Elsevier

Human Pathology

Volume 44, Issue 11, November 2013, Pages 2432-2437
Human Pathology

Original contribution
IgG4-positive plasma cells in granulomatosis with polyangiitis (Wegener's): a clinicopathologic and immunohistochemical study on 43 granulomatosis with polyangiitis and 20 control cases

https://doi.org/10.1016/j.humpath.2013.05.023Get rights and content

Summary

Granulomatosis with polyangiitis (GPA) (Wegener's) may mimic IgG4-related disease (IgG4-RD) on histologic examination of some biopsies, especially those from head and neck sites. IgG4 immunostaining is often performed in this context for differential diagnosis with IgG4-RD. Herein, we report the results of IgG4-positive (IgG4+) cells in 43 cases of GPA including 26 previously published cases as well as the newly added cases from the lung and kidney. We also included 20 control cases without any clinical evidence of GPA or IgG4-RD that consisted of chalazion (n = 8), chronic sinusitis (n = 8), and chronic tonsillitis (n = 4). Forty-three biopsies diagnosed as GPA were from sinonasal mucosa/oral cavity/nasopharynx (n = 14), orbit/periorbital tissue (n = 7), lung/pleura (n = 14), kidney (n = 4), skin (n = 3), and dura (n = 1). Of 43 biopsies, 8 (18.6%) revealed increased IgG4+ cells (>30 per high-power field and >40% in IgG4+/IgG+ ratio) and originated from sinonasal (n = 4) or orbital/periorbital (n = 4) regions. The IgG4+ cells and IgG4+/IgG+ ratio in these cases ranged from 37 to 139 per high-power field and 44% to 83%, respectively. None of the control cases had increased IgG4+ cells. In conclusion, increased IgG4+ cells can be seen in sinonasal or orbital/periorbital biopsies of GPA, which could pose as a pitfall in the diagnosis of IgG4-RD. However, GPA in other organs and controls did not show increased IgG4+ cells when using the above threshold. The biologic or clinical importance of increased IgG4+ cells in GPA cases involving head and neck region is uncertain, and a further study might be warranted to address the potential pathogenic relationship between IgG4-RD and GPA in those cases.

Introduction

IgG4-related disease (IgG4-RD) is a newly recognized fibroinflammatory condition that now often enters to the differential diagnosis with various inflammatory diseases such as Wegener granulomatosis. Wegener granulomatosis has been recently renamed as granulomatosis with polyangiitis (GPA) (Wegener's), and we used this new name to comply with the current nomenclature. On histologic examination, some biopsies from GPA patients can mimic IgG4-RD because the inflammatory background in GPA may be rich in plasma cells and accompanied by fibrosis and/or obliterated blood vessels as in IgG4-RD [1], [2], [3]. Moreover, GPA cases from the upper respiratory tract or orbit might lack classic morphologic features such as necrotizing vasculitis, parenchymal necrosis, and palisading granulomas [4], [5]. IgG4 immunostaining is now often performed in this context to evaluate the possibility of IgG4-RD.

In our initial study based on 26 GPA cases [6], we reported increased IgG4+ cells in 8 cases, all of which were from the head and neck sites. We expanded the study with more GPA cases in other sites confirmed by a thorough clinical and pathologic assessment because it was not entirely clear whether one can conclude that increased IgG4+ cells can be only seen in the head and neck GPA cases, given the small number of the biopsies from other organs in that study. Moreover, the prevalence of IgG4+ cells has not been reported in the cases of various nonspecific inflammatory conditions involving the head and neck. Therefore, we sought to assess the prevalence of IgG4+ cells in GPA cases along with some nonspecific inflammatory conditions in the head and neck sites as controls.

Section snippets

Case selection

Cases with the diagnosis of GPA were identified via electronic search from our surgical pathology file during a period of 1994 to 2011. We retrieved 43 biopsies from various body sites that included sinus/nasopharynx (n = 13), oral cavity (n = 1), orbital region (n = 7), lung/pleura (n = 14), kidney (n = 4), skin (n = 3), and dura (n = 1). Additional 20 control cases from the head and neck areas were selected via electronic search, to survey the prevalence of IgG4+ cells in nonspecific

Results

Of 43 patients, 8 (18.6%) showed increased IgG4+ plasma cells with the IgG4+ cell count at 63 ± 32 per HPF (mean ± 2 SDs; range, 37-139) and the IgG4+/IgG+ ratio at 66% ± 16% (range, 44%-83%), respectively. All of these 8 biopsies with increased IgG4+ cells were from the head and neck areas including sinonasal and orbital regions (Fig. 1). None of the biopsies from other sites met the criteria for increased IgG4+ cells (>30 per HPF and >40% in IgG4+/IgG+ cells). All cases showed some of the

Discussion

The present study demonstrated increased IgG4+ cells in 18.6% of 43 GPA cases from all sites and in 38.1% of 21 GPA cases from head and neck sites. To our knowledge, this is the largest series looking into the IgG4+ cell counts in GPA. We confirmed the diagnosis of GPA using the current guidelines by modified American College of Rheumatology criteria in conjunction with a careful histopathologic examination. In addition, the clinicopathologic diagnosis of GPA was further supported by the

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This study was presented in part at the International Symposium on IgG4-Related Disease held on October 4 to 7, 2011, in Boston, MA, and a part of this study has been published in an open access journal.

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