.
Germinomas
Germinomas, also known as dysgerminomas or extra-gonadal seminomas, are the most common type of intracranial GCT. These tumours have a distinct treatment and prognosis implications, and are often classified separately to other types of GCTs. While these tumours can be aggressive, they often respond well to treatment and can have an excellent prognosis.
In some cases, germinomas can increase levels of human chorionic gonadotropin (HCG), which is a hormone produced by the placenta (an organ that develops alongside a fetus during pregnancy) during early stages of pregnancy. In men, this hormone acts similarly to the luteinising hormone (LH), which is responsible for regulating sperm production and signalling for the production of testosterone. In females, this hormone is responsible for the production of progesterone during and after puberty. Excess levels of these hormones can cause a variety of side effects, including fertility issues.
Non-Germinomatous GCTs
Non-germinomatous GCTs encompass all other germ-cell tumours that are not germinomas. These tumours are less common, and tend to develop and metastasise more quickly than germinomas. Non-germinomatous GCTs can be categorised into five primary subtypes.
Embryonal Carcinomas
Embryonal carcinomas are a rare subtype of all intracranial GCTs, and often develop from primordial germ cells (germ cells that have not yet developed into gametes). In many cases, these tumours are found as a component of mixed GCTs. These tumours are often aggressive, are likely to metastasise, and may not have as good of a prognosis as other GCTs.
In some cases, embryonal carcinomas can increase the levels of HCG and alpha-fetoprotein (AFP), which is a hormone produced by the liver that is responsible for transporting heavy metal ions in fetal blood during the early stages of pregnancy.
Endodermal Sinus Tumours (Yolk Sac Tumours)
Endodermal sinus tumours, also known as yolk sac tumours, are a rare type of intracranial GCT that develops in the yolk sac of an embryo. These tumours often increase levels of AFP in the blood, and may occur as a component of a mixed GCT. These tumours are often aggressive, and may not have as good of a prognosis as other GCTs.
Choriocarcinomas
Choriocarcinomas are rare and aggressive intracranial GCTs that often develop from trophoblastic cells, which are specialised cells in the placenta. It is often fast growing, has a high metastasis rate, and may be a part of a mixed germ-cell tumour. While they are aggressive, they can have a good prognosis when caught early.
In most cases, intracranial choriocarcinomas increase the levels of HCG in the blood.
Teratomas
A teratoma is a rare type of intracranial GCT that contains bodily tissue, such as hair, bone, muscle and teeth. They can be broadly classified into different categories based on age of presentation:
- Intra-axial: intra-axial intracranial GCTs generally occur prior to birth or in the newborn period. These tumours are large, increasing head circumference and making childbirth difficult.
- Extra-axial: extra-axial intracranial GCTs generally occur in childhood or early adulthood. They tend to be smaller than intra-axial intracranial GCTs.
Teratomas can also be classified based on how the cells look under the microscope:
- Mature teratoma: cells look similar to healthy tissue but contain bodily tissue that shouldn’t be present within the brain (such as skin, hair, muscle, bone, etc.). These tumours are generally benign (non-cancerous).
- Immature teratoma: cells look similar to those found in a foetus, and also have components not generally found in the brain. These tumours are generally malignant (cancerous), but can have a good prognosis when found early.
- Teratoma with malignant transformation: a malignant GCT transforms into a malignant non-germ cell tumour, also known as a somatic (all cells that are not germ cells) malignancy. These tumours are highly aggressive, and may not have as good of a prognosis as other GCTs.
Mixed Germ-Cell Tumours
Mixed GCTs are cancers that develop from a variety of different cancerous cells. These cells can be a mix of germinoma and non-germinomatous tumour cells, or cells from various non-germinomatous GCTs. When a mixed germ-cell tumour is found, they are often treated similarly to non-germinomatous tumours due to their similar growth and metastasis rates. These tumours are often aggressive, and may not have as good of a prognosis as other GCTs.
Treatment
If an intracranial GCT is detected, it will be staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you. However, brain cancers are rarely staged, as they rarely spread to other parts of the body. Instead, they are generally graded from I-IV.
Because of how rare intracranial GCTs are, there is currently no standard grading system for this disease. Instead of grading, your doctor will recommend a treatment plan based on the following factors:
- Cancer type.
- Cancer location.
- Whether or not the cancer has metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment options for germinomas and non-germinomatous GCTs often differ.
Treatment for Germinomas
Treatment options for germinomas may include:
- Chemotherapy.
- Radiation therapy.
Most germinomas respond well to these two treatment options, however clinical trials and palliative care can also be used where necessary.
Treatment for Non-Germinomatous Germ-Cell Tumours
Treatment options for non-germinomatous GCTs may include:
- Surgery to remove as much of the tumour as possible (where possible).
- Radiation therapy.
- Chemotherapy.
- Stem-cell transplant.
- Immunotherapy.
- Targeted therapy.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page.
Risk factors
Because of how rare intracranial GCTs are, there has been limited research done into the risk factors of this disease.
Early symptoms
Symptoms of an intracranial GCT in the pineal gland region may include:
- Hydrocephalus (fluid build-up in the brain), which carries its own set of symptoms:
- Headaches.
- Nausea and/or vomiting.
- Difficulties with eye movement.
- Difficulties with balance.
- Difficulties with walking.
- Fatigue.
- Memory problems.
- Seizures.
- Behavioural and/or cognitive changes.
- Vision changes, such as double vision and difficulty looking up.
Symptoms of an intracranial GCT in the suprasellar region or pituitary gland may include:
- Irregular sleep.
- Early puberty in children.
- Delayed puberty in children.
- Stunted growth in children.
- Changes in eyesight, such as loss of peripheral vision or loss of vision.
- Diabetes insipidus (disorder causing fluid imbalance in the body), which carries its own set of symptoms:
- Frequent urination.
- Intense thirst.
- Isolated growth hormone deficiency, which carries its own set of symptoms:
- Poor growth.
- Impaired hair and/or nail growth.
- Delayed development of teeth.
- Delayed puberty.
- Hypoglycaemia (low blood sugar levels) in infants and toddlers.
- Decreased energy levels.
- Increased fat around the face and/or abdomen.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have an intracranial GCT, they will order a variety of diagnostic tests to confirm the diagnosis, and refer you to a specialist for treatment.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Neurological exam
A neurological examination assesses sensory and motor functions, and can generally be done in your GPs office. The doctor may check your vision, hearing, balance, coordination, strength and reflexes, depending on the signs and symptoms you have described.
Endocrine studies & blood tests
Endocrine studies involve blood and/or urine tests and imaging tests (see below) to analyse your hormone levels and detect any abnormalities. Some of these tests may include:
- General blood test to assess overall health.
- Blood tests to measure levels of:
- Glucose.
- Oestrogen.
- Testosterone.
- Prolactin.
- Growth hormone (GH).
- Adrenocorticotrophic hormone (ACTH).
- Thyroid stimulating hormone (TSH)
- Luteinising hormone (LH).
- Follicle stimulating hormone (FSH).
- 24-hour urine test, which measures levels of cortisol levels in your urine.
- High-dose dexamethasone suppression test.
- Low-dose dexamethasone suppression test.
Imaging tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), and/or positron emission tomography (PET scan), depending on where it is suspected the tumour is. The doctor may also look at other parts of the body and look for signs of metastasis, which can determine if you have an adenoma or a cancerous tumour.
Biopsy
Once the location of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. In most cases, this may be done by either an excision biopsy (where the lymph node is completely or partially removed), a fine needle biopsy (a fine needle is inserted into the lymph node to remove a sample), or a core needle biopsy (where a bigger needle is inserted into the lymph node to remove a sample). Both of these procedures are often performed as a day surgery.
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage intracranial GCTs have good prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer recurrence.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.