Hydatidiform moles: differential diagnosis, diagnostic reproducibility, genetics and ancillary techniques to refine diagnosis

Distinction of hydatidiform moles from non-molar specimens and sub-classification of hydatidiform moles as complete hydatidiform mole (CHM) versus partial hydatidiform mole (PHM) are important. Risk of persistent gestational trophoblastic disease and clinical management differ for these entities. Diagnosis based on morphology is subject to interobserver variability. The unique genetics of CHMs, PHMs, and non-molar specimens allow for certain techniques, including immunohistochemical analysis of p57 expression and PCR-based DNA genotyping, to refine diagnosis. p57 immunostaining identifies CHMs, which lack p57 expression due to lack of maternal DNA, but does not distinguish PHMs from non-molar specimens since both express p57 due to the presence of maternal DNA. Genotyping distinguishes purely androgenetic CHMs from diandric triploid PHMs and both of these from biparental non-molar specimens by comparing villous and decidual DNA patterns to determine the parental source and ratios of polymorphic alleles. An algorithmic approach using these ancillary techniques is advocated.