Gestational trophoblastic disease

Gestational trophoblastic disease (GTD) results from the abnormal proliferation of trophoblastic tissue and encompasses a wide spectrum of diseases, including ¹⁴:

• tumor-like lesions
  • exaggerated placental site reaction
  • placental site nodule and plaque
• abnormal (non-molar) villous lesions
• molar pregnancies
  • partial hydatidiform mole
  • complete hydatidiform mole
  • invasive and metastatic hydatiform moles
• gestational trophoblastic neoplasms
  • epithelioid trophoblastic tumor
  • placental site trophoblastic tumor
  • gestational choriocarcinoma
  • mixed trophoblastic tumor

Epidemiology

Women older than 40 years and younger than 20 years may be at higher risk.

Clinical presentation

The presentation is variable:

• uterus larger than pregnancy age
• abnormally high β-hCG
• hyperemesis
• hypertension
• theca-lutein cysts

Pathology

A common characteristic of all gestational trophoblastic disease is an abnormal proliferation of trophoblast, but different components predominate in different tumors.

Classification

Molar pregnancies:

• partial hydatidiform mole (PHM)
  • 69XXX or 69XXY (paternal and maternal chromosomes)
  • may have a fetus or fetal components
  • β-hCG moderately elevated
  • no cellular atypia
• complete hydatidiform mole (CHM)
  • commonest (up to 80%) manifestation of GTD
  • 46XX or 46XY: paternal chromosomes only
  • no fetus
  • β-hCG markedly elevated
  • atypia of cells present
  • treatment involves
    • curettage +/- hysterectomy in older women ¹¹
    • follow-up urinary β-hCG for 6-12 months
  • may progress to
    • invasive mole: ≈15% 
    • choriocarcinoma: ≈5%
• invasive and metastatic hydatidiform moles
  • distorts uterine zonal structures
  • boundaries between a tumor and myometrium are irregular and indistinct ³
  • may also invade parametrial tissue and blood vessels ⁴

Gestational trophoblastic neoplasms (GTN)​:

• placental site trophoblastic tumor (PSTT)
  • rare form
  • produces small amounts of β-hCG
  • raise human placental lactogen (hPL) levels
• epithelioid trophoblastic tumor (ETT) ⁹
  • extremely rare form
• gestational choriocarcinoma
  • may look identical to hydatidiform mole
  • arises following known molar pregnancy (50%), miscarriage (30%), normal pregnancy (20%)
  • can appear to have less vascularity than an invasive mole
  • higher β-hCG levels even than a complete mole
  • solid component with the visualized invasion
  • tends to invade myometrium through venous plexuses
    • patients often can present with multiple metastases without an easily identified primary, as it can often be small in an otherwise normal placenta
  • metastases can occur in
    • lungs: ~80%
    • vagina: ~30%
    • pelvis: 20% 
    • liver and brain: ~10% ^12,13
• mixed trophoblastic tumor