Bone marrow that is positive for Epstein-Barr virus encoded RNA-1 by in situ hybridization is related with a poor prognosis in patients with extranodal natural killer/T-cell lymphoma, nasal type

Background and Objectives. Extranodal NK/T-cell lymphoma, nasal type is an aggressive lymphoma that is always associated with Epstein-Barr virus (EBV). This study was done to evaluate the use of EBV-encoded RNA-1 in situ hybridization (EBER-1 ISH) to detect occult micrometastasis in the bone marrow (BM) of patients with nasal NK/T-cell lymphoma. Design and Methods. A total of 23 patients who underwent BM biopsy for routine pre-therapeutic evaluation were enrolled in the study. We used EBER-1 ISH to investigate the expression of EBER-1 in 30 BM specimens. The clinical correlation and therapeutic outcomes of these patients were analyzed. In addition, genomic analysis of EBV was performed in five patients. Results. Conventional morphologic examinations failed to identify any lymphoma involvement in the 23 BM specimens obtained at initial staging. However, 10 of the 23 BM were positive for EBER-1. A lower survival rate was seen in patients with BM positive for EBER-1. Only the BM EBER-1 ISH result was shown to be an independent variable predicting overall survival in stage I and II patients (p=0.027; hazard ratio for death 0.066, 95% confidence interval, 0.006 to 0.733), suggesting that EBER-1 positivity in BM is the major determinant of a poor prognosis. However, discrepancies in the EBV strains between the primary tumor and BM existed in two of the five studied patients. Interpretations and Conclusions. We suggest that EBER-1 ISH should be performed on BM specimens of patients with nasal NK/T-cell lymphoma to identify the presence of EBER-1 positive cells, which appears to carry a poor prognosis. Whether or not the EBER-1 positive cells in the BM of nasal NK/T-cell lymphoma patients are true tumor cells requires further study.