Interobserver Agreement in Dysplasia Grading of Intraductal Papillary Mucinous Neoplasms: Performance of Kyoto Guidelines and Optimization of Endomicroscopy Biomarkers through Pathology Reclassification

Matthew Leupold; Wei Chen; Ashwini K Esnakula; Wendy L Frankel; Stacey Culp; Philip A Hart; Ahmed Abdelbaki; Zarine K Shah; Erica Park; Peter Lee; Mitchell L Ramsey; Samuel Han; Hamza Shah; Jordan Burlen; Georgios I Papachristou; Zobeida Cruz-Monserrate; Mary Dillhoff; Jordan M Cloyd; Timothy M Pawlik; Somashekar G Krishna

doi:10.1016/j.gie.2024.11.023

Interobserver Agreement in Dysplasia Grading of Intraductal Papillary Mucinous Neoplasms: Performance of Kyoto Guidelines and Optimization of Endomicroscopy Biomarkers through Pathology Reclassification

Gastrointest Endosc. 2024 Nov 16:S0016-5107(24)03733-7. doi: 10.1016/j.gie.2024.11.023. Online ahead of print.

Authors

Matthew Leupold¹, Wei Chen², Ashwini K Esnakula², Wendy L Frankel², Stacey Culp³, Philip A Hart⁴, Ahmed Abdelbaki⁴, Zarine K Shah⁵, Erica Park⁴, Peter Lee⁴, Mitchell L Ramsey⁴, Samuel Han⁴, Hamza Shah⁴, Jordan Burlen⁴, Georgios I Papachristou⁴, Zobeida Cruz-Monserrate⁶, Mary Dillhoff⁷, Jordan M Cloyd⁸, Timothy M Pawlik⁸, Somashekar G Krishna⁹

Affiliations

¹ Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
² Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
³ Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
⁴ Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
⁵ Department of Radiology, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
⁶ Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; The James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
⁷ Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
⁸ The James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
⁹ Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; The James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. Electronic address: somashekar.krishna@osumc.edu.

PMID: 39557199
DOI: 10.1016/j.gie.2024.11.023

Abstract

Background and aims: Interobserver agreement (IOA) among pancreaticobiliary (PB) pathologists in evaluating high-grade dysplasia and/or invasive carcinoma (HGD-IC) of IPMNs remains understudied. EUS-guided needle-based confocal endomicroscopy (nCLE) can evaluate papillary architecture in branch-duct (BD)-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 pre-surgical EUS-nCLE against reclassified pathology.

Methods: Subjects in prospective clinical trials (2015-2023) with resected IPMNs were included. Blinded PB-pathologists independently reviewed histopathology, achieving a consensus diagnosis. The accuracy of cyst fluid next-generation sequencing (NGS) analysis, EUS-nCLE, and Kyoto-HRS in predicting HGD-IC was compared with the reclassified pathology.

Results: Among 64 subjects, 25 (39%) exhibited HGD-IC (17 HGD, 8 IC). Disagreements occurred in 14% of cases with substantial IOA (kappa=0.70; 95%CI: 0.53-0.88) between two PB-pathologists for differentiating HGD-IC vs. low-grade dysplasia. 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 NGS (n=47) to detect HGD-IC was 6.3%, 100%, and 68%, respectively. A unique subset of IPMNs were identified in all (n=8, p=0.01) cases where pre-surgical EUS-nCLE underestimated dysplasia revealing a distinct micropapillary architecture on post-surgical 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.