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Gestational trophoblastic disease (GTD) refers to a spectrum of interrelated but histologically distinct tumors originating from the placenta (Table 37-1) (Hui, 2014a,b). These diseases are characterized by a reliable tumor marker, which is the β-subunit of human chorionic gonadotropin (β-hCG), and have varied tendencies for local invasion and spread.

TABLE 37-1Modified WHO Classification of GTD

Gestational trophoblastic neoplasia (GTN) refers to the subset of GTD that develops malignant sequelae. These tumors require formal staging and typically respond favorably to chemotherapy. Most commonly, GTN develops after a molar pregnancy but may follow any gestation. The prognosis for most GTN cases is excellent, and patients are routinely cured, even with widespread metastases. The outlook for preservation of fertility and for successful subsequent pregnancy outcomes is equally bright (Vargas, 2014; Wong, 2014). Accordingly, although GTD is uncommon, because the opportunity for cure is great, clinicians should be familiar with its presentation, diagnosis, and management.


The incidence of GTD has remained fairly constant at approximately 1 to 2 per 1000 deliveries in North America and Europe (Eysbouts, 2016; Gockley, 2016; Lybol, 2011). Although historically higher incidence rates have been reported in parts of Asia, some of this disparity may reflect discrepancies between population-based and hospital-based data collection (Chong, 1999; Kim, 2004; Matsui, 2003). Improved socioeconomic conditions and dietary changes may be partly responsible as well. That said, certain Southeast Asian populations as well as Hispanics and Native Americans living in the United States do have increased incidences (Drake, 2006; Smith, 2003; Tham, 2003).

Maternal age at the upper and lower extremes carries a higher risk of GTD (Gockley, 2016). This association is much greater for complete moles, whereas the risk of partial molar pregnancy varies relatively little with age. One explanation relates to ova from older women having higher rates of abnormal fertilization. Similarly, older paternal age has been associated with a greater risk (La Vecchia, 1984; Parazzini, 1986).

A history of prior unsuccessful pregnancies also raises the risk of GTD. For example, previous spontaneous abortion at least doubles the risk of molar pregnancy (Parazzini, 1991). More significantly, a personal history of GTD increases the risk of developing a molar gestation in a subsequent pregnancy at least tenfold. The frequency in a subsequent conception is approximately 1 percent, and most cases mirror the same type of mole as the preceding pregnancy (Garrett, 2008; Sebire, 2003). ...

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