Gestational Trophoblastic Disease

Gestational trophoblastic disease (GTD) comprises a group of rare tumors originating from cells that would normally develop into the placenta during pregnancy. The spectrum of disease includes hydatidiform mole (complete or partial), invasive mole, gestational choriocarcinoma, and placental site trophoblastic tumor. GTD can be either benign or malignant.

Epidemiology

• Incidence
  • Hydatidiform mole
    • 1/600 spontaneous abortions
    • 1/1,000 pregnancies; regional differences observed
  • Gestational trophoblastic neoplasm (GTN)
    • 1/20,000-40,000 pregnancies
      • 50% post-term pregnancies
      • 25% post-molar 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 partial or complete hydatidiform molar pregnancies
• Asian, American Indian, African (GTN only) ancestry
• Older maternal age – women >40
• Familial disease – rare
  • 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 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 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
    • Complete hydatidiform mole (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 hCG
    • 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, CNS, hepatic
  • Most ETTs present many years after full-term delivery; similar pattern for PSTT
    • Most common sign and symptom is amenorrhea or abnormal vaginal bleeding