Hashimoto's Thyroiditis with Increased IgG4-Positive Plasma Cells: Using Thyroid-Specific Diagnostic Criteria May Identify Early Phase IgG4 Thyroiditis

Background: A subset of Hashimoto's thyroiditis (HT), reported as immunoglobulin G4 (IgG4) thyroiditis, is characterized by IgG4+ plasma cell-rich inflammation and marked sclerotic changes, which suggests a close relationship with immunoglobulin G4-related disease (IgG4-RD). However, to date, there is no consensus regarding the cutoff values used to define a significant IgG4+ plasma cell count in thyroid inflammation. We, therefore, sought to validate both the cutoff value of the comprehensive diagnostic criteria (CVC) and the cutoff value of thyroid-specific diagnostic criteria (CVT) for diagnosing IgG4 thyroiditis. Methods: One hundred twenty cases of HT were retrospectively reviewed. According to the CVC (IgG4+ plasma cells >10/HPF (high-power field) and IgG4+/IgG+ plasma cell ratio >40%) and the CVT (IgG4+ plasma cells >20/HPF and IgG4+/IgG+ plasma cell ratio >30%), cases were subclassified as IgG4 thyroiditis or non-IgG4 thyroiditis. Clinical, serological, sonographic, and histopathological characteristics of the two subsets, and the cases diagnosed as IgG4 thyroiditis using different thresholds were compared. Results: Both the CVC and CVT identified the same set of distinct clinical, laboratory, and sonographic features of the cases diagnosed as IgG4 thyroiditis. All 120 cases of HT were able to be divided into four distinct groups. Group A included the 25 cases who were assigned as IgG4 thyroiditis by both the CVC and CVT, whereas Group D included the 85 cases who did not meet either of the cutoff values. Group B and Group C comprised the borderline cases who only met one of the two thresholds. Based on histological evaluation, the cases in Group B who met the CVT demonstrated similar histological features of IgG4 thyroiditis. Conclusions: Although both of the cutoff values can efficiently distinguish IgG4 thyroiditis from its non-IgG4 counterpart, the thyroid-specific cutoff value (CVT, IgG4+ plasma cells >20/HPF, and IgG4+/IgG+ plasma cell ratio >30%) can better identify borderline cases of HT with more fibrotic changes, which may represent an early phase lesion of IgG4 thyroiditis. We propose a new series of clinical and pathological diagnostic clues for both endocrinologists and pathologists to improve the early recognition of IgG4 thyroiditis.