Use of Serum Level of Immunoglobulin G4 in the Differential Diagnosis of Autoimmune Pancreatitis and Pancreatic Cancer

Abstract

Background: To determine the diagnostic performance of elevated serum Immunoglobulin G4 (IgG4) in the diagnosis of autoimmune pancreatitis (AIP) and its ability to distinguish AIP from pancreatic cancer. Methods: We retrospectively analyzed serum IgG4 levels in 865 patients with suspected AIP. There were 57 patients with confirmed AIP, 146 with pancreatic cancer, 9 with idiopathic pancreatitis, 104 with acute pancreatitis, 106 with chronic pancreatic disease, and 443 with other pancreatic conditions, including benign enlargement of pancreas, abdominal pain, or obstructive jaundice. Results: The median serum IgG4 level was significantly greater in AIP patients than in patients with other pancreatic diseases (442.0 vs. 73.8 mg/dL, p＜0.001). Based on an IgG4 cutoff value of 132 mg/dL (determined by receiver operating curve analysis), the sensitivity, specificity, and positive predictive values in the differential diagnosis of AIP and pancreatic cancer were 94.7%, 78.8%, and 63.5% respectively. Use of an IgG4 cutoff of 132 mg/dL meant that 31 of 146 patients (21.2%) with pancreatic cancer had elevated serum IgG4, 3 of 57 patients with AIP (5.2%) did not have elevated serum IgG4, and the positive and negative predictive values for diagnosis of AIP were 63.5% and 97.5% respectively. Conclusion: Serum IgG4 concentrations were significantly greater in AIP patients than in patients with other pancreatic diseases. A serum concentration of IgG4 that is more than 2 times the upper limit of normal is highly suggestive of AIP, but does not totally rule out pancreatic cancer. Mild (＜2-fold) elevations in serum IgG4 were present in many subjects without AIP, including 16.4% of subjects with pancreatic cancer. IgG4 elevation in a patient with a low pretest probability of having AIP is likely to represent a false positive. However, the high predictive value and high positive likelihood ratio confirm the good performance of 2-fold cutoff value in the differential diagnosis of AIP and pancreatic cancer.Background: To determine the diagnostic performance of elevated serum Immunoglobulin G4 (IgG4) in the diagnosis of autoimmune pancreatitis (AIP) and its ability to distinguish AIP from pancreatic cancer. Methods: We retrospectively analyzed serum IgG4 levels in 865 patients with suspected AIP. There were 57 patients with confirmed AIP, 146 with pancreatic cancer, 9 with idiopathic pancreatitis, 104 with acute pancreatitis, 106 with chronic pancreatic disease, and 443 with other pancreatic conditions, including benign enlargement of pancreas, abdominal pain, or obstructive jaundice. Results: The median serum IgG4 level was significantly greater in AIP patients than in patients with other pancreatic diseases (442.0 vs. 73.8 mg/dL, p＜0.001). Based on an IgG4 cutoff value of 132 mg/dL (determined by receiver operating curve analysis), the sensitivity, specificity, and positive predictive values in the differential diagnosis of AIP and pancreatic cancer were 94.7%, 78.8%, and 63.5% respectively. Use of an IgG4 cutoff of 132 mg/dL meant that 31 of 146 patients (21.2%) with pancreatic cancer had elevated serum IgG4, 3 of 57 patients with AIP (5.2%) did not have elevated serum IgG4, and the positive and negative predictive values for diagnosis of AIP were 63.5% and 97.5% respectively. Conclusion: Serum IgG4 concentrations were significantly greater in AIP patients than in patients with other pancreatic diseases. A serum concentration of IgG4 that is more than 2 times the upper limit of normal is highly suggestive of AIP, but does not totally rule out pancreatic cancer. Mild (＜2-fold) elevations in serum IgG4 were present in many subjects without AIP, including 16.4% of subjects with pancreatic cancer. IgG4 elevation in a patient with a low pretest probability of having AIP is likely to represent a false positive. However, the high predictive value and high positive likelihood ratio confirm the good performance of 2-fold cutoff value in the differential diagnosis of AIP and pancreatic cancer.