Wednesday 19 November 2003
hyper-IgG4 disease, IMAD, IgG4 syndrome, IgG4 disease, IgG4-associated multifocal systemic fibrosclerosis, IgG4-associated immune complex multiorgan autoimmune disease, IgG4-related plasmacytic disease, hyper-IgG4 disease, multifocal systemic fibrosclerosis (MSF), systemic multifocal fibrosclerosis, inflammatory fibrotic disease, IgG4-Related Disease; IgG4-assotiated diseases; IgG4-related disease
Definition: The IMAD or ’hyper-IgG4 disease’ is a chronic inflammatory disease, characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. IgG4-related disease has been identified in various organs, but whether or not there are organ-specific characteristics related to the etiologic factors is still unknown.
Multifocal systemic fibrosclerosis (MSF) is a multisystem disease, which often mimics malignancy.
A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis.
On the basis of the location of the lesions, the patients can be classified into 5 groups:
head and neck (20%)
hepatic and pancreatobiliary (20%)
All groups have similar clinicopathologic features in various aspects. However, there are some organ-specific features: for example, the proportion of the female patients was significantly higher in the head and neck group, serum IgG4 concentrations were significantly higher in the head/neck and systemic groups, and all kidney lesions were associated with extrarenal disease.
Unique pathologic features were dense fibrosis in dacryoadenitis, numerous lymph follicles in sialadenitis and dacryoadenitis, and obliterative arteritis in lung lesions.
Malignant tumors (lung cancers, malignant lymphoma) can beidentified after the diagnosis of IgG4-related disease in some patients, all in the systemic group.
- sclerosing cholangitis
- sclerosing cholecystitis
- retroperitoneal fibrosis (16426926, 16938531)
- mediastinal fibrosis (16426926, 16938531)
- mesenteric fibrosis
- pelvic fibrosis
- Riedel thyroiditis
- fibrotic pseudotumor of the orbit
- fibrosis of the salivary glands
- sclerosing pancreatitis (autoimmune pancreatitis) (AIP)
- sclerosing dacryoadenitis
- central diabetes insipidus
constrictive pericarditis (17727980)
pulmonary vasculitis (17539856)
lymphadenopathy with increased IgG4+ plasma cells
inflammatory pseudotumors (17895762)
- pulmonary inflammatory pseudotumor (16084938)
- cervical epidural pseudotumor (10879775)
- suprasellar pseudotumor (17954209)
- bilateral diffuse retrobulbar pseudotumor (8512488)
intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils
majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles
significant increase in IgG4-positive plasma cells compared with controls
inflammatory myofibroblastic tumour
plasma cell granuloma
severe systemic disease
IgG4-expressing plasma cells
Applying the consensus statement on the pathology of IgG4-related disease to lacrimal gland lesions.
Andrew N, Kearney D, Selva D.
Mod Pathol. 2013 Aug;26(8):1150-1. doi : 10.1038/modpathol.2013.46. No abstract available
PMID: 23903493 [PubMed - indexed for MEDLINE]
Applying the consensus statement on the pathology of IgG4-related disease to lacrimal gland lesions. Andrew N, Kearney D, Selva D. Mod Pathol. 2013 Aug;26(8):1150-1. doi : 10.1038/modpathol.2013.46 PMID: 23903493 [Free]
Consensus statement on the pathology of IgG4-related disease. Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, Klöppel G, Heathcote JG, Khosroshahi A, Ferry JA, Aalberse RC, Bloch DB, Brugge WR, Bateman AC, Carruthers MN, Chari ST, Cheuk W, Cornell LD, Fernandez-Del Castillo C, Forcione DG, Hamilos DL, Kamisawa T, Kasashima S, Kawa S, Kawano M, Lauwers GY, Masaki Y, Nakanuma Y, Notohara K, Okazaki K, Ryu JK, Saeki T, Sahani DV, Smyrk TC, Stone JR, Takahira M, Webster GJ, Yamamoto M, Zamboni G, Umehara H, Stone JH. Mod Pathol. 2012 May 18. PMID: 22596100
IgG4-Related Disease: A Cross-sectional Study of 114 Cases. Zen Y, Nakanuma Y. Am J Surg Pathol. 2010 Dec;34(12):1812-9. PMID: 21107087
Kasashima S, Zen Y, Kawashima A, Konishi K, Sasaki H, Endo M, Matsumoto Y, Kawakami K, Kasashima F, Moriya M, Kimura K, Ohtake H, Nakanuma Y. Inflammatory Abdominal Aortic Aneurysm: Close Relationship to IgG4-related Periaortitis. Am J Surg Pathol. 2008 Feb;32(2):197-204. PMID: 18223321
Cornell LD, Chicano SL, Deshpande V, Collins AB, Selig MK, Lauwers GY, Barisoni L, Colvin RB. Pseudotumors due to IgG4 immune-complex tubulointerstitial nephritis associated with autoimmune pancreatocentric disease. Am J Surg Pathol. 2007 Oct;31(10):1586-97. PMID: 17895762
Cheuk W, Yuen HK, Chan JK.Chronic sclerosing dacryoadenitis: part of the spectrum of IgG4-related Sclerosing disease? Am J Surg Pathol. 2007 Apr;31(4):643-5. PMID: 17414116
Kojima M, Sipos B, Klapper W, Frahm O, Knuth HC, Yanagisawa A, Zamboni G, Morohoshi T, Klöppel G. Autoimmune pancreatitis: frequency, IgG4 expression, and clonality of T and B cells. Am J Surg Pathol. 2007 Apr;31(4):521-8. PMID: 17414098
Deshpande V, Chicano S, Finkelberg D, Selig MK, Mino-Kenudson M, Brugge WR, Colvin RB, Lauwers GY. Autoimmune pancreatitis: a systemic immune complex mediated disease.Am J Surg Pathol. 2006 Dec;30(12):1537-45. PMID: 17122509
Watson SJ, Jenkins DA, Bellamy CO. Nephropathy in IgG4-related systemic disease. Am J Surg Pathol. 2006 Nov;30(11):1472-7. PMID: 17063091
Cornell LD, Chicano SL, Deshpande V, Collins AB, Selig MK, Lauwers GY, Barisoni L, Colvin RB. Pseudotumors due to IgG4 Immune-Complex Tubulointerstitial Nephritis Associated With Autoimmune Pancreatocentric Disease. Am J Surg Pathol. 2007 Oct;31(10):1586-1597. PMID: 17895762
Neild GH, Rodriguez-Justo M, Wall C, Connolly JO. Hyper-IgG4 disease: report and characterisation of a new disease. BMC Med. 2006 Oct 6;4:23. PMID: 17026742
Taniguchi T, Kobayashi H, Fukui S, Ogura K, Saiga T, Okamoto M. A case of multifocal fibrosclerosis involving posterior mediastinal fibrosis, retroperitoneal fibrosis, and a left seminal vesicle with elevated serum IgG4. Hum Pathol. 2006 Sep;37(9):1237-9; PMID: 16938531
Zen Y, Sawazaki A, Miyayama S, Notsumata K, Tanaka N, Nakanuma Y. A case of retroperitoneal and mediastinal fibrosis exhibiting elevated levels of IgG4 in the absence of sclerosing pancreatitis (autoimmune pancreatitis). Hum Pathol. 2006 Feb;37(2):239-43. PMID: 16426926
Zen Y, Kitagawa S, Minato H, Kurumaya H, Katayanagi K, Masuda S, Niwa H, Fujimura M, Nakanuma Y. IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung. Hum Pathol. 2005 Jul;36(7):710-7. PMID: 16084938