Posttransplant Epstein-Barr virus-associated myogenic tumors involving bone

Abstract

BACKGROUND Epstein–Barr virus (EBV)–associated myogenic tumors in immunocompromised patients were recently recognized, but their biologic behavior remains only partially understood. Although observations so far have permitted the recognition of similarities between posttransplant myogenic tumors and posttransplant lymphoproliferative disorders (PTLD), the number of reports are still few, and new experiences continue to be informative. METHODS The authors describe what they believe is the first example of posttransplant EBV‐associated myogenic tumor involving bone, which is also remarkable for its multicentric symmetric limb distribution. Immunohistochemistry of tumor cells for myogenic antigens (desmin and smooth muscle actin), EBV antigens (latency proteins latent membrane protein‐1 [LMP‐1], Epstein–Barr nuclear antigen‐2 [EBNA‐2], and ZEBRA), p53, and bcl‐2 was examined by standard avidin‐biotin‐peroxidase complex methods. Molecular techniques investigated in situ hybridization for Epstein–Barr virus–encoded messenger RNAs (EBERs) and single‐strand conformation polymorphism analysis for p53 mutation. RESULTS Although the biologic behavior of this tumor was uncertain, the reduction of immunosuppression arrested tumor growth for 5 years, at the expense of some loss in renal function. The occurrence of episodes of acute cellular rejection required pulse therapy, resulting in the appearance of new lesions in both liver and lungs. Despite these complications, a balance between control of this multicentric tumor growth and allograft survival has been maintained for 8 years. CONCLUSIONS To the authors' knowledge, this example of posttransplant myogenic tumor is the first described in the bone. It shows partial response to immunomodulation with persistent tumor, with prolonged survival of the renal allograft. Cancer 2000;89:467–72. © 2000 American Cancer Society.

Expression of EBV Latent Antigens, Mammalian Target of Rapamycin, and Tumor Suppression Genes in EBV-Positive Smooth Muscle Tumors: Clinical and Therapeutic Implications

“…Although we acknowledge the lack of consistency in the expression of EBNAs and LMPs in all EBV+SMT tumors, this is likely due to the inadequate sensitivity of our assay rather than artifactual findings. Indeed, LMP1 was also undetected in previous studies, raising the possibility that the amount of LMP1 expressed is below the threshold of detection (14,16,18). Our findings of a type III latency pattern are further supported by the consistent activation of Cp and in some cases, Wp promoters.…”

“…It is plausible that tapering of immunosuppression may slow down EBV+SMT tumor kinetics by improving immunity (15,16). Because of historically reported poor response to chemotherapy in EBV+ SMT, we did not treat any of our patients with cytotoxic chemotherapy (14,15).…”

Molecular and Clinicopathological Analysis of Epstein-Barr Virus–Associated Posttransplant Smooth Muscle Tumors

“…The femaleto-male ratio was 1:1.2 (no statistical significance) (2-41). The majority of PTSMT developed after kidney transplantation (n = 38/68, 60%) (2,4,6,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) and the site of tumor manifestation was mainly the liver/transplant liver (n = 38/68, 56%) (2,(5)(6)(7)10,11,15,(17)(18)(19)(20)(21)24,25,(27)(28)(29)(30)(31)(33)(34)(35)(36)38,41). PTSMT occurred in a total of 11 transplant Liver (n = 10/68, 15%) Heart (n = 9/68, 13%) Lung (n = 4/68, 6%) Heart + lung (n = 1/68, 2%) Bone marrow (n = 3/68, 4%)…”

“…Other therapies-without surgery-were reduced immunosuppression (n = 8/45, 18%) (4,9,22,24,27,29,36,40), chemotherapy (n = 2/45, 4%) (17,30) and palliative radiation of a cerebral PTSMT (n = 1/45, 2%; patient died after 2 months) (23). In four cases (9%) (5,6,18,34), no specific therapy had been performed, including one patient with multiple PTSMT and 60 months survival (6).…”

“…Remarkably, the main site of tumor manifestation was the liver and the transplant liver (2,(5)(6)(7)10,11,15,(17)(18)(19)(20)(21)24,25,(27)(28)(29)(30)(31)(33)(34)(35)(36)38,41). Other solid grafts were less frequently affected; kidney transplants in particular rarely developed PTSMT, although kidneys were the most frequently transplanted organ in all patients with subsequent PTSMT (2,4,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). We could demonstrate that the tumor cells originate from the donor in hepatic PTSMT (#1).…”