Conjunctival Reactive Lymphoid Hyperplasia with Delayed Corneal Immune Infiltrates in the Setting of Systemic Epstein–Barr Virus Infection

PURPOSE: To report an unusual case of conjunctival reactive lymphoid hyperplasia occurring in close temporal association with systemic Epstein-Barr virus (EBV) infection, presenting with preseptal cellulitis-like features and followed by delayed corneal immune infiltrates (CI). METHODS: A single-patient case report. RESULTS: A 21-year-old woman developed marked unilateral painless periorbital edema, ptosis, and a firm 360-degree yellow-white conjunctival infiltrative lesion after a viral prodrome. Orbital magnetic resonance imaging showed enhancing conjunctival and episcleral involvement, raising concern for ocular adnexal lymphoma or another infiltrative disorder. EBV VCA IgM, VCA IgG, EBNA IgG, and plasma EBV DNA were positive, suggesting recent/resolving or possibly reactivated systemic EBV infection when interpreted together with the clinical presentation and reactive lymphocytes. Biopsy showed a mixed lymphoid, histiocytic, eosinophilic, and plasmacytic infiltrate with a low Ki-67 index. Immunohistochemistry and kappa/lambda light-chain evaluation supported a polytypic, nonclonal process. Targeted sequencing was negative for clinically significant variants, including BRAF or MAP2K1, supporting a minor nonclonal reactive Langerhans-type population. Epstein-Barr encoding region in situ hybridization was negative on limited tissue and was interpreted as not supporting latent EBV-driven clonal lymphoproliferation. The conjunctival lesion regressed with topical corticosteroid and cyclosporine therapy. Delayed perilimbal CI and stromal haze subsequently developed and partially persisted during follow-up. CONCLUSION: Recent or resolving systemic EBV infection may be temporally associated with conjunctival reactive lymphoid hyperplasia mimicking preseptal cellulitis. Delayed CIs may represent an additional feature of this inflammatory spectrum, although causality remains unproven without lesion-specific EBV detection.