Orbital progressive transformation of germinal centers as part of the spectrum of IgG4-related ophthalmic disease: Clinicopathologic features of three cases

Progressive transformation of germinal centers (PTGC) is a form of follicular hyperplasia recently associated with immunoglobulin G4-related disease (IgG4-RD), but the ophthalmic manifestations of this combination are poorly described. In this retrospective case series, we present three cases of IgG4-related orbital disease (IgG4-ROD) showing varying degrees of PTGC involving the orbit and lacrimal gland. Three adult women presented with ill-defined lacrimal gland enlargement. Histologic sections showed variable fibrosis and large, irregular lymphoid follicles with prominent mantle zones penetrating the germinal centers, highlighted by Bcl-2 and/or IgD immunostains. The interfollicular areas contained a mixture of plasma cells, scattered histiocytes and eosinophils. Mixed T and B-cells were present, and no signs of monoclonality were identified. All cases showed more than 100 IgG4 positive cells per high power field. Epstein-Barr virus in situ hybridization performed in one case was negative. The serum IgG4 level was tested in one case and showed elevation above the normal range. After 2-10 months of follow-up, the patients showed either near-complete resolution or no remaining signs of ophthalmic disease. Increasing awareness of these PTGC in extra-nodal locations, including the orbit, may provide a better understanding of the histologic spectrum of this disease.