Ki-67 Proliferation Index in Lymphoma Subtypes: Immunohistochemical Analysis With Clinicopathological Correlations and Prognostic Implications

Background: The Ki-67 proliferation index (PI) is a well-established marker of tumor growth activity in lymphomas.Despite its diagnostic utility, standardized cutoff values and subtype-specific reference ranges remain poorly defined.This study evaluated Ki-67 expression across major lymphoma subtypes and its ability to discriminate between lymphoma groups of different biological behavior.Methods: A retrospective cross-sectional study was conducted on 87 confirmed lymphoma cases retrieved from the pathology archives of hospitals in Al-Madinah Al-Munawwarah, Saudi Arabia.Immunohistochemistry using the MIB-1 monoclonal antibody was performed on formalin-fixed paraffin-embedded (FFPE) tissue.Ki-67 PI was assessed by manual counting of at least 500 tumor cells in hot-spot areas.Statistical analyses included the Kruskal-Wallis test, Mann-Whitney U test, chi-square test, and receiver operating characteristic (ROC) curve analysis.Results: The cohort comprised 87 cases: diffuse large B-cell lymphoma (DLBCL) (n = 27, 31.0%),follicular lymphoma (FL) (n = 16, 18.4%), Hodgkin lymphoma (HL) (n = 13, 14.9%), mantle cell lymphoma (MCL) (n = 10, 11.5%), T-cell lymphomas (TCL) (n = 9, 10.3%), marginal zone/other indolent B-cell lymphomas (MZL) (n = 7, 8.0%), and Burkitt lymphoma (BL) (n = 5, 5.7%).Mean Ki-67 PI differed significantly across subtypes (p<0.001):BL (92.4 ± 4.2%), TCL (71.8 ± 18.3%), DLBCL (68.5 ± 16.7%), HL (52.3 ± 14.6%), MCL (38.6 ± 22.4%), FL (28.7 ± 15.8%), and MZL (22.3 ± 11.6%).For ROC analysis, HL was analyzed as a separate intermediate-behavior group, with the aggressive group comprising DLBCL, BL, and TCL (n = 41) and the indolent group comprising FL, MCL, and MZL (n = 33).A Ki-67 cutoff of 40% showed good discriminatory ability (area under the ROC curve (AUC) = 0.87, sensitivity = 92.7%,specificity = 75.8%).Conclusion: Ki-67 PI demonstrates meaningful variation across lymphoma subtypes.A cohort-derived cutoff of 40% showed good discrimination between the predefined aggressive and indolent non-Hodgkin lymphoma (NHL) groups, although it should be regarded as exploratory.Standardized Ki-67 assessment may support routine lymphoma diagnostics, with application of subtype-specific thresholds once diagnosis is established, pending external validation and wider methodological harmonization across laboratories.