Clinicopathologic Analysis of Kikuchi-Fujimoto Disease and Etiologic Exploration Using Metagenomic Next-Generation Sequencing

Abstract

Context.— Kikuchi-Fujimoto lymphadenitis, also known as Kikuchi–Fujimoto disease (KFD), is a self-limited lymphoproliferative disease, with no definitive causative agent confirmed by traditional methods. Objectives.— To further explore the clinicopathologic features of KFD and clarify related pathogenic factors. Design.— A retrospective analysis was performed in a collection of KFD cases to review the clinical and histopathologic features, and metagenomics next-generation sequencing (mNGS) was used in 64 formalin-fixed, paraffin-embedded (FFPE) tissues from patients with KFD. Results.— One hundred five of the 170 patients with KFD (61.8%) were female; 10 patients had autoimmune diseases. Four pathologic subtypes were classified: necrotic (45.9%, 78 of 170), phagocytic (32.4%, 55 of 170), proliferative (17.1%, 29 of 170), and xanthomatous (4.7%, 8 of 170). Patients younger than 40 years with unilateral cervical lymphadenopathy and small vessel fibrinous degeneration accounted for significant differences among the 4 pathologic subtypes (P < .05). Among 64 patients with KFD, 9 had detectable bacterial or viral DNA—of 6 bacterial cases, 1 involved Chlamydia psittaci; while of 3 viral cases, 1 involved human beta herpesvirus 6B and 2 involved Epstein-Barr virus. No significant relationships were found between the pathologic subtypes and specific pathogens. Conclusions.— Only a small proportion of patients with KFD had autoimmune diseases or infections from specific pathogens, suggesting that KFD is likely a reactive lesion of lymph nodes to various circumstances. To our knowledge, this is the first and the largest study to detect pathogens with the use of mNGS on FFPE samples in KFD. Our study also further confirms that mNGS can be used on FFPE samples to detect potentially infectious agents in clinical settings.