IgG4-related disease is a multi-organ immune-mediated chronic fibroinflammatory condition characterized by elevated serum
IgG4 concentrations, tumefaction, and tissue infiltration by IgG4-positive plasma cells. The exact etiology of
IgG4-related disease remains unclear with no known role of the
IgG4 molecule itself being identified. Although the pancreas and salivary glands are the main organs affected, the involvement of other organs has also been reported. This multi-organ disease mimics a large number of malignant, infectious, and inflammatory disorders; therefore, a prompt differential diagnosis is important for selecting the right therapeutic strategy. Early
steroid therapy assists in preventing tissue
fibrosis, parenchymal extinction, and severe functional impairments in the affected organs. The definitive and prompt diagnosis of
IgG4-related disease requires both histopathological confirmation and clinicopathological correlations. A histopathological examination is mandatory to exclude neoplastic or inflammatory conditions that mimic
IgG4-related disease. The histological changes that occur are basically similar in any organ manifestation, with several site-specific findings being recognized. This chapter summarizes general rules for the pathological examination of
IgG4-related disease, as well as the histopathological features and differential diagnoses of major organ manifestations.