What causes gestational trophoblastic neoplasia (GTN)?

From the Guidelines

Gestational trophoblastic neoplasia (GTN) is primarily caused by abnormal proliferation of trophoblastic tissue, which normally forms the placenta during pregnancy, as stated in the NCCN Guidelines for Gestational Trophoblastic Neoplasia 1. The most common cause of GTN is a hydatidiform mole (molar pregnancy), which occurs when there is abnormal fertilization of an egg.

• Complete moles typically have 46 chromosomes, all from the father,
• while partial moles usually have 69 chromosomes (triploidy). Other causes include persistent trophoblastic disease following a normal pregnancy, miscarriage, or ectopic pregnancy. Key risk factors include:
• maternal age (under 20 or over 40 years),
• previous molar pregnancy (increasing risk by 1-2%),
• and possibly nutritional deficiencies. The abnormal trophoblastic cells produce excessive human chorionic gonadotropin (hCG) and can invade the uterine wall or metastasize to other organs if left untreated. GTN encompasses several conditions including:
• invasive mole,
• choriocarcinoma,
• placental site trophoblastic tumor,
• and epithelioid trophoblastic tumor. Early detection through monitoring hCG levels after any pregnancy event is crucial for successful treatment, which typically involves chemotherapy with methotrexate or actinomycin-D for low-risk disease, or combination chemotherapy for high-risk disease, as outlined in the 2019 NCCN guidelines 1.

From the Research

Causes of Gestational Trophoblastic Neoplasia (GTN)

The exact causes of GTN are not explicitly stated in the provided studies. However, the studies suggest that GTN is a rare tumor that originates from pregnancy, including invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor 2, 3, 4, 5.

Risk Factors and Diagnosis

The diagnosis of GTN is made according to the International Federation of Gynecology and Obstetrics (FIGO) 2000 criteria, which include:

• Four or more plateaued human chorionic gonadotropin (hCG) concentrations over three weeks
• Rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more
• An elevated but falling hCG concentrations six or more months after molar evacuation (although this criterion is no longer used by many centers) 2 The studies also mention that GTN can be diagnosed with a pathological diagnosis of choriocarcinoma or placental site trophoblastic tumor/epithelioid trophoblastic tumor 2, 3, 4.

Types of GTN

The studies identify the following types of GTN:

• Invasive mole
• Choriocarcinoma
• Placental site trophoblastic tumor
• Epithelioid trophoblastic tumor 2, 3, 4, 5 These types of GTN can be treated with chemotherapy, with single-agent chemotherapy being effective for low-risk GTN and multi-agent chemotherapy being used for high-risk GTN 2, 3, 4, 5.

Treatment and Management

The treatment and management of GTN involve:

• Chemotherapy (single-agent or multi-agent)
• Surgery (in some cases)
• Radiation therapy (in some cases) 2, 3, 4, 5, 6 The studies suggest that the management of GTN has been heterogeneous, but the emergence of expert networks has helped to harmonize its management 5.