Diagnostic application of Epstein-Barr virus-encoded RNA in situ hybridisation

Pathology. 2004 Aug;36(4):301-8. doi: 10.1080/0031302042000224584.


Aims: Epstein-Barr virus (EBV) has been implicated in the pathogenesis of nasopharyngeal carcinoma and a range of proliferative lymphoid conditions. In situ hybridisation (ISH) looking for virus-encoded RNA (EBER) transcripts is performed simply using a commercially available probe. We aimed to examine the application of this test in a routine diagnostic setting.

Methods: In total, 26 cases in which EBV ISH was requested for diagnostic purposes were examined. We looked at the indication for testing, the result and its implication for the final diagnosis.

Results: Cases were classified into three categories: possible nasopharyngeal carcinoma; possible EBV-related lymphoma; and possible immunodeficiency-associated lymphoproliferative disorder. Six of nine cases of possible nasopharyngeal carcinoma were EBV ISH positive (3/3 primary and 3/6 secondary), confirming the diagnosis. Three of 14 possible lymphoma cases were EBV ISH positive which, along with appropriate ancillary tests, assisted in making the diagnoses of Burkitt's lymphoma, lymphomatoid granulomatosis and extranodal NK/T-cell lymphoma of nasal type. All of three immunodeficiency-associated cases were EBV ISH positive. Two of these were post-transplant lymphoproliferative disorders, monomorphic type. The third case was classified as HIV-related polymorphic lymphoproliferative disorder.

Conclusions: In our experience, EBV ISH is a straightforward and rapid procedure to perform, giving unequivocal results. Used in the appropriate clinicopathological setting it can be a highly useful ancillary diagnostic aid.

MeSH terms

  • Aged
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / diagnosis*
  • Epstein-Barr Virus Nuclear Antigens / analysis
  • Female
  • Herpesvirus 4, Human / genetics*
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • In Situ Hybridization*
  • Lymphoproliferative Disorders / diagnosis
  • Lymphoproliferative Disorders / virology
  • Male
  • Middle Aged
  • Nasopharyngeal Neoplasms / diagnosis
  • Nasopharyngeal Neoplasms / virology
  • Polymerase Chain Reaction
  • RNA, Viral*
  • Sensitivity and Specificity


  • Epstein-Barr Virus Nuclear Antigens
  • RNA, Viral