Introduction

Essentials of Diagnosis

Hydatidiform Mole

• Amenorrhea.
• Irregular uterine bleeding.
• Serum hCG ß-subunit < 40,000 mU/mL.
• Passage of grape-like clusters of enlarged edematous villi per vagina.
• Ultrasound of uterus with characteristic “snowstorm” image and no fetus or placenta.
• Cytogenetic composition is 46,XX (85%), completely of paternal origin.

General Considerations

Gestational trophoblastic disease is a spectrum of disorders that includes hydatidiform mole, invasive mole, and choriocarcinoma. Partial moles generally show evidence of an embryo or gestational sac; are polyploid, slower-growing, and less symptomatic; and often present clinically as a missed abortion. Partial moles tend to follow a benign course, while complete moles have a greater tendency to become choriocarcinomas.

The highest rates of gestational trophoblastic disease occur in some developing countries, with rates of 1:125 pregnancies in certain areas of Asia. In the United States, the frequency is 1:1500 pregnancies. Risk factors include low socioeconomic status, a history of mole, and age below 18 or above 40. Approximately 10% of women require further treatment after evacuation of the mole; 5% develop choriocarcinoma.

Clinical Findings

A. Symptoms and Signs
Excessive nausea and vomiting occur in over one-third of patients with hydatidiform mole. Uterine bleeding, beginning at 6-8 weeks, is observed in virtually all instances. In about one-fifth of cases, the uterus is larger than would be expected in a normal pregnancy of the same duration. Bilaterally enlarged cystic ovaries are sometimes palpable. They are the result of ovarian hyperstimulation due to excess of hCG.

Preeclampsia-eclampsia, frequently of the fulminating type, may develop during the second trimester of pregnancy, but this is unusual.

Choriocarcinoma may be manifested by continued or recurrent uterine bleeding after evacuation of a mole or following delivery, abortion, or ectopic pregnancy. The presence of an ulcerative vaginal tumor, pelvic mass, or evidence of distant metastatic tumor may be the presenting observation. The diagnosis is established by pathologic examination of curettings or by biopsy.

B. Laboratory Findings
A serum hCG ß-subunit value above 40,000 mU/mL or a urinary hCG value in excess of 100,000 units/24 h increases the likelihood of hydatidiform mole.

C. Imaging
Ultrasound has virtually replaced all other means of preoperative diagnosis of hydatidiform mole. A preoperative chest film is indicated to rule out pulmonary metastases of trophoblast.

Treatment

A. Specific (Surgical) Measures
The uterus should be emptied as soon as the diagnosis of hydatidiform mole is established, preferably by suction. Ovarian cysts should not be resected nor ovaries removed; spontaneous regression of theca lutein cysts will occur with elimination of the mole.

If malignant tissue is discovered at surgery or during the follow-up examination, chemotherapy is indicated.

Thyrotoxicosis indistinguishable clinically from that of thyroid origin may occur. While hCG usually has minimal TSH-like activity, the very high hCG levels associated with moles result in the release of T3 and T4 and cause hyperthyroidism. Patients thyrotoxic on this basis should be stabilized with ß-blockers prior to induction of anesthesia for their surgical evacuation. Surgical removal of the mole promptly corrects the thyroid overactivity.

B. Follow-Up Measures
Effective contraception (preferably birth control pills) should be prescribed. Weekly quantitative hCG level measurements are initially required. Following successful surgical evacuation, moles show a progressive decline in hCG. After two negative weekly tests (< 5 mU/mL), the interval may be increased to monthly for 6 months and then to every 2 months for a total of 1 year. If levels plateau or begin to rise, the patient should be evaluated by repeat chest film and D&C before the initiation of chemotherapy.

C. Antitumor Chemotherapy
For low-risk patients with a good prognosis, methotrexate, 0.4 mg/kg intramuscularly over a 5-day period, or dactinomycin, 10-12 ug/kg/d intravenously over a 5-day period, is used (see Table 40-3). Patients with a poor prognosis should be referred to a cancer center, where multiple-agent chemotherapy probably will be given. The side effects - anorexia, nausea and vomiting, stomatitis, rash, diarrhea, and bone marrow depression - usually are reversible in about 3 weeks and can be ameliorated by the administration of leucovorin (0.1 mg/kg). Repeated courses of methotrexate 2 weeks apart generally are required to destroy the trophoblast and maintain a zero chorionic gonadotropin titer, as indicated by ß-hCG determination.

D. Supportive Measures
Oral contraceptives (if acceptable) or another reliable birth control method should be prescribed to avoid the hazard and confusion of elevated hCG from a new pregnancy. The hCG levels should be negative for a year before pregnancy is again attempted. In the pregnancy following a mole, the hCG level should be checked 6 weeks postpartum.

Prognosis

Five years survival after courses of chemotherapy, even when metastases have been demonstrated, can be expected in at least 85% of cases of choriocarcinoma.

Seckl MJ et al: Choriocarcinoma and partial hydatidiform moles. Lancet 2000;356:36.

Shapter AP et al: Gestational trophoblastic disease. Obstet Gynecol Clin North Am 2001;28:805.