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1 Pathological Features of IgG4-related Disease 1) Division of Pathology, Kanazawa University Hospital 2) Department of Human Pathology, Kanazawa University Graduate School of Medicine NICHIDOKU-IHO Vol. 53 No (2008) Yoh Zen, M.D., Ph.D., 1) and Yasuni Nakanuma, M.D., Ph.D. 2) Summary IgG4-related diseases have been identified in a variety of organ systems. Irrespective of the organ of origin, IgG4-related disease is pathologically characterized by diffuse lymphoplasmacytic infiltration, irregular fibrosis, occasional eosinophil infiltration, and obliterative phlebitis. Immunostaining of IgG4 reveals diffuse infiltration of IgG4-positive plasma cells in each lesion. IgG4-related diseases can manifest diffuse infiltrative or localized nodular lesions in each organ. Idendified IgG4-related diseases can be summarized as follows: autoimmune pancreatitis, sclerosing cholangitis, hepatic inflammatory pseudotumor, chronic sclerosing sialadenitis, chronic sclerosing dacryoadenitis, interstitial pneumonia, pulmonary inflammatory pseudotumor, retroperitoneal fibrosis, and inflammatory abdominal aneurysm. In addition, they could occur at different sites or asynchronously in a patient. Clinico-radiologically, IgG4- related diseases sometimes pose difficulty in differentiating from true neoplasms. However, it is important to pathologically differentiate IgG4-related diseases from other autoimmune and/or lymphoproliferative disorders. This is because IgG4-related diseases may respond appropriately to steroid therapy with accurate diagnosis. IgG4 IgG4 IgG4 IgG4 IgG4 IgG4 IgG4 IgG4
2 EVG IgG4IgG IgG4 1 IgG4 2 IgG4 IgG4 3 IgG4 2 1 IgG4 2 IgG4 IgG4 2 2 IgG4 4 IgG4 IgG4 4 IgG4 IgG4 IgG4 1A B 1C 5 HE
3 EVG 1DIgG4 IgG4 1EF 6 7 IgG4 IgG4 IgG4 IgG4 IgG4 IgG4 IgG4 IgG4 IgG A 8 IgG4 IgG4 primary sclerosing cholangitispsc 9 PSC IgG4 PSC IgG4 PSC IgG4 PSC IgG4 3BD 3C IgG4 IgG4 PSC 7 IgG4 410 Kuttner 4AB IgG4 4C 4 Sjögren Sjögren Sjögren Sjögren IgG4 IgG4
4 Mikulicz Mikulicz MikuliczIgG4 11 Mikulicz
5 IgG4PSC
6 IgG4IgG4 IgG IgG IgG4 IgG4 14 IgG4 5A non-specific interstitial pneumonia NSIPpattern 5BC IgG4 5D IgG4 IgG IgG4 15 IgG4
7 IgG4IgG4
8 CT EVG IgG4 6ACIgG4 6D 6E IgG IgG4 IgG4
9 IgG4 IgG4 19 IgG4 heterogeneous fibrohistiocytic type plasma cell granulomalymphoplasmacytic type inflammatory myofibroblastic tumor IgG4 lymphoplasmacytic typeplasma cell granuloma IgG4 20 lymphoplasmacytic type plasma cell granuloma IgG4 2 IgG4 IgG4 IgG4 IgG4 21 IgG4 IgG4 IgG4 IgG4 retrospective IgG4 IgG4 22 IgG4 2 prospective study IgG4 22 7AC IgG4 IgG4 7DE IgG4 IgG4 periaortitis + 3 IgG4 3 IgG4 -related periaortitis 22 IgG4 23 IgG4 IgG4 IgG4 IgG4
10 IgGIgG4 IgG4 IgG4 17 IgG4 IgG4 IgG4
11 IgG4 7 IgG4 IgG4 Th2 T 24 IgG4 IgG Hamano H, Kawa S, Horiuchi A, et al: High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med : , Hamano H, Kawa S, Ochi Y, et al: Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis. Lancet : , Deshpande V, Chicano S, Finkelberg D, et al: Autoimmune pancreatitis: a systemic immune complex mediated disease. Am J Surg Pathol : , Kitagawa S, Zen Y, Harada K, et al: Abundant IgG4- positive plasma cell infiltration characterizes chronic sclerosing sialadenitis (Küttners tumor). Am J Surg Pathol : , Kawaguchi K, Koike M, Tsuruta K, et al: Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas. Hum Pathol : , Kamisawa T, Funata N, Hayashi Y, et al: Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut : , Zen Y, Harada K, Sasaki M, et al: IgG4-related sclerosing cholangitis with and without hepatic inflammatory pseudotumor, and sclerosing pancreatitis-associated sclerosing cholangitis: do they belong to a spectrum of sclerosing pancreatitis? Am J Surg Pathol : , Hamano H, Kawa S, Uehara T, et al: Immunoglobulin G4- related lymphoplasmacytic sclerosing cholangitis that mimics infiltrating hilar cholangiocarcinoma: part of a spectrum of autoimmune pancreatitis? Gastrointest Endosc : , Björnsson E, Chari ST, Smyrk TC, et al: Immunoglobulin G4 associated cholangitis: description of an emerging clinical entity based on review of the literature. Hepatology : , Takahira M, Kawano M, Zen Y, et al: IgG4-Related chronic sclerosing dacryoadenitis. Arch Ophthalmol : , Yamamoto M, Harada S, Ohara M, et al: Clinical and pathological differences between Mikuliczs disease and Sjögrens syndrome. Rheumatology (Oxford) : , Taniguchi T, Ko M, Seko S, et al: Interstitial pneumonia associated with autoimmune pancreatitis. Gut : 770, Takato H, Yasui M, Ichikawa Y, et al: Nonspecific interstitial pneumonia with abundant IgG4-positive cells infiltration, which was thought as pulmonary involvement of IgG4-related autoimmune disease. Intern Med : , Nieminen U, Koivisto T, Kahri A, et al: Sjögrens syndrome with chronic pancreatitis, sclerosing cholangitis, and pulmonary infiltrations. Am J Gastroenterol : , Zen Y, Kitagawa S, Minato H, et al: IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung. Hum Pathol : , Hamed G, Tsushima K, Yasuo M, et al: Inflammatory lesions of the lung, submandibular gland, bile duct and prostate in a patient with IgG4-associated multifocal systemic fibrosclerosis. Respirology : , Taniguchi T, Hamasaki A, Okamoto M: A case of suspected lymphocytic hypophysitis and organizing pneumonia during maintenance therapy for autoimmune pancreatitis associated with autoimmune thrombocytopenia. Endocr J : , Kobayashi H, Shimokawaji T, Kanoh S, et al: IgG4-positive pulmonary disease. J Thorac Imaging : , 2007
12 Zen Y, Kasahara Y, Horita K, et al: Inflammatory pseudotumor of the breast in a patient with a high serum IgG4 level: histologic similarity to sclerosing pancreatitis. Am J Surg Pathol : , Zen Y, Fujii T, Sato Y, et al: Pathological classification of hepatic inflammatory pseudotumor with respect to IgG4- related disease. Mod Pathol : , Zen Y, Sawazaki A, Miyayama S, et al: A case of retroperitoneal and mediastinal fibrosis exhibiting elevated levels of IgG4 in the absence of sclerosing pancreatitis (autoimmune pancreatitis). Hum Pathol : , Kasashima S, Zen Y, Kawashima A, et al: Inflammatory abdominal aortic aneurysm: close relationship to IgG4- related periaortitis. Am J Surg Pathol : , Matsumoto Y, Kasashima S, Kawashima A, et al: A case of multiple immunoglobulin G4-related periarteritis: a tumorous lesion of the coronary artery and abdominal aortic aneurysm. Hum Pathol : , Zen Y, Fujii T, Harada K, et al: Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology. : , 2007
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