Lymphadenopathy is frequently observed in patients with immunoglobulin G4-related disease (IgG4-RD) and sometimes appears as the first manifestation of the disease. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity, with at least 5 histological subtypes. Indeed, lymph node biopsy may be performed under the suspicion that the lymphadenopathy is a malignant lymphoma or other lymphoproliferative disorder. The diagnosis of IgG4-RD is characterized by both elevated serum IgG4 (>135？mg/dL) and histopathological features, including a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells (IgG4+/IgG+ plasma cell ratio >40%). However, patients with hyper-interleukin (IL-) 6 syndromes such as multicentric Castleman’s disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD. Owing to these factors, IgG4-RD cannot be differentiated from hyper-IL-6 syndromes on the basis of histological findings alone. Laboratory analyses are crucial to differentiate between the 2 diseases. Hyper-IL-6 syndromes are characterized by elevated serum levels of IgG, IgA, IgM, and C-reactive protein (CRP); thrombocytosis; anemia; hypoalbuminemia; hypocholesterolemia. In contrast, IgG4-RD does not share any of these characteristics. Therefore, the diagnosis of IgG4-RD requires not only pathological findings but also clinical and laboratory analyses. 1. Introduction Immunoglobulin G4-related disease (IgG4-RD) frequently involves lymph nodes in a localized or systemic fashion [1–3]. Indeed, approximately 80% of patients with autoimmune pancreatitis (IgG4-related pancreatitis) has lymphadenopathy, most commonly involving the mediastinal and intraabdominal lymph nodes [4]. Moreover, lymphadenopathy sometimes appears as the first manifestation of IgG4-RD [1–3]. IgG4-RD is an inflammatory condition characterized by a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells; an IgG4+/IgG+ plasma cell ratio of >40% is an important diagnostic criterion for the disease [3, 5]. Patients with IgG4-related lymphadenopathy occasionally show systemic lymphadenopathy and elevated serum levels of IgG4 and IgE, and less often show low titers of various autoantibodies [1–3, 5, 6]. Therefore, the disease often shares clinical characteristics with malignant lymphoma, multicentric Castleman’s disease, and immune-mediated conditions [1–3, 7, 8]. However, the patients often show an excellent response to steroid therapy and do not show the B symptoms
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