Granulosa cell tumours (GCTs) are rare carcinomas (cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs arising from cellsthe basic structural and functional unit of all living things 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 tumourstumours that produce and secrete hormones or non-functional tumourstumours that do not produce and secrete 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 tumoura tissue mass that forms from groups of unhealthy cells 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
If a GCT is detected, it will be staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas 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 (nodea small lump or mass of tissue in your body) indicates whether the cancer has spread to nearby lymph nodessmall bean-shaped structures that filters harmful substances from lymph fluid.
- 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 tissuea group of cells that work together to perform a function.
- 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 localisedaffecting only one area of body 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 advancedat a late stage, far along or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 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 testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, 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:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, potentially including:
- Local excisionto surgically remove/cut out of the tumour.
- Hysterectomycomplete or partial removal of the uterus.
- Bilateral salpingo-oophorectomyremoval of both ovaries and fallopian tubes.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Granulosa Cell Tumour Treatment and Fertility
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.
Risk factors
Because of how rare GCTs are, there has been minimal research done into the riskthe possibility that something bad will happen 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.
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.
- Constipationa condition where a person has difficulty passing faeces/stools.
- Polyuriafrequent 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 menorrhagiamenstrual bleeding that lasts more than a week, bleeding in between periods, or unexplained amenorrhoeaabscense of menstrual 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
If your doctor suspects you have a GCT, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Pelvic examinationa physical exam of the external and internal female pelvic organs.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- Pelvic ultrasounda type of medical imaging that uses sound waves to create detailed images of the organs and structures within the pelvis, including the uterus, ovaries, and surrounding tissues.
- Transvaginal ultrasounda type of pelvic ultrasound that involves inserting a device (known as a transducer) into the vagina to produce sound waves and create images of internal female reproductive organs in greater detail.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Biopsyremoval of a section of tissue to analyse for cancer cells.
