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Gestational Trophoblastic Disease

Depending on histopathologic changes that occur in the trophoblast cells of the chorionic villi, gestational trophoblastic disease takes one of three forms. The first is hydatidiform mole, a nonmalignant neoplasm that forms on the chorion (the outer layer of the membrane containing amniotic fluid). The second form, commonly called invasive mole (chorioadenoma destruens), is a self-limiting, malignant tumor that occurs when trophoblastic tissue continues to grow and locally invades the uterine myometrium and pelvic blood supply. The third category is choriocarcinoma, a serious, rapidly developing. but rare, carcinoma. Neoplastic trophoblasts proliferate without cystic villi and may metastasize profusely throughout the body.

Gestational trophoblastic disease is reported to occur in about 1 in every 2,000 pregnancies. Recent research indicates that the incidence would be much higher if all cases of the disorder were identified. Some cases aren't recognized because the pregnancy is aborted early and the products of conception aren't available for analysis. The incidence is increased in women from low socioeconomic groups, older women, and multiparous women. The incidence is highest in Asian women, especially those from Southeast Asia.

With prompt diagnosis and appropriate treatment. the prognosis is usually excellent for patients with hydatidiform or invasive mole; about 10% of patients with hydatidiform mole develop choriocarcinoma. Recurrence is possible in about 2% of patients.


Hydatidiform mole is a condition which develops when a pregnancy has many complications. Conception takes place, but placental tissue grows very fast, rather than supporting the growth of a fetus.

The result is a tumor, rather than a baby. This is known as a molar pregnancy.

Choriocarcinoma is a similar type of growth. In approximately one-half of cases of choriocarcinoma, the preceding factor is hydatidiform mole. However, only 5 - 10% of molar pregnancies are associated with later choriocarcinoma. Therefore, choriocarcinoma remains an uncommon, yet almost always curable, cancer that can be associated with pregnancy.

Signs and Symptoms

A patient with hydatidiform mole may report vagina, bleeding, ranging from brownish red spotting to bright red hemorrhage. She may report passing tissue that resembles grape clusters. Her history may also include lower abdominal cramps, such as those that accompany spontaneous abortion, hyperemesis, and signs and symptoms of preeclampsia.

On inspection, a uterus that is exceptionally large for the patient's gestational date is detected. On pelvic examination. you may discover grapelike vesicles in the vagina. Palpation may reveal ovarian enlargement due to theca-lutein cysts. Auscultation of the uterus may reveal the absence of fetal heart tones normally noted during a previous visit.

A patient with choriocarcinoma typically reports vaginal bleeding. If the disease has metastasized, she may also report hemoptysis, cough, dyspnea, head­ache, dizzy spells, weakness, paralysis, and rectal bleeding.

Occasionally, a patient with choriocarcinoma may exhibit an acute abdomen due to rupture of the uterus, liver, or theca-lutein cyst. On inspection, the uterus may be enlarged, with blood coming through the os. A tumor may be visible in the vagina.

Diagnostic tests

Radioimmunoassay of HCG levels. performed frequently, can allow early and accurate diagnosis. HCG levels that are extremely elevated for early pregnancy indicate gestational trophoblastic disease.

Histologic examination of possible hydatid vesicles is used to confirm the diagnosis.

Ultrasonography performed after the third month shows grapelike clusters rather than a fetus.

Amniography, a procedure that introduces a water-soluble dye into the uterus, may reveal the absence of a fetus (performed only when the diagnosis is in question).

Doppler ultrasonography demonstrates the absence of fetal heart tones.

Hemoglobin level and hematocrit, red blood cell count, prothrombin time, partial thromboplastin time, fibrinogen levels, and hepatic and renal function findings are abnormal.

White blood cell count and erythrocyte sedimentation rate are increased.

Chest X-rays, computed tomography scanning, and magnetic resonance imaging may be used to identify choriocarcinoma metastasis.

Lumbar puncture may reveal early cerebral metastasis if HCG is in the cerebrospinal fluid.

Differential diagnosis is used to rule out normal pregnancy, threatened abortion, uterine leiomyomas, multiple gestation, and incorrect gestational date


Gestational trophoblastic disease necessitates uterine aracuation by dilatation and curettage, abdominal hysterectomy, or instrument or suction curettage, depending on uterine size. I.V. oxytocin may be used to promote uterine contractions.

Postoperative treatment varies, depending on the amount of blood lost and complications. If no complications develop, hospitalization is usually brief and normal activities can be resumed quickly, as tolerated.

Because of the possibility of choriocarcinoma development following hydatidiform mole, scrupulous follow up care is essential. Such care includes monitoring HCG levels once weekly until titers are negative for 3 consecutive weeks; then once monthly for 6 months; then every 2 months for 6 months. It also includes chest X-rays to check for lung metastasis once monthly until HCG titers are negative, then once every 2 months for 1 year.

Another pregnancy should be postponed until at least 1 year after all titers and X-ray findings are negative. An oral contraceptive is indicated to prevent pregnancy.

Prophylactic chemotherapy with either methotrexate or actinomycin D after evacuation of the uterus has been successful in preventing malignant gestational trophoblastic disease. Chemotherapy with combination therapy and irradiation are used for metastatic choriocarcinoma.


Although careful monitoring after the removal of hydatidiform mole or termination of pregnancy may not prevent the development of choriocarcinoma, it is essential in early identification of the condition, which improves outcome.

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