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… the terminal extremities of the chorionic villi are converted into transparent vesicles with clear, viscid contents. These vary in size from minute bodies a few millimetres in diameter to cystic structures the size of hazel-nuts, and hang in clusters from the villous stems, to which they are connected by thin pedicles, giving to the external surface of the chorion a grape-like appearance.

—J. Whitridge Williams (1903)


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 into 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 and the malignant invasive mole. Invasive mole is deemed malignant due to its marked penetration into and destruction of the myometrium and its ability to metastasize.

Nonmolar trophoblastic neoplasms include choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. These three are differentiated by the type of trophoblast they contain.

The malignant forms of gestational trophoblastic disease are termed gestational trophoblastic neoplasia (GTN). These include invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Other terms applied to GTN are malignant gestational trophoblastic disease and persistent gestational trophoblastic disease. These malignancies develop weeks or years following any type of pregnancy, but frequently follow a hydatidiform mole.

Each of the GTN malignancy types is histologically distinct and varies in its propensity to invade and metastasize. However, histological confirmation is typically not available. Instead, measurement of serum hCG levels combined with clinical findings— rather than a histological specimen—is used to diagnose and treat this malignancy. Accordingly, GTN is often identified and effectively treated as a group.

In the past, these metastatic tumors had a prohibitively high mortality rate. However, with chemotherapy, most tumors currently are highly curable. Early-stage GTN is typically cured with single-agent chemotherapy, whereas later-stage disease usually responds to combination chemotherapy (Ngan, 2015).


The classic histological findings of molar pregnancy include trophoblast proliferation and villi with stromal edema (Fig. 20-1). The degree of histological changes, karyotypic differences, and the absence or presence of embryonic elements are used to classify them as either complete or partial moles. 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. (Used with permission from Dr. Brian Levenson.) B. Low-magnification photomicrograph shows generalized edema and cistern ...

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