Detection of Epstein-Barr viral RNA in malignant lymphomas of the upper aerodigestive tract

Am J Surg Pathol. 1994 Sep;18(9):938-46. doi: 10.1097/00000478-199409000-00009.


Recent studies have suggested a probable etiologic association between Epstein-Barr virus (EBV) and nasal lymphomas, irrespective of geographic location. This study was performed to investigate the strength of association of EBV with non-Hodgkin's lymphomas of the upper aerodigestive tract, based on a large series of cases that have been thoroughly immunophenotyped on frozen tissues. A sensitive in situ hybridization technique was used to detect EBV encoded RNA (EBER) in paraffin sections. Among 30 cases of nasal/nasopharyngeal T-cell lymphoma, 25 (83.3%) were EBER-positive. In the positive cases, most of the neoplastic cells showed strong nuclear signals. Further analysis of this group of tumors showed that all 21 cases (100%) with a CD56+ CD3-phenotype were EBER positive, whereas four of nine cases (44.4%) with a CD56-negative immunophenotype were positive. Only one of 10 cases (10%) of nasal/nasopharyngeal B-cell lymphoma was EBER positive; the positive case was a diffuse mixed-cell lymphoma and could not be distinguished morphologically from the negative cases. Among the 21 cases of lymphoma of the tonsils and back of the tongue (20 B-lineage and one T-lineage), none was EBER positive. In the normal mucosa of the nose/nasopharynx or tonsil (20 cases studied), only very rare EBER-positive small lymphocytes were found in two cases. The almost exclusive detection of EBER in nasal/nasopharyngeal T-cell neoplasms among the lymphomas of the upper aerodigestive tract suggests that EBV probably plays an etiologic role in the pathogenesis of this group of tumors and is not simply a passenger virus, and neither is this merely a site-dependent phenomenon in view of the weak association with nasal/nasopharyngeal B-cell lymphoma.

Publication types

  • Review

MeSH terms

  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Lymphoma / microbiology*
  • Lymphoma / pathology
  • Nasopharyngeal Neoplasms / microbiology*
  • Nasopharyngeal Neoplasms / pathology
  • Nose Neoplasms / microbiology*
  • Nose Neoplasms / pathology
  • RNA, Viral / analysis*
  • RNA-Binding Proteins / genetics
  • Ribosomal Proteins*
  • Tonsillar Neoplasms / microbiology*
  • Tonsillar Neoplasms / pathology


  • RNA, Viral
  • RNA-Binding Proteins
  • Ribosomal Proteins
  • RPL22 protein, human