Gestational Trophoblastic Disease

Neoplasms of trophoblastic origin can follow a spontaneous abortion, an ectopic pregnancy, or a full-term pregnancy. A hydatidiform mole is a pregnancy in which the villi have become hydropic and trophoblastic elements have proliferated. Chorioadenoma destruens (invasive mole) is a local invasion of the myometrium by the hydatidiform mole. Choriocarcinoma is an invasive, usually widely metastatic tumor composed of malignant trophoblastic cells without hydropic villi. Placental site trophoblastic tumor, consisting of intermediate trophoblastic cells that persist after a term pregnancy, is rare.

A hydatidiform mole is more common after pregnancies in very young (< 17 yr) or older (late 30s and 40s) patients, occurring in about 1 in 2000 gestations in the USA. For unknown reasons, the incidence in Asiatic countries approaches 1 in 200. More than 80% of hydatidiform moles are benign and spontaneously regress. However, 15 to 20% tend to persist and 2 to 3% are followed by choriocarcinoma (in about 1 in 25,000 to 45,000 pregnancies).

Symptoms, Signs, and Diagnosis
A hydatidiform mole is often manifested within 10 to 16 wk after conception by a rapidly enlarging uterus, which is often larger than expected for estimated gestational age. Vaginal bleeding, lack of fetal movement, absent fetal heart sounds, and severe nausea and vomiting are common. Passage of grapelike molar tissue suggests the diagnosis, and histologic examination confirms it. Pelvic ultrasonography, although not infallible, is helpful in diagnosis.
Human chorionic gonadotrophin (hCG) is produced by the proliferated trophoblastic tissue, and high serum levels of the β subunit of hCG (β-hCG) aid in the diagnosis of a gestational trophoblastic disease.

Complications of a partial or complete mole include intrauterine infection and septicemia, hemorrhage, toxemia, and development of persistent gestational trophoblastic disease. Placental site trophoblastic tumor, because of its intramural location, tends to cause bleeding; it may infiltrate adjacent tissues and occasionally metastasizes to distant sites. Choriocarcinoma, which is highly malignant, metastasizes early and widely via venous and lymphatic systems.

Treatment
If the hydatidiform mole spontaneously regresses, the patient should use oral contraceptives (unless otherwise contraindicated) for 6 mo. If a mole does not regress, it must be removed (evacuated). The treatment of choice is suction curettage, followed by oxytocin stimulation and light curettage of the uterus. Hysterotomy is no longer used unless a suction aspirator is unavailable and the uterus is large. Hysterectomy may be selected, based on age, parity, and future pregnancy plans. A chest x-ray should be obtained and serum β-hCG titers determined after removal. The titer should progressively fall to a normal level in < 10 to 12 wk. If persistent gestational trophoblastic disease is diagnosed and the patient requires chemotherapy, she should take oral contraceptives for 12 mo after successful treatment.

Patients with persistently high or rising β-hCG levels may have an invasive mole or choriocarcinoma. A formal metastatic evaluation and then treatment (usually chemotherapy) are required. After evaluation, the disease is classified as nonmetastatic or metastatic. Metastatic disease is further classified as producing a good or poor prognosis.

All patients with nonmetastatic gestational trophoblastic disease can be treated with a single chemotherapeutic drug (methotrexate or dactinomycin). However, hysterectomy may be considered for patients > 40 yr or those desiring sterilization and may be required for those with severe infection or uncontrolled bleeding. A few patients with nonmetastatic disease who do not respond to a single drug may be candidates for a hysterectomy or may ultimately require a multidrug regimen. Virtually 100% of patients with nonmetastatic disease can be cured.

The prognosis for patients with metastatic disease has greatly improved with development of effective multidrug chemotherapy regimens. Patients with low-risk metastatic disease, as determined by the WHO scoring system (

see Table 241-8), are sometimes treated with a single drug. Patients with high-risk metastatic disease require aggressive multidrug chemotherapy. Overall, the cure rate for high-risk patients is 60 to 80%.

For patients with a history of hydatidiform mole, the risk of recurrence is about 1% in subsequent pregnancies. These patients should have an ultrasound examination early in pregnancy to confirm a normal intrauterine pregnancy. Gestational trophoblastic disease does not compromise fertility and does not increase the incidence of congenital anomalies, pregnancy wastage, or prenatal or perinatal complications.

Provided by ArmMed Media
Revision date: July 8, 2011
Last revised: by Jorge P. Ribeiro, MD