Spectrum Of IgG4-related Disease Research Articles

Issue Highlights

Issue Highlights

Right ethmoid eosinophilic angiocentric fibrosis with orbital extension

IntroductionEosinophilic angiocentric fibrosis (EAF) is a slowly progressive, benign disease involving the mucosa of the upper airways or, more rarely, the orbit. It belongs to the spectrum of IgG4-related disease. Case reportThe authors report the case of a 61-year-old man who presented with orbital involvement (visual loss, pain, proptosis, and eyelid oedema), headache and nasal obstruction. Imaging revealed a right ethmoido-orbital mass infiltrating the periorbital fat and enveloping the optic nerve. Histological examination concluded on a diagnosis of EAF in the presence of perivascular infiltration by inflammatory cells, predominantly eosinophils, and zones of “onion skin” fibrosis. Immunohistochemistry attributed these lesions to IgG4-related disease. Initial treatment with corticosteroids followed by dapsone failed to control the disease and resulted in severe steroid dependence. Surgical ethmoidectomy with resection of the lamina papyracea was performed to allow displacement of the eyeball into the nasal cavity in the event of another episode. DiscussionThe combination of surgery and rituximab achieved lasting pain relief with no recurrence of exophthalmos.

Idiopathic retroperitoneal fibrosis and its overlap with IgG4-related disease.

Retroperitoneal fibrosis (RPF) is a rare disease characterised by fibrous tissue proliferation in the retroperitoneum, with encasement of the ureters and large vessels of the abdomen as the most destructive of potentially severe complications. It can either be idiopathic, or secondary to infections, malignancies, or the use of certain drugs. The idiopathic form accounts for approximately 75% of the cases, and is usually responsive to immunosuppressive therapy. In recent years, the emergence of a new clinical entity, IgG4-related disease (IgG4-RD), shed light on many fibro-inflammatory disorders once thought to be separate clinical entities, although frequently associated in the so-called multifocal fibrosclerosis. Among these, together with sclerosing pancreatitis and cholangitis, pseudotumour of the orbit, idiopathic mediastinal fibrosisand other conditions, is idiopathic retroperitoneal fibrosis (IRF). Both IRF and IgG4-RD can be associated with a wide variety of disorders, usually governed by immune-mediated (and particularly auto-immune) mechanisms. In our review, we discuss the clinical and therapeutic challenges IRF presents to the internist, as well as the meaning of its recent inclusion in the IgG4-RD spectrum from a clinical practice standpoint.

Pathogenesis and clinical spectrum of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a disease of the biliary tract, which has been documented in the literature since 1867. This disease has a strong predilection for affecting men and can be seen in individuals as young as 2 years of age. PSC has a strong associated with inflammatory bowel disease, more commonly with ulcerative colitis, and is also part of the clinical spectrum of IgG4-related diseases. Small-duct PSC, a variant of PSC, also has an association with inflammatory bowel disease. The exact pathogenesis of PSC is not well understood at present, however, is likely a combination of a genetic predisposition with alteration of the molecular structure of the gut. Abnormal serum liver chemistry and presence of certain autoimmune markers are usually the first indicators leading to a diagnosis of PCS, however, these may often be normal in early stages of this disease. The diagnosis is made by cholangiography, which is now considered the gold standard. PSC is a known pre-malignant condition. Such patients have an increased risk of developing cholangiocarcinoma, gallbladder neoplasia, and colon cancer. Many new treatment modalities have emerged in the recent past, including anti-tumor necrosis factor- α and anti-integrins; however, liver transplantation is the only known cure for PSC. Despite past and present research, PSC remains an enigmatic biliary disease with few viable treatment options.

Riedel's thyroiditis association with IgG4-related disease

IgG4-positive (+) plasma cells have been reported in both Riedel's thyroiditis (RT) and Hashimoto's thyroiditis (HT). These cells are the hallmark of IgG4-related disease (IgG4-RD). We sought to determine whether RT is part of IgG4-RD spectrum. This was a case-control study performed at a tertiary medical centre. We included RT cases from the period 1958 to 2008 that had sufficient paraffin-embedded tissue for IgG4 immunostaining. Controls were patients with HT, age and gender matched, with similar pathology criteria. The main outcome measures were the intensity of the IgG4 staining and the clinical and histological correlates with IgG4-RD. Six pairs of RT and HT were analysed. The mean age was 44·7years. In both groups, 5/6 cases had positive IgG4 staining. The mean number of IgG4+cells/ HPF, normalized to the degree of inflammation, was 3·2±3·0 SD (RT) vs 0·9±0·7 (HT), P=0·15, for fibrotic areas and 2·1±2·3 SD vs 1·0±0·8 (P=0·39) for areas with lymphoid aggregates. We found the number of IgG4+ cells in RT to be inversely correlated with the duration of disease (P=0·046). Three RT cases had associated comorbidities from the IgG4-RD spectrum while none of the HT cases had such conditions. Riedel's thyroiditis is a component of IgG4-RD with the density of the IgG4+ lymphocytic infiltrate being time dependent. In this small study, we did not identify differences in IgG4 infiltration between RT and HT, minimizing the utility of this marker in RT diagnosis.

Association of newly diagnosed type 1 diabetes and autoimmune pancreatitis.

SummaryAutoimmune pancreatitis is a new nosological entity in which a lymphocytic infiltration of the exocrine pancreas is involved. The concomitant onset of autoimmune pancreatitis and type 1 diabetes has been recently described suggesting a unique immune disturbance that compromises the pancreatic endocrine and exocrine functions. We report a case of type1 diabetes onset associated with an autoimmune pancreatitis in a young patient who seemed to present a type 2 autoimmune polyglandular syndrome. This rare association offers the opportunity to better understand pancreatic autoimmune disorders in type 1 diabetes.Learning points:The case makes it possible to understand the possibility of a simultaneous disturbance of the endocrine and exocrine function of the same organ by one autoimmune process.The diagnosis of type 1 diabetes should make practitioner seek other autoimmune diseases. It is recommended to screen for autoimmune thyroiditis and celiac diseases. We draw attention to consider the autoimmune origin of a pancreatitis associated to type1 diabetes.Autoimmune pancreatitis is a novel rare entity that should be known as it is part of the IgG4-related disease spectrum.

IgG4-related skin disease may have distinct systemic manifestations: a systematic review.

IgG4-related disease (IgG4-RD) is an increasingly prevalent protean multisystem disorder characterized by single or multi-organ infiltration of IgG4-bearing plasma cells. Skin involvement has been recognized and is relevant to proper diagnosis. A systematic literature review of 50 cases involving the skin reveals that patients with IgG4-related skin disease show predominant involvement of the head and neck and have a distinct pattern of systemic involvement, also favoring the head and neck - lymphatics, orbit, salivary, and lacrimal glands - but generally lacking pancreaticobiliary involvement (16% of cases), which by contrast is a predominant manifestation in systemic IgG4-RD (60% with pancreaticobiliary involvement). We summarize clinical and pathologic descriptive data from this systematic review. We review differential diagnosis and propose a diagnostic scheme for stratifying probability of disease based upon comprehensive integration of clinical, histopathologic, and laboratory data. Plasmacyte infiltration and storiform fibrosis are prominent in IgG4-related skin disease, but obliterative venulitis is less common than in the prototypical IgG4-related disease manifestation of autoimmune pancreatitis. IgG4 tissue and serum values, with a mean (±95% CI) in the reviewed cases of 132.8 ± 32.6 IgG4-positive plasma cells per high-power field and 580 ± 183.8 mg/dl, respectively, are incorporated into the suggested criteria. The distinct set of manifestations identified by this systematic review and the proposed diagnostic considerations, while requiring further validation in prospective studies, highlight the need to consider that IgG4-related skin disease defines a unique systemic disease complex along the spectrum of IgG4-RD.

Deconstructing IgG4-related disease involvement of midline structures: Comparison to common mimickers

Objective: A series of destructive and tumefactive lesions of the midline structures have been recently added to the spectrum of IgG4-related disease (IgG4-RD). We examined the clinical, serological, endoscopic, radiological, and histological features that might be of utility in distinguishing IgG4-RD from other forms of inflammatory conditions with the potential to involve the sinonasal area and the oral cavity.Methods: We studied 11 consecutive patients with erosive and/or tumefactive lesions of the midline structures referred to our tertiary care center. All patients underwent serum IgG4 measurement, flow cytometry for circulating plasmablast counts, nasal endoscopy, radiological studies, and histological evaluation of tissue specimens. The histological studies included immunostaining studies to assess the number of IgG4 + plasma cells/HPF for calculation of the IgG4+/IgG + plasma cell ratio.Results: Five patients with granulomatosis with polyangiitis (GPA), three with cocaine-induced midline destructive lesions (CIMDL), and three with IgG4-RD were studied. We found no clinical, endoscopic, or radiological findings specific for IgG4-RD. Increased serum IgG4 and plasmablasts levels were not specific for IgG4-RD. Rather, all 11 patients had elevated blood plasmablast concentrations, and several patients with GPA and CIMDL had elevated serum IgG4 levels. Storiform fibrosis and an IgG4+/IgG + plasma cell ratio >20% on histological examination, however, were observed only in patients with IgG4-RD.Conclusions: Histological examination of bioptic samples from the sinonasal area and oral cavity represents the mainstay for the diagnosis of IgG4-RD involvement of the midline structures.

Idiopathic Mediastinal Fibrosis: a Systemic Immune-Mediated Disorder. A Case Series and a Review of the Literature

Mediastinal fibrosis is a rare disease characterised by fibrous proliferation in the mediastinum. It can be idiopathic or secondary to several conditions such as infections and malignancies. Anecdotal reports have described idiopathic mediastinal fibrosis (IMF) in association with other fibro-inflammatory or autoimmune diseases.We report nine new IMF cases recently seen at our Fibro-Inflammatory Disease Clinic and reviewed the IMF cases reported in the English language literature throughout 2006-2016. The purposes of our literature search were to assess the frequency of the association between IMF and other immune-mediated disorders and to analyse which disorders most often coexist with IMF. Of our nine IMF cases, one was associated with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, one with large-vessel arteritis, three with idiopathic retroperitoneal fibrosis (one of which was IgG4-related), one with pancreatitis and one with IgG4-related seminal vesicle involvement. The remaining two cases, in which IMF was not associated with any other disease, were both classifiable as IgG4-related. The literature review showed that, of the 84 IMF cases identified, 27 (32%) were associated with other idiopathic autoimmune or fibro-inflammatory disorders, particularly small-vessel vasculitis, Behçet disease, retroperitoneal fibrosis and other conditions belonging to the IgG4-related disease spectrum. Based on our own data and the literature review, we conclude that IMF is often associated with other autoimmune or fibro-inflammatory diseases; therefore, its clinical management requires an accurate screening of associated conditions. Immune-mediated mechanisms may be shared by these disorders.

Idiopathic Retroperitoneal Fibrosis.

Idiopathic retroperitoneal fibrosis (RPF), reviewed herein, is a rare fibro-inflammatory disease that develops around the abdominal aorta and the iliac arteries, and spreads into the adjacent retroperitoneum, where it frequently causes ureteral obstruction and renal failure. The clinical phenotype of RPF is complex, because it can be associated with fibro-inflammatory disorders involving other organs, is considered part of the spectrum of IgG4-related disease, and often arises in patients with other autoimmune conditions. Obstructive uropathy is the most common complication, although other types of renal involvement may occur, including stenosis of the renal arteries and veins, renal atrophy, and different types of associated GN. Environmental and genetic factors contribute to disease susceptibility, whereas the immunopathogenesis of RPF is mediated by different immune cell types that eventually promote fibroblast activation. The diagnosis is made on the basis of computed tomography or magnetic resonance imaging, and positron emission tomography is a useful tool in disease staging and follow-up. Treatment of idiopathic RPF aims at relieving ureteral obstruction and inducing disease regression, and includes the use of glucocorticoids, combined or not with other traditional immunosuppressants. However, biologic therapies such as the Bcell-depleting agent rituximab are emerging as potentially efficacious agents in difficult-to-treat cases.

IgG4-related disease with coronary arteritis

We have read with great interest the recently published article entitled “IgG4-related systemic disease with coronary arteritis and aortitis, causing recurring critical coronary ischemia” written by Tran MN and his colleagues [ [1] Tran M.N. Langguth D. Hart G. et al. IgG4-related systemic disease with coronary arteritis and aortitis, causing recurring critical coronary ischemia. Int. J. Cardiol. 2015; 201: 33-34 Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar ]. This paper described a 72 year old male with complex presentation of IgG4-related disease (IgG4-RD) with aortitis and coronary arteritis. IgG4-RD is a systemic immune-mediated disease characterized pathologically by the infiltration of IgG4-bearing plasma cells into involved organs and raised IgG4 levels [ [2] Stone J.H. Zen Y. Deshpande V. IgG4-RD. N. Engl. J. Med. 2012; 366: 539-551 Crossref PubMed Scopus (1873) Google Scholar ]. The cardinal clinical feature of IgG4-RD is single or multiple organ swelling and the organs more frequently involved are the pancreas, salivary/lacrimal glands, biliary tree, kidneys, thyroid gland, lungs, and aorta [ [3] Brito-Zerón P. Ramos-Casals M. Bosch X. et al. The clinical spectrum of IgG4-related disease. Autoimmun. Rev. 2014; 13: 1203-1210 Crossref PubMed Scopus (198) Google Scholar ].

Spectrum of IgG4-related disease on multi-detector CT: a 5-year study of a single medical center data

To discuss the diverse imaging features of pancreatic and extra-pancreatic lesions of IgG4-related disease (IgG4-RD) on multi-detector CT (MDCT). This retrospective study was approved by our institutional research ethics board, and informed consent was waived. From 2008 to 2013, 159 patients including 120 men (mean age 57 years; range 27-79 years) and 39 women (mean age 51 years; range 25-83 years) who met the comprehensive diagnostic criteria for IgG4-RD (2011) were enrolled. MDCT images consisted of 153 abdominal images, 64 pelvic images, 64 thoracic images, and 8 neck images were retrospectively analyzed in consensus by two radiologists with expertise in the CT diagnosis of IgG4-RD. Only 11 (11/153, 7.2%) IgG4-RD patients had been found with no pancreatic involvement. 145 (145/159, 91.2%) patients had various extra-pancreatic lesions, including involvement of biliary tree (93/153, 60.8%), peri-pancreatic vessels (66/153, 43.1%), IgG4-related lymphadenopathy, peri-abdominal aorta arteritis or retroperitoneal fibrosis, head and neck lesions, etc. Renal lesions were found in 26 (26/153, 17.0%) IgG4-RD patients with 4 types of renal parenchymal involvement. Lung lesions were found in 44 (44/64, 68.7%) IgG4-RD patients, which were classified into 7 types. Pancreatic and various extra-pancreatic lesions may be involved in IgG4-RD patients frequently with typical imaging findings. It is useful to recognize the atypical or uncommon imaging features to help the diagnosis of IgG4-RD together with other serologic or histopathologic findings.

IgG4-Related Disease and Retroperitoneal Fibrosis

IgG4-related disease (IgG4-RD) has been observed to affect almost every organ system, with consistent histopathologic findings across systems. IgG4-RD can mimic malignant, infectious, and inflammatory disorders; accordingly, consideration of the histopathologic features of tissue biopsies and rigorous clinicopathologic correlations are essential to avoid misdiagnosis. Since the early 2000s, IgG4-RD has increasingly been recognized as a cause of what was previously referred to as “idiopathic” retroperitoneal fibrosis (RPF), and this IgG4-related RPF is now considered to comprise an important subset of IgG4-RD. This review includes an overview of IgG4-RD and discusses the pathology, pathophysiology, and clinical manifestations of IgG4. IgG4-related RPF is also discussed in this review, with topics including IgG4-related RPF versus RPF of other causes, the differences between RPF and other subsets of IgG4-RD, and treatment of both IgG4-RD and IgG4-related RPF. Figures show the histopathology features of IgG4-RD, immunostaining of tissue for IgG4, IgG4-related RPF and chronic periaortitis, “Mikulicz disease”, IgG4-RD of the lung, IgG4-related renal disease, and type 1 (IgG4-related) pancreatitis. The table lists conditions known previously by other names that often fall within the spectrum of IgG4-RD. This review contains 7 highly rendered figures, 1 table, and 66 references.

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

Idiopathic fibrosing mediastinitis: spectrum of imaging findings with emphasis on its association with IgG4-related disease

PurposeThe purpose of this study was to review the clinicoradiological features of idiopathic fibrosing mediastinitis (FM). MethodsThe records of six patients with idiopathic FM were retrospectively reviewed. ResultsThe most common presenting symptom was cough. There were three localized forms and three diffuse forms. Definitive histological diagnosis was most commonly made with mediastinoscopy. Interestingly, three of our patients had disease manifestations of IgG4-related disease (IgG4-RD) outside the mediastinum. ConclusionThe imaging findings of idiopathic FM vary depending on the involved mediastinal structures. Therapeutic options include medical treatment, stenting, or surgery. Radiologists should pay attention to the possible association of idiopathic FM with extrathoracic manifestations of the IgG4-RD spectrum.

Graves'-like orbitopathy: do not forget IgG4-related disease.

ultrasonographic and/or serological evidence of autoimmune thyroid disease makes diagnosis of GO even more uncertain. Thus, if in typical cases imaging is confirmatory, then in doubtful circumstances it is mandatory. Many conditions may cause exophthalmos and/or extraocular muscle enlargement mimicking GO. Table 1 offers a list of these conditions, for some of which etiology is uncertain. IgG4-related disease is a recently described fibroinflammatory multiorgan disorder characterized by tumefactive lesions, lymphoplasmacytic infiltration with abundant IgG4-positive plasma cells, storiform fibrosis and frequently (but not always) elevated serum IgG4 levels (see [4] for an excellent and exhaustive review of this disease). Initially described in the context of autoimmune pancreatitis, IgG4-related disease may indeed affect several extrapancreatic sites, including the thyroid and the orbit. Riedel’s (fibrosclerosing) thyroiditis has been shown immunohistochemically to be comprised within the spectrum of IgG4-related disease [5]. The fibrous variant of Hashimoto’s thyroiditis might also be closely related to IgG4-related disease [6]. Graves’-like orbitopathy was described in a patient with autoimmune pancreatitis and very high serum IgG4 concentrations, in the absence of thyroid autoimmune disease or related thyroid dysfunction [7]. Clinical features were similar to those of moderate-to-severe and active GO. Imaging was characterized by enlarged extraocular muscles (with tendon sparing) and lacrimal gland, and expansion of the adipose tissue; there was an excellent response of orbital changes to intravenous glucocorticoids and orbital radiotherapy [7]. An additional case was described at the Mayo Clinic: the patient had a longlasting diagnosis of “GO”, treated many times with oral glucocorticoids because of repeated recurrences [8]. The patient was eventually submitted to orbital Graves’ orbitopathy (GO) affects about 25 % of patients with hyperthyroidism due to Graves’ disease [1], is usually mild and infrequently progressive [2, 3], although moderate-to-severe or (rare) sight-threatening forms do exist and require aggressive treatments [1]. In most cases, the onset of GO is temporally related to the onset of hyperthyroidism, but in some instances the orbital disease may precede or follow the onset of hyperthyroidism by months or years [1]. In addition, it is known that GO may less frequently develop in patients with euthyroid or hypothyroid Hashimoto’s thyroiditis [1]. The diagnosis of GO is simple and straightforward in the typical patient who, in addition to signs and symptoms of hyperthyroidism, has positive TSHreceptor antibody tests, bilateral eye symptoms (lacrimation, grittiness, photophobia, diplopia) and signs (exophthalmos, periorbital soft tissue swelling, ocular dysmotility, rarely visual defects). Diagnosis is confirmed by imaging studies showing enlarged extraocular muscles (with tendon sparing) and/or expansion of the orbital fibroadipose tissue [1]. Diagnostic problems arise particularly in those patients who are not hyperthyroid and have asymmetrical or unilateral orbital involvement. The presence of euthyroid/hypothyroid chronic autoimmune thyroiditis does not guarantee that orbital disease be related to GO; the absence of thyroid

IgG4 antibodies in autoimmune polyglandular disease and IgG4-related endocrinopathies: pathophysiology and clinical characteristics.

This review discusses the IgG4-related disease spectrum (IgG4-RD), the autoimmune polyglandular syndromes (APS), the association of IgG4 with APS, and possible pathobiology. IgG4-RD is a multiorgan autoimmune disorder characterized by fibrous inflammation, IgG4-positive plasma cell infiltration in affected tissues, and elevated serum concentrations of IgG4. IgG4-RD can affect any organ and has a heterogeneous presentation. Consensus criteria for diagnosis in specific organs have been established. The recognition and diagnosis of IgG4-RD are crucial because the disease responds favorably to immunosuppression (e.g., glucocorticoids, rituximab). The precise mechanisms leading to disease are unknown, but IgG4 antibodies may undergo a half antibody exchange, which renders them incapable of activating the complement pathway. Despite significant advances in disease recognition and treatment strategies, the disorder remains poorly understood. The precise role of IgG4, whether it is protective or pathogenic, is still being debated.

Autoimmune pancreatitis in the context of IgG4-related disease: review of imaging findings.

Current understanding of autoimmune pancreatitis (AIP) recognizes a histopathological subtype of the disease to fall within the spectrum of IgG4-related disease. Along with clinical, laboratory, and histopathological data, imaging plays an important role in the diagnosis and management of AIP, and more broadly, within the spectrum of IgG4-related disease. In addition to the defined role of imaging in consensus diagnostic protocols, an array of imaging modalities can provide complementary data to address specific clinical concerns. These include contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging for pancreatic parenchymal lesion localization and characterization, endoscopic retrograde and magnetic resonance cholangiopancreatography (ERCP and MRCP) to assess for duct involvement, and more recently, positron emission tomography (PET) imaging to assess for extra-pancreatic sites of involvement. While the imaging appearance of AIP varies widely, certain imaging features are more likely to represent AIP than alternate diagnoses, such as pancreatic cancer. While nonspecific, imaging findings which favor a diagnosis of AIP rather than pancreatic cancer include: delayed enhancement of affected pancreas, mild dilatation of the main pancreatic duct over a long segment, the "capsule" and "penetrating duct" signs, and responsiveness to corticosteroid therapy. Systemic, extra-pancreatic sites of involvement are also often seen in AIP and IgG4-related disease, and typically respond to corticosteroid therapy. Imaging by CT, MR, and PET also play a role in the diagnosis and monitoring after treatment of involved sites.

A Case of IgG4-Related Sclerosing Mesenteritis Associated with Crohn's Disease

Sclerosing mesenteritis (SM) is a rare disease characterized by chronic nonspecific mesenteric inflammation and fibrosis of unknown etiology. Some tumefactive SM shows diffuse accumulation of IgG4-positive plasma cells and is considered as a part of the spectrum of IgG4-related disease. An association between inflammatory bowel disease and IgG4-related disease has been indicated. A 45-year-old woman visited our hospital due to weight loss with intermittent lower abdominal discomfort. Pelvic ultrasound revealed a mass-like lesion in the abdominal wall and pelvis MRI demonstrated a 5.9 cm sized wall-enhancing mass with heterogeneous signal intensity from right adnexa to the abdominal wall. Tumor resection and adhesiolysis was done because of severe adhesion with the small bowel, colon, bladder, uterus, and abdominal wall. Appendectomy was also performed due to adhesion and edematous change. Histological examination of the resected mass showed findings that were compatible with IgG4-related SM. The resected appendix showed chronic granulomatous inflammation without evidence of tuberculosis. She was diagnosed with Crohn's disease after undergoing colonoscopy and CT enterography. Herein, we report a rare case of IgG4-related SM that occurred in conjunction with Crohn's disease.

IgG4-related Disease of the Genitourinary Tract

IgG4-related disease (IgG4-RD) is a recently established albeit well recognized fibro-inflammatory condition with distinctive features including a characteristic histopathological appearance; a propensity to develop tumefactive lesions in multiple body sites; and oft elevated serum IgG4 levels. The consensus statement on IgG-4 RD equips practicing pathologists with a set of working guidelines for the diagnosis of pathologic lesions identified in a host of different organ system affected with this disease. The diagnosis of IgG4-RD requires the combined presence of the characteristic histopathological appearance and increased numbers of IgG4-positive plasma cells. The essential histopathological features include a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. Tissue IgG4-positive plasma cell counts and IgG4: IgG ratios are significant ancillary aids in establishing the diagnosis. The spectrum of IgG4-RD continues to expand and involve multiple body sites. The genitourinary system comprising of the kidneys, ureters, urinary bladder, urethra, prostate gland, testes and penis is one of the multiple organ systems to be affected by IgG4-RD. This review describes the clinical and histopathologic patterns of involvement of the genitourinary system by IgG4-RD, in association with serologic and radiological features.