儿童系统性EB病毒阳性T细胞淋巴瘤临床病理分析一例及文献复习

doi:10.16150/j.1671-2870.2020.01.013

摘要/Abstract

摘要：

目的：探讨1例儿童系统性EB病毒（Epstein-Barr virus, EBV）阳性T细胞淋巴瘤的临床和病理特征,以加深医师对该病诊断及鉴别方法的认识。方法：综合分析1例儿童系统性EBV阳性T细胞淋巴瘤患者的临床表现、病理形态、免疫表型及基因检测结果,结合近年文献进行探讨。结果：患者为11岁男孩,表现为四肢及躯干皮疹4年余,以螨虫过敏治疗而迁延不愈。患儿近2个月反复发热,出现全身淋巴结肿大和噬血细胞综合征。淋巴结活检示小到中等大的淋巴样细胞弥漫增生;免疫组织化学检测显示,肿瘤细胞CD3（+++）、CD4（+）、TIA-1（+++）、颗粒酶B（+++）、MIB-1 （80%+）;EBV原位杂交示EBER（+++）;T细胞受体（T cell receptor, TCR）基因克隆性重排显示TCRγ克隆性重排。患儿病理诊断为儿童系统性EBV阳性T细胞淋巴瘤。结论：儿童系统性EBV阳性T细胞淋巴瘤是一种少见的EBV感染活化的细胞毒性T细胞克隆性增殖性疾病,临床病程呈暴发性、侵袭性,常伴有噬血细胞综合征,病理需要与侵袭性自然杀伤细胞白血病/淋巴瘤、EBV感染相关淋巴增生性病变及皮肤原发性γδT细胞淋巴瘤鉴别。

关键词: Epstein-Barr 病毒, 成熟T细胞淋巴瘤, 临床病理学, 免疫表型

Abstract:

Objective: To investigate the clinicopathological characteristics of systemic Epstein-Barr virus (EBV) positive T-cell lymphoma of childhood and improve the understanding of the new diagnostic criteria. Methods: Clinical presentations, pathological characteristics, gene detection results and immunohistochemical phenotyping of biopsy tissue from a case of systemic EBV positive T-cell lymphoma of childhood were analyzed and the relevant literature was reviewed. Result: The 11-year-old boy with prolonged mite allergy treatment and no responsive rash on limbs and torso presented recurrent high fever, generalized lymphadenopathy and hemophagocytic syndrome. Lymph node biopsy revealed diffuse proliferation of small to intermediate neoplastic T cells, which was possibly originated in interfollicular area and positive for CD3（+++）, CD4（+）, TIA-1（+++）, GranzymeB（+++） and MIB-1 (>80% positive). The in situ hybridization of EBV (EBER) was positive （+++） and clonal TCRγ gene rearrangemen was also detected. The diagnosis of systemic EBV positive T-cell lymphoma was thus established. Conclusions: Systemic EBV-positive T-cell lymphoma of childhood is a rare systemic illness characterized by clonal proliferation of EBV-infected T cells and aggressive and fulminant clinical course often associated with hemophagocytic syndrome, which requires differentiation with medical conditions such as invasive NK cells, leukemia/lymphoma, EBV infection associated lymphoproliferative lesions and primary cutaneous gamma-delta T-cell lymphoma.

Key words: Epstein-Barr virus, Mature T-cell lymphoma, Clinicopathology, Immunophenotypes

中图分类号:

R733

李芹芹, 金晓龙, 袁菲. 儿童系统性EB病毒阳性T细胞淋巴瘤临床病理分析一例及文献复习[J]. 诊断学理论与实践, 2020, 19(1): 63-68.

LI Qinqin, JIN Xiaolong, YUAN Fei. Clinical and pathological analysis of systemic Epstein-Barr virus positive T-cell lymphoma of childhood:A case report and literature review[J]. Journal of Diagnostics Concepts & Practice, 2020, 19(1): 63-68.

图/表 4

参考文献 19

[1]	Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms[J]. Blood,2016, 127(20):2375-2390. doi: 10.1182/blood-2016-01-643569 URL
[2]	Hong M, Ko YH, Yoo KH, et al. EBV-positive T/NK-cell lymphoproliferative disease of childhood[J]. Korean J Pathol, 2013, 47(2):137-147. doi: 10.4132/KoreanJPathol.2013.47.2.137 URL
[3]	周小鸽, 张燕林, 谢建兰, 等. 对 EB 病毒相关淋巴组织增殖性疾病的理解和认识对[J]. 中华病理学杂志, 2016, 45(12):817-821.
[4]	Virelizier JL, Lenoir G, Griscelli C. Persistent Epstein-Barr virus infection in a child with hypergammaglobulinaemia and immunoblastic proliferation associated with a selective defect in immune interferon secretion[J]. Lancet, 1978, 2(8083):231-234. pmid: 79029
[5]	Quintanilla-Martinez L, Kimura H, Jaffe ES, et al. EBV-positive T-cell lymphoproliferative disorders of childhood fM1[M]// Swerdlow S, Campo E, Harris NL, et al. World Health Organization classification of tumors. WHO classification of tumours of haematopoi eric and lymphoid tissues. France: IARC Press, 2008:278-280.
[6]	Sevilla DW, El-Mallawany NK, Emmons FN, et al. Spectrum of childhood Epstein-Barr virus-associated T-cell proliferations and bone marrow findings[J]. Pediatr Dev Pathol, 2011, 14(1):28-37. doi: 10.2350/09-12-0753-OA.1 URL
[7]	Rodríguez-Pinilla SM, Barrionuevo C, García J, et al. Epstein-Barr virus-positive systemic NK/T-cell lymphomas in children: report of six cases[J]. Histopathology, 2011, 59(6):1183-1193. doi: 10.1111/j.1365-2559.2011.04047.x pmid: 22175898
[8]	Xiao HJ, Li J, Song HM, et al. Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorders manifested as gastrointestinal perforations and skin lesions: A case report[J]. Medicine (Baltimore), 2016, 95(5):e2676. doi: 10.1097/MD.0000000000002676 URL
[9]	Kimura H, Hoshino Y, Kanegane H, et al. Clinical and virologic characteristics of chronic active Epstein-Barr virus infection[J]. Blood. 2001 Jul 15; 98(2):280-286. doi: 10.1182/blood.v98.2.280 pmid: 11435294
[10]	Kimura H, Morishima T, Kanegane H, et al. Prognostic factors for chronic active Epstein-Barr virus infection[J]. J Infect Dis, 2003, 187(4):527-533. doi: 10.1086/367988 URL
[11]	金妍, 周小鸽, 何乐健, 等. 儿童系统性EB病毒阳性T细胞淋巴组织增殖性疾病的临床病理观察[J]. 中华病理学杂志, 2009, 38(9):600-608.
[12]	Okano M, Kawa K, Kimura H, et al. Proposed guidelines for diagnosing chronic active Epstein-Barr virus infection[J]. Am J Hematol, 2005, 80(1):64-69. doi: 10.1002/ajh.20398 URL
[13]	王杰松, 杨瑜, 何鸿鸣, 等. P-Gemox方案与P-GDP方案治疗NK/T细胞淋巴瘤的疗效比较[J]. 安徽医学, 2018, 39(10):1202-1206
[14]	Kimura H, Ito Y, Kawabe S, et al. EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases[J]. Blood, 2012, 119(3):673-686. doi: 10.1182/blood-2011-10-381921 URL
[15]	王微, 遆红娟, 农琳, 等. 儿童系统性EB病毒阳性T细胞淋巴增殖性疾病临床病理学分析[J]. 北京大学学报:医学版, 2012, 44(4):594-598.
[16]	Leeborg N, Russell T, Fan G. Systemic Epstein-Barr virus positive T-cell lymphoproliferative disease of childhood[J]. Pathol Case Rev, 2012, 17:120-124. doi: 10.1097/PCR.0b013e318258eeba URL
[17]	Kimura H, Hoshino Y, Kanegane H, et al. Clinical and virologic characteristics of chronic active Epstein-Barr virus infection[J]. Blood, 2001, 98(2):280-286. doi: 10.1182/blood.v98.2.280 pmid: 11435294
[18]	Sato E, Ohga S, Kuroda H, et al. Allogeneic hematopoie-tic stem cell transplantation for Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disease in Japan[J]. Am J Hematol, 2008, 83(9):721-727. doi: 10.1002/ajh.21247 URL
[19]	Kawa K, Sawada A, Sato M, et al. Excellent outcome of allogeneic hematopoietic SCT with reduced-intensity conditioning for the treatment of chronic active EBV infection[J]. Bone Marrow Transplant, 2011, 46(1):77-83. doi: 10.1038/bmt.2010.122 URL