Immunoglobulin G4-related chronic rhinosinusitis: a pitfall in the differential diagnosis of granulomatosis with polyangiitis, Rosai-Dorfman disease, and fungal rhinosinusitis

Immunoglobulin G4 (IgG4)-related chronic rhinosinusitis (CRS) has recently been proposed to be a new clinical entity of nasal disease, with no consensually agreed criteria for diagnosis. Moreover, the pathological features of IgG4-related CRS often overlap with other sinonasal inflammatory and autoimmune diseases such as granulomatosis with polyangiitis (GPA), Rosai-Dorfman disease (RDD) and fungal rhinosinusitis (FRS). We aimed to explore the specific similarities and differences in clinicopathologic features between IgG4-related CRS, and GPA, RDD and FRS, in order that these conditions can be diagnosed more accurately. Biopsy specimens collected from nasal mucosa of 20 IgG4-related CRS, 10 GPA, 10 RDD and 10 FRS patients were assessed by hematoxylin and eosin staining and immunohistochemical techniques for specific histochemical differences. The number of IgG4-positive plasma cells /high-power fields (HPF) in biopsies from IgG4-related CRS patients (mean = 79.6 ± 51.59; range = 15/HPF to 230/HPF) was significantly higher than in biopsies from GPA (mean = 13 ± 9.428; P < .0001) and RDD (mean = 12.5 ±  8.267; P < .0001) patients, but not from FRS (mean = 47.4 ± 26.48; P > .05) patients. Similarly, the ratio of IgG4/IgG-positive plasmacytes was >40% in 90% (18/20) of IgG4-related CRS patients, compared to >40% in 10% (1/10) of GPA patients, 20% (2/10) of RDD patients and 20% (2/10) of FRS patients. The sinonasal diseases GPA, RDD and FRS might present with similar histopathologic features such as the increased numbers of plasma cells and fibrosis, which are characteristic of IgG4-related CRS. A comprehensive consideration combining the clinical signs and symptoms with a histopathological assessment of IgG4-positive plasma cells may provide accurate diagnoses of these conditions.