Histology-Independent Signature Distinguishes Kikuchi-Fujimoto Disease/Systemic Lupus Erythematosus-Associated Lymphadenitis From Benign and Malignant Lymphadenopathies

Am J Clin Pathol. 2020 Jul 7;154(2):215-224. doi: 10.1093/ajcp/aqaa036.

Abstract

Objectives: Kikuchi-Fujimoto disease (KFD) and systemic lupus erythematosus (SLE) are benign entities with histologic features that raise concern about malignancy and infection. We searched for a histology-independent KFD/SLE signature relying on only immunophenotype and basic clinical characteristics.

Methods: A histology-independent KFD/SLE signature was generated using 975 excised lymph nodes with flow immunophenotyping, including 16 cases of KFD/SLE. This signature was then evaluated in 1,198 fine-needle aspiration (FNA) specimens.

Results: The top flow cytometry discriminant for KFD/SLE was uniform CD38+ expression on CD19+ events. Immunohistochemistry demonstrated nodules of IgD+, IgM- B cells surrounding necrotizing and activated T-cell areas. A signature combining 6 flow cytometry criteria with age and sample site had a positive predictive value of 88% for KFD/SLE, which had a prevalence of 1.6%. All 4 signature-positive FNA cases with follow-up excision were KFD/SLE. At a second institution, 4 of 5 KFD/SLE cases passed the top discriminant.

Conclusions: A flow cytometry signature combined with age and biopsy site identifies KFD/SLE independent of histology, suggesting a shared immune composition and independently confirming that KFD/SLE represents a distinct entity. Unexpectedly, an IgD+CD38+ small B-cell population is a distinctive feature of KFD/SLE, suggesting a possible pathologic role for anergic/autoreactive B cells.

Keywords: Flow cytometry; Histiocytic necrotizing lymphadenitis; Kikuchi-Fujimoto disease; Lymph node.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry
  • Histiocytic Necrotizing Lymphadenitis / diagnosis*
  • Histiocytic Necrotizing Lymphadenitis / pathology
  • Humans
  • Immunophenotyping
  • Lupus Erythematosus, Systemic / pathology*
  • Lymph Nodes / pathology*
  • Lymphadenitis / diagnosis*
  • Lymphadenitis / pathology
  • Lymphadenopathy / diagnosis*
  • Lymphadenopathy / pathology
  • Male