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• W2010121114 abstract "Immunocompromised patients have an increased incidence of developing primary neoplasms, including lymphomas, skin cancers, and other carcinomas. However, mesenchymal neoplasms are uncommon in these patients. Recently, Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) have been increasingly recognized in these patients, mainly in organ transplant recipients and acquired immunodeficiency syndrome (AIDS) patients (1, 2). These tumors have a strong association with Epstein-Barr virus (EBV) infection and different clinicopathologic features from those of conventional smooth muscle tumors occurring in immunocompetent patients (3). EBV-SMT are rare and occur mostly in renal transplant recipients (0.7%) (1). Moreover, only three cases of EBV-SMT occurring after hematopoietic stem cell transplantation (HSCT) have been reported and all of them were pediatric cases (1, 4, 5). We herein describe the first adult case of EBV-SMT after HSCT that was concomitant with another malignant tumor. A 60-year-old female patient presented to our hospital with generalized fatigue in 2011. She had been diagnosed with acute lymphoblastic leukemia in 2003 and undergone unrelated allogeneic bone marrow transplantation during her second complete remission in 2009. She had been receiving immunosuppressive therapy with tacrolimus, prednisolone, and mycophenolate mofetil for severe graft-versus-host disease (GVHD) for about 2 years. Computed tomography (CT) scans revealed multiple masses in the liver, endometrial thickening, and nodules in the peritoneum (Fig. 1). Percutaneous needle biopsies of the liver were performed. A microscopic examination showed relatively small spindle-shaped neoplastic cells with a high nuclear-cytoplasmic ratio, irregular nuclei, and perivascular infiltration. Immuno histochemically, the neoplastic cells exhibited positivity for α-smooth muscle actin, h-caldesmon, and EBV nuclear antigen (EBNA) 2 (Fig. 2), but the stainings for CD21, CD34, desmin, and S100-protein were all negative (data not shown). The tumor cells also showed nuclear positivity for in situ hybridization for EBV-encoded RNA 1 (EBER-1) transcripts (Fig. 2). Intratumoral lymphocytic infiltration was not conspicuous; however, scattered CD3+CD79a− T lymphocytes were seen (data not shown). In the patient’s whole blood, the level of EBV DNA was slightly elevated (47 copies/mL). Based on these findings, a diagnosis of hepatic EBV-SMT was made. Subsequent biopsies of the uterine endometrium and peritoneum were performed, and pathological examination revealed that these were serous adenocarcinoma. To recover her immunity, the tacrolimus and mycophenolate mofetil were discontinued, and the prednisolone dosage was tapered. Three months later, a CT scan showed partial regression of the lesions in the liver. Five months after the initial diagnosis of EBV-SMT, she died of carcinomatous peritonitis. Because an autopsy was not performed, it was not clear whether EBV-SMT involved the other lesions besides liver.FIGURE 1: An abdominal CT scan showed tumors in the liver (A), the endometrium (B), and the peritoneum (C). Pathological findings resulted in EBV-SMT of the liver and serous adenocarcinoma of the endometrium and peritoneum.FIGURE 2: The histological features of the EBV-SMT. A, a liver biopsy showed relatively small spindle-shaped cells with a high nuclear-cytoplasmic ratio and irregular nuclei (H&E stain). Immunohistochemical staining showed that the neoplastic cells were positive for α-smooth muscle actin (B), h-caldesmon (C), and EBNA2 (D). The tumor cells were positive for EBER-1 (E).Although EBV-SMT tend to exclusively occur in immunocompromised patients, EBV-SMT occurring after HSCT are extremely rare (1, 4, 5). EBV-SMT have been reported to develop at a later stage after transplantation than EBV-associated posttransplant lymphoproliferative disorders, suggesting that prolonged immunosuppression is requisite for the development (1). In our case, the long-term and combined immunosuppressive therapy probably had a major impact on the development of EBV-SMT. Deyrup et al. showed that multiple lesions of EBV-SMT are the result of multiple EBV infection events, rather than metastasis (3). Although our patient had tumors at multiple sites, these histological findings revealed concomitant EBV-SMT and serous adenocarcinoma. Because long-term immunosuppression and GVHD are risk factors for also secondary malignancies, biopsies of multiple sites should be performed not to miss the concomitant other neoplasms in patients receiving long-term immunosuppressive therapy. EBV-SMT express α-smooth muscle actin and h-caldesmon, while the desmin expression is inconsistent (2, 3, 6). EBER-1 positivity allows the distinction of EBV-SMT from other conventional smooth muscle tumors (3, 7). CD21, the EBV receptor expressed on B lymphocytes, is frequently positive in AIDS-associated EBV-SMT, but usually negative in posttransplant EBV-SMT (1), suggesting a different mechanism of EBV entry between the two clinical entities. In posttransplant EBV-SMT, EBV may enter into smooth muscle cells via CD21-independent mechanisms, which may reflect the tropism of EBV for epithelial cells (8). Recent studies have suggested an association between EBV-SMT and the activation of the Akt/mammalian target of rapamycin (mTOR) signal pathway (9, 10). However, in our case, the expression of phosphorylated (p)-Akt was focally positive and p-mTOR was negative (data not shown). In conclusion, with the increasing number of individuals on long-term immunosuppression, EBV-SMT may be encountered more frequently in the future. EBV-SMT should be included in the differential diagnoses of a mesenchymal tumor in immunocompromised patients, even patients after HSCT. Furthermore, if the patients have multiple lesions, we recommend performing biopsies from multiple sites not to miss the concomitant other neoplasms. Eiko Hayase 1 Katsuya Fujimoto1 Tomoko Mitsuhashi2 Yutaka Hatanaka2 Miho Yoshida1 Ryo Takemura1 Junko Iwasaki1 Souichi Shiratori1 Junichi Sugita1 Takeshi Kondo1 Junji Tanaka1 Masahiro Imamura3 Yoshihiro Matsuno2 Takanori Teshima1 1 Department of Hematology Hokkaido University Graduate School of Medicine Hokkaido, Japan 2 Department of Surgical Pathology Hokkaido University Hospital Hokkaido, Japan 3 Department of Hematology Sapporo Hokuyu Hospital Hokkaido, Japan" @default.
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• W2010121114 date "2014-01-15" @default.
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• W2010121114 title "Epstein-Barr Virus-Associated Smooth Muscle Tumors After Bone Marrow Transplantation" @default.
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