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

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.