Riedel's thyroiditis with increased IgG4 plasma cells: evidence for an underlying IgG4-related sclerosing disease?

BACKGROUND: Riedel's thyroiditis (RT) is a very rare chronic fibrosing disorder of unknown etiology that is often associated with multifocal fibrosclerosis (MFS). Immunoglobulin (Ig) G4-related sclerosing disease (IgG4-RSD), a new clinico-pathological entity also associated with MFS, is characterized by IgG4+ plasma cell infiltration and fibrosis in one or more organs. Although the association of RT and IgG4-RSD has been suggested, it has seldom been studied or reported. We report a classical case of RT with serological (IgG4 levels) and immunohistochemical (IgG and IgG4) assessment, in search of an underlying IgG4-RSD.

PATIENT: The patient was a 57-year-old woman who underwent a subtotal thyroidectomy for a long-standing goiter with a rapidly enlarging isthmic nodule.

RESULTS: Histopathological examination of the surgical specimen revealed all of the morphological features of RT and IgG4-RSD, including partial fibrosis of the thyroid gland with destruction of the thyroid follicular architecture; obliterative phlebitis; and a mixed infiltrate composed of lymphocytes, eosinophils, and plasma cells. The fibro-inflammatory process extended beyond the thyroid capsule into the surrounding tissues. Immunohistochemical examination revealed approximately 70 IgG4+ plasma cells per high power field (HPF) with an IgG4/IgG ratio of 35%. Although serum levels of IgG4 were normal (20 mg/dL), total IgG levels were slightly elevated (1370 mg/dL). There was no evidence of involvement of other organs at the time of RT diagnosis.

CONCLUSIONS: The morphological similarities between RT and IgG4-RSD suggest that these entities are closely related. Therefore, RT with increased IgG4+ plasma cells, with or without elevated IgG4 serum levels, may represent the first clinical manifestation of an underlying IgG4-RSD. However, due to the rarity of both conditions and the limited specificity and sensitivity of both IgG4 serum levels and IgG/IgG4 immunohistochemistry in the diagnosis of IgG4-RSD, further studies are needed to verify this hypothesis.