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

Abstract

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 ¼ 28) and a non-IgG4 thyroiditis group (n ¼ 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.

IgG4-related Hashimoto’s thyroiditis – A new variant of a well known disease

“…identified 14% of patients in the IgG4 thyroiditis group as having only mild fibrosis in the stroma, whereas 38% in the non-IgG4 thyroiditis group were found to meet the diagnostic criteria for the fibrous variant of HT. Some authors found that the IgG4 thyroiditis group was significantly associated with the presence of a predominant interfollicular pattern of fibrosis, while the fibrosis in the non-IgG4 thyroiditis group was mainly interlobular (19).…”

“…In fact, none of the patients in the IgG4 thyroiditis group reported by Li and cols. showed involvement of other organs (19). Therefore, in a patient with confirmed IgG4-related HT and no additional signs and symptoms, we consider that it is not mandatory to discard general IgG4-related disease.…”

IgG4 Related Disease of the Head and Neck

“…In a series of elegant papers, Kakudo identified a variant of Hashimoto's thyroiditis (IgG4 related thyroiditis) that showed elevated numbers of IgG4 positive plasma cellsdefined as greater than 20 IgG4 positive plasma cells per HPF, and an IgG4 to IgG ratio of greater than 30 % [3,23]. There were significant differences between patients with IgG4 positive thyroiditis and IgG4 negative thyroiditis.…”

“…Some groups now believe that a significant proportion of cases of fibrosing Hashimoto's thyroiditis, and a minority of cases with classic Hashimoto's thyroiditis belong to the spectrum of IgG4 related disease [3,4,[23][24][25][26]. However, unlike most other manifestations of the disease, both forms of thyroiditis (now termed IgG4 related thyroiditis) remain confined to the thyroid, and systemic manifestations have not been recognized [3,4,23,24]. Nonetheless, a significant proportion of patients with autoimmune pancreatitis and IgG4 related disease show evidence of hypothyroidism, thus arguing for an association between this thyroid disease and IgG4 related disease [27].…”

“…In addition, involvement of the upper aerodigestive tract and paranasal sinuses is well recognized. With regards to the thyroid, Riedel thyroiditis (RT) is characterized as a member of the IgG4 related disease spectrum, however, the relationship between Hashimoto's thyroiditis (as well as its fibrosing variant) is still a matter of debate [3,4].…”