儿童系统性EB病毒阳性T细胞淋巴组织增殖性疾病临床病理分析

目的 探讨儿童系统性EB病毒阳性T细胞淋巴组织增殖性疾病(CSEBV+T-LPD)的临床病理特征及免疫表型.方法 通过免疫组织化学、原位杂交、基因重排技术,分析11例CSEBV+T-LPD患者临床病理特征,并进行随访.结果 临床特征:男性5例,女性6例,中位年龄13岁(3~19岁),中位病程6个月(3~25个月).其中4例诊断为淋巴瘤,男女各2例,中位年龄15岁,中位病程4.5个月.11例患者主要症状有反复持续发热(10例)、多发淋巴结肿大(10例)、脾大(7例)、肝大(4例).组织病理学特征:4例淋巴瘤患者表现为淋巴细胞片状或弥漫性增生,细胞体积中等偏大,增生细胞较单一;7例良性病变者增生细胞较混杂,增生淋巴细胞散在其中,体积中等偏大或大.免疫表型:全部患者增生细胞大多数为T细胞,均强弱不等地表达CD3ε.2例淋巴瘤患者、1例良性病变者中CD8单阳性,4例淋巴瘤患者、1例良性病变者有T细胞抗原丢失.全部患者EBV-EBER阳性.T细胞受体(TCR)基因检测:3例淋巴瘤患者、1例良性病变者检测到克隆性重排.病理分级:淋巴瘤患者均为A3级,良性病变者1例为A2级、6例为A1级.结论 CSEBV+T-LPD是一系列涵盖不同发展阶段的疾病谱,诊断需结合临床特征、病理形态、免疫表型、EBV-EBER原位杂交及TCR基因检测等综合分析.患者年龄偏大,增生细胞较单一、 弥漫或片状,CD8单阳性,T细胞抗原丢失尤其CD5、EBV-EBER高表达,TCR克隆性重排,病理分级为A3级等因素对于鉴别良、恶性病变可能有重要提示意义.

Clinicopathological analysis of systemic EB virus-positive T-cell lymphoproliferative disease in childhood

Objective To investigate the clinicopathological and immunophenotypic features of systemic EB virus (EBV)-positive T-cell lymphoproliferative disease of childhood (CSEBV+T-LPD). Methods The clinicopathological features of 11 patients with CSEBV + T-LPD were reviewed by using immunohistochemistry, fluorescence in situ hybridization, gene rearrangement method. The follow-up data were collected. Results Of the 11 patients, 5 cases were male and 6 cases were female. The median age was 13 years old (3-19 years old) and the disease course was 6 months (3-25 months). 2 male and 2 female patients were diagnosed with lymphoma. The median age was 15 years old, and the median disease course was 4.5 months. The major symptoms included continued fever (10/11), lymphadenectasis (10/11), splenomegaly (7/11), hepatomegaly (4/11). Histopathology: 4 cases of lymphoma showed lymphocyte flaky or diffuse hyperplasia, and cell volume was too large, isolated hyperplasia cells; 7 cases of benign lesions were mixed cells, and proliferation of lymphocytes were scattered with moderate big or much bigger volume. Immunophenotyping: all biopsies exhibited prominent T cell proliferation, as defined by immunohistochemical staining of CD3ε. 2 cases of CD8 single positive in 4 lymphoma patients, 1 case of CD8 single positive in 7 cases of benign lesions. T-cell antigen loss was detected in all the patients , while only 1 loss case was found in patients with benign lesions. All cases were positive for EBV-EBER. T-cell receptor (TCR) gene detection: 3 lymphoma patients with TCR gene cloning rearrangement, 1 case of benign lesions with cloned rearrangement . Pathology classification: 4 cases of lymphoma were A3 , 1 case of benign lesions was A2 , 6 cases of benign lesions were A1. Conclusions CSEBV+T-LPD comprises a wide spectrum of diseases. The diagnosis should combine with clinical features, pathological morphology, immune phenotype, EBV-EBER in situ hybridization and TCR gene detection. Furthermore, elderly patients, with single hyperplasia of cells, diffuse or flake, CD8 single positive, T cell antigen loss especially CD5, high expression of EBV-EBER, TCR clonal rearrangement, A3 pathological grading, may play a key role in differentiating benign and malignant lesions.