[1259] IgG4 Positive Plasma Cells in Sclerosing Variant of Mucoepidermoid Carcinoma: A New and Evolving Concept

W Tian, E Yakirevich, A Matoso, D Gnepp. Alpert Medical School of Brown University, Providence, RI

Background: IgG4-related sclerosing disease is a recently described syndrome with unique histological features characterized by intense lymphoplasmacytic infiltrates with increased IgG4+ plasma cells, & dense stromal sclerosis. The disease spectrum frequently includes benign inflammatory diseases, such as sclerosing pancreatitis, cholangitis & 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 & lymphoplasmacytic infiltrates. Our goal was to further characterize lymphoplasmacytic infiltrates with respect to IgG4 expression.
Design: Six sclerosing MECs from our pathology service over the past 20 years were selected. In addition, 11 regular MEC with lymphoplasmacytic infiltrates, 4 CSS, & 12 cases of non-sclerosing chronic sialadenitis (CS) were evaluated. Formalin fixed paraffin embedded sections were stained for IgG4 & IgG by IHC. Images were captured under 400X magnification that correspond to a field area of 0.0675 mm2. The number of IgG & IgG4 positive plasma cells was quantified in the same field from five different areas, & the IgG4+ to IgG+ ratio was calculated.
Results: The 6 sclerosing MECs were characterized by prominent sclerosis & dense lymphoid predominantly peritumoral infiltrates rich in plasma cells. None of sclerosing MEC patients had IgG4-related sclerosing disease. The absolute number of IgG4+ plasma cells was significantly increased in sclerosing MEC as compared to regular type (75 vs 20 per image field, P<0.05). Furthermore, the ratio of IgG4+/IgG+ plasma cells was markedly elevated in sclerosing MEC as compared to the regular type (46.5 vs 17, P<0.005). In CSS, absolute numbers of IgG+ plasma cells & IgG4+/IgG+ ratio were significantly increased as compared to CS (P<0.005).

Sclerosing MEC n=6 Mean (range)MEC n=11CSS n=4CS n=12
IgG475 (18-190)20 (3-42)52 (7-108)2 (0-11)
IgG172 (54-279)108 (23-212)88 (37-152)63 (3-288)
IgG4/IgG46.5 (22-75)17 (5-33)54 (30-79)4.5 (0-23)

Conclusions: This study is the first to demonstrate increased IgG4 plasma cells in sclerosing MEC. This increase in malignant sclerotic disease is similar to that in inflammatory autoimmune conditions such as SCC. Association of the elevated IgG4+ plasma cells with increased fibrosis in sclerosing variant of MEC suggests a role of IgG4+ plasma cells in fibrogenesis and may be a new concept related to sclerosis in cancer.
Category: Head & Neck

Tuesday, March 23, 2010 9:15 AM

Platform Session: Section G, Tuesday Morning


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