New developments in the pathology of malignant lymphoma. A review of the literature published from September–August 2017

As I wrote in the editorial in this issue [1], it is rare to see single-authored original articles in the medical literature, but in this review, there is an exception. I.J. Miller retrieved 46 cases of Epstein Bar virus (EBV) positive lymphomas from the archives of his laboratory and looked carefully at the distribution of EBV early RNA (EBER)positive cells [2]. I imagine that he or she was reviewing a case and wondered what it means that the number of EBER-positive neoplastic cells is so variable. It is a question that was commonly asked to me at “meet the professor” sessions or by residents and my answer was often that it might be technical, but that I really do not know. I never took the step to look into this issue a bit deeper and am happy that Miller did. Of the 46 cases, 7 had nonuniform staining among the neoplastic cells. Four of those cases showed a uniform admixture of EBER+ and EBER− cells, compatible with the prevailing theory of episomal EBV loss with cell replication. However, three cases showed a partial and zonal pattern which suggests that EBV infection occurred after the lymphoma was already established. In case 1, an EBV-follicular lymphoma (FL) and an EBV+ diffuse large B cell lymphoma (DLBCL) of activated B cell type (ABC) were contiguous in a lymph node. Both components showed a BCL2 translocation by fluorescence in situ hybridization (FISH). In case 2, a DLBCL of germinal center type (GCB) in an human immunodeficiency virus (HIV) positive patient contained clusters of EBER+ lymphoma cells with the morphology of Reed-Sternberg (RS) cells. In case 3, an ulcerated and perforated DLBCL in the stomach there was a superficial swath of EBER+ neoplastic cells accompanied by a relative absence of reactive T cells. In all 3 cases, the cells in EBER+ areas expressed latent membrane protein-1 and were strongly positive for CD30. Miller concluded that these three cases suggest that in a subset of EBV+ DLBCLs, EBV infection may not be the “first hit.” A nice piece of work, which indeed can be done by a single person. Nevertheless, it is my experience that discussion on data improve the quality of the research, so I welcome multi-authored articles!