Abnormal Villous Morphology Associated with Triple Trisomy of Paternal Origin

Norris-Kirby, Alexis; Hagenkord, Jill; Kshirsagar, Malti; Ronnett, Brigitte M.; Murphy, Kathleen M.

doi:10.2353/jmoldx.2010.090184

Cited by 18 publications

(11 citation statements)

References 30 publications

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“…Also for academic interest, further investigation of the non-molar specimen with double trisomy involving chromosomes 7 and 13 (which was initially interpreted as a partial hydatidiform mole by morphology) via singlenucleotide polymorphism array analysis identified triple trisomy of paternal origin involving chromosomes 7, 13, and 20. 42 There were 21 cases with more complex genotypes than those of typical molar and non-molar specimens. Of these, 14 were classifiable as forms of androgenetic/biparental mosaic specimens (11 of these are described in detail in our previous study).…”

Section: Modern Pathology (2014) 27 238-254mentioning

confidence: 99%

“…40 In addition, some non-molar specimens with cytogenetic abnormalities such as trisomy can simulate partial hydatidiform moles, causing problems in diagnostic reproducibility. 41,42 In 2007, we began a prospective analysis of all potentially molar products of conception specimens encountered on the Gynecologic Pathology Service of The Johns Hopkins Hospital, Baltimore, MD using immunohistochemical analysis of p57 expression and molecular genotyping with short tandem repeat markers. 25,31,43 The current study summarizes the results of nearly 6 years of analysis, providing a summary of the characteristics of a large series of hydatidiform moles and non-molar specimens assessed by these techniques as well as the assessment of the performance of these methods in clinical practice.…”

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confidence: 99%

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Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping

et al. 2014

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Immunohistochemical analysis of cyclin-dependent kinase inhibitor 1C (CDKN1C, p57, Kip2) expression and molecular genotyping accurately classify hydatidiform moles into complete and partial types and distinguish these from non-molar specimens. Characteristics of a prospective series of all potentially molar specimens encountered in a large gynecologic pathology practice are summarized. Initially, all specimens were subjected to both analyses; this was later modified to triage cases for genotyping based on p57 results: p57-negative cases diagnosed as complete hydatidiform moles without genotyping; all p57-positive cases genotyped. Of the 678 cases, 645 were definitively classified as complete hydatidiform mole (201), partial hydatidiform mole (158), non-molar (272), and androgenetic/biparental mosaic (14); 33 were unsatisfactory, complex, or problematic. Of the 201 complete hydatidiform moles, 104 were p57-negative androgenetic and an additional 95 were p57-negative (no genotyping), 1 was p57-positive (retained maternal chromosome 11) androgenetic, and 1 was p57-non-reactive androgenetic; 90 (85%) of the 106 genotyped complete hydatidiform moles were monospermic and 16 were dispermic. Of the 158 partial hydatidiform moles, 155 were diandric triploid, with 154 p57-positive, 1 p57-negative (loss of maternal chromosome 11), and 1 p57-non-reactive; 3 were triandric tetraploid, with 2 p57-positive and 1 p57-negative (loss of maternal chromosome 11). Of 155 diandric triploid partial hydatidiform moles, 153 (99%) were dispermic and 2 were monospermic. Of the 272 non-molar specimens, 259 were p57-positive biparental diploid, 5 were p57-positive digynic triploid, 2 were p57-negative biparental diploid (no morphological features of biparental hydatidiform mole), and 6 were p57-non-reactive biparental diploid. Of the 14 androgenetic/biparental mosaics with discordant p57 expression, 6 were uniformly mosaic and 8 had a p57-negative androgenetic molar component. p57 expression is highly correlated with genotyping, serves as a reliable marker for diagnosis of complete hydatidiform moles, and identifies androgenetic cell lines in mosaic conceptions. Cases with aberrant and discordant p57 expression can be correctly classified by genotyping.

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Section: Modern Pathology (2014) 27 238-254mentioning

confidence: 99%

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confidence: 99%

Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping

et al. 2014

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“…Prior to the discovery of the molecular basis of PHM, association of trisomies (trisomy 2 in particular) with hydatidiform moles has also been suggested (8). A recent case report described a triple trisomy of paternal origin mimicking PHM (7). However, other studies have not found significant differences in the villous morphology based on the parental origin of the extra chromosomes in trisomic gestations (9).…”

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confidence: 96%

“…The morphologic overlaps between PHM and chromosomal trisomies have long been recognized (5)(6)(7)(8)(9)(10). In addition, other morphologic mimics of PHM include complete hydatidiform mole (CHM), diploid hydropic abortions and digynic triploidy in early gestations, and placental mesenchymal dysplasia at later gestational age (GA) (11).…”

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confidence: 98%

Partial Hydatidiform Mole

Buza

Hui

2013

International Journal of Gynecological Pathology

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Histologic diagnosis of partial hydatidiform mole (PHM) continues to be problematic, and DNA genotyping has recently become cost-effective for precise separation of PHM from its mimics. We performed a comprehensive reevaluation of histologic parameters of PHM in correlation with DNA genotyping. A total of 143 early abortion specimens were subjected to genotyping as part of the routine workup, resulting in 60 cases of PHM, 52 cases of various chromosomal trisomies, and 31 cases of nonmolar diploid gestations. All available hematoxylin and eosin slides were reviewed retrospectively by 2 gynecologic pathologists blinded to the genotyping results. Significant histologic overlaps were present among genetically confirmed PHM, hydropic abortions, and chromosomal trisomy syndromes. The following morphologic parameters emerged with diagnostic significance for PHM: villus size, presence of 2 villous populations, round or oval pseudoinclusions, at least moderate villous hydrops, cistern formation, and trophoblastic hyperplasia. The most sensitive morphologic features for PHM included villous hydrops (86% sensitivity) or the presence of at least 1 of the following 3 parameters: 2 villous populations, round or oval pseudoinclusions, and cisterns (84% sensitivity). The presence of cisterns and villous size ≥2.5 mm had the highest positive predictive value (90%) for PHM. In conclusion, no single or combined morphologic features are sufficient for definitive diagnosis of PHM. The presence of any one of the following histologic findings should prompt DNA genotyping workup to rule out PHM: round or oval pseudoincludions, cistern formation, 2 populations of villi, and a villous size of ≥2.5 mm.

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“…Despite these differences, a substantial degree of morphologic overlap exists between these 2 types of HMs. In addition, distinction of HMs from NMs can be problematic in several situations, including: (a) products of conception specimens (POCs) with abnormal villous morphology (a nonmolar type of villous abnormality having some morphologic features suggestive of a PHM but lacking the diandric triploidy required for a definitive diagnosis of PHM, sometimes attributable to other genetic abnormalities such as trisomy) 7,46,49,51 ; (b) early nonmolar abortuses with prominent trophoblastic hyperplasia; (c) hydropic abortuses; and (d) mosaic/chimeric conceptions. 25,26,30,51,57 These problems are partially because of the fact that histologic criteria for diagnosis of HMs are imperfect, not all pathologists apply criteria similarly, and because the histologic appearance can vary depending on gestational age.…”

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Diagnostic Reproducibility of Hydatidiform Moles

Vang

Gupta²,

et al. 2012

American Journal of Surgical Pathology

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Distinction of hydatidiform moles (HMs) from non-molar specimens (NMs) and subclassification of HMs as complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs) are important for clinical practice and investigational studies; yet, diagnosis based solely on morphology is affected by interobserver variability. Molecular genotyping can distinguish these entities by discerning androgenetic diploidy, diandric triploidy, and biparental diploidy to diagnose CHMs, PHMs, and NMs, respectively. Eighty genotyped cases (27 CHMs, 27 PHMs, and 26 NMs) were selected from a series of 200 potentially molar specimens previously diagnosed using p57 immunostaining and genotyping. Cases were classified by 3 gynecologic pathologists on the basis of H&E slides (masked to p57 immunostaining and genotyping results) into 1 of 3 categories (CHM, PHM, or NM) during 2 diagnostic rounds; a third round incorporating p57 immunostaining results was also conducted. Consensus diagnoses (those rendered by 2 of 3 pathologists) were determined. Genotyping results were used as the gold standard for assessing diagnostic performance. Sensitivity of a diagnosis of CHM ranged from 59% to 100% for individual pathologists and from 70% to 81% by consensus; specificity ranged from 91% to 96% for individuals and from 94% to 98% by consensus. Sensitivity of a diagnosis of PHM ranged from 56% to 93% for individual pathologists and from 70% to 78% by consensus; specificity ranged from 58% to 92% for individuals and from 74% to 85% by consensus. The percentage of correct classification of all cases by morphology ranged from 55% to 75% for individual pathologists and from 70% to 75% by consensus. The κ values for interobserver agreement ranged from 0.59 to 0.73 (moderate to good) for a diagnosis of CHM, from 0.15 to 0.43 (poor to moderate) for PHM, and from 0.13 to 0.42 (poor to moderate) for NM. The κ values for intraobserver agreement ranged from 0.44 to 0.67 (moderate to good). Addition of the p57 immunostain improved sensitivity of a diagnosis of CHM to a range of 93% to 96% for individual pathologists and 96% by consensus; specificity was improved from a range of 96% to 98% for individual pathologists and 96% by consensus; there was no substantial impact on diagnosis of PHMs and NMs. Interobserver agreement for interpretation of the p57 immunostain was 0.96 (almost perfect). Even with morphologic assessment by gyneco-logic pathologists and p57 immunohistochemistry, 20% to 30% of cases will be misclassified, and, in particular, distinction of PHMs and NMs will remain problematic.

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Abnormal Villous Morphology Associated with Triple Trisomy of Paternal Origin

Cited by 18 publications

References 30 publications

Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping

Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping

Partial Hydatidiform Mole

Diagnostic Reproducibility of Hydatidiform Moles

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