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Uchino K, Notohara K, Uehara T, Kuraishi Y, Itakura J, Matsukawa A. Utility of gastric biopsy in diagnosing IgG4-related gastrointestinal disease. Pathol Int 2020; 71:124-134. [PMID: 33378576 DOI: 10.1111/pin.13059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 11/27/2020] [Accepted: 11/30/2020] [Indexed: 01/13/2023]
Abstract
The utility of gastric biopsy for diagnosing immunoglobulin (Ig)G4-related gastrointestinal disease (IgG4-GID) remains unclear. Bottom-heavy plasmacytosis (BHP) is a distinct feature of IgG4-GID. To clarify the feasibility of using gastric biopsies to diagnose BHP in IgG4-GID, we analyzed the histological features and immunostaining of gastric biopsy specimens from 31 known IgG4-related disease (IgG4-RD) patients and we assessed the presence of BHP in 1696 consecutive routine gastric biopsies. Cases with both >10 IgG4-positive plasma cells per high-power field and an IgG4/IgG-positive ratio >40% were defined as IgG4-high. Ten of the 31 IgG4-RD patients were concluded to have IgG4-GID, in which IgG4-positive plasma cells were notably detected at the deeper part of the mucosa. Six cases displayed BHP whereas the remaining four cases showed transmural infiltration with concomitant Helicobacter pylori-associated gastritis. In addition to BHP, we identified two unique histologic features for IgG4-GID: plasmacytic aggregation in the muscularis mucosae and permeative plasmacytic infiltration between fundic glands in the non-atrophic mucosa. Six of the routine cases (0.35%) displayed BHP, including a case with IgG4-RD. IgG4-GID can be suspected by the presence of gastric biopsy specimens with characteristic histological features. Such cases are recommended to undergo further examinations to determine whether IgG4-RD is present.
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Affiliation(s)
- Kaori Uchino
- Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.,Department of Anatomic Pathology, Kurashiki Central Hospital, Okayama, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Okayama, Japan
| | - Takeshi Uehara
- Department of Laboratory Medicine, Shinshu University School of Medicine, Nagano, Japan
| | - Yasuhiro Kuraishi
- Department of Gastroenterology, Shinshu University School of Medicine, Nagano, Japan
| | - Junya Itakura
- Department of Anatomic Pathology, Kurashiki Central Hospital, Okayama, Japan
| | - Akihiro Matsukawa
- Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
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Sarkar A, Pitchumoni CS. The protean manifestations of IgG4-RD in gastrointestinal disorders. Dis Mon 2015; 61:493-515. [DOI: 10.1016/j.disamonth.2015.09.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Jani N, Buxbaum J. Autoimmune pancreatitis and cholangitis. World J Gastrointest Pharmacol Ther 2015; 6:199-206. [PMID: 26558153 PMCID: PMC4635159 DOI: 10.4292/wjgpt.v6.i4.199] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 06/22/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
Autoimmune pancreatitis (AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4 (IgG4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreatic manifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings.
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Hiyoshi Y, Oki E, Zaitsu Y, Ando K, Ito S, Saeki H, Morita M, Yamamoto H, Baba H, Maehara Y. IgG4-related disease of the ileocecal region mimicking malignancy: A case report. Int J Surg Case Rep 2014; 5:669-72. [PMID: 25194601 PMCID: PMC4189076 DOI: 10.1016/j.ijscr.2014.08.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2014] [Revised: 08/04/2014] [Accepted: 08/04/2014] [Indexed: 12/24/2022] Open
Abstract
The colonic IgG4-RD is rare. We report the case of a74-year-old female with IgG4-RD of the ileocecal region. The patient was diagnosed asmalignant lymphoma and underwent right-hemi colectomy. Postoperative pathologicalexamination revealed IgG4-RD of the ileocecal region. Surgical resection for IgG4-RDis necessary for cases with concerns of malignancy. INTRODUCTION Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease characterized by chronic fibrosing inflammation with abundant IgG4-positive plasma cells, and responds well to steroids. Previous reports of IgG4-RD have focused on pancreatic and extrapancreatic including the gastrointestinal tract, however, the colonic IgG4-RD is rare. PRESENTATION OF CASE We herein report the case of a 74-year-old female with edematous wall thickening of the terminal ileum to the lower ascending colon confirmed by several preoperative imaging studies, who underwent right hemi-colectomy for suspected malignant lymphoma. The resected specimen showed an irregular wall thickness with subserosal sclerosis, and the lesion was 10 cm in length from the terminal ileum to the ascending colon. The patient was diagnosed with IgG4-RD by pathological examinations, which demonstrated an increased number of IgG4-positive plasma cells (150/HPF), and an elevated IgG4/IgG ratio (50%). DISCUSSION Gastrointestinal IgG4-RD appears to be difficult to diagnose prior to surgical resection because of its rarity, and the similarity of its features to malignancy. The measurement of the serum IgG4 levels, immunohistochemical examination of biopsy specimens and use of several imaging modalities might help us to diagnose the disease without surgical resection, and this disease can generally be treated with steroid therapy. However, surgical resection for IgG4-RD may still be also necessary for patients with concerns regarding malignancy or with intractable gastrointestinal obstruction caused by this disease. CONCLUSION Gastrointestinal IgG4-RD often mimics malignancy, and we should therefore consider this disease in the differential diagnosis of colonic lesions in order to optimize the treatment.
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Affiliation(s)
- Yukiharu Hiyoshi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan.
| | - Eiji Oki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Yoko Zaitsu
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Koji Ando
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Shuhei Ito
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Hiroshi Saeki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Masaru Morita
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Hidetaka Yamamoto
- Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
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Yamashita H, Naitoh I, Nakazawa T, Hayashi K, Miyabe K, Shimizu S, Kondo H, Yoshida M, Umemura S, Hori Y, Ohara H, Takahashi S, Joh T. A comparison of the diagnostic efficacy in type 1 autoimmune pancreatitis based on biopsy specimens from various organs. Pancreatology 2014; 14:186-92. [PMID: 24854614 DOI: 10.1016/j.pan.2014.03.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2013] [Revised: 02/26/2014] [Accepted: 03/03/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Comprehensive immunostaining evaluation of the biopsy specimens from various organs with type 1 autoimmune pancreatitis (AIP) has not been elucidated. Our aim was to clarify which of these biopsy specimens and counting method could be a useful tool for supporting the diagnosis of AIP. METHODS We retrospectively evaluated biopsy specimens from pancreas (n = 19), stomach (n = 28), duodenum (n = 27), duodenal papilla (n = 25), colon (n = 19), liver (n = 11), bile duct (n = 24), and minor salivary gland (n = 13) in 36 patients with AIP. Positive IgG4 immunostaining (>10 plasma cells/high-power field [HPF]) and positive IgG4/IgG ratio (>40%) of biopsy specimens from 8 sites of 6 organs in one HPF and an average from 3 HPFs were compared between AIP and controls. RESULTS The sensitivity of IgG4 immunostaining for AIP in one HPF were 16% in pancreas, 14% in stomach, 15% in duodenum, 52% in duodenal papilla, 11% in colon, 27% in liver, 21% in bile duct and 8% in minor salivary gland, respectively. The positive IgG4 immunostaining of the duodenal papilla in one HPF showed the highest sensitivity (52%) and accuracy (73%) among the 8 sites. It also showed the highest sensitivity among 4 different counting methods (IgG4 immunostaining in one HPF and 3 HPFs, both IgG4 immunostaining and IgG/IgG4 ratio in one HPF and 3 HPFs), but there were no significant differences with respect to specificity and accuracy. CONCLUSIONS IgG4 immunostaining of swollen duodenal papilla with more than 10 IgG4-positive plasma cells in at least one HPF is useful for supporting the diagnosis of AIP.
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Affiliation(s)
- Hiroaki Yamashita
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
| | - Takahiro Nakazawa
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kazuki Hayashi
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Katsuyuki Miyabe
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shuya Shimizu
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hiromu Kondo
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Michihiro Yoshida
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shuichiro Umemura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yasuki Hori
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hirotaka Ohara
- Department of Community-based Medical Education, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Satoru Takahashi
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takashi Joh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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Kuwata G, Kamisawa T, Koizumi K, Tabata T, Hara S, Kuruma S, Fujiwara T, Chiba K, Egashira H, Fujiwara J, Arakawa T, Momma K, Horiguchi S. Ulcerative colitis and immunoglobulin G4. Gut Liver 2013; 8:29-34. [PMID: 24516698 PMCID: PMC3916684 DOI: 10.5009/gnl.2014.8.1.29] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Revised: 02/20/2013] [Accepted: 04/03/2013] [Indexed: 12/11/2022] Open
Abstract
Background/Aims Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4. Methods Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients. Results UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05). Conclusions UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity.
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Affiliation(s)
- Go Kuwata
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Koichi Koizumi
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Taku Tabata
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Seiichi Hara
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Sawako Kuruma
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Takashi Fujiwara
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Kazuro Chiba
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Hideto Egashira
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Junko Fujiwara
- Department of Endoscopy, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Takeo Arakawa
- Department of Endoscopy, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Kumiko Momma
- Department of Endoscopy, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
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Koizumi S, Kamisawa T, Kuruma S, Tabata T, Chiba K, Iwasaki S, Endo Y, Kuwata G, Koizumi K, Shimosegawa T, Okazaki K, Chiba T. Immunoglobulin G4-related gastrointestinal diseases, are they immunoglobulin G4-related diseases? World J Gastroenterol 2013; 19:5769-5774. [PMID: 24124321 PMCID: PMC3793131 DOI: 10.3748/wjg.v19.i35.5769] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Revised: 05/30/2013] [Accepted: 07/19/2013] [Indexed: 02/06/2023] Open
Abstract
In immunoglobulin G4 (IgG4)-related disease (RD), organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs. Although infiltration of many IgG4-positive plasma cells is detected in the gastric and colonic mucosa and major duodenal papilla of patients with autoimmune pancreatitis, it cannot be diagnosed as a gastrointestinal lesion involved in IgG4-RD, because none of the following is observed in these lesions: a mass-like formation; dense fibrosis; or obliterative phlebitis. Based on our review of the literature, there appear to be two types of IgG4-related gastrointestinal disease. One is a gastrointestinal lesion showing marked thickening of the wall of the esophagus and stomach, consisting of dense fibrosis with abundant infiltration of IgG4-positive plasma cells, which usually show submucosal spreading. The other is an IgG4-related pseudotumor occurring in gastrointestinal regions such as the stomach, colon, and major duodenal papilla, showing polypoid or mass-like lesions. Most solitary IgG4-related gastrointestinal lesions that are not associated with other IgG4-RD appear to be difficult to diagnose. It is of utmost importance to rule out malignancy. However, these lesions may respond to steroid therapy. To avoid unnecessary resection, IgG4-related gastrointestinal diseases should be considered in the differential diagnosis.
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Wu L, Li W, Huang X, Wang Z. Clinical features and comprehensive diagnosis of autoimmune pancreatitis in China. Digestion 2013; 88:128-134. [PMID: 24008239 DOI: 10.1159/000353597] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Accepted: 06/05/2013] [Indexed: 02/04/2023]
Abstract
AIM To search for the key factors of autoimmune pancreatitis (AIP) in China and to improve the early identification of AIP in order to avoid misdiagnosing it as pancreatic carcinoma. METHODS Clinical, imaging, laboratory, and pathological data about AIP were collected and analyzed from 1996 to 2011 in The Chinese People's Liberation Army General Hospital. RESULTS A total of 33 patients (male 29, female 4) aged 35-76 years (52.3 ± 9.3 years) meeting the International Consensus Diagnostic Criteria for type 1 (n = 32) or type 2 (n = 1) AIP were included. With improved understanding of AIP, the misdiagnosis rate and unnecessary laparotomy rate was decreased from 95.7% (22/23) and 91.3% (21/23) before 2006, to 20.0% (2/10) (p = 0.001) and 0.0% (p = 0.001) respectively after 2006. The major symptoms were jaundice in (24/33, 72.7%) and abdominal pain (12/33, 36.4%). Half of the patients had other accompanied autoimmune disorders. Laboratory tests showed an elevated level of serum IgG in 9 out of 11 patients (81.8%) and an increased eosinophil count in 16 out of 33 patients (48.5%). The serum IgG4 levels were twice the upper limit of the normal value. CT scan showed a low-contrast margin characterized by a capsule-like rim in 24 of 32 patients (75.0%). Pathologic examinations showed fibrosis and infiltration of massive lymphocytes and plasma cells in the pancreas. Prednisone was given to the patients and proved to be quite effective for all of them (12/12, 100%). CONCLUSION Type 1 AIP shows a sex predilection compared with type 2 AIP in China. In order to diagnose AIP exactly, a comprehensive strategy, especially including imaging and pathological examination, should be used. With growing awareness, fewer AIP patients with this diagnosis would be misdiagnosed and incorrectly treated.
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Affiliation(s)
- Lili Wu
- Department of Gastroenterology and Hepatology, The Chinese People's Liberation Army General Hospital, Beijing, China
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Fujita A, Sakai O, Chapman MN, Sugimoto H. IgG4-related disease of the head and neck: CT and MR imaging manifestations. Radiographics 2013; 32:1945-58. [PMID: 23150850 DOI: 10.1148/rg.327125032] [Citation(s) in RCA: 113] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Immunoglobulin G4 (IgG4)-related disease is a recently established systemic disease that commonly involves the head and neck, including the salivary glands, lacrimal glands, orbits, thyroid gland, lymph nodes, sinonasal cavities, pituitary gland, and larynx. Although the definitive diagnosis of IgG4-related disease requires histopathologic analysis, elevated serum IgG4 levels are helpful in making the diagnosis. Because of the proposed clinical diagnostic criteria for this disease, cross-sectional imaging modalities such as computed tomography (CT) and magnetic resonance (MR) imaging play an important diagnostic role. CT and MR imaging findings of IgG4-related disease are usually nonspecific. At CT, involved organs may demonstrate enlargement or decreased attenuation; at T2-weighted MR imaging, they may have relatively low signal intensity owing to their increased cellularity and amount of fibrosis. Some pathologic entities involving the head and neck are now considered to be part of the IgG4-related disease spectrum, including idiopathic orbital inflammatory syndrome (inflammatory pseudotumor), orbital lymphoid hyperplasia, Mikulicz disease, Küttner tumor, Hashimoto thyroiditis, Riedel thyroiditis, and pituitary hypophysitis. Because involvement of multiple sites is common in IgG4-related disease, radiologists should be familiar with manifestations of this systemic process outside the head and neck, in organs such as the pancreas, bile ducts, gallbladder, kidneys, retroperitoneum, mesentery, lungs, gastrointestinal tract, and blood vessels. Moreover, IgG4-related disease usually demonstrates a dramatic response to corticosteroid therapy, and radiologists should be familiar with its clinical and imaging manifestations to avoid a delay in diagnosis or unnecessary invasive interventions.
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Affiliation(s)
- Akifumi Fujita
- Department of Radiology, Jichi Medical University, School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
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Vlachou PA, Khalili K, Jang HJ, Fischer S, Hirschfield GM, Kim TK. IgG4-related sclerosing disease: autoimmune pancreatitis and extrapancreatic manifestations. Radiographics 2012; 31:1379-402. [PMID: 21918050 DOI: 10.1148/rg.315105735] [Citation(s) in RCA: 141] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Autoimmune pancreatitis is the pancreatic manifestation of IgG4-related sclerosing disease, which recently was recognized as a distinct disease entity. Numerous extrapancreatic organs, such as the bile ducts, gallbladder, kidneys, retroperitoneum, thyroid, salivary glands, lung, mediastinum, lymph nodes, and prostate may be involved, either synchronously or metachronously. Most cases of autoimmune pancreatitis are associated with elevated serum IgG4 levels; extensive IgG4-positive plasma cells; and infiltration of lymphocytes into various organs, which leads to fibrosis. There are several established diagnostic criteria systems that are used to diagnose autoimmune pancreatitis and that rely on a combination of imaging findings of the pancreas and other organs, serologic findings, pancreatic histologic findings, and response to corticosteroid therapy. It is important to recognize multiorgan involvement of IgG4-related sclerosing disease and be familiar with its clinical and imaging features because it demonstrates a favorable response to treatment.
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Affiliation(s)
- Paraskevi A Vlachou
- Department of Medical Imaging and Pathology, University of Toronto, Toronto, Canada
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Immunoglobulin G4 immunostaining of gastric, duodenal, or colonic biopsies is not helpful for the diagnosis of autoimmune pancreatitis. Clin Gastroenterol Hepatol 2012; 10:91-4. [PMID: 21946123 DOI: 10.1016/j.cgh.2011.09.008] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2011] [Revised: 08/23/2011] [Accepted: 09/10/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The aim of this study was to evaluate the specificity of the infiltration of digestive tract mucosa by immunoglobulin (Ig) G4-positive plasma cells in patients with autoimmune pancreatitis (AIP), as compared with normal or inflammatory mucosa. METHODS Plasma cell infiltration, CD138 and IgG4 immunostaining of digestive biopsies were compared in 4 groups of patients: AIP type 1 (n = 19); AIP type 2 (n = 4) with inflammatory bowel disease (IBD); IBD without pancreatic disorders (n = 20); and controls (n = 26). RESULTS With AIP type 1 versus controls, more plasma cells were present in the gastric mucosa of AIP (P = .02) without difference concerning IgG4+ plasma cells at any biopsy site. With AIP type 1 versus IBD, colonic mucosa was more often abnormal (P = .004), and more CD138 (P = .02) and IgG4 plasma cells (P = .0002) were counted in the colon biopsies of IBD. With AIP type 2 versus IBD, no difference for plasma cell and IgG4 infiltration was found. CONCLUSIONS IgG4-positive plasma cells are not more numerous in the digestive mucosa of AIP patients than in controls, but they are more abundant in the colon of IBD patients than in AIP patients.
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Abstract
OBJECTIVES Autoimmune pancreatitis (AIP) and its extrapancreatic lesions seem to be clinical manifestations of organs involved in IgG4-related systemic disease. To clarify whether the stomach is a target organ, gastric function was evaluated in patients with AIP. METHODS In 6 patients with AIP, gastric emptying was assessed by Carbon 13 (¹³C) acetate breath test before and after steroid therapy. Based on 4-hour breath samples, the half ¹³CO₂ excretion time (T(1/2)) and the time of maximal excretion (T(max)) were calculated as gastric emptying parameters. Data of 20 healthy volunteers were used as controls. The number of IgG4-positive plasma cells in gastrofiberscopic biopsy specimens was counted before and after steroid therapy. RESULTS Both T(1/2) and T(max) in patients with AIP decreased significantly after steroid therapy (T(1/2): 1.89 ± 0.21 hours vs 1.69 ± 0.15 hours, P = 0.046; and T(max): 1.1 ± 0.2 hours vs 0.96 ± 0.2 hours, P = 0.027), and became similar to those of the controls (T(1/2): 1.69 ± 0.32 hours and T(max): 0.98 ± 0.2 hour). The number of IgG4-positive plasma cells infiltrating the gastric mucosa decreased after steroid therapy. CONCLUSIONS Gastric emptying was impaired in patients with AIP and improved to the reference range after steroid therapy. The stomach may be a target organ of IgG4-related systemic disease.
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Takuma K, Kamisawa T, Tabata T, Inaba Y, Egawa N, Igarashi Y. Utility of pancreatography for diagnosing autoimmune pancreatitis. World J Gastroenterol 2011; 17:2332-7. [PMID: 21633599 PMCID: PMC3098401 DOI: 10.3748/wjg.v17.i18.2332] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2010] [Revised: 12/14/2010] [Accepted: 12/21/2010] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify pancreatographic findings that facilitate differentiating between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) on endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP).
METHODS: ERCP findings of 48 AIP and 143 PC patients were compared. Diagnostic accuracies for AIP by ERCP and MRCP were compared in 30 AIP patients.
RESULTS: The following ERCP findings suggested a diagnosis of AIP rather than PC. Obstruction of the main pancreatic duct (MPD) was more frequently detected in PC (P < 0.001). Skipped MPD lesions were detected only in AIP (P < 0.001). Side branch derivation from the narrowed MPD was more frequent in AIP (P < 0.001). The narrowed MPD was longer in AIP (P < 0.001), and a narrowed MPD longer than 3 cm was more frequent in AIP (P < 0.001). Maximal diameter of the upstream MPD was smaller in AIP (P < 0.001), and upstream dilatation of the MPD less than 5 mm was more frequent in AIP (P < 0.001). Stenosis of the lower bile duct was smooth in 87% of AIP and irregular in 65% of PC patients (P < 0.001). Stenosis of the intrahepatic or hilar bile duct was detected only in AIP (P = 0.001). On MRCP, diffuse narrowing of the MPD on ERCP was shown as a skipped non-visualized lesion in 50% and faint visualization in 19%, but segmental narrowing of the MPD was visualized faintly in only 14%.
CONCLUSION: Several ERCP findings are useful for differentiating AIP from PC. Although MRCP cannot replace ERCP for the diagnostic evaluation of AIP, some MRCP findings support the diagnosis of AIP.
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Kamisawa T, Takuma K, Tabata T, Inaba Y, Egawa N, Tsuruta K, Hishima T, Sasaki T, Itoi T. Serum IgG4-negative autoimmune pancreatitis. J Gastroenterol 2011; 46:108-16. [PMID: 20824290 DOI: 10.1007/s00535-010-0317-2] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2010] [Accepted: 07/12/2010] [Indexed: 02/04/2023]
Abstract
BACKGROUND Autoimmune pancreatitis (AIP) is considered to be a pancreatic lesion of IgG4-related systemic disease, but about 20% of AIP patients do not have elevated serum IgG4 levels. This study aimed to clarify the pathophysiology of AIP patients without elevated serum IgG4 levels. METHODS Fifty-eight AIP patients were divided into 2 groups: those with elevated serum IgG4 levels (>135 mg/dl; SIgG4-positive AIP) and those without (SIgG4-negative AIP). The 2 groups' clinical, serological, radiological, and histological findings, as well as salivary and lacrimal gland function, were compared. RESULTS Serum IgG4 levels were elevated in 45 AIP patients and normal in 13 patients. In SIgG4-negative AIP patients, the female ratio tended to be high; obstructive jaundice was less likely; abdominal pain and acute pancreatitis were more likely; segmental swelling of the pancreatic body and/or tail was more common; sclerosing extrapancreatic lesions, salivary and lacrimal gland dysfunction, and abundant infiltration of IgG4-positive plasma cells in the gastric mucosa were less likely; and conservative follow-up was sometimes implemented. Histological examination of the pancreas of SIgG4-negative AIP showed lymphoplasmacytic sclerosing pancreatitis (LPSP) rather confined to the pancreas (n = 4), inadequate material (n = 2), and pancreatic fibrosis showing infiltration of lymphocytes without infiltration of IgG4-positive cells or neutrophils (n = 2). CONCLUSIONS Clinicopathological features of SIgG4-negative AIP differed from those of SIgG4-positive AIP. Some SIgG4-negative AIP cases are LPSP rather confined to the pancreas. SIgG4-negative AIP may include idiopathic duct-centric pancreatitis (IDCP) or sclerosing pancreatitis other than LPSP or IDCP, but further studies are needed to clarify this issue.
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Affiliation(s)
- Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.
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Kamisawa T, Takuma K, Egawa N, Tsuruta K, Sasaki T. Autoimmune pancreatitis and IgG4-related sclerosing disease. Nat Rev Gastroenterol Hepatol 2010; 7:401-9. [PMID: 20548323 DOI: 10.1038/nrgastro.2010.81] [Citation(s) in RCA: 145] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Autoimmune pancreatitis (AIP) is a unique form of pancreatitis in which the pathogenesis is suspected to involve autoimmune mechanisms. AIP sometimes mimics pancreatic cancer in its presentation, but as AIP responds dramatically to steroid therapy, accurate diagnosis is necessary. AIP is currently diagnosed on the basis of a combination of characteristic clinical, serological, morphological and histopathological features. However, its diagnosis remains a clinical challenge and there are no internationally agreed diagnostic criteria. Another type of AIP called 'idiopathic duct-centric chronic pancreatitis' or 'AIP with granulocytic epithelial lesion' has been reported in Western countries. IgG4-related sclerosing disease is a systemic disease in which IgG4-positive plasma cells and T lymphocytes extensively infiltrate various organs. Organs with tissue fibrosis and obliterative phlebitis, such as the pancreas, salivary gland and retroperitoneum, show clinical manifestations; AIP seems to represent one manifestation of IgG4-related sclerosing disease. As a mass is formed in most cases of IgG4-related sclerosing disease, a malignant tumor is frequently suspected on initial presentation. Clinicians should consider IgG4-related sclerosing disease in the differential diagnosis to avoid unnecessary surgery.
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Affiliation(s)
- Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan.
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17
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Diagnostic utility of biopsy specimens for autoimmune pancreatitis. J Gastroenterol 2009; 44:765-73. [PMID: 19430718 DOI: 10.1007/s00535-009-0052-8] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2008] [Accepted: 03/15/2009] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Infiltration of IgG4-positive plasma cells in the pancreas and other organs is characteristic of autoimmune pancreatitis (AIP). However, it is undetermined whether needle or forceps biopsy of pancreas or other organs is indeed useful for the diagnosis of AIP. We aimed to clarify this point. METHODS Among 39 AIP patients, tissue sampling without laparotomy was performed in 27. Biopsy of pancreas, gastric mucosa, liver, bile duct, and duodenal papilla was performed in 15, 17, 11, 5 and 7, respectively. The obtained specimens were examined for IgG4-positive plasma cells. We also examined gastric mucosa of 18 patients with pancreatic cancer as controls. When the number of IgG4-positive plasma cells was more than 10 per high-power field, we regarded it as diagnostic. RESULTS Diagnostic sensitivity in pancreas, gastric mucosa, liver, bile duct, and duodenal papilla was 47% (7/15), 47% (8/17), 36% (4/11), 0% (0/5), and 57% (4/7), respectively. CONCLUSIONS Sensitivity of IgG4 immunostaining was unsatisfactory when tissue sampling was performed by needle or forceps biopsy. Biopsy of gastric mucosa might be a good subsidiary diagnostic tool.
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Shimosegawa T, Kanno A. Autoimmune pancreatitis in Japan: overview and perspective. J Gastroenterol 2009; 44:503-17. [PMID: 19377842 DOI: 10.1007/s00535-009-0054-6] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2009] [Accepted: 02/26/2009] [Indexed: 02/06/2023]
Abstract
Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, i.e., association of extrapancreatic organ involvements. Initially misunderstood because it can be accompanied by other autoimmune disorders, such as Sjögren's syndrome or primary sclerosing cholangitis (PSC), AIP is now known to be associated with unique types of sialadenitis and cholangitis distinct from Sjögren's syndrome or PSC. Now the concept of "IgG4-related sclerosing disease" has become widely accepted and the list of organs involved continues to increase. With worldwide recognition, an emerging issue is the clinical definition of other possible types of autoimmune-related pancreatitis called "idiopathic duct-centric chronic pancreatitis (IDCP)" and "AIP with granulocyte epithelial lesion (GEL)" and their relation to AIP with lymphoplasmacytic sclerosing pancreatitis (LPSP). The time has arrived to establish clinical diagnostic criteria of AIP based on international consensus and to discuss regional and racial differences in the clinicopathological features of AIP. Consensus guidelines are also required for the ideal use of steroids in the treatment of AIP to suppress recurrence efficiently with minimal side effects. There are many issues to be settled in AIP; international collaboration of experts in the pancreas field is necessary to clarify the entire picture of this unique and important disease.
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Affiliation(s)
- Tooru Shimosegawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
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Morselli-Labate AM, Pezzilli R. Usefulness of serum IgG4 in the diagnosis and follow up of autoimmune pancreatitis: A systematic literature review and meta-analysis. J Gastroenterol Hepatol 2009; 24:15-36. [PMID: 19067780 DOI: 10.1111/j.1440-1746.2008.05676.x] [Citation(s) in RCA: 92] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
High circulating serum immunoglobulin G4 (IgG4) levels have been proposed as a marker of autoimmune pancreatitis (AIP). The aim of the present study was to review the data existing in the English literature on the usefulness of the IgG4 serum levels in the diagnosis and follow up of patients with AIP. A total of 159 patients with AIP and 1099 controls were described in seven selected papers reporting the usefulness of serum IgG4 in diagnosing AIP. In total, 304 controls had pancreatic cancer, 96 had autoimmune diseases, and the remaining 699 had other conditions. The summary receiver-operating characteristic curve analysis was carried out by means of Meta-DiSc open-access software. Serum IgG4 showed good accuracy in distinguishing between AIP and the overall controls, pancreatic cancer and other autoimmune diseases (area under the curve [+/- SE]: 0.920 +/- 0.073, 0.914 +/- 0.191, and 0.949 +/- 0.024, respectively). The studies analyzed showed significantly heterogeneous specificity values in each of the three analyses performed. The analysis of the four studies comparing AIP and pancreatic cancers also showed significantly heterogeneous values of sensitivities and odds ratios. Regarding the usefulness of IgG4 as a marker of efficacy of steroid treatment, a decrease in the serum concentrations of IgG4 was found in the four available studies. The serum IgG4 subclass is a good marker of AIP, and its determination should be included in the diagnostic workup of this disease. However, the heterogeneity of the studies published until now means that more studies are necessary in order to better evaluate the true accuracy of IgG4 in discriminating AIP versus other autoimmune diseases.
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Joo M, Chang SH, Kim H, Gardner JM, Ro JY. Primary gastrointestinal clear cell sarcoma: report of 2 cases, one case associated with IgG4-related sclerosing disease, and review of literature. Ann Diagn Pathol 2008; 13:30-5. [PMID: 19118779 DOI: 10.1016/j.anndiagpath.2008.10.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Clear cell sarcoma (CCS) is a distinctive soft tissue sarcoma that shows melanocytic differentiation. Primary gastrointestinal (GI) CCSs have been rarely reported, but to our knowledge, no association between GI CCSs and immunoglobulin G4 (IgG4)-related sclerosing disease has been described in the literature. We experienced 2 cases of CCS that arose in the small intestine and metastasized to the liver. Histologic features and immunophenotype were typical of CCS. One of them showed a unique peritumoral sclerosing inflammatory reaction, which was highly reminiscent of IgG4-related sclerosing inflammatory disease. Dense lymphoplasmacytic infiltration with extensive sclerosis and obliterative phlebitis was observed in the immediate vicinity of the primary and metastatic tumors, but not in the distant areas from the tumor. The average number of IgG4-positive plasma cells was more than 50 per high-power field. We report 2 cases of primary GI CCS with one case showing a unique peritumoral IgG4-related lymphoplasmacytic sclerosing inflammation.
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Affiliation(s)
- Mee Joo
- Department of Pathology, Inje University Ilsan Paik Hospital, Goyang, South Korea
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Gincoul R, Pujol B, Dumortier J, Scoazec JY, Hervieu V, Crombe-Ternamian A, Pilleul F, Napoléon B, Ponchon T. [Bile duct involvement in autoimmune pancreatitis: classification and treatment]. GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE 2008; 32:914-921. [PMID: 18472376 DOI: 10.1016/j.gcb.2007.12.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
Autoimmune pancreatitis is a rare disease characterized by inflammation of the pancreatic parenchyma, irregular narrowing of the pancreatic duct, periductal lymphoplasmacytic infiltration and fibrosis at histological examination, the presence of autoantibodies and hypergammaglobulinemia, as well as the possible association of cholangitis and other autoimmune diseases. There is a favorable response to steroid therapy. We report the case of a patient with autoimmune pancreatitis with bile duct involvement and peripheral eosinophilia, requiring long-term immunosuppressant treatment. The diagnosis of a diffuse form of AIP was made without direct histological evidence and based on indirect imaging, clinical and laboratory findings in an autoimmune context. The histological and imaging studies of bile duct involvement and the favourable response to steroids were additional arguments.
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Affiliation(s)
- R Gincoul
- Service d'hépatogastroentérologie, pavillon H, hôpital Edouard-Herriot, Lyon cedex 03, France.
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Abstract
We report a case of autoimmune pancreatitis involving the colonic mucosa. Although serum level of IgG4 was normal, computed tomography and endoscopic retrograde cholangiopancreatography showed diffuse enlargement of the pancreas and irregular narrowing of the pancreatic ducts, respectively. Colonoscopy revealed a polypoidal lesion in the ascending colon. A lymphoplasmacytic infiltration was seen both in the pancreas and in the polypoidal lesion of the colon. Furthermore, immunohistochemical analysis showed abundant IgG4-positive plasma cells in these lesions. This is the first case report of a simultaneous occurrence of autoimmune pancreatitis and a colonic polypoidal lesion, both of which are characterized with increased IgG4 responses.
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Abstract
Based on histological and immunohistochemical examination of various organs of patients with autoimmune pancreatitis (AIP), a novel clinicopathological entity of IgG4-related sclerosing disease has been proposed. This is a systemic disease that is characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. Clinical manifestations are apparent in the pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung, and prostate, in which tissue fibrosis with obliterative phlebitis is pathologically induced. AIP is not simply pancreatitis but, in fact, is a pancreatic disease indicative of IgG4-related sclerosing diseases. This disease includes AIP, sclerosing cholangitis, cholecystitis, sialadenitis, retroperitoneal fibrosis, tubulointerstitial nephritis, interstitial pneumonia, prostatitis, inflammatory pseudotumor and lymphadenopathy, all IgG4-related. Most IgG4-related sclerosing diseases have been found to be associated with AIP, but also those without pancreatic involvement have been reported. In some cases, only one or two organs are clinically involved, while in others, three or four organs are affected. The disease occurs predominantly in older men and responds well to steroid therapy. Serum IgG4 levels and immunostaining with anti-IgG4 antibody are useful in making the diagnosis. Since malignant tumors are frequently suspected on initial presentation, IgG4-related sclerosing disease should be considered in the differential diagnosis to avoid unnecessary surgery.
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Kakar S, Smyrk TC. Autoimmune pancreatitis: negotiating the labyrinth of terminology, diagnosis and differential diagnosis. ACTA ACUST UNITED AC 2008. [DOI: 10.1016/j.mpdhp.2008.04.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Saeki K, Hozawa S, Miyata N, Nishizawa T, Soma H, Iwao Y, Kameyama K, Hibi T. IgG4-negative autoimmune pancreatitis with sclerosing cholangitis and colitis: possible association with primary sclerosing cholangitis? Intern Med 2008; 47:943-8. [PMID: 18480579 DOI: 10.2169/internalmedicine.47.0613] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
We report a case of autoimmune pancreatitis (AIP) with cholangiography and histopathology showing features characteristic of primary sclerosing cholangitis (PSC) and colitis. A 55-year-old previously-healthy man was diagnosed with anti-nuclear antibody (ANA)-positive AIP according to the finding of serum biochemistry, abdominal US (ultrasonography), CT (computed tomography) and ERCP (endoscopic retrograde cholangiopancreatography). However, bead-like strictures of intrahepatic bile ducts were also found and liver tissue showed onion skin-like periductal fibrosis but no anti-IgG4-positive cells. In addition, colon fiberscopy showed a pancolitis similar to ulcerative colitis indicating that, in this case, there may be an association with PSC. Here, we report a rare case of IgG4-negative AIP with sclerosing cholangitis and colitis with many clinical features that support an association with PSC.
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Affiliation(s)
- Keita Saeki
- Division of Gastroenterology, Department of Internal Medicine, Keio University School of Medicine, Tokyo
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Abstract
Recent advances in understanding of pancreatitis and advances in technology have uncovered the veils of idiopathic pancreatitis to a point where a thorough history and judicious use of diagnostic techniques elucidate the cause in over 80% of cases. This review examines the multitude of etiologies of what were once labeled idiopathic pancreatitis and provides the current evidence on each. This review begins with a background review of the current epidemiology of idiopathic pancreatitis prior to discussion of various etiologies. Etiologies of medications, infections, toxins, autoimmune disorders, vascular causes, and anatomic and functional causes are explored in detail. We conclude with management of true idiopathic pancreatitis and a summary of the various etiologic agents. Throughout this review, areas of controversies are highlighted.
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Abstract
Chronic autoimmune pancreatitis is an entity distinct from all other forms of chronic pancreatitis. It is expressed by signs of acute or chronic pancreatitis, sometimes associated with cholestatic jaundice. In imaging, it may appear as diffuse (duct destructive) or pseudotumoral lesions. These 2 aspects are probably different clinical forms of chronic autoimmune pancreatitis. Some autoimmune diseases are associated with chronic autoimmune pancreatitis, but not consistently. One such disease involves a bile disorder very similar to primary sclerosing cholangitis but responsive to corticosteroid treatment. Pancreatitis may be a sign of intestinal inflammatory diseases (and vice versa): testing for Crohn's disease and ulcerative rectocolitis is justified in patients with idiopathic pancreatitis. Chronic autoimmune pancreatitis must be routinely considered in patients with a pancreatic tumor that is for a clinical, epidemiologic, serologic or imaging reason not completely consistent with pancreatic adenocarcinoma. A short corticosteroid therapy (< 4 weeks) is probably less harmful in a patient with pancreatic adenocarcinoma than pancreatectomy (or chemotherapy) in patients with chronic autoimmune pancreatitis. Diagnosis depends on a body of clinical and radiologic evidence. The diagnostic value of serologic markers and especially of autoantibodies must be clarified in the future.
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Affiliation(s)
- Philippe Lévy
- Pôle des Maladies de l'Appareil Digestif, Hôpital Beaujon, Clichy, France.
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28
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Abstract
OBJECTIVES To evaluate the clinical significance of a swollen main duodenal papilla and the associated immunohistopathologic findings in patients with autoimmune pancreatitis (AIP). METHODS Seventeen consecutive patients with AIP registered between April 2001 and October 2005 who underwent both endoscopic retrograde cholangiopancreatography and endoscopic biopsy were enrolled in this study. The endoscopic features, stromal inflammatory cell infiltrate (SICI), and results of immunohistochemical examination of the duodenal papilla using IgG4, CD3, and CD79a antibodies were retrospectively reviewed. These findings in the AIP patients were compared with those in 12 patients with chronic alcoholic tumor-forming pancreatitis (CAP). The numbers of cells in the SICI and of IgG4-positive plasma cells per high-power field were counted in all the histopathologic specimens. RESULTS A swollen main duodenal papilla was observed in 11 (11 [64.7%]/17) patients with AIP and 4 (4 [33.3%]/12) patients with CAP (P < 0.05). Resolution of the swollen main duodenal papilla was observed in all of these 11 patients with AIP (11 [100%]/11) in response to treatment with corticosteroids. On the other hand, the 6 patients without elevated serum IgG4 or a swollen duodenal papilla, but with a swollen pancreas, improved even without corticosteroid treatment. The number of cells in the SICI in the AIP patients was significantly higher than that in the CAP patients. Although in 13 of 17 AIP patients, infiltration by IgG4-positive plasma cells was detected in the duodenal papilla, no such significant infiltration of the duodenal papilla by IgG4-positive plasma cells was observed in the patients with CAP (P < 0.05). More predominant T-cell infiltration of the duodenal papilla was recognized in the AIP patients than in the CAP patients (P < 0.05). CONCLUSIONS These results suggest that a swollen main duodenal papilla with IgG4-positive plasma cell and T-cell-dominant infiltration and an abundant stromal cell infiltrate are characteristic findings in AIP. We suggest that these findings may be valuable adjuncts to the diagnosis of AIP as well as for selecting suitable candidates for corticosteroid therapy.
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Deheragoda MG, Church NI, Rodriguez-Justo M, Munson P, Sandanayake N, Seward EW, Miller K, Novelli M, Hatfield ARW, Pereira SP, Webster GJM. The use of immunoglobulin g4 immunostaining in diagnosing pancreatic and extrapancreatic involvement in autoimmune pancreatitis. Clin Gastroenterol Hepatol 2007; 5:1229-34. [PMID: 17702660 DOI: 10.1016/j.cgh.2007.04.023] [Citation(s) in RCA: 97] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Autoimmune pancreatitis (AIP) is recognized increasingly as a multisystem disorder. We evaluated the use of immunoglobulin (Ig)G4 immunostaining of pancreatic and extrapancreatic biopsy specimens to make a definitive diagnosis of AIP. METHODS Seventeen biopsy specimens and 3 gallbladder resections were assessed from 11 patients with clinical and radiologic features of AIP. Biopsy specimens from pancreas, liver, colon, stomach, duodenum, bone marrow, salivary gland, and kidney were analyzed morphologically, immunostained for IgG4-positive plasma cells, and compared with controls. RESULTS Positive IgG4 immunostaining enabled a definitive diagnosis in 10 of 11 (91%) AIP patients. In both pancreatic and extrapancreatic tissues, high levels of IgG4 immunostaining (>10 IgG4-positive plasma cells/high-power field) were found in 17 of 20 (85%) specimens from AIP patients compared with 1 of 175 (0.6%) specimens from controls (P < .05). Positive extrapancreatic IgG4 immunostaining was found in 8 of 11 (73%) patients, including all those with diagnostic features in the pancreas. Increased tissue IgG4 was found irrespective of serum IgG4 level. CONCLUSIONS The finding of IgG4 immunostaining within a range of clinically involved tissues supports the hypothesis that AIP is a multisystem disease. Positive IgG4 immunostaining in extrapancreatic tissues may allow a definitive diagnosis of AIP to be made in those with evidence of pancreatic disease, without the necessity of pancreatic biopsy or surgical exploration. Immunostaining of involved tissue for IgG4 may be particularly useful when AIP is suspected clinically but the serum IgG4 level is normal.
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Affiliation(s)
- Maesha G Deheragoda
- Department of Histopathology, University College Hospital, London, United Kingdom
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31
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Abstract
PURPOSE OF REVIEW As in our previous reviews, we endeavor to review important new observations in chronic pancreatitis made in the past year. Topics recently reviewed were truncated to accommodate a surge in publications on clinical aspects of chronic pancreatitis, which contained new observations or insights into new or old concepts. RECENT FINDINGS Cystic fibrosis carriers have been found to be at increased risk of pancreatitis. Autoimmune pancreatitis may belong to a multiorgan immunoglobulin G4-related autoimmune disease, and the natural history of chronic pancreatitis differs among the etiologies. Diffusion-weighted magnetic resonance imaging improves upon previous methodologies for diagnosing reduced pancreatic exocrine secretion, and fecal elastase-1 has been found to be a poor test for diagnosing pancreatic malabsorption. Visceral hyperalgesia or heightened central pain perception may contribute to pain in chronic pancreatitis. Instruments are evolving to assess quality of life in chronic pancreatitis, and fibrolytic agents have been found to have therapeutic promise. SUMMARY Researchers this past year have further characterized genetic, molecular and clinical aspects of chronic pancreatitis. Advancing the understanding of fibrogenesis, mechanisms of exocrine insufficiency, calcification, and pain and continuing development/modification of diagnostic tests should lead to improved prevention, detection and treatment of the condition. More accurate quantification of outcomes is critical for translating potential therapies from bench to bedside.
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Affiliation(s)
- Matthew J DiMagno
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
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Kamisawa T, Okamoto A. Autoimmune pancreatitis: proposal of IgG4-related sclerosing disease. J Gastroenterol 2006; 41:613-25. [PMID: 16932997 PMCID: PMC2780632 DOI: 10.1007/s00535-006-1862-6] [Citation(s) in RCA: 376] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2006] [Accepted: 06/20/2006] [Indexed: 02/06/2023]
Abstract
Autoimmune pancreatitis (AIP) is a peculiar type of pancreatitis of presumed autoimmune etiology. Many new clinical aspects of AIP have been clarified during the past 10 years, and AIP has become a distinct entity recognized worldwide. However, its precise pathogenesis or pathophysiology remains unclear. As AIP dramatically responds to steroid therapy, accurate diagnosis of AIP is necessary to avoid unnecessary surgery. Characteristic dense lymphoplasmacytic infiltration and fibrosis in the pancreas may prove to be the gold standard for diagnosis of AIP. However, since it is difficult to obtain sufficient pancreatic tissue, AIP should be diagnosed currently based on the characteristic radiological findings (irregular narrowing of the main pancreatic duct and enlargement of the pancreas) in combination with serological findings (elevation of serum gamma-globulin, IgG, or IgG4, along with the presence of autoantibodies), clinical findings (elderly male preponderance, fluctuating obstructive jaundice without pain, occasional extrapancreatic lesions, and favorable response to steroid therapy), and histopathological findings (dense infiltration of IgG4-positive plasma cells and T lymphocytes with fibrosis and obliterative phlebitis in various organs). It is apparent that elevation of serum IgG4 levels and infiltration of abundant IgG4-positive plasma cells into various organs are rather specific to AIP patients. We propose a new clinicopathological entity, "IgG4-related sclerosing disease", and suggest that AIP is a pancreatic lesion reflecting this systemic disease.
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Affiliation(s)
- Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan
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Lopez-Tomassetti Fernandez EM, Luis HD, Malagon AM, Gonzalez IA, Pallares AC. Recurrence of inflammatory pseudotumor in the distal bile duct: Lessons learned from a single case and reported cases. World J Gastroenterol 2006; 12:3938-43. [PMID: 16804988 PMCID: PMC4087951 DOI: 10.3748/wjg.v12.i24.3938] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Inflammatory myofibroblastic tumors (IMTs) or inflammatory pseudotumors (IPs) have been extensively discussed in the literature. They are usually found in the lung and upper respiratory tract. However, reporting of cases involving the biliopancreatic region has increased over recent years. Immunohistochemical study of these lesions limited to the pancreatic head or distal bile duct seems to be compatible with those observed in a new entity called autoimmune pancreatitis, but usually intense fibrotic reaction (zonation) predominates producing a mass. When this condition is limited to the pancreatic head, the common bile duct might be involved by the inflammatory process and jaundice may occur often resembling adenocarcinoma of the pancreas. We have previously reported a case of IMT arising from the bile duct associated with autoimmune pancreatitis which is an extremely rare entity. Four years after Kaush-Whipple resection, radiological examination on routine follow-up revealed a tumor mass, suggesting local recurrence. Ultrasound-guided FNA confirmed our suspicious diagnosis. This present case, as others, suggests that persistent follow-up is necessary in order to prevent irreversible liver damage at this specific location.
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Affiliation(s)
- E M Lopez-Tomassetti Fernandez
- Department of Gastrointestinal Surgery, University Hospital of Canary Islands, Ofra s/n. La Cuesta, La Laguna, Santa Cruz de Tenerife, Spain.
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