Single Nucleotide Polymorphism-Based Chromosomal Microarray Evaluation of Hydatidiform Moles: A US National Reference Laboratory Experience

Objectives: This retrospective study evaluated 1) benefits of single nucleotide polymorphism (SNP)-based chromosomal microarrays (CMAs) in the diagnosis of complete hydatidiform mole (CHM) and partial HM (PHM) in products of conception (POC) and amniotic fluid (AF) specimens, and 2) frequency of whole-genome uniparental disomy (wgUPD) and triploidy in POC and AF specimens received at a US national reference laboratory. Methods: We reviewed consecutive 2138 POC and 3230 AF specimens and identified the cases with wgUPD and triploidy which are associated with molar pregnancy. Results: Of 2138 consecutive POC specimens tested, SNP-based CMA detected wgUPD in 10 (0.47%) and triploidy in 84 (3.93%). Of the 10 wgUPD cases, 9 (90%) were confirmed as CHM. Of 3230 consecutive AF specimens, the array detected wgUPD in 1 case (0.03%) and triploidy in 11 (0.34%). Conclusions: SNP-based microarray allows detection of wgUPD in POC and AF specimens at a US national reference laboratory. Correctly diagnosing HM and differentiating CHM from PHM are important for clinical management. The effective SNP-based CMA detection of wgUPD in CHM may enable physicians to monitor patients at risk for gestational trophoblastic disease and neoplasm. Conventional chromosome analysis of POC has a high failure rate, cannot be performed on formalin-fixed paraffin embedded samples, and cannot detect wgUPD. Further multi-institutional collaborative assessmen on accuracy, cost-effectiveness, and adequate access to SNP-based CMA, may lead this testing platform to be considered as the first-tier analysis tool for POC specimens, including those showing PHM or CHM.