Effect of Positive Bone Marrow EBV In situ Hybridization in Staging and Survival of Localized Extranodal Natural Killer/T-Cell Lymphoma, Nasal-Type

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Abstract
Purpose: The aim of the study was to determine the effect of EBV-encoded RNA-1 in situ hybridization (EBER-1 ISH) in bone marrow specimens on survival outcome in patients with clinical stage I/II natural killer/T-cell lymphoma. Experimental Design: We systematically did EBER-1 ISH on 182 archival bone marrow tissues from 91 patients who were diagnosed of stage I/II natural killer/T-cell lymphoma and analyzed the correlation between bone marrow EBER-1 ISH status and survival. We defined minimal bone marrow involvement and definite bone marrow involvement to distinguish the subgroups who revealed EBV-positive cells from normal marrow by EBER-1 ISH from those who showed typical neoplastic cells in bone marrow biopsies. Results: In total, 17 of the 91 (18.7%) patients showed positivity for EBER-1 ISH at least in one of the bilateral bone marrow biopsies with 14 minimal bone marrow involvements and 3 definite bone marrow involvements. Patients with positive bone marrow EBER-1 ISH showed significantly poorer overall survival than those who were negative for bone marrow EBER-1 ISH (median survival, 16.1 months versus not reached; P = 0.045). Conclusion: Considering a high proportion of stage I/II patients (15.4%) with minimal in bone marrow specimens, bone marrow EBER-1 ISH should be routinely done in all patients with localized disease for more accurate staging.

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