Flow Cytometry Signature for Kikuchi-Fujimoto/Lupus Lymphadenitis Derived From 975 Benign and Malignant Lymphadenopathies

Abstract

Abstract Introduction Kikuchi lymphadenitis is a benign disease with histologic features that can be challenging to discern from malignant or infectious diagnoses. Furthermore, Kikuchi lymphadenitis and systemic lupus erythematosus–associated lymphadenitis (KD/SLE) show overlapping histologic features. We used flow cytometry to evaluate if KD/SLE has a distinct immunophenotype from other lymphadenopathies. Methods and Materials Sixteen cases of KD/SLE were compared to 959 control cases at Stanford by flow cytometry for three scenarios: KD/SLE versus T-cell lymphomas, all benign cases, and all benign and malignant cases. Select cases of KD/SLE and benign lymph nodes were analyzed by immunohistochemistry to evaluate the B-cell characteristics. A test set of five KD cases were compared to five normal controls from an independent institution to evaluate cross-platform reproducibility of the KD/SLE flow cytometry signature. Results The most discriminatory signature for KD/SLE versus all other benign cases comprised two surface antigen pairs (high CD38+ CD19+, low large-cell CD57+ CD3+), patient age, lymph node location, and four additional flow antigens (100% sensitivity, 99.6% specificity). The signature for KD/SLE versus T-cell lymphomas consisted of two flow antigens (high CD38+ CD19+ and high CD3) and patient age (100% sensitivity, 100% specificity). Based on the flow data, immunohistochemistry was performed to evaluate the B-cell characteristics. We observed clusters of IgD-positive B cells surrounding activated T-cell foci without IgM expression, suggesting that these cells represent either naive cells or memory IgD-positive B cells. Flow cytometry showed increased CD23 with minimal CD5 expression, supporting the hypothesis of naive functional anergic/autoreactive IgD+ IgM– B cells. Conclusion We have identified a signature that can distinguish Kikuchi disease and systemic lupus erythematosus from a large cohort of benign and malignant entities, likely reflecting a shared stable underlying etiology of KD/SLE. Our study provides a valuable tool to enhance the ability to accurately diagnose KD/SLE.