IgG4-related lymphadenopathy

IgG4-related lymphadenopathy is a nodal manifestation of IgG4-related disease (IgG4RD) which is characterized by increased polytypic IgG4+ plasma cells and IgG4+/IgG+ plasma cell ratio in lymph nodes and morphologically manifested as various patterns of reactive lymphadenopathy: Castleman disease-like, follicular hyperplasia, interfollicular expansion, progressive transformation of germinal centers and inflammatory pseudotumor-like. It typically presents with solitary or multiple, mild to moderate lymph node enlargement in otherwise asymptomatic patients. The serum IgG4 level is frequently elevated but C-reactive protein often remains normal. In patients not having a history of IgG4RD or manifestation of extranodal IgG4RD, a diagnosis of IgG4-lymphadenopathy should only be made with great caution given the non-specific morphologic features that can overlap with ANCA-associated vasculitis, interleukin-6 syndromes, Rosai-Dorfman disease, inflammatory myofibroblastic tumor, syphilis, lymphoma, and plasma cell neoplasia. Elevated IgG4 parameters, appropriate morphologies, and clinical correlation are essential to make the diagnosis of IgG4-lymphadenopathy more specific and clinically meaningful.