Epstein-Barr virus-associated multicentric leiomyosarcoma in an adult patient after heart transplantation - Case report and review of the literature

Epstein-Barr virus (EBV)-associated smooth muscle tumors following solid or gan transplantation are extremely rare, with only 12 cases reported in the literature thus far. The exact pathogenetic role of EBV infection in the on cogenesis of these soft tissue tumors in immunodeficient patients and the b iologic behavior of such tumors is still unclear. We report a 26-year-old m an in whom multiple smooth muscle tumors developed 36 to 51 months after he art transplantation. All tumors, two synchronous liver nodules, two subsequ ently occurring paravertebral tumors. and a single tumor in a vein at the l eft ankle were surgically resected. The tumor tissue was processed for rout ine histology and immunohistochemical (IHC) stains. Additionally, competiti ve polymerase-chain-reaction (PCR), reverse-transcriptase PCR (RT-PCR), as well as in situ hybridization (ISH) were used for EBV particle quantificati on and gene transcription analysis. The histologic features and immunohisto chemical profiles were consistent with leiomyosarcoma in all tumor nodules. EBV infection was detected in >95% of tumor cell nuclei by EBER 1/2 ISH. C ompetitive PCR revealed 3105 EBV particles per milligram of tumor tissue. T he EBV gene expression pattern analyzed by RT-PCR and IHC corresponded to t he latency type III with specific expression of EBNA1, EBNA2, LMP1, and LMP 2A genes. Under continuous antiviral therapy (famcyclovir) the patient curr ently shows no evidence of disease. Our data indicate that EBV infection pl ays a causal role in the development of smooth muscle tumors following orga n transplantation. A latency type III, identical to EBV-associated posttran splant lymphoproliferative disorders, was identified and suggests a common pathogenetic mechanism in the development of these histogenetically distinc t neoplasms. The fact that the patient currently shows no evidence of disea se may be the result of the continuous administration of antiviral therapy because the soft tissue recurrences of the leiomyosarcoma occurred while th e patient was nor receiving antiviral prophylaxis.