Fibrosing Variant of Hashimoto's Thyroiditis Is an IgG4 Related Disease
Amelia E Huck, William C Faquin, John H Stone, Gunnlaugur P Nielsen, Vikram Deshpande. Massachusetts General Hospital and Harvard Medical School, Boston, MA
Background: Hashimoto's thyroiditis (HT) and the fibrosing variant of Hashimoto's thyroiditis (FVHT) are immune-mediated tumefactive lesions of the thyroid. IgG4-related disease (IgG4-RD) is now a widely recognized multi-organ system disease characterized by elevated serum and tissue concentrations of IgG4. The sine qua non of IgG4-RD is its histologic appearance: lymphoplasmacytic inflammation, storiform fibrosis, and obliterative phlebitis. Recent data from Japan suggest that a subset of patients with HT also belong to the IgG4-RD spectrum. We address several questions pertaining to the relationship among HT and FVHT and the association of each of these diseases with IgG4-RD.
Design: We evaluated 28 consecutive cases of HT and 9 cases of FVHT. The clinical, demographic, and serological data were recorded. The slides were stained immunohistochemically using antibodies to IgG4 and IgG, and the degrees of plasma cell infiltration and IgG4 staining within samples were quantified. For each case, the number of plasma cells staining for IgG4 and IgG was assessed in non-overlapping high-power fields.
Results: Hypothyroidism was noted in 62% of HT and 85% of FVHT. Thyroid peroxidase antibodies were positive in all 10 cases of HT and all 4 cases of FVHT. FVHT demonstrated an exaggerated lobular pattern with lobules separated by storiform type fibrosis. This histological appearance was remarkably similar to the interlobular stroma of IgG4-associated sialadenitis and the type 1 variant of autoimmune pancreatitis. Follicular cells were predominantly arranged in a microfollicular pattern, and an intense inflammatory infiltrate composed of lymphocytes and plasma cells was identified between follicles. The mean IgG4 counts per HPF in HT and FVHT were 4.9 and 27, respectively. The mean IgG4:IgG ratios in HT and FVHT were 19.0% and 61.4%, respectively.
|Mean IgG4 per HPF||Mean IgG per HPF||Mean IgG4/IgG ratio|
|Hashimoto's thyroiditis||4.9 (8.1)||22.7 (12.6)||19% (22.7)|
|Fibrosing variant of Hashimoto's thyroiditis||27.0 (17.9)||43.5 (19.5)||61.4% (30.6)|