Ovarian cancer is a type of carcinoma that causes one or more tumours to develop in the ovaries. The ovaries are a pair of small, walnut shaped organs that are responsible for the release of eggs (ovum) during the female reproductive cycle.
Germ-cell ovarian cancer is a rare subtype of this disease. Germ cells are the biological cells that develop into the gametes (or reproductive cells), such as the ovum and sperm. These cancers usually only affect one ovary.
Germ-cell ovarian cancers are generally diagnosed in teenagers and young adults; however, it can affect almost anyone with ovaries – including women, teenagers, transgender men, non-binary individuals, and intersex people - at any age.
Types of Ovarian Germ-Cell Tumours
There are many subtypes of Ovarian germ-cell tumours, which are categorised by the cells that the cancer originates from.
Dysgerminomas
Dysgerminomas, also known as germinomas, are the most common subtype of ovarian germ-cell tumours. They generally arise from primordial germ cells, which are germ cells that have not yet developed into gametes. These tumours have a distinct treatment and prognosis implications, and are often classified seperately 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, dysgerminomas 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 dygerminomas. 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.
Teratomas
A teratoma is a common type GCT that contains bodily tissue, such as hair, bone, muscle and teeth. They can be broadly classified into different categories 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.
Embryonal Carcinoma
Embryonal carcinomas are a rare subtype of ovarian germ-cell tumours that often develop from primordial germ cells, which are germ cells that have not yet developed into gametes. Embryonal carcinomas generally have a good prognosis.
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
Endodermal sinus tumours, or yolk sac tumours, are the second most common type of ovarian germ-cell tumour. These types of tumours develop in the lining of the yolk sac of an embryo, and can be found in young infants and children. These tumours often increase levels of AFP in the blood, and may occur as a component of a mixed GCT. Endodermal sinus tumours are highly aggressive, and may not have as good of a prognosis as other germ-cell tumour subtypes.
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.
There are two primary types of choriocarcinomas:
- Gestational choriocarcinoma (most common type, develops during pregnancy, after an abortion or after a miscarriage).
- Non-gestational choriocarcinoma (choriocarcinomas not associated with pregnancy).
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 ovarian cancer 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.
Ovarian cancers can be staged using the Federation of Gynecology and Obstetrics (FIGO) system from stage I to IV:
- Stage I: cancer cells are confined to one or both ovaries only. This stage is also known as early-stage cancer.
- Stage II: cancer cells have grown deeper into nearby organs in the pelvis, such as the uterus, fallopian tubes, bladder and/or bowel. This is also known as localised cancer.
- Stage III: the cancer has become larger and has spread beyond the pelvis into the lining of the abdomen (peritoneum). Lymph nodes are also often affected. This is also known as advanced or metastatic cancer.
- Stage IV: the cancer has spread to more distant organs, such as the lungs or the liver. This is also known as advanced or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Grade I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
- Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.
- Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.
Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. In particular, they may look for mutations in the hereditary breast cancer genes (BRCA1 and BRCA2), which can cause an increased risk in developing ovarian cancer. They will then discuss the most appropriate treatment option for you.
Treatment is dependent on several factors, including fertility, type, stage of disease and overall health.
Treatment options for the germ-cell sub-type may include:
- Surgery, potentially including:
- Total hysterectomy (removal of the uterus).
- Bilateral salpingo-oophorectomy (removal of both ovaries and fallopian tubes).
- Unilateral salpingo-oophorectomy (removal of one ovary and fallopian tube).
- Lymphadenectomy (removal of affected lymph nodes).
- Removal of other organs (only required in some cases where the cancer has spread beyond the pelvis).
- Chemotherapy.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia Treatment Options page.
Ovarian Cancer Treatment and Fertility
Treatment for ovarian cancer may make it difficult to become pregnant. If fertility is important to you, discuss your options with your doctor and a fertility specialist prior to the commencement of treatment.
Risk factors
While the cause of germ-cell ovarian cancer remains unknown, the following factors may increase your risk of developing the disease:
- Having a family history of ovarian, breast, uterine and/or bowel cancer.
- A mutation in the BRCA 1 and BRCA 2 genes.
- Having Lynch syndrome.
- Having certain medical conditions such as endometriosis.
- Use of hormone replacement therapy (HRT).
- Having a history of tobacco smoking.
- Being obese.
- Reproductive history, including:
- Women who have never had children.
- Women who have had assisted reproduction.
- Women who have had children over the age of 35.
- Having early puberty.
- Having late menopause.
- Having Ashkenazi Jewish ancestry.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
Early-stage germ-cell ovarian cancer may be asymptomatic. As the cancer progresses, some of the following symptoms may appear:
- Abdominal bloating/swelling.
- Abdominal/pelvic pain and/or pressure.
- Changes in appetite, such as feeling full quickly or not feeling hungry.
- Urinary changes, such as changes in frequency and urgency.
- Changes in bowel habits, such as constipation and diarrhoea.
- Unexplained weight loss or weight gain.
- Unexplained fatigue.
- Indigestion and/or heartburn.
- Changes in menstrual periods, such as irregular periods, unusual vaginal bleeding, or vaginal bleeding post menopause.
- Pain during sex.
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 germ-cell ovarian cancer, they may order the following tests to confirm the diagnosis and refer you to a specialist for treatment.
Pelvic examination
The doctor will inspect the abdomen for any swelling or masses, followed by your genitalia. The doctor will then insert two fingers into your vagina while simultaneously pressing on your abdomen with their other hand to feel your uterus and ovaries. Following this, the doctor may use a device called a speculum into your vagina, which will separate the vaginal walls and allow viewing of your vaginal canal and cervix for any visible abnormalities. You many request a family member, friend, or nurse to be present during this exam.
Imaging tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), pelvic ultrasound (including abdominal and trans-vaginal ultrasounds) and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and looks for signs of metastasis.
Blood tests
A blood test may be taken to assess your overall health and help guide treatment decisions. Additional blood tests may be conducted to check for tumour markers, which are indicative of cancer cells. The most common tumour marker for ovarian cancer is CA125. Levels of CA125 may be higher in cases of ovarian cancer, but are not used as a screening tool as high CA125 levels can be higher for other reasons. Blood tests may also examine your full blood count (FBC) and levels of hormones and chemicals in your blood.
Biopsy
Once the location of the cancer has been identified, the doctor will perform an diagnostic procedure to determine your diagnosis. In many cases, diagnosis is confirmed after surgical removal of the affected ovary. However, if it is suspected the cancer has spread, the doctor will perform a biopsy to remove a section of tissue using a needle. This is often done by a fine needle aspiration (FNA), a core needle biopsy (CNB), or by surgical means (excisional or incisional biopsy). In patients who are suspected to have ovarian cancer, diagnosis can often be confirmed after surgery to remove the ovary These samples will then be analysed for cancer cells.
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 the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage germ-cell ovarian cancers have a better 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. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.