IgG4-related Sclerosing Cholangitis With and Without Hepatic Inflammatory Pseudotumor, and Sclerosing Pancreatitis-associated Sclerosing Cholangitis

Abstract

Sclerosing cholangitis (SC) is a heterogeneous disease entity. Different etiologies such as choledocholithiasis, biliary tumor, or pericholangitis can manifest as SC. Hepatic inflammatory pseudotumor (IP) is rarely associated with SC (sclerosing cholangitis associated with hepatic inflammatory pseudotumor; SC-hepatic IP), but sclerosing pancreatitis (SP) is not infrequently associated with bile duct lesions (sclerosing pancreatitis-associated sclerosing cholangitis; SP-SC). In this study, we compared the histologic changes of hepatic hilar and extrahepatic bile duct lesions of SC (7 cases), SC-hepatic IP (5 cases), SP-SC (5 cases), and typical primary sclerosing cholangitis (PSC) (5 cases). Histologically, all SP-SC cases showed extensive and dense fibrosis with marked lymphoplasmacytic infiltration, many eosinophils, and obliterative phlebitis. Four cases of SC showed bile duct lesions similar to those of SP-SC, whereas other three cases of SC showed milder lymphoplasmacytic infiltration, scant eosinophilic cell infiltration, and no obliterative phlebitis. All SC-hepatic IP cases showed bile duct lesions identical to those of SP-SC. Immunohistochemically, many IgG4-positive plasma cells were found in the bile duct lesions of all SP-SC cases, 4 SC cases with marked lymphoplasmacytic infiltration, and all SC-hepatic IP cases. By contrast, IgG4-positive plasma cells were scarce or hardly found in the remaining 3 SC cases and all PSC cases. In conclusion, 4 SC cases and all SC-hepatic IP cases showed bile duct lesions identical to those of SP-SC, suggesting that these three conditions may be a single disease entity. Their pathogenesis may be similar or closely related to that of SP, and in that respect they may represent an IgG4-related biliary disease. They may respond to steroid therapy as SP does.

IgG4-associated cholangitis: a comparative histological and immunophenotypic study with primary sclerosing cholangitis on liver biopsy material

“…Several recent series have described the hepatic manifestations of IgG4-associated cholangitis. 7,[13][14][15][16][17] The involvement of large bile ducts is characterized by a dense transmural inflammatory infiltrate resembling that observed in the pancreas. 7 Three Japanese studies have previously examined the biliary pathology of IgG4-associated cholangitis.…”

“…7,[13][14][15][16][17] The involvement of large bile ducts is characterized by a dense transmural inflammatory infiltrate resembling that observed in the pancreas. 7 Three Japanese studies have previously examined the biliary pathology of IgG4-associated cholangitis. 12,17,18 In the largest series of 16 cases, 12 the authors distinguished five histological patterns of involvement, namely (1) portal inflammation, (2) large duct damage, (3) portal sclerosis with scarce inflammation, (4) lobular hepatitis, and (5) cholestasis.…”

“…[3][4][5] Among these, autoimmune pancreatitis-associated sclerosing cholangitis has recently received significant attention, in part, because of the steroid-responsive nature of this disease. 4,6,7 Similar to manifestations of IgG4-associated disease, autoimmune pancreatitis-associated sclerosing cholangitis shows increased numbers of IgG4-positive plasma cells, justifying the recently suggested nomenclature of IgG4-associated cholangitis. 6 As IgG4-associated cholangitis is a steroid-responsive process, whereas primary sclerosing cholangitis is typically steroid resistant, it is thus vital for management to distinguish IgG4-associated cholangitis from primary sclerosing cholangitis.…”

A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details

“…For example, 73% of patients with AIP have shown wall thickening or sclerosing changes in extrapancreatic bile ducts on endoscopic ultrasonography (EUS) and intraductal ultrasonography (IDUS), though only 26% of patients with AIP demonstrated sclerosing changes by ERCP [37]. However, many individuals without AIP have shown IgG4-related SC with isolated biliary tract involvement [38, 39]. In IgG4-related SC, stenosis is usually observed in the lower part of the common bile duct.…”

Distinct histopathological features of Hashimoto's thyroiditis with respect to IgG4-related disease

“…This disease process was initially recognized in relation to autoimmune pancreatitis in 2001. [3][4][5] Since then, many other IgG4-related lesions similar to autoimmune pancreatitis have been reported all over the world, including retroperitoneal fibrosis, 5 sclerosing cholangitis, 6 sclerosing sialadenitis, 7 tubulointerstitial nephritis, 8 inflammatory pseudotumor, 9,10 and inflammatory aortic aneurysm. 11 IgG4-related disease is characterized by elevated serum IgG4 levels, and in the clinical setting, by the alleviation of symptoms after steroid therapy.…”