Original contributionIgG4-positive plasma cells in granulomatosis with polyangiitis (Wegener's): a clinicopathologic and immunohistochemical study on 43 granulomatosis with polyangiitis and 20 control 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
References (17)
- et al.
Diagnostic value and limitations of orbital biopsy in Wegener's granulomatosis
Ophthalmology
(1992) - et al.
Consensus statement on the pathology of IgG4-related disease
Mod Pathol
(2012) - et al.
IgG4-positive plasma cell infiltration in the diagnosis of autoimmune pancreatitis
Mod Pathol
(2007) - et al.
Use of immunohistochemistry for IgG4 in the distinction of autoimmune pancreatitis from peritumoral pancreatitis
Hum Pathol
(2010) - et al.
Practical pulmonary pathology: a diagnostic approach
(2011) - et al.
IgG4-related sclerosing disease: a critical appraisal of an evolving clinicopathologic entity
Adv Anat Pathol
(2010) Pathological features of IgG4-related sclerosing disease
Curr Opin Rheumatol
(2011)- et al.
Interpretation of head and neck biopsies in Wegener's granulomatosis. A pathologic study of 126 biopsies in 70 patients
Am J Surg Pathol
(1990)
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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.