IgG4-related Cholecystitis Research Articles

Isolated IgG4-related cholecystitis: Case reports

Isolated IgG4-related cholecystitis: Case reports

Isolated IgG4-related cholecystitis mimicking an advanced gallbladder cancer: Don't fall into the trap.

A 59-year old women developed spontaneous jaundice without fever and after a progressive loss of 10 kg in 6 months. Iconography showed an enlarged gallbladder with gallstones and thickening walls responsible for an intrahepatic bile duct dilatation with infiltration of the hepatic pedicle and a portal stenosis (Fig. 1). Jaundice spontaneously resolved but cholestasis remained. Surgical and radiological guided biopsy were performed twice without contributive histology. We decided to proceed to a right portal vein embolization in the aim to proceed to an extended right hepatectomy. Fortunately, definitive histology of the last biopsy revealed inflammatory condition with a high IgG4-plasmocytes rate although the patient's serum concentration of IgG4 was moderate (1.39 g/L, normal rate: 0.86–1.35 g/L) and initially considered as not significant. A complete check up was performed and concluded that it was the unique location of an IgG4-related disease [ [1] Lanzillotta M. Mancuso G. Della-Torre E. Advances in the diagnosis and management of IgG4 related disease. BMJ. 2020; 369: m1067https://doi.org/10.1136/bmj.m1067 Crossref PubMed Scopus (97) Google Scholar ]. Corticotherapy was introduced.

Xanthogranulomatous cholecystitis with histologic features suggestive of IgG4 related cholecystitis - A morphologic overlap with IgG4 related disease

AimsBoth xanthogranulomatous cholecystitis (XGC) and IgG4-related cholecystitis (IgG4-CC) are rare chronic fibroinflammatory tumefactive diseases of the gallbladder, which cause a strong confusion with resectable malignancy in view of their mass forming tendency with extension into the liver. We aim to study the histopathologic features of xanthogranulomatous cholecystitis with regard to IgG4-related cholecystitis in extended cholecystectomy specimens. Methods and resultsSixty cases of extended cholecystectomy with liver wedge resection, diagnosed as XGC on histopathology from January 2018 to December 2021 were retrieved from the archives. Representative sections were reviewed by two pathologists independently. Immunohistochemistry was performed for IgG4 and IgG4/IgG was derived. The cases were dichotomized in two groups on the basis of IgG4 positive plasma cells. Six cases with >50 IgG4 positive plasma cells had storiform fibrosis, IgG4/IgG ratio >0.40 and extra-cholecystic extension. Of these, 50 % had obliterative phlebitis and 66.7 % had perineural plasma cell wrapping. ConclusionsA small subset of XGC cases (~10 %) had morphologic overlap with IgG4-CC, but should not be overcalled as the diagnosis of IgG4-RD requires an integrative approach based on clinical, serologic and imaging criteria and not solely on histopathology.

Misdiagnosis of carcinoma gall bladder in endemic regions

BackgroundIncidental carcinoma gall bladder and benign disease in radical cholecystectomy specimen is the cause of concern. We attempted to find out the incidence and reasons thereof in the present study.MethodsPresent study is a retrospective analysis of a prospectively maintained database between July 2002 and July 2019. All patients with a diagnosis of carcinoma gall bladder admitted for surgery were included.ResultsOut of 148 patients, 110 patients had carcinoma gall bladder (CAGB), while 38 patients (25.7%) had incidental carcinoma (under-diagnosis). Radical resection was done in 61/110 (55.4%) patients with clinical CAGB, where 15 (24.6%) patients had benign pathology (“over-diagnosis”). Overdiagnosis was due to xanthogranulomatous cholecystitis (n = 9), chronic cholecystitis (n = 2), tuberculosis (n = 2) and IgG4 related cholecystitis (n = 2). Among 61 patients, a history of weight loss and anorexia were significantly associated with malignancy. Asymmetrical wall thickness was significantly more common in benign mimickers.Among patients with incidental carcinoma, preoperative ultrasonography reported normal wall thickness of gall bladder in 28 (73.7%), thickened gall bladder wall in 6, and polyp in 3 patients. The resectability rate among incidental carcinoma was 27/38 (71.05%).ConclusionOver-diagnosis of the carcinoma gall bladder was present in 24.6%. On the other hand, incidental carcinoma comprised 25.7% of all admissions for carcinoma gall bladder with resectability of 71%.

Isolated IgG4-related cholecystitis with localized gallbladder wall thickening mimicking gallbladder cancer: a case report and literature review

BackgroundIgG4-related cholecystitis, which is a manifestation of IgG4-related disease in the gallbladder, is associated with autoimmune pancreatitis or IgG4-related sclerosing cholangitis in most cases; isolated gallbladder lesions without systemic manifestations are very rare. Gallbladder wall thickening is often diffuse, but sometimes localized, in which case, differentiation from gallbladder cancer becomes difficult. The characteristic features of IgG4-related cholecystitis on imaging that would enable differentiation from gallbladder cancer remain poorly described.Case presentationWe present a rare case of isolated IgG4-related cholecystitis with localized gallbladder wall thickening that was clinically difficult to distinguish from malignancy before resection. An 82-year-old man was referred to our hospital because of gallbladder wall thickening on abdominal ultrasonography without any symptoms. Dynamic computed tomography of the abdomen showed localized wall thickening from the body to the fundus of the gallbladder that was enhanced from an early stage with a prolonged contrast effect. There were no other findings, such as pancreatic enlargement and bile duct dilatation. Magnetic resonance cholangiopancreatography revealed neither dilatation nor stenosis of the bile duct and pancreatic duct. Endoscopic ultrasonography (EUS) showed a smooth layered thickening of the gallbladder wall with a maximum thickness of 6 mm and a well-preserved outermost hyperechoic layer in the same area. Laparoscopic cholecystectomy was performed because malignancy could not be completely ruled out. Pathological examination of a resected specimen revealed IgG4-positive plasma cell infiltration, fibrosis, and phlebitis. Although the serum IgG4 level measured after resection was normal, the condition was ultimately diagnosed as probable IgG4-related cholecystitis according to the 2020 revised comprehensive diagnostic criteria for IgG4-related disease. The EUS images reflected the pathological findings, in which lymphocytic infiltration was distributed in a laminar fashion in the gallbladder wall.ConclusionsAlthough rare, isolated IgG4-related cholecystitis with localized wall thickening mimicking gallbladder cancer remains a clinical problem. A smooth laminar thickening of the gallbladder wall on EUS imaging could be one of the most informative characteristics for differentiating IgG4-related cholecystitis from gallbladder cancer.

Role of Preoperative Percutaneous Needle Biopsy for Differentiation Gallbladder Cancer from Caner-Mimicking Cholecystitis

Introduction: Differentiation gallbladder cancer from cancer mimicking cholecystitis, such as xanthogranulomatous cholecystitis or IgG4 related cholecystitis is still challenging, and it is necessary for differentiation them for avoiding unnecessary radical resection in benign lesion or incomplete resection for cancer. We analyzed value of preoperative percutaneous needle biopsy for differentiation them.

Gallbladder wall thickening in patients with IgG4-related diseases, with special emphasis on IgG4-related cholecystitis

Objectives Gallbladder (GB) wall thickening sometimes occurs in patients with autoimmune pancreatitis (AIP), a condition for which the name, IgG4-related cholecystitis, was proposed. We examined the radiological findings of the GB in patients with IgG4-related diseases and clinical features of patients with GB wall thickening and presented a hypothesis of its pathogenesis. Materials and methods GB wall thickening was defined by thickness ≥ 4 mm. GB wall thickness was examined in 258 patients with IgG4-related disease. Clinical and imaging findings of 200 patients with AIP with and without GB wall thickening were then compared. Results GB wall thickening was detected in 58 patients (29%) with AIP and two patients with isolated IgG4-related sclerosing cholangitis. In the 60 GBs examined, wall thickening was diffuse, with the walls possessing a smooth inner surface. No GB wall thickening was detected among the 56 patients with IgG4-related disease without AIP or IgG4-related sclerosing cholangitis. Bile duct stenosis was detected in 56 patients (97%) with AIP with GB wall thickening. Intraductal ultrasonography indicated cystic duct wall thickening connected to bile duct wall thickening in 11 of 14 (79%) patients with AIP or IgG4-related sclerosing cholangitis with GB wall thickening. Forty-eight patients in whom IgG4-related cholecystitis was diagnosed experienced resolution of the GB wall thickening after receiving steroid therapy. Conclusions Most cases of GB wall thickening in IgG4-related diseases are closely associated with IgG4-related sclerosing cholangitis and may be a manifestation of IgG4-related disease throughout the biliary tract, including the bile duct, cystic duct, and GB.

Clinical and Image Characteristics of IgG4-Related Sclerosing Cholecystitis.

Since autoimmune pancreatitis (AIP) was established as a new disease entity, sclerosing change with abundant immunoglobulin-4 (IgG4)-positive plasma cells, storiform fibrosis, and obliterative phlebitis are main pathological features in IgG4-related diseases. Regarding IgG4-related sclerosing cholecystitis (IgG4-CC), which is occasionally associated with AIP cases and is rarely isolated, there are no diagnostic criteria and insufficient perceptions of the image findings. Although there have been some reports on IgG4-CC, differentiation between IgG4-CC and gallbladder cancer is very difficult in some cases with a localized lesion. In this review, we especially focused on image findings of IgG4-CC and summarized its image features for diagnostic assistance. The ultrasonography and CT findings of IgG4-CC could be classified into diffuse and localized types. Based on these findings, the presence of wall thickening with an intact or smooth mucosal layer, followed by a homogenously thickened outer layer, would be a helpful morphological finding to distinguish IgG4-CC from gallbladder cancer.

Clinical strategies for differentiating IgG4-related cholecystitis from gallbladder carcinoma to avoid unnecessary surgical resection.

Immunoglobulin G4 (IgG4)-related cholecystitis (IgG4-C) is often difficult to distinguish from gallbladder carcinoma (GBC). This study aimed to determine a practical strategy for differentiating between IgG4-C and GBC to avoid unnecessary surgical resection. The expression of IgG4 in the gallbladder was detected by immunohistochemistry. The clinicopathological and radiological characteristics of IgG4-C patients and GBC patients were analyzed retrospectively. Immunohistochemistry revealed that IgG4 was upregulated in the plasma cells of IgG4-C tissues. The median serum total bilirubin levels were significantly higher in the patients with IgG4-C than in those with GBC (45.8 µmol L-1 vs. 29.9 µmol L-1). The serum γ-GGT levels were higher in IgG4-C patients than in GBC patients, whereas the serum levels of CA125 were significantly higher in GBC patients than in IgG4-C patients. The imaging scans were helpful for differentiating IgG4-C from GBC based on the presence of a layered pattern and Rokitansky-Aschoff sinuses in the gallbladder wall. There were no statistically significant differences in age, presence of abdominal pain, level of emaciation between the two groups. Our study demonstrated that the combination of imaging with serum total bilirubin, γ-GGT and CA125 levels can offer added preoperative diagnostic value and reduce the rate of IgG4-C misdiagnosis.

A rare case of localized IgG4-related sclerosing cholecystitis mimicking gallbladder cancer.

Objective: IgG4-related sclerosing cholecystitis is generally associated with IgG4-related sclerosing cholangitis and presents with diffuse, circumferential thickening of the gallbladder wall. We report a rare case of localized IgG4-related sclerosing cholecystitis without IgG4-related sclerosing cholangitis, which was difficult to differentiate from gallbladder cancer preoperatively.Patient: A 56-year-old man with suspected IgG4-related disease or gallbladder cancer was admitted to our ward. The serum IgG4 level was elevated at 721 mg/dL. Computed tomography (CT) demonstrated focal wall thickening of the gallbladder fundus. Drip infusion cholecystocholangiography with CT revealed no dilation, stenosis, or border irregularity of the bile duct.Results: For diagnostic and treatment purposes, cholecystectomy with wedge resection of the gallbladder bed was performed. The pathological diagnosis was IgG4-related sclerosing cholecystitis.Conclusion: It is difficult to differentiate IgG4-related sclerosing cholecystitis from gallbladder cancer in cases involving localized thickening of the gallbladder wall. In similar cases, surgical resection with cancer in mind might be performed based on present clinical knowledge.

IgG4-related cholecystitis presenting as Mirizzi syndrome

IgG4-related cholecystitis presenting as Mirizzi syndrome

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

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

Immunoglobulin G4-related sclerosing cholecystitis presenting as gallbladder cancer: a case report.

Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic inflammatory syndrome, and an understanding of its characteristics is currently evolving. IgG4-related cholecystitis is a manifestation of IgG4-related sclerosing disease in the gallbladder. This case report describes the clinical, radiographic, and histopathological findings in a young male patient who presented with a synchronous mass in the gallbladder. Serum levels of IgG4 and the IgG4/IgG ratio were normal, and there was no associated autoimmune pancreatitis. Therefore, establishing a preoperative diagnosis of IgG4-related cholecystitis was very difficult, and a differential diagnosis of gallbladder cancer infiltrating the liver was suggested. Postoperative histopathological examination established a diagnosis of IgG4-related cholecystitis definitively. A preoperative diagnosis of IgG4-related cholecystitis, although possible, would have been highly challenging in this case. It is difficult to establish whether surgical intervention is necessary in IgG4-related cholecystitis. Because malignant tumors are frequently suspected with this clinical presentation, surgical intervention should be undertaken only after due deliberation.

胆嚢癌との鑑別が困難であった孤立性IgG4関連胆嚢炎の1例

胆嚢癌との鑑別が困難であった孤立性IgG4関連胆嚢炎の1例

Recent advances in the concept and pathogenesis of IgG4-related disease in the hepato-bilio-pancreatic system.

Recent studies have proposed nomenclatures of type 1 autoimmune pancreatitis (AIP) (IgG4-related pancreatitis), IgG4-related sclerosing cholangitis (IgG4-SC), IgG4-related cholecystitis, and IgG4-related hepatopathy as IgG4-related disease (IgG4-RD) in the hepato-bilio-pancreatic system. In IgG4-related hepatopathy, a novel concept of IgG4-related autoimmune hepatitis (AIH) with the same histopathological features as AIH has been proposed. Among organs involved in IgG4-RD, associations with pancreatic and biliary lesions are most frequently observed, supporting the novel concept of “biliary diseases with pancreatic counterparts.” Targets of type 1 AIP and IgG4-SC may be periductal glands around the bile and pancreatic ducts. Based on genetic backgrounds, innate and acquired immunity, Th2-dominant immune status, regulatory T (Treg) or B cells, and complement activation via a classical pathway may be involved in the development of IgG4-RD. Although the role of IgG4 remains unclear in IgG4-RD, IgG4-production is upregulated by interleukin 10 from Treg cells and by B cell activating factor from monocytes/basophils with stimulation of toll-like receptors/nucleotide-binding oligomerization domain-like receptors. Based on these findings, we have proposed a hypothesis for the development of IgG4-RD in the hepato-bilio-pancreatic system. Further studies are necessary to clarify the pathogenic mechanism of IgG4-RD.