Absence of Epstein-Barr virus in anaplastic large cell lymphoma: a study of 64 cases classified according to World Health Organization criteria

The frequency of Epstein-Barr virus (EBV) in anaplastic large cell lymphoma (ALCL) has been controversial. The interpretation of previous studies is complicated by the use of nonuniform EBV detection methods and the inclusion of cases of CD30-positive diffuse large B-cell lymphoma and so-called "ALCL, Hodgkin-like," as defined in the Revised European-American Lymphoma classification scheme. In the current World Health Organization (WHO) classification system, both of these tumors are excluded from the ALCL category. Also, recently developed antibodies (eg, the antibody specific for PAX-5/B-cell-specific activator protein [BSAP]) provide new, sensitive tools for identifying neoplasms of B-cell lineage that can morphologically resemble ALCL. In this study we evaluated 64 cases of ALCL of T- or null-cell lineage, defined according to the WHO classification system, for the presence of EBV. All tumors were negative for B-cell antigens, including PAX-5/BSAP and CD20 or CD79a. The study group included 27 (42%) anaplastic lymphoma kinase (ALK)-positive (18 T-cell and 9 null-cell) and 37 (58%) ALK-negative (30 T-cell and 7 null-cell) tumors analyzed by in situ hybridization for EBV-encoded RNA (EBER) or immunohistochemistry for EBV-latent membrane protein type 1. All 64 cases were negative for EBV. We conclude, based on the current definition of ALCL in the WHO classification, there is no role for EBV in ALCL arising in Western patients. We suggest that published reports of EBV in a small proportion of ALCL cases in Western patients can be explained by the inclusion of tumors no longer considered to be in the current classification of ALCL, such as CD30-positive anaplastic tumors of B-cell origin.