ObjectivesRemitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare inflammatory arthritis, with a higher incidence of malignancy. The aim of this study is to identify biomarkers for predicting malignancy in RS3PE.MethodsA total of 51 patients with RS3PE from September 2007 to May 2019 were retrospectively reviewed and followed for up to 5 years, with 15 patients with osteoarthritis (OA) and 14 patients with elderly-onset rheumatoid arthritis (EORA) as disease controls. Serum levels of angiogenesis cytokines were measured by electrochemiluminescent immunoassay and Luminex Human Magnetic Assay. Clinical data and laboratory parameters were analyzed to identify risk factors for malignancy.ResultsA total of forty-eight RS3PE patients (94.1%) were available with follow-up data, 8 patients (16.7%) were diagnosed with malignancy, of which 6 patients were hematological tumor, and 2 patients were solid tumor. Serum levels of basic fibroblast growth factor (bFGF) were exclusively higher in RS3PE patients with malignancy [14.21 (7.52, 23.18) ng/mL] than RS3PE patients without malignancy [4.32 (2.88, 7.42) ng/mL], OA [3.20 (2.20, 5.30) ng/mL] and EORA [3.20 (2.20, 5.30) ng/mL]. The optimal cut-off value of bFGF for malignancy was 10ng/mL in RS3PE. Logistic regression analysis indicated that elevation of bFGF was a risk factor for malignancy in RS3PE.ConclusionsThis study indicated that bFGF was elevated in RS3PE patients with malignancy and could serve as a biomarker for predicting paraneoplastic RS3PE.