Cystic Smooth-muscle Tumor of the Liver and Spleen Associated with Epstein-Barr Virus after Renal Transplantation

Abstract

Immunosuppression is known to favor the development of various types of tumors. After organ transplantation, the risk of lymphoproliferative disease, whether clonal or not, is particularly increased and clearly associated with Epstein-Barr virus infection. We report a case of an unusual large cystic tumor of the liver with satellite hepatic and splenic nodules occurring 4 years after renal transplantation. Radiologic examination showed a rich vascularization of the tumor. Light and electron microscopy of a surgical liver biopsy, completed by an immunohistochemical study, demonstrated a well-differentiated tumor of smooth-muscle origin. Using in situ hybridization, we showed large amounts of Epstein-Barr virus messenger RNAs within the tumor cells. In addition, Southern blot analysis revealed that viral DNA was present in the form of a single monoclonal episome within the tumor. The polymerase chain reaction analysis of the genomic DNA of tumoral cells also indicated a monoclonal pattern. At last, the tumor was shown to be of host origin. Six months later, and despite three courses of chemotherapy, the tumoral lesions were unchanged. This case underlines the role of Epstein-Barr virus infection in the development of unusual and clonal smooth-muscle tumors after organ transplantation. The evolution of these rare tumors is uncertain.

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

“…As could be expected from the known risk profiles of PTLD (1), most of these patients were children and the PTLD manifested significantly earlier than the PTSMT. PTSMT with associated PTLD manifest predominantly in kidney transplant patients (2,4,6,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), and although, PTSMT generally developed later in kidney transplanted patients, the specific type of graft was not associated with incidence of PTSMT. In contrast, PTSMT manifest more often in adults, but earlier in younger patients.…”

“…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%)…”

“…Including our own five patients and data from 40 other case reports (2)(3)(4)(5)(7)(8)(9)(10)(11)(12)14,(17)(18)(19)(21)(22)(23)(26)(27)(28)(29)31,(34)(35)(36)(37)(38)40), we could analyze the morphological details. More than 50% of PTSMT were smaller than 5 cm (median diameter of unifocal tumor or the largest multifocal tumor 4 cm, range 0.8-15 cm).…”

“…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).…”