Clinicopathologic Analysis of 34 Japanese Patients With EBV-Associated Reactive Lymphoid Hyperplasias.
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The 5th edition of the WHO classification of haematolymphoid tumours introduces the concept of hyperplasias arising in immune deficiency and dysregulation (IDD), which are frequently associated with Epstein-Barr virus (EBV). These lesions can be histologically classified as follicular hyperplasia (FH), infectious mononucleosis-like hyperplasia (IMH), or plasmacytic hyperplasia. Although EBV-associated reactive lymphoid hyperplasia (EBV-RLH) has been recognized in various IDD settings, comprehensive clinicopathologic analyses remain limited. We analyzed 34 Japanese patients with EBV-RLH. The IDD settings primarily included autoimmune diseases (with or without immunosuppressive therapy), chemotherapy for prior malignancies, aging, post-hematopoietic stem cell transplantation, and HIV infection. No patient exhibited histologic transformation or died due to EBV-RLH. Three patients had concurrent hematologic malignancies, and 12 had immune dysregulation related to prior chemotherapy. Histologically, 20 cases showed FH, 6 IMH, and 8 nonspecific patterns. EBER-positive cells were distributed in both interfollicular areas and germinal centers (GCs) in 27 cases (79%) and confined to interfollicular areas in 7. Six cases exhibited intensive aggregation of EBER-positive cells in one or a few GCs. Double staining confirmed that most EBER-positive cells expressed CD79a but not CD3. IGH and TCRG PCR analyses were successful in 24 cases: 21 were negative for both rearrangements, and 3 showed clonal rearrangements (1 double, 1 IGH-only, and 1 TCRG-only). EBV-RLH generally followed an indolent course; however, it may coexist with hematologic malignancies or develop after multichemotherapy. Careful histopathologic evaluation is essential to avoid overlooking concurrent malignancy or unnecessary treatment.