Autoimmune pancreatitis-related cholecystitis: a morphologically and immunologically distinctive form of lymphoplasmacytic sclerosing cholecystitis Wei-Lia Wang, Alton B Farris, Gregory Y Lauwers & Vikram Deshpande The James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Date of submission 16 May 2008 Accepted for publication 11 November 2008 Wang W-L, Farris A B, Lauwers G Y & Deshpande V (2009) Histopathology 54, 829–836 Autoimmune pancreatitis-related cholecystitis: a morphologically and immunologically distinctive form of lymphoplasmacytic sclerosing cholecystitis Aims: Gallbladder involvement in autoimmune pancre- atitis (AIP) is reported to be histologically similar to that seen in primary sclerosing cholangitis (PSC) and biliary obstruction secondary to pancreatic ductal adenocarcinoma (PDAC). The aim was to identify unique morphological and immunological features that could help distinguish gallbladders of AIP from those associated with PSC and PDACs. Methods and results: Archival gallbladders from well- characterized individuals with AIP (n = 22), PSC (n = 13) and PDAC (n = 23) were examined. Quanti- tative immunohistochemical analysis for IgG and IgG4 plasma cells was performed and an IgG4 ⁄ IgG ratio was derived. Dense extramural infiltrates were almost exclusively seen in AIP cases (41%), but seen in only 4% of PDAC-associated cases and 0% of PSC cases (P = 0.001). Phlebitis was more frequently noted in AIP cases (41%) (P = 0.03). Inflammatory nodules were almost exclusively seen in AIP (27%) (P = 0.04). AIP gallbladders showed higher IgG4 ⁄ IgG ratios (P = 0.0001) than PDAC-associated and PSC gallblad- ders. Conclusions: The findings support our hypothesis that gallbladder involvement in AIP is a primary manifes- tation of this disease and not a secondary phenomenon related to biliary obstruction. In conjunction with imaging and serology, examination of the gallbladder could provide collaborative evidence of AIP. Evaluation of the gallbladder could also distinguish PSC from AIP- related cholangitis. Keywords: autoimmune pancreatitis, chronic cholecystitis, gallbladder, primary sclerosing cholangitis Abbreviations: AIP, autoimmune pancreatitis; HPF, high-power field; PDAC, pancreatic ductal adenocarcinoma; PSC, primary sclerosing cholangitis Introduction Autoimmune pancreatitis (AIP) is an inflammatory, and frequently mass-forming lesion of the pancreas. 1 The disease is often associated with elevated levels of serum IgG4, and is characteristically responsive to steroid therapy. 2 Approximately one-third of patients will also show extrapancreatic manifestations, among the most common of which are involvement of the biliary tree, i.e. sclerosing cholangitis and of the liver, i.e. hepatic inflammatory pseudotumour. 3–5 One-quarter of AIP gallbladders show a dense and diffuse lymphoplasmacytic infiltrate, the so-called dif- fuse acalculous lymphoplasmacytic cholecystitis. 6 Although this variant of chronic cholecystitis was initially believed to be exclusively associated with primary sclerosing cholangitis (PSC), similar histolog- ical features have subsequently been observed in other secondary cholangiopathies, including biliary obstruc- tion secondary to malignancy, and choledocholithia- sis. 6–8 Many of these diseases can be clinically and Address for correspondence: V Deshpande, MD, Gastrointestinal Pathology Service, Department of Pathology, Warren 2, Massachu- setts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. e-mail: vdeshpande@partners.org Ó 2009 The Authors. Journal compilation Ó 2009 Blackwell Publishing Limited. Histopathology 2009, 54, 829–836. DOI: 10.1111/j.1365-2559.2009.03315.x