EBV-POSITIVE B-CELL ULCERATIVE PROLIFERATION IN THE ORAL CAVITY

Abstract

<h3>Objective</h3> Lymphoproliferative disorders (LPDs) are a group of conditions characterized by excessive production of lymphocytes manifested by lymphadenopathy, monoclonal lymphocytosis, and bone marrow infiltration. LPDs are often associated with Epstein-Barr virus (EBV) infection. EBV-associated LPDs most commonly appear in the setting of immunocompromised status such as HIV and in transplantation with the extended use of immunosuppressive medications. Individuals with primary immunodeficiency disorders, such as common variable immunodeficiency disease (CVID) or severe combined immunodeficiency, are also at risk of LPD. <h3>Case Summary</h3> A 67-year-old woman complained of mouth ulcerations for 3 months before presentation that were progressively getting worse. Past medical history included CVID, CD4 lymphopenia, rhinosinusitis, eosinophilic asthma, chronic back pain, anxiety, and depression. Medications included immunoglobulin replacement therapy, mepolizumab, montelukast, albuterol, cetirizine, bupropion, clonazepam, fluoxetine, and gabapentin. The patient was allergic to penicillin and azithromycin. Past surgical history was notable for removal of skin melanoma and total knee replacement. Review of systems included a 3-month, 25-lb weight loss, odynophagia, constipation, weakness, and fatigue. Extraoral examination was unremarkable. Intraoral examination revealed 3 × 2 cm² necrotizing palatal ulcerations bilaterally. Necrotizing ulceration was also noted on multiple areas of the gingiva. Differential diagnosis included acute necrotizing ulcerative periodontitis, deep fungal infection (aspergillosis), and lymphoma/LPD. Complete blood count with differential, EBV polymerase chain reaction (PCR), cytomegalovirus PCR and maxillofacial computed tomography (CT) were ordered. The CT scan was unremarkable and laboratory evaluation was negative except for positive EBV PCR. Oral biopsy demonstrated EBV positive B-cell ulcerative proliferation. Positron emission tomography/CT showed widespread fluorodeoxyglucose (FDG)-avid lymphadenopathy. An axillary lymph node biopsy showed atypical lymphoid proliferation in a background of atypical and reactive follicular hyperplasia most consistent with EBV-negative follicular lymphoma, which appeared histologically distinct from the oral EBV-positive LPD. The patient is currently being treated with single-agent rituximab therapy. <h3>Conclusions</h3> EBV may cause oral diseases including infectious mononucleosis, oral hairy leukoplakia, necrotizing ulcerative mucositis, non-Hodgkin's lymphoma, and EBV-related LPD. Persistent oral lesions in patients with CVID could be related to underlying systemic disease. This case is unique because the patient seemingly had follicular lymphoma unrelated to her EBV-positive LPD oral disease, yet in the setting of severe immunosuppression from CVID.