Gestational Trophoblastic Disease

What Is Gestational Trophoblastic Disease?

Gestational trophoblastic disease (GTD) is a group of rare tumors that involve abnormal growth of cells inside a woman's uterus. GTD does not develop from cells of the uterus like cervical cancer or endometrial (uterine lining) cancer do. Instead, these tumors start in the cells that would normally develop into the placenta during pregnancy. (The term "gestational" refers to pregnancy.)

GTD begins in the layer of cells called the trophoblast that normally surrounds an embryo. (Tropho- means "nutrition," and -blast means "bud" or "early developmental cell.") Early in normal development, the cells of this layer form tiny, finger-like projections known as villi. These villi grow into the lining of the uterus. In time, the trophoblast layer develops into the placenta, the organ that protects and nourishes a growing fetus.

Most GTDs are benign (non cancerous) and they don't invade deeply into body tissues or spread to other parts of the body. But some are cancerous. Because not all of these tumors are cancerous, this group of tumors may be referred to as gestational trophoblastic disease, gestational trophoblastic tumors, or gestational trophoblastic neoplasia. (The word neoplasia simply means "new growth.")

All forms of GTD can be treated. And in most cases the treatment produces a complete cure.

Types of gestational trophoblastic disease

The main types of gestational trophoblastic diseases are:

• hydatidiform mole (complete or partial)
• invasive mole
• choriocarcinoma
• placental site trophoblastic tumor

Hydatidiform mole

The most common form of GTD is called a hydatidiform mole, also known as a molar pregnancy. The moles are actually villi that have become swollen with fluid. The swollen villi grow in clusters that look like bunches of grapes. Although this is called a molar "pregnancy," it is not possible for a normal baby to form. Hydatidiform moles are not cancerous, but they may develop into cancerous GTDs.

There are 2 types of hydatidiform moles: complete and partial.

A complete hydatidiform mole most often develops when either 1 or 2 sperm cells fertilize an "empty" egg cell (a cell that contains no nucleus or DNA). All the genetic material comes from the father's sperm cell. Therefore, there is no fetal tissue.

Surgery can totally remove most complete moles, but in as many as 1 in 5 women there will be some persistent molar tissue (see "Persistent gestational trophoblastic disease" below). Most often this is an invasive mole, but in rare cases it is a choriocarcinoma, a malignant (cancerous) form of GTD. In either case it will require further treatment.

A partial hydatidiform mole develops when 2 sperm fertilize a normal egg. These tumors contain some fetal tissue, but this is often mixed in with the trophoblastic tissue. It is important to know that a viable (able to live) fetus is not being formed.

Partial moles are usually completely removed by surgery. Only a small number of women with partial moles need further treatment after initial surgery. Partial moles rarely develop into malignant GTD.

Persistent gestational trophoblastic disease

This is not a separate type of GTD, but a term used to describe GTD that is not cured by initial surgery. Persistent GTD occurs when the tumor has grown into the muscle layer of the uterus (myometrium). Surgery to scrape the inside of the uterus (called suction dilation and curettage, or D&C) removes only the inner layer of the uterus. It does not remove the tumor deep in the muscular wall of the uterus.

Most cases of persistent GTD are invasive moles, although in rare cases they are choriocarcinomas or placental site trophoblastic tumors (see below).

Invasive mole

An invasive mole (formerly known as chorioadenoma destruens) is a hydatidiform mole that grows into the myometrium. Invasive moles can be either complete or partial, but complete moles become invasive much more often than partial moles. Invasive moles develop in a little less than 1 out of 5 women who have had a complete mole removed. The risk of developing an invasive mole in these women increases if:

• There is a long time (more than 4 months) between the last menstrual period and treatment.
• The uterus has become very large.
• The woman is older than 40 years.
• The woman has had GTD in the past.

Because these moles have grown into the uterine muscle layer, they aren't completely removed by surgery. Invasive moles sometimes go away on their own, but most require treatment with chemotherapy.

A tumor or mole that grows completely through the myometrium may result in bleeding, which can be life threatening.

In about 15% of cases, the tumor spreads (metastasizes) to other parts of the body, most often the lungs.

Choriocarcinoma

Choriocarcinoma is a malignant form of GTD. It is much more likely than other types of GTD to grow quickly and spread to organs away from the uterus.

Although choriocarcinoma most often develops from a complete hydatidiform mole, it can also occur after a partial mole, a normal pregnancy, or a pregnancy in which the fetus is lost early.

Rarely, choriocarcinomas can develop in other parts of the body in both men and women. These are not related to pregnancy. They may develop in the ovaries, testicles, chest, or abdomen. In these cases, choriocarcinoma is usually mixed with other types of cancer, forming a mixed germ cell tumor. Choriocarcinomas starting in these locations are not considered to be gestational and are not discussed in this document. Non-gestational choriocarcinoma tends to be less responsive to chemotherapy and has a less favorable prognosis (outlook) than gestational choriocarcinoma. For more information, see the American Cancer Society documents, Ovarian Cancer and Testicular Cancer.

Placental site trophoblastic tumor

Placental site trophoblastic tumor (PSTT) is a very rare form of GTD that develops where the placenta attaches to the uterus. This tumor most often develops after a normal pregnancy or abortion, but it may also develop after a complete or partial mole is removed.

Most PSTTs do not spread to other sites in the body. But these tumors have a tendency to invade the muscle layer of the uterus.

Although most forms of GTD are very sensitive to chemotherapy drugs, PSTTs are not. Instead, they are treated with surgery, aimed at completely removing disease.

Do We Know What Causes Gestational Trophoblastic Disease?

All forms of gestational trophoblastic disease (GTD) begin after an egg cell is fertilized by a sperm cell. Normally, the sperm and egg cells each provide a set of 23 chromosomes (bits of DNA that contain our genes) to create a cell with 46 chromosomes. This cell will start dividing to eventually become a fetus.

In complete hydatidiform moles, the problem most often arises when a sperm cell fertilizes an abnormal egg cell that contains no chromosomes. The reason the egg contains no chromosomes is not known. After fertilization, the chromosomes from the sperm duplicate themselves, so there are 2 copies of identical chromosomes that both come from the sperm. This situation prevents normal development, and no fetus is formed. Instead, a complete hydatidiform mole develops. Less often, a complete mole forms when an abnormal egg without any chromosomes is fertilized by 2 sperm cells. Again, there are 2 copies of the father's chromosomes and none from the mother, and no fetus forms.

Partial hydatidiform moles result when 2 sperm cells fertilize a normal egg at the same time. The fertilized egg contains 3 sets of chromosomes (69) instead of the usual 2 sets (46). An embryo with 3 sets of chromosomes cannot grow into a fully developed infant. This situation leads to an abnormal (malformed) fetus along with some normal placental tissue and a partial hydatidiform mole.

Invasive moles are hydatidiform moles that begin to grow into the muscle layer of the uterus. They develop more often from complete moles than from partial moles. It's not clear exactly what causes this to happen.

Most choriocarcinomas develop from persistent hydatidiform moles (usually complete moles). They can also develop when bits of tissue are left behind in the uterus after spontaneous (miscarriage) or intended abortion or after delivery of a baby following an otherwise normal pregnancy. Researchers have found changes in certain genes that are commonly found in choriocarcinoma cells, although it is not clear what causes these changes.

Can Gestational Trophoblastic Disease Be Found Early?

The best way to find gestational trophoblastic disease (GTD) early is to have routine prenatal care by a qualified health care professional. Usually, a woman has certain signs and symptoms, such as vaginal bleeding, that suggest something may be wrong. (These symptoms are discussed in the section, "How is gestational trophoblastic disease diagnosed?") These signs will prompt the doctor to look for the cause of trouble.

Often, moles or tumors cause swelling in the uterus that seems like a normal pregnancy. But a doctor can usually tell that this isn't a normal pregnancy during a routine ultrasound exam. A blood test for human chorionic gonadotropin (HCG) can also show that something is abnormal. This substance is normally elevated in the blood of pregnant women, but it may be very high if there is GTD.

Fortunately, even if it is not detected early, GTD is a very treatable (and usually curable) form of cancer.

Because women who have had one molar pregnancy are at increased risk, doctors can be especially careful in checking their future pregnancies with beta-HCG tests and transvaginal or pelvic sonograms. (These tests are described in the next section.)

How Is Gestational Trophoblastic Disease Treated?

This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

The first part of this section describes the various types of treatments used for gestational trophoblastic disease (GTD). This information is followed by a description of the most common approaches used for these cancers based on the type and classification of GTD.

Making treatment decisions

After GTD is diagnosed and staged, your medical team can recommend one or more treatment options. Choosing a treatment plan is an important decision, so be sure to take time and think about all of the choices.

No matter what type or stage of GTD a woman has, treatment is available. Your treatment choice depends on many factors. The location and the extent of the disease are very important. So too are the type of GTD present, the level of human chorionic gonadotropin (HCG), duration of the disease, sites of metastasis if any, and the extent of prior treatment. In selecting a treatment plan, you and your medical team will also consider your age, general state of health, and personal preferences.

It is important to begin treatment as soon as possible after GTD has been detected. The main methods of treatment are surgery, chemotherapy, and radiation therapy. Sometimes the best approach uses a combination of 2 or more of these methods.