Unifocal and multifocal reactive lymphoid hyperplasia vs follicular lymphoma of the ocular adnexa

Am J Ophthalmol. 2010 Sep;150(3):412-426.e1. doi: 10.1016/j.ajo.2010.04.007.


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

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

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Biomarkers, Tumor / metabolism*
  • Child
  • Conjunctival Neoplasms / diagnosis*
  • Conjunctival Neoplasms / metabolism
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Immunophenotyping
  • Ki-67 Antigen / metabolism
  • Lymphoma, Follicular / diagnosis*
  • Lymphoma, Follicular / metabolism
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Orbital Neoplasms / diagnosis*
  • Orbital Neoplasms / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-bcl-6
  • Pseudolymphoma / diagnosis*
  • Pseudolymphoma / metabolism
  • Retrospective Studies


  • Antigens, CD
  • BCL6 protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6