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Gestational
trophoblastic disease is proliferation of trophoblastic tissue in
pregnant or recently pregnant women. Manifestations may include
excessive uterine enlargement, vomiting, vaginal bleeding, and preeclampsia,
particularly during early pregnancy. Diagnosis includes measurement
of the β subunit of human
chorionic gonadotropin and pelvic ultrasonography and confirmation
by biopsy. Tumors are removed by D & C. If disease persists
after removal, chemotherapy is indicated.
Gestational trophoblastic disease is a tumor originating from the trophoblast, which surrounds the blastocyst and develops into the chorion and amnion (see Conception and Prenatal Development). This disease can occur during or after an intrauterine or ectopic pregnancy. If the disease occurs during a pregnancy, spontaneous abortion, eclampsia, or fetal death typically occurs; the fetus rarely survives. Some forms are malignant; others are benign but behave aggressively.
Pathology
Classification is morphologic. A hydatidiform mole is an abnormal pregnancy in which villi become edematous (hydropic) and trophoblastic tissue proliferates. Chorioadenoma destruens (invasive mole) is local invasion of the myometrium by a hydatidiform mole. Choriocarcinoma is an invasive, usually widely metastatic tumor composed of malignant trophoblastic cells and lacking hydropic villi; most of these tumors develop after a hydatidiform mole. Placental site trophoblastic tumors, which are rare, consist of intermediate trophoblastic cells that persist after a term pregnancy. They may invade adjacent tissues or metastasize.
Hydatidiform moles are most common among women < 17 or > 35. They occur in about 1/2000 gestations in the US. For unknown reasons, incidence in Asiatic countries approaches 1/200. Most (> 80%) hydatidiform moles are benign and regress spontaneously. The rest may persist, tending to become invasive; 2 to 3% are followed by choriocarcinoma.
Symptoms,
Signs, and Diagnosis
Initial manifestations of a hydatidiform mole suggest early pregnancy, but the uterus often becomes larger than expected within 10 to 16 wk gestation. Vaginal bleeding, lack of fetal movement, absent fetal heart sounds, and severe vomiting are common. Passage of grapelike tissue strongly suggests the diagnosis. Complications may include uterine infection, sepsis, hemorrhagic shock, and preeclampsia, which may occur during early pregnancy. Placental site trophoblastic tumors tend to cause bleeding. Choriocarcinoma usually manifests with symptoms due to metastases. Gestational trophoblastic disease does not impair fertility or predispose to prenatal or perinatal complications (eg, congenital malformations, spontaneous abortions).
If gestational trophoblastic disease is suspected, testing includes measurement of serum β subunit of human chorionic gonadotropin (β-hCG) and pelvic ultrasonography. Findings (eg, very high β-hCG levels) may suggest the diagnosis, but biopsy is required.
Treatment
Hydatidiform mole, invasive mole, and placental site trophoblastic tumor are evacuated by suction curettage. Alternatively, if childbearing is not planned, hysterectomy may be done.
After tumor removal, gestational trophoblastic disease is classified clinically to determine whether additional treatment is needed. (The clinical classification system does not correspond to the morphologic classification system.) A chest x-ray is taken, and serum β-hCG is measured. If the β-hCG level does not normalize within 10 wk, the disease is classified as persistent. Persistent disease requires CT of the brain, chest, abdomen, and pelvis. Results dictate whether disease is classified as nonmetastatic or metastatic. In metastatic disease, risk of death may be low or high (see
Table 3: Gynecologic Tumors: NIH Criteria for Poor-Prognosis Metastatic Gestational Trophoblastic Disease ).
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Table 3
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NIH Criteria for Poor-Prognosis
Metastatic Gestational Trophoblastic
Disease
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Urinary hCG excretion > 100,000 IU in 24 h
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Duration of disease > 4 mo (interval since prior pregnancy)
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Brain or liver metastases
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Disease after full-term pregnancy
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Serum hCG > 40,000 mIU/mL
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Failed prior chemotherapy
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WHO score > 8
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hCG = Human chorionic gonadotropin.
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Persistent disease is usually treated with chemotherapy. Treatment is considered successful if at least 3 consecutive serum β-hCG measurements at 1-wk intervals are normal. Typically, oral contraceptives (any is acceptable) are given for 6 to 12 mo; alternatively, any effective contraceptive method can be used. Nonmetastatic disease can be treated with a single chemotherapeutic drug ( methotrexate or dactinomycin ). Alternatively, hysterectomy is considered for patients > 40 or those desiring sterilization and may be required for those with severe infection or uncontrolled bleeding. If single-drug chemotherapy is ineffective, hysterectomy or multidrug chemotherapy is indicated. Virtually 100% of patients with nonmetastatic disease can be cured.
Low-risk metastatic disease is treated with single or multiple drug chemotherapy. High-risk metastatic disease requires aggressive multidrug chemotherapy. Cure rates are 90 to 95% for low-risk and 60 to 80% for high-risk disease.
Hydatidiform mole recurs in about 1% of subsequent pregnancies. Patients who have had a mole require ultrasonography early in subsequent pregnancies.
Last full review/revision November 2005
Content last modified November 2005
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