Immunoglobulin G4-related hepatobiliary disease

Immunoglobuline G4-related disease (IgG4-RD) is a systemic disease that can involve virtually any organs including the biliary tract and liver. The biliary tract involvement of IgG4-RD is known as IgG4-sclerosing cholangitis (IgG4-SC) and may or may not present with an inflammatory pseudotumor. Large bile ducts such as extrahepatic, hilar, and perihilar ducts are typically affected and demonstrate marked bile duct wall thickening and develop strictures. Histologically, the involved ducts show transmural dense lymphoplasmacytic infiltrates with storiform fibrosis extending into peribiliary glands and periductal soft tissue. The luminal epithelium is usually preserved. Tissue eosinophilia and obliterative phlebitis are also frequently noted. Liver biopsy findings of IgG4-SC are heterogeneous and rather nonspecific, but two features specific to IgG4-SC have been described: >10 IgG4-positive plasma cell/HPF and small portal-based fibroinflammatory nodules. Secondary changes, due to downstream bile duct obstruction are often appreciated. When considering the differential diagnosis, primary sclerosing cholangitis and cholangiocarcinoma are great clinical and histologic mimics of IgG4-SC. Liver involvement in IgG4-RD has not been well characterized and includes IgG4-hepatopathy and IgG4-related autoimmune hepatitis (AIH). IgG4-hepatopathy is a generic term covering hepatic lesions related to IgG4-RD and /or IgG4-SC. It includes primary liver parenchymal changes inherent to IgG4-RD, liver parenchymal involvement of IgG4-SC, and secondary changes related to IgG4-SC. IgG4-related AIH is characterized by clinical and histologic features of classical AIH but with prominent (>10/HPF) IgG4-positive plasma cells. It is unclear whether this represents a hepatic manifestation of IgG4-RD or a subset of AIH with increased IgG4-positive plasma cells at the present time. Synchronous or metachronous involvement of other organs, offers a clue to make this distinction. IgG4 immunohistochemistry has an important role in diagnosing IgG4-RD. But the diagnosis cannot be made solely based on the number of IgG4-positive plasma cells, and results need to be interpreted with caution as increased IgG4-positive plasma cells can be seen in other inflammatory conditions or even in malignancy.