title: Early stage of Epstein-Barr virus lytic infection leading to the "starry sky" pattern formation in endemic Burkitt lymphoma.
abstract: BACKGROUND
  Burkitt lymphoma (BL) is histologically characterized by a "starry sky" appearance, representing scattered macrophages that have phagocytosed cell debris among proliferating lymphoma cells. As is well known, almost all the neoplastic cells of endemic BL are infected with Epstein-Barr virus (EBV). Previous studies have indicated that most of the EBV in B cells is latent, and few virus particles enter the lytic cycle.
  
  
  OBJECTIVE
  To examine the histologic relationship between EBV infection stages and the formation of the starry sky pattern in African endemic BL tissues.
  
  
  METHODS
  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 lymphoma cells within and around the lacunae in starry sky figures. 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.
authors.affiliation: Division of Oral Pathology and Bone Metabolism, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. fujishu@net.nagasaki-u.ac.jp
authors.forename: Shuichi
authors.initials: S
authors.lastname: Fujita
authors.forename: Nathan
authors.initials: N
authors.lastname: Buziba
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumatori
authors.forename: Masachika
authors.initials: M
authors.lastname: Senba
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Kan
authors.initials: K
authors.lastname: Toriyama
mesh_terms: D000293:Adolescent; D000328:Adult; D002051:Burkitt Lymphoma / Q000175:diagnosis / Q000473:pathology* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000473:pathology* / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D008297:Male; D012367:RNA, Viral / Q000032:analysis; D014764:Viral Proteins / Q000032:analysis; D017735:Virus Latency
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins