Granulosa cell tumours (GCTs) are rare carcinomas (cancer arising from cells in kin or tissues that line organs) that are found in ovaries, a pair of ova (egg)-producing organs in the female reproductive tract. It is the most common type of sex-cord stromal tumours, which are tumours that develop in the tissues of the ovaries or the testicles. GCTs can present as either functional tumours (tumours that secrete and produce hormones), or non-functional tumours (tumours that do not secrete and produce hormones).
There are two types of GCTs, that are categorised by the appearance of the cells under the microscope and the ages they appear in patients. The first and most common type is adult granulosa cell tumours (AGCTs), which develops from mature granulosa cells. This type of tumour generally affects women around the age of 50, and can be diagnosed prior to, during or after menopause. The less common type of GCT is juvenile GCT (JGCT), which develops from immature granulosa cells. This type of cancer generally affects premenarchal girls (girls who have not begun menstruating) or young women.
While GCTs are most common in women within these age ranges, they can affect anyone with ovaries - including women, children, teenagers, transgender men, non-binary individuals, and intersex people - at any age.
Treatment
Treatment for GCTs may make it difficult to become pregnant. If fertility is important to you, discuss your options with your doctor prior to the commencement of treatment.
If a 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.
Cancers can be staged using the TNM staging system:
- T (tumour) indicates the size and depth of the tumour.
- N (nodes) indicates whether the cancer has spread to nearby lymph nodes.
- M (metastasis) indicates whether the cancer has spread to other parts of the body.
This system can also be used in combination with a numerical value, from stage 0-IV:
- Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissue.
- Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
- Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localised cancer.
- Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
- Stage IV: the cancer has spread to other tissues and organs in the body. 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. They will then discuss the most appropriate treatment option for you.
Treatment is dependent on several factors, including fertility, age, stage of disease and overall health.
Treatment options for GCTs may include:
- Surgery, potentially including:
- Local excision of the tumour.
- Total hysterectomy (complete removal of the uterus).
- Bilateral salpingo-oophorectomy (removal of both ovaries and fallopian tubes).
- Radiation therapy.
- Chemotherapy.
- Clinical trials.
- Palliative care.
For more information on treatment options, please refer to the Rare Cancers Australia Treatment Options page.
Risk factors
Because of how rare GCTs are, there has been minimal research done into the risk factors of this disease. However, some potential links have been identified:
- Chromosomal mutations (specifically, trisomy 12, monosomy 22 and deletion of chromosome 6).
- Peutz Jeghers syndrome.
- Potters’ syndrome.
- Ollier disease (juvenile GCT).
- Maffucci disease (juvenile GCT).
- Certain medications, including selective estrogen receptor modulators (SERM), clomiphene citrate and gonadotropins.
- Endometrial or ovarian cancers.
In childhood cancers, it may be beneficial to ask your treating team about genome sequencing (a study to analyse your DNA) to better understand the contributors and genetic risk factors of this disease.
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
The symptoms of a GCT will vary based on:
- Whether or not the patient has started menstruating.
- Whether or not the patient has gone through, or is going through, menopause.
General symptoms
These symptoms may appear in anyone with a GCT, regardless of age, menstruation status and menopause status:
- Abdominal pain.
- Abdominal bloating.
- Constipation.
- Frequent urination.
Premenarchal girls
Menarche is defined as the first menstrual cycle in girls. Girls who have a GCT and have not begun menstruation may have precocious puberty, which is when puberty begins too early (usually before age 8 in girls and 9 in boys). The symptoms of precocious puberty include:
- Increased pubic hair.
- Early breast development.
- Increased growth.
- Vaginal bleeding (which may or may not be associated with menstruation).
These girls may also go on to have early menarche, which is the first menstrual cycle before age 11.
Menstruating women
Women who have experienced menstruation for any length of time and have a GCT may experience changes in menstruation, such as menorrhagia (menstrual bleeding that lasts more than a week), bleeding in between periods, or unexplained amenorrhea (absence of periods).
Menopausal/post-menopausal women
The most common symptom of a GCT in menopausal/post-menopausal women is vaginal bleeding.
Not everyone with the symptoms above will have cancer, but see your GP if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have a GCT, they may order the following 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.
Imaging & blood 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 cancer is. The doctor may also look at other parts of the body and looks for signs of metastasis. Additionally, a blood test may be taken to assess your overall health and help guide treatment decisions.
Biopsy
Once the location(s) of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. The tissue sample will then be analysed for cancer cells. This can be done by a fine needle aspiration (FNA) or a core needle biopsy (CNB).
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 GCTs 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.