Etiology

The underlying mechanism for molar pregnancy (MP) is not entirely understood. An important component is the presence of excess paternal chromosomes. There is a greater risk of malignant transformation in the presence of a diandric diploid homozygous conception, suggesting a genetic component for the more aggressive form of the disease.[16]​ Rare hereditary forms of recurrent MP suggest an imprinting defect may be an important contributor to disease pathogenesis.[17][18][19]

Pathophysiology

Complete hydatidiform moles have a 46 XX or 46 XY karyotype that is derived entirely of paternal DNA.[20] This is typically the result of fertilization either of a chromosomally empty egg with a haploid sperm that then duplicates its chromosomes by two sperm. By contrast, partial hydatidiform moles contain a karyotype of either 69 XXX or 69 XXY, and contain both maternal and paternal genetic material.[20] This pathology usually arises from fertilization either of a haploid ovum by a single sperm, and duplication of paternal haploid chromosomes, or by two sperm.

Partial moles may contain histologic or macroscopic evidence of fetal parts, fetal circulation, and fetal red blood cells. Complete moles do not contain these elements.[21]

Both partial and complete molar pregnancies contain abnormal and hydropic chorionic villi, which produce high levels of human chorionic gonadotropin (hCG); however, the villi of a complete mole are more edematous, more diffuse, and the increased volume of trophoblast produces more hCG.[22] The hCG glycoprotein hormone is a heterodimer, composed of alpha and beta subunits. The alpha subunit is common to other hormones, such as luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone, but the beta subunit is unique to hCG.[3]​ The higher elevations in serum hCG levels seen in complete molar pregnancies are associated with a greater incidence of severe medical sequelae such as hyperemesis gravidarum, early-onset gestational hypertension, preeclampsia, theca lutein cysts, and hyperthyroidism.[23][24][25][26]​​​​​

Classification

Clinical classification[4]​​

Gestational trophoblastic disease (GTD)

  • Benign trophoblastic tumors

    • Subtle abnormalities in placental pathology such as exaggerated placental sites, and placental site nodules (PSN) and PSN with atypical features (ASPN).

Hydatidiform moles

  • Partial hydatidiform mole

  • Complete hydatidiform mole

Gestational trophoblastic neoplasia (GTN)

  • Malignant invasive mole

  • Choriocarcinoma

  • Placental site trophoblastic tumor (PSTT)

  • Epithelioid trophoblastic tumor (ETT)

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