Nomogram-based pathological diagnosis and differential diagnosis of ocular disorders with IgG4-positive plasma cells and lymphoid hyperplasia

Certain orbital diseases characterized by lymphoproliferative lesions with IgG4-positive plasma cells include IgG4-related ophthalmic disease (IgG4-ROD), MALT lymphoma, inflammatory pseudotumor, and reactive lymphoid hyperplasia. Diagnostic challenges arise when distinguishing IgG4-ROD from MALT lymphoma, especially when IgG4-positive MALT lymphoma of the ocular adnexa shows a high density of IgG4-positive plasma cells (> 50/HPF) and B-cell clonality testing produces limited or equivocal results. To enhance diagnostic support for entities presenting these overlapping histomorphological features, this study aimed to develop a comprehensive diagnostic model that integrates clinical features, histopathological patterns, and immunohistochemical markers to assist in the initial differentiation of ocular adnexal MALT lymphoma from IgG4-ROD and to help identify cases that may require further clinical evaluation. This retrospective study included 184 patients with lymphoproliferative lesions featuring IgG4-positive plasma cells. Data were randomly split into training and internal validation cohorts at a 7:3 ratio. A multinomial logistic regression model was constructed and visualized as a pathology-oriented nomogram. Model performance was assessed using ROC curves, calibration curves, and decision curve analysis. Multivariate multinomial logistic regression analysis identified the IgG4+/IgG+ ratio, MNDA expression, and lymphoid proliferation pattern as core predictors for disease classification. Multi-class ROC analysis revealed excellent discriminatory performance: in the training cohort, the area under the curve (AUC) values for Type 1, 2, and 3 were 0.998 (95% CI: 0.995–1.000), 0.970 (95% CI: 0.944–0.990), and 0.975 (95% CI: 0.953–0.993), respectively. The corresponding AUC values in the validation cohort were 0.998 (95% CI: 0.992–1.000), 0.963 (95% CI: 0.917–0.991), and 0.935 (95% CI: 0.870–0.979). The nomogram showed strong discriminatory performance among IgG4-positive plasma cell-associated ophthalmic diseases with lymphoid hyperplasia in the present cohort and may serve as a useful adjunctive tool to support initial clinicopathological differential diagnosis.