Ancillary Techniques in Distinction of Androgenetic/Biparental Diploid Mosaic Conceptions from Hydatidiform Moles
Gloria H Lewis, Cheryl DeScipio, Kathleen M Murphy, Russell Vang, Brigitte M Ronnett. The Johns Hopkins Medical Institutions, Baltimore, MD; ProPath, Dallas, TX
Background: Recent studies have demonstrated the value of ancillary techniques, including p57 immunohistochemistry (IHC) and short tandem repeat (STR) genotyping, for distinction of hydatidiform moles (HM) from non-molar specimens (NM) and for subtyping HM as complete hydatidiform moles (CHM) and partial hydatidiform moles (PHM). With rare exceptions, CHM are p57-negative and androgenetic diploid; PHM are p57-positive and diandric triploid; and NM are p57-positive and biparental diploid. Androgenetic/biparental diploid mosaic conceptions (ABDMC) have some morphologic features that simulate HM but are genetically distinct in that they contain an admixture of p57-negative androgenetic diploid and p57-positive biparental diploid cells. Combined p57 IHC and STR genotyping of ABDMC has not been reported.
Design: This study characterizes 9 ABDMC identified in a series of 390 products of conception specimens subjected to p57 IHC and STR genotyping. Fluorescence in situ hybridization (FISH) was performed on 4 to further assess ploidy.
Results: All cases were characterized by hydropically enlarged, variably sized and shaped villi, with some having distinct stromal hypercellularity. In 4 cases, the villi lacked trophoblastic hyperplasia whereas in 5 there was a focal villous component with trophoblastic hyperplasia and features of CHM. The villi lacking trophoblastic hyperplasia were characterized by discordant p57 expression within individual villi (p57-positive cytotrophoblast and p57-negative villous stromal cells) whereas the villous components having trophoblastic hyperplasia were uniformly p57-negative in both cell types. STR genotyping of multiple villous areas in each case demonstrated variable paternal:maternal allele ratios of >2:1. FISH demonstrated diploidy in 4 cases, including 2 with a CHM component. These results are consistent with an admixture of androgenetic diploid (p57-negative) and biparental diploid (p57-positive) cell lines. In 2 cases with a CHM component, persistent gestational trophoblastic disease (GTD) developed, with one patient requiring hysterectomy despite chemotherapy; no metastatic GTD was found in either.
Conclusions: ABDMC, including those with a CHM component, can be recognized by their distinctive p57 expression patterns and confirmed as such by their unique genotyping results, thus preventing misclassification as typical CHM, PHM, or NM. The presence of androgenetic cell lines, particularly in those with a CHM component, warrants follow-up due to some risk of persistent GTD.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 2:30 PM
Platform Session: Section B, Tuesday Afternoon