P3464 - Evaluation of Interobserver Agreement in Dysplasia Classification for IPMNs and the Impact on Pre-Surgical Risk Stratification

Matthew Leupold, MD¹, Wei Chen, ¹, Ashwini Esnakula, MBBS¹, Wendy Frankel, MD¹, Stacey Culp, PhD², Phil Hart, MD¹, Ahmed RM. Abdelbaki, MBBCh¹, Zarine K. Shah, MD¹, Erica Park, MD¹, Peter J Lee, MD¹, Mitchell L. Ramsey, MD¹, Sam Han, MD¹, Hamza Shah, MD¹, Jordan Burlen, MD¹, Georgios Papachristou, MD, PhD¹, Zobeida Cruz-Monserrate, PhD¹, Mary Dillhoff, MD¹, Jordan Cloyd, MD¹, Timothy Pawlik, MD¹, Somashekar G Krishna, MD^1
1The Ohio State University Wexner Medical Center, Columbus, OH; ²Ohio State University, Columbus, OH

Introduction: 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. We compared the performance of the Kyoto guidelines’ high-risk criteria (HRC) 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-HRC 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-HRC and EUS-nCLE were 52%, 95%, 78%, and 68%, 87%, 80%, respectively. Integrating nCLE with Kyoto-HRC 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 (n=8, p=0.01) in which pre-surgical EUS-nCLE underestimated dysplasia revealed a distinct micropapillary architecture on post-surgical histopathology. These IPMNs (n=7) lacked GNAS mutations (100%, p=0.01), and 7 of 8 (88%, p=0.01) were located in the pancreatic body/tail.

Discussion: Despite substantial interobserver agreement among experienced PB-pathologists, a second review is recommended for accurate dysplasia grading in BD-IPMNs due to its impact on patient prognosis and biomarker research validity. Preoperative EUS-nCLE with Kyoto-HRC improves sensitivity for HGD-IC without sacrificing accuracy; however, there is a need to identify additional biomarkers for accurate risk stratification of a distinct subpopulation of BD-IPMNs with micropapillary architecture.



Disclosures:


Matthew Leupold, MD¹, Wei Chen, ¹, Ashwini Esnakula, MBBS¹, Wendy Frankel, MD¹, Stacey Culp, PhD², Phil Hart, MD¹, Ahmed RM. Abdelbaki, MBBCh¹, Zarine K. Shah, MD¹, Erica Park, MD¹, Peter J Lee, MD¹, Mitchell L. Ramsey, MD¹, Sam Han, MD¹, Hamza Shah, MD¹, Jordan Burlen, MD¹, Georgios Papachristou, MD, PhD¹, Zobeida Cruz-Monserrate, PhD¹, Mary Dillhoff, MD¹, Jordan Cloyd, MD¹, Timothy Pawlik, MD¹, Somashekar G Krishna, MD¹. P3464 - Evaluation of Interobserver Agreement in Dysplasia Classification for IPMNs and the Impact on Pre-Surgical Risk Stratification, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.