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. 2025 Aug 9;20(1):92.
doi: 10.1186/s13000-025-01695-2.

Clinical analysis of histiocytic necrotizing lymphadenitis in adults with fever of unknown origin: a retrospective study

Nana Xie  1 , Wencong Zhang  1 , Fangbing Tian  1 , Jia Chen  1 , Wenyuan Zhang  1 , Qiurong Ruan #  2 , Jianxin Song #  3
Affiliations

Clinical analysis of histiocytic necrotizing lymphadenitis in adults with fever of unknown origin: a retrospective study

Nana Xie et al. Diagn Pathol. .

Abstract

Purpose: To comprehensively analyze the clinical data of histiocytic necrotizing lymphadenitis (HNL) in adults with fever of unknown origin (FUO), with the aim of enabling precise diagnosis.

Patients and methods: A total of 15 HNL patients with FUO were enrolled. The analysis encompassed clinical manifestations, laboratory parameters 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) imaging profiles, pathological features and therapeutic responses.

Results: All patients presented with fever and lymphadenopathy (predominantly cervical). Laboratory findings included leukopenia (3.28 × 10⁹/L [2.40-4.97]), elevated LDH (306 U/L [187-524]), ESR (40 mm/h [30-51]), ferritin (457.1 ng/mL [206-1823.3]), and CRP (25 mg/L [6.1-34.8]) 18F-FDG PET/CT detected metabolic lymph node abnormalities in 13 cases, primarily cervical and axillary. The pathological features were extensive coagulative necrosis of lymph nodes with reactive hyperplasia of histiocytes as well as positive or scattered positivity IHC CD3, CD4, CD8 and CD68. Corticosteroid achieved favorable responses, with only 2 cases progressing during follow-up.

Conclusion: In clinical practice, patients with fever and lymphadenopathy should be given due attention. Pathological examination remains the gold standard for diagnosing HNL. Glucocorticoid therapy has proven effective, and the majority of patients with HNL exhibit a favorable prognosis.

Keywords: 18F-FDG PET/CT; Clinical manifestations; Fever of unknown origin; Histiocytic necrotizing lymphadenitis; Pathological features.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This research adhered to the Declaration of Helsinki principles and was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-IRB20230425). Given its retrospective design, the committee waived informed consent.The study involved no personal identifying info, posed minimal risk to subjects, and couldn’t proceed with consent requirements. The researcher replaced personal info with anonymous identifiers to ensure confidentiality and used aggregate data for publication and presentation to protect subjects’ privacy. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
A 26-year-old female was admitted with fever for 14 days. Pathological results of the left axillary lymph node showed the necrotic stage of HNL by H&E staining. The necrotic foci were distributed in patches, and a large number of nuclear fragments could be seen within the necrotic foci and no neutrophils were observed (40 times, A; 200 times, B). Perilesional tissue exhibits reactive hyperplasia, characterized by proliferating histiocytes, immunoblasts, and lymphocytes. (40 times, C; 200 times, D)
Fig. 2
Fig. 2
Pathological IHC profiling of HNL in lymph node tissue. CD8-positive cytotoxic T lymphocytes showed dense infiltration surrounding necrotic lesion (40 times, A; 200 times, B). CD68-expressing histiocytes were prominently proliferated adjacent to necrosis (40 times, C; 200 times, D). Focal histiocytes exhibited weak MPO immunostaining (40 times, E; 200 times, F)
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