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IgG4-positive plasma cells in Hashimoto thyroiditis: IgG4-related disease or inflammation-related IgG4-positivity?

. 2020 Sep ; 128 (9) : 531-538. [epub] 20200706

Language English Country Denmark Media print-electronic

Document type Journal Article

Grant support
VTR Pirkanmaa Hospital District:
Pirkanmaa Cancer Foundation
Charles University Research Funds

Despite the interest of researchers in IgG4-related disease (IgG4-RD), many questions still remain unanswered regarding the thyroid gland. We aimed to clarify the relationship between IgG4-positive plasma cells and the histopathological pattern in the Hashimoto thyroiditis (HT) in a Finnish series. HT specimens (n = 280) were retrieved from the Department of Pathology, Fimlab Laboratories. After re-evaluation, 82 (29%) cases (72 females and 10 males, 52 ± 17 years) with significant fibrosis were selected. CD38, IgG and IgG4 positivity in plasma cells was evaluated by immunohistochemistry. Adjusted IgG4-positive plasma cells per HPF > 20 and IgG4- to IgG-positive plasma cell ratio > 30% were adopted as threshold criteria and related to other morphological features. IgG4-positive HT group included 13 cases (15% from fibrotic HT, 4.6% from all HT, 50 ± 15 years, 11 females) with adjusted HPF count 30 ± 5 (23-40) IgG4-positive cells. IgG4-positivity significantly correlated with the presence of lobulation, oncocytic metaplasia and certain type of fibrosis, fibrosis spread outside the gland, lymphocytes/plasma cells epithelial penetration, the predominance of microfollicles and follicular atrophy in the present study. Despite the persisting uncertainty whether HT is IgG4-RD, HT with IgG4-positive plasma cells is histopathologically distinct entity with some geographic variability.

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Hashimoto H. Zur Kenntnis der lymphomatösen Veränderung der Schilddrüse (struma lymphomatosa). Arch für Klin Chir 1912;97:219-48.

Nikiforov YE, Biddinger PW, Thompson LDR. Chronic lymphocytic thyroiditis (Hashimoto or Autoimmune Thyroiditis). In: Nikiforov YE, Biddinger PW, Thompson LDR, eds. Diagnostic pathology and molecular genetics of the thyroid: a comprehensive guide for practicing thyroid pathology. Alphen aan den Rijn: Wolters Kluwer N.V., 2018: 60-71.

Katz SM, Vickery AL. The fibrous variant of Hashimoto’s thyroiditis. Hum Pathol 1974;5:161-170.

Kamisawa T, Funata N, Hayashi Y, Eishi Y, Koike M, Tsuruta K, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol 2003;38:982-4.

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

Stone JH, Zen Y, Deshpande V. Mechanisms of disease: IgG4-related disease. N Engl J Med 2012;366:539-51.

Bledsoe JR, Della-Torre E, Rovati L, Deshpande V. IgG4-related disease: review of the histopathologic features, differential diagnosis, and therapeutic approach. APMIS 2018;126:459-76.

Stone JH, Khosroshahi A, Deshpande V, Chan JKC, Heathcote JG, Aalberse R, et al. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum 2012;64:3061-3067.

Deshpande V, Zen Y, Chan JKC, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol 2012;25:1181-92.

Apperley ST, Hyjek EM, Musani R, Thenganatt J. Intrathoracic Rosai Dorfman disease with focal aggregates of IgG4-bearing plasma cells case report and literature review. Ann Am Thorac Soc 2016;13:666-70.

Chang SY, Keogh KA, Lewis JE, Ryu JH, Cornell LD, Garrity JA, et al. IgG4-positive plasma cells in granulomatosis with polyangiitis (Wegener’s): A clinicopathologic and immunohistochemical study on 43 granulomatosis with polyangiitis and 20 control cases. Hum Pathol 2013;44:2432-7.

Culver EL, Bateman AC. IgG4-related disease: Can non-classical histopathological features or the examination of clinically uninvolved tissues be helpful in the diagnosis? J Clin Pathol 2012;65:963-9.

Gianella P, Dulguerov N, Arnoux G, Pusztaszeri M, Seebach JD. Thyroid Rosai-Dorfman disease with infiltration of IgG4-bearing plasma cells associated with multiple small pulmonary cysts. BMC Pulm Med 2019;19:83.

Siddiquee Z, Zane NA, Smith RN, Stone JR. Dense IgG4 plasma cell infiltrates associated with chronic infectious aortitis: Implications for the diagnosis of IgG4-related disease. Cardiovasc Pathol 2012;21:470-5.

Strehl JD, Hartmann A, Agaimy A. Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders. J Clin Pathol 2011;64:237-43.

Sah RP, Chari ST. Serologic issues in IgG4-related systemic disease and autoimmune pancreatitis. Curr Opin Rheumatol 2011;23:108-13.

Rotondi M, Carbone A, Coperchini F, Fonte R, Chiovato L. DIAGNOSIS OF ENDOCRINE DISEASE: IgG4-related thyroid autoimmune disease. Eur J Endocrinol 2019;180:R175-R183.

Dahlgren M, Khosroshahi A, Nielsen GP, Deshpande V, Stone JH. Riedel’s thyroiditis and multifocal fibrosclerosis are part of the IgG4-related systemic disease spectrum. Arthritis Care Res 2010;62:1312-8.

Pusztaszeri M, Triponez F, Pache JC, Bongiovanni M. Riedel’s thyroiditis with increased IgG4 plasma cells: Evidence for an underlying IgG4-related sclerosing disease? Thyroid 2012;22:964-8.

Li Y, Bai Y, Liu Z, Ozaki T, Taniguchi E, Mori I, et al. Immunohistochemistry of IgG4 can help subclassify Hashimoto’s autoimmune thyroiditis. Pathol Int 2009;59:636-41.

Li Y, Nishihara E, Hirokawa M, Taniguchi E, Miyauchi A, Kakudo K. Distinct clinical, serological, and sonographic characteristics of Hashimoto’s thyroiditis based with and without IgG4-positive plasma cells. J Clin Endocrinol Metab 2010;95:1309-17.

Li Y, Zhou G, Ozaki T, Nishihara E, Matsuzuka F, Bai Y, et al. Distinct histopathological features of Hashimotos thyroiditis with respect to IgG4-related disease. Mod Pathol 2012;25:1086-97.

Li Y, Wang X, Liu Z, Ma J, Lin X, Qin Y, et al. Hashimoto's thyroiditis with increased IgG4-positive plasma cells: using thyroid-specific diagnostic criteria may identify early phase IgG4 thyroiditis. Thyroid 2020;30:251-61.

Deshpande V, Huck A, Ooi E, Stone JH, Faquin WC, Nielsen GP. Fibrosing variant of Hashimoto thyroiditis is an IgG4 related disease. J Clin Pathol 2012;65:725-8.

Raess PW, Habashi A, El Rassi E, Milas M, Sauer DA, Troxell ML. Overlapping morphologic and immunohistochemical features of hashimoto thyroiditis and IgG4-related thyroid disease. Endocr Pathol 2015;26:170-7.

Jokisch F, Kleinlein I, Haller B, Seehaus T, Fuerst H, Kremer M. A small subgroup of hashimoto’s thyroiditis is associated with IgG4-related disease. Virchows Arch 2016;468:321-7.

McLeod DSA, Caturegli P, Cooper DS, Matos PG, Hutfless S. Variation in rates of autoimmune thyroid disease by race/ethnicity in US military personnel. JAMA - J Am Med Assoc 2014;311:1563-5.

Chui MH, Cassol CA, Asa SL, Mete O. Follicular epithelial dysplasia of the thyroid: Morphological and immunohistochemical characterization of a putative preneoplastic lesion to papillary thyroid carcinoma in chronic lymphocytic thyroiditis. Virchows Arch 2013;462:557-63.

Zhang J, Zhao L, Gaeo Y, Liu M, Li T, Huang Y, et al. A classification of Hashimoto’s thyroiditis based on immunohistochemistry for IgG4 and IgG. Thyroid 2014;24:364-70.

Kojima M, Hirokawa M, Kuma H, Nishihara E, Masawa N, Nakamura N, et al. Distribution of IgG4- and/or IgG-positive plasma cells in Hashimoto’s thyroiditis: An immunohistochemical study. Pathobiology 2010;77:267-72.

Wallace ZS, Zhang Y, Perugino CA, Naden R, Choi HK, Stone JH. Clinical phenotypes of IgG4-related disease: An analysis of two international cross-sectional cohorts. Ann Rheum Dis 2019;78:406-12.

Brito-Zerón P, Bosch X, Ramos-Casals M, Stone JH. IgG4-related disease: Advances in the diagnosis and treatment. Best Pract Res Clin Rheumatol 2016;30:261-78.

Taşli F, Özkök G, Argon A, Ersöz D, Yağci A, Uslu A, et al. The role of IgG4 (+) plasma cells in the association of Hashimoto’s thyroiditis with papillary carcinoma. APMIS 2014;122:1259-65.

Arora K, Rivera M, Ting DT, Deshpande V. The histological diagnosis of IgG4-related disease on small biopsies: challenges and pitfalls. Histopathology 2019;74:688-98.

Deshpande V. IgG4 related disease of the head and neck. Head Neck Pathol 2015;9:24-31.

Yu Y, Zhang J, Lu G, Li T, Zhang Y, Yu N, et al. Clinical relationship between IgG4-positive Hashimoto’s thyroiditis and papillary thyroid carcinoma. J Clin Endocrinol Metab 2016;101:1516-24.

Pusztaszeri MP, Faquin WC, Sadow PM. Tumor-associated inflammatory cells in thyroid carcinomas. Surg Pathol Clin 2014;7:501-14.

Hagström J, Heikkilä A, Siironen P, Louhimo J, Heiskanen I, Mäenpää H, et al. TLR-4 expression and decrease in chronic inflammation: Indicators of aggressive follicular thyroid carcinoma. J Clin Pathol 2012;65:333-8.

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