STEPTRACKERREPRODUCTIVE + ONCOLOGY | PATHOLOGY + GENETICS | HIGH-YIELD REVIEW

Gestational Trophoblastic Disease

Placental tissue that overgrows — two kinds of mole, the invasive mole, and choriocarcinoma that responds so well to chemotherapy.

FOCUS ON
Complete mole: 46,XX all paternal, no fetus, diffuse hydropic villi, very high hCG, big uterus, "snowstorm" US, p57 negative, more cancer risk. Partial mole: 69 chromosomes, fetal parts, focal changes, lower risk. Very high hCG → hyperthyroidism, hyperemesis, theca lutein cysts, preeclampsia before 20 weeks. Choriocarcinoma: no villi, spreads by blood to lungs, methotrexate.
DISORDER
GENETICS · MECHANISM
FEATURES
CLUE
Complete hydatidiform mole
46,XX (usually): empty egg + one sperm that duplicates; all chromosomes paternal (46,XY by dispermy possible)
No fetal tissue; diffuse trophoblast proliferation; swollen villi ("bunch of grapes")
p57 negative (maternally expressed gene absent)
Complete mole — clinical
Huge trophoblast mass → ↑↑ hCG
Bleeding in 1st–2nd trimester, uterus larger than dates, passing grape-like tissue; "snowstorm" on US
~15–20% persistent GTN; ~2–3% choriocarcinoma
Partial hydatidiform mole
Triploid (69,XXY/XXX/XYY): normal egg + two sperm
Fetal parts present; focal villous swelling; uterus normal or small for dates; hCG mildly ↑
p57 positive · low malignancy risk
hCG-related effects
hCG shares the α subunit with TSH, LH, FSH
Hyperthyroidism, hyperemesis gravidarum, theca lutein cysts
Mostly with complete mole
Early preeclampsia
Abnormal placentation with large trophoblast mass
Hypertension + proteinuria before 20 weeks
Always think mole
Invasive mole
Molar villi invade the myometrium
Persistent or rising hCG after evacuation; can perforate the uterus
Responds to methotrexate
Gestational choriocarcinoma
Malignant cyto- and syncytiotrophoblast, no villi; after mole (~50%), abortion, normal pregnancy or ectopic
Hemorrhagic mass; early blood spread to lungs (hemoptysis, cannonball nodules), vagina, brain, liver; very high hCG
Highly chemosensitive (methotrexate, actinomycin D)
Placental site trophoblastic tumor
Intermediate trophoblast
Makes hPL; only modestly ↑ hCG
Chemo-resistant → hysterectomy
Management of a mole
Remove tissue, then watch for persistence
Suction curettage → weekly hCG until undetectable, then monthly
Reliable contraception during follow-up
Risk factors
Extremes of maternal age, prior mole
Teen or > 35–40 years; Asian ancestry
Prior mole ↑ recurrence

Mechanism — where the chromosomes come from

Empty eggNo maternal DNA
+
1 sperm duplicates
→
46,XX complete moleAll paternal, no fetus
Normal egg
+
2 sperm
→
69 chromosomes — partial moleFetal parts

Paternal genes drive trophoblast growth; maternal genes drive embryo growth — so all-paternal tissue is all placenta.

Complete vs partial mole

FEATURE
COMPLETE
PARTIAL
Karyotype
46,XX (paternal)
69,XXX/XXY
Fetal parts
No
Yes
Villi
Diffuse swelling
Focal swelling
hCG
↑↑↑
Mildly ↑
Uterine size
Large for dates
Normal / small
p57 stain
Negative
Positive
Persistent GTN
15–20%
< 5%

How it's tested

COMMON CONFUSIONChoriocarcinoma has no villi; invasive mole does. Both raise hCG after a mole, but only choriocarcinoma is a true malignant tumor of trophoblast alone.
THE TRAPA woman with hyperthyroid symptoms, a big uterus and first-trimester bleeding doesn't have Graves — hCG from a complete mole is stimulating the TSH receptor.
YOUR APPROACHBleeding + hCG level + uterine size + ultrasound → mole type (karyotype, p57) → evacuate → follow hCG → treat persistent disease with methotrexate.

If you see… think…

Uterus large for dates, very high hCG, snowstorm US, no fetus → complete mole
Karyotype 46,XX all paternal → complete mole
Triploid conceptus with fetal parts → partial mole
Molar tissue with no p57 staining → complete mole
Hypertension and proteinuria at 16 weeks → molar pregnancy
Tremor, tachycardia, low TSH with a mole → hCG-driven hyperthyroidism
Bilateral ovarian cysts with very high hCG → theca lutein cysts
hCG rising after mole evacuation → persistent GTN (invasive mole/choriocarcinoma)
Hemoptysis months after a pregnancy, ↑↑ hCG, no villi → choriocarcinoma
First-line drug for low-risk GTN → methotrexate