Gestational Trophoblastic Disease — Complete vs Partial Mole, hCG Follow-up, GTN and the FIGO Score

Gestational trophoblastic disease (GTD) is a group of tumours defined by abnormal proliferation of trophoblast, the cells that make hCG. StatPearls divides it into hydatidiform moles (HM), which contain villi, and trophoblastic neoplasms, which lack villi. The malignant forms are called gestational trophoblastic neoplasia (GTN).

Moles make up roughly 80% of all GTD and are benign; more than 80% of moles resolve after evacuation. The incidence is highest in South-East Asia and Japan (about 2 per 1,000 pregnancies). Risk factors are extremes of maternal age and a previous mole.

A complete mole forms when an empty (enucleated) egg is fertilised by two sperm, or by one haploid sperm that then duplicates. All chromosomes are therefore paternal; only the mitochondrial DNA is maternal. About 90% are 46,XX and 10% are 46,XY. A partial mole is usually triploid (69,XXX, 69,XXY or 69,XYY) from a haploid ovum fertilised by two sperm, so both maternal and paternal DNA are expressed.

p57 is a maternally expressed (paternally imprinted) gene. Because a complete mole has no maternal genome, p57 staining is absent; this helps separate a complete mole from a partial mole and from a hydropic abortion. The main histological mimic of a mole is a hydropic abortion.

Most moles are diagnosed in the first trimester. The commonest symptom is vaginal bleeding, which may be dark-brown or 'prune-juice' from old blood, and some women pass grape-like vesicles. The high hCG causes hyperemesis, and early-onset hypertension.

• Hyperthyroidism (tachycardia, tremor) after about 14–16 weeks, from the thyrotropic effect of very high hCG.
• Pre-eclampsia before 20 weeks should make you suspect a complete mole.
• Theca lutein cysts — bilateral enlarged ovaries that regress as hCG falls; warn about torsion and rupture.
• Uterus larger than dates in a complete mole; in more than 50% there is a size–date discrepancy.
• Respiratory distress from trophoblastic embolisation, pulmonary oedema or thyroid storm is rare but dangerous.

Ultrasound shows the classic 'snowstorm' / 'bunch of grapes' pattern of a complete mole. A partial mole is often missed on scan and presents as an incomplete or missed abortion; the diagnosis is made on histology of the curettage specimen. Fetal heart tones may be heard in a partial mole because fetal tissue is present.

Stabilise first: treat pre-eclampsia (labetalol or hydralazine; magnesium sulfate for eclampsia), correct anaemia, and give beta-blockers if hyperthyroid, as anaesthesia can precipitate thyroid storm. Give anti-D immunoglobulin to Rh(D)-negative women. Evacuate as soon as the patient is medically stable.

• Suction evacuation (dilatation and ultrasound-guided aspiration) is the method of choice, with blood, ICU and anaesthesia support for a markedly enlarged uterus.
• Hysterectomy is an option for women over about 40 or who have completed their family; it does not abolish the risk of metastatic disease, so hCG follow-up is still required.
• Prophylactic chemotherapy is discouraged by a recent Cochrane review.
• A second evacuation may be considered for persistently raised hCG when perforation or haemorrhage risk is low.
• Send tissue for histology — it separates complete from partial mole.

Every woman with a mole needs hCG surveillance. StatPearls states that serum hCG is checked weekly after evacuation until undetectable. Protocols differ by country; the principle is the same. Thereafter monitoring continues at monthly intervals: in the UK scheme, women whose hCG is negative within 56 days of evacuation are low risk and are checked monthly for 6 months from evacuation.

• In reviews of European protocols, a complete mole is followed monthly for 6 months after the first normal value; in a partial mole, two consecutive normal weekly values are needed and follow-up can stop one month later if hCG stays negative.
• Advise reliable contraception during follow-up; oral contraceptives are a safe option. A new pregnancy would make hCG uninterpretable.
• After any later pregnancy, check hCG at 6 and 10 weeks to exclude reactivation.

GTN is suspected when hCG plateaus (less than 10% variation over 3–4 measurements), rises across three consecutive assays, or remains positive for more than 6 months. Histological evidence of choriocarcinoma, or metastases, also establishes GTN. Workup includes pelvic ultrasound and chest imaging, with CT or MRI to look for extra-uterine disease.

A total of 0–6 is low risk and 7 or more is high risk. An ultra-high-risk category (score of 13 or more, or extensive metastasis) was added in the 2015 FIGO update.

Non-metastatic GTN can be cured with initial single-agent therapy. With brain metastases the team may add radiotherapy, and a lumbar puncture to assess the CSF-to-serum hCG ratio is used when brain imaging is negative. Hysterectomy remains an option for chemoresistance, severe disease or when fertility is not desired.

An invasive mole is a mole whose trophoblast and villi penetrate the myometrium; it follows a molar pregnancy. Choriocarcinoma shows diffuse, penetrative growth with biphasic to triphasic sheets of mononuclear tumour cells capped by multinucleate syncytiotrophoblast, lymphovascular tumour thrombi and no villi. It can follow a mole, abortion or term pregnancy.

• Most high-risk GTN presents with metastases months or years after the causative pregnancy.
• Lung metastases cause dyspnoea, haemoptysis or pleuritic pain; brain metastases cause headache, seizures or hemiparesis.
• Menstrual irregularity is not always present, so the diagnosis can be missed. hCG in any woman of reproductive age with unexplained metastases should raise suspicion.
• In men, choriocarcinoma usually arises within a mixed germ cell tumour.