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

IgG4-associated cholangitis is a steroid-responsive hepatobiliary inflammatory condition associated with autoimmune pancreatitis that clinically and radiologically mimics primary sclerosing cholangitis. In this study, we conducted a morphological and immunohistochemical analysis of liver material obtained from individuals with IgG4-associated cholangitis, and compared these with well-characterized cases of primary sclerosing cholangitis. The study group consisted of 10 patients ( 9 biopsy and 1 hepatectomy case) with IgG4-associated cholangitis and 17 patients with primary sclerosing cholangitis ( 16 needle biopsy and 1 hepatectomy case). All patients with IgG4-associated cholangitis had pancreatic involvement as well, and six pancreatectomy samples revealed characteristic histopathological features of autoimmune pancreatitis. Primary sclerosing cholangitis cases were defined by the presence of a characteristic ERCP appearance. Clinical, pathological, radiological, and follow-up data were recorded for all cases. Portal and periportal inflammation was graded according to Ishak's guidelines. Immunohistochemical stains for IgG and IgG4 were performed. The cohort of patients with IgG4-associated cholangitis ( mean age: 63 years) was older than individuals with primary sclerosing cholangitis ( mean age: 44 years). Seven of these cases showed intrahepatic biliary strictures. IgG4-associated cholangitis liver samples showed higher portal (P = 0.06) and lobular (P = 0.009) inflammatory scores. Microscopic portal-based fibro-inflammatory nodules that were composed of fibroblasts, plasma cells, lymphocytes, and eosinophils were exclusively observed in five of the IgG4-associated cholangitis cases (50%). More than 10 IgG4-positive plasma cells per HPF ( high power field) were observed in 6 of the IgG4-associated cholangitis cases ( mean: 60, range: 0-140 per HPF), whereas all primary sclerosing cholangitis cases showed significantly lesser numbers ( mean: 0.08, range: 0-1 per HPF). On a liver biopsy, the histological features of IgG4-associated cholangitis may be distinctive, and in conjunction with IgG4 immunohistochemical stain, may help distinguish this disease from primary sclerosing cholangitis. Modern Pathology ( 2009) 22, 1287-1295; doi: 10.1038/modpathol.2009.94; published online 24 July 2009