Clinicopathological Features of Kikuchi-Fujimoto Disease: Retrospective Observational Study

Introduction:

Kikuchi-Fujimoto disease (KFD), is a rare inflammatory disease of unknown etiology, typically presenting with transient fever and cervical lymphadenopathy. It is recently classified as a tumor-like lesion in the World Health Organization Classification 5^th Edition. There are few large-scale studies on patient demographics and clinical course. This study aims to report detailed clinicopathological features of KFD.

Methods:

We reviewed 112 cases of KFD diagnosed at Okayama University Department of Pathology and Oncology, Okayama, Japan between 2012 and 2022. Patients who were diagnosed with autoimmune diseases or bacterial/tuberculous lymphadenitis after the initial presentation as KFD were excluded.

Results:

The average age of the included cases was 29.4 years (range:6 to 77 years) with slight female predominance (n = 51/115, 44.3% for male; n = 61/115, 53.0% for female). For the included cases of 30 years or older, there were more females than males. The cervical lymph nodes were the most commonly affected sites (85%). For the 70 patients who had complete follow-up data available in the electric medical records, the recurrence rate was 23%, without a difference between males and females. Laboratory tests demonstrated significantly lower complement 4 (C4) levels (p = 0.038) and a higher rate of positive antinuclear antibodies (p = 0.007) in the relapsed cases than in the cases without documented recurrence. The mean number of days prior to confirm the diagnosis was 71.5 days. Among the representative lymph node histology classification, proliferative type was the most common (n = 75; 77%), followed by necrotizing (n = 22; 22%), and xanthomatous (n = 1; 1%). The patients with necrotizing type had significantly enlarged lymph nodes (p = 0.047) and longer duration of symptoms (p = 0.009) compared to the proliferating type.

Discussion:

The present study provides data from a large KFD cohort to provide comprehensive clinicopathological information to date. While KFD is known to predominantly affect female, there were considerably more males up to age 30 than females, Being young and adolescent male KFD patients was associated with atypical features. Future studies are warranted to confirm the findings noted in the results, to clarify clinicopathological differences in the male young adolescent KFD, and further characterize the classical female KFD cases, including histological features, treatment responses, and association with autoimmune or malignant hematology conditions.

Conclusion:

In this study, we analyzed a large number of KFD cases and clarified characteristics. The comprehensive clinicopathological features provided by the present results may be useful in elucidating the pathogenesis and predicting the clinical course of such clinically challenging cases, including association with autoimmune diseases and its long-term outcomes.

Habermann:Lilly: Other: Data Monitoring Committee. Dispenzieri:Alnylam: Research Funding; Takeda: Consultancy, Research Funding; Janssen: Research Funding; HaemaloiX: Research Funding; Pfizer: Research Funding; BMS: Consultancy, Research Funding; Alexion: Consultancy, Research Funding.