Top

Published in:

01-12-2010 | Original Paper

IgG4-related meningeal disease: clinico-pathological features and proposal for diagnostic criteria

Authors: Katherine M. Lindstrom, John B. Cousar, M. Beatriz S. Lopes

Published in: Acta Neuropathologica | Issue 6/2010

Abstract

IgG4-related disease has evolved from originally being recognized as a form of pancreatitis to encompass diseases of numerous organs including the hypophysis and one reported case of dural involvement. A search of the University of Virginia, Division of Neuropathology files for 10 years identified ten cases of unexplained lymphoplasmacytic meningeal inflammation that we then evaluated using immunohistochemical stains for IgG4 and IgG. Ten control cases including sarcoidosis (4), tuberculosis (1), bacterial abscess (2), Langerhans cell histiocytosis (2), and foreign body reaction (1) were also examined. The number of IgG4-positive plasma cells was counted in five high power fields (HPFs) and an average per HPF was calculated. Cases that contained greater than ten IgG4-positive cells/HPF were considered to be IgG4-related. Five of the study cases met these criteria, including one case of leptomeningeal inflammation. All cases exhibited the typical histological features of IgG4-related disease including lymphoplasmacytic inflammation, fibrosis, and phlebitis. The dural-based lesions appear to represent a subset of the cases historically diagnosed as idiopathic hypertrophic pachymeningitis. While the leptomeningeal process most closely resembles non-vasculitic autoimmune inflammatory meningoencephalitis. Given these findings, IgG4-related meningitis should be considered in the differential diagnosis of meningeal inflammatory lesions after stringent clinical and histologic criteria are used to rule out other possible diagnoses.

Aalberse RC, Stapel SO, Schuurman J, Rispens T (2009) Immunoglobulin G4: an odd antibody. Clin Exp Allergy 39:469–477. doi:10.1111/j.1365-2222.2009.03207.x CrossRefPubMed

Adler JR, Sheridan W, Kosek J, Linder S (1991) Pachymeningitis associated with a pulmonary nodule. Neurosurgery 29:283–287CrossRefPubMed

Alexander GE, Provost TT, Stevens MB, Alexander EL (1981) Sjogren syndrome: central nervous system manifestations. Neurology 31:1391–1396PubMed

Aoki S, Nakazawa T, Ohara H, Sano H, Nakao H, Joh T et al (2005) Immunohistochemical study of autoimmune pancreatitis using anti-IgG4 antibody and patients’ sera. Histopathology 47:147–158. doi:10.1111/j.1365-2559.2005.02204.x CrossRefPubMed

Ashkenazi E, Constantini S, Pappo O, Gomori M, Averbuch-Heller L, Umansky F (1991) Hypertrophic spinal pachymeningitis: report of two cases and review of the literature. Neurosurgery 28:730–732CrossRefPubMed

Bateman AC, Deheragoda MG (2009) IgG4-related systemic sclerosing disease—an emerging and under-diagnosed condition. Histopathology 55:373–383. doi:10.1111/j.1365-2559.2008.03217.x CrossRefPubMed

Berger JR, Snodgrass S, Glaser J, Post MJ, Norenberg M, Benedetto P (1989) Multifocal fibrosclerosis with hypertrophic intracranial pachymeningitis. Neurology 39:1345–1349PubMed

Caselli RJ, Boeve BF, Scheithauer BW, O’Duffy JD, Hunder GG (1999) Nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM): a reversible form of encephalopathy. Neurology 53:1579–1581PubMed

Castillo P, Woodruff B, Caselli R, Vernino S, Lucchinetti C, Swanson J et al (2006) Steroid-responsive encephalopathy associated with autoimmune thyroiditis. Arch Neurol 63:197–202. doi:10.1001/archneur.63.2.197 CrossRefPubMed

10.

Chan SK, Cheuk W, Chan KT, Chan JK (2009) IgG4-related sclerosing pachymeningitis: a previously unrecognized form of central nervous system involvement in IgG4-related sclerosing disease. Am J Surg Pathol 33:1249–1252. doi:10.1097/PAS.0b013e3181abdfc2 CrossRefPubMed

11.

Charcot JM, Joffroy A (1869) Deux cas d’atrophie musculaire progressive avec lesions de las substance grise et des faisceaux anterolateraux de la moelle epiniere. Arch Physiol Norm Pathol 2:354–367; 629–649, 744–769

12.

Chari ST, Smyrk TC, Levy MJ, Topazian MD, Takahashi N, Zhang L et al (2006) Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol 4:1010–1016. doi:10.1016/j.cgh.2006.05.017; quiz 934CrossRefPubMed

13.

Cheuk W, Yuen HK, Chan JK (2007) Chronic sclerosing dacryoadenitis: part of the spectrum of IgG4-related Sclerosing disease? Am J Surg Pathol 31:643–645. doi:10.1097/01.pas.0000213445.08902.11 CrossRefPubMed

14.

Cheuk W, Yuen HK, Chu SY, Chiu EK, Lam LK, Chan JK (2008) Lymphadenopathy of IgG4-related sclerosing disease. Am J Surg Pathol 32:671–681. doi:10.1097/PAS.0b013e318157c068 CrossRefPubMed

15.

Church NI, Pereira SP, Deheragoda MG, Sandanayake N, Amin Z, Lees WR et al (2007) Autoimmune pancreatitis: clinical and radiological features and objective response to steroid therapy in a UK series. Am J Gastroenterol 102:2417–2425. doi:10.1111/j.1572-0241.2007.01531.x CrossRefPubMed

16.

Clark A, Zeman RK, Choyke PL, White EM, Burrell MI, Grant EG et al (1988) Pancreatic pseudotumors associated with multifocal idiopathic fibrosclerosis. Gastrointest Radiol 13:30–32. doi:10.1007/BF01889019 CrossRefPubMed

17.

D’Andrea G, Trillo G, Celli P, Roperto R, Crispo F, Ferrante L (2004) Idiopathic intracranial hypertrophic pachymeningitis: two case reports and review of the literature. Neurosurg Rev 27:199–204. doi:10.1007/s10143-004-0321-1 CrossRefPubMed

18.

Deheragoda MG, Church NI, Rodriguez-Justo M, Munson P, Sandanayake N, Seward EW et al (2007) The use of immunoglobulin g4 immunostaining in diagnosing pancreatic and extrapancreatic involvement in autoimmune pancreatitis. Clin Gastroenterol Hepatol 5:1229–1234. doi:10.1016/j.cgh.2007.04.023 CrossRefPubMed

19.

Deshpande V, Chicano S, Finkelberg D, Selig MK, Mino-Kenudson M, Brugge WR et al (2006) Autoimmune pancreatitis: a systemic immune complex mediated disease. Am J Surg Pathol 30:1537–1545. doi:10.1097/01.pas.0000213331.09864.2c CrossRefPubMed

20.

Dumont AS, Clark AW, Sevick RJ, Myles ST (2000) Idiopathic hypertrophic pachymeningitis: a report of two patients and review of the literature. Can J Neurol Sci 27:333–340PubMed

21.

Epstein O, Chapman RW, Lake-Bakaar G, Foo AY, Rosalki SB, Sherlock S (1982) The pancreas in primary biliary cirrhosis and primary sclerosing cholangitis. Gastroenterology 83:1177–1182PubMed

22.

Guidetti B, La Torre E (1967) Hypertrophic spinal pachymeningitis. J Neurosurg 26:496–503. doi:10.3171/jns.1967.26.5.0496 CrossRefPubMed

23.

Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T et al (2001) High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 344:732–738CrossRefPubMed

24.

Hamano H, Kawa S, Ochi Y, Unno H, Shiba N, Wajiki M et al (2002) Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis. Lancet 359:1403–1404CrossRefPubMed

25.

Hori M, Makita N, Andoh T, Takiyama H, Yajima Y, Sakatani T et al (2010) Long-term clinical course of IgG4-related systemic disease accompanied by hypophysitis. Endocr J 57(6):485–492

26.

Kamisawa T, Egawa N, Nakajima H (2003) Autoimmune pancreatitis is a systemic autoimmune disease. Am J Gastroenterol 98:2811–2812. doi:10.1111/j.1572-0241.2003.08758.x CrossRefPubMed

27.

Kamisawa T, Funata N, Hayashi Y, Eishi Y, Koike M, Tsuruta K et al (2003) A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol 38:982–984. doi:10.1007/s00535-003-1175-y CrossRefPubMed

28.

Kamisawa T, Funata N, Hayashi Y, Tsuruta K, Okamoto A, Amemiya K et al (2003) Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut 52:683–687CrossRefPubMed

29.

Kamisawa T, Chen PY, Tu Y, Nakajima H, Egawa N, Tsuruta K et al (2006) Pancreatic cancer with a high serum IgG4 concentration. World J Gastroenterol 12:6225–6228PubMed

30.

Kamisawa T, Okamoto A (2006) Autoimmune pancreatitis: proposal of IgG4-related sclerosing disease. J Gastroenterol 41:613–625. doi:10.1007/s00535-006-1862-6 CrossRefPubMed

31.

Kamisawa T, Okamoto A (2008) IgG4-related sclerosing disease. World J Gastroenterol 14:3948–3955CrossRefPubMed

32.

Kanno A, Satoh K, Kimura K, Masamune A, Asakura T, Unno M et al (2005) Autoimmune pancreatitis with hepatic inflammatory pseudotumor. Pancreas 31:420–423CrossRefPubMed

33.

Kasashima S, Zen Y, Kawashima A, Endo M, Matsumoto Y, Kasashima F (2009) A new clinicopathological entity of IgG4-related inflammatory abdominal aortic aneurysm. J Vasc Surg 49:1264–1271. doi:10.1016/j.jvs.2008.11.072 (discussion 1271)CrossRefPubMed

34.

Kawa S, Hamano H (2003) Autoimmune pancreatitis and bile duct lesions. J Gastroenterol 38:1201–1203. doi:10.1007/s00535-003-1213-9 CrossRefPubMed

35.

Kawaguchi K, Koike M, Tsuruta K, Okamoto A, Tabata I, Fujita N (1991) Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas. Hum Pathol 22:387–395CrossRefPubMed

36.

Kim KP, Kim MH, Song MH, Lee SS, Seo DW, Lee SK (2004) Autoimmune chronic pancreatitis. Am J Gastroenterol 99:1605–1616. doi:10.1111/j.1572-0241.2004.30336.x CrossRefPubMed

37.

Kitagawa S, Zen Y, Harada K, Sasaki M, Sato Y, Minato H et al (2005) Abundant IgG4-positive plasma cell infiltration characterizes chronic sclerosing sialadenitis (Kuttner’s tumor). Am J Surg Pathol 29:783–791CrossRefPubMed

38.

Kloppel G, Luttges J, Lohr M, Zamboni G, Longnecker D (2003) Autoimmune pancreatitis: pathological, clinical, and immunological features. Pancreas 27:14–19CrossRefPubMed

39.

Kojima M, Sipos B, Klapper W, Frahm O, Knuth HC, Yanagisawa A et al (2007) Autoimmune pancreatitis: frequency, IgG4 expression, and clonality of T and B cells. Am J Surg Pathol 31:521–528. doi:10.1097/01.pas.0000213390.55536.47 CrossRefPubMed

40.

Komatsu K, Hamano H, Ochi Y, Takayama M, Muraki T, Yoshizawa K et al (2005) High prevalence of hypothyroidism in patients with autoimmune pancreatitis. Dig Dis Sci 50:1052–1057CrossRefPubMed

41.

Kupersmith MJ, Martin V, Heller G, Shah A, Mitnick HJ (2004) Idiopathic hypertrophic pachymeningitis. Neurology 62:686–694PubMed

42.

Li Y, Bai Y, Liu Z, Ozaki T, Taniguchi E, Mori I et al (2009) Immunohistochemistry of IgG4 can help subclassify Hashimoto’s autoimmune thyroiditis. Pathol Int 59:636–641. doi:10.1111/j.1440-1827.2009.02419.x CrossRefPubMed

43.

Lyons MK, Caselli RJ, Parisi JE (2008) Nonvasculitic autoimmune inflammatory meningoencephalitis as a cause of potentially reversible dementia: report of 4 cases. J Neurosurg 108:1024–1027. doi:10.3171/JNS/2008/108/5/1024 CrossRefPubMed

44.

Mamelak AN, Kelly WM, Davis RL, Rosenblum ML (1993) Idiopathic hypertrophic cranial pachymeningitis report of three cases. J Neurosurg 79:270–276. doi:10.3171/jns.1993.79.2.0270 CrossRefPubMed

45.

Masaki Y, Dong L, Kurose N, Kitagawa K, Morikawa Y, Yamamoto M et al (2009) Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis 68:1310–1315. doi:10.1136/ard.2008.089169 CrossRefPubMed

46.

Miyoshi H, Uchida K, Taniguchi T, Yazumi S, Matsushita M, Takaoka M et al (2008) Circulating naive and CD4 + CD25 high regulatory T cells in patients with autoimmune pancreatitis. Pancreas 36:133–140. doi:10.1097/MPA.0b013e3181577553 CrossRefPubMed

47.

Montefusco PP, Geiss AC, Bronzo RL, Randall S, Kahn E, McKinley MJ (1984) Sclerosing cholangitis, chronic pancreatitis, and Sjogren’s syndrome: a syndrome complex. Am J Surg 147:822–826CrossRefPubMed

48.

Naffzinger HC, Stern WE (1949) Chronic pachymeningitis; report of a case and review of the literature. Arch Neurol Psychiatry 62:383–411

49.

Neild GH, Rodriguez-Justo M, Wall C, Connolly JO (2006) Hyper-IgG4 disease: report and characterisation of a new disease. BMC Med 4:23. doi:10.1186/1741-7015-4-23 CrossRefPubMed

50.

Okazaki K, Uchida K, Ohana M, Nakase H, Uose S, Inai M et al (2000) Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response. Gastroenterology 118:573–581CrossRefPubMed

51.

Otsuki M, Chung JB, Okazaki K, Kim MH, Kamisawa T, Kawa S et al (2008) Asian diagnostic criteria for autoimmune pancreatitis: consensus of the Japan-Korea symposium on autoimmune pancreatitis. J Gastroenterol 43:403–408. doi:10.1007/s00535-008-2205-6 CrossRefPubMed

52.

Riku S, Kato S (2003) Idiopathic hypertrophic pachymeningitis. Neuropathology 23:335–344CrossRefPubMed

53.

Shimatsu A, Oki Y, Fujisawa I, Sano T (2009) Pituitary and stalk lesions (infundibulo-hypophysitis) associated with immunoglobulin G4-related systemic disease: an emerging clinical entity. Endocr J 56:1033–1041CrossRefPubMed

54.

Shrestha B, Sekiguchi H, Colby TV, Graziano P, Aubry MC, Smyrk TC et al (2009) Distinctive pulmonary histopathology with increased IgG4-positive plasma cells in patients with autoimmune pancreatitis: report of 6 and 12 cases with similar histopathology. Am J Surg Pathol 33:1450–1462. doi:10.1097/PAS.0b013e3181ac43b6 CrossRefPubMed

55.

Taniguchi T, Ko M, Seko S, Nishida O, Inoue F, Kobayashi H et al (2004) Interstitial pneumonia associated with autoimmune pancreatitis. Gut 53:770 (author reply 770–771)PubMed

56.

Uchida K, Okazaki K, Asada M, Yazumi S, Ohana M, Chiba T et al (2003) Case of chronic pancreatitis involving an autoimmune mechanism that extended to retroperitoneal fibrosis. Pancreas 26:92–94CrossRefPubMed

57.

Uchiyama-Tanaka Y, Mori Y, Kimura T, Sonomura K, Umemura S, Kishimoto N et al (2004) Acute tubulointerstitial nephritis associated with autoimmune-related pancreatitis. Am J Kidney Dis 43:e18–e25CrossRefPubMed

58.

van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL et al (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98–3936. Leukemia 17:2257–2317. doi:10.1038/sj.leu.2403202 CrossRefPubMed

59.

Wong S, Lam WY, Wong WK, Lee KC (2007) Hypophysitis presented as inflammatory pseudotumor in immunoglobulin G4-related systemic disease. Hum Pathol 38:1720–1723. doi:10.1016/j.humpath.2007.06.011 CrossRefPubMed

60.

Yamamoto H, Yamaguchi H, Aishima S, Oda Y, Kohashi K, Oshiro Y et al (2009) Inflammatory myofibroblastic tumor versus IgG4-related sclerosing disease and inflammatory pseudotumor: a comparative clinicopathologic study. Am J Surg Pathol 33:1330–1340CrossRefPubMed

61.

Yamamoto M, Takahashi H, Sugai S, Imai K (2005) Clinical and pathological characteristics of Mikulicz’s disease (IgG4-related plasmacytic exocrinopathy). Autoimmun Rev 4:195–200. doi:10.1016/j.autrev.2004.10.005 CrossRefPubMed

62.

Yamamoto M, Takahashi H, Ohara M, Suzuki C, Naishiro Y, Yamamoto H et al (2006) A case of Mikulicz’s disease (IgG4-related plasmacytic disease) complicated by autoimmune hypophysitis. Scand J Rheumatol 35:410–411. doi:10.1080/03009740600758110 CrossRefPubMed

63.

Yamashita K, Haga H, Mikami Y, Kanematsu A, Nakashima Y, Kotani H et al (2008) Degree of IgG4+ plasma cell infiltration in retroperitoneal fibrosis with or without multifocal fibrosclerosis. Histopathology 52:404–409. doi:10.1111/j.1365-2559.2007.02959.x CrossRefPubMed

64.

Yoneda K, Murata K, Katayama K, Ishikawa E, Fuke H, Yamamoto N et al (2007) Tubulointerstitial nephritis associated with IgG4-related autoimmune disease. Am J Kidney Dis 50:455–462. doi:10.1053/j.ajkd.2007.05.018 CrossRefPubMed

65.

Yoshimura Y, Takeda S, Ieki Y, Takazakura E, Koizumi H, Takagawa K (2006) IgG4-associated prostatitis complicating autoimmune pancreatitis. Intern Med 45:897–901CrossRefPubMed

66.

Zamboni G, Luttges J, Capelli P, Frulloni L, Cavallini G, Pederzoli P et al (2004) Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens. Virchows Arch 445:552–563. doi:10.1007/s00428-004-1140-z CrossRefPubMed

67.

Zen Y, Harada K, Sasaki M, Sato Y, Tsuneyama K, Haratake J et al (2004) 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 28:1193–1203CrossRefPubMed

68.

Zen Y, Kasahara Y, Horita K, Miyayama S, Miura S, Kitagawa S et al (2005) Inflammatory pseudotumor of the breast in a patient with a high serum IgG4 level: histologic similarity to sclerosing pancreatitis. Am J Surg Pathol 29:275–278CrossRefPubMed

69.

Zen Y, Kitagawa S, Minato H, Kurumaya H, Katayanagi K, Masuda S et al (2005) IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung. Hum Pathol 36:710–717. doi:10.1016/j.humpath.2005.05.011 CrossRefPubMed

70.

Zen Y, Sawazaki A, Miyayama S, Notsumata K, Tanaka N, Nakanuma Y (2006) A case of retroperitoneal and mediastinal fibrosis exhibiting elevated levels of IgG4 in the absence of sclerosing pancreatitis (autoimmune pancreatitis). Hum Pathol 37:239–243. doi:10.1016/j.humpath.2005.11.001 CrossRefPubMed

71.

Zen Y, Fujii T, Harada K, Kawano M, Yamada K, Takahira M et al (2007) Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology 45:1538–1546. doi:10.1002/hep.21697 CrossRefPubMed

72.

Zen Y, Fujii T, Sato Y, Masuda S, Nakanuma Y (2007) Pathological classification of hepatic inflammatory pseudotumor with respect to IgG4-related disease. Mod Pathol 20:884–894. doi:10.1038/modpathol.3800836 CrossRefPubMed

73.

Zen Y, Inoue D, Kitao A, Onodera M, Abo H, Miyayama S et al (2009) IgG4-related lung and pleural disease: a clinicopathologic study of 21 cases. Am J Surg Pathol 33:1886–1893. doi:10.1097/PAS.0b013e3181bd535b CrossRefPubMed

74.

Zen Y, Onodera M, Inoue D, Kitao A, Matsui O, Nohara T et al (2009) Retroperitoneal fibrosis: a clinicopathologic study with respect to immunoglobulin G4. Am J Surg Pathol 33:1833–1839CrossRefPubMed

75.

Zhang L, Notohara K, Levy MJ, Chari ST, Smyrk TC (2007) IgG4-positive plasma cell infiltration in the diagnosis of autoimmune pancreatitis. Mod Pathol 20:23–28. doi:10.1038/modpathol.3800689 CrossRefPubMed

Title: IgG4-related meningeal disease: clinico-pathological features and proposal for diagnostic criteria
Authors: Katherine M. Lindstrom
John B. Cousar
M. Beatriz S. Lopes
Publication date: 01-12-2010
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 6/2010
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-010-0746-2

At a glance: The STEP trials

Springer Medicine

IgG4-related meningeal disease: clinico-pathological features and proposal for diagnostic criteria

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2010

Sensory circumventricular organs in health and disease

Neuropathology of the recessive A673V APP mutation: Alzheimer disease with distinctive features

Variably protease-sensitive prionopathy in a PRNP codon 129 heterozygous UK patient with co-existing tau, α synuclein and Aβ pathology

Loss of SMARCB1/INI1 expression in poorly differentiated chordomas

Neuropathology in Parkinson’s disease with mild cognitive impairment

Benedikt Volk (1940–2010): in search of new horizons—voyages of a curious mind