title: Unifocal and multifocal reactive lymphoid hyperplasia vs follicular lymphoma of the ocular adnexa.
abstract: OBJECTIVE
  To characterize the differentiating histopathologic and immunophenotypic features of reactive lymphoid hyperplasia (RLH) and follicular lymphoma of the ocular adnexa.
  
  
  METHODS
  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.
authors.affiliation: David G. Cogan Laboratory of Ophthalmic Pathology, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Stacy
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Jakobiec
authors.forename: Lynn
authors.initials: L
authors.lastname: Schoenfield
authors.forename: Arun D
authors.initials: AD
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D003230:Conjunctival Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D019394:Ki-67 Antigen / Q000378:metabolism; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009918:Orbital Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D019310:Pseudolymphoma / Q000175:diagnosis* / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D015703:Antigens, CD; C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6