Kingma D W, Shad A, Tsokos M, Fest T, Otsuki T, Frekko K, Werner E, Werner A, Magrath I, Raffeld M, Jaffe E S
Hematopathology Section, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892, USA.
Am J Surg Pathol. 1996 Dec;20(12):1511-9. doi: 10.1097/00000478-199612000-00011.
The association of Epstein-Barr virus (EBV) with smooth-muscle tumors was recently reported in the setting of acquired immunodeficiency syndrome (AIDS) and post-transplantation. We report a case of an EBV-associated smooth-muscle tumor arising in a post-transplant (PT) patient who previously was treated successfully for two EBV-associated PT large-cell lymphomas. A 4-year-old girl required cardiac transplantation for dilated cardiomyopathy when she was aged 23 months. Her PT regimen included cyclosporine, azothiaprine, and diltiazem. At 16 months PT, she presented with anemia, guaiac-positive stools, and an abdominal mass diagnosed as diffuse large-cell lymphoma of B-cell phenotype. Immunosuppressive therapy was reduced, and interferon and i.v. immunoglobulin were initiated. She rapidly developed signs of rejection, and a cardiac biopsy was performed, revealing grade IIIB rejection. Subsequently, immunosuppressive therapy increased. At 23 months PT, a biopsy was done of a large pelvic mass that was diagnosed as immunoblastic large-cell lymphoma. After treatment with chemotherapy and retinoic acid, the size of the mass markedly decreased. Follow-up computed tomography scan revealed multiple liver nodules. A needle biopsy of the liver showed a smooth-muscle tumor of indeterminate grade. Both the lymphomas and the smooth-muscle tumor contained EBV within > 95% of tumor cells by Epstein-Barr (EBER1) in situ hybridization, were of strain type A by Epstein-Barr nuclear antigen-2 (EBNA-2) polymerase chain reaction (PCR) and contained an identical 30 base-pair deletion (amino acids 346-355) of the latent membrane protein (LMP)-1 oncogene by PCR analysis. Notably, the initial large-cell lymphoma and the subsequent immunoblastic lymphoma each contained a unique p53 mutation, suggesting that they were distinct. These data suggest that the same virus contributed to the pathogenesis of both the malignant lymphomas and the smooth-muscle tumor.
爱泼斯坦-巴尔病毒（EBV）与平滑肌肿瘤的关联最近在获得性免疫缺陷综合征（AIDS）及移植后情况下有相关报道。我们报告了1例移植后（PT）患者发生的EBV相关平滑肌肿瘤病例，该患者此前曾成功治疗过2例EBV相关的PT大细胞淋巴瘤。一名4岁女孩在23个月大时因扩张型心肌病接受心脏移植。她的PT治疗方案包括环孢素、硫唑嘌呤和地尔硫䓬。移植后16个月，她出现贫血、粪便隐血阳性及腹部肿块，诊断为B细胞表型的弥漫性大细胞淋巴瘤。免疫抑制治疗减量，并开始使用干扰素和静脉注射免疫球蛋白。她很快出现排斥反应迹象，遂进行心脏活检，显示为IIIB级排斥反应。随后，免疫抑制治疗增加。移植后23个月，对一个大的盆腔肿块进行活检，诊断为免疫母细胞性大细胞淋巴瘤。经化疗和维甲酸治疗后，肿块大小明显缩小。后续的计算机断层扫描显示肝脏有多个结节。肝脏穿刺活检显示为分级不明的平滑肌肿瘤。通过爱泼斯坦-巴尔（EBER1）原位杂交，淋巴瘤和平滑肌肿瘤中超过95%的肿瘤细胞内均含有EBV；通过爱泼斯坦-巴尔核抗原-2（EBNA-2）聚合酶链反应（PCR）检测为A株型；通过PCR分析，两者的潜伏膜蛋白（LMP）-1癌基因均有相同的30个碱基对缺失（氨基酸346 - 355）。值得注意的是，最初的大细胞淋巴瘤和随后的免疫母细胞淋巴瘤各自含有独特的p53突变，提示它们是不同的。这些数据表明，同一病毒促成了恶性淋巴瘤和平滑肌肿瘤的发病机制。
