Does Autoimmune Pancreatitis Increase the Risk of Pancreatic Carcinoma?

Gupta, Rajib; Khosroshahi, Arezou; Shinagare, Shweta; Vilas, Carlos; Ferrone, Cristina R.; Lauwers, Gregory Y.; Stone, John H.; Deshpande, Vikram

doi:10.1097/mpa.0b013e31826bef91

Cited by 78 publications

(76 citation statements)

References 21 publications

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“…Many patients are misdiagnosed initially as having adenocarcinoma of the pancreas -sometimes only after the performance of a modified pancreatectomy. Several cases of pancreatic cancer have been reported in patients with previous IgG4-related AIP, but a clear relationship between the two conditions still needs to be fully verified [23,24]. Secondary diabetes mellitus and malabsorption might complicate longstanding pancreatic disease.…”

Section: Overview Of Clinical Manifestationsmentioning

confidence: 99%

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Immunology of IgG4-related disease

Della‐Torre

Lanzillotta

Doglioni

2015

Clinical and Experimental Immunology

183

215

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SummaryImmunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that derives its name from the characteristic finding of abundant IgG4 1 plasma cells in affected tissues, as well as the presence of elevated serum IgG4 concentrations in many patients. In contrast to fibrotic disorders, such as systemic sclerosis or idiopathic pulmonary fibrosis in which the tissues fibrosis has remained largely intractable to treatment, many IgG4-RD patients appear to have a condition in which the collagen deposition is reversible. The mechanisms underlying this peculiar feature remain unknown, but the remarkable efficacy of B cell depletion in these patients supports an important pathogenic role of B cell/T cell collaboration. In particular, aberrant T helper type 2 (Th2)/ regulatory T cells sustained by putative autoreactive B cells have been proposed to drive collagen deposition through the production of profibrotic cytokines, but definitive demonstrations of this hypothesis are lacking. Indeed, a number of unsolved questions need to be addressed in order to fully understand the pathogenesis of IgG4-RD. These include the identification of an antigenic trigger(s), the implications (if any) of IgG4 antibodies for pathophysiology and the precise immunological mechanisms leading to fibrosis. Recent investigations have also raised the possibility that innate immunity might precede adaptive immunity, thus further complicating the pathological scenario. Here, we aim to review the most recent insights on the immunology of IgG4-RD, focusing on the relative contribution of innate and adaptive immune responses to the full pathological phenotype of this fibrotic condition. Clinical, histological and therapeutic features are also addressed.

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Section: Overview Of Clinical Manifestationsmentioning

confidence: 99%

“…Obstructive jaundice, diabetes mellitus, abdominal pain, pale stool, malabsorption Biliary tree/gallbladder [23,24] IgG4-related sclerosing cholangitis Jaundice, weight loss, abdominal pain Liver [24] IgG4-related hepatitis (hepatic inflammatory pseudotumour)…”

Section: Pathologymentioning

confidence: 99%

Immunology of IgG4-related disease

Della‐Torre

Lanzillotta

Doglioni

2015

Clinical and Experimental Immunology

183

215

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“…These findings suggest the possibility of a close association between AIP and pancreatobiliary cancer. Gupta et al [10] inspected resected pancreata to clarify the prevalence of pancreatic intraepithelial neoplasia (PanIN) in 28 cases of AIP, and identified that 23 cases (82 %) showed PanIN; grades 2 and 3 PanIN were demonstrated in 7 (25 %) cases and 1 case, respectively, thus strongly indicating an elevated risk of pancreatic malignancy.…”

Section: Aip and Pancreatobiliary Cancermentioning

confidence: 99%

Association between autoimmune pancreatitis and malignancy

Hirano

Isayama

Tada

et al. 2014

Clin J Gastroenterol

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Chronic inflammatory diseases are often associated with malignancy, and this phenomenon occurs even in the field of gastroenterology. For example, chronic pancreatitis has been reported to be highly associated with the occurrence of pancreatic cancer. However, the association between autoimmune pancreatitis (AIP) and pancreatic cancer is still an unsolved problem. As AIP is associated with immunoglobulin G4-related disease, which causes a variety of inflammatory and fibrotic lesions, the association between AIP and total malignancies is also a matter of interest. Here, we discuss the association between AIP and malignancy. As for the association between AIP and pancreatic cancer, there is no conclusive evidence, although several reports have suggested that the relative risk of pancreatic cancer is high in AIP. Concerning the association between AIP and total malignancies, there are two reports from Japan. Neither report supported the idea that chronic inflammation in AIP caused the increased risk of total malignancies. However, one report proposed the possibility that AIP might develop as a paraneoplastic syndrome in some patients because many cancers occurred within 1 year of AIP diagnosis, and thereby concluded that patients with AIP were at high risk of having various cancers. The paraneoplastic syndrome hypothesis should be tested in future studies.

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“…[27][28][29][30] Cases of salivary duct carcinoma arising in the background of IgG4-associated sialadenitis and pancreatic carcinoma associated with autoimmune pancreatitis have also been reported. 31,32 In summary, the role of IgG4 in the pathogenesis of IgG4-related disease is currently unknown. Plasma cells in myeloma patients are mature immunocompetent cells that have undergone somatic hypermutation and class switch recombination.…”

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confidence: 99%

IgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related disease

et al. 2014

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IgG4-related disease is a newly described systemic fibroinflammatory process, characterized by increase in IgG4-positive plasma cells. Its pathogenesis, including the role of IgG4, remains poorly understood. Plasma cell myeloma is typically associated with a large monoclonal serum spike, which is frequently of IgG isotype. We sought to identify and characterize a subset of IgG4-secreting myeloma, as it may provide a biological model of disease with high serum levels of IgG4. Six out of 158 bone marrow biopsies (4%) from patients with IgG myeloma expressed IgG4. Four patients were men and two were women, with a mean age of 64 (range 53-87) years. Imaging showed fullness of pancreatic head (1), small non-metabolic lymphadenopathy (1), and bone lytic lesions (6). Two patients developed necrotizing fasciitis. All had elevated serum M-protein (mean 2.4, range 0.5-4.2 g/dl), and none had definite signs or symptoms of IgG4-related disease. Four myelomas had plasmablastic morphology. Four had kappa and two had lambda light chain expression. Three cases expressed CD56. Two patients had a complex karyotype. In conclusion, the frequency of IgG4 myeloma correlates with the normal distribution of IgG4 isoform. The patients with IgG4 myeloma appear to have a high rate of plasmablastic morphology and could be predisposed to necrotizing fasciitis. Despite high serum levels of IgG4, none had evidence of IgG4-related disease. These findings suggest that the increased number of IgG4-positive plasma cells is not the primary etiologic agent in IgG4-related disease. Elevated serum levels of IgG4 is not sufficient to produce the typical disease presentation and should not be considered diagnostic of IgG4-related disease.

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Does Autoimmune Pancreatitis Increase the Risk of Pancreatic Carcinoma?

Abstract: These findings raise concern that AIP is associated with an elevated risk of malignancy and should prompt additional studies.

Cited by 78 publications

References 21 publications

Immunology of IgG4-related disease

Immunology of IgG4-related disease

Association between autoimmune pancreatitis and malignancy

IgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related disease

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