Infiltration Of IgG4-positive Cells Research Articles

The 2023 revised diagnostic criteria for IgG4-related dacryoadenitis and sialadenitis.

For the diagnosis of IgG4-related dacryoadenitis and sialadenitis, either revised comprehensive diagnostic criteria or organ-specific diagnostic criteria for IgG4-related dacryoadenitis and sialadenitis in 2008 were applied; however, the collected knowledge for IgG4-related dacryoadenitis and sialadenitis required us to revise the criteria for IgG4-related dacryoadenitis and sialadenitis. The board member of Japanese Study Group for IgG4-related Dacryoadenitis and Sialadenitis revised the diagnostic criteria for IgG4-related dacryoadenitis and sialadenitis. We collected the clinical questions to be revised and performed a review of the literature. When the data were insufficient, additional data collection was performed. After the revision, public comments were collected. The three major points were revised. 1. Asymmetric or under two pairs of dacryoadenitis and sialoadenitis were included as IgG4-related dacryoadenitis and sialadenitis. 2. The thresholds of IgG4-positive cell infiltration were adjusted to an IgG4+/IgG+ ratio >0.4 and IgG4+ cells >10 per high power field. 3. The labial salivary gland biopsy was allowed to diagnose IgG4-related dacryoadenitis and sialadenitis. The revised diagnostic criteria for IgG4-related dacryoadenitis and sialadenitis solved several issues with the previous criteria. It will improve the early diagnosis of IgG4-related dacryoadenitis and sialadenitis, especially in situations without enough resources for a biopsy.

Common Characteristics of Sinonasal Inflammation Associated with IgG4-Related Disease and Other Chronic Inflammatory Diseases: A Retrospective Observational Study

Plain Language SummaryImmunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4 levels and tissue IgG4-positive cells. A part of IgG4-RD patients has sinonasal lesions. Because other inflammatory diseases also have features common to IgG4-RD, accurate knowledge of IgG4-RD is required. However, very little is known about IgG4-related rhinosinusitis. This study retrospectively analyzed clinicopathological features of IgG4-related rhinosinusitis and compared IgG4-related rhinosinusitis with other inflammatory diseases. Seven patients with sinonasal lesions and high serum IgG4 levels were retrospectively reviewed. Six of 7 patients were diagnosed with IgG4-RD, while one was diagnosed with granulomatosis with polyangiitis (GPA). In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and computed tomography showed ethmoid sinus involvement in 5 patients (83%), which shared common features with eosinophilic sinusitis (ECRS). However, no patients showed histopathological eosinophil infiltration. Although the patient with GPA revealed tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient also had saddle nose and positivity of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA), which indicated GPA. We diagnosed the patient with GPA, which is a known mimicker of IgG4-RD. In this study, the patients with IgG4-related rhinosinusitis had clinical and pathological characteristics similar to those of ECRS and GPA. IgG4-related rhinosinusitis should be diagnosed based on not only tissue infiltration of IgG4-positive cells but also systemic findings including nasal findings and serum ANCA levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration.

Prognostic implication of IgG4 and IgG1-positive cell infiltration in the lung in patients with idiopathic interstitial pneumonia

Immunoglobulin (Ig) G4-positive cells are rarely observed in the lungs of patients with idiopathic interstitial pneumonias (IIPs). IgG1 may be more pathogenic than IgG4, with IgG4 having both pathogenic and protective roles in IgG4-related disease (IgG4-RD). However, the role of both IgG1 and IgG4 in IIPs remains unclear. We hypothesized that patients with IgG4-positive interstitial pneumonia manifest different clinical characteristics than patients with IgG4-RD. Herein, we identified the correlation of the degree of infiltration of IgG1- and IgG4-positive cells with IIP prognosis, using a Japanese nationwide cloud-based database. We included eighty-eight patients diagnosed with IIPs after multidisciplinary discussion, from April 2009 to March 2014. IgG4-positive cell infiltration was identified in 12/88 patients with IIPs and 8/41 patients with idiopathic pulmonary fibrosis (IPF). Additionally, 31/88 patients with IIPs and 19/41 patients with IPF were diagnosed as having IgG1-positive cell infiltration. IgG4-positive IIPs tended to have a better prognosis. Conversely, overall survival in cases with IgG1-positive IPF was significantly worse. IIPs were prevalent with IgG1- or IgG4-positive cell infiltration. IgG1-positive cell infiltration in IPF significantly correlated with a worse prognosis. Overall, evaluating the degree of IgG1-positive cell infiltration may be prognostically useful in cases of IPF.

Primary Hyper-IgE-Related Salivary Gland Disease: A New Disease Entity.

To clarify the clinicopathological characteristics of primary hyper-IgE-related salivary gland disease (PHIESD), which is a newly proposed entity. Fifteen consecutive patients pathologically diagnosed with chronic sialadenitis were enrolled, and their clinicopathological features were comprehensively analyzed. (1) multiple salivary gland enlargement; (2) elevated serum IgE and/or IgE-positive cell infiltration in salivary gland tissues; (3) histology-confirmed lymphoplasmacytic infiltration; (4) exclusion of other known diseases. The male-to-female ratio was 5:10. The median age was 21 (range, 3-63) years. The average number of affected glands was 3.7 ± 1.4. Submandibular, parotid, and sublingual glands were involved in 15, 8, and 2 patients, respectively. Comorbid diseases included allergic diseases in seven patients and autoimmune diseases in two. Elevated serum IgE (median 175 kU/L) was seen in all patients. Serum IgG4 was slightly elevated in three patients. Histologically, most patients had mild lesions, including mild lymphocyte infiltration (60%) and focal fibrosis (66.7%). Lymphoid follicular formation (53.3%), moderate to severe lymphocytic inflammation (40%) and severe fibrosis (33.3%) were also observed. Immunohistochemically, IgE-positive cells infiltrated mainly around the ducts, with scattered infiltration of IgG4-positive, mast, and interleukin-4 positive cells. During follow-up (median, 46months) of ten patients without intervention and two with immunosuppressive therapy, no significant changes in gland size or serum IgE level were noted. PHIESD manifests as homogeneous enlargement of multiple salivary glands and elevated serum IgE. Histopathology further verifies the diagnosis. It might be associated with anaphylaxis or autoimmune dysfunction. Conservative treatment is suggested. 4 Laryngoscope, 132:2132-2138, 2022.

Investigation of IgG4-positive cells in idiopathic multicentric Castleman disease and validation of the 2020 exclusion criteria for IgG4-related disease.

Patients with plasma cell type idiopathic multicentric Castleman disease (PC‐iMCD) often show elevated serum IgG4 levels and IgG4‐positive cell infiltration in tissues due to overproduction of interleukin‐6, and may meet the diagnostic criteria for IgG4‐related disease (IgG4‐RD). Although PC‐iMCD has been listed as a major exclusion disease for IgG4‐RD, distinguishing between these diseases is challenging due to a lack of highly specific diagnostic biomarkers. In 2020, we proposed exclusion criteria of IgG4‐RD mimickers. In this paper, we validated the accuracy of the criteria in excluding one of the mimickers, PC‐iMCD, from IgG4‐RD. Validation was performed on 57 PC‐iMCD patients (39 presenting lymph node lesions and 19 with lung lesions) and 29 IgG4‐RD patients (22 presenting lymph node lesions and seven with lung lesions). According to our results, 20.5% of the PC‐iMCD patients with lymph node lesions and 42.1% of those with lung lesions met the diagnostic criteria for IgG4‐RD. All these patients with PC‐iMCD were excluded from a diagnosis of IgG4‐RD by the proposed criteria. Additionally, 6.9% of IgG4‐RD patients met the exclusion criteria. Thus, if the exclusion criteria are met, diagnosis should be made based on a combination of findings including organ distribution of disease, response to steroid therapy, and other pathological findings.

S1483 A 20-Year-OId Female With Obstructive Jaundice and a Pancreatic Head Mass: A Case Report of Type 2 Autoimmune Pancreatitis

Introduction: Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that may be associated with IgG4 laden lymphoplasmacytic infiltration and fibrosis in multiple organs. It accounts for only a small percentage of all patients with chronic pancreatitis. It can present with abdominal pain, jaundice, recurrent acute pancreatitis, or clinical findings similar to pancreatic cancer. Radiologic findings can also be similar to the above. Therefore, it is important to fully understand the radiologic and histologic nuances of AIP. We review a case of a 20-year-old female who presented with abdominal pain and jaundice who was subsequently diagnosed with Type 2 AIP. Case Description/Methods: A patient with no known past medical history presented with one week of abdominal pain. Imaging demonstrated a normal appearing pancreas with a nodular area of soft tissue fullness at the junction of the pancreatic head and body. Patient returned a few weeks later with jaundice. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a significant biliary stricture which was stented. EUS with biopsies demonstrated mild acute on chronic inflammation of the ampulla and mild acute inflammation of the pancreatic head as well as benign pancreatic parenchyma with edema, very focal fibrosis, and focal neutrophilic infiltrate in acini and intralobular small ducts. Steroids were prescribed leading to resolution of signs and symptoms. Discussion: Initial presentation of AIP can mimic that of other pancreatic pathology so further imaging with biopsy is necessary to make a final diagnosis. Type 1 and Type 2 AIP both have histologic findings of periductal infiltration of plasma cells and lymphocytes, peculiar storiform fibrosis, and venulitis. Type 1 typically has a high number of IgG4 positive plasma cells and can be associated with various systemic lesions related to IgG4 positive cell infiltrates. Type 2 is known for intraluminal and intraepithelial neutrophils in small to medium ducts and acini causing destruction of the duct lumen and is considered a pancreatic specific disease. In both types imaging tends to show diffuse parenchymal enlargement with delayed enhancement and ductal strictures without significant upstream dilatation. Treatment of AIP consists of steroids with Type 1 known to have relapses requiring re-treatment. Based on the histologic and radiologic findings a presumptive diagnosis of Type 2 AIP was made. Response to steroid treatment and no evidence of relapse confirmed the diagnosis.Figure 1.: A single severe stenosis seen in the lower third of the common bile duct.

Tertiary lymphoid tissue in early\u2010stage IgG4-related tubulointerstitial nephritis incidentally detected with a tumor lesion of the ureteropelvic junction: a case report

BackgroundIgG4-related kidney disease causes renal impairment of unknown pathogenesis that may progress to kidney failure. Although ectopic germinal centers contribute to the pathogenesis of the head and neck lesions of IgG4-related disease, the presence of tertiary lymphoid tissue (TLT) containing germinal centers in IgG4-RKD has rarely been reported. Case presentationWe report a 72-year-old Japanese man who had IgG4-related tubulointerstitial nephritis (TIN) with TLT formation incidentally detected in a resected kidney with mass lesion of IgG4-related ureteritis in the ureteropelvic junction. During follow-up for past surgical resection of a bladder tumor, renal dysfunction developed and a ureter mass was found in the right ureteropelvic junction, which was treated by nephroureterectomy after chemotherapy. Pathology revealed no malignancy but abundant IgG4-positive cell infiltration, obliterative phlebitis and storiform fibrosis, confirming the diagnosis of IgG4-related ureteritis. In the resected right kidney, lymphoplasmacytes infiltrated the interstitium with focal distribution in the renal subcapsule and around medium vessels without storiform fibrosis, suggesting the very early stage of IgG4-TIN. Lymphocyte aggregates were also detected at these sites and consisted of B, T, and follicular dendritic cells, indicating TLT formation. IgG4-positive cells infiltrated around TLTs.ConclusionsOur case suggests that TLT formation is related with the development of IgG4-TIN and our analysis of distribution of TLT have possibility to elucidate IgG4-TIN pathophysiology.

IgG4-related focal retroperitoneal fibrosis in ureter suggestive of colon cancer recurrence and resected laparoscopically: a case report

BackgroundImmunoglobulin G4-related disease (IgG4-RD) is a novel disease concept of unknown cause that is characterized by abundant infiltration of IgG4-positive cells, mass-forming lesions, and elevated serum IgG4 levels. The infiltration of IgG4-positive plasma cells and lymphocytes causes swelling, inflammation, fibrosis, and obliterative phlebitis in multiple organs. On the other hand, IgG4-RD occurring in the ureters has rarely been reported. To our knowledge, this is the first report of laparoscopic partial ureteral resection for IgG4-related focal retroperitoneal fibrosis in a ureter with suspected colon cancer recurrence.Case presentationA 72-year-old man with a history of sigmoid colon cancer visited Shiga University of Medical Science Hospital for regular follow-up in December 2019. Enhanced abdominal computed tomography revealed a mass involving the left ureter. Furthermore, fluorine-18 fluorodeoxyglucose positron emission tomography showed significant accumulation of fluorodeoxyglucose uptake in the same region. Due to the possibility of colon cancer recurrence, a laparoscopic excisional biopsy with partial ureteral resection was performed. Histologically, IgG4-positive plasma cell infiltration exceeding 10 cells per high-power field and a high ratio of IgG4-positive/IgG-positive cells exceeding 40% were observed. The postoperative serum IgG4 level was 384 mg/dL. With the application of these findings to the diagnostic algorithm in the comprehensive diagnostic criteria for IgG4-RD, the mass-forming lesion was diagnosed as definitive IgG4-related focal retroperitoneal fibrosis.ConclusionsIgG4-RD should be considered in the differential diagnosis of retroperitoneal lesions. Moreover, laparoscopic surgery may be useful for making the diagnosis in difficult-to-biopsy cases.

Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.

BackgroundAlthough increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear. Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases. This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls. We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.MethodsWe collected sera from 12 IgG4RD patients and 8 healthy controls. IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix. IgG4 N-glycans were analyzed by S-BIO GlycanMap® Xpress methodology.ResultsSignificant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls. Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans. Furthermore, there were no significant differences in the glycosylation of IgG4 N-glycans between patients with and without individual organ involvement of IgG4RD.ConclusionsAlthough IgG4 has anti-inflammatory properties, IgG4 G0 and F1 glycans were increased in patients with IgG4RD. Our results suggest that decreased galactosylation of IgG4 is not related to complement activation and the differences of individual organ involvement in IgG4RD. IgG4 fucosylation change may be related to complement activation in IgG4RD. Further investigation is needed to clarify the role of IgG4 in IgG4RD.

Xanthogranulomatous cholecystitis shows overlapping histological features with IgG4-related cholecystitis.

Xanthogranulomatous cholecystitis (XGC), an unusual histological variant of chronic cholecystitis, is characterised by mixed foamy histiocytic and lymphoplasmocytic infiltration and fibrosis. Radiologically, the poorly defined nodular growth pattern often leads to the misinterpretation of XGC as gallbladder cancer. In this study, we aimed to identify the relationship of XGC with IgG4-related cholecystitis. We re-evaluated 57 surgically resected XGCs and 104 conventional chronic cholecystitis cases, according to the histological features observed in IgG4-related disease, including lymphoplasmocytic infiltration, storiform fibrosis, obliterative phlebitis, and IgG4-positive plasma cells. XGCs contained a significantly increased mean number of IgG4-positive plasma cells [34.8/high-power field (HPF)] as compared with conventional chronic cholecystitis (4.8/HPF; P<0.001), and 16 XGCs (28%) harboured >50 IgG4-positive cells per HPF. Nine XGCs (16%), including one case with IgG4-related autoimmune pancreatitis, showed 'the histological features suggestive of IgG4-related disease', as described in the consensus statement regarding this condition. Extracholecystic inflammatory extension (seven cases, P=0.009) and mass-forming lesions (eight cases, P<0.001) were more frequently seen in XGC cases with histological features suggestive of IgG4-related disease than in cases without those microscopic changes. XGCs with IgG4-positive cell infiltration are considered to be mimickers, as xanthogranulomatous inflammation generally contradicts a diagnosis of IgG4-related disease and is weakly associated with other typical organ manifestations of IgG4-related disease. However, XGC may be a concurrent condition, particularly in patients with IgG4-related disease in other organs.

Application value of immunoglobulin G4 detection in unexplained liver injuries

Objective To investigate the expression level of immunoglobulin G (IgG)4 cells in patients previously diagnosed as unexplained liver injuries, and to analyze whether these patients could be diagnosed as immunoglobulin G4-related disease (IgG4-RD). The clinical characteristics of patients with IgG4 positive cells infiltration in liver tissues who did not met IgG4-RD diagnosis criteria were also analyzed. Methods From August 2010 to July 2016, 33 patients with unexplained liver injuries even after liver biopsy were enrolled. Immunostaining of IgG and IgG4 in liver tissue slices was performed. Whether the patients met the IgG4-RD diagnosis criteria was analyzed. Also, the relation between IgG4 positive cell infiltration in liver tissues and serum parameters (alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptadase (GGT), IgG), the classification of liver inflammation and stage of liver fibrosis were analyzed. Chi-square, Fisher exact probability method, t test and Wilcoxon rank and inspection were used for statistical analysis. Results Among 33 patients with unexplained liver injuries, average age of onset of the disease was (50.48±14.52) years old. Ten patients (30.3%) presented with different degree of IgG4 positive cells infiltration in liver. In one patient, the IgG4 positive cell number in liver tissue was over 10/high-powered field (HPF), IgG4+ /IgG+ ratio was over 40%, the serum IgG4 increased and low density nodules in the left hepatic lobe level, which met the diagnostic criteria of IgG4-RD. Serum parameters of liver function of this patient were as follows: ALT 948 U/L, AST 658 U/L, ALP 176 U/L, GGT 197 U/L, TBil 21.5 μmol/L, DBil 10.0 μmol/L. According to whether there were IgG4 positive cells infiltration in liver tissues, 33 patients were divided into IgG4 positive cells infiltration group (IgG4 positive group, 10 cases) and no IgG4 positive cells infiltration group (IgG4 negative group, 23 cases). The medium levels of ALT, AST, ALP and GGT in the IgG4 positive group and the IgG4 negative group were 26.0 U/L vs 31.0 U/L, 28.5 U/L vs 32.0 U/L, 114.0 U/L vs 77.0 U/L, 65.0 U/L vs 36.0 U/L, respectively and there were no statistically significant differences (Z=-0.098, -0.216, -0.862, -0.705; all P>0.05). The serum IgG level of the IgG4 positive group was higher than that of the IgG4 negative group (17.15 g/L vs 13.65 g/L), and the difference was statistically significant (Z=-1.776, P=0.035). Conclusions IgG4-RD may be the reason of liver injury. There are no significant differences in clinical charateristics, serum parameters and inflammation degree in liver tissue between patients with or without IgG4 positive cells infiltration. Key words: Unexplained liver injury; Immunoglobulin G4; Immunoglobulin G4-related disease

Interleukin-33 produced by M2 macrophages and other immune cells contributes to Th2 immune reaction of IgG4-related disease

IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and marked infiltration of IgG4-positive cells in multiple organs. Interleukin-33 (IL-33) is a recently described cytokine that is secreted by damaged epithelial cells, macrophages, and dendritic cells, and potently activates helper T type 2 (Th2) immune responses, which have been suggested to play a major role in IgG4 production of IgG4-RD. Here, we assessed the expression of IL-33 and related molecules in the salivary glands (SGs) of patients with IgG4-RD versus that in patients with Sjögren’s syndrome (SS) and controls. Expression of IL-33 and its receptor (ST2) was strongly detected around ectopic germinal centers (GCs) in the SGs from patients with IgG4-RD, whereas IL-33 was expressed only in epithelial cells in patients with SS and controls. Moreover, IL-33 and CD68+/CD163+ macrophages were mainly distributed around ectopic GCs in patients with IgG4-RD. Double immunofluorescence staining showed that IL-33 expression co-localized with CD68+/CD163+ macrophages. Finally, mRNA expression levels of IL-33 showed a positive correlation to those of Th2 cytokines (IL-4 and IL-13) in patients with IgG4-RD. Our data suggest that IL-33 produced by M2 macrophages might contribute to the pathogenesis of IgG4-RD via aberrant activation of Th2 immune responses.

IgG4-positive cell infiltration in various cardiovascular disorders - results from histopathological analysis of surgical samples

BackgroundThe diagnosis of Immunoglobulin G4 (IgG4)-related disease (IgG4-RD), in general, depends on serum IgG4 concentrations and histopathological findings; therefore, diagnosis of IgG4-RD in cardiovascular organs/tissues is often difficult owing to the risk of tissue sampling.MethodsPrevalence of IgG4-positive lymphoplasmacytic infiltration in 103 consecutive cardiovascular surgical samples from 98 patients with various cardiovascular diseases was analyzed immunohistochemically.ResultsThe diagnoses of the enrolled patients included aortic aneurysm (abdominal, n = 8; thoracic, n = 9); aortic dissection (n = 20); aortic stenosis (n = 24), aortic regurgitation (n = 10), and mitral stenosis/regurgitation (n = 17). In total, 10 (9.7%) of the 103 specimens showed IgG4-positive cell infiltration with various intensities; five of these were aortic valve specimens from aortic stenosis, and IgG4-positive cell infiltration was present at >10 /HPF in three of them. In one aortic wall sample from an abdominal aortic aneurysm, various histopathological features of IgG4-RD, such as IgG4-positive cell infiltration, obliterating phlebitis, and storiform fibrosis, were observed.ConclusionsIgG4-positive cell infiltration was observed in 9.7% of the surgical cardiovascular specimens, mainly in the aortic valve from aortic stenosis and in the aortic wall from aortic aneurysm. Whether IgG4-positive cell infiltration has pathophysiological importance in the development or progression of cardiovascular diseases should be investigated in future studies.

A case of alopecia as IgG4-related skin disease

A 53-year-old man with autoimmune pancreatitis as IgG4-related disease presented alopecia. Immunostaining showed perifollicular infiltration of IgG4-positive cells and perifollicular/intrafollicular infiltration of predominantly CD4-positive cells, especially in the upper and lower parts. Alopecia areata is characterized by perifollicular/intrafollicular lymphocyte infiltration of the lower bulb and inflammation in the upper dermis. We determined the patient had IgG4-related skin disease, rather than alopecia areata. Alopecia as IgG4-related skin disease has not been reported previously.

Value of serum IgG4 in IgG4-related disease

Immunoglobulin G4(IgG4)-related disease (IgG4-RD) is a new systemic and chronic autoimmune disease. It is characterized by increased serum levels of IgG4 and infiltration of abundant IgG4-positive cells in various organs and tissues.It is needed to distinguish IgG4-RD and other diseases which will induce high level of serum IgG4 and infiltration of abundant IgG4-positive cells in tissues. This study described the value of serum IgG4 in IgG4-RD.(Chin J Lab Med, 2016, 39: 817-819) Key words: Autoimmune diseases; Immunoglobulin G; Pancreatitis; Nephritis, interstitial

Probable IgG4-related sclerosing disease presenting as a gastric submucosal tumor with an intense tracer uptake on PET/CT: a case report

A 44-year-old man consulted an internist because of abnormalities in an upper gastrointestinal series. It showed an elevated lesion with central depression in the greater curvature of the middle part of the stomach. Upper gastrointestinal endoscopy showed an elevated lesion with central depression, bridging hold, and no abnormalities of the gastric mucosa in the greater curvature of the middle part of the stomach. Endoscopic ultrasonography showed a submucosal tumor derived from the muscle layer of the stomach. Computed tomography showed a 22-mm tumor in the upper part of the stomach. Integrated position emission tomography/computed tomography (PET/CT) showed an intense tracer uptake by the tumor. Based on these findings, a gastrointestinal stromal tumor was suspected and laparoscopic endoscopic cooperative surgery was performed. A histopathological examination showed lymphoplasmacytic infiltration and fibrosis, and an immunohistochemical analysis showed the infiltration of IgG4-positive lymphoplasmacytic cells. The probable diagnosis was IgG4-related sclerosing disease of the stomach. We herein describe a rare case of probable IgG4-related sclerosing disease which presented as a gastric submucosal tumor. PET/CT is a useful imaging technique for the diagnosis and follow-up of this disease.

IgG4 Associated Cholangitis

IgG4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by an infiltration of lymphoplasmacytic enriched IgG4-positive plasma cells, variable degrees of fibrosis and mass forming lesions. Previously, this disorder was known as IgG4 multi-organ lymphoproliferative syndrome (IgG4 MOSLP), IgG4 sclerosing disease, or IgG4-related systemic plasmocytic syndrome (SIPS). The most common clinical manifestations are parotid inflammation, lymphadenopathy and autoimmune pancreatitis.

Immunoglobulin G4-related pathologic features in inflammatory neuropathies.

To evaluate the pathologic significance of immunoglobulin G4 (IgG4) in patients with inflammatory peripheral neuropathy. We clinicopathologically examined 149 consecutive patients with peripheral neuropathy who had clusters of inflammatory cells with or without vasculitis in sural nerve biopsy specimens and in whom we were able to assess the serum IgG4 levels. Elevation of serum IgG4 levels and infiltration of IgG4-positive plasma cells, which are currently defined as the diagnostic criteria for IgG4-related disease, were found in 35 and 29 patients, respectively. In the 44 patients exhibiting either elevated serum IgG4 levels or IgG4-positive cell infiltration, the diagnoses prior to the examination of IgG4 in serum and pathologic samples included microscopic polyangiitis (12 patients) and eosinophilic granulomatosis with polyangiitis, or Churg-Strauss syndrome (19 patients). Thirty-four patients (77%) had findings of vasculitis as indicated by the destruction or obstruction of the vessel walls. Sixteen (36%) of these patients had fibrinoid necrosis. Axonal degeneration without evidence of demyelination was observed irrespective of the presence of vasculitis. The extent of fibrosis, assessed as the fibrotic area in the epineurium, significantly correlated with the grade of IgG4-positive cell infiltration (p < 0.01). Elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells were observed in a subgroup of patients with inflammatory neuropathy, particularly in patients diagnosed with primary systemic vasculitis, including microscopic polyangiitis. Epineurial IgG4-positive plasma cell infiltration correlated with the extent of epineurial fibrosis.

Pathological Comparison of Nasal Manifestation of IgG4‐Related Disease and Allergic Rhinitis

Objectives: Immunoglobulin (Ig) G4-related disease has been widely known to affect many organs including the lacrimal gland, salivary gland, pancreas, retroperitoneal, etc. There are a few reports concerning the nasal lesion of this disease. However, the difference between the nasal manifestation of IgG4-related disease and allergic rhinitis (AR) has not been clarified. We compared the pathological findings in nasal specimens of IgG4-related disease with those of allergic rhinitis. Methods: Nasal mucosa was obtained from patients with IgG4-related disease and AR. We examined the infiltration of IgG4 positive cells and other infiltrating cells. These infiltrating cells in IgG4-related disease group were compared with those in the AR group. We also assessed the number of nasal glands in IgG4-related disease and the AR group. Results: The number of IgG4-positive plasma cells was significantly higher in the IgG4-related disease group than that in the AR group. CD3 and CD4 positive cells were also significantly higher in the IgG4-related disease group than in the AR group. The number of nasal glands was decreased in the IgG4-related disease group less than the AR group. Conclusions: The number of IgG4, CD3, and CD4 positive cells was significantly higher in the IgG4-related disease group than that in the AR group. There is a possibility that the nasal manifestations of IgG4-related disease might be different from AR.

Relationship between autoimmune pancreatitis and pancreatic cancer: A single-center experience

ObjectivesOrdinary chronic pancreatitis (CP), such as alcoholic CP, is well established to have the increased risk for pancreatic cancer (PaC), nevertheless an association between autoimmune pancreatitis (AIP) and PaC is still unknown. The aims of this study are to examine the frequency of patients who developed PaC during follow-up after being diagnosed with type 1 AIP and to compare the incidence rate of PaC between patients with type 1 AIP and CP. MethodsSixty-three patients with type 1 AIP and 41 patients with CP were enrolled. We examined development of PaC during follow-up from their clinical records. ResultsThe mean follow-up period was 62.4 months in AIP group and 49.2 months in CP group. The occurrence of PaC was observed in 3 patients with AIP during the mean follow-up period of 94.7 months (range, 31–186), whereas a single CP patient developed PaC 38 months after CP diagnosis. The incident rate of PaC during follow-up was comparable between the 2 groups [4.8% (3/63) in type 1 AIP group vs. 2.4% (1/41) in CP group]. In all of 3 AIP patients who developed accompanying PaC, the clinical remission of AIP was achieved with maintenance steroid therapy, when tumors were discovered. In the histological examination of one surgical patient with PaC, lymphoplasmacytic infiltration in storiform fibrosis with abundant IgG4-positive cell infiltration was observed around the PaC area. ConclusionsSimilar to patients with ordinary CP, surveillance for development of PaC is needed at regular interval during follow-up in AIP patients.