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Diagnostic Reproducibility of Hydatidiform Moles: Ancillary Techniques (p57 Immunohistochemistry and Molecular Genotyping) Improve Morphologic Diagnosis

Vang, Russell MD*,†; Gupta, Mamta MBBS*; Wu, Lee-Shu-Fune MHS; Yemelyanova, Anna V. MD*; Kurman, Robert J. MD*,†,§; Murphy, Kathleen M. PhD*; DeScipio, Cheryl PhD*,†; Ronnett, Brigitte M. MD*,†

The American Journal of Surgical Pathology: March 2012 - Volume 36 - Issue 3 - p 443–453
doi: 10.1097/PAS.0b013e31823b13fe
Original Articles

Distinction of hydatidiform moles (HMs) from nonmolar 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 gynecologic pathologists and p57 immunohistochemistry, 20% to 30% of cases will be misclassified, and, in particular, distinction of PHMs and NMs will remain problematic.

Departments of *Pathology

Gynecology & Obstetrics, The Johns Hopkins University School of Medicine and Hospital

Department of International Health, Bloomberg School of Public Health, The Johns Hopkins University

§Department of Oncology, The Johns Hopkins University School of Medicine and Hospital, Baltimore, MD

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Present address: Kathleen M. Murphy, PhD, ProPath, Dallas, TX.

Correspondance: Brigitte M. Ronnett, MD, Department of Pathology, The Johns Hopkins Hospital, Weinberg 2242, 401N. Broadway, Baltimore, MD 21231 (e-mail:

© 2012 Lippincott Williams & Wilkins, Inc.