title: Epstein-Barr virus (EBV)-associated smooth-muscle tumor arising in a post-transplant patient treated successfully for two PT-EBV-associated large-cell lymphomas. Case report.
abstract: The association of Epstein-Barr virus (EBV) with smooth-muscle tumors was recently reported in the setting of acquired immunodeficiency syndrome (AIDS) and post-transplantation. We report a case of an EBV-associated smooth-muscle tumor arising in a post-transplant (PT) patient who previously was treated successfully for two EBV-associated PT large-cell lymphomas. A 4-year-old girl required cardiac transplantation for dilated cardiomyopathy when she was aged 23 months. Her PT regimen included cyclosporine, azothiaprine, and diltiazem. At 16 months PT, she presented with anemia, guaiac-positive stools, and an abdominal mass diagnosed as diffuse large-cell lymphoma of B-cell phenotype. Immunosuppressive therapy was reduced, and interferon and i.v. immunoglobulin were initiated. She rapidly developed signs of rejection, and a cardiac biopsy was performed, revealing grade IIIB rejection. Subsequently, immunosuppressive therapy increased. At 23 months PT, a biopsy was done of a large pelvic mass that was diagnosed as immunoblastic large-cell lymphoma. After treatment with chemotherapy and retinoic acid, the size of the mass markedly decreased. Follow-up computed tomography scan revealed multiple liver nodules. A needle biopsy of the liver showed a smooth-muscle tumor of indeterminate grade. Both the lymphomas and the smooth-muscle tumor contained EBV within > 95% of tumor cells by Epstein-Barr (EBER1) in situ hybridization, were of strain type A by Epstein-Barr nuclear antigen-2 (EBNA-2) polymerase chain reaction (PCR) and contained an identical 30 base-pair deletion (amino acids 346-355) of the latent membrane protein (LMP)-1 oncogene by PCR analysis. Notably, the initial large-cell lymphoma and the subsequent immunoblastic lymphoma each contained a unique p53 mutation, suggesting that they were distinct. These data suggest that the same virus contributed to the pathogenesis of both the malignant lymphomas and the smooth-muscle tumor.
authors.affiliation: Hematopathology Section, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Kingma
authors.forename: A
authors.initials: A
authors.lastname: Shad
authors.forename: M
authors.initials: M
authors.lastname: Tsokos
authors.forename: T
authors.initials: T
authors.lastname: Fest
authors.forename: T
authors.initials: T
authors.lastname: Otsuki
authors.forename: K
authors.initials: K
authors.lastname: Frekko
authors.forename: E
authors.initials: E
authors.lastname: Werner
authors.forename: A
authors.initials: A
authors.lastname: Werner
authors.forename: I
authors.initials: I
authors.lastname: Magrath
authors.forename: M
authors.initials: M
authors.lastname: Raffeld
authors.forename: E S
authors.initials: ES
authors.lastname: Jaffe
mesh_terms: D000008:Abdominal Neoplasms / Q000473:pathology / Q000821:virology*; D002675:Child, Preschool; D004279:DNA, Viral / Q000737:chemistry; D005260:Female; D015321:Gene Rearrangement; D016027:Heart Transplantation; D006566:Herpesviridae Infections / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008113:Liver Neoplasms / Q000821:virology; D016393:Lymphoma, B-Cell / Q000473:pathology / Q000821:virology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology / Q000821:virology*; D009379:Neoplasms, Muscle Tissue / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000821:virology; D014412:Tumor Virus Infections / Q000821:virology*
chemical_list: D004279:DNA, Viral; D007166:Immunosuppressive Agents