Supplementary Material for: Systematic Review and Meta-Analysis of the Diagnostic Accuracy of the World Health Organization International System for Reporting Pancreatic Cytopathology

Introduction
The World Health Organization (WHO), in collaboration with the International Academy of Cytology and the International Agency for Research on Cancer, has introduced a standardized reporting system for pancreatic cytopathology. This system refines diagnostic categories, integrates malignancy risk estimates, and aligns with the WHO Classification of Tumours. It builds on the Papanicolaou Society of Cytopathology framework, improving risk stratification through categories such as pancreatic neoplasm-low risk/grade (PaN-Low) and pancreatic neoplasm-high risk/grade (PaN-High). This study evaluates the diagnostic accuracy of fine-needle aspiration biopsy (FNAB) for pancreatic lesions using the WHO system.
Methods
A systematic literature search was performed in the PubMed and EMBASE databases, using predefined keywords- “pancreas”, “FNAB”, and “diagnostic accuracy”. Meta-analysis was conducted to determine sensitivity and specificity at different diagnostic thresholds: “PaN-High considered positive,” “Suspicious for Malignancy considered positive,” and “Malignant considered positive,” excluding inadequate samples from each study. To assess diagnostic accuracy, summary receiver operating characteristic curves were generated, and the diagnostic odds ratio (DOR) was pooled.
Results
Five studies met the inclusion criteria. The risk of malignancy ranged from 3% (Negative) to 99% (Malignant). Sensitivity and specificity varied across cut-offs: Malignant (83%, 100%), Suspicious and above (92%, 98%), and PaN-High and above (93%, 96%). DOR values confirmed high diagnostic accuracy.
Conclusion
The system effectively stratifies lesions based on malignant potential, with the “Suspicious” and “Malignant” categories demonstrating high predictive value. Expanding the diagnostic threshold to include “PaN-High” further improves sensitivity without significantly compromising specificity, making it a valuable classification for clinical practice.