Gestational trophoblastic disease (GTD) is a group of tumors defined by abnormal trophoblastic proliferation. Trophoblasts produce human chorionic gonadotropin (hCG). GTD is divided into hydatidiform moles (HM), which contain villi, and other trophoblastic neoplasms, which lack villi. The nonmolar or malignant forms of GTD are called gestational trophoblastic neoplasia (GTN) and include the invasive mole, choriocarcinoma, epithelioid trophoblastic tumor (ETT), and placental site trophoblastic tumor (PSTT). These malignancies can occur weeks or even years following any pregnancy but occur most commonly after a molar pregnancy.

The first description of GTD was by Hippocrates around 400 BC. However, it wasn't until 1895 that Felix Marchand discovered the association between pregnancy and GTD. When healthy trophoblastic tissue penetrates the endometrium, it creates the placenta, a rich uterine vasculature connecting the fetus and mother.

HM, or molar pregnancy, originates from the placenta. HM is categorized as a complete or partial mole and is usually considered the noninvasive form of GTD. Although HMs are usually considered benign, they are premalignant and can potentially become malignant and invasive.

Although the behavior of a healthy trophoblast is well-controlled in benign GTD, the regulatory mechanisms can become dysfunctional, resulting in highly invasive vascular and metastatic tumors. GTN involves the malignant entities of GTD, including invasive mole, choriocarcinoma, ETT, and PSTT, all of which can metastasize and be fatal if not treated in a timely and effective manner.

An invasive mole occurs when abnormal trophoblastic cells penetrate deeply into the uterine wall, potentially leading to complications. The rapid growth of abnormal tissue characterizes this condition and can result in abnormal uterine bleeding.

Choriocarcinoma is a rare and aggressive neoplasm. The 2 significant choriocarcinoma subtypes, namely gestational and nongestational, have very different biological activity and prognoses. Choriocarcinoma predominately occurs in women but can also occur in men, usually as part of a mixed germ cell tumor.

ETT is a rare and distinctive subtype of GTN arising from the trophoblastic cells that contribute to the placenta during pregnancy. Characterized by its epithelioid cell morphology, ETT is known for its potential to present as an aggressive tumor. This variant often occurs in reproductive-aged women and can be associated with abnormal vaginal bleeding or a mass in the uterine cavity.

PSTT is another rare and distinctive form of GTN originating from the placental implantation site. Unlike more common trophoblastic tumors, PSTT tends to develop months or even years after a normal pregnancy, often following a term or molar gestation. This tumor is characterized by slow growth and can manifest with irregular vaginal bleeding.