自然杀伤/T细胞淋巴瘤的生物学行为和临床及诊断研究进展_West China Medical Journal

Authors：

王雪梅 ¹ , 程佳汉 ² ,  徐才刚 ¹

Corresponding author：

徐才刚, Email: wangxm1205@163.com

Keywords：

淋巴瘤; 自然杀伤/T细胞; EB病毒; 病理; 诊断

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自然杀伤（NK）/T细胞淋巴瘤（NKTCL）作为非霍奇金淋巴瘤（NHL）的独立类型，在亚洲、拉丁美洲地区发病率明显高于西方国家。其发病与EB病毒（EBV）感染关系密切，而遗传因素、农药、化学溶剂等与其发病有一定相关性。病理组织学上以血管中心和多形淋巴网状内皮细胞的破坏性浸润为特征，表达T或NK细胞抗原，以及T细胞内抗原-1、粒酶B、穿孔素等细胞毒颗粒相关蛋白，组织标本中绝大部分EBV编码的小分子RNA检测阳性。临床上以中轴区受累为多见，早期病变常局限，进展期则呈侵袭性生长、少数可发生远处转移。目前诊断主要依靠组织标本的病理学检查，CD2+、CD3ε+及CD56+可作为诊断该肿瘤较特异的免疫组织化学标记；同时，EBV相关成分及白介素-9、白介素-10和γ-干扰素等相关细胞因子和蛋白的检出对诊断具有积极帮助，卟啉钙黏蛋白15则可望成为诊断NK细胞来源肿瘤的新的重要标记。近年来，影像学检查、尤其18氟标记脱氧葡萄糖正电子发射型计算机断层扫描显像仪对诊断的价值更加受到重视，有利于与B细胞来源淋巴瘤鉴别，并对NKTCL的分期及预后判断有一定价值。

Citation： 王雪梅,程佳汉,徐才刚. 自然杀伤/T细胞淋巴瘤的生物学行为和临床及诊断研究进展. West China Medical Journal, 2012, 27(3): 455-458. doi: Copy

1.	Aoki R, Karube K, Sugita Y, et al. Distribution of malignant lymphoma in Japan: analysis of 2260 cases, 2001-2006[J]. Pathol Int, 2008, 58(3): 174-182.
2.	Ko YH, Kim CW, Park CS, et al. REAL classi?cation of malignant lymphomas in the republic of Korea[J]. Cancer, 2008, 83(4): 806-812.
3.	李敏, 刘翠苓, 黄欣, 等. 中国人淋巴瘤不同病理学类型的分布特点分析. 第十一届中国抗癌协会全国淋巴瘤学术大会教育论文集[C]. 2009: 455-456.
4.	Aozasa K, Takakuwa T, Hongyo T, et al. Nasal NK/T-cell lymphoma: epidemiology and pathogenesis[J]. Int J Hematol, 2008, 87(2): 110-117.
5.	冯沿芬, 吴秋良, 宗永生. 鼻腔鼻窦非霍奇金淋巴瘤免疫表型及其与EB病毒感染的关系[J]. 癌症, 2007, 26(11): 1170-1176.
6.	Assaf C, Gellrich S, Whittaker S, et al. CD 56-positive haematological neoplasms of the skin: a multicentre study of the cutaneous lymphoma project group of the European organisation for research and treatment of cancer[J]. Clin Pathol, 2007, 60(9): 981-989.
7.	Mitarnun W, Suwiwat S, Pradutkanchana J. Epstein-Barr virus-associated extranodal non-Hodgkin’s lymphoma of the sinonasal tract and nasopharynxin Thailand[J]. Asian Pac J Cancer Prev, 2006, 7(1): 91-94.
8.	Liu A, Nakatsuka S, Yang WI, et al. Expression of cell adhesion molecules and chemokine receptors: angioinvasiveness in nasal NK/T cell lymphoma[J]. Oncol Rep, 2005, 13(4): 613-620.
9.	Kuo TT, Shih LY, Tsang NM. Nasal NK/T cell lymphoma in Taiwan: a clinicopathologic study of 22 cases, with analysis of histologic subtypes, Epstein-Barr virus LMP-1 gene association, and treatment modalities[J]. Int J Surg Pathol, 2004, 12(4): 375-387 .
10.	Ramakrishnan R, Donahue H, Garcia1 D, et al. Epstein-Barr virus BART9 miRNA modulates LMP1 levels and affects growth rate of nasal NK T cell lymphomas[J]. PLoS ONE, 2011, 6(11): e27271.
11.	Asada H, Saito-Katsuragi M, Niizeki H. Mosquito salivary gland extracts induce EBV-infected NK cell oncogenesis via CD4+ T cells in patients with hypersensitivity to mosquito bites[J]. J Invest Dermatol, 2005, 125(5): 956-961.
12.	Chiu BCH, Dave BJ, Blair A, et al. Agricultural pesticide use and risk of t(14;18)-defined subtypes of non-Hodgkin lymphoma[J]. Blood, 2006, 108(4): 1363-1369.
13.	Aozasa K, Takakuwa T, Hongyo T, et al. Nasal NK/T-cell lymphoma: epidemiology and pathogenesis [J]. Int J Hematol, 2008, 87(2): 110-117.
14.	Ng SB, Selvarajan V, Huang G, et al. Activated oncogenic pathways and therapeutic targets in extranodal nasal-type NK/T-cell lymphoma revealed by gene expression profiling[J]. J Pathol, 2010, 223(4): 496-510.
15.	Bossard C, Belhadj K, Reyes F, et al. Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d’Etude des Lymphomes de l’Adulte (GELA) trials[J]. Blood, 2007, 109(5): 2183-2189.
16.	HuangY, Reynies A, Leval L, et al. Gene expression profiling identifies emerging oncogenic pathways in extranodal NK/T-cell lymphoma, nasal type[J]. Blood, 2010, 115(6): 1226-1237.
17.	唐琼兰, 刘卫平, 李甘地, 等. 西南地区鼻和鼻型NK/T细胞淋巴瘤的临床病理特征及预后分析[J]. 肿瘤, 2003, 23(5): 411-413.
18.	Pongpruttipan T, Kummalue T, Bedavanija A, et al. Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter study from Thailand[J]. Diagn Pathol, 2011, 6(1): 79-90.
19.	Kwong YL. Natural killer-cell malignancies: diagnosis and treatment[J]. Leukemia, 2005, 19(12): 2186-2194.
20.	Li YX, Fang H, Liu QF, et al. Clinical features and treatment outcome of nasal-type NK/T-cell lymphoma of Waldeyer ring[J]. Blood, 2008, 112(8): 3057-3064.
21.	Li YX, Liu QF, Fang H, et al. Variable Clinical Presentations of Nasal and Waldeyer Ring Natural Killer/T-Cell Lymphoma[J]. Clin Cancer Res, 2009, 15(8): 2905-2912.
22.	Kitazawa Y, Saito F, Nomura S, et al. A case of hemophagocytic lymphohistiocytosis after the primary Epstein-Barr virus infection[J]. Clin Appl Thromb Hemost, 2007, 13(3): 323-328.
23.	Imashuku S, Kuriyama K, Sakai R, et al. Treatment of Epstein-Barr virus associated hemophagocytic lymphohistiocytosis ( EBV-HLH) in young adults: a report from the HLH study center[J]. Med Pediatr Oncol, 2003, 41(2): 103-109.
24.	Ianka GE. Hemophagocytic syndromes[J]. Blood Rev, 2007, 21(5): 245-253.
25.	周小鸽. EB病毒小RNA检测的临床病理学意义[J]. 中华病理学杂志, 2006, 35(6): 321-323.
26.	Kwong YL, Anderson BO, Adwani R, et al. Management of T-cell and natural-killer-cell neoplasms in Asia: consensus statement from the Asian Oncology Summit 2009[J]. Lancet Oncol, 2009, 10(11): 1093-1101.
27.	Ishii H, Ogino T, Berger C, et al. Clinical usefulness of serum EBV DNA levels of BamHI W and LMP1 for nasal NK/T-cell lymphoma[J]. J Med Virol, 2007, 79(5): 562-572.
28.	Harabuchi Y, Takahara M, Kishibe K, et al. Nasal natural killer (NK)/T-cell lymphoma: clinical, histological, virological and genetic features[J]. Int J Clin Oncol, 2009, 14(3): 181-190.
29.	Nagato T, Kobayashi H, Kishibe K, et al. Expression of Interleukin-9 in Nasal Natural Killer/T-Cell Lymphoma Cell Lines and Patients[J]. Clin Cancer Res, 2005, 11(23): 8250-8257.
30.	Quermalet VR, Giustiniani J, Cardine AM, et al. Protocadherin 15 (PCDH15): a new secreted isoform and a potential marker for NK/T cell lymphomas[J]. Oncogene, 2006, 25(19): 2807-2811.
31.	农琳, 张爽, 李阳, 等. C型凝集素样自然杀伤(NK)细胞受体在结外鼻型NK/T细胞淋巴瘤中表达及意义[J]. 中华病理学杂志, 2010, 39(5): 319-324.
32.	Kim J, Kim EY, Lee SK, et al. Extranodal nasal-type NK/T-cell lymphoma: computed tomography findings of head and neck involvement[J]. Acta Radiol, 2010, 51(2): 164-169.
33.	Ou CH, Chen CCC, Ling JC, et al. Nasal NK/T-cell lymphoma: computed tomography and magnetic resonance imaging findings[J]. J Chin Med Assoc, 2007, 70(5): 207-212.
34.	Karantanis D, Subramaniam RM, Peller PJ, et al. The value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in extranodal natural killer/T-cell lymphoma[J]. Clin Lymphoma Myeloma, 2008,8(2): 94-99.
35.	Kako1 S, Izutsu1 K, Ota Y, et al. FDG-PET in T-cell and NK-cell neoplasms[J]. Ann Oncol, 2007, 18(10): 1685-1690.
36.	Chan WKS, Au WY, Wong CYO, et al. Metabolic activity measured by 18F FDG PET in natural killer-cell lymphoma compared to aggressive B-and T-cell lymphomas[J]. Clin Nuclear Med, 2010, 35(8): 571-575.
37.	Tsukamoto N, Kojima M, Hasegawa M, et al. The usefulness of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and a comparison of 18F-FDG-PET with 67gallium scintigraphy in the evaluation of lymphoma[J]. Am Cancer Societ, 2007, 110(3): 652-659.
38.	马林峰, 樊卫. 淋巴瘤病灶对18F-FDG摄取与不同病理亚型的关系[J]. 癌症, 2009, 28(4): 425-430.

1. 　Aoki R, Karube K, Sugita Y, et al. Distribution of malignant lymphoma in Japan: analysis of 2260 cases, 2001-2006[J]. Pathol Int, 2008, 58(3): 174-182.
2. 　Ko YH, Kim CW, Park CS, et al. REAL classi?cation of malignant lymphomas in the republic of Korea[J]. Cancer, 2008, 83(4): 806-812.
3. 　李敏, 刘翠苓, 黄欣, 等. 中国人淋巴瘤不同病理学类型的分布特点分析. 第十一届中国抗癌协会全国淋巴瘤学术大会教育论文集[C]. 2009: 455-456.
4. 　Aozasa K, Takakuwa T, Hongyo T, et al. Nasal NK/T-cell lymphoma: epidemiology and pathogenesis[J]. Int J Hematol, 2008, 87(2): 110-117.
5. 　冯沿芬, 吴秋良, 宗永生. 鼻腔鼻窦非霍奇金淋巴瘤免疫表型及其与EB病毒感染的关系[J]. 癌症, 2007, 26(11): 1170-1176.
6. 　Assaf C, Gellrich S, Whittaker S, et al. CD 56-positive haematological neoplasms of the skin: a multicentre study of the cutaneous lymphoma project group of the European organisation for research and treatment of cancer[J]. Clin Pathol, 2007, 60(9): 981-989.
7. 　Mitarnun W, Suwiwat S, Pradutkanchana J. Epstein-Barr virus-associated extranodal non-Hodgkin’s lymphoma of the sinonasal tract and nasopharynxin Thailand[J]. Asian Pac J Cancer Prev, 2006, 7(1): 91-94.
8. 　Liu A, Nakatsuka S, Yang WI, et al. Expression of cell adhesion molecules and chemokine receptors: angioinvasiveness in nasal NK/T cell lymphoma[J]. Oncol Rep, 2005, 13(4): 613-620.
9. 　Kuo TT, Shih LY, Tsang NM. Nasal NK/T cell lymphoma in Taiwan: a clinicopathologic study of 22 cases, with analysis of histologic subtypes, Epstein-Barr virus LMP-1 gene association, and treatment modalities[J]. Int J Surg Pathol, 2004, 12(4): 375-387 .
10. 　Ramakrishnan R, Donahue H, Garcia1 D, et al. Epstein-Barr virus BART9 miRNA modulates LMP1 levels and affects growth rate of nasal NK T cell lymphomas[J]. PLoS ONE, 2011, 6(11): e27271.
11. 　Asada H, Saito-Katsuragi M, Niizeki H. Mosquito salivary gland extracts induce EBV-infected NK cell oncogenesis via CD4+ T cells in patients with hypersensitivity to mosquito bites[J]. J Invest Dermatol, 2005, 125(5): 956-961.
12. 　Chiu BCH, Dave BJ, Blair A, et al. Agricultural pesticide use and risk of t(14;18)-defined subtypes of non-Hodgkin lymphoma[J]. Blood, 2006, 108(4): 1363-1369.
13. 　Aozasa K, Takakuwa T, Hongyo T, et al. Nasal NK/T-cell lymphoma: epidemiology and pathogenesis [J]. Int J Hematol, 2008, 87(2): 110-117.
14. 　Ng SB, Selvarajan V, Huang G, et al. Activated oncogenic pathways and therapeutic targets in extranodal nasal-type NK/T-cell lymphoma revealed by gene expression profiling[J]. J Pathol, 2010, 223(4): 496-510.
15. 　Bossard C, Belhadj K, Reyes F, et al. Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d’Etude des Lymphomes de l’Adulte (GELA) trials[J]. Blood, 2007, 109(5): 2183-2189.
16. 　HuangY, Reynies A, Leval L, et al. Gene expression profiling identifies emerging oncogenic pathways in extranodal NK/T-cell lymphoma, nasal type[J]. Blood, 2010, 115(6): 1226-1237.
17. 　唐琼兰, 刘卫平, 李甘地, 等. 西南地区鼻和鼻型NK/T细胞淋巴瘤的临床病理特征及预后分析[J]. 肿瘤, 2003, 23(5): 411-413.
18. 　Pongpruttipan T, Kummalue T, Bedavanija A, et al. Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter study from Thailand[J]. Diagn Pathol, 2011, 6(1): 79-90.
19. 　Kwong YL. Natural killer-cell malignancies: diagnosis and treatment[J]. Leukemia, 2005, 19(12): 2186-2194.
20. 　Li YX, Fang H, Liu QF, et al. Clinical features and treatment outcome of nasal-type NK/T-cell lymphoma of Waldeyer ring[J]. Blood, 2008, 112(8): 3057-3064.
21. 　Li YX, Liu QF, Fang H, et al. Variable Clinical Presentations of Nasal and Waldeyer Ring Natural Killer/T-Cell Lymphoma[J]. Clin Cancer Res, 2009, 15(8): 2905-2912.
22. 　Kitazawa Y, Saito F, Nomura S, et al. A case of hemophagocytic lymphohistiocytosis after the primary Epstein-Barr virus infection[J]. Clin Appl Thromb Hemost, 2007, 13(3): 323-328.
23. 　Imashuku S, Kuriyama K, Sakai R, et al. Treatment of Epstein-Barr virus associated hemophagocytic lymphohistiocytosis ( EBV-HLH) in young adults: a report from the HLH study center[J]. Med Pediatr Oncol, 2003, 41(2): 103-109.
24. 　Ianka GE. Hemophagocytic syndromes[J]. Blood Rev, 2007, 21(5): 245-253.
25. 　周小鸽. EB病毒小RNA检测的临床病理学意义[J]. 中华病理学杂志, 2006, 35(6): 321-323.
26. 　Kwong YL, Anderson BO, Adwani R, et al. Management of T-cell and natural-killer-cell neoplasms in Asia: consensus statement from the Asian Oncology Summit 2009[J]. Lancet Oncol, 2009, 10(11): 1093-1101.
27. 　Ishii H, Ogino T, Berger C, et al. Clinical usefulness of serum EBV DNA levels of BamHI W and LMP1 for nasal NK/T-cell lymphoma[J]. J Med Virol, 2007, 79(5): 562-572.
28. 　Harabuchi Y, Takahara M, Kishibe K, et al. Nasal natural killer (NK)/T-cell lymphoma: clinical, histological, virological and genetic features[J]. Int J Clin Oncol, 2009, 14(3): 181-190.
29. 　Nagato T, Kobayashi H, Kishibe K, et al. Expression of Interleukin-9 in Nasal Natural Killer/T-Cell Lymphoma Cell Lines and Patients[J]. Clin Cancer Res, 2005, 11(23): 8250-8257.
30. 　Quermalet VR, Giustiniani J, Cardine AM, et al. Protocadherin 15 (PCDH15): a new secreted isoform and a potential marker for NK/T cell lymphomas[J]. Oncogene, 2006, 25(19): 2807-2811.
31. 　农琳, 张爽, 李阳, 等. C型凝集素样自然杀伤(NK)细胞受体在结外鼻型NK/T细胞淋巴瘤中表达及意义[J]. 中华病理学杂志, 2010, 39(5): 319-324.
32. 　Kim J, Kim EY, Lee SK, et al. Extranodal nasal-type NK/T-cell lymphoma: computed tomography findings of head and neck involvement[J]. Acta Radiol, 2010, 51(2): 164-169.
33. 　Ou CH, Chen CCC, Ling JC, et al. Nasal NK/T-cell lymphoma: computed tomography and magnetic resonance imaging findings[J]. J Chin Med Assoc, 2007, 70(5): 207-212.
34. 　Karantanis D, Subramaniam RM, Peller PJ, et al. The value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in extranodal natural killer/T-cell lymphoma[J]. Clin Lymphoma Myeloma, 2008,8(2): 94-99.
35. 　Kako1 S, Izutsu1 K, Ota Y, et al. FDG-PET in T-cell and NK-cell neoplasms[J]. Ann Oncol, 2007, 18(10): 1685-1690.
36. 　Chan WKS, Au WY, Wong CYO, et al. Metabolic activity measured by 18F FDG PET in natural killer-cell lymphoma compared to aggressive B-and T-cell lymphomas[J]. Clin Nuclear Med, 2010, 35(8): 571-575.
37. 　Tsukamoto N, Kojima M, Hasegawa M, et al. The usefulness of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and a comparison of 18F-FDG-PET with 67gallium scintigraphy in the evaluation of lymphoma[J]. Am Cancer Societ, 2007, 110(3): 652-659.
38. 　马林峰, 樊卫. 淋巴瘤病灶对18F-FDG摄取与不同病理亚型的关系[J]. 癌症, 2009, 28(4): 425-430.

West China Medical Journal

自然杀伤/T细胞淋巴瘤的生物学行为和临床及诊断研究进展

Abstract Full text Figures/Tables Video References Cited by

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