Gestational trophoblastic disease
For patient information on Hydatiform mole, click here
For patient information on Choriocarcinoma, click here
Synonyms and keywords: GTD, pregnancy-related tumors, trophoblastic diseases

# Overview
Gestational trophoblastic disease (GTD) includes a spectrum of disease states affecting pregnant individuals and range from benign conditions such as complete and partial molar pregnancy, exaggerated placental site tumor (EPS), and placental-site nodule (PSN) to malignant disorders (gestational trophoblastic neoplasia) such as invasive mole, choriocarcinoma (CC), placenta-site trophoblastic tumor (PSTT), and epitheloid trophoblastic tumors (ETT). Hydatidiform moles are a benign entities which may be either complete or partial. These benign moles may occasionally transform into invasive moles, which are malignant and may even progress to choriocarcinoma. Gestational trophoblasts may invade uterine tissue. GTD may simulate pregnancy due to increased uterine size, however they contain abnormal fetal tissue and typically the uterus is inappropriately large for date. This tissue may grow at the same rate as a normal pregnancy, and produces beta human chorionic gonadotropin (beta-hCG), a hormone produced by the placenta, which is measured to monitor fetal well-being after implantation. While GTD overwhelmingly affects women of child-bearing age, it may rarely occur in postmenopausal women.

# Classification
Gestational trophoblastic disease (GTD) may be classified as follows:
- Hydatidiform mole (HM).
- Complete HM
- Partial HM
- Gestational trophoblastic neoplasia:
- Invasive mole
- Choriocarcinoma
- Placental-site trophoblastic tumor (PSTT); (very rare)
- Epithelioid trophoblastic tumor (ETT); (extremely rare)

# Epidemiology
The reported incidence of GTD varies widely worldwide, from a low of 23 per 100,000 pregnancies (Paraguay) to a high of 1,299 per 100,000 pregnancies (Indonesia). However, at least part of this variability is caused by differences in diagnostic criteria and reporting. The reported incidence in the United States is about 110 to 120 per 100,000 pregnancies. The prevalence rates of both hydatidiform mole and choriocarcinoma have declined over the past three decades in all groups, which may be due to better awareness of the condition leading to risk factor avoidance, dietary improvement and decreased overall birth rate.

## Hydatidiform Mole
- The worldwide prevalence of molar pregnancy varies according to geographic region, ranging from 1200 per 100,000 pregnancies in Indonesia, India, and Turkey to 100-200 per 100,000 pregnancies in Japan and China and 50 to 100 per 100,000 pregnancies in North America and Europe.

## Choriocarcinoma
- The reported incidence of choriocarcinoma, the most aggressive form of GTD, in the United States is about 2 to 7 per 100,000 pregnancies. The U.S. age-standardized (1960 World Population Standard) incidence rate of choriocarcinoma is about 0.18 per 100,000 women between the ages of 15 years and 49 years.
- The reported prevalence of choriocarcinoma varies widely according to the geographic region, and ranges from a low of 2 per 100,000 pregnancies in the United States to a high of 202 per 100,000 pregnancies in China.

# Risk Factors
Risk factors for gestational trophoblastic disease include the following:
- Maternal age (younger than 20 and greater than 35 years of age- bimodal distribution, relative risk 1.1 to 11)
- History of hydatidiform mole (including positive family history- associated with a 1 % risk in subsequent pregnancies, 25 % with history of more than one prior hydatidiform mole)
- Low levels of carotene and vitamin A
- Blood groups A or AB
- Prior spontaneous abortions
- Multigravida women

# Clinical Features
Gestational trophoblastic disease (GTD) may present with the following clinical features:
- Vaginal bleeding
- Rapidly enlarging uterus
- Elevated human chorionic gonadotropin (hCG) levels
- Pelvic pain or sensation of pressure
- Anemia
- Hyperemesis gravidarum
- Hyperthyroidism (secondary to the homology between the beta-subunits of hCG and thyroid-stimulating hormone (TSH), which causes hCG to have weak TSH-like activity)
- Preeclampsia early in pregnancy
- Neurological symptoms (in cases of brain metastasis from choriocarcinoma)
- Anxiety
- Weight loss
- Insomnia
- Abdominal swelling
The following table outlines the variation in clinical presentations of molar pregnancy (complete, partial and invasive), choriocarcinoma, placental-site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT):

# Differential Diagnosis
Gestational trophoblastic disease must be differentiated from other causes of hyperthyroidism such as Grave's disease and toxic nodular goiter. The following table differentiates these causes of hyperthyroidism:

# Prognostic Factors and Survivorship
The prognosis for cure of patients with GTDs is good even when the disease has spread to distant organs, especially when only the lungs are involved. Therefore, the traditional TNM staging system has limited prognostic value. The probability of cure depends on the following:
- Histologic type (invasive mole or choriocarcinoma).
- Extent of spread of the disease/largest tumor size.
- Level of serum beta-hCG.
- Duration of disease from the initial pregnancy event to start of treatment.
- Number and specific sites of metastases.
- Nature of antecedent pregnancy.
- Extent of prior treatment.
Selection of treatment depends on these factors plus the patients desire for future pregnancies. The beta-hCG is a sensitive marker to indicate the presence or absence of disease before, during, and after treatment. Given the extremely good therapeutic outcomes of most of these tumors, an important goal is to distinguish patients who need less-intensive therapies from those who require more-intensive regimens to achieve a cure.