Background Sclerosing pancreatitis is a unique form of pancreatitis that is characterized by irregular narrowing of the main pancreatic duct, lymphoplasmacytic inflammation of the pancreas, and hypergammaglobulinemia and that responds to glucocorticoid treatment. Preliminary studies suggested that serum IgG4 concentrations are elevated in this disease but not in other diseases of the pancreas or biliary tract. Methods We measured serum IgG4 concentrations using single radial immunodiffusion and an enzyme-linked immunosorbent assay in 20 patients with sclerosing pancreatitis, 20 age- and sex-matched normal subjects, and 154 patients with pancreatic cancer, ordinary chronic pancreatitis, primary biliary cirrhosis, primary sclerosing cholangitis, or Sjogren's syndrome. Serum concentrations of immune complexes and the IgG4 subclass of immune complexes were determined by means of an enzyme-linked immunosorbent assay with monoclonal rheumatoid factor. Results The median serum IgG4 concentration in the patients ...

https://www.nejm.org/doi/pdf/10.1056/NEJM200103083441005

High serum IgG4 concentrations in patients with sclerosing pancreatitis.

Consensus statement on the pathology of IgG4-related disease

IgG4-related disease.

IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4+ plasma cells Although IgG4-RD is not rare and is clinically important, its clinical diagnostic criteria have not been established Comprehensive diagnostic criteria for IgG4-RD, including the involvement of various organs, are intended for the practical use of general physicians and nonspecialists Two IgG4-RD study groups, the Umehara and Okazaki teams, were organized by the Ministry of Health, Labor and Welfare Japan As IgG4-RD comprises a wide variety of diseases, these groups consist of physicians and researchers in various disciplines, including rheumatology, hematology, gastroenterology, nephrology, pulmonology, ophthalmology, odontology, pathology, statistics, and basic and molecular immunology throughout Japan, with 66 and 56 members of the Umehara and Okazaki teams, respectively Collaborations of the two study groups involved detailed analyses of clinical symptoms, laboratory results, and biopsy specimens of patients with IgG4-RD, resulting in the establishment of comprehensive diagnostic criteria for IgG4-RD Although many patients with IgG4-RD have lesions in several organs, either synchronously or metachronously, and the pathological features of each organ differ, consensus has been reached on two diagnostic criteria for IgG4RD: (1) serum IgG4 concentration >135 mg/dl, and (2) >40% of IgG+ plasma cells being IgG4+ and >10 cells/high powered field of biopsy sample Although the comprehensive diagnostic criteria are not sufficiently sensitive for the diagnosis of type 1 IgG4-related autoimmune pancreatitis (IgG4-related AIP), they are adequately sensitive for IgG4-related Mikulicz’s disease (MD) and kidney disease (KD) In addition, the comprehensive diagnostic criteria, combined with organ-specific diagnostic criteria, have increased the sensitivity of diagnosis to 100% for IgG4-related MD, KD, and AIP Our comprehensive diagnostic criteria for IgG4-RD are practically useful for general physicians and nonspecialists

Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011

Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases. To investigate the pathophysiology of AIP, we immunohistochemically examined the pancreas and other organs in eight patients with AIP, and in controls, using anti-CD4-T and CD8-T cell subsets, as well as IgG4 antibodies. In AIP patients, severe or moderate infiltration of IgG4-positive plasma cells associated with CD4- or CD8-positive T lymphocytes was detected in the peripancreatic tissue (6/6), bile duct (8/8), gallbladder (8/8), portal area of the liver (3/3), gastric mucosa (5/7), colonic mucosa (2/2), salivary glands (1/2), lymph nodes (6/6), and bone marrow (2/2), as well as in the pancreas (8/8). There were few IgG4-positive plasma cells at the same sites in controls. These results suggest that AIP is not simply pancreatitis but that it is a pancreatic lesion involved in IgG4-related systemic disease with extensive organ involvement. We propose a new clinicopathological entity, of a systemic IgG4-related autoimmune disease in which AIP and its associated diseases might be involved.

A new clinicopathological entity of IgG4-related autoimmune disease

Characteristic pancreatic duct appearance in autoimmune chronic pancreatitis: A case report and review of the Japanese literature

https://www.gastrojournal.org/article/S0016-5085(97)00386-7/pdf

Long-term follow-up of patients with chronic pancreatitis and K-ras gene mutation detected in pancreatic juice

This is the first case of gastric schwannoma that exhibited increased accumulation of [(18)F] fluorodeoxyglucose (FDG) on positron emission tomography (PET) imaging The patient was a 60-year-old woman in whom esophagogastroduodenoscopy showed a submucosal tumor, about 25 mm in size, in the upper body of the stomach, with ulceration at the top of the tumor Endoscopic ultrasonography revealed a well-defined hypoechoic mass located in the proper muscle layer of the stomach The specimen taken from the tumor showed only inflammatory degenerative tissue Abdominal computed tomography revealed a tumor in the upper body of the stomach FDG-PET showed FDG uptake (standardized uptake value [SUV] max 58) coincident with the tumor Hence, the tumor was diagnosed initially as a gastrointestinal stromal tumor of the stomach Laparoscopic partial gastrectomy was performed Pathological examination showed that the tumor consisted of spindle cells with large nuclei, and mitosis was absent The Ki-67 labeling index of the tumor cells was 4% Immunohistochemically, the tumor cells showed a positive reaction for S-100 protein, whereas they were negative for KIT, CD 34, and alpha-smooth muscle actin protein The tumor was diagnosed as a benign gastric schwannoma Gastric schwannoma should be included in the differential diagnosis of submucosal tumors of the stomach with FDG uptake

/pdf/gastric-schwannoma-exhibiting-increased-fluorodeoxyglucose-gv3gukaa0f.pdf

Gastric schwannoma exhibiting increased fluorodeoxyglucose uptake

CA242 has been proved to be useful in the diagnosis of pancreatic cancer. The aim of the present study was to clarify the mechanisms contributing to the high specificity of CA242 as compared with CA19-9 resulting from scarce serum elevation of this antigen in patients with chronic pancreatitis by correlating serum levels and endoscopic retrograde choledocho-pancreatography (ERCP) findings and by immunohistochemical analysis. Serum CA19-9 levels were significantly elevated in patients with calcification and with main pancreatic duct (MPD) stenosis or obstruction. On the other hand, serum CA242 levels showed no significant elevation in patients with such factors. Even though such pathological conditions were considered to lead to the stagnation of pancreatic juice, serum CA242 levels seemed to be less affected than serum CA19-9 levels. Immunohistochemical studies of chronic pancreatitis tissues revealed that CA242 was expressed less frequently and less intensely than CA19-9, and the difference in expression was more prominent in the centroacinar cells and terminal ductules. From the results of the present study, it is conceivable that CA242 is less influenced by the stagnation of the pancreatic juice than CA19-9 because of the low levels of expression in ductal systems, which results in the release of this antigen into the circulation in lower amounts than that of CA19-9.

Naoyuki Furuya

Papers

High serum IgG4 concentrations in patients with sclerosing pancreatitis.

Characteristic pancreatic duct appearance in autoimmune chronic pancreatitis: A case report and review of the Japanese literature

Long-term follow-up of patients with chronic pancreatitis and K-ras gene mutation detected in pancreatic juice

Gastric schwannoma exhibiting increased fluorodeoxyglucose uptake

Comparative study of CA242 and CA19-9 in chronic pancreatitis.