Development and clinical application of a histopathology-based pathological scoring system for IgG4-related disease

IgG4-related disease (IgG4-RD) diagnosis remains challenging due to subjective histopathological interpretation. This study aimed to develop and internally evaluate a quantitative pathological scoring system to improve diagnostic accuracy. We retrospectively reviewed 96 patients with marked lymphoplasmacytic infiltration diagnosed between 2012 and 2024, classified as IgG4-RD (n = 47) or non-IgG4-RD (n = 49) according to the 2019 ACR/EULAR criteria. Eight histopathological parameters were quantified, including IgG4⁺/CD138⁺ ratio, IgG4⁺ plasma cell count/high-power field, storiform fibrosis, obliterative venulitis, perineural inflammation, tertiary lymphoid structures, nerve bundles, and eosinophilic infiltration. Mann-Whitney U test, ROC curve analyses, subgroup analyses, and calibration curve were performed. A weighted scoring system was constructed based on parameter diagnostic performance. Significant intergroup differences were observed in all parameters except lymphoplasmacytic infiltration (all P < 0.05). The 12-point scoring system (≥5.5-point threshold) demonstrated excellent diagnostic accuracy (AUC 0.996, 95% CI: 0.988-1.000), with 95.74% sensitivity and 100.00% specificity. A simplified four-parameter version achieved an AUC of 0.994 (0.986-1.000), sensitivity 93.62%, and specificity 100.00%. This novel histopathology-based scoring system provides a standardized, reproducible tool for IgG4-RD diagnosis, enhancing objectivity and consistency in pathological assessment, and serves as a valuable complement to existing diagnostic frameworks for routine clinical practice.