The Use of Immunoglobulin G4 Immunostaining in Diagnosing Pancreatic and Extrapancreatic Involvement in Autoimmune Pancreatitis

doi:10.1016/j.cgh.2007.04.023

Clinical Gastroenterology and Hepatology

Volume 5, Issue 10, October 2007, Pages 1229-1234

https://doi.org/10.1016/j.cgh.2007.04.023 Get rights and content

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.

Section snippets

Patients

Eleven consecutive patients (all male) seen in our center between 2004 and 2006 in whom a diagnosis of AIP was made and in whom archival tissue and biopsy specimens obtained at admission to our unit were available for assessment, were included in the study. The diagnosis of AIP was suspected on the basis of clinical and radiologic features⁴ using published diagnostic criteria for the disease.⁸ Patient details, the histologic material available for analysis, and the initial histologic diagnoses

Morphologic Appearances of Biopsy Tissue on H and E Sections

Two tissue samples (1 bone marrow trephine from patient 2, and a gastric biopsy specimen from patient 4) were normal morphologically and therefore were not analyzed further.

In 18 of 20 specimens (9 of 11 patients) the original diagnosis made on H&E sections alone was that of an organ-specific chronic inflammatory condition, or nonspecific features (Table 1).

On review of the pancreatic biopsy specimens, characteristic morphologic features of AIP were seen in 3 of 4 (75%). In addition, the

Discussion

AIP is now accepted to be a global disease,6, 25 and not confined to Japan, from where most reports have arisen. As more cases and small series have been published, the involvement of extrapancreatic tissues has been appreciated, and it may be that the pancreas represents just one target of a multisystem disease.⁵ Although new diagnostic criteria for AIP have placed greater importance on extrapancreatic disease5, 19 than did previous criteria,¹ all require pancreatic histology to make a

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The use of immunohistochemistry for IgG4 in the diagnosis of autoimmune pancreatitis: A systematic review and meta-analysis
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Citation Excerpt :
For those patients, other collateral evidence is needed for an AIP diagnosis. Normal serum IgG4 would not obviate the need for tissue IgG4 immunostaining, because a positive tissue IgG4 immunostaining of a pancreatic and/or extrapancreatic biopsy will occur irrespective of serum IgG4 levels in patients with AIP [6–8]. Moreover, in patients with indeterminate imaging features for AIP, elevated serum IgG4 alone is never sufficient to diagnose type 1 AIP as the ICDC state that two or more lines of strong collateral evidence are needed for cases with indeterminate imaging.
The diagnosis of autoimmune pancreatitis (AIP) remains challenging, especially when serum IgG4 is normal or imaging features are indeterminate. We performed a systematic review and meta-analysis to evaluate the performance of IgG4 immunostaining of pancreatic, biliary, and ampullary tissues as a diagnostic aid for AIP.
A comprehensive literature search of the PubMed, EMBASE, and Ovid MEDLINE databases was conducted until February 2020. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. A random-effects model was used to summarize the diagnostic odds ratio and other measures of accuracy.
The meta-analysis included 20 studies comprising 346 patients with AIP and 590 patients with other pancreatobiliary diseases, including 371 pancreatobiliary malignancies. The summary estimates for tissue IgG4 in discriminating AIP and controls were as follows: diagnostic odds ratio 38.86 (95% confidence interval (CI), 18.70–80.75); sensitivity 0.64 (95% CI, 0.59–0.69); specificity 0.93 (95% CI, 0.91–0.95). The area under the curve was 0.939 for tissue IgG4 in discriminating AIP and controls. Subgroup analysis revealed no significant difference in diagnostic accuracy according to control groups (pancreatobiliary cancer versus other chronic pancreatitis) and sampling site (pancreas versus bile duct/ampulla).
Current data demonstrate that IgG4 immunostaining of pancreatic, biliary, and ampullary tissue has a high specificity but moderate sensitivity for diagnosing AIP. IgG4 immunostaining may be useful in supporting a diagnosis of AIP when AIP is clinically suspected, but a combination of imaging and serology does not provide a conclusive diagnosis.
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2020, Advances in Medical Sciences
Autoimmune pancreatitis is a rare form of chronic pancreatitis. The first descriptions of the disease date back to the 1990s. Etiology is multifactorial, with the use of genetic, environmental and complex immunological mechanisms. It is classified into two subtypes. Type 1 is part of a group of diseases called IgG4-related disease. Clinically is autoimmune pancreatitis manifested by icterus and abdominal discomfort. It can rarely present as acute pancreatitis. There is also a completely asymptomatic form of the disease. The diagnosis is based on abnormalities in histology, imaging methods, serology, the involvement of other organs in relation to IgG4-related disease, and a significant positive response to corticosteroid therapy. Differential diagnosis between the focal form of autoimmune pancreatitis and pancreatic cancer can be complicated, with endosonography playing an important role. In the treatment, we use corticosteroids and other immunosuppressants including biological therapy. Patients with the asymptomatic disease should also be treated to prevent late complications and exocrine and endocrine insufficiency. In addition to drug treatment, endoscopic and/or surgical treatment may be necessary. Even after recovery, the disease can relapse. The relationship between autoimmune pancreatitis and malignancies has not been clearly confirmed. The goal of this review is to provide a comprehensive look at autoimmune pancreatitis and translate latest scientific knowledge into clinical practice.
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There is too little experience with either EUS-guided or radiology-guided FNA or core biopsies of pancreas to obtain sufficient cytologic or histologic tissue to make a diagnosis (Fig. 5).17,34–36 The additional immunostaining for IgG4 in extrapancreatic tissue may also support the diagnosis of AIP.37 Only after pancreatic malignancy has been ruled out, including a negative EUS-guided FNA, should a diagnostic steroid trial be conducted.7
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Original article—liver, pancreas, and biliary tractThe Use of Immunoglobulin G4 Immunostaining in Diagnosing Pancreatic and Extrapancreatic Involvement in Autoimmune Pancreatitis

Section snippets

Patients

Morphologic Appearances of Biopsy Tissue on H and E Sections

Discussion

Clin Gastroenterol Hepatol

Gastroenterology

Clin Radiol

Pancreatology

Hum Pathol

Gastroenterology

Gastroenterology

Chronic pancreatitis caused by an autoimmune abnormalityProposal of the concept of autoimmune pancreatitis

Dig Dis Sci

Long term prognosis of duct narrowing chronic pancreatitis: strategy for steroid treatment

Pancreas

Treating patients with autoimmune pancreatitis: results from a long term follow up study

Pancreatology

Autoimmune pancreatitis: response to therapy in a UK series

Gastroenterology

Diagnostic criteria for autoimmune pancreatitis by the Japan Pancreas Society

J Jpn Pancreas Soc

Autoimmune related pancreatitis

Gut

Extrapancreatic lesions in autoimmune pancreatitis

J Clin Gastroenterol

Original article—liver, pancreas, and biliary tract
The Use of Immunoglobulin G4 Immunostaining in Diagnosing Pancreatic and Extrapancreatic Involvement in Autoimmune Pancreatitis