Distinct histopathological features of Hashimoto's thyroiditis with respect to IgG4-related disease

Mod Pathol. 2012 Aug;25(8):1086-97. doi: 10.1038/modpathol.2012.68. Epub 2012 May 4.


A form of Hashimoto's thyroiditis with lymphoplasmacytic sclerosing changes and increased numbers of IgG4-positive plasma cells has recently been reported in the literature. These histopathological features suggest that this subtype of Hashimoto's thyroiditis may be closely related to IgG4-related disease. Therefore, this unique form of IgG4-related Hashimoto's thyroiditis, which is referred to as IgG4 thyroiditis, has its own clinical, serological, and sonographic features that are distinct from those associated with non-IgG4 thyroiditis. IgG4 thyroiditis shares similarities with the well-known fibrous variant of Hashimoto's thyroiditis; however, the detailed histopathological features of IgG4 thyroiditis have not been well established. Based on immunostaining results, 105 patients with Hashimoto's thyroiditis were divided into an IgG4 thyroiditis group (n=28) and a non-IgG4 thyroiditis group (n=77). As in our previous reports, IgG4 thyroiditis was associated with a patient population of a younger age, a lower female-to-male ratio, rapid progression, higher levels of thyroid autoantibodies, subclinical hypothyroidism, and diffuse sonographic echogenicity. Histopathologically, this group revealed severe lymphoplasmacytic infiltration, dense stromal fibrosis, marked follicular cell degeneration, numerous micro-follicles, and notable giant cell/histiocyte infiltration. Importantly, the IgG4-related group did not completely overlap with fibrous variant of Hashimoto's thyroiditis. Four cases (14%) in the IgG4 thyroiditis group presented only mild fibrosis in the stroma, whereas 29 cases (38%) in the non-IgG4 thyroiditis group met the diagnostic criteria for fibrous variant of Hashimoto's thyroiditis. Furthermore, we observed three patterns of stromal fibrosis in Hashimoto's thyroiditis: interfollicular fibrosis, interlobular fibrosis, and scar fibrosis. The IgG4 thyroiditis group was significantly associated with the presence of predominant interfollicular fibrosis. In conclusion, IgG4 Hashimoto's thyroiditis presents histopathological features quite distinct from its non-IgG4 counterpart.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Disease Progression
  • Female
  • Fibrosis / immunology
  • Fibrosis / pathology
  • Hashimoto Disease / immunology
  • Hashimoto Disease / pathology*
  • Humans
  • Immunoglobulin G / immunology*
  • Lymphocytes / pathology
  • Male
  • Middle Aged
  • Plasma Cells / immunology
  • Plasma Cells / pathology
  • Sex Factors
  • Stromal Cells / immunology
  • Stromal Cells / pathology
  • Thyroid Gland / immunology
  • Thyroid Gland / pathology
  • Thyroidectomy
  • Thyroiditis, Autoimmune / immunology
  • Thyroiditis, Autoimmune / pathology*
  • Young Adult


  • Immunoglobulin G