导管内乳头状黏液性肿瘤发育异常分级的观察者间一致性：京都指南的表现及通过病理重新分类对内镜下生物标志物的优化
Interobserver agreement in dysplasia grading of intraductal papillary mucinous neoplasms: performance of Kyoto guidelines and optimization of endomicroscopy biomarkers through pathology reclassification.
作者信息
Leupold Matthew, Chen Wei, Esnakula Ashwini K, Frankel Wendy L, Culp Stacey, Hart Philip A, Abdelbaki Ahmed, Shah Zarine K, Park Erica, Lee Peter, Ramsey Mitchell L, Han Samuel, Shah Hamza, Burlen Jordan, Papachristou Georgios I, Cruz-Monserrate Zobeida, Dillhoff Mary, Cloyd Jordan M, Pawlik Timothy M, Krishna Somashekar G
机构信息
Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
出版信息
Gastrointest Endosc. 2025 Jun;101(6):1155-1165.e6. doi: 10.1016/j.gie.2024.11.023. Epub 2024 Nov 16.
BACKGROUND AND AIMS
Interobserver agreement (IOA) among pancreaticobiliary (PB) pathologists in evaluating high-grade dysplasia and/or invasive carcinoma (HGD-IC) of intraductal papillary mucinous neoplasms (IPMNs) remains understudied. EUS-guided needle-based confocal endomicroscopy (nCLE) can evaluate papillary architecture in branch duct IPMNs. We assessed IOA among PB pathologists in classifying dysplasia in resected IPMNs and compared the performance of the Kyoto guidelines' high-risk stigmata (HRS) and presurgical EUS-nCLE against reclassified pathology.
METHODS
Participants in prospective clinical trials (2015-2023) with resected IPMNs were included. Blinded PB pathologists independently reviewed histopathology, achieving a consensus diagnosis. The accuracies of cyst fluid next-generation sequencing analysis, EUS-nCLE, and Kyoto HRS in predicting HGD-IC were compared with the reclassified pathology.
RESULTS
Among 64 participants, 25 (39%) exhibited HGD-IC (17 HGD, 8 invasive carcinoma). Disagreements occurred in 14% of cases with substantial IOA (κ = 0.70; 95% confidence interval, 0.53-0.88) between 2 PB pathologists for differentiating HGD-IC versus low-grade dysplasia (LGD). To detect HGD-IC, the sensitivity, specificity, and accuracy of Kyoto HRS and EUS-nCLE were 52%, 95%, 78% and 68%, 87%, 80%, respectively. Integrating nCLE with Kyoto HRS improved sensitivity to 80%, with specificity and accuracy at 82% and 81%, respectively. The sensitivity, specificity, and accuracy of next-generation sequencing (n = 47) to detect HGD-IC were 6.3%, 100%, and 68%, respectively. A unique subset of IPMNs were identified in all (n = 8, P = .01) cases where presurgical EUS-nCLE underestimated dysplasia revealing a distinct micropapillary architecture on postsurgical histopathology.
CONCLUSIONS
Despite substantial IOA among experienced PB pathologists, a second pathologist's review may be warranted for dysplasia classification in IPMNs under certain circumstances. Incorporating an imaging biomarker such as EUS-nCLE with Kyoto HRS improves sensitivity for HGD-IC without sacrificing accuracy.
背景与目的
胰腺胆管（PB）病理学家在评估导管内乳头状黏液性肿瘤（IPMNs）的高级别异型增生和/或浸润性癌（HGD-IC）时的观察者间一致性（IOA）仍未得到充分研究。超声内镜引导下基于针的共聚焦内镜检查（nCLE）可评估分支导管IPMNs的乳头状结构。我们评估了PB病理学家在对切除的IPMNs中的异型增生进行分类时的IOA，并比较了京都指南的高风险特征（HRS）和术前超声内镜nCLE与重新分类的病理结果的表现。
方法
纳入2015 - 2023年进行IPMNs切除的前瞻性临床试验参与者。不知情的PB病理学家独立审查组织病理学，达成共识诊断。将囊液二代测序分析、超声内镜nCLE和京都HRS预测HGD-IC的准确性与重新分类的病理结果进行比较。
结果
64名参与者中，25名（39%）表现为HGD-IC（17例高级别异型增生，8例浸润性癌）。在2名PB病理学家区分HGD-IC与低级别异型增生（LGD）时，14%的病例存在分歧，观察者间一致性较高（κ = 0.70；95%置信区间，0.53 - 0.88）。为检测HGD-IC，京都HRS和超声内镜nCLE的敏感性、特异性和准确性分别为52%、95%、78%和68%、87%、80%。将nCLE与京都HRS结合可将敏感性提高到80%，特异性和准确性分别为82%和81%。二代测序（n = 47）检测HGD-IC的敏感性、特异性和准确性分别为6.3%、100%和68%。在所有术前超声内镜nCLE低估异型增生的病例（n = 8，P = 0.01）中均发现了IPMNs的一个独特子集，术后组织病理学显示出独特的微乳头结构。
结论
尽管经验丰富的PB病理学家之间存在较高的IOA，但在某些情况下，对于IPMNs中的异型增生分类，可能仍需要第二位病理学家进行审查。将超声内镜nCLE等影像生物标志物与京都HRS相结合可提高HGD-IC的敏感性，且不牺牲准确性。
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