Unifocal and Multifocal Reactive Lymphoid Hyperplasia vs Follicular Lymphoma of the Ocular Adnexa

Abstract

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.