EBV‐encoded RNA1‐positive cells in the bone marrow specimens of patients with EBV‐negative lymphomas and sarcomas

Abstract

Epstein‐Barr virus (EBV) infection is associated with pathogenesis of various cancers, including extranodal natural killer/T‐cell lymphoma, nasal type (ENKL). ENKL tumor cells are positive for EBV‐encoded RNA1 (EBER1), which is the most useful marker to identify ENKL tumor cells in histopathology. Currently, EBER1 in situ hybridization (ISH) is recommended to evaluate bone marrow (BM) involvement of ENKL. However, the actual burden of EBER1‐positive cells in normal BM specimens remains unclear. In the present study, we performed EBER1 ISH on 111 BM specimens, which were obtained during an initial staging procedure in patients with EBV‐negative cancers and were also negative for BM involvement. One or more EBER1‐positive cells per whole specimen were observed in 38 specimens (34%). The number of EBER1‐positive cells was distributed as follows: single positive cell, n = 17; two positive cells, n = 13; three positive cells, n = 3; and four positive cells, n = 5. These findings suggest that four or fewer EBER1‐positive cells can be observed in BM specimens of patients with non‐EBV‐related cancers. The clinical implications of a small number of EBER1‐positive cells in BM specimens of patients with ENKL should be evaluated in further studies.

Assessment of Bone Marrow Involvement in Extranodal NK/T-Cell Lymphoma: Positron Emission Tomography versus Bone Marrow Biopsy, and the Significance of Minimal Involvement by EBV+ Cells (KROG 18-09)

“…Furthermore, hematopathologists frequently grapple with uncertainty when a limited number of EBV+ cells are detected by EBER-ISH, as the exact origin of these cells often remains unknown. This ambiguity stems from the fact that EBV+ cells can be identified in patients without EBV-related malignancy [ 22 , 23 ]. In this study, patients classified as early stage by PET/CT with minimal BM involvement mainly received definitive radiation or concurrent chemoradiation.…”