IgG4-positive plasma cells can be elevated in malignant hepato-biliary and pancreatic diseases and do not allow discrimination between neoplastic and autoimmune disease

Aims: Diagnosis of IgG4 associated cholangitis (IAC) and autoimmune pancreatitis (AIP) is challenging since both autoimmune diseases frequently mimic the clinical and radiological profile of hilar cholangiocarcinoma and pancreatic adenocarcinoma, respectively. High levels of IgG4-positive plasma cells on histology have been described as specific diagnostic parameter of IAC and AIP. This study aims to evaluate this specificity by analysing the frequency of IgG4-positive plasma cells in malignant diseases of the pancreatico-biliary tract. Methods: Sixty-one patients with malignant tumours of the hepatobiliary tract or pancreas were analysed: 23 cases with hilar cholangiocarcinoma, 19 cases with pancreatic adenocarcinoma, 19 cases with hepatocellular carcinoma which served as control group. According to the Mayo clinic HISORt criteria, histology of the patients was re-evaluated and classified in IgG4-positive (≥ 20 IgG4-positive plasma cells per high power field) and IgG4-negative individuals (< 20 IgG4-positive plasma cells per high power field). Perioperative serology and radiological imaging studies were assessed as well. Results: Five of 19 (32%) of patients with hilar cholangiocarcinoma eligible for analysis and 5 of 19 (26%) patients with pancreatic adenocarcinoma were IgG4-positive. Patients with hilar cholangiocarcinoma positive for IgG4 showed a significant higher degree of cholestasis (median serum total bilirubin level 3.6mg/dl vs. 1.8mg/dl; p=.040) and increased serum alanin-aminotransferase (median 343 U/L vs. 63U/L, p=.042) compared to IgG4-negative patients. Amongst IgG4-positive individuals 5 of 6 patients with hilar cholangiocarcinoma and 3 of 5 patients with pancreatic adenocarcinoma showed similarity to IAC or AIP on radiological imaging.