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

Mod Pathol. 2009 Oct;22(10):1287-95. doi: 10.1038/modpathol.2009.94. Epub 2009 Jul 24.


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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoimmune Diseases / complications*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Biopsy, Needle
  • Cholangiopancreatography, Magnetic Resonance
  • Cholangitis / immunology*
  • Cholangitis / pathology
  • Cholangitis / therapy
  • Cholangitis, Sclerosing / immunology*
  • Cholangitis, Sclerosing / pathology
  • Cholangitis, Sclerosing / therapy
  • Diagnosis, Differential
  • Female
  • Hepatectomy
  • Humans
  • Immunoglobulin G / blood*
  • Immunohistochemistry
  • Immunophenotyping
  • Liver / immunology*
  • Liver / pathology
  • Liver / surgery
  • Male
  • Middle Aged
  • Pancreatitis / complications*
  • Pancreatitis / immunology
  • Pancreatitis / pathology
  • Plasma Cells / immunology
  • Predictive Value of Tests
  • Steroids / therapeutic use


  • Immunoglobulin G
  • Steroids