Gestational Trophoblastic Disease
Summary of Key Points
Incidence and Epidemiology
• The incidence of complete hydatidiform mole is approximately 1 in 1200 pregnancies in the United States.
• The incidence of partial hydatidiform mole is approximately 1 in 650 pregnancies.
• Repeat moles occur in approximately 1 in 125 pregnancies, and third moles occur in approximately 1 in 5 pregnancies.
• Complete hydatidiform mole is usually due to an androgenetic diploid conception, in which a haploid sperm fertilizes an egg that lacks female chromosomes.
• A partial hydatidiform mole develops when dispermy occurs, and the resulting conceptus is triploid.
Pathology
• Earlier diagnosis of complete hydatidiform mole due to improved ultrasound and human chorionic gonadotropin (hCG) assays has made the pathological diagnosis of complete hydatidiform mole more difficult because of its resemblance to partial hydatidiform mole and nonmolar abortions.
• Hydatidiform mole is characterized by hydropic villi with trophoblastic hyperplasia.
• Invasive mole is characterized by invasion of myometrium by hydropic villi surrounded by hyperplastic trophoblasts.
• Choriocarcinoma is characterized by sheets of neoplastic cytotrophoblasts and syncytiotrophoblasts invading tissue and is associated with necrosis and hemorrhage. Hematogenous spread occurs early.
• Placental site and epithelioid trophoblastic tumors are rare forms of choriocarcinoma made up of mononuclear cells from intermediate trophoblast at the implantation site that invade the myometrium. Both placental site and epithelioid trophoblastic tumors metastasize late and are relatively resistant to chemotherapy.
Clinical Features
• Hydatidiform mole commonly presents in the first trimester with vaginal bleeding.
• Complete hydatidiform mole is usually diagnosed by ultrasound because of the abnormal appearance of the placenta and the absence of a fetus.
• Partial hydatidiform mole can be difficult to diagnose by ultrasound and is usually confirmed pathologically.
• Persistent postmolar gestational trophoblastic neoplasia is usually nonmetastatic and is characterized by a rising hCG level and persistent bleeding due to residual molar tissue.
• Metastatic postmolar gestational trophoblastic neoplasia (GTN) usually involves the lungs and, rarely, the brain, liver, and other distant sites.
• The diagnosis of gestational trophoblastic neoplasia after a miscarriage or term pregnancy is frequently delayed and commonly presents with significant disease.
Primary Therapy
• Single-agent therapy is usually curative in patients with stage I, II, and III disease who have low prognostic scores (<7). There is evidence that patients with low-risk GTN (scores of 5 and 6) but a large tumor burden (hCG >100,000 mIU/mL) commonly require multiagent chemotherapy to achieve cure.
• Patients with stage II, III, and IV disease who have high-risk scores (≥7) require combination chemotherapy for optimal outcome.
• Survival rates of 100% in patients with stage I, II, and III disease and 80% in patients with stage IV disease should be achieved.
• Response to therapy and remission are determined by hCG levels, which should be tested weekly during chemotherapy.
• Patients with high-risk disease should be treated with three or four consolidation courses after the hCG titer normalizes.
1. Which of the following statements about molar pregnancy is false?
A Partial hydatidiform moles are always triploid.
B Repeat hydatidiform moles occur in approximately 1 : 100 pregnancies.
C Complete hydatidiform moles are due to an androgenetic diploid conception in which a haploid sperm fertilizes an egg that lacks female chromosomes.
D The diagnosis of molar pregnancy is now being made earlier because of the introduction of genetic testing.
2. The pathological diagnosis of molar pregnancy depends upon which of the following criteria?
3. After evacuation of a molar pregnancy, the clinical diagnosis of gestational trophoblastic neoplasia is based on which of the following findings?
A A plateau or rise in the hCG level
B Persistence of hCG for more than 6 months
4. The optimal initial treatment for a 26-year-old patient with postterm stage III gestational trophoblastic neoplasia and a International Federation of Gynecologists and Obstetricians score of 4 is
A Hysterectomy followed by single-agent chemotherapy
B Single-agent chemotherapy without hysterectomy
D Hysterectomy followed by multiagent chemotherapy
E Resection of pulmonary metastases with adjunctive single-agent chemotherapy
5. Which of the following statements about subsequent pregnancy after a molar gestation is/are true?
A All subsequent pregnancies after a molar gestation should be considered high risk.
B Recurrent molar pregnancy can be detected by the 10th week of gestation.
C Subsequent pregnancy after a molar gestation is associated with an increased risk of congenital abnormalities.
D Subsequent pregnancy after evacuation of a molar gestation should not be undertaken until the hCG level has been undetectable for at least 12 months.
E Patients who become pregnant before the hCG level becomes undetectable should be treated with chemotherapy.
1. Answer: D. The diagnosis of molar pregnancy is made by sonography and human chorionic gonadotropin (hCG) levels. Genetic tests are sometimes used to determine if a molar pregnancy is partial or complete.
2. Answer: A and B. Local invasion occurs with molar pregnancy but is not required for the diagnosis. Flow cytometry is used to determine ploidy to distinguish between a partial and complete mole. P57 immunohistochemical staining is used to identify an early complete mole when the histologic criteria are equivocal.
3. Answer: A, B, C, and E. Heavy vaginal bleeding can occur because of retained molar tissue but does not necessarily mean that she has developed invasive mole.
4. Answer: B. WHO Prognostic Score of 4 places the patient in a low-risk category that is associated with a cure rate of approximately 80% with single-agent chemotherapy. Patients who become resistant to single-agent chemotherapy can be cured with second-line multiagent protocols. When metastatic disease is present, the main indications for hysterectomy are heavy bleeding and infection.
5. Answer: B. Sonographic evaluation at 10 weeks of gestation has a high degree of accuracy in detecting both partial and complete moles. Sonograms performed prior to the 10th week will detect a failed pregnancy but may not be able to determine whether the pregnancy is molar or nonmolar.
