Warthin-like papillary thyroid carcinoma with immunoglobulin G4-positive plasma cells possibly related to Hashimoto’s thyroiditis

Abstract

Hashimoto’s thyroiditis with heavy lymphoplasmacytic infiltration is a common comorbidity of immunoglobulin G4 (IgG4)-related thyroiditis and Warthin-like papillary thyroid carcinoma (WL-PTC). We hypothesized that WL-PTC may have a strong association with IgG4-related thyroiditis. To validate this hypothesis, we clinically and immunohistochemically studied 17 WL-PTC cases. Fourteen patients (82.4%) had anti-thyroglobulin antibody and were confirmed to have Hashimoto’s thyroiditis through microscopic analysis. Among them, five (29.4%) had disease consistent with IgG4-related thyroiditis but did not exhibit a “storiform” pattern or obliterative phlebitis. IgG4-related diseases were not found in other organs. No cases with serum IgG4 level of >135 mg/dL were noted. A total of 94.1% of WL-PTC cases had IgG4-positive plasma cells (⁺PCs) in the stroma, and cases with rich IgG4⁺PCs were more frequently associated with Hashimoto’s thyroiditis than those with poor IgG4⁺PCs. In this study, all three cases without Hashimoto’s thyroiditis had poor IgG4⁺PCs, and one of them did not exhibit IgG4⁺PCs in the stroma of WL-PTC and Hashimoto’s thyroiditis. Nodal metastatic lesions were seen in eight cases, all of which were not WL-PTC. As such, we should consider that the Hashimoto’s disease with rich IgG4⁺PCs seen in our cases is representative of non-IgG4-related disease and not IgG4-related disease involving multiple organs. This study is the first to demonstrate the presence of IgG4⁺PCs in the stroma of WL-PTC. We concluded that the appearance of IgG4⁺PCs in the stroma of WL-PTC may be related to Hashimoto’s thyroiditis with rich IgG4⁺PC.