Molecular genetic testing from paraffin-embedded tissue distinguishes nonmolar hydropic abortion from hydatidiform mole

Background: Diagnosis of hydatidiform mole by histology and ploidy analysis is limited by overlap of criteria for nonmolar hydropic abortion, complete mole, and partial mole. With early presentation, diagnosis is difficult due to limited tissue and lack of clinical features. Accurate diagnosis of these entities is important for both prognosis and patient management. We assessed a polymerase chain reaction (PCR) assay for polymorphic short tandem repeats (STR) for discrimination between nonmolar hydropic abortion, complete mole, and partial mole based on the genetic composition of molar pregnancies, Methods: Seventeen cases of products of conception (POC) diagnosed by histology and flow cytometry ploidy analysis were studied retrospectively. PCR was performed using maternal and chorionic villus DNA extracted from microdissected, formalin-fixed, paraffin-embedded tissue sections. Allelic patterns for up to eight well-characterized polymorphic STR loci were determined using the GenePrint Fluorescent STR System (Promega Corporation, Madison, WI). The presence of three villus alleles at a single locus was interpreted as partial mole. Detection of only one allele in the villi, different from all maternal allele(s) at the same locus, was interpreted as a complete mole. Results: This technique identified eight complete moles previously diagnosed as complete mole (3), hydatidiform mole, otherwise unspecified (1), hydropic villi (2), hydropic villi versus partial mole (1), and partial mole (1). The diagnoses of five partial moles by the molecular assay were consistent with the diagnoses by histology and flow cytometry. One nonmolar gestation was identified, which had been diagnosed previously as hydropic villi. In three cases, maternal DNA amplification was insufficient for definitive diagnosis. Conclusion: Molecular genetic testing of POC from paraffin-embedded tissue accurately distinguishes complete mole, partial mole, and nonmolar hydropic abortion. Identification of triploidy by flow cytometry can confirm a histological impression of partial mole. Histological and ploidy analysis of POC results in underdiagnosis of complete moles.