Objective: To analyze the clinical characteristics of malignant lymphoma that closely resembles IgG4-related disease (IgG4-RD).

Methods: This study retrospectively analysis involving 31 patients who were lymphoma mimicking, IgG4-RD and 50 contemporaneous IgG4-RD patients serving as controls. Lymphoma mimicking IgG4-RD was defined as presenting with masses in the typical sites of IgG4-RD, with or without elevated serum IgG4 levels, and ultimately confirmed to be lymphoma. The clinical data, including the extent of lymph node involvement, maximum diameter of lymph nodes, systemic symptoms, and laboratory parameters were assessed. Student's t-test, the Mann-Whitney test, and the chi-squared test were used to compare the two groups.

Results: Fever emerged as a distinctive feature in lymphoma patients. Compared to IgG4-RD, lymphoma patients exhibited a greater extent of lymph node involvement (p < 0.001), larger maximum diameters of lymph nodes (p = 0.007), and higher frequency of enlargement in supraclavicular (41.9% vs 10.0%; p = 0.001), armpit (45.2% vs 16.0%; p = 0.004), retroperitoneal (70.9% vs 10.0%; p < 0.001), and groin lymph nodes (41.9% vs 8.0%; p < 0.001). In contrast, IgG4-RD patients were more likely to show involvement of submandibular gland (58.0% vs 29.0%; p = 0.015) and pancreatic (44.0% vs 9.7%; p = 0.001). Additionally, lymphoma patients presented with higher levels of erythrocyte sedimentation rate (ESR) (p = 0.010), C-reactive protein (CRP) (p < 0.001), and lactate dehydrogenase (LDH) (p = 0.002), along with a higher prevalence of anemia (35.5% vs 4.0%; p < 0.001) and lower albumin levels (p = 0.039), while IgG4-RD patients had higher IgG4/IgG ratio (p < 0.001) and lower complement 3 (C3) (p = 0.009) levels than lymphoma patients.

Conclusions: Although patients with malignant lymphoma and IgG4-RD share some overlapping presentations, they differ significantly in some distinct features, including fever, pattern of lymph node and organ involvement distribution, and some laboratory parameters. Key Points • IgG4-related disease (IgG4-RD) is an immune-mediated disorder characterized by elevated serum IgG4 levels, presenting lymphadenopathy and tumor-like sclerosing lesions in extranodal sites. • Lymphoma, a malignancy that originates from lymphocytes, can present with a variety of clinical manifestations, including painless swelling of lymph nodes and enlargement of different organs. • While patients with malignant lymphoma and IgG4-RD share certain overlapping clinical presentations, they exhibit significant differences in distinct features, including fever, patterns of lymph node and organ involvement, and various laboratory parameters.