Departments of Pathology, The Johns Hopkins University School of Medicine and Hospital, Baltimore, MD 21231, USA.
Am J Surg Pathol. 2012 Dec;36(12):1747-60. doi: 10.1097/PAS.0b013e31825ea736.
Distinction of hydatidiform moles from nonmolar specimens (NMs) and subclassification of hydatidiform moles as complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) are important for clinical practice and investigational studies; however, 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, 26 NMs) were selected from a series of 200 potentially molar specimens previously diagnosed using p57 immunohistochemistry and genotyping. Cases were classified by 6 pathologists (3 faculty level gynecologic pathologists and 3 fellows) on the basis of morphology, 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 in each group) were also determined. Performance of experienced gynecologic pathologists versus fellow pathologists was compared, using genotyping results as the gold standard. Correct classification of CHMs ranged from 59% to 100%; there were no statistically significant differences in performance of faculty versus fellows in any round (P-values of 0.13, 0.67, and 0.54 for rounds 1 to 3, respectively). Correct classification of PHMs ranged from 26% to 93%, with statistically significantly better performance of faculty versus fellows in each round (P-values of 0.04, <0.01, and <0.01 for rounds 1 to 3, respectively). Correct classification of NMs ranged from 31% to 92%, with statistically significantly better performance of faculty only in round 2 (P-values of 1.0, <0.01, and 0.61 for rounds 1 to 3, respectively). Correct classification of all cases combined ranged from 51% to 75% by morphology and 70% to 80% with p57, with statistically significantly better performance of faculty only in round 2 (P-values of 0.69, <0.01, and 0.15 for rounds 1 to 3, respectively). p57 immunostaining significantly improved recognition of CHMs (P<0.01) and had high reproducibility (κ=0.93 to 0.96) but had no impact on distinction of PHMs and NMs. Genotyping provides a definitive diagnosis for the ∼25% to 50% of cases that are misclassified by morphology, especially those that are also unresolved by p57 immunostaining.
葡萄胎与非葡萄胎标本（NM）的鉴别以及葡萄胎的分类（完全性葡萄胎（CHM）和部分性葡萄胎（PHM））对临床实践和研究都很重要；然而，仅基于形态学的诊断受到观察者间变异性的影响。分子基因分型通过辨别雄激素二倍体、二倍体三体型和双亲二倍体来区分这些实体，分别诊断 CHM、PHM 和 NM。从之前使用 p57 免疫组化和基因分型诊断的 200 例潜在葡萄胎标本中选择了 80 例基因分型病例（27 例 CHM、27 例 PHM、26 例 NM）。在两轮诊断中，由 6 名病理学家（3 名妇科病理学家和 3 名研究员）根据形态学对病例进行分类，不了解 p57 免疫染色和基因分型结果，分为 3 类（CHM、PHM 或 NM）中的 1 类；还进行了第三轮包含 p57 免疫染色结果的分类。还确定了共识诊断（每组由 3 名病理学家中的 2 名做出的诊断）。使用基因分型结果作为金标准，比较了有经验的妇科病理学家与研究员病理学家的表现。CHM 的正确分类范围为 59%至 100%；在任何一轮中， faculty 与研究员之间的表现均无统计学差异（第 1 至 3 轮的 P 值分别为 0.13、0.67 和 0.54）。PHM 的正确分类范围为 26%至 93%，在每一轮中 faculty 与研究员之间的表现均有统计学差异（第 1 至 3 轮的 P 值分别为 0.04、<0.01 和 <0.01）。NM 的正确分类范围为 31%至 92%，仅 faculty 在第二轮中表现出统计学差异（第 1 至 3 轮的 P 值分别为 1.0、<0.01 和 0.61）。仅通过形态学的所有病例的正确分类范围为 51%至 75%，结合 p57 的正确分类范围为 70%至 80%，第二轮中 faculty 仅表现出统计学差异（第 1 至 3 轮的 P 值分别为 0.69、<0.01 和 0.15）。p57 免疫染色显著提高了 CHM 的识别率（P<0.01），且具有较高的可重复性（κ=0.93 至 0.96），但对 PHM 和 NM 的区分没有影响。基因分型为约 25%至 50%因形态学而误诊的病例提供了明确的诊断，特别是那些 p57 免疫染色也未解决的病例。
