Gestational Trophoblastic Disease

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

Indications for Ordering

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.
Test Name and Number	Comments
Alpha Subunit of Pituitary Glycoprotein Hormones 0092526 Method: Immunoradiometric Assay
Beta-hCG, Serum Quantitative 0070025 Method: Chemiluminescent Immunoassay
Beta-hCG, Serum Qualitative 0020063 Method: Immunoassay
Beta-hCG, Urine Qualitative 0020229 Method: Immunoassay