Review of IgG4-related Hashimoto Thyroiditis With Best Practice Recommendations for Diagnosis and Reporting

Found in virtually any organ system, immunoglobulin (Ig) G4-related disease (RD) is a recently recognized immune-mediated, systemic, a fibroinflammatory disease characterized histologically by storiform fibrosis, obliterative phlebitis, and lymphoplasmacytic infiltrate with IgG4-positive plasma cells (PCs). IgG4-related Hashimoto thyroiditis (IgG4-RHT), also called IgG4-related thyroiditis, shares many features with IgG4-RD but is distinct in several ways. A case of IgG4-RHT in a 51-year-old African American female is assembled together with a literature review which uncovered 82 cases of IgG4-RHT. The findings and criteria which the respective authors used to reach their diagnoses are analyzed. Findings common to all studies are lymphoplasmacytic infiltration and IgG4-positive staining, while most describe follicular atrophy (95.2%, 79/83). Stromal fibrosis involving >33% of thyroid architecture was reported in 74% (58/78) of cases. While few reports observed storiform fibrosis, all describe lack of obliterative phlebitis or systemic involvement. Discrepancies between reports exist in immunostaining thresholds, as well as grading systems for stromal fibrosis. Based on our review of the literature and experience, we propose a set of best practice recommendations for the diagnosis of IgG4-RHT. Our diagnostic criteria are (1) lack of extrathyroidal IgG4-RD, (2) the fibroinflammatory process should not extend beyond the thyroid capsule, (3) stromal fibrosis comprises at least 30% of the involved tissue, (4) >30% IgG4/IgG ratio, with absolute immunostaining cutoffs varying by the degree of stromal fibrosis: for >50% stromal fibrosis use >20 IgG4+PCs/HPF, for 30% to 50% fibrosis use >30 IgG4+PCs/HPF, (5) fibrosis infiltrates the interlobular/interfollicular space, (6) features of follicle injury, and (7) obliterative phlebitis is not required.