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.