Lymph node biopsy confirmed histiocytic necrotizing lymphadenitis in all 15 patients with fever of unknown origin, despite imaging findings that suggested lymphoma or infection in most cases. All patients improved with corticosteroid therapy, and recurrence was uncommon during follow-up.
Researchers analyzed 15 adults with fever of unknown origin (FUO) at Tongji Hospital, Wuhan, China, between 2014 and 2021. All presented with fever lasting an average of 36 days and lymphadenopathy, most frequently cervical. Positron emission tomography/computed tomography (PET/CT) detected hypermetabolic lymph nodes in 13 patients, mainly cervical and axillary, with splenic hypermetabolism in 5 cases and bone marrow involvement in 2. Based on imaging, clinicians suggested lymphoma in 5 cases, infectious disease in 3, and other diagnoses in 5, with only 1 case correctly suspected as possible histiocytic necrotizing lymphadenitis (HNL).
Laboratory testing showed leukopenia in 60%, anemia in 47%, and thrombocytopenia in 13%. Inflammatory markers were elevated in most cases: erythrocyte sedimentation rate in 93%, C-reactive protein in 60%, and serum ferritin in 80%. Procalcitonin was elevated in nearly 90%.
Biopsies showed disrupted lymph node architecture with coagulative necrosis, karyorrhectic debris, and reactive histiocytes but no neutrophils. Immunohistochemistry demonstrated positivity for T-cell markers and histiocyte marker CD68. Epstein–Barr virus testing was negative in all evaluated samples.
“The absence of neutrophil infiltration in HNL, as observed in our pathological examinations, is a key histopathological feature that can be conducive to differentiate it from other inflammatory or neoplastic conditions,” wrote lead study author Nana Xie, MD, of the Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, and colleagues.
Prior to diagnosis, all patients had received antibiotics. Once HNL was confirmed, patients were treated with corticosteroids, and 3 also received intravenous immunoglobulin. All improved and were discharged. During at least 3 years of follow-up, 1 patient experienced recurrent HNL, and 1 developed systemic lupus erythematosus with positive autoantibodies.
Patients met criteria for FUO, defined as fever above 38.3 °C lasting at least 3 weeks with no cause identified after multiple evaluations. HNL was confirmed histologically according to the 2024 World Health Organization classification.
The researchers noted the study was limited by its single-center design and small sample size. They recommended additional research to identify clinical markers that could assist in earlier FUO diagnosis.
The study reported no funding and no competing interests.
Source: Diagnostic Pathology