The association of Epstein-Barr virus with smooth-muscle tumors occurring after organ transplantation

N Engl J Med. 1995 Jan 5;332(1):19-25. doi: 10.1056/NEJM199501053320104.


Background: Epstein-Barr virus (EBV) has been associated with nasopharyngeal carcinoma, some lymphomas, and lymphoproliferative disease after organ transplantation. Many lymphoproliferative tumors that occur after transplantation are clonal, a property that classifies them as neoplastic. Clonality can be determined by analysis of the extrachromosomal circular DNA episomes produced by EBV infection.

Methods: We describe three young children in whom smooth-muscle tumors developed 18 months to 5 1/2 years after liver transplantation with immunosuppression. We examined the tumors by microscopy and with immunohistochemical studies and molecular genetic analyses of the EBV DNA:

Results: The tumors were composed of spindle cells with smooth-muscle features and resembled those described in patients with the acquired immunodeficiency syndrome. Immunohistochemical analysis was negative for EBV latent membrane protein and EBV receptor (CD21), but positive for EBV nuclear antigen 2. In situ hybridization revealed nuclear EBV sequences, and molecular genetic analysis showed the EBV genome to be clonal in all three patients.

Conclusions: Smooth-muscle tumors that developed after organ transplantation contained clonal EBV, suggesting that the virus has a role in the development of these neoplastic lesions.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / virology
  • DNA, Viral / isolation & purification
  • Fatal Outcome
  • Female
  • Herpesviridae Infections / diagnosis*
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Immunosuppression Therapy / adverse effects
  • Infant
  • Infant, Newborn
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Liver Transplantation*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / virology
  • Muscle, Smooth / pathology
  • Muscle, Smooth / virology*
  • Retroperitoneal Neoplasms / pathology
  • Retroperitoneal Neoplasms / virology
  • Tumor Virus Infections / diagnosis*


  • DNA, Viral