Figure 12.1 Photomicrograph of a PHM demonstrating varying-sized chorionic villi with focal swelling and focal trophoblastic hyperplasia.

Complete Hydatidiform Mole

Vaginal bleeding is the most common presenting symptom in patients with a complete mole, with onset between weeks 6 and 16 of the pregnancy. The finding of a markedly elevated hCG value is suggestive of the diagnosis, with serum hCG levels of greater than 100,000 frequently detected. In the presence of significantly elevated hCG levels, symptoms such as excessive uterine enlargement for gestational age, hyperemesis gravidarum, thyrotoxicosis, and preeclampsia may be present, although they are less common now than in previous years due to earlier detection as a result of the advancements in ultrasonography, early prenatal care, and improved sensitivity of hCG testing. On pelvic ultrasound, half of patients are found to have ovarian theca lutein cysts, resulting from hyperstimulation of the ovaries by high circulating levels of hCG.

The diagnosis of complete mole is made via ultrasonography, which is a sensitive and reliable technique for diagnosis. Because of marked swelling of the chorionic villi, a complete mole produces a characteristic vesicular sonographic pattern known as a “snowstorm” appearance.

Complete moles have the potential for uterine invasion or distant spread. Following molar evacuation, uterine invasion and metastasis occur in 15% and 4% of the patients, respectively. Interestingly, the trend to earlier diagnosis of a complete mole does not appear to have affected the incidence of postmolar tumors.

Factors that predispose to postmolar tumors include signs of marked trophoblastic proliferation; these include hCG level of more than 100,000 mIU/mL, uterine size greater than that at gestational age, and theca lutein cysts more than 6 cm in diameter. An increased risk of postmolar GTN has also been observed in women over 40 years of age and in women with multiple molar pregnancies.

Partial Hydatidiform Mole

Patients with a partial mole generally present with the signs and symptoms of a missed or incomplete abortion. Hence, the diagnosis of partial mole is usually made after histologic review of curettage specimens. Sonographic findings significantly associated with the diagnosis of partial mole include focal cystic changes in the placenta and a ratio of the transverse to anteroposterior dimension of the gestational sac greater than 1.5. Patients with partial moles do not present with markedly elevated hCG values as often as patients with complete moles.

Complete and partial moles also differ in their levels of free β- and α-subunits of hCG. Whereas complete moles have higher levels of free β-hCG, partial moles have higher levels of free α-hCG. The mean ratios of percentage free β-hCG to free α-hCG in complete and partial moles are 20.9 and 2.4, respectively. The risk of developing GTN following PHM has been reported from 0% to 11%.

Surgical Evacuation

After diagnosis of a molar pregnancy, the patient should be carefully evaluated to identify the potential presence of medical complications including preeclampsia, electrolyte imbalance, hyperthyroidism, and anemia because any of these may complicate a planned surgical evacuation.

Although hysterectomy is an option for women who no longer desire fertility and are at high a priori risk for development of GTN (age > 40, hCG > 100,000), suction curettage is recommended in most patients because it is a highly effective therapeutic option with minimal perioperative risks.

As the cervix is being dilated, the surgeon may encounter brisk uterine bleeding. Therefore, all patients should be typed and crossed for blood products in advance. Shortly after commencing suction evacuation, uterine bleeding is generally well controlled and in most cases the uterus will rapidly regress in size. When suction evacuation is thought to be complete, a sharp curettage should be gently performed to remove any residual chorionic tissue.

Patients who are Rh negative should receive Rh immune globulin at the time of evacuation because Rh D factor is expressed on trophoblast.

Role of Prophylactic Chemotherapy

The use of prophylactic chemotherapy at the time of molar evacuation remains controversial. In one trial, chemoprophylaxis significantly reduced the incidence of postmolar tumor from 15%–20% to 3%–8%. However, routine administration of chemotherapy exposes all patients to toxicity while benefiting only a relative few. In light of this, most institutions reserve the use of chemoprophylaxis to patients who are at particularly high risk for GTN or are unable or unwilling to comply with serial hCG assays. Massad et al. observed that among 40 indigent women with molar pregnancy, 33 (82%) did not fully comply with hCG follow-up and 5 (13%) were lost to follow-up before remission.

Hormonal Follow-Up

After molar evacuation, patients should be followed with weekly hCG values until they are normal for 3 weeks, and then with monthly values until they are normal for at least 6 months. After achieving nondetectable hCG levels, the risk of relapse appears to be very low.

All patients should be encouraged to use effective contraception during the entire interval of follow-up. Oral contraceptive pills are the contraception of choice because they also have the added benefit of hormonal suppression of the hypothalamic–pituitary–ovarian axis. This mitigates the risk of having an erroneously elevated hCG assay due to cross-reactivity with endogenous LH. Intrauterine devices should not be inserted until the patient achieves normal hCG levels because of the risk of uterine perforation, bleeding, and infection if residual tumor is present. Patients who have an absolute contraindication to oral contraceptives should be educated about the importance of barrier protection.

GESTATIONAL TROPHOBLASTIC NEOPLASMS

Diagnosis

Postmolar GTN is diagnosed when hCG levels plateau or rise during follow-up after molar evacuation. A plateau is defined as a less than 10% decline in four measurements taken over three weeks; a rise is defined as greater than 20% increase in three measurements taken over two weeks. Therefore, the diagnosis of GTN is based on laboratory data and does not require histologic confirmation.

Pathologic Considerations

GTN may have the histologic pattern of molar tissue, choriocarcinoma, or PSTT. Choriocarcinoma does not contain chorionic villi but is composed of sheets of both anaplastic cytotrophoblast and syncytiotrophoblast. PSTT is uncommon and is composed almost entirely of mononuclear intermediate trophoblast and does not contain chorionic villi. Measurement of serum hCG is not reliable in PSTT because secretion occurs focally. Instead, PSTT secretes human placental lactogen and should be drawn in any patient in whom this diagnosis is suspected.

Natural History of GTN

Nonmetastatic Disease

Locally invasive GTN develop in 15% of patients following evacuation of a complete mole and infrequently after other gestations. An invasive trophoblastic tumor may perforate through the myometrium, producing intraperitoneal bleeding, or erode into uterine vessels, causing vaginal hemorrhage. A bulky necrotic tumor may also serve as a nidus for infection.

Metastatic Disease

Metastatic GTN occurs in 4% of patients after evacuation of a complete mole and infrequently after other pregnancies. The most common metastatic sites are the lung (80%), vagina (30%), brain (10%), and liver (10%). Because fragile vessels perfuse trophoblastic tumors, metastases are often hemorrhagic, making biopsy of any suspected metastases high risk. Patients may present with signs and symptoms of bleeding from metastases such as hemoptysis, intraperitoneal bleeding, or acute neurologic deficits. Cerebral and hepatic metastases are uncommon unless there is concurrent involvement of the lungs and/or vagina.

Patients with pulmonary metastases commonly have asymptomatic lesions on chest radiography, although they may present with dyspnea, chest pain, cough, or hemoptysis. Trophoblastic emboli may cause pulmonary arterial occlusion and lead to right heart strain and pulmonary hypertension.

Gynecologic symptoms may be minimal or absent, and the antecedent pregnancy may be remote in time. The patient may be thought to have a primary pulmonary disease because respiratory symptoms may be dramatic. Vaginal lesions may present with irregular bleeding or purulent discharge and are most commonly located in the fornices or suburethrally. As with other metastatic lesions, these are also notorious for brisk bleeding.

Staging System

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