IgG4-related disease complicated with diffuse and chronic gastrointestinal inflammation leading to small intestinal perforation.

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a systemic inflammatory disease characterised by elevated serum IgG4, IgG4+ cell infiltration, storiform fibrosis, and obliterative phlebitis. While IgG4-RD can affect various organs, gastrointestinal tract involvement is less common. Here, we report a 70-year-old female with IgG4-RD complicated with diffuse and chronic gastrointestinal inflammation, which led to small intestinal perforation. She had been suffering from anorexia, abdominal pain, vomiting, and diarrhoea and hospitalised due to recurrent ileus. Consequently, she was referred due to small intestinal perforation required for surgical intervention. Pathology revealed acute and chronic inflammation with massive IgG4+ plasmacyte infiltration into mucosa of the small intestine and ischaemic change secondarily caused by chronic inflammation. Random biopsies from the mucosa of stomach, duodenum, ileum, and colon also revealed diffuse and massive IgG4+ plasmacyte infiltration in stomach, duodenum, small intestine, and colon. She was diagnosed with IgG4-RD based on the pathological findings and elevated serum IgG4 levels. Glucocorticoid rapidly ameliorated the symptoms. IgG4-RD may cause gastrointestinal manifestations, and histopathological assessment should be considered, even in the absence of specific characteristics of IgG4-RD.

Usual Interstitial Pneumonia Pattern Interstitial Lung Disease Developed in a Patient with IgG4-related Chronic Sclerosing Sialadenitis.

A 69-year-old man was diagnosed with immunoglobulin (Ig) G4-related disease (IgG4-RD) at 62 years old. At that time, he had high serum IgG4 levels and bilateral submandibular gland swelling on CT; thus, a gland biopsy was performed. Because a reticular shadow was found on chest CT, a lung surgical biopsy was also performed. The specimens revealed usual interstitial pneumonia (UIP) pattern interstitial pneumonia with some IgG4-positive cells. The patient was subsequently followed up without treatment. His forced vital capacity and radiological findings progressively deteriorated, consistent with UIP pattern interstitial lung disease but different from a lung lesion of IgG4-RD.

Immunoglobulin (Ig) G4-related sclerosing cholangitis in patients resected for presumed perihilar cholangiocarcinoma: a 10-year experience.

BACKGROUND: This study aimed to investigate the incidence of immunoglobulin (Ig) G4-related sclerosing cholangitis (IgG4-SC) in patients resected for perihilar cholangiocarcinoma (PHC) in a designated hospital from 2010 to 2019. We also aimed to evaluate the diagnostic dilemma of IgG4-SC clinically. METHODS: Between January 2010 and December 2019, all patients who underwent radical resection due to presumed PHC were included. Independent pathologists scored bile duct samples based on the International Consensus Pathology Criteria for IgG4-related Disease (ICPD). RESULTS: Of the 289 patients who underwent radical resection of primary liver cancer, 26 (9%) were diagnosed as benign, without histological evidence of malignancy, among them, 23 had sclerosing inflammation, 1 had cystadenoma, and 2 had xanthogranulomatous cholangitis. Additionally, 18 had a definitive diagnosis of IgG4-SC. The misdiagnosis rate was 19% (54/289), of which, 26 patients had benign disease, and 28 patients had malignancies. CONCLUSIONS: It is difficult to distinguish IgG-SC from PHC. The misdiagnosis has resulted in a large number of ineffective hepatectomies. Improving the detection rate of serum IgG4 (sIgG4) may therefore avoid misdiagnosis, surgery, and life-threatening complications.

Reprint of: Pathologic manifestations of Immunoglobulin(Ig)G4-related lung disease.

Immunoglobulin(Ig)G4-related disease (IgG4-RD) is a fibroinflammatory condition that can affect virtually any organ and usually presents as tumefactive lesions involving multiple sites. Characteristic histopathology of IgG4-RD consists of dense lymphoplasmacytic infiltrate, fibrosis (often in storiform pattern), and obliterative phlebitis, accompanied by tissue infiltration of IgG4-positive plasma cells with or without elevation of serum IgG4 level. Despite a general similarity in the morphologic manifestations of IgG4-RD, site-specific unique morphologic features have been described in some organs including the lung. Compared with other sites, pulmonary involvement by IgG4-RD has been recognized more recently, and lung biopsy interpretation for this condition is often challenging, as both a relative paucity of pathognomonic features and a plethora of overlapping findings with other fibroinflammatory processes of the lung. This review is focused on the morphologic spectrum of IgG4-related lung disease documented in the current literature and on the pertinent issues in the differential diagnoses with other conditions encountered in the lung.

Endoscopic approaches for the diagnosis of autoimmune pancreatitis.

Autoimmune pancreatitis (AIP) is characterized by diffuse pancreatic enlargement and irregular narrowing of the main pancreatic duct (MPD). Immunoglobulin (Ig)G4-related sclerosing cholangitis (IgG4-SC) associated with AIP frequently appears as a bile duct stricture. Therefore, it is important to differentiate AIP and IgG4-SC from pancreatic cancer and cholangiocarcinoma or primary sclerosing cholangitis, respectively. Endoscopy plays a central role in the diagnosis of AIP and IgG4-SC because it provides imaging of the MPD and bile duct strictures as well as the ability to obtain tissue samples for histological evaluations. Diffuse irregular narrowing of MPD on endoscopic retrograde cholangiopancreatography (ERCP) is rather specific to AIP, but localized narrowing of the MPD is often difficult to differentiate from MPD stenosis caused by pancreatic cancer. A long stricture (>1/3 the length of the MPD) and lack of upstream dilatation from the stricture (<5 mm) might be key features of AIP on ERCP. Some cholangiographic features, such as segmental strictures, stric tures of the lower bile duct, and long strictures with prestenotic dilatation, are more common in IgG4-SC than in cholangiocarcinoma. Endoscopic ultrasonography (EUS) reveals diffuse hypoechoic pancreatic enlargement, sometimes with hypoechoic inclusions, in patients with AIP. In addition, EUS-elastography and contrast-enhanced harmonic EUS have been developed with promising results. The usefulness of EUS-guided fine-needle aspiration has been increasingly recognized for obtaining adequate tissue samples for the histological diagnosis of AIP. Further improvement of endoscopic procedures and devices will contribute to more accurate diagnosis of AIP and IgG4-SC.

Sigmoid sinus occlusion infiltrated by inflammatory myofibroblastic tumor from mastoid.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) and some types of immunoglobulin (Ig) G4-related disease are often involved in the spectrum of inflammatory pseudotumor (IPT) and the concept of IgG4-related IPT/IMT has recently been proposed. METHODS: A 38-year-old man complained of initial symptoms of blurred vision and headache. RESULTS: A tumor was found in the right mastoid, which caused occlusion of the right sigmoid sinus and intracranial hypertension. A diagnosis of IMT with IgG4+ plasma cell infiltration was established by surgical, pathological, and immunohistochemistry findings. His symptoms were completely relieved after corticosteroid therapy and no recurrence was detected during 22 months of follow-up. CONCLUSION: A case with cerebral venous sinus infiltrated by IMTs in the head and neck has never been reported; corticosteroid therapy proved satisfactory in IMT with IgG4+ plasma cell infiltration.

Role of endoscopy in the diagnosis of autoimmune pancreatitis and immunoglobulin G4-related sclerosing cholangitis.

Autoimmune pancreatitis (AIP) must be differentiated from pancreatic carcinoma, and immunoglobulin (Ig)G4-related sclerosing cholangitis (SC) from cholangiocarcinoma and primary sclerosing cholangitis (PSC). Pancreatographic findings such as a long narrowing of the main pancreatic duct, lack of upstream dilatation, skipped narrowed lesions, and side branches arising from the narrowed portion suggest AIP rather than pancreatic carcinoma. Cholangiographic findings for PSC, including band-like stricture, beaded or pruned-tree appearance, or diverticulum-like outpouching are rarely observed in IgG4-SC patients, whereas dilatation after a long stricture of the bile duct is common in IgG4-SC. Transpapillary biopsy for bile duct stricture is useful to rule out cholangiocarcinoma and to support the diagnosis of IgG4-SC with IgG4-immunostaining. IgG4-immunostaining of biopsy specimens from the major papilla advances a diagnosis of AIP. Contrast-enhanced endoscopic ultrasonography (EUS) and EUS elastography have the potential to predict the histological nature of the lesions. Intraductal ultrasonographic finding of wall thickening in the non-stenotic bile duct on cholangiography is useful for distinguishing IgG4-SC from cholangiocarcinoma. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used to exclude pancreatic carcinoma. To obtain adequate tissue samples for the histological diagnosis of AIP, EUS-Tru-cut biopsy or EUS-FNA using a 19-gauge needle is recommended, but EUS-FNA with a 22-gauge needle can also provide sufficient histological samples with careful sample processing after collection and rapid motion of the FNA needles within the pancreas. Validation of endoscopic imaging criteria and new techniques or devices to increase the diagnostic yield of endoscopic tissue sampling should be developed.

Supraglottic immunoglobulin-G4 related plasma cell granuloma: case report and literature review.

BACKGROUND: Granuloma of the upper aerodigestive tract is a rare presentation of immunoglobulin-G4 (IgG4)-related disease. Since the disease process was defined in 2003, only 2 cases affecting the laryngopharynx have been reported in the literature. METHODS AND RESULTS: A 62-year-old white man presented with persistent productive cough of brown sputum, globus symptoms, dysphagia, odynophagia, dysphonia, otalgia, and general malaise over a period of 2 months. Investigations revealed IgG4-positive plasma cell granuloma of the supraglottic region. This was successfully treated with oral corticosteroids. CONCLUSION: Because IgG4 testing is not performed routinely, management recommendations have been poorly defined. We reviewed the literature and discuss herein the clinical characteristics, pathology, diagnosis, and management. The authors theorize that IgG4-related disease involving the larynx and pharynx may be more common than suggested by the paucity of reported cases.