Morphology combined withHER2D-DISH ploidy analysis to diagnose partial hydatidiform mole: an evaluation audit using molecular genotyping

Abstract

AimsA 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 byHER2dual-colour dual-hapten in situ hybridisation (D-DISH) ploidy determination.MethodsOver 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 ofHER2D-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.ResultsThirty-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.ConclusionsThis study validates the use ofHER2D-DISH ploidy analysis to support the diagnosis of a morphologically suspected PHM in our practice.

Appraisal of hydatidiform mole incidence and registration rates in Ireland following the establishment of a National Gestational Trophoblastic Disease Registry

“…HER2 DDISH ploidy assay did not overdiagnose PHM when audited by molecular genotyping. 23 In terms of a population bias accounting for differences in incidence rates, we did not observe births to younger mothers in Ireland where the average maternal age was 32.5 years compared with the European average (30.6 years). In terms of ethnicity, the majority of babies (77%) were born to mothers of Irish nationality.…”

Novel scoring system provides high separation of diploidy and triploidy to aid partial hydatidiform mole diagnosis: an adaption ofHER2D-DISH for ploidy analysis

“…This audit achieved 100% sensitivity and specificity (95% CI: ≥92%, n=36) confirming the accuracy of our novel scoring system. 22 It is important to note that ploidy analysis, while valuable in distinguishing diploid from triploid conceptuses, does not identify the genomic origin of the additional chromosomal complement in a triploid conceptus. This raises concerns about the potential overdiagnosis of PHM based on ploidy alone, as there is a risk of mistakenly including digynic triploid conceptuses.…”

“…9 However, recent auditing of our service using molecular genotyping demonstrated that HER2 D-DISH ploidy analysis did not lead to misdiagnosing PHM due to digynic triploidy. 22 This suggests that, from a practical viewpoint, laboratories using morphological assessment supported by an accessible ploidy assay may (a) accurately exclude PHM by confirming diploid conceptus status and (b) confirm triploid status in suspected PHM cases without a substantial risk of overdiagnosis by miscategorising digynic triploid conceptuses.…”