What designates a molar pregnancy from a non-molar pregnancy in Triploidy (trisomy) XXY?

Distinguishing Molar from Non-Molar Pregnancy in Triploidy XXY

In triploidy XXY (69,XXY), the designation of molar pregnancy (partial hydatidiform mole) versus non-molar pregnancy depends on the parental origin of the extra haploid chromosome set: diandric triploidy (two paternal contributions) produces partial molar changes, while digynic triploidy (two maternal contributions) results in a non-molar hydropic abortion. 1

Genetic Origin Determines Classification

Diandric Triploidy = Partial Molar Pregnancy

• Partial hydatidiform moles (PHM) arise from fertilization of a single ovum by two sperm (dispermic fertilization), resulting in diandric triploid conceptions that may be 69,XXX, 69,XXY, or 69,XYY 1
• The extra paternal genome contribution drives the characteristic molar pathology 1
• This represents the genetic mechanism underlying partial molar pregnancy in all triploid cases 1

Digynic Triploidy = Non-Molar Hydropic Abortion

• When triploidy results from two maternal chromosome sets and one paternal set (digynic), the pregnancy presents as a hydropic abortion without molar features 2
• Digynic triploidy was found in 15 of 24 cases (62.5%) in one molecular analysis series, while diandric triploidy (partial mole) occurred in 9 cases (37.5%) 2

Histopathological Features

Partial Molar Characteristics (Diandric Origin)

• PHMs show patchy villous hydropic change with scattered abnormally shaped irregular villi, trophoblastic pseudoinclusions, and patchy trophoblast hyperplasia 1
• These features distinguish partial moles from complete moles, which show more uniform villous architecture with abnormal trophoblast hyperplasia, stromal hypercellularity, and collapsed villous blood vessels 1

Critical Diagnostic Challenge

• The morphological distinction between non-molar miscarriage (especially with chromosomal abnormality like digynic triploidy) and PHM can be difficult on histology alone 1
• Histomorphological overlap between partial molar pregnancy and hydropic abortions creates diagnostic uncertainty without molecular testing 2

Ancillary Diagnostic Techniques Required

Molecular Methods Are Essential

• Ancillary techniques are required for accurate diagnosis, including immunostaining with p57KIP2 (negative in complete moles but positive in partial moles and non-molar pregnancies), ploidy analysis by in situ hybridization or flow cytometry, or molecular genotyping 1
• Concomitant histopathological analysis of placental tissue and molecular analysis of placental and maternal DNA leads to correct diagnosis 2
• Molecular genotyping can determine whether triploidy is diandric (molar) or digynic (non-molar) by analyzing parental contributions 1, 2

Timing Affects Detection

• Triploidy is associated with molar changes less often in the first trimester than in the second or third trimester 3
• Most triploid spontaneous abortions escape detection on ultrasound or macroscopic examination in early pregnancy 3
• All cases of triploidy associated with partial mole in one series were diagnosed before 25 weeks' gestation 4

Clinical Implications

Phenotypic Overlap

• Only 24% of triploid fetuses showed histologic features of partial hydatidiform mole in the placenta at autopsy, despite all being chromosomally triploid 5
• There was no difference in fetal phenotype between triploid infants associated with partial moles and those with non-molar placentas 5
• This emphasizes that fetal phenotype alone cannot distinguish molar from non-molar triploidy 5

Risk Stratification Importance

• The distinction matters clinically because partial moles carry a 0.5-1% risk of persistent gestational trophoblastic disease (pGTD)/gestational trophoblastic neoplasia (GTN), requiring hCG surveillance 1
• Non-molar triploid pregnancies do not carry this malignant potential 1

Common Pitfalls to Avoid

• Do not rely on histology alone - the sensitivity of histology for triploidy ranges between 87.3-94.4%, with specificity between 81.7-85.9% 3
• Do not assume all triploidy is molar - digynic triploidy represents a significant proportion of cases and lacks molar features 2
• Do not skip molecular testing in ambiguous cases - genotyping is the definitive method to determine parental origin and thus molar versus non-molar status 1, 2