Gestational trophoblastic disease (GTD) represents a variety of diseases arising from the placenta. The most common is the hydatidiform mole. Gestational trophoblastic neoplasia (GTN) indicates processes that have the capacity for local invasion and/or metastasis, and include invasive moles, gestational choriocarcinomas, and placental site tumors.¹ The incidence of hydatiform moles in the United States is about one 1 in 1000 to 1200 pregnancies. Malignant sequelae after the evacuation of the mole occur in about 20%. Gestational choriocarcinoma occurs in about 1 in 20,000 to 40,000 pregnancies. Although these diseases are not particularly common, women with GTD are seen for pregnancy, or arrive at emergency centers with bleeding, and sonography is almost universally the first imaging test performed.¹

GTDs are a group of disorders that are thought to originate through fertilization of the ovum by 1 or more spermatozoa in either a normal or abnormal manner. This is in contrast to the nongestational forms of choriocarcinoma that can arise in the ovary or testicle and do not involve fertilization or a prior gestational event. The trophoblastic neoplasms arise from the trophoblastic elements of the developing blastocyst, and therefore retain certain inherent characteristics, such as the ability to invade underlying tissues and the ability to synthesize human chorionic gonadotropin (hCG).

The principal role of sonography in GTD is in establishing the diagnosis of hydatidiform mole.² A characteristic sonographic appearance of hydropic villi occurs with most molar pregnancies. Sonography is also considered an important adjunctive test to serial β-hCG assays in malignant trophoblastic disease. With sonography, it is sometimes possible to demonstrate uterine invasion by trophoblastic tissue.³ It can also be used to monitor the response of the tumor to therapy, and the presence of other metastatic sites can be ascertained.⁴ Color Doppler sonography affords detection in areas of abnormal blood flow within the myometrium and can be used as a means to monitor the effectiveness of chemotherapy (Figure 30-1).⁵

GTD has been classified in a variety of ways (Table 30-1). Initial attempts at classification were based on histopathologic criteria. Currently, with the use of hCG monitoring, patients have been classified according to a clinical staging system. The use of different classification systems has probably contributed to confusion among obstetricians and sonologists concerning the sonographic categorization of these diseases. In this chapter, the sonographic features of the various forms of GTD are presented relative to both the pathologic and clinical classifications.

Because the sonographic features of an invasive mole and choriocarcinoma are similar, they are presented under the same heading. Accordingly, the discussion portion of the chapter is divided into 2 major categories of GTD: molar pregnancies and malignant GTDs. Although it may be difficult to differentiate the various pathologic types of gestational trophoblastic disorders by their sonographic features alone, the combination of clinical, laboratory, and sonographic findings can usually specify the type and extent of trophoblastic disease that is present.

Histopathologic

This classification divides trophoblastic diseases into hydatidiform mole, invasive mole (chorioadenoma destruens), choriocarcinoma, and placenta site trophoblastic tumor based on histopathologic criteria.

Hydatidiform mole is characterized by marked edema and enlargement of the chorionic villi, producing vesicular structures. The vesicles are the characteristic that allows sonographic identification. These changes are accompanied by disappearance of the villus blood vessels and proliferation of the trophoblast (cytotrophoblast and syncytiotrophoblast) that line the villi (Figure 30-2). Although moles with an abundantly proliferative trophoblast may have a greater likelihood of being malignant, it is not possible to accurately predict the malignant potential of a given mole based on the histologic appearance. Approximately 20% of complete moles are followed by additional malignant sequelae of invasive mole or choriocarcinoma.⁶ Further classification of hydatidiform mole based on histopathologic criteria has not proven to be an accurate prognostic indication to select the 20% of patients with a molar pregnancy who will subsequently develop malignant disease.⁷

Invasive mole (chorioadenoma destruens) is the term used to describe trophoblastic disease where there has been invasion into the myometrium of the uterus. Grossly, a vesicular structure is preserved (Figure 30-3). Microscopic examination will reveal edematous villi invading the myometrium. There is often abundant trophoblastic proliferation of the remaining villi. Where the villi invade the underlying myometrium, some hemorrhage is produced. Necrosis, however, is absent. Hysterectomy is rarely used in the treatment of trophoblastic disease today. Therefore, the diagnosis of invasive mole is rarely made based on surgical pathology.

Choriocarcinoma is characterized by the lack of any remaining villus structure. Microscopic examination will reveal sheets of highly malignant trophoblast with proliferation of both cytotrophoblast and syncytial trophoblast (Figure 30-4). There is associated hemorrhage and necrosis, which is the other hallmark of choriocarcinoma. Choriocarcinoma accounts for approximately 5% of all GTDs.⁷ Local pelvic metastases and lung metastases are the most common, but liver, brain, kidney, and bowel metastases may occur as well.

Placental site trophoblastic tumors (PSTTs) are extremely rare and arise from the placental implanation site, resembling a form of syncytial endometritis. The myometrium is invaded by the trophoblastic cells, and vascular invasion is usually seen. Human chorionic gonadotropin levels are low, whereas human placental lactogen is secreted by the cells. Whereas the other forms of GTN respond to chemotherapy, PSTTs are not responsive to medical therapy, and are treated by hysterectomy.¹

Clinical Aspects

Careful follow-up of patients with hCG monitoring and the use of chemotherapy as the main mode of therapy rather than surgery has led to a replacement of the histopathologic classification by a more practical clinical classification of GTD. This clinical classification still recognizes hydatidiform moles, both the complete and partial types.

Any patient with a pathologic diagnosis of choriocarcinoma or invasive mole is considered to have malignant GTD, as are patients who develop plateauing or rising hCG levels, as defined by the 2000 FIGO staging. Patients are not classified as having malignant GTD solely by a pathologic diagnosis of hydatidiform mole; such patients may or may not follow a malignant clinical course.⁴ Patients with malignant GTD are further subdivided into nonmetastatic or metastatic groups. Clinical experience in treating patients with trophoblastic disease has further identified a group of patients with metastatic disease that is considered to be at high risk.^8,9 This includes patients with liver or brain metastasis, β-hCG levels above 40,000 mIU/mL before therapy, an interval of more than 4 months between pregnancy and initiation of therapy, failure of previous chemotherapy, and trophoblastic disease that develops after a full-term pregnancy.¹⁰ These high-risk patients require especially diligent radiologic and sonographic evaluation in their follow-up.

Pathogenesis

The pathogenesis of hydatidiform mole has remained a subject of considerable speculation for many years. The work of Kajii and Ohama,¹¹ however, demonstrated that hydatidiform mole results from the fertilization of an “empty egg,” that is, an ovum without any active chromosomal material. The chromosomes of the sperm, finding no chromosomal complement from the ovum, reduplicate themselves, resulting in a 46,XX molar pregnancy. This has also been called a complete mole or classic mole. In complete mole, there is complete lack of fetal development, so there are no identifiable fetal parts or fetal membranes that can be seen in this situation. Complete moles are associated with different degrees of trophoblastic proliferation and may follow either a benign or malignant clinical course. Only about 20% of cases will eventually pursue a malignant course.⁶

Some cases of hydatidiform mole are found to contain a small complement of fetal structure, such as a placenta with membranes, or even a developed fetus. This is referred to as a partial mole. These cases usually involve some edema of the villi but relatively little trophoblastic proliferation. Hydropic degeneration is present, but with some elements associated with fetal structures, the designation partial mole has been made.¹² Although subsequent malignancy has been reported, partial moles are almost always benign.¹³ In a partial mole, the fetus usually has significant congenital anomalies and a triploid karyotype.¹⁴ Two sets of chromosomes are of paternal origin, and the third set is of maternal origin, usually leading to a karyotype of 69 XXY or 69 XXX.

A fetus with a coexisting molar pregnancy can occur. This is much less common than a partial molar pregnancy; however, it can grossly appear similar to the partial mole. This disorder is thought to result from a dizygotic pregnancy, with one fetus resulting from a normal fertilization and the other being a complete molar pregnancy.¹⁵ In these patients, a fetus and normal placenta can usually be identified, in contrast to a partial molar pregnancy where a normal placenta is not present.