Site(s) of Involvement Serum IgG4 Level (mg/dL) Treatment with Steroid IgG4-Related Disease Of The Gastrointestinal Tract: A Tertiary Care Hospital Experience Woo Cheal Cho, MD1, Saverio Ligato, MD1, Richard Cartun, PhD1, Anshu Trivedi, MD1 1Department of Pathology and Laboratory Medicine, Hartford Hospital, Hartford, CT BACKGROUND Patient No. Age (years) Sex Site(s) of Involvement Type of Specimen Serum IgG4 Level (mg/dL) Treatment with Steroid 1 74 M Pancreas S - N 2 73 Pancreas, bile duct, gallbladder 3 47 B 4 72 F 5 51 6 79 7 64 Bile duct 104.9 [4.0-86.0] 8 59 539 [4.0-86.0] 9 15 Mesentery (periduodenal) 271.9 [11.0-157.0] Y 10 25 Mesentery (periappendiceal) Y(& 6-MP) 11 61 Mesentery (pericolonic) 12 68 Mesentery (periileal) 13 14 46 Retroperitoneum 41 16 60 RESULTS (CONT.) IgG4-related disease (IgG4-RD) is a newly recognized clinicopathologic entity characterized by dense fibrosis and lymphoplasmacytic infiltration rich in IgG4-positive plasma cells. It often manifests as sclerosing mass lesions and is associated with an elevated serum IgG4 level. IgG4-RD is a systemic disorder that can affect virtually any organ system, with type 1 autoimmune pancreatitis (AIP) being the prototypic lesion for IgG4-RD. We report our 10-year experience with IgG4-RD as a tertiary care hospital, with a primary focus on the gastrointestinal tract, and discuss the challenges associated with the diagnosis. The primary sites in order of frequency were as follows: pancreas (6), mesentery (5), bile duct (3), retroperitoneum (3), and gallbladder (1). Serum IgG4 levels were obtained in 19% (3/16) of patients, all of whom were found have elevated serum IgG4 levels (range, 104.9-539.0 mg/dL). In 1 patient, a serum total IgG level was obtained instead, which was elevated at 1852 mg/dL. 13% (2/16) of patients had a history of malignancy and 6% (1/16) of patients had another documented autoimmune disease. Of 6 patients with IgG4-related sclerosing pancreatitis (type 1 AIP), 33% (2/6) of them had a history of alcohol abuse. 13% (2/16) of patients were treated with steroid alone or combination of steroid and immunosuppressive therapy. Of 2 patients who received treatment, 1 patient experienced a relapse. STUDY DESIGN We searched our laboratory database for patients with suspected IgG4-RD encountered over a 10-year period (2006-2016), using the following terms: “IgG4,” “autoimmune pancreatitis,” “autoimmune sclerosing cholangitis,” “retroperitoneal fibrosis,” and “inflammatory pseudotumor.” All slides and electronic medical records were retrospectively reviewed. CONCLUSION In our study, only a small portion of patients were further tested by serology and received treatment with steroid following tissue diagnosis. Although histology remains the gold standard for the diagnosis of IgG4-RD, the complete spectrum of histologic changes may not be seen, particularly in a biopsy specimen. Given the fact that IgG4-RD is steroid-responsive, therefore, increased awareness of this entity among clinicians is crucial for not only accurate and timely diagnosis but also proper management. Table 1. Histologically confirmed cases of IgG4-RD. Patient 1 had a markedly elevated serum IgG level of 1,852 mg/dL (reference, 639-1,349 mg/dL), but serum IgG4 level was not obtained. History of autoimmune disease (granulomatosis with polyangiitis) was seen in Patient 7. History of malignancy was seen in Patients 1 (metastatic melanoma) and 7 (colonic adenocarcinoma). History of alcohol abuse was seen in Patients 2 and 3. Relapse was seen in Patient 10 (2 months following treatment). *6-MP denotes 6-mercaptopurine. S and B represent surgical and biopsy specimens, respectively. RESULTS EVG IgG IgG4 In total, the material examined consisted of 11 surgical and 5 biopsy specimens, all of which were histologically confirmed to have IgG4-RD in at least 1 organ. Of 16 cases, 63% were male and the median age at diagnosis was 60.5 years (range, 15-79). Figure 1. Example of IgG4-RD (Patient 14). Retroduodenal/retroperitoneal biopsy showing diffuse lymphoplasmacytic infiltrates and focal obliterative vasculitis in a background of dense fibrosis. IgG4: IgG-positive plasma cell ratio was calculated to be approximately 50%.