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.