Plasma Cell IgG4 Positivity in Orbital Biopsies of Non-IgG4-related Conditions

The IgG4-related disease (IgG4-RD) is a systemic condition defined as a fibro-inflammatory disorder, characterized by the occurrence of tumor-like lesions in multiple organs including the eye adnexa. The main diagnostic criterion is based on histopathological findings, especially on the IgG4/IgG plasma cell ratio. In this article, we reviewed the literature of non-IgG4-RD orbital conditions with IgG4 positivity. There were 20 reports of inflammatory non-IgG4-RD orbital lesions and 14 reports of orbital lymphoid proliferations with significant IgG4 positivity. The role of plasma cells IgG4 in the pathogenesis of non-IgG4-RD is not clear. Considering the large spectrum of diseases caused by a variety of different etiopathogenic mechanisms, we think that the common denominator of IgG4 in these conditions might be related to the peculiar properties of down regulation of immune response of the IgG4 and not to a specific link to IgG4-RD.