Gestational Trophoblastic Disease
Overview
Gestational trophoblastic disease (GTD) is a spectrum of disorders arising from abnormal proliferation of trophoblastic tissue, ranging from the premalignant conditions of complete and partial hydatidiform mole through to the malignant forms — invasive mole, choriocarcinoma, and the very rare placental site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). Where there is biochemical or clinical evidence of persistent disease after a molar pregnancy — most commonly a plateaued or rising serum hCG — the condition is termed gestational trophoblastic neoplasia (GTN).
Classification
- Complete hydatidiform mole (CM): diploid, purely androgenetic in origin (typically 46,XX, occasionally 46,XY), arising from fertilisation of an empty ovum. No fetal tissue is present. Villi show diffuse hydropic swelling and trophoblastic hyperplasia.
- Partial hydatidiform mole (PM): triploid, diandric-monogynic in origin (typically 69,XXY), arising from dispermic fertilisation of a normal ovum. Fetal or fetal-derived tissue is usually present. Villous change is focal rather than diffuse.
- Invasive mole: molar tissue that invades the myometrium, usually diagnosed clinically/biochemically rather than histologically (histology requires hysterectomy specimen).
- Choriocarcinoma: a highly malignant tumour of trophoblastic origin that can follow a molar pregnancy, miscarriage, ectopic pregnancy, or term delivery, with a propensity for early haematogenous spread (lung, liver, brain).
- PSTT/ETT: rare tumours of intermediate trophoblast that secrete relatively little hCG for their bulk and are relatively chemoresistant; hysterectomy is often required.
Complete and partial mole together are the most common presentations; approximately 15% of complete moles and a much smaller proportion of partial moles (roughly 0.5–1%) progress to GTN requiring treatment.
Diagnosis
- Most molar pregnancies now present incidentally on first-trimester ultrasound rather than with classical heavy bleeding or hyperemesis, reflecting earlier scanning.
- Ultrasound: complete mole classically shows a heterogeneous, "snowstorm"-like intrauterine mass with multiple small cystic spaces and no identifiable fetus, sometimes with bilateral theca lutein cysts; partial mole shows a more subtle picture, often with a gestational sac/fetal tissue alongside focal placental cystic change. Ultrasound alone cannot reliably exclude or diagnose molar pregnancy, so histological examination of retained products of conception is required.
- Serum hCG: typically markedly elevated in complete mole (often disproportionate to gestational age) but is not diagnostic on its own — histology confirms the diagnosis of complete mole, partial mole, and PSTT/ETT. Diagnosis of GTN, by contrast, does not require histological confirmation and is made on hCG criteria (a plateau or rise in hCG after evacuation, or persistently elevated hCG at a defined interval, or histological confirmation of choriocarcinoma).
- All products of conception from miscarriage or termination should be sent for histological examination when no fetal parts have been identified sonographically, precisely to avoid missing a molar pregnancy.
Management
- Suction curettage under ultrasound guidance is the evacuation method of choice for both complete and partial moles where the uterine size allows; medical evacuation (e.g. prostaglandins) is generally avoided where possible because of a theoretically increased risk of embolisation of trophoblastic tissue and need for chemotherapy, but may be necessary in some partial moles with a large fetus.
- Oxytocin infusion should be withheld until evacuation is underway/completed, to reduce the risk of embolisation.
- Anti-D prophylaxis should be given to Rhesus-negative women after evacuation of a partial mole (fetal red cells may be present); it is not required for a confirmed complete mole (no fetal tissue), though in practice anti-D is often given if evacuation occurs before mole type is confirmed.
- Every woman with confirmed GTD must be registered with one of the UK's regional trophoblastic screening centres — Charing Cross Hospital (London), Weston Park Hospital (Sheffield), or Ninewells Hospital (Dundee, covering Scotland) — which coordinate national hCG surveillance under the RCOG-established registration scheme.
- Chemotherapy is reserved for GTN, risk-stratified using the FIGO/WHO prognostic scoring system (factors include age, antecedent pregnancy type, interval since index pregnancy, pre-treatment hCG, tumour size, site and number of metastases, and prior failed chemotherapy). Low-risk disease (score ≤6) is typically treated with single-agent methotrexate (with folinic acid rescue); high-risk disease (score ≥7) requires multi-agent chemotherapy (commonly EMA/CO). Treatment and follow-up of GTN and choriocarcinoma is centralised at the specialist screening centres.
Follow-up
- After evacuation, hCG is monitored regularly (typically every 1–2 weeks initially) until normal, then monthly.
- Duration of follow-up depends on how quickly hCG normalises after evacuation:
- If hCG returns to normal within 56 days of the pregnancy event, follow-up continues for 6 months from the date of evacuation.
- If hCG takes longer than 56 days to normalise, follow-up continues for 6 months from the date hCG first becomes normal.
- This 56-day rule stratifies risk: women whose hCG normalises quickly have a substantially lower subsequent risk of GTN than those who take longer, allowing shorter, less intensive surveillance in the low-risk group.
- Contraception during hCG follow-up: women should avoid pregnancy for the duration of hCG surveillance, because a new pregnancy makes it impossible to interpret hCG trends and could mask relapse. Barrier methods or the combined/progestogen-only pill are appropriate during surveillance. An intrauterine device (IUCD) should not be inserted until hCG has returned to normal, because of the risk of uterine perforation into abnormal trophoblastic tissue and because it can cause bleeding that confuses the clinical picture.
- Once follow-up is complete with normal hCG, there is no need for long-term contraceptive restriction; a future pregnancy carries a small (roughly 1 in 80, i.e. ~1%) risk of a further molar pregnancy, so an early dating ultrasound is recommended in the next pregnancy, and the products of any subsequent pregnancy loss should again be sent for histology.
High-Yield Exam Points
- Complete mole = diploid, androgenetic (46,XX), no fetal tissue, "snowstorm" ultrasound appearance; partial mole = triploid, diandric (69,XXY), fetal tissue present.
- Diagnosis of complete/partial mole and PSTT/ETT requires histology; diagnosis of GTN is made on hCG criteria alone, no histology needed.
- Suction curettage is first-line evacuation; oxytocin is withheld until evacuation is underway to reduce embolisation risk.
- Give anti-D to Rhesus-negative women after evacuation of a partial mole.
- All GTD is registered with one of three UK centres: Charing Cross (London), Weston Park (Sheffield), Ninewells (Dundee).
- Follow-up: 6 months from evacuation if hCG normalises within 56 days; 6 months from normalisation if it takes longer than 56 days.
- Avoid pregnancy during hCG surveillance; avoid IUCD insertion until hCG has normalised — barrier or pill contraception is preferred during follow-up.
- Around 15% of complete moles and a much smaller proportion (~1%) of partial moles progress to GTN requiring chemotherapy.
- Low-risk GTN (FIGO/WHO score ≤6): single-agent methotrexate with folinic acid rescue. High-risk GTN (score ≥7): multi-agent chemotherapy (e.g. EMA/CO).
- Risk of a further molar pregnancy in a future pregnancy is low (~1%) — recommend early ultrasound next pregnancy.
Source: RCOG Green-top Guideline No. 38 (September 2020 (4th edition, published in *BJOG*; RCOG scheduled reassessment 2 years post-publication, full update at 3 years))
Read the original on rcog.org.uk
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