Morphology combined with HER2 D-DISH ploidy analysis to diagnose partial hydatidiform mole: an evaluation audit using molecular genotyping.

Aims: A hydatidiform mole (HM) is classified as complete (CHM) or partial (PHM) based on its morphology and genomic composition. Ancillary techniques are often required to confirm a morphologically suspected PHM diagnosis. This study sought to evaluate the clinical accuracy of PHM diagnosis using morphological assessment supported by HER2 dual-colour dual-hapten in situ hybridisation (D-DISH) ploidy determination.

Methods: Over a 2-year period, our unit examined 1265 products of conception (POCs) from which 103 atypical POCs were diagnosed as PHM or non-molar conceptuses with the assistance of HER2 D-DISH ploidy analysis. We retrospectively audited a sample of 40 of these atypical POCs using short tandem repeat genotyping. DNA extracted from formalin-fixed paraffin-embedded tissue was genotyped using 24 polymorphic loci. Parental alleles in placental villi were identified by comparison to those in maternal decidua. To identify triploid PHM cases, we sought three alleles of equal peak height or two alleles with one allele peak twice the height of the other at each locus.

Results: Thirty-six of the 40 cases (19 PHM and 17 non-molar) were successfully genotyped and demonstrated complete concordance with the original diagnosis. All PHMs were diandric triploid of dispermic origin. In two non-molar diploid cases, we identified suspected trisomies (13 and 18), which potentially explains the pregnancy loss in these cases.

Conclusions: This study validates the use of HER2 D-DISH ploidy analysis to support the diagnosis of a morphologically suspected PHM in our practice.