IgG4(+) plasma cells in sclerosing variant of mucoepidermoid carcinoma.

IgG4-related sclerosing disease is a recently described syndrome with unique histologic features characterized by intense lymphoplasmacytic infiltrates with increased IgG4 plasma cells and dense stromal sclerosis. The disease spectrum frequently includes benign inflammatory diseases, such as autoimmune pancreatitis, cholangitis, and chronic sclerosing sialadenitis (CSS). Mucoepidermoid carcinoma (MEC) is the most common primary malignancy in the salivary gland. The rare sclerosing variant of MEC is characterized by dense stromal sclerosis and lymphoplasmacytic infiltrates. Our goal was to further characterize lymphoplasmacytic infiltrates with respect to IgG4 expression. Six sclerosing MECs from our pathology service over the past 20 years were selected. In addition, 11 regular MECs with lymphoplasmacytic infiltrates, 4 CSS cases, and 12 nonsclerosing chronic sialadenitis cases were evaluated. None of the sclerosing MEC patients had IgG4-related sclerosing disease. The absolute number of IgG4 plasma cells was significantly increased in sclerosing MEC as compared with the regular type (75 vs. 20 per image field; P<0.05). Furthermore, the proportion of IgG4/IgG plasma cells was markedly elevated in sclerosing MEC as compared with the regular type (46.5% vs. 17%; P<0.05). In CSS, IgG4/IgG ratio was significantly increased as compared with nonsclerosing chronic sialadenitis (54% vs. 6.73%; P<0.01). This study is the first to demonstrate increased IgG4 plasma cells in sclerosing MEC. The association of elevated IgG4 plasma cells with increased fibrosis in the sclerosing variant of MEC suggests a role of IgG4 plasma cells in fibrogenesis and may be a new concept related to sclerosis in cancer.