Hydatidiform Moles: Ancillary Techniques to Refine Diagnosis

Abstract

Context.— Distinction of hydatidiform moles from nonmolar specimens and subclassification of hydatidiform moles as complete hydatidiform mole versus partial hydatidiform mole are important for clinical practice and investigational studies. Risk of persistent gestational trophoblastic disease and clinical management differ for these entities. Diagnosis based on morphology is subject to interobserver variability and remains problematic, even for experienced gynecologic pathologists. Objectives.— To explain how ancillary techniques target the unique genetic features of hydatidiform moles to establish diagnostic truth, highlight the issue of diagnostic reproducibility and importance of diagnostic accuracy, and illustrate use of p57 immunohistochemistry and polymerase chain reaction–based DNA genotyping for diagnosis. Data Sources.— Sources are the author's 10-year experience using ancillary techniques for the evaluation of potentially molar specimens in a large gynecologic pathology practice and the literature. Conclusions.— The unique genetics of complete hydatidiform moles (purely androgenetic), partial hydatidiform moles (diandric triploid), and nonmolar specimens (biparental, with allelic balance) allow for certain techniques, including immunohistochemical analysis of p57 expression (a paternally imprinted, maternally expressed gene) and genotyping, to refine diagnoses of hydatidiform moles. Although p57 immunostaining alone can identify complete hydatidiform moles, which lack p57 expression because of a lack of maternal DNA, this analysis does not distinguish partial hydatidiform moles from nonmolar specimens because both express p57 because of the presence of maternal DNA. Genotyping, which compares villous and decidual DNA patterns to determine the parental source and ratios of polymorphic alleles, distinguishes purely androgenetic complete hydatidiform moles from diandric triploid partial hydatidiform moles, and both of these from biparental nonmolar specimens. An algorithmic approach to diagnosis using these techniques is advocated.

Paternal uniparental isodisomy of tyrosine hydroxylase locus at chromosome 11p15.4: spectrum of phenotypical presentations simulating hydatidiform moles

“…Complete hydatidiform moles characteristically demonstrate loss of p57 expression in villous cytotrophoblast and stromal cells as a result of their paternal-only genome. However, aberrant p57 expression with abnormal villous morphology has been documented in diploid and biparental gestations including familial biparental complete mole and Beckwith-Wiedemann syndrome [23]. Loss of p57 expression and abnormal villous morphology resulting from paternal uniparental isodisomy may be erroneously interpreted as a complete mole without molecular genetic studies [24].…”

A fetus coexisting with a complete hydatidiform mole with trisomy 9 of maternal origin

“…Morphological assessment of a hydatidiform mole could be a challenge in some cases, even for experienced pathologists, in which high interobserver and intraobserver variability exist . Nonmolar entities such as chromosomal trisomy syndromes were also reported to exhibit some histological features of molar pregnancy .…”

Update on the pathology of gestational trophoblastic disease

“…Short tandem repeat (STR) genotyping has emerged as the most useful ancillary technique, not only distinguishing moles from their mimics, and complete mole from partial mole, but also able to distinguish gestational from non‐gestational trophoblastic disease, as well as recurrent from new molar disease . STR genotyping can be performed on formalin‐fixed, paraffin‐embedded tissue.…”