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Gestational trophoblastic disease (GTD) is the term used to encompass a group of tumors typified by abnormal trophoblast proliferation. Trophoblast produces human chorionic gonadotropin (hCG). Thus, the measurement of this peptide hormone in serum is essential for GTD diagnosis, management, and surveillance. GTD histologically is divided into hydatidiform moles, which are characterized by the presence of villi, and nonmolar trophoblastic malignant neoplasms, which lack villi.

Hydatidiform moles are excessively edematous immature placentas (Benirschke, 2012). These include the benign complete hydatidiform mole and partial hydatidiform mole (Table 13-1). The third member is the malignant invasive mole (Hui, 2014b). Invasive mole is deemed malignant because of its marked penetration into and destruction of the myometrium and its ability to metastasize.

TABLE 13-1Modified WHO Classification of GTD

Nonmolar trophoblastic neoplasms include choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor (Hui, 2014a). These three are differentiated by the trophoblast type that they contain.

Under the GTD umbrella term, the malignant forms of GTD are termed gestational trophoblastic neoplasia (GTN). These include invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. These malignancies develop weeks or years following any type of pregnancy, but more frequently follow hydatidiform mole.

Each GTN malignancy type is histologically distinct and varies in its propensity to invade and metastasize. However, these diagnoses are infrequently identified from an actual histological specimen. Instead, measurement of serum hCG levels and clinical findings are more often used to diagnose and treat this malignancy. Accordingly, GTN is often managed as a single composite clinical entity. With chemotherapy, most tumors currently are highly curable.


Classic histological findings of molar pregnancy include trophoblast proliferation and villi with stromal edema (Fig. 13-1). The degree of histological changes, karyotype and immunostaining differences, and the absence or presence of embryonic elements are used to classify them as either complete or partial hydatidiform moles (Table 13-2). These two also vary in their associated risks for developing medical comorbidities and postevacuation GTN. Of the two, GTN more frequently follows complete hydatidiform mole.


Complete hydatidiform mole. A. Gross specimen with characteristic vesicles of variable size. (Photograph contributed by Dr. Sasha Andrews. Reproduced with permission from Patel S, Roberts S, Rogers V, et al [eds]: Williams Obstetrics Study Guide, 25th ed. New York, NY: McGraw Hill; 2019.) B. Low-magnification photomicrograph shows generalized edema and cistern formation (black asterisks) within avascular villi. Haphazard trophoblastic hyperplasia is marked by a yellow asterisk on the right. (Reproduced ...

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