Gestational trophoblastic diseases (GTDs) are a rare group of diseases that develop during the early stages of pregnancy. More specifically, they develop from trophoblastic cells after the fertilisation of an ova (or egg) by sperm. These diseases can be benign (non-cancerous) or malignant (cancerous).
After fertilisation, tissue forms surrounding around the embryo (fertilised egg) made up of trophoblastic cells. These cells help the embryo attach to the uterus, and help to form a significant portion of the placenta (an organ that develops throughout pregnancy to provide oxygen and nutrition to the developing baby).
GTDs are most commonly diagnosed in women under the age of 20, or over the age of 40. However, it can affect anyone with the ability to get pregnant – including women, teenagers, transgender men, non-binary individuals, and intersex people – at any age.
Types of Gestational Trophoblastic Diseases
There are two primary types of GTDs: hydatidiform moles (also known as molar pregnancy), and gestational trophoblastic neoplasia's.
Hydatidiform Moles (Molar Pregnancy)
Hydatidiform moles (HMs), also known as a molar pregnancy, is the most common type of GTD. This disease occurs when the sperm fertilises the egg, but a baby is not developed. Instead, excess trophoblastic tissue resembling sacs of fluid forms in grape-like clusters within the uterus. In most cases, HMs are benign, however they can develop into a malignant invasive mole, or a gestational trophoblastic neoplasia.
There are two types of molar pregnancy.
Partial Hydatidiform Moles
A partial HM occurs when two sperm fertilise the same egg at the same time, resulting in a fertilised egg with the normal amount of maternal DNA, but double the normal amount of paternal DNA. Because of this genetic abnormality, the embryo cannot fully develop, and the fetus will be non-viable. The treatment for this type of tumour is surgery, which is often curative.
Complete Hydatidiform Moles
A complete HM occurs when two sperm fertilise an egg with no maternal DNA, resulting in an egg that only contains paternal DNA. As a result, an embryo is unable to develop, and a fetus cannot be formed. The treatment for this type of tumour is surgery, which is often curative.
Gestational Trophoblastic Neoplasias
Gestational trophoblastic neoplasias (GTNs) are rarer types of GTDs that are often malignant. There are several different types of GTNs that can occur.
Invasive Moles
Invasive moles are rare GTDs that occur when trophoblastic cells invade the muscle layer of the uterus (myometrium). In some cases, invasive moles are the result of an untreated partial or complete HMs. These tumours are often metastatic and may be aggressive, but can have a good prognosis.
Choriocarcinomas
Choriocarcinomas are a rare type of carcinoma (cancer arising from tissues that line organs) that often form from untreated molar pregnancies. In rare instances, they can also develop from trophoblastic tissue left after a miscarriage, abortion, or the delivery of a healthy baby. These tumours are aggressive and may metastasise, but can have a good prognosis.
Placental-Site Trophoblastic Tumours
Placental-site trophoblastic tumours (PSTTs) are very rare tumours that develops where the placenta was attached to the uterine wall. These tumours develop very slowly, and may not be discovered until several months or years after the pregnancy. PSTTs can metastasise, however, they can have a good prognosis.
Epithelioid Trophoblastic Tumours
Epithelioid trophoblastic tumours (ETTs) are very rare tumours that are often found in the cervix or lower end of the uterus. They behave very similarly to PSTTs, and can also have a good prognosis.
Non-Gestational Trophoblastic Diseases
Non-gestational trophoblastic disease (NGTD) are very rare malignancies that are not associated with pregnancy. In many cases, NGTDs occur as a choriocarcinoma in the ovary as a rare variant of germ-cell tumour. However, some cases of non-gestational placental site trophoblastic tumours have been reported. NGTDs can be aggressive, and may not have as good of a prognosis as GTDs.
Treatment
If a GTD 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.
Measuring hCG Levels
The hCG (human chorionic gonadotropin) hormone is a hormone produced by the placenta throughout all types of pregnancy, including molar pregnancy. Measuring the levels of these hormones can help your doctor distinguish between a molar pregnancy and GTNs. After you have a molar pregnancy removed, the hCG levels in your blood should become low after 4-6 weeks. If this happens, the doctor will conclude that you have had a molar pregnancy, and no further staging would be required.
However, if after the removal of the molar pregnancy the hCG levels in your blood have increased (or remain the same), it would be assumed that you have a type of GTN, and more tests would be required. After diagnosis, the cancer would be staged using the FIGO staging system.
FIGO Staging System
Gynaecological cancers, such as GTDs, can be staged using the Federation of Gynaecology and Obstetrics (FIGO) system from stage I to IV:
- Stage I: cancer cells are confined to the uterus 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 ovaries, 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.
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 Options
Treatment is dependent on several factors, including location, stage of disease and overall health.
Treatment for GTDs may include:
- Surgery, potentially including:
- Dilation & Curettage (D&C) (surgical procedure where the doctor dilates the cervix to scrap out abnormal tissues with a spoon-shaped instrument called a curette).
- 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).
- Chemotherapy.
- Radiation 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 some GTDs are, there have been limited risk factors identified for this disease. These factors include:
- Becoming pregnant before 20 years of age.
- Becoming pregnant after 35 years of age.
- Having a history of molar pregnancy.
- Having a history of miscarriage.
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
Patients with GTDs may appear asymptomatic in the early stages of the disease. As the cancer progresses, some of the following symptoms may appear.
Symptoms of a Molar Pregnancy
The symptoms of a molar pregnancy may include:
- Vaginal bleeding (not associated with menstruation).
- Nausea and/or vomiting.
- Pre-eclampsia (a common pregnancy complication characterised by high blood pressure and proteinuria (excess protein in urine)).
- Enlarged uterus.
- Abdominal pain and/or swelling.
- Anaemia.
- Abnormally high hCG levels.
- Overactive thyroid, which has its own set of symptoms:
- Fast and/or irregular heartbeat.
- Shakiness.
- Abnormal sweating.
- Frequent bowel movements.
- Difficulty sleeping.
- Feelings of anxiety or irritability.
- Unexplainable weight loss.
Symptoms of an Invasive Mole
Symptoms of an invasive mole generally include:
- Persistent vaginal bleeding.
- Enlarged uterus.
- Nausea and/or vomiting.
- High hCG levels.
Symptoms of a Choriocarcinoma
The symptoms of a choriocarcinoma may include:
- Abdominal pain and/or swelling.
- Vaginal bleeding (not associated with menstruation).
- Anaemia.
- Pelvic pain and/or mass.
If the tumour has become metastatic, patients may experience additional symptoms depending on where it has spread to:
- Cough.
- Shortness of breath.
- Chest pain.
- Headaches.
- Dizziness.
- Seizures.
Symptoms of a Placental-site Trophoblastic Tumour
Symptoms of a PSTT may include:
- Vaginal bleeding (not associated with menstruation).
- Loss of periods (amenorrhoea).
Symptoms of an Epithelioid Trophoblastic Tumour
Symptoms of an ETT may include:
- Vaginal bleeding (not associated with menstruation).
- High hCG levels.
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 GTD, 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.
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.
Urine & Blood Tests
Urine and blood tests are used to assess overall health and detect any abnormalities. Some of these tests may include:
- General blood test to assess overall health.
- Blood chemistry and/or blood hormone studies, which analyse the levels of certain hormones and other substances in the blood.
- Serum tumour marker test.
- Urinalysis, which analyses the colour of your urine and its contents (e.g., sugar, protein, red and/or white blood cells etc.).
Lumbar Puncture
A lumbar puncture, or spinal tap, involves inserting a needle between two vertebrae in the lower spine and extracting a sample of cerebrospinal fluid (CSF) for analysis. A local anaesthetic or sedative is given prior to the procedure. Your doctor will discuss any risks and possible complications with you prior to the procedure.
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.
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 GTDs 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.