Immunoglobulin G4 Immunostaining Research Articles

Clinicopathological study of surgically treated non-neoplastic diseases of the pancreas with special reference to autoimmune pancreatitis.

After the popularization of serum immunoglobulin G4 (IgG4) measurement and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in our institute, surgical resection for non-neoplastic diseases of the pancreas became less common. Although the incidence of such false-positive cases was clarified in the 10-year period after the introduction of these measures (2009-2018), these data were not compared with the 30years before 2009 (1979-2008). This study was performed to determine the percentage of autoimmune pancreatitis (AIP) that was included during the latter period and how the numbers of false-positive cases differed between the two periods. From 1979 to 2008, 51 patients had clinical suspicion of pancreatic carcinoma (false-positive disease). Among these 51 patients, 32 non-alcoholic patients who had tumor-forming chronic pancreatitis (TFCP) were clinically, histologically, and immunohistochemically compared with 11 patients who had TFCP during the latter 10-year period. Retrospective IgG4 immunostaining of false-positive TFCP revealed 14 (35.0%) cases of AIP in the former 30years versus 5 (45.5%) in the latter 10years. There were 40 (5.9%) cases of TFCP among 675 patients in the former 30years and 11 (0.9%) among 1289 patients in the latter 10years. When the TFCP ratio of pancreatic resections and the AIP ratio of false-positive TFCPs were compared between the two periods, the TFCP ratio was 5.9% versus 0.9% and the AIP ratio was 35.0% versus 45.5%, respectively. It can thus be speculated that IgG4 measurement and EUS-FNA are absolutely imperative for the diagnosis of TFCP.

Clinical Images: Dacryoadenitis in eosinophilic granulomatosis with polyangiitis mimicking immunoglobulin G4-related disease.

The patient, a 26-year-old woman, presented with a 2-week history of acute swelling in both lacrimal glands (A). She had recently developed uncontrolled asthma and nasal polyps. The laboratory test results were notable for an absolute eosinophil count of 5300 cells per μl (reference range 100-400 μl), exceeding 50% of circulating leukocytes. The antineutrophil cytoplasmic antibody test result was negative. Magnetic resonance imaging of the head confirmed swelling of the bilateral lacrimal glands (B, yellow arrowheads) and rhinosinusitis. A biopsy of her lacrimal gland revealed eosinophil-rich necrotizing granulomatous inflammation with vasculitis (C). Her serum immunoglobulin G4 (IgG4) level was slightly elevated (265 mg/dl, normal upper limit is 121 mg/dl), but IgG4 immunostaining of the biopsy specimen did not show a significant finding. A diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) was made. Treatment with 30 mg of prednisone was initiated, which was gradually tapered without glucocorticoid-sparing agents over 12 months. The swelling of her lacrimal glands resolved, and she was free of symptoms, including asthma and lacrimal gland swelling, at the 12-month follow-up. In summary, EGPA can present with lacrimal gland swelling and mimic IgG4-related Mikulicz disease (1, 2). A histopathological examination of the swollen lacrimal gland is the key to differentiating EGPA from IgG4-related Mikulicz disease in such cases. Disclosureform Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Immunoglobulin G4-related disease diagnosed by prostate biopsy: a case report

BackgroundImmunoglobulin G4-related disease is characterized by swelling of various organs throughout the body and nodules/hypertrophic lesions. However, its cause remains unknown. We report a case of immunoglobulin G4-related disease that was diagnosed based on the histopathological findings of prostate biopsy.Case presentationA 72-year-old Japanese man had been treated by a nearby doctor for hypertension, but subsequently developed lower urinary tract symptoms and was prescribed an α1 blocker for 1 year. However, the patient was subsequently referred to our department because his symptoms did not improve. Prostate-specific antigen was 1.258 ng/ml; however, the nodule was palpable in the right lobe on digital rectal examination, and magnetic resonance imaging suggested Prostate Imaging and Reporting and Data System category 3. Therefore, transrectal prostate needle biopsy (12 locations) under ultrasound was performed. Histopathological examination revealed no malignant findings, although infiltration of lymphocytes and plasma cells, and partial fibrosis were observed. No remarkable findings of obstructive phlebitis were observed. Immunoglobulin G4-related disease was suspected, and immunoglobulin and immunoglobulin G4 immunostaining was performed. Immunoglobulin G4 positive plasma cells were observed in a wide range, immunoglobulin G4 positive cells were noted at > 10 per high-power field, and the immunoglobulin G4 positive/immunoglobulin G positive cell ratio was > 40%. Serum immunoglobulin G4 levels were high at 1600 mg/dl. Enhanced abdominal computed tomography findings suggested periaortitis. Additionally, multiple lymphadenopathies were observed around the abdominal aorta. The patient was accordingly diagnosed with immunoglobulin G4-related disease definite, diagnosis group (definite). We proposed steroid treatment for periaortic soft tissue lesions and lower urinary tract symptoms; however, the patient was refused treatment. A computed tomography scan 6 months after diagnosis revealed no changes in the soft tissue lesions around the aorta. Follow-up computed tomography examinations will be performed every 6 months.ConclusionIf immunoglobulin G4-related disease is suspected and a highly invasive examination is required for histopathological diagnosis, this can be performed by a relatively minimally invasive prostate biopsy for patients with lower urinary tract symptoms. Further evidence is needed to choose an optimal candidate for prostate biopsy for lower urinary tract symptoms patients with suspicion of immunoglobulin G4-related disease. For patients with lower urinary tract symptoms with immunoglobulin G4-related disease or a history, performing a prostate biopsy may avoid unnecessary treatment. However, if steroid therapy is ineffective, surgical treatment should be considered.

Development of IgG4-related pancreatitis and kidney disease 7 years after the onset of undiagnosed lymphadenopathy: A case report.

This report describes a patient diagnosed with immunoglobulin G4 (IgG4)-related pancreatitis and kidney disease 7 years after the onset of undiagnosed lymphadenopathy. A 48-year-old Japanese woman presented with fatigue and leg oedema. Computed tomography showed perigastric lymphadenopathy, for which she underwent a laparoscopic biopsy of the perigastric lymph nodes. Although histopathological examination of the lymph nodes did not lead to a definitive diagnosis, serological tests revealed elevated serum IgG4 levels (558 mg/dl) and IgG4 immunostaining of the lymph nodes showed IgG4-positive plasma cell infiltration, leading to the suspicion of IgG4-related disease. Further workup revealed no organ lesion other than lymphadenopathy. At age 55 years, despite having no subjective symptoms, contrast-enhanced computed tomography showed low-density lesions in the tail of the pancreas and the left kidney. Histopathological examination showed lymphocyte infiltration, consisting of a mixture of plasma cells and eosinophils, in both organs and obliterative phlebitis in the pancreas. IgG4 immunostaining of the kidney specimens showed 160 IgG4-positive cells per high-powered field, with the IgG4+/IgG+ cell ratio being almost 100%, leading to a diagnosis of IgG4-related pancreatitis and kidney disease. Treatment with prednisolone for 2 months resulted in lesion improvement. Although the diagnosis of IgG4-related lymphadenopathy is often challenging in patients with lymphadenopathy alone, findings in the present patient emphasise the importance of long-term follow-up, as it may allow early detection of involvement of other organs by IgG4-related disease.

Pediatric Eosinophilic Esophagitis Is Associated With Increased Lamina Propria Immunoglobulin G4-Positive Plasma Cells.

Eosinophilic esophagitis (EoE) is considered a TH2-mediated food allergy disease that leads to submucosal esophageal fibrosis and strictures. Recent studies focused on adults with EoE identified a strong association with elevated esophageal IgG4 immunostaining. Our study aimed to determine the association of IgG4 with EoE in pediatric patients. Using our local EoE research registry, we identified 41 adequate biopsies from EoE patients. We used 10 age- and sex-matched patients with no diagnostic abnormalities at endoscopy or on biopsy. Using a monoclonal antibody to Immunoglobulin G4 (IgG4), we determined the maximum density of IgG4-positive plasma cells (IgG4-PC) per high-power field (hpf). Using a semi-quantitative assessment, we also graded the noncellular staining of the lamina propria and epithelium. Our EoE cohort consisted predominantly of boys with an average age of 5.9 years and 63% had a documented IgE-based food allergy. Median peak eosinophilia was 40 eosinophils/hpf and the median IgG4-PC density was 39/hpf in the active esophagitis patients, compared with a median of 0 IgG4-PC/hpf in the non-EoE patients (P = 0.0001). EoE patients with a food allergy showed a significantly higher IgG4-PC density (44.5/hpf) than those without a food allergy (8/hpf; P = 0.0385). There was no significant association between IgG4-PC density and peak eosinophilia (r = 0.0011). We demonstrate that active esophagitis in pediatric EoE patients is associated with elevated levels of IgG4-positive plasma cells, which was more significant in EoE patients with a documented food allergy. Our study also adds to the growing literature that EoE may involve more than just an exaggerated TH2 immune response.

Immunoglobulin G4 (IgG4)-Positive Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma and Idiopathic Orbital Inflammation.

To report clinical and pathological characteristics of idiopathic orbital inflammation and ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma with immunoglobulin G4 (IgG4)-positive plasma cells. A retrospective histopathological review and clinical case series. A total of 51 biopsy samples from January 2005 to December 2015 were used in this study, including 21 cases of biopsy-confirmed idiopathic orbital inflammation and 30 cases of biopsy-confirmed ocular adnexal MALT lymphoma. Most cases of ocular adnexal lymphoma were conjunctival tissue. Retrospective immunohistochemical studies were performed to estimate the IgG4 and IgG4/IgG ratios. Histopathologic features, demographic and clinical data, radiologic findings, treatment, and follow-up information for each patient were analyzed. Among idiopathic orbital inflammation, 6 (28.6%) of the 21 patients were diagnosed as "probable" ocular adnexal IgG4-related diseases and 13 (43.3%) of the 30 patients were diagnosed as MALT lymphoma with IgG4-positive plasma cells. Six cases of 13 IgG4-positive MALT lymphoma group had contralateral chronic inflammatory lesions infiltrated by IgG4-positive plasma cells, which was significantly (p = 0.007) higher than that in the IgG4-negative group. Conjunctival involvement was 69% of the IgG4-positive MALT lymphoma cases. Bilateral involvement of the ocular adnexa was significantly (p = 0.02) more frequent among IgG4-positive MALT lymphoma patients than that in IgG4-positive idiopathic orbital inflammation patients. Recurrence rate in the IgG4-positive group was higher (p = 0.05) than that in the IgG4-negative group but not significantly. This study presented an unusual framework of ocular adnexal IgG4-related inflammation, in conjunctiva. It is important to understand contralateral chronic inflammatory lesions and their relationship with IgG4-positive MALT lymphoma. Tissue biopsy and IgG4 immunostaining are required for all cases because IgG4-positive MALT lymphoma can arise from a pre-existing IgG4-positive chronic inflammatory lesions. This is the first study that performs IgG4 immunostaining for tissue from a relatively large number of conjunctival MALT lymphomas in a single center. Therefore, it will help to diagnose conjunctival lymphoproliferative disease.

Hipofisitis linfoplasmocitaria con expresión de IgG4

Immunoglobulin G4 (IgG4)-related lymphoplasmacytic hypophysitis is a recently known entity. It belongs to the IgG4-related diseases (IgG4-RD), in which one or more organs may be involved, with compressive or obstructive symptoms, or dysfunctionality due to cellular infiltration. The pituitary gland can be isolatedly affected. Clinically, lymphoplasmacytic hypophysitis presents with diabetes insipidus, hypopituitarism and/or symptoms of an occupying sellar mass, being the non-secreting sellar adenomas and other types of hypophysitis the main differential diagnosis. In order to reach the diagnosis, the presence of pituitary enlargement or pituitary stalk thickening on an MRI scan, a distinctive histopathology with positive for IgG4 immunostaining in more than 10 plasma cells per high-power field, and elevated serum IgG4 levels, confirms this type of hypophysitis. As this entity has an excellent response to glucocorticoids, the diagnosis suspicion may avoid an unnecessary surgery in most patients.

Immunoglobulin G4-related ophthalmic disease presenting as uveitis

This report documents a 47-year-old man who presented with back pain, uveitis and an elevated Westergren sedimentation rate. On biopsy, a paraspinal lesion showed a nonspecific chronic inflammatory cell infiltrate. The eye symptoms, after initially responding to immunosuppressive therapy, worsened and progressed to pain, resulting in an extirpation of the right eye. The histopathology of the excised eye showed an inflammatory pseudotumor marked by a lymphoplasmacytic infiltrate, areas of fibrosis, rare evidence of obliterative phlebitis and, focally, over 20 Immunoglobulin G4 (IgG4)-positive staining cells per high power microscopic field. IgG4-related ophthalmic disease is a relatively rare inflammatory lesion involving the eye and periorbital region. It is defined by a marked lymphoplasmacytic cell infiltrate, fibrosis obliterative phlebitis and increased IgG4 immunostaining (at least 10 cells per high power microscopic field in excised tissue). The entity is not unique to the eye, and has been described in other organs including the brain, endocrine organs, liver and kidney. The clinical presentation is often related to the location of the inflammatory infiltrates, and treatment involves the use of corticosteroids and other immunosuppressive agents. It is important to recognize IgG4-related ophthalmic disease because the condition appears to put patients at increased risk of developing lymphoma.

Frequency of immunoglobulin G4‐related aortitis in cases with aortic resection and their clinical characteristics compared to other aortitises

To identify the frequency of immunoglobulin G4 (IgG4)-related aortitis in patients who undergo aorta surgery and are diagnosed by pathology as having chronic aortic inflammation and to compare IgG4-related aortitis with other non-infectious aortitises in terms of clinical characteristics. The aorta specimen pathological reports of 1418 patients who underwent aortic aneurysm or dissection surgery were reviewed. In total, 41 had chronic aortic inflammation without atherosclerosis, cancer or infection. Their aorta biopsy specimens were subjected to IgG4 immunostaining. IgG4-related aortitis was diagnosed if the IgG4-positive plasma cell count exceeded 50 per high power field (HPF), the ratio of IgG4-positive to IgG-positive plasma cells exceeded 50% and dense lymphoplasmacytic infiltration, fibrosis and/or obliterative phlebitis were observed. Of the 41 non-infectious aortitis cases, 29, six and six had idiopathic aortitis, Takayasu's arteritis and Behcet's aortitis, respectively. Of the 29 idiopathic aortitis cases, three had IgG4-related aortitis. All were male and > 65 years of age. Two had thoracic aortic aneurysms and one had an abdominal aortic aneurysm. Their IgG4-positive plasma cell counts were 60/HPF or higher; lymphoplasmacytic infiltration and/or fibrosis, but not obliterative phlebitis, were observed. The IgG4-related aortitis cases were older (67 [range, 65-69] years) than the Takayasu's arteritis (47.5 [38-58] years) or Behcet's aortitis (47 [31-56] years) cases and more likely to be male than the Takayasu's arteritis cases (100% vs. 17%). In patients with chronic aortic inflammation, 7% had IgG4-related aortitis. This disease may be more common in older male patients than in other demographic groups.

Ulcerative Colitis and Immunoglobulin G4

Background/AimsUlcerative 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.MethodsAssociations 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.ResultsUC 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).ConclusionsUC 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.

Surgical Debulking for Idiopathic Dacryoadenitis: A Diagnosis and a Cure

Idiopathic inflammatory tumor of the lacrimal gland, also called idiopathic dacryoadenitis, generally is treated with high-dose, long-term systemic corticosteroids, despite their limited success, high recurrence rate, and incidence of drug-induced side effects. This study describes the outcome of patients with idiopathic dacryoadenitis who were managed with surgical debulking. Retrospective case series from 2 tertiary referral centers. Forty-six patients (46 lacrimal glands). Review of the clinical records, radiologic scans, and histopathologic specimens, with additional immunoglobulin G4 immunostaining. Clinical signs and symptoms at 2 months after the surgery and off medications. Before referral, 41% (19 of 46) of the patients had received systemic high-dose corticosteroids, after which they all showed recurrence, of whom 26% (5 of 19) became dependent on corticosteroids. At referral, all patients underwent debulking surgery of the inflammatory lacrimal gland mass for diagnostic and therapeutic reasons. Additionally, intralesional or systemic low-dose corticosteroids were given during the operation or the first postoperative days in 54% (25 of 46) of the patients. At 2 months after the debulking surgery, a full clinical recovery was seen in 80% (37 of 46) of the patients. A recurrence occurred in 8% (3 of 37) of the patients 4 months and 2.2 and 4.6 years later. Surgical failure (20%; 9 of 46) was correlated with prior corticosteroid treatment (P = 0.002, Fisher exact test), but not with sclerosing inflammation present in 28% (13 of 46). The median follow-up time was 7.2 years (range, 0.7-18 years). Debulking biopsy procedures for idiopathic dacryoadenitis, in addition to being diagnostic, may be therapeutic.

Periaortitis, Coronary Vasculitis and Retro-Orbital Pseudotumor in a Patient with Immunoglobulin G4-Related Sclerosing Vasculitis

Immunoglobulin G4 (IgG4)-related sclerosing vasculitis is characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. Serum IgG4 level and immunostaining with anti-IgG4 antibody are useful for the diagnosis. In this article, a 61-year-old male patient who was admitted with the complaints of dyspnea, diffuse edema and chest pain and presented with increased pericardial fluid and serum IgG4 level was reported. Thoracoabdominal computed tomography (CT) scan demonstrated a soft tissue mass starting at arcus aorta and surrounding thoracal and abdominal aorta. After biopsy was obtained, the patient was diagnosed with IgG4-related sclerosing vasculitis.

IgG4 immunostaining of duodenal papillary biopsy specimens may be useful for supporting a diagnosis of autoimmune pancreatitis

Autoimmune pancreatitis (AIP) is now considered to be part of an immunoglobulin G4 (IgG4)-related systemic fibroinflammatory disease. We evaluated whether IgG4 immunostaining of duodenal papillary biopsy specimens is useful for supporting a diagnosis of AIP. A prospective study. A tertiary academic center. We obtained 2 forceps biopsy specimens from the major duodenal papilla (MDP) of 19 symptomatic AIP patients during ERCP before steroid administration. As a control, biopsy specimens were obtained from the MDP of patients with pancreatic cancer (n = 35), cholangiocarcinoma (n = 20), ampullary cancer (n = 11), ordinary chronic pancreatitis (n = 18), and AIP in remission (n = 16) and immunohistochemically examined. Specimens were considered positive for IgG4 immunostaining if there were more than 10 IgG4-positive plasma cells per high-power field. Positive IgG4 immunostaining of the MDP was found in 10 (53%) of 19 symptomatic AIP patients, but was absent in the control groups. Among symptomatic AIP patients (n = 19), 5 (83%) of 6 AIP patients with elevated serum IgG4 levels exhibited positive IgG4 staining of the MDP, whereas 5 (38%) of 13 AIP patients with normal serum IgG4 levels showed positive IgG4 staining of the MDP. Nine of 19 symptomatic AIP patients also underwent pancreatic biopsy, and positive IgG4 immunostaining of the MDP was observed in patients with positive pancreas IgG4 staining (4/6, 67%), but not in patients with negative pancreas IgG4 staining (0/3). Small symptomatic AIP patient population. Positive IgG4 immunostaining of the MDP was an extremely specific and moderately sensitive tool for the diagnosis of AIP. IgG4 immunostaining of the MDP may be useful for supporting a diagnosis of AIP, especially when AIP is suspected clinically but serum IgG4 levels are normal or pancreatic tissue is not available.

The role of Movat pentachrome stain and immunoglobulin G4 immunostaining in the diagnosis of autoimmune pancreatitis

Autoimmune pancreatitis is highly responsive to steroid therapy, but because it mimics pancreatic cancer, it often precipitates unnecessary surgery. Adequate diagnostic tests are needed to permit appropriate medical therapy. Lymphocytic and obliterative phlebitis are reported in the majority of cases, as are elevated IgG4-positive plasma cells, indicating their high sensitivity. Their specificities, especially when used in conjunction, however, remain largely unknown. Movat pentachrome vascular and IgG4 immunohistochemical stains were performed on a total of 15 autoimmune pancreatitis cases (11 pancreatic resections and 4 biopsies), 39 usual-type alcoholic or idiopathic chronic pancreatitis cases, 35 pancreatic ductal adenocarcinoma-associated chronic pancreatitis cases, and 29 normal pancreata. Marked and diffuse lymphocytic and obliterative venulitis were detected in all 15 cases of autoimmune pancreatitis on Movat staining (100% sensitivity). Only a single carcinoma-associated chronic pancreatitis case among all of the controls showed diffuse benign venulitis that was nonobliterative (99% specificity). Nine of 13, 9 autoimmune pancreatitis cases showed marked IgG4 immunopositivity at ⩾10 positive plasma cells per × 400 field (69% sensitivity). No increased IgG4 plasma cells were found in any of 103 controls (100% specificity). In combination, all of the autoimmune pancreatitis cases had at least one (13/13) and most had both markers (9/13), whereas none of the controls had both markers. Overall, these combined stains show very promising diagnostic utility and should be considered in combination with clinical and serologic analyses in the evaluation of chronic pancreatitis suspicious for malignancy. Future validating studies on preoperative biopsies with outcome data following steroid therapy will be essential.

Immunoglobulin G4-associated cholangitis

Immunoglobulin G4-associated cholangitis is a recently identified clinical entity characterized by infiltration of immunoglobulin G4 -bearing plasma cells in bile ducts and other affected tissues. This review is focused mainly on the most recent studies published during the last 2 years that have increased our understanding of this clinical entity. Investigations concerning the immune mechanisms, liver histology in immunoglobulin G4-associated cholangitis and reports of clinical and radiological features of the condition as well as medical therapy are discussed. Immunoglobulin G4-associated cholangitis was found to be characterized by overproduction of T helper 2 cells, and regulatory cytokines (interleukin-10 and transforming growth factor-beta) were upregulated in the affected tissues. Immunoglobulin G4 immunostaining in a range of clinically involved tissues in patients with immunoglobulin G4-associated cholangitis and autoimmune pancreatitis was found to be important for diagnostic purposes, which is probably most useful in cases with normal immunoglobulin G4 levels. It has become apparent that multiple measurements of immunoglobulin G4 levels in patients with clinically suspected immunoglobulin G4-associated cholangitis are important, revealing abnormally high levels in patients with normal immunoglobulin G4 on initial testing. Most patients respond to steroids initially but disease relapse seems to be common. A significant proportion of primary sclerosing cholangitis patients have elevated immunoglobulin G4 levels.

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

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. 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. 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. 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.

Immunoglobulin G4 associated cholangitis: Description of an emerging clinical entity based on review of the literature

During the last decade, patients with steroid responsive sclerosing cholangitis have been described in a number of case reports and a few cases series. These patients meet diagnostic criteria for primary sclerosing cholangitis (PSC) but seem to have a better prognosis and are often, but not always, associated with autoimmune pancreatitis (AIP). Unlike biliary strictures in PSC, most PSC-like biliary strictures seen in association with AIP respond well to steroids and some have been shown to resolve after immunosuppressive treatment during prolonged follow-up. In addition, steroid-responsive dominant bile duct lesions, sometimes mimicking infiltrating hilar cholangiocarcinoma, without pancreatic abnormalities have also been reported. Here we review the literature on this emerging clinical entity and suggest that this condition of steroid responsive biliary strictures be named Immunoglobulin G4 (IgG4) Associated Cholangitis (IAC). We performed an electronic database search of MEDLINE for case reports and case series of sclerosing cholangitis with pancreatitis and/or pancreatic mass (1960–July 2006). Articles were limited to English and these case reports and cases series were reviewed and all references on the combination of sclerosing cholangitis and pancreatitis as well as IgG4 positive cholangitis without pancreatic involvement not identified by our original search were obtained. Terminology and Definition