Early stage of epstein-Barr Virus Lytic infection leading to the ‘‘Starry Sky’’ Pattern formation in Endemic Burkitt Lymphoma

Abstract

Context.—Burkitt lymphoma (BL) is histologically char- acterized by a ‘‘starry sky’’ appearance, representing scat- tered macrophages that have phagocytosed cell debris among proliferating lymphoma cells. As is well known, al- most all the neoplastic cells of endemic BL are infected with Epstein-Barr virus (EBV). Previous studies have indi- cated that most of the EBV in B cells is latent, and few virus particles enter the lytic cycle.Objective.—To examine the histologic relationship be- tween EBV infection stages and the formation of the starry sky pattern in African endemic BL tissues.Design.—Tissue samples from 44 patients with African endemic BL were examined with immunohistochemistry and in situ hybridization. We used EBV-encoded small RNA (EBER) as a marker of latent infection, and BamHI H left frame 1 (BHLF1) and BamHI Z EBV replication activator (ZEBRA) as lytic cycle markers.Results.—In all cases, signals for EBER were found in most neoplastic lymphocytes, and in 73% of cases, signals for BHLF1 and/or ZEBRA were recognized in the lympho- ma cells within and around the lacunae in starry sky fig- ures. The mean number of lacunae per unit area in cases positive for lytic cycle markers was significantly higher than that in negative cases ( P , .001). Conclusions.—Our findings suggest that EBV-infected lymphoma cells in the lytic cycle, which eventually lapse into cell death, are phagocytosed prior to their rupture by macrophages that have migrated into the parenchyma. We emphasize that transition of EBV-infected lymphoma cells to the lytic cycle is one of the histomorphogenetic factors influencing the formation of starry sky pattern in endemic BL.