IgG4-positive Cells Research Articles

IgG4-Related Hashimoto's Thyroiditis of the Thyroid Gland

Immunoglobulin (Ig) G4-related Hashimoto's thyroiditis is a newly discovered subtype of Hashimoto's thyroiditis and characterized by thyroid inflammation and marked fibrosis. IgG4-related Hashimoto's thyroiditis is very rare and there has been relatively little information available to date. A 46-year-old woman with a past history of thyroid dysfunction visited our outpatient clinic for severe anterior neck swelling. She complained of swallowing discomfort and pain due to severe goiter and was successfully treated with total thyroidectomy. Immunohistochemistry showed thyroid invasion by IgG4-positive cells and an IgG4/IgG ratio over 40%. The patient was diagnosed with IgG4-related Hashimoto's thyroiditis. We report a very rare case of IgG4-related Hashimoto's thyroiditis with severe goiter. A more comprehensive understanding of the IgG4-related Hashimoto's thyroiditis may help physicians to allow proper diagnosis and treatment of patients with severe goiter.

Analysis of IgG4-positive clones in affected organs of IgG4-related disease

Objective: We investigated class switch reaction (CSR) in affected organs and evaluated whether the same or genetically related clones exist in IgG4-RD.Methods: We studied three patients with IgG4-RD. Total cellular RNA was extracted from salivary glands and peripheral blood and lung tissue. Activation-induced cytidine deaminase (AID) and immunoglobulin heavy chain third complementarity determining region (IgVH-CDR3) of IgM and IgG4 were detected by reverse transcription polymerase chain reaction (RT-PCR). We analyzed the clonal relationship of infiltrating IgG4-positive cells, as compared with IgM. We determined the existence of common clones among organs and patients.Result: AID was expressed in salivary glands of all patients and lung tissue in one. Closely related IgVH-CDR3 sequences in infiltrating IgG4-positive cells were detected in salivary glands and lung tissue. Identical IgVH-CDR3 sequence between IgM and IgG4 in salivary glands was detected in one patient, indicating CSR in salivary glands. Identical IgVH-CDR3 sequences of IgG4-positive cells were detected between salivary glands and peripheral blood in two patients. Four identical sequences of IgVH-CDR3 existed between patients. Interestingly, one of the four sequences was detected in all patients.Conclusion: Our results demonstrate the existence of common antigen(s) shared by patients with IgG4-RD.

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.

A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis.

IgG4-related disease is a newly defined disease characterized by elevated serum IgG4 levels and infiltration of affected organs by IgG4-positive plasma cells. Recently, increased IgG4 levels were reported to be closely related with malignancy. To assess the relationship between IgG4 and the progression of gastric cancer, we immunohistochemically stained in this study gastric cancer tissue samples for IgG4-positive cells using an anti-IgG4 antibody. In addition, pre- and postoperative serum concentrations of IgG4 were measured, using an enzyme-linked immunosorbent assay. In gastric cancer samples, the number of CD138-positive plasma cells was significantly lower and the number of IgG4-positive cells significantly higher than in non-cancerous gastric mucosa. The number of IgG4-positive cells was significantly correlated with gross tumor appearance, tumor depth, lymph node metastasis, venous invasion, and lymphatic invasion. Prognosis was significantly poorer in patients with a high number of IgG4-positive cells than in those with a low number. Multivariate analysis indicated that both the number of IgG4-positive cells and the depth of tumor invasion were independently prognostic of survival. In conclusion, in gastric cancer, the number of IgG4-positive cells is increased and this is closely associated with gastric cancer progression.

IgG4-related sialodacryoadenitis and chronic rhinosinusitis: a clinicopathologic analysis of 13 cases

To study the clinicopathologic characteristics of IgG4-related sialodacryoadenitis and chronic rhinosinusitis (CRS). A total of 13 patients (patient group) were evaluated clinically and biopsy specimens from the lacrimal/salivary glands (n=12) and nasal mucosa (n=8) were reviewed and immunohistochemistry was performed to assess IgG-and IgG4-positive cells. Similarly, nine patients with IgG4-related sialodacryoadenitis without CRS and 10 patients with common CRS were included as controls. There were 8 male patients and 5 female patients. The age of patients ranged from 32 to 71 years (mean 50.2 years). The patient group had higher serum IgG4 concentration than that of the control group (P<0.05). Lymphoplasmacytic infiltration, lymphoid follicle formation and sclerosis were prominent in lacrimal/salivary glands in both groups; however the magnitude of IgG4-positive plasmacytic infiltration in the patient group was significantly higher than that of the control group (P<0.05). Similarly, evaluation of nasal mucosa revealed greater lymphocytic and plasmacytic infiltration, and lymphoid follicle formation, together with significantly higher amount of IgG4-positive plasma cell infiltration in the patient group compared to the common CRS group (P<0.05). IgG4-related disease (IgG4-RD) simultaneously involving lacrimal/salivary glands and nasal cavity/paranasal sinuses is rare and characterized by a combination of IgG4-positive plasma cell infiltration involving lacrimal/salivary glands and nasal mucosa along with an increased serum level of IgG4. As a systemic disease, early and accurate diagnosis is therefore of great importance, and unnecessary surgery should be avoided.

リンパ節転移を伴う甲状腺癌を疑ったIgG4関連甲状腺炎（準確診群）の1切除例

We present a case of probably IgG4-related thyroiditis with lymphadenopathy. The patient was a 70-year-old Japanese female who was undergoing hemodialysis and had undergone a right hemi-thyroidectomy in 1989 due to carcinoma. In December 2010, an ultrasonography study revealed a hypoechoic small lesion in thyroid gland. When the patient was admitted to our hospital in November 2013, the lesion and regional lymph nodes had enlarged and we suspected that they were metastatic thyroid cancer. We performed a residual total thyroidectomy and regional lymph node dissection in August 2014. At that time, lymphoplasmacytic infiltration and fibrosis were observed histopathologically in thyroid tissue. Immunohistochemical studies revealed infiltrated lymphocytes and plasma cells were markedly IgG-positive, and the ratio of IgG4-positive to IgG-positive cells was over 40%. We therefore diagnosed the patient with IgG4-related thyroiditis. The cervical lymph nodes were metastases of papillary carcinoma from 25 years earlier. The patient remains well without any recurrences 33 months after the surgery.

Overview of IgG4-Related Tubulointerstitial Nephritis and Its Mimickers.

Tubulointerstitial nephritis (TIN) is the most common form of renal involvement in IgG4-related disease. It is characterized by a dominant infiltrate of IgG4-positive plasma cells in the interstitium and storiform fibrosis. Demonstration of IgG4-positive plasma cells is essential for diagnosis, but the number of IgG4-positive cells and the ratio of IgG4-positive/IgG-positive plasma cells may vary from case to case and depending on the methods of tissue sampling even in the same case. IgG4-positive plasma cells can be seen in TIN associated with systemic lupus erythematosus, Sjögren syndrome, or anti-neutrophil cytoplasmic antibody–associated vasculitis, which further add diagnostic confusion and difficulties. To have a more clear view of IgG4-TIN and to delineate differential points from other TIN with IgG4-positive plasma cell infiltrates, clinical and histological features of IgG4-TIN and its mimickers were reviewed. In the rear part, cases suggesting overlap of IgG4-TIN and its mimickers and glomerulonephritis associated with IgG4-TIN were briefly described.

Esophageal Involvement of Immunoglobulin G4-Related Disease

AbstarctImmunoglobulin G4 (IgG4)-related disease is characterized by the typical histopathological features of a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, a high ratio of IgG4- to IgG-positive cells, storiform fibrosis (cellular fibrosis organized in an irregular whorled pattern), obliterative phlebitis, and variable presence of eosinophils. The disease exhibits systemic involvement but very rarely involves the esophagus.A 33-year-old man was admitted to our hospital for evaluation of a 1-year history of progressive dysphagia. Neck imaging revealed a 3.9-cm mass in the cervical esophagus and multifocal calcified lymph nodes in the lower neck and mediastinum. Two previous tertiary hospitals failed to diagnose the patient's condition despite the use of ultrasound-guided needle biopsy of the neck tumor. We performed neck imaging studies, a flexible endoscopic swallowing study, high-resolution manometry, upper endoscopy, and a review of the previous pathologic slides. The patient was finally diagnosed with IgG4-related esophagitis and showed a good response to corticosteroid therapy.We herein report a rare case of dysphagia associated with IgG4-related disease and present a review of the literature.

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.

Concomitant occurrence of Mikulicz's disease and immunoglobulin G4-related chronic rhinosinusitis: a clinicopathological study of 12 cases.

Concomitant occurrence of Mikulicz's disease (MD) and immunoglobulin (Ig)G4-related chronic rhinosinusitis (IgG4-related CRS) is extremely rare. We evaluated the clinicopathological features of MD patients with concomitant IgG4-related CRS (CRS-MD). Twelve CRS-MD patients were evaluated clinically and biopsy samples were taken from the lacrimal/salivary glands (n=12) and nasal mucosa (n=7) for assessment of IgG4-positive cells, using immunohistochemical techniques. Similarly, nine MD patients and 10 patients with common CRS were evaluated as controls. CRS-MD patients had higher serum IgG and IgG4 concentrations than MD patients (P<0.05 for both). Lymphoplasmacytic infiltration, lymphoid follicle formation and sclerosis was prominent in the lacrimal/salivary glands in both groups; however, the magnitude of IgG4-positive plasma cells infiltration in the CRS-MD group was significantly higher compared to the MD group (P=0.004). Similarly, evaluation of nasal mucosa revealed greater lymphocyte, plasma cell and eosinophil infiltration and lymphoid follicle formation, together with significantly higher IgG4-positive plasma cell infiltration in the CRS-MD group compared to the common CRS group (P=0.004). Concomitant MD and IgG4-related CRS were characterized by a combination of IgG4-positive plasma cells infiltration in the lacrimal/salivary glands and the nasal mucosa and increased serum IgG4.

Overview of the Immunoglobulin G4-related Disease Spectrum

Immunoglobulin G4 (IgG4)-related disease is a newly named fibroinflammatory condition characterized by tumefactive lesions that contain dense lymphoplasmacytic infiltrates rich in IgG4-positive cells. Elevated serum IgG4 concentrations also often accompany IgG4-related disease. Many medical conditions that were long viewed as diseases confined to single organs (e.g., Mikulicz disease, type 1 autoimmune pancreatitis, Riedel’s thyroiditis, multifocal fibrosclerosis, inflammatory pseudotumor, mediastinal fibrosis, retroperitoneal fibrosis, and etc.) are now designated as part of the spectrum of IgG4-related disease. The preferred nomenclature suggested by a committee of international experts uses the prefix “IgG4-related-” for individual organ involvement, regardless of the organ system affected. One exception is type 1 autoimmune pancreatitis (IgG4-related pancreatitis). Comprehensive diagnostic criteria for IgG4-related disease and organ-specific diagnostic criteria (e.g., IgG4-related dacryoadenitis and sialadenitis, type 1 autoimmune pancreatitis, IgG4-related kidney disease and IgG4-related sclerosing cholangitis) can aid clinicians in the diagnosis of this erratic condition. Keywords: Immunoglobulin G4-related disease, Autoimmune pancreatitis, Autoimmune diseases Keywords: 면역글로불린 G4 연관질환, 자가면역췌장염, 자가면역질환

Clinicopathological Analysis of Ocular Adnexal Extranodal Marginal Zone B-Cell Lymphoma with IgG4-Positive Cells.

This study aims to analyze clinical and pathological characteristics of ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL) accompanying IgG4-positive cells. Fifty patients with a diagnosis of primary non-conjunctival ocular adnexal EMZL were enrolled in this study. The number of IgG4-positive cells and the ratio of IgG/IgG4 were evaluated by immunohistochemistry in the biopsy specimens. The patients were divided into two groups based on the absolute number and the ratio of IgG4-positive cells (IgG4-posivite vs IgG4-negative groups). The demographic data, clinical staging at diagnosis, histopathological characteristics, and response to initial treatment were comparatively analyzed between the 2 groups. Five (10%) of 50 patients were defined as IgG4-positive group, and all the cases showed characteristic histological features such as extensive plasma cell infiltration and dense fibrosis. Most of these patients (4 of 5 patients) had lymphoma of the lacrimal gland. The patients from the IgG4-positive group showed a lower response rate to initial treatment (87.5 vs 33%, p = 0.03) than IgG4-negative group with a median follow-up period of 38 months. A part of the ocular adnexal EMZLs were accompanied with IgG4-positive cells. Significantly, most IgG4-positive ocular adnexal EMZLs occurred in the lacrimal gland, and can be related with a more frequent treatment failure.

Collagenous gastritis: a morphologic and immunohistochemical study of 40 patients

Collagenous gastritis is a rare condition defined histologically by a superficial subepithelial collagen layer. This study further characterizes the morphologic spectrum of collagenous gastritis by evaluating a multi-institutional series of 40 patients (26 female and 14 male). The median age at onset was 16 years (range 3–89 years), including 24 patients (60%) under age 18. Twelve patients (30%) had associated celiac disease, collagenous sprue, or collagenous colitis. Hematoxylin and eosin slides were reviewed in biopsies from all patients and tenascin, gastrin, eotaxin, and IgG4/IgG immunohistochemical stains were applied to a subset. The distribution of subepithelial collagen favored the body/fundus in pediatric patients and the antrum in adults. There were increased surface intraepithelial lymphocytes (>25 lymphocytes/100 epithelial cells) in five patients. Three of these patients had associated celiac and/or collagenous sprue/colitis, while the remaining two had increased duodenal lymphocytosis without specific etiology. An eosinophil-rich pattern (>30 eosinophils/high power field) was seen in 21/40 (52%) patients. Seven patients' biopsies demonstrated atrophy of the gastric corpus mucosa. Tenascin immunohistochemistry highlighted the subepithelial collagen in all 21 specimens evaluated and was a more sensitive method of collagen detection in biopsies from two patients with subtle subepithelial collagen. No increased eotaxin expression was identified in 16 specimens evaluated. One of the twenty-three biopsies tested had increased IgG4-positive cells (100/high power field) with an IgG4/IgG ratio of 55%. In summary, collagenous gastritis presents three distinct histologic patterns including a lymphocytic gastritis-like pattern, an eosinophil-rich pattern, and an atrophic pattern. Eotaxin and IgG4 were not elevated enough to implicate these pathways in the pathogenesis. Tenascin immunohistochemistry can be used as a sensitive method of collagen detection.

IgG4-related disease of the breast: a systemic disease whose mammary manifestations mimic breast cancer

IgG4-related disease is a newly identified disease entity that has begun to attract attention, and international consensus diagnostic criteria for the condition have recently been proposed. The characteristic features of IgG4-related disease are lymphoplasmacytic infiltration involving a high proportion of IgG4-positive cells, fibrosis exhibiting a storiform pattern, and obliterative phlebitis. It can affect various organs, including the breast (in rare cases). IgG4-related disease has previously been referred to as inflammatory myofibroblastic tumor, plasma cell granuloma, or pseudolymphoma. We have experienced a case of IgG-related disease of the breast. Clinically and cytologically, the lesion was somewhat similar to a malignant tumor. An immunohistochemical examination of a core needle biopsy sample resulted in a correct diagnosis. In addition, a review of the patient’s clinical history revealed that the disease had affected areas other than the breast. Clinicians should be aware that breast lesions can be a focal manifestation of systemic disease, and overdiagnosis should be avoided by performing appropriate pathological analysis.

IgG4 related sclerosing mastitis: expanding the morphological spectrum of IgG4 related diseases

IgG4 related disease (IgG4RD) is a recently recognised condition characterised by mass forming lesions associated with storiform fibrosis, obliterative phlebitis, lymphoplasmacytic infiltrate rich in IgG4 positive plasma cells and elevated serum IgG4 levels. Although rare, mammary involvement has been reported as IgG4 related sclerosing mastitis, the morphological counterpart of a growing family of IgG4 related diseases. A total of 17 cases belonging to mass forming benign inflammatory breast lesions such as plasma cell mastitis, granulomatous lobular mastitis, non-specific mastitis and inflammatory pseudotumour were investigated as a possible member of IgG4 related sclerosing mastitis. Clinical, radiological, histopathological and immunohistochemistry findings were noted in all cases. Cases diagnosed as inflammatory pseudotumour showed all the histopathological features of IgG4RD along with increased number of IgG4 positive plasma cells and IgG4/IgG ratio >40%. However, only a few IgG4 positive cells were seen in plasma cell mastitis, granulomatous lobular mastitis and non-specific mastitis cases. These cases also did not fulfill the morphological criteria for the diagnosis of IgG4 related diseases. IgG4RD should be excluded in plasma cell rich lesions diagnosed on core biopsies by IgG4 immunostaining. This can avoid unnecessary surgery as IgG4 related diseases respond to simple and effective steroid treatment.

Diagnosis and treatment of autoimmune pancreatitis: experience with 100 patients

Autoimmune pancreatitis (AIP) is increasingly recognized as a unique subtype of pancreatitis. This study aimed to analyze the diagnosis and treatment of AIP patients from a tertiary care center in China. One hundred patients with AIP who had been treated from January 2005 to December 2012 in our hospital were enrolled in this study. We retrospectively reviewed the data of clinical manifestations, laboratory tests, imaging examinations, pathological examinations, treatment and outcomes of the patients. The median age of the patients at onset was 57 years (range 23-82) with a male to female ratio of 8.1:1. The common manifestations of the patients included obstructive jaundice (49 patients, 49.0%), abdominal pain (30, 30.0%), and acute pancreatitis (11, 11.0%). Biliary involvement was one of the most extrapancreatic manifestations (64, 64.0%). Fifty-six (56.0%) and 43 (43.0%) patients were classified into focal-type and diffuse-type respectively according to the imaging examinations. The levels of serum IgG and IgG4 were elevated in 69.4% (43/62) and 92.0% (69/75) patients. Pathological analysis of specimens from 27 patients supported the diagnosis of lymphoplasmacytic sclerosing pancreatitis, and marked (>10 cells/HPF) IgG4 positive cells were found in 20 (74.1%) patients. Steroid treatment and surgery as the main initial treatments were given to 41 (41.0%) and 28 (28.0%) patients, respectively. The remission rate after the initial treatment was 85.0%. Steroid was given as the treatment after relapse in most of the patients and the total remission rate at the end of follow-up was 96.0%. Clinical manifestations, laboratory tests, imaging and pathology examinations in combination could increase the diagnostic accuracy of AIP. Steroid treatment with an initial dose of 30 or 40 mg prednisone is effective and safe in most patients with AIP.

Detection of immunoglobulins containing plasma cells in the thymus, bursa of Fabricius and spleen of vaccinated broiler chickens with Newcastle disease virus vaccine

Mobilization of immunoglobulins (Igs)-containing plasma cells (IgA, IgG and IgM) in the spleen, bursa of Fabricius and thymus was investigated in broiler chickens that were vaccinated with Newcastle disease virus (NDV) vaccine. In the thymus, the Igs-containing plasma cells were distributed in the cortex and medulla. Their frequency and distribution were higher at D14 and at D28. The number of IgG- and IgM-positive cells was greater than IgA-positive cells in thymus. In the bursa of Fabricius, Igs-containing plasma cells were distributed beneath the capsules; within and around the bursal follicles. Their frequency of occurrence significantly peaked at D14 and at D28 in comparison to day-old chickens, and IgG-positive cells were significantly greater than the IgA- and IgM-positive cells in the bursa of vaccinated chickens. In the spleen, Igs-containing plasma cells were distributed in the white pulp, around the trabeculae, and in the periarterial lymphatic sheath. In this secondary lymphatic tissue, IgG- and IgM-positive cell numbers significantly greater than IgA-positive cells. In conclusion, mobilization of more Igs-positive cells in lymphoid tissues of broiler chickens is due to the effect of NDV vaccine as well as the advancement of age.

Recurrent severe acute hepatitis caused by hypereosinophilic syndrome associated with elevated serum immunoglobulin G4 levels.

A 46-year-old male was admitted to our hospital with severe acute hepatitis, hypereosinophilia, and serum immunoglobulin G4 (IgG4) elevation. Plasma exchange was performed, and he was treated by prednisolone; however, his hepatitis recurred twice over the following twelve months. Transjuglar liver biopsy was performed at the third onset, which demonstrated extensive hepatocyte necrosis, congestion, and severe eosinophil infiltration. We diagnosed hypereosinophilic syndrome (HES)-related hepatitis. Although no cholangitis was detected by imaging and pathological diagnosis, IgG4-positive cells were detected in the liver and bone marrow. Furthermore, the elevation of serum IgG4 levels was associated with the eosinophil count and his clinical condition. After the addition of azathioprine to his treatment regimen, no reoccurrence was observed. IgG4-positive cells may have contributed to the severity and refractoriness of this recurrent acute HES-related hepatitis.

A Case of IgG4-Negative Sclerosing Cholangitis and Autoimmune Pancreatitis Responsive to Steroids

Introduction: IgG4-related disease (IRD) is a multi-organ fibroinflammatory syndrome characterized by typical histopathology, tissue infiltration with IgG4-positive cells, and elevation of serum IgG4. Manifestations of IgG4-associated systemic disease include IgG4-associated cholangitis (IAC) and autoimmune pancreatitis (AIP, type 1). Various diagnostic criteria have been suggested, combining the serologic measurement of IgG4 levels with characteristic clinical, radiologic, and histologic findings. Herein, we present a case that defied classification and thus presented a substantial diagnostic and therapeutic dilemma. Case Report: A 70-year-old male presented to the emergency department with complaints of pruritis, anorexia, weight loss, and painless jaundice. A CT of the abdomen was notable for diffuse intrahepatic biliary ductal dilatation with multiple abrupt annular strictures. MRCP revealed a 2.9-cm posterior pancreatic head mass and thus initial diagnostic concern was for pancreatic malignancy. ERCP with biliary duct dilation and stent placement was performed and a biopsy showed atypical biliary epithelium with inflammation but no evidence of malignancy. An EUS was performed and FNA specimen obtained, with histology demonstrating nonspecific chronic inflammation without IgG4 positivity by immunoperoxidase staining. Total serum IgG levels were elevated, but the IgG4 subset was within normal limits (28.8). The CA 19-9 level was 228. After excluding malignancy, the patient was empirically treated with oral prednisone 40 mg daily for 4 weeks and tapered gradually. His symptoms abated and radiologic findings of biliary duct dilatation and stricturing, as well as the pancreatic mass, resolved. At 1-year follow-up, he has been weaned off steroids and is symptom free. Discussion: IRD is an under-recognized protean disorder, mimicking many systemic conditions. Our case demonstrates the gap in current diagnostic classification of IRD. AIP and IAC should be suspected in patients with unexplained biliary strictures and pancreatic diseases regardless of serum IgG4 levels, as this finding is present in only 50-90% of patients. Evaluation for possible pancreatic and biliary malignancies should take primary precedence. However, when malignancy is excluded and features of AIP are present despite negative serologic and histologic evaluation, an empiric steroid trial is reasonable and may prove diagnostic, as AIP is nearly universally steroidresponsive.Figure 1

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.