Gestational Trophoblastic Disease
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Direct answer
A uterus large for dates with first-trimester bleeding, passage of grape-like vesicles and an hCG far exceeding the gestational age is the classic presentation of hydatidiform mole — the commonest form of gestational trophoblastic disease. Complete moles are diploid and entirely paternal in origin (46,XX or 46,XY, empty ovum fertilised by one sperm that duplicates or two sperm), have no fetus, and carry real malignant potential; partial moles are triploid (69,XXY and variants) with fetal parts, milder changes, and rarely progress. Choriocarcinoma, the overtly malignant end of the spectrum, disseminates haematogenously early, contains cytotrophoblast and syncytiotrophoblast without villi, and is one of the most chemotherapy-curable human cancers.
What you must remember
- Complete mole: diploid, all-paternal DNA, diffuse villous oedema with central cisterns, diffuse trophoblastic proliferation, no fetal vessels, p57 negative (paternal genome lacks the maternal imprint); clinically presents with excessive uterine size, hyperemesis, early pre-eclampsia (before 20 weeks) and hyperthyroidism from hCG cross-stimulation of TSH receptors.
- Partial mole: triploid (usually 69,XXY — dispersion of a haploid ovum), focal changes with scattered normal villi, fetal vessels and fetal parts possible, p57 positive; uterus small for dates, hCG lower; malignant potential is low.
- Invasive mole: myometrial or vascular invasion by whole villi — the commonest form of persistent post-molar disease; metastases may respond to single-agent chemotherapy.
- Choriocarcinoma: biphasic trophoblast without villi, haemorrhagic and necrotic, haematogenous spread to lung (cannonball shadows), brain, liver and vagina; follows mole in half of cases, normal pregnancy or abortion in the rest; very chemosensitive (methotrexate for low risk).
- Placental site trophoblastic tumour: intermediate trophoblast, low hCG, relative chemoresistance — hysterectomy often needed.
- Diagnosis and follow-up hinge on hCG: serial plateau or rise after evacuation indicates persistent disease; contraception during surveillance prevents confusing a new pregnancy with relapse.
- The FIGO/WHO scoring (based on age, antecedent pregnancy interval, pre-treatment hCG, tumour size and site, number of metastases and prior failed chemotherapy) separates single-agent from multi-agent treatment; Indian referral centres manage these on standardised protocols with high cure rates.
- Quantitative anchors: post-evacuation hCG should fall steadily and become negative, commonly by about 8-12 weeks; surveillance typically continues six months to a year after normalisation.
- Ovarian theca-lutein cysts, bilateral and multilocular, result from hCG hyperstimulation and regress spontaneously after evacuation.
A worked case from evacuation to cure
A 24-year-old primigravida at what should be ten weeks reports painless vaginal bleeding and hyperemesis. The uterus measures eighteen weeks, blood pressure is 150/95 with proteinuria — pre-eclampsia before mid-pregnancy is itself a mole clue — and a "snowstorm" pattern appears on ultrasound with no fetus. Serum hCG is several hundred thousand IU per litre. Suction evacuation is performed, and the specimen shows diffusely oedematous avascular villi with circumferential trophoblastic hyperplasia: complete mole, confirmed by p57 negativity on immunohistochemistry (the maternally imprinted gene product is absent because the genome is entirely paternal).
The operation is the beginning, not the end. Serial weekly hCG falls steadily for six weeks, then plateaus and rises — persistent trophoblastic disease. Staging (pelvic ultrasound, chest radiograph, CT head if indicated) assigns her to low-risk disease, treated with single-agent methotrexate until hCG normalises, then consolidation cycles. Had histology shown biphasic trophoblast without villi invading the myometrium with lung cannonballs, it would be choriocarcinoma — multi-agent EMACO in high-risk disease, curable even when metastatic, one of oncology's great successes.
A specimen with a fetus and only focal changes — triploid partial mole — still needs surveillance, though progression to neoplasia is uncommon.
Where students slip
Three confusions decide the marks. First, complete versus partial karyotype: complete mole is diploid-and-all-paternal with no fetus, partial is triploid with fetal tissue — candidates invert this under time pressure; anchor on "complete = complete absence of maternal contribution and of fetus". Second, choriocarcinoma versus invasive mole on histology: villi present (even in a metastasis) means invasive mole; pure trophoblast without villi means choriocarcinoma — the only way to tell them apart. Third, the follow-up discipline: a rising or plateauing post-evacuation hCG is persistent disease, and pregnancy during surveillance must be prevented (hormonal contraception) because a new gestation regenerates hCG and blinds monitoring. A favourite viva extra: explain hyperthyroidism in mole — massive hCG acts as a weak TSH analogue at the TSH receptor; and the theca-lutein cysts are the same hCG acting on the ovaries.
Frequently asked questions
What is the genetic origin of a complete hydatidiform mole?
Diploid androgenetic DNA, entirely paternal — an empty ovum fertilised by a single sperm that duplicates, or by two sperm — expressed as p57 negativity.
How does a partial mole differ in karyotype and histology?
Triploidy (69,XXY and variants) with focal villous oedema, focal trophoblastic proliferation, fetal vessels and possible fetal parts, p57 positive.
Which histological feature separates choriocarcinoma from invasive mole?
Choriocarcinoma is pure malignant trophoblast (cytotrophoblast plus syncytiotrophoblast) without chorionic villi, whereas invasive mole retains villous structures.
Why does hyperthyroidism accompany some moles?
Very high hCG cross-reacts with the TSH receptor as a weak agonist, stimulating thyroid hormone release.
What indicates persistent trophoblastic disease after evacuation?
A plateau or rise in serial hCG values — the trigger for staging and chemotherapy under FIGO/WHO risk scoring.
Which tumour marker monitors gestational trophoblastic neoplasia through treatment?
Serum hCG, measured serially to negativity and then at intervals during surveillance, with contraception maintained throughout.