Gestational trophoblastic disease is a spectrum of diseases that take origin from the placenta.

Epidemiology

• Incidence
  • Hydatidiform mole
    • 1/600 therapeutic abortions
    • 1/1,500 pregnancies
  • Gestational trophoblastic neoplasm (GTN)
    • Overall risk - 1/20,000-40,000 pregnancies
      • 50% post term pregnancies
      • 25% post molar pregnancies
      • 25% post other gestational events
    • Choriocarcinoma risk - 1/50,000
• Age - childbearing years
• Sex - exclusively female
• Ethnicity - increased risk in Latin America, Middle East and Southeast Asia

Risk Factors

• Previous molar pregnancy (risk in next pregnancy is 1%)
  • 2,000 times  increased risk for GTN following partial or complete hydatidiform molar pregnancies
• Asian ancestry (7-10 times higher risk)
• Older maternal age (women >40 years of age have 5-10 times higher risk of complete molar pregnancy)
• Familial disease - rare; NALP7 mutation

Pathophysiology

• Hydatidiform mole
  • Placental villi become edematous and form small grape-like structures
  • Classification
    • Partial hydatidiform mole (PHM) - focal trophoblastic proliferation with mixture of normal villi and edematous villi; embryo, cord and amniotic structures are present; triploid genome
    • Complete hydatidiform mole (CHM) - hydropic degeneration of all villi; no embryo, cord or amniotic structures present; diploid genome 80% of the time
    • Invasive mole - mole with invasion into the myometrium; rarely metastasizes
    • May coexist with a normal pregnancy
    • May be a precursor to GTN
• Gestational trophoblastic neoplasm
  • Gestational choriocarcinoma - neoplastic syncytiotrophoblast and cytotrophoblast elements without chorionic villi; usually metastasize early
  • Epithelioid trophoblastic tumor - chorionic-type extravillous trophoblastic cells in the chorion laeve; rare
  • Placental site trophoblastic tumor - absence of villi, proliferation of intermediate trophoblast cells in the myometrium; usually limited to uterus; rare

Clinical Presentation

• Hydatidiform mole
  • Most frequently diagnosed in the first half of pregnancy
  • Most common symptom is abnormal vaginal bleeding
  • Other symptoms include uterine enlargement not commensurate with dates, absent fetal heart tones, hyperemesis, pregnancy-induced hypertension, hyperthyroidism (CHM)
• Gestational trophoblastic neoplasm
  • May have subtle symptoms
  • Most common symptom is abnormal vaginal bleeding during or after a pregnancy
  • Common to present with metastatic symptoms
    • Pulmonary metastatic disease is most common

Diagnosis

• Hydatidiform mole
  • Indications for testing -  suspicion of mole based on clinical presentation
  • Laboratory testing
    • Beta-hCG - elevated above expected for gestational age for PHM; marked elevation (>100,000) in 40-50% for CHM
    • DNA content/cell cycle analysis - used to distinguish partial from complete moles
  • Imaging studies
    • Pelvic ultrasound - no fetal heart tones, mixed echogenic pattern replacing placenta
• Gestational trophoblastic neoplasm
  • Indications for testing - suspicion of gestational neoplasia
  • Laboratory testing
    • Beta-hCG - markedly elevated or continued rise after pregnancy
  • Imaging studies
    • Pelvic ultrasound
    • Chest X-ray
    • MRI/CT to rule out disseminated metastatic disease

Disease Monitoring

• Beta-hCG - monitor in a sequential fashion
  • Hydatidiform mole - monitored for return to normal values for up to one year (monthly once normalized); pregnancy discouraged during this period  
  • Gestational trophoblastic neoplasm - hCG during chemotherapy to determine remission; then 2 week intervals for first 3 months, and then monthly thereafter for 1 year; hCG yearly thereafter

Differential Diagnosis

• Hydatidiform mole -  multiple gestation pregnancy
• Gestational trophoblastic neoplasm -  metastatic cancer from another site