Gestational trophoblastic disease (GTD) is most often found either as a result of abnormal signs or symptoms during pregnancy or from the results of certain tests during routine prenatal care.

Signs and symptoms

It's important to let your doctor know about any abnormal symptoms you are having during pregnancy. Your doctor may suspect that gestational trophoblastic disease (GTD) is present based on a typical pattern of signs and symptoms. Many of these may also be caused by conditions other than GTD. Still, if you have any of these, it's important to see your doctor right away so the cause can be found and treated, if needed.

Complete and partial hydatidiform moles (molar pregnancies)

Most of these symptoms are much more common with complete moles than with partial moles.

Vaginal bleeding: Almost all women with complete hydatidiform moles have irregular vaginal bleeding during pregnancy. It occurs a little less often with partial moles. Bleeding typically starts during the first trimester (13 weeks) of pregnancy. Women with GTD often pass blood clots or watery brown discharge from the vagina. Sometimes, pieces of the moles resembling a bunch of grapes become dislodged from the uterus and are discharged through the vagina.

Anemia: In cases of serious or prolonged bleeding, a woman's body is not able to replace red blood cells as fast as they are lost. This can lead to anemia (low red blood cell counts). Symptoms can include fatigue and shortness of breath, especially with physical activity.

Abdominal swelling: The uterus and abdomen tend to get bigger faster in a complete molar pregnancy than they do in a normal pregnancy. Abnormal uterine enlargement occurs in about 1 out 4 women with complete moles but rarely in women with partial moles.

Vomiting: Many women have nausea and vomiting during the course of a typical pregnancy. With GTD, however, the vomiting may be more frequent and severe than normal.

Pre-eclampsia: Pre-eclampsia (toxemia) can occur as a complication of a normal pregnancy (usually in the third trimester). It can also develop during the first or second trimester of a complete molar pregnancy. Pre-eclampsia causes high blood pressure, headache, exaggerated reflexes, swelling in the hands or feet, and too much protein leaking into the urine. It affects a small number of women with complete moles but is rare in women with partial moles.

Hyperthyroidism: Hyperthyroidism (having an overactive thyroid gland) occurs in less than 10% of women with complete hydatidiform moles. Symptoms of hyperthyroidism can include rapid heartbeat, warm skin, and mild tremors (shaking).

The signs and symptoms of partial hydatidiform moles tend to be less severe than those of complete moles. Some symptoms, such as frequent vomiting or an overactive thyroid gland, rarely, if ever, occur with partial moles.

Partial moles are often diagnosed after what is thought to be a miscarriage. The molar pregnancy is found when the uterus is scraped during a dilation and curettage (D & C) and the products of conception are looked at under a microscope.

Most of the symptoms above, except for bleeding, are less common than in the past because they tend to occur late in the course of the disease. Most women with GTD are now diagnosed early because of the use of blood tests and ultrasound early in pregnancy.

Invasive moles and choriocarcinoma

These more invasive forms of GTD sometimes develop after a complete mole has been removed and less commonly after a partial mole. The tumors can also develop after a normal pregnancy, ectopic pregnancy (where the fetus grows outside of the uterus, such as inside a fallopian tube), or miscarriage.

Bleeding: The most common symptom is vaginal bleeding. Rarely, the tumor grows through the uterine wall, which can cause bleeding into the abdominal cavity along with severe abdominal pain.

Infection: In larger tumors, some of the tumor cells may die, creating an area where bacteria can grow. Infection may develop, which can cause vaginal discharge, crampy pelvic pain, and fever.

Abdominal swelling: Like hydatidiform moles, more invasive forms of GTD can expand the uterus, causing abdominal swelling. Human chorionic gonadotropin (HCG), a hormone made by the tumor (see below), may cause fluid-filled cysts (called theca lutein cysts) to form in the ovaries, which can also contribute to abdominal swelling.

Lung symptoms: The lung is a common site for distant spread of GTD. Spread to the lungs may cause coughing up of blood, a dry cough, chest pain, or trouble breathing.

Vaginal mass: These tumors can sometimes spread to the vagina, which can cause vaginal bleeding or a pus-like discharge. The doctor may also notice a cancerous growth on the vagina during a pelvic exam.

Other symptoms of distant spread: Symptoms depend on where the spread occurs. If GTD has spread to the brain, symptoms can include headache, vomiting, dizziness, seizures, or paralysis on one side of the body. Spread to the liver can cause abdominal pain and a yellowing of the skin or eyes (jaundice).

Placental site trophoblastic tumors

Bleeding: As with other forms of GTD, the most common symptom is vaginal bleeding into the vagina. This disease may grow through the uterine wall, which can cause bleeding into the abdominal cavity and severe abdominal pain.

Abdominal swelling: While placental site trophoblastic tumors are not likely to spread to distant sites, they may cause the uterus to enlarge.

Blood and urine tests

Blood and urine tests can be used to help diagnose GTD.

Human chorionic gonadotropin (HCG): Trophoblastic cells of both normal placentas and GTD make a hormone called human chorionic gonadotropin (HCG), which is vital in supporting a pregnancy. HCG is released into the blood, and some of it is excreted in the urine. This hormone consists of 2 chemical components, and the commonly-used blood and urine tests measure one of these, called beta-HCG (βHCG).

HCG is normally found only in the blood or urine of pregnant women. In fact, finding HCG in urine is the basis of most pregnancy tests.

Since complete moles usually release more HCG than a normal placenta, measurements of HCG levels in the blood can help diagnose them. (Sometimes this test result can be falsely high because of certain other substances in the bloodstream. This can be resolved by also testing the urine for HCG.)

However, not all women with GTD have HCG levels that are higher than those seen in a normal pregnancy. For example, most women with partial moles or placental site trophoblastic tumors have normal or only slightly increased HCG levels.

HCG tests can also help tell if GTD may be present after a pregnancy or miscarriage, as the level of HCG should normally fall to an undetectable level soon afterward.

Along with helping to diagnose GTD, blood HCG levels are also very useful in women already known to have GTD. They can be used to:

• help estimate the amount of GTD present in a patient's body. Higher levels of HCG may mean that more tumor cells are present in the body.
• determine if treatment is working. HCG levels should drop to normal levels after treatment.
• detect GTD that has come back after treatment

Monitoring HCG levels is especially important during treatment and follow-up to make sure the disease has gone away or has not returned. The HCG test is generally very accurate. In rare cases, patients may have abnormal substances (antibodies) in their blood that interfere with the HCG test. When these patients' blood samples are tested, the HCG levels appear higher than they really are, a situation known as "phantom HCG." In some cases, women have been diagnosed with GTD when they actually do not have any GTD. If doctors notice that the blood (or serum) levels of HCG are high but the urine levels are not, they can order special tests to distinguish between truly elevated HCG levels and "phantom HCG.".

Other blood tests: Other tests may provide indirect evidence of GTD. For example, red blood cell counts can detect anemia (having too few red blood cells), which can be caused by uterine bleeding.

For women diagnosed with GTD, blood tests are often used to watch for side effects from chemotherapy. Blood cell counts are done to watch the health of the bone marrow (where new blood cells are made), while blood chemistry tests can be used to check the condition of the liver and kidneys.

Imaging tests

Imaging tests use sound waves, x-rays, magnetic fields, or radioactive substances to create pictures of the inside of your body. Imaging tests may be done for a number of reasons, including to help find out whether a tumor is present and to learn how far it may have spread.

Ultrasound (sonogram)

Ultrasound can identify most cases of GTD, and will likely be the first test done if your doctor suspects there may be a problem.

How it works: This test uses sound waves to produce images of internal organs. A small microphone-like instrument called a transducer emits sound waves and picks up the echoes as they bounce off body tissues. The echoes are converted into a black and white image by a computer. That image is then displayed on a computer screen.

What it's like to have the test: Ultrasound is an easy procedure. It uses no radiation, which is why it is often used to look at developing fetuses. During an ultrasound exam, you simply lie on a table while a technician or doctor moves the transducer over the skin on the part of your body being examined. Usually, the skin is first lubricated with gel.

Ultrasonography can also be done with a small transducer placed in the vagina. This is called transvaginal ultrasonography and is often used for women suspected of having GTD during the first trimester of their pregnancy.

What doctors look for: In a normal pregnancy, ultrasound imaging shows a picture of the developing fetus inside the womb.

In a complete molar pregnancy, however, the ultrasound shows that there is no fetus. (The rare exception, occurring in less than 1% of cases, would be a "twin" pregnancy in which one of the twins is a normal fetus and the other is a hydatidiform mole.) Instead, the ultrasound detects the large, grape-like swollen villi that are typical of GTD.

In a partial molar pregnancy, ultrasound can show an abnormally formed placenta. If a fetus is seen, it is often deformed.

Ultrasound is also used to help find out if a mole is invading local tissues. If blood levels of HCG are still elevated after the mole has been removed, more exams may need to be done.

Chest x-ray

A chest x-ray may be done in cases of persistent GTD to see if it has spread to your lungs, which is very unlikely unless your cancer is far advanced. However, CT scans of the chest are done more often if your doctor suspects persistent or advanced disease. A plain x-ray of your chest can be done in any outpatient setting.

Computed tomography (CT) scan

The CT scan is an x-ray test that produces detailed cross-sectional images of your body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you while you lie on a table. A computer then combines these pictures into images of slices of the part of your body being studied. Unlike a regular x-ray, a CT scan creates detailed images of the soft tissues in the body.

Before the test, you may be asked to drink a contrast solution and/or receive an IV (intravenous) line through which a contrast dye is injected. This helps better outline structures in your body.

The contrast may cause some flushing (a feeling of warmth, especially in the face). Some people are allergic and get hives. Rarely, more serious reactions like trouble breathing or low blood pressure can occur. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays.

CT scans take longer than regular x-rays. You need to lie still on a table while they are being done. During the test, the table moves in and out of the scanner, a ring-shaped machine that completely surrounds the table. You might feel a bit confined by the ring you have to lie in while the pictures are being taken.

This test may be done to see if the GTD has spread elsewhere, such as the lungs, brain, or liver. If your doctor suspects the GTD has spread to any of these sites, a CT or MRI scan may be done.

Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a very detailed image of parts of the body. A contrast material called gadolinium is often injected into a vein before the scan to better see details.

MRI scans are a little more uncomfortable than CT scans. First, they take longer -- often up to an hour. Second, you have to lie inside a narrow tube, which is confining and can upset people with claustrophobia (a fear of enclosed spaces). Newer, "open" MRI machines can sometimes help with this if needed. The machine also makes buzzing and clicking noises that you may find disturbing. Some centers provide headphones with music to block this out.

MRI scans are most helpful in looking at the brain and spinal cord. They are most likely to be used if persistent GTD has already been found to have spread elsewhere, such as to the lungs.

Positron emission tomography (PET) scan

PET scans involve injecting a form of radioactive sugar (known as fluorodeoxyglucose or FDG) into the blood. The amount of radioactivity used is very low. Because cancer cells in the body are growing rapidly, they absorb large amounts of the radioactive sugar. A special camera can then create a picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI scan, but it provides helpful information about your whole body.

PET scans are sometimes useful if your doctor thinks the cancer may have spread (or returned after treatment) but doesn't know where. PET scans can be used instead of several different imaging tests because they scan your whole body.

Some newer machines are able to perform both a PET and CT scan at the same time (PET/CT scan). This allows the radiologist to compare areas of higher radioactivity on the PET with the appearance of that area on the CT.

Other tests

While doctors can often be fairly certain of a diagnosis of GTD based on symptoms, blood test results, and imaging tests, the diagnosis is often made after a D&C in patients with abnormal bleeding. The cells from the tumor are removed and viewed under a microscope. The cells from different types of GTD each look different under the microscope. (D&C is described in the section, "How is gestational trophoblastic disease treated?")