To characterize the differentiating histopathologic and immunophenotypic features of reactive lymphoid hyperplasia (RLH) and follicular lymphoma of the ocular adnexa.

Retrospective case study with clinical follow-up and review of the literature.

Clinical records of 9 cases of RLH and 6 cases of follicular lymphoma from 2 institutions were reviewed. Light microscopic evaluation and immunohistochemical stains including CD20, CD3, CD5, CD21, CD23, BCL-2, BCL-6, CD10, kappa, lambda, and Ki67 were used to distinguish the 2 categories.

RLH preferentially involved the conjunctiva, whereas follicular lymphoma had a propensity to involve the lacrimal gland. Microscopic analysis with immunohistochemical staining distinguished RLH from follicular lymphoma. BCL-2 was positive in follicular centers of follicular lymphoma but not in RLH. CD10 identified follicular center cells and Ki67 quantified cells in S-phase. CD21 and CD23 detected dendritic cell scaffoldings of indistinct germinal centers. None of the patients with RLH developed lymphoma during their clinical courses (up to 18 years). However, 3 patients with orbital, but not conjunctival, RLH developed immunohistochemically proven multifocal nonophthalmic supradiaphragmatic adnexal RLH (sites included lung, parotid, axillary nodes, and uvea). All 6 patients with follicular lymphoma had disseminated disease.

A correct diagnosis of RLH vs follicular lymphoma can be reliably established employing immunohistochemical methods. A heretofore undescribed “multifocal RLH” syndrome must be distinguished from follicular lymphoma. Conjunctival RLH can usually be managed surgically without radiotherapy, but “multifocal RLH” required systemic treatment in 2 of 3 patients. Follicular lymphoma requires systemic chemotherapy if discovered beyond stage 1E.