Early stage of Epstein-Barr virus lytic infection leading to the "starry sky" pattern formation in endemic Burkitt lymphoma

Arch Pathol Lab Med. 2004 May;128(5):549-52. doi: 10.5858/2004-128-549-ESOEVL.


Context: 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.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Burkitt Lymphoma / diagnosis
  • Burkitt Lymphoma / pathology*
  • Burkitt Lymphoma / virology
  • Child
  • Child, Preschool
  • Disease Progression
  • Epstein-Barr Virus Infections / pathology*
  • Epstein-Barr Virus Infections / virology
  • Female
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification
  • Herpesvirus 4, Human / physiology
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Infant
  • Male
  • RNA, Viral / analysis
  • Viral Proteins / analysis
  • Virus Latency


  • RNA, Viral
  • Viral Proteins