scholarly journals Histopathologic Overlap between Fibrosing Mediastinitis and IgG4-Related Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Tobias Peikert ◽  
Bijayee Shrestha ◽  
Marie Christine Aubry ◽  
Thomas V. Colby ◽  
Jay H. Ryu ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Plasma Cells ◽  
Immunosuppressive Agents ◽  
Granulomatous Disease ◽  
Obliterative Phlebitis ◽  
Fibrosing Mediastinitis ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

Fibrosing mediastinitis (FM) and IgG4-related disease (IgG4-RD) are two fibroinflammatory disorders with potentially overlapping clinical and radiological features. In this paper, we looked for histopathologic features of IgG4-RD and enumerated infiltrating IgG4-positive plasma cells within mediastinal tissue biopsies from FM patients. We identified 15 consecutive FM surgical mediastinal tissue biopsies between 1985 and 2006. All patients satisfied the clinical and radiological diagnostic criteria for FM. All patients had either serological or radiological evidence of prior histoplasmosis or granulomatous disease, respectively. Formalin-fixed paraffin-embedded tissue sections of all patients were stained for H&E, IgG, and IgG4. Three samples met the predefined diagnostic criteria for IgG4-RD. In addition, characteristic histopathologic changes of IgG4-RD in the absence of diagnostic numbers of tissue infiltrating IgG4-positive plasma cells were seen in a number of additional cases (storiform cell-rich fibrosis in 11 cases, lymphoplasmacytic infiltrate in 7 cases, and obliterative phlebitis/arteritis in 2 cases). We conclude that up to one-third of histoplasmosis or granulomatous-disease-associated FM cases demonstrate histopathological features of IgG4-RD spectrum. Whether these changes occur as the host immune response against Histoplasma or represent a manifestation of IgG4-RD remains to be determined. Studies to prospectively identify these cases and evaluate their therapeutic responses to glucocorticoids and/or other immunosuppressive agents such as rituximab are warranted.

scholarly journals Needle biopsy compared with surgical biopsy: pitfalls of small biopsy in histologial diagnosis of IgG4-related disease

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Yanying Liu ◽  
Fei Yang ◽  
Xiying Chi ◽  
Yuxin Zhang ◽  
Jiangnan Fu ◽  
...  
Keyword(s):  
Needle Biopsy ◽  
Plasma Cells ◽  
Classification Criteria ◽  
Histological Diagnosis ◽  
Obliterative Phlebitis ◽  
Surgical Biopsy ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Significant Difference ◽  
Storiform Fibrosis

Abstract Objective The growing utilization of needle biopsy has challenged the current pathology consensus of IgG4-related disease (IgG4-RD). The aims of this study were to identify the histological characteristics of needle biopsy and surgical specimens and evaluate the ability of needle biopsy in histological diagnosis of IgG4-RD. Methods Biopsies from patients who were referred to as IgG4-RD by the 2019 ACR/EULAR IgG4-RD classification criteria in Peking University People’s Hospital from 2012 to 2019 were re-evaluated. Typical histological features and diagnostic categories were compared between needle biopsy and surgical biopsy. Results In total, 69 patients met the 2019 ACR/EULAR classification criteria and 72 biopsies of them were re-evaluated. All cases showed lymphoplasmacytic infiltrate, while storiform fibrosis and obliterative phlebitis were only present in 35 (48.6%) and 23 (31.9%) specimens, respectively. Storiform fibrosis was more likely to be seen in retroperitoneum lesion (P = 0.033). Surgical biopsy showed significantly higher IgG4+ plasma cells/high-power field (IgG4/HPF) count (P < 0.01) and higher proportion of IgG4/HPF > 10 (P < 0.01). No significant difference was observed with regard to the ratio of IgG4+ plasma cells/IgG+ plasma cells (IgG4/IgG) (P = 0.399), storiform fibrosis (P = 0.739), and obliterative phletibis (P = 0.153). According to the 2011 comprehensive diagnostic criteria, patients who performed a needle biopsy were less likely to be probable IgG4-RD (P = 0.045). Based on the 2011 pathology consensus, needle biopsy was less likely to be diagnosed as IgG4-RD (P < 0.01), especially to be highly suggestive IgG4-RD (P < 0.01). Only 1/18 (5.6%) needle salivary specimens fulfilled the cutoff of IgG4/HPF > 100, which was significantly less than 15/23 (65.2%) of surgical ones (P < 0.01). Conclusions Needle biopsy shows an inferiority in detecting IgG4/HPF count but not in IgG4/IgG ratio, storiform fibrosis, and obliterative phlebitis. Compared with surgical samples, needle biopsy is less likely to obtain a histological diagnosis of IgG4-RD. A different IgG4/HPF threshold for needle biopsy of the salivary glands may be considered.

scholarly journals Are Classification Criteria for IgG4-RD Now Possible? The Concept of IgG4-Related Disease and Proposal of Comprehensive Diagnostic Criteria in Japan

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kazuichi Okazaki ◽  
Hisanori Umehara
Keyword(s):  
Diagnostic Criteria ◽  
Plasma Cells ◽  
Elevated Serum ◽  
Serum Levels ◽  
Mikulicz’S Disease ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Biopsy Specimens ◽  
Organ Specific ◽  
Low Sensitivity

Recent studies suggest simultaneous or metachronous lesions in multiorgans characterized by elevated serum levels of IgG4 and abundant infiltration of IgG4-positive plasma cells with various degrees of fibrosis. Two Japanese research committees for IgG4-RD, one from fibrosclerosis (Okazaki team) and the other from lymph proliferation (Umehara team) supported by the “Research Program for Intractable Disease” of the Ministry of Health, Labor, and Welfare of Japan, have agreed with the unified nomenclature as “IgG4-RD” and proposed the comprehensive diagnostic criteria (CDC) for IgG4-RD. Validation of the CDC demonstrated satisfactory sensitivity for the practical use of general physicians and nonspecialists but low sensitivity in the organs to be difficult in taking biopsy specimens such as type1 autoimmune pancreatitis (IgG4-related AIP), compared with IgG4-related sialadenitis/dacryoadenitis (Mikulicz's disease) and IgG4-related kidney disease. Although the diagnostic criteria covering all IgG4-RD are hard to be established, combination with the CDC and organ-specific diagnostic criteria should improve sensitivity.

scholarly journals IgG4-Related Sclerosing Cholangitis: Rarely Diagnosed, but not a Rare Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Sylvia Drazilova ◽  
Eduard Veseliny ◽  
Patricia Denisa Lenartova ◽  
Dagmar Drazilova ◽  
Jakub Gazda ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Sclerosing Cholangitis ◽  
Plasma Cells ◽  
Histological Finding ◽  
Good Prognosis ◽  
High Serum ◽  
Obliterative Phlebitis ◽  
Igg4 Related Disease ◽  
Serum Igg4 ◽  
Storiform Fibrosis

IgG4-related sclerosing cholangitis, a biliary manifestation of an IgG4-related disease, belongs to the spectrum of sclerosing cholangiopathies which result in biliary stenosis. It presents with signs of cholestasis and during differential diagnosis it should be distinguished from cholangiocarcinoma or from other forms of sclerosing cholangitis (primary and secondary sclerosing cholangitis). Despite increasing information and recently established diagnostic criteria, IgG4-related sclerosing cholangitis remains underdiagnosed in routine clinical practice. The diagnosis is based on a combination of the clinical picture, laboratory parameters, histological findings, and a cholangiogram. Increased serum IgG4 levels are nonspecific but are indeed a part of the diagnostic criteria proposed by the Japan Biliary Association and the HISORt criteria for IgG4-SC. High serum IgG4 retains clinical utility depending on the magnitude of elevation. Approximately 90% of patients have concomitant autoimmune pancreatitis, while 10% present with isolated biliary involvement only. About 26% of patients have other organ involvement, such as IgG4-related dacryoadenitis/sialadenitis, IgG4-related retroperitoneal fibrosis, or IgG4-related renal lesions. A full-blown histological finding characterized by IgG4-enriched lymphoplasmacytic infiltrates, obliterative phlebitis, and storiform fibrosis is difficult to capture in practice because of its subepithelial localization. However, the histological yield is increased by immunohistochemistry, with evidence of IgG4-positive plasma cells. Based on a cholangiogram, IgG-4 related sclerosing cholangitis is classified into four subtypes according to the localization of stenoses. The first-line treatment is corticosteroids. The aim of the initial treatment is to induce clinical and laboratory remission and cholangiogram normalization. Even though 30% of patients have a recurrent course, in the literature data, there is no consensus on chronic immunosuppressive maintenance therapy. The disease has a good prognosis when diagnosed early.

scholarly journals IgG4-Related Disease in a Urachal Tumor

2014 ◽  
Vol 2014 ◽  
pp. 1-3
Author(s):  
Travis W. Dum ◽  
Da Zhang ◽  
Eugene K. Lee
Keyword(s):  
Plasma Cells ◽  
Elevated Serum ◽  
Needle Aspiration ◽  
Lung Lesion ◽  
High Rate ◽  
Mediastinal Lymphadenopathy ◽  
Obliterative Phlebitis ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Serum Igg4

IgG4-related disease is a newly recognized fibroinflammatory disorder that has the ability to affect nearly every organ system. It is characterized by tumefactive lesions and fibrosis and closely mimics neoplasms. Only one case of IgG4-related bladder mass has been reported in the literature, but there are no reports of IgG4-related disease in a urachal mass. Herein, we report a 26-year-old male who initially presented with symptoms of recurrent UTI. Work-up revealed a 6 cm urachal tumor, a 1.4 cm pulmonary lesion, and mediastinal lymphadenopathy; all metabolically active on PET scan and suspicious for urachal adenocarcinoma. Lung lesion fine needle aspiration and TURBT pathology revealed inflammation but no evidence of malignancy. The patient underwent a partial cystectomy and umbilectomy with pathology demonstrating dense plasmacytic cells, a high rate of immunohistochemistry staining positive for IgG4 plasma cells, a storiform pattern of fibrosis, and an obliterative phlebitis. Furthermore, the patient had an elevated serum IgG4 level of 227 mg/dL (range 2.4–121 mg/dL). IgG4-related disease is a newly recognized fibroinflammatory disorder that can mimic neoplastic processes and a high index of suspicion and accurate tissue pathology is necessary for an accurate diagnosis.

IgG4-Related Disease of the Gastrointestinal Tract: A 21st Century Chameleon

2015 ◽  
Vol 139 (6) ◽  
pp. 742-749 ◽  
Author(s):  
Vikram Deshpande
Keyword(s):  
Gastrointestinal Tract ◽  
Personal Experience ◽  
Plasma Cells ◽  
Diagnostic Algorithm ◽  
Obliterative Phlebitis ◽  
Immunoglobulin G4 ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Lymphoplasmacytic Infiltrate ◽  
Histologic Changes

Context Immunoglobulin G4 (IgG4)–related disease is a systemic fibroinflammatory disease capable of affecting virtually any organ. Although the pancreas and hepatobiliary system are commonly affected, involvement of the tubular gut is unusual. The pancreatic manifestations of this disease (autoimmune pancreatitis) often mimic pancreatic carcinoma, whereas the hepatobiliary manifestations are mistaken for cholangiocarcinoma or primary sclerosing cholangitis. The characteristic histologic features include a dense lymphoplasmacytic infiltrate, storiform-type fibrosis, and obliterative phlebitis. An increase in IgG4+ plasma cells and an IgG4 to IgG ratio of more than 40% are considered obligatory components of the diagnostic algorithm. Objective To review the challenges associated with the diagnosis of IgG4-related disease of the gastrointestinal tract. Data Sources A review of pertinent literature, along with the author's personal experience, based on institutional and consultation materials. Conclusion The complete spectrum of histologic changes is seldom captured in a biopsy specimen, and thus, the histopathology findings are best interpreted within the overall clinical context. Increased IgG4+ plasma cells are identified in a variety of benign and malignant diseases of the gastrointestinal tract.

scholarly journals The Cellular and Molecular Bases of Allergy, Inflammation and Tissue Fibrosis in Patients with IgG4-related Disease

2020 ◽  
Vol 21 (14) ◽  
pp. 5082
Author(s):  
Song-Chou Hsieh ◽  
Chieh-Yu Shen ◽  
Hsien-Tzung Liao ◽  
Ming-Han Chen ◽  
Cheng-Han Wu ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Elevated Serum ◽  
Clinical Manifestations ◽  
Malignant Neoplasms ◽  
Th2 Response ◽  
Obliterative Phlebitis ◽  
Inflammatory Reactions ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Serum Igg4

IgG4-related disease (IgG4-RD) is a spectrum of complex fibroinflammatory disorder with protean manifestations mimicking malignant neoplasms, infectious or non-infectious inflammatory process. The histopathologic features of IgG4-RD include lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis together with increased in situ infiltration of IgG4 bearing-plasma cells which account for more than 40% of all IgG-producing B cells. IgG4-RD can also be diagnosed based on an elevated serum IgG4 level of more than 110 mg/dL (normal < 86.5 mg/mL in adult) in conjunction with protean clinical manifestations in various organs such as pancreato–hepatobiliary inflammation with/without salivary/lacrimal gland enlargement. In the present review, we briefly discuss the role of genetic predisposition, environmental factors and candidate autoantibodies in the pathogenesis of IgG4-RD. Then, we discuss in detail the immunological paradox of IgG4 antibody, the mechanism of modified Th2 response for IgG4 rather than IgE antibody production and the controversial issues in the allergic reactions of IgG4-RD. Finally, we extensively review the implications of different immune-related cells, cytokines/chemokines/growth factors and Toll-like as well as NOD-like receptors in the pathogenesis of tissue fibro-inflammatory reactions. Our proposals for the future investigations and prospective therapeutic strategies for IgG4-RD are shown in the last part.

IgG4-related disease: an atypical presentation of steroid-responsive renal mass

2021 ◽  
Vol 14 (5) ◽  
pp. e240611
Author(s):  
Shu Hui Ng ◽  
Jing Shin Tay ◽  
Ee Ling Lai
Keyword(s):  
Renal Mass ◽  
Plasma Cells ◽  
Normal Serum ◽  
Obliterative Phlebitis ◽  
Related Disease ◽  
First Line Therapy ◽  
Igg4 Related Disease ◽  
Serum Igg ◽  
Storiform Fibrosis ◽  
Lymphoplasmacytic Infiltration

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disease characterised by dense lymphoplasmacytic infiltration rich in IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. Serum IgG4 levels are typically elevated but half of the patients had normal serum IgG4 levels. IgG4-RD represents a spectrum of diseases that involve various organs such as the pancreas, liver, kidneys, and salivary glands often manifesting as diffuse organ enlargement or a mass-like lesion mimicking cancer. An increased incidence of malignancy among patients with IgG4-RD has been reported. Thus, differentiating malignancy from IgG4-RD manifestation is important as the treatment differs. Glucocorticoids are considered first-line therapy and should be started early to prevent fibrosis. Patients usually have an excellent clinical response to steroids, and poor steroid response is indicative of an alternative diagnoses such as malignancy. This case report describes a case of IgG4-RD with renal mass in a young man that resolved with glucocorticoid therapy alone.

IgG4-related Disease in Thymus. A Very Rare Case of Chronic Fibrosis Mimicking Sarcoidosis

2017 ◽  
Vol 103 (1_suppl) ◽  
pp. S19-S24 ◽  
Author(s):  
Sara Simonetti ◽  
Noelia Pérez Muñoz ◽  
Josefa López Vivancos ◽  
Lluís Sanchez Sitjes ◽  
Javier Cesar Herranz Pérez ◽  
...  
Keyword(s):  
Plasma Cells ◽  
English Literature ◽  
Histopathological Analysis ◽  
Obliterative Phlebitis ◽  
Thymic Tissue ◽  
Positive Ratio ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Storiform Fibrosis ◽  
Serological Data

IgG4-related disease (IgG4-RD) is a multi-organ immune-mediated chronic fibroinflammatory condition, with unclear certain etiology. It is morphologically characterized by storiform fibrosis, dense IgG4-positive lympho-plasmacytic infiltrate, and obliterative phlebitis. It was recognized as a systemic condition as recently as 2003. IgG4-RD has been described in virtually every organ, forming sclerosing masses, and often mimicking tumors. Clinically, patients present unspecific symptoms and this condition is often recognized incidentally. The epidemiology remains poorly studied, but it has been noted that in the majority of recorded instances, patients are middle-aged men. IgG4-RD could mimic conditions other than tumors, such as infection, inflammation, or other systemic disorders. To ensure accuracy of diagnosis, an exhaustive histopathological analysis is required, together with clinical, radiological, and serological data. Thymic fibrosis in the absence of other primary thymic lesions is a very rare occurrence; in English literature only 1 case has been reported with scattered IgG4 plasma cells infiltrate and focal obliterative phlebitis. We will describe, for the first time, the case of a 49-year-old man displaying an anterior mediastinic, hilar, and intramyocardial mass simulating a sarcoidosis, with a definitive diagnosis of IgG4-related thymic fibrosis extending to the mediastinum and the heart. At the histological examination, we found many features of IgG4-RD in the thymic tissue, such as diffused storiform fibrosis, dense lymphoplasmacytic infiltrate with abundant plasma cells IgG4 positive (ratio IgG/IgG4: 40%), obliterative phlebitis, eosinophilic infiltrate, and Castleman-like lymphoid follicles. We discussed the differential diagnosis and reviewed the literature and the other cases of IgG4-related diseases that had been diagnosed in our department.

IgG4-related disease: a clinical perspective

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_3) ◽  
pp. iii123-iii131 ◽  
Author(s):  
Federica Maritati ◽  
Francesco Peyronel ◽  
Augusto Vaglio
Keyword(s):  
Plasma Cells ◽  
Organ Damage ◽  
Inflammatory Disorder ◽  
Obliterative Phlebitis ◽  
Steroid Resistant ◽  
Related Disease ◽  
Resistant Disease ◽  
Igg4 Related Disease ◽  
Lymphoplasmacytic Infiltrate ◽  
Storiform Fibrosis

Abstract IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder that can affect almost any organ. Common presentations include major salivary and lacrimal gland enlargement, orbital disease, autoimmune pancreatitis, retroperitoneal fibrosis and tubulointerstitial nephritis. The main histopathological features are a dense, polyclonal, lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, storiform fibrosis and obliterative phlebitis. The precise pathogenic mechanisms of IgG4-RD are still unclear. CD4+ T and B cells, including IgG4-expressing plasmablasts, constitute the major inflammatory cell populations and are believed to cause organ damage and tissue fibrosis. The diagnosis of the disease may be challenging and should be based on specific histopathological findings, typical laboratory and radiological aspects and an appropriate clinical context. The first-line treatment of IgG4-RD is based on glucocorticoids, which are usually efficacious. However, B cell depletion induced by rituximab has also been found to induce remission in steroid-resistant disease or has been used as steroid-sparing agent for relapsing disease. This review provides an update on clinical and therapeutic aspects of IgG4-RD.

scholarly journals IgG4-related intracranial disease

2018 ◽  
Vol 32 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Shahine Goulam-Houssein ◽  
Jeffrey L Grenville ◽  
Katerina Mastrocostas ◽  
David G Munoz ◽  
Amy Lin ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Surgical Intervention ◽  
Case Series ◽  
Hypertrophic Pachymeningitis ◽  
Diagnostic Challenge ◽  
Perineural Spread ◽  
Related Disease ◽  
The Third ◽  
Igg4 Related Disease ◽  
Intracranial Involvement

IgG4-related disease (IgG4-RD) is a multi-organ chronic inflammatory process caused by infiltration of IgG4-positive plasma cells in one or more organs. Intracranial involvement has only recently become better recognized. Our case series adds to the growing literature on the varying presentations of intracranial IgG4 by describing the clinical and imaging findings of three patients who presented to our institution with intracranial involvement. Our first patient presented with a mass-forming IgG4 pachymeningitis mimicking a sphenoid wing meningioma, which is to our knowledge the largest mass-forming pachymeningitis published in the literature. Our second case depicts another presentation of extensive IgG4 pachymeningitis involving both cavernous sinuses and surrounding Meckel’s caves. The third case describes a patient with presumed lymphocytic hypophysitis, which was later determined to be IgG4-related hypophysitis with concomitant pachymeningitis and perineural spread along the optic nerves. The delayed diagnoses in our cases illustrates the diagnostic challenge that clinicians face in differentiating intracranial IgG4-RD from other infiltrative diseases such as sarcoidosis, granulomatous disease, tuberculosis and lymphoma. Earlier consideration of IgG4-related hypophysitis and hypertrophic pachymeningitis in the differential diagnosis can prevent significant morbidity including unnecessary surgical intervention and organ failure secondary to extensive fibrosis.

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