Obstetrics and Gynaecology chapters
Gestational trophoblastic disease: molar pregnancy and choriocarcinoma
Gestational trophoblastic disease covers complete and partial moles, invasive mole and choriocarcinoma. This chapter explains their genetics, how a mole presents, the snowstorm scan, suction evacuation, hCG follow-up and when chemotherapy is needed.
- Gestational trophoblastic disease (GTD) is abnormal growth of trophoblast: complete and partial hydatidiform mole, invasive mole and choriocarcinoma.
- A mole classically gives bleeding, a uterus larger than dates, severe vomiting and a very high hCG, with a snowstorm (cluster of vesicles) on ultrasound.
- Treat by suction evacuation, then serial hCG until normal; a rising or static hCG means persistent trophoblastic neoplasia, which is highly chemosensitive (methotrexate).
On this page
Overview
Gestational trophoblastic disease (GTD) is a group of disorders in which the trophoblast, the part of the conception that normally forms the placenta, grows abnormally. The group includes:
- Complete hydatidiform mole
- Partial hydatidiform mole
- Invasive mole
- Choriocarcinoma
Moles are benign but can persist or turn malignant. Every trophoblastic lesion makes hCG, so hCG is both the diagnostic test and the tumour marker for follow-up. The disease matters in Pakistan because it is commoner in Asian women, and because a missed mole can present months later as metastatic choriocarcinoma.
Definitions and classification
| Term | Meaning |
|---|---|
| Hydatidiform mole | Abnormal conception with swollen, fluid-filled (hydropic) villi and trophoblast overgrowth |
| Invasive mole | Molar villi grow into the myometrium; may perforate the uterus |
| Choriocarcinoma | Malignant tumour of trophoblast with no villi; spreads early by blood |
| Persistent trophoblastic disease (gestational trophoblastic neoplasia) | hCG fails to fall to normal after evacuation; treated with chemotherapy |
A rare further type, the placental site trophoblastic tumour, arises from the implantation site and makes relatively little hCG.
Risk factors
- Previous molar pregnancy (the strongest factor).
- Extremes of maternal age: teenagers and older women.
- Asian origin.
Pathology and genetics
The two moles differ in where their chromosomes come from. This is a favourite MCQ.
| Feature | Complete mole | Partial mole |
|---|---|---|
| Origin | An empty ovum (no maternal DNA) fertilised by one sperm that duplicates, or by two sperm | A normal ovum fertilised by two sperm (or by a single sperm whose chromosomes double) |
| Karyotype | 46,XX (usually), all paternal: androgenesis | Triploid, 69 chromosomes: two paternal sets and one maternal |
| Fetal tissue | Absent | Present (fetal parts or a nonviable fetus) |
| Villi | Most villi swollen | Some swollen, some normal |
| Trophoblast growth | Diffuse, all round the villi | Focal |
| Risk of choriocarcinoma | About 2-3% | Minimal |
Complete = Completely father's (46,XX), no baby. Partial = Plus one extra set (69), Part of a baby.
Grossly, the villi look like a bunch of grapes.
Clinical features
The classic picture is a woman in the first half of pregnancy with:
- Vaginal bleeding, sometimes with passage of grape-like vesicles.
- Uterus larger than expected for the dates (in a partial mole it may be normal or small).
- Severe nausea and vomiting (hyperemesis), because of very high hCG.
- No fetal heart in a complete mole.
- Bilateral theca-lutein ovarian cysts: multiple cysts driven by gonadotrophin stimulation; they settle once hCG falls.
- Hyperthyroidism: hCG has weak thyroid-stimulating activity, so very high levels can make the thyroid overactive.
- Pre-eclampsia before 20 weeks: pre-eclampsia can occur in a mole even without a fetus, which shows that trophoblast drives the disease.
Today most moles are found early on a routine scan, before these features appear. Many are discovered only when tissue from a "miscarriage" is sent for histology.
Pre-eclampsia before 20 weeks should make you think of a molar pregnancy.
Hyperemesis, a big uterus and very high hCG also occur with multiple pregnancy. The scan separates them.
Investigations
| Test | Finding |
|---|---|
| Serum hCG | Much higher than expected for gestation |
| Ultrasound | Intrauterine mass with many small cystic spaces: "snowstorm" or "cluster of grapes"; no fetal heart (complete mole); theca-lutein cysts in the ovaries |
| Histology of evacuated tissue | Confirms the diagnosis and the type of mole |
| Baseline tests | Blood group, FBC, thyroid function if hyperthyroid features, chest X-ray if hCG stays high |
Management of a molar pregnancy
- Uterine evacuation by suction curettage, ideally by an experienced operator.
- Do not use misoprostol (or other agents) to ripen the cervix or empty the uterus. Medical evacuation can push trophoblast into the circulation and leaves tissue behind.
- Send all tissue for histology.
- Anti-D for a rhesus-negative woman: Ten Teachers lists molar pregnancy among first-trimester events needing anti-D (250 IU in the first trimester).
- Registration with a specialist follow-up centre. In the UK this is national; in Pakistan, follow-up is usually arranged by the treating gynaecology unit, so check local arrangements.
- Serial hCG until it is undetectable, then continued follow-up as the centre advises.
- Avoid oestrogens (for example the combined pill) during follow-up, as Ten Teachers advises, and avoid a new pregnancy until follow-up is complete, because a new pregnancy would raise hCG and hide a relapse.
The whole follow-up depends on hCG. A plateau or rise after evacuation means persistent trophoblastic neoplasia.
A woman who has had a mole should have hCG checked after every future pregnancy, since choriocarcinoma can follow any pregnancy.
Gestational trophoblastic neoplasia
This includes invasive mole and choriocarcinoma (and the rare placental site tumour).
Choriocarcinoma
- Malignant trophoblast with no villi.
- The preceding pregnancy is:
| Preceding event | Share of cases |
|---|---|
| Hydatidiform mole | About 50% |
| Miscarriage or ectopic pregnancy | About 20% |
| Normal term pregnancy | About 20-30% |
- Spreads early through the blood, most often to the lungs ("cannonball" shadows on chest X-ray, haemoptysis), and also to the vagina, brain and liver.
- Serum hCG is very high and is the marker for treatment.
- It may present as secondary postpartum haemorrhage or irregular bleeding months after a pregnancy.
- It is more common in Asia and Africa.
Treatment
- Gestational choriocarcinoma is very chemosensitive: it is one of the few cancers that single drugs can cure.
- Methotrexate (an antifolate that blocks DNA synthesis in dividing trophoblast) is the standard drug for lower-risk disease.
- Higher-risk disease needs combination chemotherapy, which includes dactinomycin (actinomycin D).
- Risk group is decided at a specialist centre using a prognostic score (based on factors such as hCG level, interval since the pregnancy and sites of spread).
- Cure rates are high, even with lung metastases.
Gestational choriocarcinoma responds well to chemotherapy; non-gestational (germ cell) choriocarcinoma of the ovary does not.
Complications
- Haemorrhage during evacuation, uterine perforation.
- Persistent trophoblastic neoplasia needing chemotherapy.
- Thyroid storm (rare) with very high hCG.
- Torsion or rupture of theca-lutein cysts.
- Recurrence in a later pregnancy.
Expect: the karyotype of complete (46,XX, all paternal, no fetus) and partial (triploid 69, fetal parts) moles; the classic presentation with bleeding, a uterus larger than dates, hyperemesis and very high hCG; the snowstorm scan; theca-lutein cysts and hyperthyroidism as hCG effects; suction evacuation as treatment and avoidance of medical evacuation; serial hCG follow-up and what a plateau means; the 2-3% choriocarcinoma risk after a complete mole; choriocarcinoma following a mole in half of cases, lung spread and methotrexate.
Quick revision
- GTD: complete mole, partial mole, invasive mole, choriocarcinoma.
- Complete: 46,XX androgenetic, no fetus, choriocarcinoma risk 2-3%.
- Partial: 69 chromosomes, fetal parts, minimal malignant risk.
- Signs: bleeding, large-for-dates uterus, hyperemesis, very high hCG, early pre-eclampsia.
- Scan: snowstorm; ovaries: bilateral theca-lutein cysts.
- Treatment: suction evacuation (no misoprostol), histology, anti-D if Rh negative.
- Follow-up: serial hCG to undetectable; no oestrogen or new pregnancy during follow-up.
- Choriocarcinoma: half follow a mole; lung spread; methotrexate, combination for high risk.
Written by The House Job from standard references (Gynaecology by Ten Teachers; Obstetrics by Ten Teachers; Basic and Clinical Pharmacology by Katzung; Davidson's Principles and Practice of Medicine).
FAQ
Why does a complete mole have no fetus?
All its chromosomes come from the father because the egg had no nucleus, and this purely paternal genome drives placental tissue without forming an embryo.
Why are theca-lutein cysts seen with a mole?
The very high hCG overstimulates both ovaries, producing multiple cysts that shrink once the mole is removed and hCG falls.
Why is medical evacuation avoided for a mole?
Drugs that make the uterus contract can push trophoblast into the bloodstream and often leave tissue behind, so suction curettage is preferred.
What does a static hCG after evacuation mean?
It means trophoblast is still growing (persistent trophoblastic neoplasia), which needs specialist assessment and usually methotrexate.