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.