IgG4 plasma cells in hematopathology: beyond IgG4-related disease

IgG4 plasma cells are well-known in the context of IgG4-related disease (IgG4-RD). Meanwhile, their role in other disorders remains enigmatic. In hematopathology practice, the presence of these cells can be non-specific in reactive lymphadenopathy, requiring clinicopathological correlation to exclude IgG4-RD. A high density of IgG4 plasma cells may help distinguish progressive transformation of germinal centers from early nodular lymphocyte-predominant Hodgkin lymphoma. IgG4 plasma cells are also present in a subset of classic Hodgkin lymphomas, particularly the nodular sclerosis subtype. Despite their morphological similarities, Rosai-Dorfman disease and IgG4-RD appear to be distinct entities. Idiopathic multicentric Castleman disease and IgG4-RD can be histologically indistinguishable, which necessitates clinical and laboratory differentiation. Marginal zone lymphoma and, rarely, myeloma can express IgG4, with some cases of marginal zone lymphoma having concurrent IgG4-RD. This review provides a comprehensive analysis of IgG4 plasma cells in hematopathology and discusses their diagnostic significance and associated challenges.