Gestational Trophoblastic Disease

Epidemiology

• Incidence
  • Hydatidiform mole
    • 1/600 spontaneous abortions
    • ~1/1,000 pregnancies; regional differences observed
  • GTN
    • 1/20,000-40,000 pregnancies
      • 50% post-term pregnancies
      • 25% postmolar pregnancies
      • 25% post-other gestational events
    • Choriocarcinoma risk – 1/50,000 pregnancies
• Age – childbearing years
• Sex – exclusively female
• Ethnicity – increased incidence in Latin America, Middle East, and Southeast Asia
  • U.S. – African Americans have the highest incidence of choriocarcinoma and the lowest survival rate

Risk Factors

• Previous molar pregnancy
  • High risk for GTN following complete hydatidiform molar pregnancy
  • Increased risk for GTN following partial hydatidiform molar pregnancy
• Asian or American Indian ancestry, or (for GTN only) African ancestry
• Older maternal age – women >40 years
• Familial disease – rare, more common in recurrent CHM
  • NLRP7 and (rarely) KHDC3L gene mutations implicated (Wang, 2009)

Pathophysiology

• All GTD is derived from trophoblastic cells that form the placenta
• Hydatidiform mole – considered benign
  • Placental villi become edematous and form small grapelike structures
  • Classification
    • PHM
      • Focal trophoblastic proliferation with mixture of normal villi and edematous villi
      • Embryo, cord, and amniotic structures are present but abnormal
      • Triploid genome (69,XXY; 69,XYY; 69,XXX) due to additional paternal haploid chromosome contribution
      • Presence of maternally expressed gene products
        • PHM – 0.5% risk
    • CHM
      • Hydropic degeneration of all villi
      • Absent embryo, cord, or amniotic structures
      • Diploid genome
      • Absence of maternally expressed gene products
        • CHM – 15% risk
• GTN – neoplastic and potentially malignant
  • Invasive, persistent, or metastatic mole – mole with invasion into the myometrium; rare "metastasis" to extrauterine sites (lung, vagina)
    • Swollen villi; hyperplastic trophoblast
    • May coexist with a normal pregnancy (rare)
  • Gestational choriocarcinoma
    • Neoplastic syncytiotrophoblast and cytotrophoblast elements without chorionic villi; hemorrhage, necrosis
    • Usually metastasizes early
  • Placental site trophoblastic tumor (PSTT)
    • Absence of villi, proliferation of intermediate trophoblast cells in the myometrium
    • Usually limited to uterus; secretes low levels of beta-human chorionic gonadotrophin (βhCG)
    • Rare
  • Epithelioid trophoblastic tumor (ETT)
    • Chorionic-type extravillous trophoblastic cells in the chorion laeve
    • Variant of PSTT – clinical behavior similar to PSTT
    • Rare

Clinical Presentation

• PHM – vaginal bleeding in the absence of other symptoms is most common presentation
• CHM
  • Most frequently diagnosed in first half of pregnancy
  • Most common symptom is abnormal vaginal bleeding – usually 6-16 weeks gestation
  • Other symptoms include the following
    • Uterine enlargement not commensurate with stage of pregnancy
    • Absent fetal heart tones
    • Hyperemesis gravidarum
    • Pregnancy-induced hypertension
    • Cystic enlargement of the ovaries
    • Hyperthyroidism
• GTN
  • Most common symptom is abnormal vaginal bleeding during or after a pregnancy
  • Commonly presents with metastatic symptoms
    • Pulmonary metastatic disease is most common – hemoptysis, shortness of breath, cough, chest pain
    • Other sites – vagina, central nervous system (CNS), liver
  • Most ETTs present many years after full-term delivery; similar pattern for PSTTs
    • Most common sign and symptom is amenorrhea or abnormal vaginal bleeding