Diagnosis and subclassification of hydatidiform moles using p57 immunohistochemistry and molecular genotyping: validation and prospective analysis in routine and consultation practice settings with development of an algorithmic approach.
ABSTRACT Distinction of hydatidiform moles (HM) from nonmolar specimens and subclassification of HMs as complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), or early CHM (eCHM) are important for clinical practice and investigational studies but diagnosis based solely on morphology suffers from poor interobserver reproducibility. Recent studies have demonstrated the use of p57 immunostaining and molecular genotyping for improving diagnosis of HMs. After performing a validation study of both techniques on 24 archival products of conception specimens (7 CHMs, 8 PHMs, 9 nonmolar), we prospectively analyzed 42 cases, largely obtained from a gynecologic pathology consultation practice, for which there was any consideration of a diagnosis of HM. After satisfactory experience with prospective cases, a modified approach was adopted, with p57 immunostaining used in conjunction with morphology to triage cases for molecular genotyping. Final diagnoses for the prospective cases based on combined morphology and ancillary testing were 24 CHMs (including 7 eCHMs), 7 PHMs, and 11 nonmolar specimens. P57 immunostaining, performed on all 66 cases, was negative in all CHMs, with the exception of 1 case of molecularly confirmed CHM with diffuse p57 expression, and positive in all PHMs and nonmolar specimens, with the exception of 3 cases of molecularly confirmed PHMs with an equivocal extent of p57 expression. Molecular genotyping of 51 cases (24 validation, 27 prospective) yielded data consistent with p57 results in the 47 cases with unequivocal p57 expression patterns and was used to establish the diagnoses for the 4 cases with aberrant or equivocal p57 results. All 17 genotyped CHMs demonstrated androgenetic diploidy, including the CHM with retained p57 expression; this case also demonstrated trisomy of chromosome 11 (retained maternal allele), accounting for the aberrant p57 expression. The remaining 14 CHMs were diagnosed by morphology and negative p57 results alone. All 15 PHMs demonstrated diandric triploidy. All genotyped nonmolar specimens demonstrated biparental diploidy. This study validates p57 immunostaining as a prospectively applicable triage assay for the diagnosis of CHMs based on morphology and a negative p57 result. Molecular genotyping is validated as a method to confirm a diagnosis of CHM by demonstrating androgenetic diploidy and to resolve p57-positive cases into diandric triploid PHMs, biparental diploid nonmolar specimens, and the rare CHM with aberrant p57 expression.
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ABSTRACT: Gestational trophoblastic disease (GTD) consists of hyperplastic and neoplastic disorders of placental trophoblast; i.e., hydatidiform moles and gestational trophoblastic tumors, respectively. While the histological diagnosis of well-developed complete hydatidiform mole and gestational choriocarcinoma is generally accurate, significant diagnostic challenges persist in the routine evaluation of early complete hydatidiform mole, partial hydatidiform mole, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Recently, the applications of new immunohistochemical markers and molecular techniques have significantly enhanced the diagnostic accuracy of various GTDs. P57 immunohistochemistry is a highly useful marker in confirming complete hydatidiform mole, including its early forms. PCR-based short tandem repeat DNA genotyping has emerged as a powerful diagnostic measure to precisely classify both complete and partial hydatidiform moles. With highly desired sensitivity and specificity, these powerful ancillary studies should be advocated and integrated into the routine diagnostic algorithm of GTD.Current Obstetrics and Gynecology Reports. 03/2013; 3(1):65-75.
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ABSTRACT: Trofoblastik lezyonlar gebelikle iliskili villöz ya da ekstravillöz trofoblasttan gelisen anormal gebelik ve neoplazi spektrumudur. Diger bir deyimle hastanin kendi hücrelerinden degil de konseptustan gelismeleri nedeniyle çok özel bir hastalik grubunu olustururlar. Degisik formlarinin her biri kendine ait mortalite riski ve kemoterapiye cevap özelligi tasimaktadir. Anormal gelismis plasenta olarak tarifleyebilecegimiz tam (komplet) ve kismi (parsiyel) mol'ün olusturdugu MOLAR LEZYONLAR ile; plasental bölge nodülü (PSN), epitelioid trofoblastik tümor (ETT), plasental bölgenin trofoblastik tümorü (PSTT) ve koriyokarsinom (CC) dan ibaret NON-MOLAR lezyonlar bu gruba girmektedir. Bazilari non-neoplastik (PSN) bazilari ise neoplastik (ETT, PSTT, CC) olan non-molar lezyonlarda, isminden de anlasilacagi üzere, trofoblast proliferasyonunda koryonik villus yoktur. Bu lezyonlarin arasinda en çok çalisilani, genetik olarak anormal gebelik olan komplet hidatidiform mol olup bu hastalarda daha sonra, aralarinda koryokarsinomun da dahil oldugu gestasyonel trofoblastik lezyon görülme olasiligi yüksek oldugundan, hastaya patolojik olarak verilen "mol hidatidiform" tanisi sonrasi klinisyen, seri sekilde β-hCG ölçümü yaparak regresyonu takip etmek zorundadir. Görünümleri ve tedavilerinin farkli olmasinin yanisira bir çok non-trofoblastik tümörün morfolojik olarak non-molar lezyonlari taklit edebilmesi nedenleri ile bu lezyonlarin tani, ayirici tanisi ile, degisik trofoblastik antitelerin kendilerine has morfolojik özelliklerini tanimak oldukça önemlidir.Jinekolojik Onkoloji, Edited by Ali Ayhan, 01/2013: chapter 112; Gunes Kitabevi, Ankara., ISBN: 9789752774490
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ABSTRACT: To present first-trimester molecular diagnosis of complete hydatidiform mole (CHM) associated with dizygotic twin pregnancy conceived by intrauterine insemination. A 32-year-old woman presented to the hospital with a huge complex cystic mass measuring about 8.5 cm × 4.1 cm in the uterine cavity and a living co-existing fetus with fetal biometry equivalent to 9 weeks. She underwent chorionic villus sampling at 13 weeks of gestation, and microsatellite genotyping for molar pregnancy test was applied. A molar pregnancy test was performed by a short tandem repeat (STR) identifier polymerase chain reaction (PCR) polymorphic marker analysis. The pregnancy was terminated at 14 weeks of gestation. Postnatal polymorphic DNA marker analysis of the placenta by quantitative fluorescent PCR (QF-PCR) was performed. Analysis of maternal blood total β-human chorionic gonadotropin revealed a high level of 551,600 mIU/mL at 10 weeks of gestation and a level of 1.0 mIU/mL at 15 weeks postpartum. The woman was doing well at 4 months after delivery. The results of STR identifier PCR polymorphic marker analysis showed androgenic conception in the complex cystic mass and biparental conception in the living fetus. Pathological analysis of the cystic mass confirmed the diagnosis of CHM. The results of QF-PCR showed biparental inheritance in the normal fetus and complete paternal homozygosity in the CHM of the abnormal fetus in all STRs, indicating dizygotic twinning and CHM of monospermy. Prenatal sonographic diagnosis of placentomegaly with many grape-like vesicles should include a differential diagnosis of CHM, partial hydatidiform mole (PHM), placental mesenchymal dysplasia (PMD), and recurrent hydatidiform mole. Microsatellite genotyping for molar pregnancy testing and zygosity testing is useful in cases of prenatal diagnosis of placentomegaly associated with many grape-like vesicles and a twin pregnancy with a living fetus in the first trimester. Copyright © 2014. Published by Elsevier B.V.Taiwanese journal of obstetrics & gynecology. 12/2014; 53(4):572-8.