Re-evaluation of "reactive lymphoid hyperplasia of the uvea": an immunohistochemical and molecular analysis of 10 cases

Abstract

Objective: Cases of uveal lymphoid proliferation previously classified as reactive lymphoid hyperplasia (RLH) were studied to correlate pathologic features with clinical outcome.

Design: Retrospective case series.

Participants: Ten cases of RLH of the uvea on file at the Armed Forces Institute of Pathology with sufficient formalin-fixed, paraffin-embedded tissue for analysis.

Methods: Clinical, histologic, immunohistochemical, and molecular (polymerase chain reaction [PCR]) characteristics of uveal lymphoid proliferations were studied.

Main outcome measures: Morphologic, immunohistochemical, and PCR characteristics of study cases.

Results: Patient age ranged from 40 to 73 years at time of enucleation, with a mean age of 55 years. Retinal detachment was noted clinically in nine patients and glaucoma in eight. All patients were treated with enucleation, and three received radiotherapy. Histologically, two cases were interpreted as RLH and eight were well-differentiated small-cell lymphoma (WDSCL). Systemic lymphoid infiltrate developed in two patients, but there were no deaths with a mean follow-up of 9.9 years. Mature lymphocytes were noted in the iris and angle structures; the atypical cells of uveal lymphoma were found in the choroid and ciliary body. Eight cases were monoclonal by B-cell and T-cell markers and/or immunoglobulin light chain restriction. Amplifiable DNA was present in 6 of 10 cases by PCR. Three cases monoclonal by cell markers were also monoclonal by PCR, but two cases monoclonal by cell markers could not be confirmed by PCR. Lymphoid follicles with germinal centers were found in two cases of RLH and five cases of WDSCL. Nine specimens demonstrated extraocular lymphoid involvement of the episclera and orbit; most appeared more benign morphologically than the choroidal infiltrates. Extraocular infiltrates of WDSCL were monoclonal by immunohistochemistry in five cases, polyclonal in one case, and indeterminate in two cases.

Conclusions: Most cases (8 of 10) previously described as RLH were low-grade B-cell lymphomas histologically and by immunohistochemistry. PCR results agreed with histologic diagnosis in four of six cases. Open-angle glaucoma was common and related mostly to lymphocytic infiltration of the angle structures. Extraocular involvement is common but may not be representative of the choroidal lesion. Prognosis is excellent in low-grade uveal lymphoid neoplasia.