complete molar pregnancy

**Genetics/pathogenesis** - Empty egg (nucleus absent or inactivated) fertilized by a haploid sperm that duplicates (about 90%, 46,XX, entirely paternal) or by 2 sperm (about 10%, 46,XY or 46,XX). - All genetic material is paternal (androgenetic), so there is no fetal tissue, amnion, or embryo. Trophoblast overgrowth predominates (paternal genes drive trophoblast growth; maternal genes drive embryo development). - Contrast with partial mole: 69,XXY (or XXX/XYY), triploid, usually 2 sperm + 1 normal ovum, with fetal parts or an embryo present.

**Pathology** - Diffuse hydropic swelling of all chorionic villi ("cluster of grapes") with diffuse circumferential trophoblastic hyperplasia. - Villi lack blood vessels. No fetal parts. - Histology shows p57 (KIP2) immunostaining is negative in a complete mole (the maternally expressed gene is absent). It is positive in a partial mole.

**Clinical presentation (first or early second trimester)** - Vaginal bleeding (most common), often painless, with passage of grape-like vesicles. - Uterine size larger than dates (about 25%) and markedly elevated β-hCG (often >100,000 mIU/mL). - hCG-related effects: hyperemesis gravidarum, early-onset preeclampsia (<20 weeks, a classic clue), hyperthyroidism (hCG resembles TSH, so there is low TSH and high free T4), and theca lutein cysts (bilateral enlarged ovaries). - No fetal heart tones.

**Diagnosis** - Pelvic ultrasound: "snowstorm" appearance (complex intrauterine mass with multiple cystic spaces), no fetus. - Serum β-hCG is very high. Definitive diagnosis is by histology after evacuation.

**Management** - Suction dilation and curettage (D&C) is the treatment of choice. - Follow weekly β-hCG until undetectable, then monthly for about 6 months. Use effective contraception during surveillance (avoid pregnancy, which would confound hCG interpretation). - Check baseline chest x-ray, since the lung is the most common metastatic site. - Rising or plateaued hCG after evacuation indicates gestational trophoblastic neoplasia (GTN). Treat with methotrexate or dactinomycin (single-agent chemotherapy for low-risk disease). Multi-agent chemotherapy (EMA-CO) is used for high-risk disease.

**Complications/associations** - Persistent gestational trophoblastic disease/GTN (about 15–20% of complete moles vs about 1–5% of partial moles). - Invasive mole (myometrial invasion) and choriocarcinoma (a malignancy of trophoblasts, with hematogenous spread to lung, then brain, liver, and vagina, and very chemosensitive). - Risk factors: extremes of maternal age (<20 or >35 years), prior molar pregnancy, and Asian ethnicity. - Can also be complicated by hemorrhage, uterine perforation, and rarely trophoblastic embolization or respiratory distress.

**High-yield pearls** - "Complete = Cluster of grapes, 46,XX, paternal only, no fetus, high hCG, p57-negative." - Early preeclampsia (<20 weeks), hyperthyroidism, and theca lutein cysts are classic clues to a mole. - Choriocarcinoma can follow a complete mole (about 50% of cases), a miscarriage, or a normal pregnancy.