Epstein-Barr virus (EBV)-associated
smooth muscle tumors following solid
organ transplantation are extremely rare, with only 12 cases reported in the literature thus far. The exact pathogenetic role of
EBV infection in the
oncogenesis of these soft tissue
tumors in immunodeficient patients and the
biologic behavior of such
tumors is still unclear. We report a 26-year-old man in whom multiple
smooth muscle tumors developed 36 to 51 months after
heart transplantation. All
tumors, two synchronous liver nodules, two subsequently occurring paravertebral
tumors, and a single
tumor in a vein at the left ankle were surgically resected. The
tumor tissue was processed for routine histology and immunohistochemical (IHC) stains. Additionally, competitive polymerase-chain-reaction (PCR),
reverse-transcriptase PCR (RT-PCR), as well as in situ hybridization (ISH) were used for EBV particle quantification and gene transcription analysis. The histologic features and immunohistochemical profiles were consistent with
leiomyosarcoma in all
tumor nodules.
EBV infection was detected in >95% of
tumor cell nuclei by EBER 1/2 ISH. Competitive PCR revealed 3105 EBV particles per milligram of
tumor tissue. The EBV gene expression pattern analyzed by RT-PCR and IHC corresponded to the latency type III with specific expression of EBNA1, EBNA2, LMP1, and LMP2A genes. Under continuous
antiviral therapy (famcyclovir) the patient currently shows no evidence of disease. Our data indicate that
EBV infection plays a causal role in the development of
smooth muscle tumors following
organ transplantation. A latency type III, identical to EBV-associated posttransplant
lymphoproliferative disorders, was identified and suggests a common pathogenetic mechanism in the development of these histogenetically distinct
neoplasms. The fact that the patient currently shows no evidence of disease may be the result of the continuous administration of
antiviral therapy because the soft tissue recurrences of the
leiomyosarcoma occurred while the patient was not receiving
antiviral prophylaxis.