Trophoblastic disease


  • Abnormal proliferation of gestational trophoblast tissue can result in a spectrum of disorders from partial hydatidiform moles to malignant choriocarcinoma
  • they are rare (1-3 in 1000 pregnancies); around 10% transform into malignant forms
  • More common in women >45 or <16
  • Can be classified based on malignancy and cytogenetic features
    • Benign
      • Partial Hydatiform mole
        • Almost always triploid, usually as a result of two sperms fertilising the egg
      • Complete Hydatiform mole
        • Almost always diploid, usually as a result of endoreduplication (duplication without mitosis) after fertilisation
  • Both hydatiform moles show degrees of villous architecture abnormalities (usually trophoblastic hyperplasia)
    • Malignant
      • Invasive hydatiform mole
      • Choriocarcinoma
      • Placental site trophoblastic tumour
      • Epithelioid trophoblastic tumour


  • Most women present with vaginal bleeding in early pregnancy or suspected miscarriage
    • Many are also diagnosed at USS
      • hydropic change/snowstorm appearance (often late signs- many women miscarry by 10 weeks gestation and the diagnosis is made at histological examination of the products of conception (even then, diagnosis can be missed)
  • Other suspicious symptoms/signs are
    • Persistent vaginal bleeding after a miscarriage/pregnancy
    • Rarely, women can present with features of metastatic disease
      • Most common area of metastasis is the lungs- so symptoms of shortness of breath, haemoptysis and chest pain
      • NB If a young woman of child-bearing age present with metastatic disease of unknown origin, consider trophoblastic disease


  • Plasma and urinary (β-)hCG (usually abnormally high
  • Histology
    • Provides definitive diagnosis
    • NB Because this is how the majority of diagnoses are made, ALL products of conception from miscarriages should be sent for histology
  • USS


  • All POC from miscarriages should be sent for histology to look for gestational trophoblastic disease
  • Suspected cases are usually managed initially with suction uterine evacuation (or dilatation and curettage)
    • usually without prostanoids (increase risk of uterine contraction which can increase likelihood of spread)
    • In benign disease, vaginal bleeding stops and serum hCG returns to normal
    • In malignant disease, there may be persistent vaginal bleeding and hCG usually either remains high or rises further
      • Women with hCG concentrations of >20000IU/l one month after evacuation should be offered chemotherapy (alternatively if there has been a rise with two consecutive measurements or if the level has failed to fall after three measurements; lastly, if hCG remains high, despite falling, after six months)
      • Severe bleeding is also an indication for chemotherapy
      • If there is evidence of malignant disease on histology, also offer chemotherapy
      • If there is any evidence of metastases in the brain, liver, GI tract or chest
  • Choice of chemotherapy depends on the severity of disease, which can be determined using WHO risk assessment


    • Methotrexate and Folinic acid is given in low-intermediate risk disease
      • Usually methotrexate given 4 doses- IM (50mg)- one every 48 hours, then the cycle is repeated every 2 weeks until hCG is <5IU/l for 6 weeks
    • Severe disease is treated with alternating etoposide/dactinomycin/methotrexate and vincristine/cyclophosphamide

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