Increased IgG4+ Cells in Duodenal Biopsies Are Not Specific for Autoimmune Pancreatitis
Maria Westerhoff, Katherine M Cebe, Paul E Swanson, Melissa P Upton. University of Washington, Seattle, WA
Background: Endoscopic ampullary biopsies showing increased IgG4+ plasma cells have been recently reported as an alternative to pancreatic biopsy in diagnosing autoimmune pancreatitis. In some institutions, pathologists are being asked to perform IgG4 immunostaining on duodenal biopsies without clear clinical indications or clear guidelines on how to interpret the significance of finding an increase in IgG4+ cells. The purpose of this study was to assess whether increased IgG4+ cells can be seen in duodenal biopsies outside the context of autoimmune pancreatitis.
Design: Duodenal biopsies from 28 patients undergoing endoscopy for suspected celiac disease (16), abdominal pain (6), recurrent pancreatitis (1), inflammatory bowel disease (IBD) surveillance (3), or post-Helicobacter pylori treatment (2) were stained immunohistochemically for IgG4.
Results: All duodenal biopsies that were histologically normal (n=5) or showed increased intraepithelial lymphocytes (IELs) without villous blunting (n=8) were negative for IgG4. Scattered IgG4+ cells (up to 10 per hpf) were found in 5 cases of 10 serologically confirmed celiac disease patients, with higher numbers of IgG4+ cells in biopsies showing significant villous blunting. In addition, there was heavy IgG4 positivity (10 to >30 per hpf) in 5 patients who had normal pancreata on ultrasound; 1 patient with recurrent pancreatitis and ulcerative colitis, 1 patient with primary sclerosing cholangitis (PSC) and ulcerative colitis, and 3 patients with confirmed celiac disease. Of these patients, the duodenal biopsies from the recurrent pancreatitis patient showed gastric heterotopia; her serum IgG4 was normal. In the PSC patient, the biopsies showed villous blunting, increased IELs, ulcer, and foveolar metaplasia. Biopsies of the celiac disease patients also showed severe villous blunting and increased IELs.
Conclusions: The finding of increased IgG4+ cells in duodenal biopsies is not specific for autoimmune pancreatitis. Even with a large number of IgG4+ cells, appropriate clinical findings and radiologic correlation are necessary to make a diagnosis of autoimmune pancreatitis. In our study, scattered IgG4+ cells were found particularly in duodenal biopsies with villous blunting and increased IELs, with 5 cases showing dense IgG4+ infiltrates. The significance of IgG4 positivity in celiac disease and in IBD is unclear. Nevertheless, the sole finding of increased IgG4+ plasma cells in biopsies is not specific for IgG4-related sclerosing disease, as seen in this study and reports of other conditions such as gastritis in pernicious anemia and in rheumatoid arthritis.
Monday, March 19, 2012 11:30 AM
Platform Session: Section D, Monday Morning