Clinical characteristics of lymphoma patients presenting with fever of unknown origin misdiagnosed with connective tissue diseases

Recognizing and diagnosing lymphoma in patients with fever of unknown origin (FUO) can be challenging, and misdiagnosis is not uncommon. To improve understanding of the clinical characteristics of lymphoma patients presenting with FUO who were misdiagnosed with autoimmune diseases. A retrospective, observational study of 140 consecutive patients with FUO and lymphoma presenting to a tertiary center between January 2017 and December 2023. Patients were divided into those who were correctly diagnosed and those misdiagnosed as connective tissue diseases (CTD) and the clinical features compared. Of 140 lymphoma patients with FUO, 21 patients (15.0%) were misdiagnosed as CTD. The median time between symptom onset and diagnosis was significantly longer in the misdiagnosed group than in the non-misdiagnosed group (11.0 (IQR 6.0, 22.5) months vs. 4.0 (2.5, 9.0) months; p = 0.001). The misdiagnosed group had significantly less lymph node and bone marrow involvement and more skin rashes than the non-misdiagnosed group (47.6% vs. 70.6%, p = 0.039; 23.8% vs. 47.9%, p = 0.040; 47.6% vs. 25.2%, p = 0.036), as well as significantly lower ESR (p = 0.026) and hsCRP (p = 0.049). The misdiagnosed group had higher frequency of ANA/ANCA (57.1% vs. 27.7%; p = 0.008) and anti-phospholipid antibody (42.9% vs. 6.1%; p = 0.008) positivity. The distribution of lymphoma subtypes was different between groups (p = 0.058). Lymphoma patients with an atypical presentation and FUO suggesting inflammatory systemic disease are easily misdiagnosed. Autoantibody positivity is not rare in lymphoma patients with an atypical presentation and FUO, so close follow-up and repeated histopathological examination may be helpful to establishing a correct diagnosis.