Inflammatory cell infiltration in tumor stroma may represent the interaction between the tumor and the immune system. The significance of immunoglobulin (Ig) G4+ plasmacytic infiltration, however, is poorly understood. Here, we analyzed the number of stromal IgG4+ plasma cells and the IgG4/IgG ratio of plasma cells in 294 primary non-small cell lung cancers (NSCLCs) using tissue microarray (TMA) and conventional surgical specimens. In TMA, 35 (12%) cases of NSCLC revealed more than 20 IgG4+ plasma cells per high-power field. In surgical specimens, most (97%) of those IgG4+ plasma cell-enriched cases showed obliterative phlebitis or arteritis, one of the key morphologic features of IgG4-related disease, within or at the periphery of the tumor. Clinically, none of the patients showed symptoms associated with IgG4-related systemic diseases. In patients with stage I squamous cell carcinoma, IgG4-enriched stroma was significantly associated with a favorable prognosis (P = .04). In conclusion, considerable IgG4+ plasma cell infiltration can be seen in a minority of cases of NSCLC and might contribute to prognostic modulation of NSCLC
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