Diagnostic Value of Lymph Node Biopsy in Adult Patients with Classic Fever of Unknown Origin Accompanied by Lymphadenopathy

Background: Lymph node biopsy is an important means of etiologic diagnosis for patients with fever of unknown origin (FUO) and lymphadenopathy. However, it is an invasive procedure and may yield negative results. It is worth exploring which kinds of patients could benefit most from lymph node biopsy. Methods: FUO patients (n = 242) who had lymphadenopathy and underwent lymph node biopsy were enrolled into this retrospective single-center study. Clinical manifestations were documented and risk factors suggestive of an underlying positive lymph node biopsy (providing diagnostic clues) and lymphoma were analyzed. Results: The etiologies were as follows: infectious disease in 10 (4.1%) cases, connective tissue diseases in 51 (21.1%) cases, neoplastic diseases in 57 (23.6%) cases, other diseases in 28 (11.6%) cases, and unknown diagnosis in 96 (39.7%) cases. A total of 88 patients (36.4%) were diagnosed through lymph node biopsy. The following four independent risk factors were found to be related to positive lymph node biopsy: male gender (OR 2.471; 95% CI 1.158–5.270; p = 0.019), no rash (OR 3.531; 95% CI 1.595–7.816; p = 0.002), shape index of the lymph node (OR 8.566; 95% CI 1.035–70.915; p = 0.046), and hypoalbuminemia (OR 3.370; 95% CI 1.470–7.728; p = 0.004). Later, 146 patients with a confirmed diagnosis (including 57 cases of lymphoma and 89 cases of non-lymphoma) were included in the analysis of lymphoma-related factors. Age older than 45 years (OR 8.663; 95% CI 3.045–24.647; p < 0.001), no rash (OR 4.946; 95% CI 1.646–14.859; p = 0.004), serositis (OR 3.588; 95% CI 1.137–11.318; p = 0.029), abnormal blood flow of the lymph node (OR 3.025; 95% CI 1.034–8.848; p = 0.043), abnormal central lymph nodes (OR 6.546; 95% CI 1.721–24.898; p = 0.006), focal lesions in the spleen (OR 13.386; 95% CI 2.067–86.706; p = 0.006), and serum lactate dehydrogenase (LDH) > 250 U/L (OR 3.885; 95% CI 1.111–13.584; p = 0.034) were independent risk factors for lymphoma. Conclusions: Lymph node biopsy is a valuable diagnostic procedure for patients with FUO and lymphadenopathy. For male patients without rash, more rounded lymph nodes, and hypoalbuminemia, we strongly recommend lymph node biopsy. Age older than 45 years, no rash, serositis, abnormal blood flow of the lymph node, abnormal central lymph nodes, focal lesions in the spleen, and serum LDH > 250 U/L are risk factors suggesting an underlying lymphoma, and multi-site biopsy should be considered if necessary.