Features Of IgG4-related Disease Research Articles

Chronic Sclerosing Sialadenitis of the Submandibular Gland and its Histopathological Spectrum in the IgG4-Related Disease: a Series of 17 Cases.

This study aimed to characterize the histopathological immunohistochemical features of chronic sclerosing sialadenitis, emphasizing the IgG4-related disease. Seventeen cases of chronic sclerosing sialoadenitis were examined for histopathological aspects, (inflammation, fibrosis, glandular parenchyma, and lymphoid follicles) and immunohistochemistry (BCL2, CD3, CD20, CD34, CD163, p63, cyclin D1, mast cell, SMA, S100A4, IgG, and IgG4) which were scored. IgG4-related disease features were investigated. Demographic and clinical data were also collected. Males predominated (10:7), with an average lesion size of 3.9cm. Common histopathological findings included reduced acinar parenchyma, lymphoid follicle formation, and ductular proliferation. CD3-positive T lymphocytes and CD34- and SMA-positive stromal fibroblasts were abundant. Nine cases (53%) showed sialoliths and three cases met the criteria for IgG4-related disease. CSS of the submandibular gland represents a reactive pattern rather than IgG4-RD as only 3 cases seemed to be related to IgG4-RD. The immunohistochemical profile revealed an abundant population of CD3-positive T lymphocytes, as opposed to regulatory proteins such as cyclin D1, demonstrating that populations of CD34- and SMA-positive stromal fibroblasts contribute to the fibrosis characteristic of CSS. In addition, our results provide a comprehensive insight into the study of CSS and its relationship with IgG4-RD.

IgG4-related Inflammatory Pseudotumor with Imaging Findings Similar to Meningioma.

IgG4-related inflammatory pseudotumor is a feature of IgG4-related disease and develops in various organs. Intracranial IgG4-related inflammatory pseudotumor is rare, and data on the clinical course and response to treatment are insufficient in the literature. We herein report a patient with IgG4-related inflammatory pseudotumor who had magnetic resonance imaging findings similar to meningioma. Tumorectomy was discontinued because of the intraoperative rapid diagnosis, which revealed the infiltration of lymphocytes and plasma cells. She received oral prednisolone therapy for IgG4-related inflammatory pseudotumor, and the tumor size had significantly decreased after six months of treatment.

Characteristics of IgG4-related disease complicated with allergic rhinitis or chronic rhinosinusitis: a large cross-sectional cohort study

In clinical practice, we found that IgG4-related disease (IgG4-RD) patients complicated with allergic rhinitis (AR)/chronic rhinosinusitis (CRS) seemed to have unique characteristics different from patients with IgG4-RD alone. In this study, demographic, clinical and laboratory characteristics of IgG4-RD patients complicated with AR/CRS were investigated. We retrospectively analyzed 756 IgG4-RD patients who were recruited in four medical centers from 2009 to 2021. We divided 756 IgG4-RD patients into 2 groups: the case group included IgG4-RD patients complicated with AR/CRS, and the control group included IgG4-RD patients without AR/CRS. 411 patients were complicated with AR/CRS among 756 IgG4-RD patients. Multiple organs involvement (≥ 3, p < 0.0001, OR 3.585 (95% CI 2.655–4.839)) and other types of allergic disease (p < 0.0001, OR 2.007 (95% CI 1.490–2.693)) were more common in the case group. Patients in the case group had a higher level of serum IgG4 (650 mg/dL vs 385 mg/dL, p < 0.0001), IgE (347 mg/dL vs 98 mg/dL, p < 0.0001) and ESR (14 mm/h vs 12 mm/h, p < 0.05). High IgE level (p < 0.01, OR 1.003 (95% CI 1.001–1.005)) and other types of allergic disease (p < 0.05, OR 3.196 (95% CI 1.146–8.908)) were risk factors for patients in the case group, in which most patients had nasal manifestations before the diagnosis of IgG4-RD. The median time interval from nasal symptoms appearance to IgG4-RD diagnosis was − 120 and − 90 months for patients complicated with AR and CRS, respectively. IgG4-RD patients are often complicated with AR/CRS and have distinct characteristics, which appear to be a subgroup of IgG4-RD. The data suggests a pathogenic association of IgG4-RD and AR/CRS.

Clinical Characteristics and CD4+ T Cell Subsets in IgG4-Related Disease.

ObjectivesTo characterize the clinical features of IgG4-related disease (IgG4-RD) and analyze the peripheral T lymphocyte subsets and cytokine levels.MethodsA total of 52 patients with newly diagnosed IgG4-RD were enrolled in the retrospective study. Baseline clinical characteristics and examinational findings were systematically reviewed.ResultsIgG4-RD patients had a male predominance, with an average age of 57.4 ± 10.3 years (range 27-81). The mean number of involved organs was 2.7 (range 1-8). Submandibular gland (57.7%) and lacrimal gland/orbit (40.4%) were the most commonly involved organs. Serum IgG4 increased in 97.9% of the patients, the median level was 1300 (585.25, 1975) mg/dl. Decreased C3 and C4 accounted for 77.8% and 55.6% of this patient cohort, respectively. Receiver operating characteristic (ROC) test indicated the possibility of lung/pleura involvement when C3 was less than 0.570 g/l (AUC = 0.788, P = 0.014), and kidney involvement when C3 was less than 0.545 g/l (AUC = 0.796, P = 0.014). Compared with healthy controls (HC), the absolute Th1 counts were higher in IgG4-RD patients (157.58 cells/μl vs. 130.54 cells/μl, P = 0.038), while the absolute counts of Th2, Th17 and T regulatory (Treg) cells, as well as Th17/Treg ratio were not statistically different. The levels of serum IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ were higher in patients with IgG4-RD as compared with HC (P < 0.001). Serum IL-10 was positively correlated with IL-4, TNF-α and IFN-γ, but uncorrelated with Treg cells. Serum IgG4 level was positively associated with the number of affected organs, eosinophil counts, and ESR, whereas inversely associated with C3, C4, IgM, and IgA.ConclusionSubmandibular and lacrimal glands are the most commonly involved organs in IgG4-RD. Serum C3 level could be a predictor of lung/pleura and kidney involvement in the disease process. Elevated Th1 cells are probably related to chronic inflammation and fibrosis. Treg cells are unlikely to play an important role in the pathogenesis of IgG4-RD.

Peri-orbital adult onset xanthogranuloma and IgG4-related disease: A case report

Adult onset xanthogranuloma (AOX) of the orbit is a rare condition defined by the presence of xanthomatous and Touton giant cells in the peri-orbital tissues. Features suggestive of IgG4-related disease (IgG4-RD) can be seen in AOX; due to a scarcity of cases, it is unclear whether these conditions are related or simply share overlapping features.1 This case study reports a patient with clinically suspected and histologically confirmed AOX of the orbital fat, who was found to have features of IgG4-RD in the lacrimal gland.

Ophthalmic involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 573 patients

PurposeTo investigate the clinical manifestations of orbital involvement in a large cohort of Chinese patients with IgG4-related disease (IgG4-RD).MethodsA total of 573 patients with IgG4-related disease were included. We described and compared the demographic, clinical, laboratory and histopathologic findings from 314 patients with IgG4-related ophthalmic disease (IgG4-ROD) and 259 with extra-ophthalmic IgG4-RD.ResultsMale predominance was found significant in extra-ophthalmic IgG4-RD only. Patients with IgG4-ROD showed younger age at diagnosis and longer duration from onset till diagnosis. In patients with extra-ophthalmic IgG4-RD, the most commonly involved extra-ophthalmic organ was pancreas; while in IgG4-ROD patients, salivary gland was most frequently affected. Multivariate analysis exhibited IgG4-ROD was associated with allergy history, higher serum IgG4/IgG ratio, multiple organs involvement and sialoadenitis. Orbital images were reviewed in 173 (55.1%) IgG4-ROD patients. Fifty-one (29.5%) patients had multiple lesions. Lacrimal gland involvement was detected in 151 (87.3%) patients, followed by extraocular muscles (40, 23.1%), other orbital soft tissue (40, 23.1%) and trigeminal nerve (8, 4.6%). Biopsy was performed from various organs in 390 cases. A dense lymphoplasmacytic infiltration and fibrosis were the main feature in orbital specimens. Storiform fibrosis and obliterative phlebitis were absent in lacrimal gland.ConclusionsLacrimal gland involvement was the most common orbital manifestation of IgG4-ROD. Patients with IgG4-ROD showed different characteristic in demographic, clinical, laboratory findings compared to patients with extra-ophthalmic IgG4-RD. These features might indicate potential differences in the pathogenesis of these two subgroups of IgG4-RD.

P27 Lymphoma-mimicker of IgG4-related dacryoadenitis and sialadenitis

Case report - IntroductionMajor salivary gland (sialadenitis) and lacrimal gland (dacryoadenitis) involvement can be a common feature of IgG4-related disease. There can be involvement of lacrimal and parotid gland which was previously called as Mikulicz disease and/or submandibular gland enlargement which was previously called Küttner tumour. These were previously mistakenly considered to be subcategories of Sjogren’s syndrome, but are now classified as IgG4-related disease. Here we discuss a case report of a patient who presented with bilateral dacryoadenitis and unilateral submandibular gland enlargement which initially was thought to be IgG4-related disease but turned out to be low-grade lymphoma.Case report - Case descriptionA 15-year-old boy presented with 6-month history of bilateral eyelid swelling. The swelling was more on the lateral side of the eyelids and was painless. It had come on suddenly over a couple of days. No history of weight loss, dry eyes, dry mouth, joint issues or skin rashes or any other symptoms. Physical examination revealed bilateral ptosis, no visual impairment and systemic examination revealed an enlarged right submandibular gland. He had initially been to a local hospital where he had investigations which included autoimmune screen including ANA, ENA, ANCA, dsDNA, serum ace and complement levels which were all negative. C1 esterase inhibitor was normal. Routine bloods including complete blood count, urea and electrolytes, thyroid stimulating hormone and erythrocyte sedimentation rate were within normal limits. Urine albumin to creatinine ratio was not raised. Hepatitis serology including Hepatitis B & C and HIV was negative. Ultrasound abdomen was unremarkable. CT scan of orbits showed bilateral enlarged lacrimal glands with patchy post contrast enhancement and the glands extending up to insertion of lateral rectus muscle. CT chest some enlarged axillary lymph nodes and nodes in lung query infective etiology. CT abdomen and pelvis was unremarkable. Ultrasound neck showed right submandibular node enlargement with colour doppler showing increased vascularity. Fine needle aspirate of the submandibular gland showed reactive lymphoid hyperplasia. He was given two short courses of steroids and each time the swelling rapidly responded to the steroids but recurred on cessation of the steroids. IgG subset analyses revealed elevated IgG4 levels of 1152mg/dl. The differential here was IgG4-related disease but as there was no clear tissue diagnosis a core biopsy of the right submandibular gland was done. This revealed tissue suspicious of low grade (extranodal marginal zone and mucosa-associated lymphoid tissue [MALT]) lymphoma and excision biopsy was performed for definitive diagnosis.Case report - DiscussionIgG4-related disease is an immune mediated fibroinflammatory condition which can affect a variety of organs and can present as tumour-like enlargement and/or organ dysfunction. The pathological findings in IgG4-related disease are lymphoplasmocytic infiltrates of IgG4-positive cells along with increased levels of serum IgG4 levels. Salivary and lacrimal glands can be commonly affected and present as enlargement, which is usually painless and bilateral. The combination of lacrimal gland enlargement with both parotid and submandibular gland enlargement is called IgG4-related Mikulicz disease.Apart from salivary glands, another commonly affected organ is the pancreas which can present as a pancreatic mass and painless jaundice, sclerosing cholangitis, retroperitoneal fibrosis, aortitis and periaortitis. Less commonly it can affect thyroid, kidney and lungs.Early recognition, diagnoses and treatment is important due to the fibroinflammatory nature of the disease. Malignancy is always in the differential and should be excluded. Steroids are the mainstay of treatment. If patients experience flare, rituximab can be added.Diagnosis should be confirmed with biopsy but histopathological findings are never alone diagnostic of IgG4-related disease and should be interpreted with clinical, serological and radiological findings.Case report - Key learning pointsAlthough this patient had typical presentation of IgG4-related disease with painless enlargement of salivary and lacrimal glands and elevated IgG4 serum levels, biopsy was imperative to get to the diagnoses of low-grade lymphoma and fine needle aspirate was not adequate. As mentioned above, biopsy in IgG4-related disease will confirm the diagnosis provided there are other supporting features (radiological and serological). However, it is imperative for excluding other important diseases like lymphoproliferative disorders.

Mass-forming immunoglobulin G4-related disease shows indolent clinical course after surgical resection, clinicopathological analysis of a series of 15 cases.

The purpose of this study is to characterize the clinicopathological features of mass-forming immunoglobulin G4-related disease (IgG4-RD). A retrospective search for cases of mass-forming IgG4-RD diagnosed at Singapore General Hospital between 2008 and 2019 was performed. A total of 15 cases of mass-forming IgG4-RD were identified. The male-to-female ratio was 2.5:1, and the median age was 61years old. The majority of cases showed a solitary lesion (12/15) with a mean size of 35mm. IgG4-RD was considered as a clinical differential diagnosis only in one case (1/15) prior to the surgical resection. Diagnostic histopathological features, such as dense lymphoplasmacytic infiltrate positive for IgG4 plasma cells (15/15), storiform fibrosis (15/15), and obliterative phlebitis (9/15), were observed in most cases. These findings were distributed heterogeneously within the lesions. Cases with single organ involvement showed a low relapse rate (2/10) and normal serum IgG4 level after surgical resection. Mass-forming IgG4-RD has a male predilection and involves various organ systems. It may be initially misdiagnosed as malignancy and undergo surgical resection. The diagnostic histological features of IgG4-RD are readily identified in different organs. However, they may be distributed heterogeneously within a single lesion. Cases of single organ involvement show an indolent clinical course and normal serum IgG4 level after surgical resection.

Clinical characteristics of igG4-related disease in the United Arab Emirates: A retrospective single-center study

Background: Demographic and clinical data of IgG4-related disease affecting solely the native population of the UAE, known as Emiratis, does not exist in the literature. Aim: To explore the demographic and clinical characteristics of IgG4-related disease in a well-defined population of Emirati patients attending Cleveland Clinic Abu Dhabi, a large tertiary center in the Middle East. Patients and Methods: The data presented is part of a retrospective cohort study, in which 15 Emirati patients with IgG4-related disease (IgG4-RD) were evaluated over 5 years from April 2015 to September 2020 at the rheumatology outpatient clinic at Cleveland Clinic Abu Dhabi. The demographic and clinical data were recorded. Descriptive statistics of the variables were applied. Results: Fifteen Emirati patients with an established diagnosis of IgG4-RD were assessed. There was a male predominance (53%) with a median age at the time of diagnosis of 47 ± 11.2 years. A 6-year lag period was noted from the initial presentation until a diagnosis of IgG4-RD was established. The most frequent comorbidities observed were hematological conditions (63%), hypertension (47%), diabetes mellitus (40%), and gastroesophageal reflux disease (40%). An elevated serum IgG4 was observed in the majority of patients at the initial presentation. Rheumatoid factor was detected in 13% and low titer of immunofluorescence antinuclear antibody in 7%. 86% of patients had a tissue biopsy with marked lymphocytic and plasmacytic infiltration being the most reported finding in 86%. Methotrexate, azathioprine, and rituximab were the most frequently prescribed disease-modifying agents. Conclusion: We report the first comprehensive analysis on a small cohort of Emirati patients with IgG4-RD. We describe disease features unique to UAE patients and demonstrate that IgG4-RD has a significant disease burden. Our results underscore the need for the IgG4-RD UAE-wide national registry to improve the quality of care of these patients.

IgG4-related disease presenting as recurrent scleritis combined with optic neuropathy

BackgroundWe report a case of atypical presentation of IgG4-related disease (IgG4-RD) with recurrent scleritis and optic nerve involvement.Case presentationA 61-year-old male presented with ocular pain and injection in his left eye for 2 months. Ocular examination together with ancillary testing led to the diagnosis of scleritis, which relapsed in spite of several courses of steroid treatment. After cessation of steroid, the patient complained of severe retro-orbital pain and blurred vision. His best corrected vision was count finger, the pupil was mid-dilated and a relative afferent pupillary defect was found. Funduscopic examination demonstrated disc swelling. Magnetic resonance imaging (MRI) showed enhancing soft tissue encasing the left globe, medial rectus muscle and optic nerve. Systemic work-up revealed multiple nodules in right lower lung and a biopsy showed histopathological characteristics of IgG4-RD. Long-term treatment with corticosteroids and a steroid-sparing agent (methotrexate) led to significant improvement in signs and symptoms with no recurrence for 2 years.ConclusionsThis case highlights the significance of IgG4-RD in the differential diagnosis of recurrent scleritis. IgG4-RD may cause optic neuropathy resulting in visual loss. Early diagnosis and proper treatment can prevent irreversible organ damage and devastating visual morbidity.

Comment on: HHV-8-negative multicentric Castleman disease patients with serological, histopathological and imaging features of IgG4-related disease: reply.

Comment on: HHV-8-negative multicentric Castleman disease patients with serological, histopathological and imaging features of IgG4-related disease: reply.

Comment on: HHV-8-negative multicentric Castleman disease patients with serological, histopathological and imaging features of IgG4-related disease

Comment on: HHV-8-negative multicentric Castleman disease patients with serological, histopathological and imaging features of IgG4-related disease

IgG4 Related Peri-aortitis: A Case Diagnosed in Combined Military Hospital, Dhaka

IgG4 related disease is a multi-organ immune-mediated condition which links many disorders previously regarded as isolated, a single-organ disease without any known underlying systemic condition. It may mimic anymalignant, infectious and inflammatory disorders. It was recognized as a unified entity only 10 years ago. Histopathology is the key to diagnosis. The three central pathology features of IgG4 related disease are lymphoplasmacytic infiltration, stroriform fibrosis, and obliterative arteritis. It is important to promptly diagnose IgG4 related disease because this disease commonly manifests as swelling of the affected organs, which must be differentiated from true neoplasms. Periaortitis or periarteritis is one of the clinical features of IgG4 related diseases. IgG4 related arterial lesions occur mainly in the aorta and its main branches and radiologically characterized by homogeneous arterial wall thickening corresponding to pathological features of IgG4 related sclerosing inflammation in the adventitia. There are 5 types of IgG4 related peri-aortitis, out of which Type 2 is most common. IgG4 related peri-aortitis generally respond to glucocorticoids in its inflammatory stage, but recurrent or refractory cases are common. Greater awareness of this disease is needed to ensure earlier diagnoses to prevent severe organ damage. A 38-year-old male was diagnosed as Type 2 IgG4 related periaortitis 2 years ago in CMH, Dhaka. He was treated with oral steroid and Azathioprine with a rewarding outcome.&#x0D; Journal of Armed Forces Medical College Bangladesh Vol.14 (2) 2018: 217-219

Thyroid Rosai-Dorfman disease with infiltration of IgG4-bearing plasma cells associated with multiple small pulmonary cysts

BackgroundRosai-Dorfman disease (RDD) is a rare histiocytosis which involves principally lymph nodes. Thyroid involvement in RDD is a very rare situation, and lung involvement is even rarer.Case presentationWe report the case of a 46-year-old woman presenting a painless mass in the right side of the neck and subacute dyspnoea. Computerised tomography (CT) scans of the neck and thorax showed a large thyroid mass causing tracheal stenosis and multiple cystic lesions in both lungs. Subtotal thyroidectomy with a tracheal segment resection and histological analysis confirmed the diagnosis of nodal and extranodal (thyroid, tracheal and probably lung) Rosai-Dorfman disease (RDD) with the presence of increased numbers of IgG4-bearing plasma cells. Clinical, functional and radiological follow up 4 years after surgery without medical treatment did not show any disease progression.ConclusionsThis case report indicates a benign course of nodal RDD with thyroid and tracheal infiltration following surgical resection, association of typical histological signs of RDD (emperipolesis) with IgG4-related disease features, and that lung cysts might be a manifestation of RDD.

Advances in IgG4-related sinonasal diseases

IgG4 related disease (IgG4-RD) is an independent clinical pathological entity which is different from common chronic inflammation and other autoimmune diseases in recent years. It often appears in the form of tumor like tissue-destructive lesions and may be accompanied by the increase of concentration of serum IgG4. Histopathology is characterized by a large number of lymphocytes and plasma cells infiltration, storiform fibrosis and occlusive phlebitis. The characteristics of IgG4-RD in nose and sinuses have not been widely investigated. The aim of the present study is to review the advances in IgG4 related sinonasal diseases from four aspects including pathogenesis, clinical features, treatment and future research directions.

Sclerosing Cholangitis Related to IgG4: Not Always a Curable Entity

IgG4-related disease is a recently-described fibro-inflammatory condition with characteristic histopathological findings in the organs involved. The most commonly affected organs are pancreas, lymph nodes, and retroperitoneum. Liver disease usually involves bile structures and therefore IgG4-related disease is considered a cause of secondary sclerosing cholangitis. One out of three patients with IgG4 sclerosing cholangitis also presents autoimmune pancreatitis, although it can be associated with manifestations in other organs. One of the main features of IgG4-related disease is its good prognosis due to the great response to glucocorticoid therapy. However, relapse of the disease is not uncommon, especially when steroid therapy is decreased or stopped. Rituximab seems to be an effective treatment to achieve remission of the disease. We report the case of a 74 year-old man diagnosed with IgG4-related disease based on increase of serum IgG4 levels, imaging and histopathological findings, with systemic involvement including sclerosing cholangitis. Despite the absence of liver fibrosis at onset, the early use of glucocorticoids and rituximab therapy, the patient presented clinical and analytical deterioration, leading to secondary biliary cirrhosis. In conclusion, this clinical case highlights the importance

The Clinicopathologic Spectrum of IgG4-Related Disease

Immunoglobulin G4-related disease is a fibroinflammatory systemic disease that is characterized by focal or diffuse organ infiltration by immunoglobulin G4-bearing plasma cells. Immunoglobulin G4-related disease may affect any organ, and a high index of suspicion is necessary for early detection to avoid irreversible fibrosis, organ dysfunction, and death. Tumor-forming lesions are common radiological features of immunoglobulin G4-related disease that need to be differentiated from malignancies. The diagnostic approach requires the integration of clinical, biochemical, and radiographic manifestations with classic histopathologic features, which remain crucial to diagnosis. The histology of immunoglobulin G4-related disease is determined by a dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis in the presence of increased immunoglobulin G4-positve plasma cells. Although immunoglobulin G4-related disease forms a distinct, clinically independent disease category, many questions and problems remain unanswered, especially on its pathogenesis and the role of immunoglobulin G4. Advances in the understanding of immunoglobulin G4-related disease are likely to change the diagnostic approach in the future and create potential targets for therapeutic purposes. Here we describe the concept of immunoglobulin G4-related disease and the most recent knowledge in the clinico-pathological characteristics on this emerging disease. This study can guide clinicians in early diagnosis and prevent unnecessary surgical resections.

LatY136F knock-in mouse model for human IgG4-related disease.

BackgroundThe adaptor protein Linker for activation of T cell (LAT) is a key signaling hub used by the T cell antigen receptor. Mutant mice expressing loss-of-function mutations affecting LAT and including a mutation in which tyrosine 136 is replaced by a phenylalanine (LatY136F) develop lymphoproliferative disorder involving T helper type 2 effector cells capable of triggering a massive polyclonal B cell activation that leads to hypergammaglobulinemia G1 and E and to non-resolving inflammation and autoimmunity. The purpose of this study was to evaluate whether the phenotypes of LatY136F knock-in mice resemble the immunohistopathological features of immunoglobulin G4-related disease (IgG4-RD).MethodsLatY136F knock-in mice were sacrificed at 4–20 weeks of age, and pancreas, kidney, salivary gland and lung were obtained. All organs were stained with hematoxylin-eosin and with Azan for estimation of collagen in fibrosis, and the severity scores of inflammation and fibrosis were evaluated. Immunostainings were performed to analyze the types of infiltrating cells. In addition, the effects of corticosteroid treatment on the development of tissue lesions and serum levels of IgG1 were assessed.ResultsTissue lesions characterized by inflammatory mononuclear cell infiltration and fibrosis were detected in pancreas, kidney, and salivary gland starting from 6 weeks of age. Immunostainings showed pronounced infiltration of plasma cells, CD4-positive T cells, and macrophages. Infiltrating plasma cells predominantly expressed IgG1. The extent of inflammation in pancreas and salivary glands was markedly reduced by corticosteroid treatment.ConclusionsLatY136F knock-in mice displayed increased production of Th2-type IgG1 (a homologue of human IgG4) and developed multiple organ tissue lesions reminiscent of those seen in patients with IgG4-RD. Moreover, the development of these tissue lesions was highly sensitive to corticosteroid treatment like in IgG4-RD. For these reasons we consider the LatY136F knock-in mouse strain to represent a promising model for human IgG4-RD.

IgG4 related disease involving the renal pelvis: a case report and the literature review

Objective To summarize the characteristics of IgG4 related disease(IgG4-RD), and to avoid unnecessary surgical procedures due to misdiagnosis. Methods Retrospective analysis of the clinical data of one case of IgG4 related disease involving the renal pelvis in our hospital, and the clinical features of IgG4 related disease involving the renal pelvis were reviewed and discussed. A 56-year-old man presented with microscopic hematuria, CT showed right renal pelvis and ureteral wall thickening, local soft tissue density, post contrast CT showed low-density renal pelvic mass and the wall of the ureter-pelvic was irregularly thicken, indicating renal pelvic cancer and lymph node metastasis. PET-CT(18F-FDG) findings indicated that the renal pelvic mass was a malignant tumor, because the glucose metabolism was very high. The preoperative diagnosis was retroperitoneal lesion, suspecting renal pelvic carcinoma or lymphoma. The patient underwent 3D laparoscopic nephroureterectomy with out preoperative biopsy. During operation, we found extensive enlargement of the right renal portal and retroperitoneal lymph nodes, including that the renal portal and the renal pelvis mass had a serious adhesion to the vena cava and renal arterial vein. Results Postoperative pathology results revealed lymphatic tissue hyperplasia and germinal center formation. Immunohistochemical staining showed that most plasma cells positive expression of IgG4 (IgG4>40%, IgG4>100 /HPF), reactive hyperplasia of lymph node, considering the IgG4 related diseases. Serum IgG4 level was 15.2 g/L(0.03-2.01 g/L)after operation. Combined with serological examination, IgG4 related disease was confirmed. There was no evidence of IgG4-related disease at any other site during the follow up period, thereby obviating the need for any additional therapy. Conclusions IgG4 related disease is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells, which leads to the enlargement of the organ or nodular/proliferative lesions. The disease can be revealed as a soft tissue tumor of the renal pelvis and be misdiagnosed as malignant tumor. Surgical intervention could be avoided according to the correct diagnosis. Key words: IgG4 related disease; Renal pelvic carcinoma; Surgery; Diagnosis and therapy

Pulmonary Inflammatory Pseudotumor and Skull Plasma Cell Granuloma as Metachronous Manifestations of IgG4-Related Disease

SESSION TITLE: Lung Pathology 3 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: IgG4 related disease is a recently identified entity that causes tumefactive lesions of organs due to lymphoplasmacytic infiltration by IgG4 positive plasma cells and leads to fibrosis. We present a young man with history of recurrent cryptogenic organizing pneumonia (COP) diagnosed retrospectively as inflammatory pseudotumor of the lung, after calvarial and meningeal plasma cell granuloma (PCG) diagnosis, both metachronous manifestations of IgG4 related disease. CASE PRESENTATION: A 28-year-old male presented to our hospital with seizures in 2016. MRI showed parietal and occipital calvarial lesions with meningeal enhancement that were resected. Biopsy showed spindle cell proliferation with mature polyclonal plasma cells and absence of ALK1 staining, consistent with PCG. IgG4 staining was positive. Computerized tomographic scan revealed chronic interstitial fibrotic changes in bilateral lung apices. On retrospective chart review, it was noted that he had presented with cough with interstitial infiltrates/fibrosis, fever and leukocytosis in 2014. At that time, an extensive infectious and connective tissue disease work up was negative and bone marrow aspiration and biopsy were normal. He was empirically treated with prednisone with subsequent resolution of symptoms. Earlier in 2009, he had presented to another hospital with fever and interstitial lung infiltrates and was treated as COP after lung biopsy. Reevaluation of the slides from 2009 biopsy was consistent with inflammatory pseudotumor of the organizing pneumonia, fibrohistiocytic type with predominant macrophages and fibrosis. DISCUSSION: Autoimmune pancreatitis was the first IgG4 disease to be characterized; however it can involve any organ. Organ involvement can be metachronous. Histopathological features of IgG4 related disease are dense lymphoplasmacytic infiltrate, storiform fibrosis and obliterative phlebitis. There is variability in findings in organs such as the lungs in which aggregates of neutrophils may be found within inflammatory infiltrates, with lack of storiform fibrosis in non-solid lesions such as interstitial pneumonia. Steroids are the first line of treatment, however patients may flare despite adequate treatment. Immunosuppressive drugs have been used as steroid-sparing agents and for maintenance therapy. Steroid-refractory disease and recurrent disease has been shown to have a good response to rituximab. Response to treatment is better during the lymphoplasmacytic infiltration stage, prior to extensive fibrosis. CONCLUSIONS: It is important to consider IgG4 related disease in tumors of any organ and if tissue biopsy is consistent with this diagnosis, extensive surgery can be avoided since the disease in the active phase responds to steroid or rituximab. Reference #1: “Inflammatory myofibroblastic tumor (plasma cell granuloma). Clinicopathologic study of 20 cases with immunohistochemical and ultrastructural observations.” Am J Clin Pathol 94(5): 538-546. DISCLOSURE: The following authors have nothing to disclose: Aditya Kotecha, Hussein Saleh, Saraschandra Vallabhajosyula, Christina Desousa, AbuFazl Mohammed, Vivek Iyer, Geetha Krishnamoorthy No Product/Research Disclosure Information