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  • Title: Refined diagnosis of hydatidiform moles with p57 immunohistochemistry and molecular genotyping: updated analysis of a prospective series of 2217 cases.
    Author: Xing D, Adams E, Huang J, Ronnett BM.
    Journal: Mod Pathol; 2021 May; 34(5):961-982. PubMed ID: 33024305.
    Abstract:
    Immunohistochemical analysis of p57 expression and molecular genotyping accurately subclassify molar specimens into complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) and distinguish these from nonmolar specimens. Characteristics of a prospective series of potentially molar specimens analyzed in a large gynecologic pathology practice are summarized. Of 2217 cases (2160 uterine, 57 ectopic), 2080 (94%) were successfully classified: 571 CHMs (570 uterine, 1 ectopic), 498 PHMs (497 uterine, 1 ectopic), 900 nonmolar (including 147 trisomies, 19 digynic triploids, and 4 donor egg conceptions), and 56 androgenetic/biparental mosaics; 137 were complex or unsatisfactory and not definitively classified. CHMs dominated in patients aged < 21 and >45 years and were the only kind of molar conception found in the latter group. Of 564 successfully immunostained CHMs, 563 (99.8%) were p57-negative (1 p57-positive [retained maternal chromosome 11] androgenetic by genotyping). Of 153 genotyped CHMs, 148 (96.7%) were androgenetic (85% monospermic) and 5 were biparental, the latter likely familial biparental hydatidiform moles. Of 486 successfully immunostained PHMs, 481 (99%) were p57-positive (3 p57-negative [loss of maternal chromosome 11], 2 unknown mechanism). Of 497 genotyped PHMs, 484 (97%) were diandric triploid (99% dispermic) and 13 were triandric tetraploid (all at least dispermic). Of 56 androgenetic/biparental mosaics, 37 had a p57-negative complete molar component (16 confirmed as androgenetic by genotyping). p57 expression is highly correlated with genotyping, serving as a reliable marker for CHMs, and identifies molar components and androgenetic cell lines in mosaic conceptions. Correlation of morphology, p57 expression, genotyping data, and history are required to recognize familial biparental hydatidiform moles and donor egg conceptions, as the former can be misclassified as nonmolar and the latter can be misclassified as dispermic CHM on the basis of isolated genotyping results.
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