自然殺傷/T細胞淋巴瘤的生物學行為和臨床及診斷研究進展_《華西醫學》

作者：

王雪梅 ¹ , 程佳漢 ² ,  徐才剛 ¹

四川大學（成都，610041） 1華西醫院血液科血液病研究室 2生命科學院生物系;

關鍵詞：

淋巴瘤自然殺傷/T細胞 EB病毒病理診斷

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自然殺傷（NK）/T細胞淋巴瘤（NKTCL）作為非霍奇金淋巴瘤（NHL）的獨立類型，在亞洲、拉丁美洲地區發病率明顯高于西方國家。其發病與EB病毒（EBV）感染關系密切，而遺傳因素、農藥、化學溶劑等與其發病有一定相關性。病理組織學上以血管中心和多形淋巴網狀內皮細胞的破壞性浸潤為特征，表達T或NK細胞抗原，以及T細胞內抗原-1、粒酶B、穿孔素等細胞毒顆粒相關蛋白，組織標本中絕大部分EBV編碼的小分子RNA檢測陽性。臨床上以中軸區受累為多見，早期病變常局限，進展期則呈侵襲性生長、少數可發生遠處轉移。目前診斷主要依靠組織標本的病理學檢查，CD2+、CD3ε+及CD56+可作為診斷該腫瘤較特異的免疫組織化學標記；同時，EBV相關成分及白介素-9、白介素-10和γ-干擾素等相關細胞因子和蛋白的檢出對診斷具有積極幫助，卟啉鈣黏蛋白15則可望成為診斷NK細胞來源腫瘤的新的重要標記。近年來，影像學檢查、尤其18氟標記脫氧葡萄糖正電子發射型計算機斷層掃描顯像儀對診斷的價值更加受到重視，有利于與B細胞來源淋巴瘤鑒別，并對NKTCL的分期及預后判斷有一定價值。

引用本文： 王雪梅,程佳漢,徐才剛. 自然殺傷/T細胞淋巴瘤的生物學行為和臨床及診斷研究進展. 華西醫學, 2012, 27(3): 455-458. doi: 復制

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, 劉翠苓, 黃欣, 等. 中國人淋巴瘤不同病理學類型的分布特點分析. 第十一屆中國抗癌協會全國淋巴瘤學術大會教育論文集[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.	馮沿芬, 吳秋良, 宗永生. 鼻腔鼻竇非霍奇金淋巴瘤免疫表型及其與EB病毒感染的關系[J]. 癌癥, 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.	唐瓊蘭, 劉衛平, 李甘地, 等. 西南地區鼻和鼻型NK/T細胞淋巴瘤的臨床病理特征及預后分析[J]. 腫瘤, 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.	周小鴿. EB病毒小RNA檢測的臨床病理學意義[J]. 中華病理學雜志, 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.	農琳, 張爽, 李陽, 等. C型凝集素樣自然殺傷(NK)細胞受體在結外鼻型NK/T細胞淋巴瘤中表達及意義[J]. 中華病理學雜志, 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.	馬林峰, 樊衛. 淋巴瘤病灶對18F-FDG攝取與不同病理亞型的關系[J]. 癌癥, 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, 劉翠苓, 黃欣, 等. 中國人淋巴瘤不同病理學類型的分布特點分析. 第十一屆中國抗癌協會全國淋巴瘤學術大會教育論文集[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. 　馮沿芬, 吳秋良, 宗永生. 鼻腔鼻竇非霍奇金淋巴瘤免疫表型及其與EB病毒感染的關系[J]. 癌癥, 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. 　唐瓊蘭, 劉衛平, 李甘地, 等. 西南地區鼻和鼻型NK/T細胞淋巴瘤的臨床病理特征及預后分析[J]. 腫瘤, 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. 　周小鴿. EB病毒小RNA檢測的臨床病理學意義[J]. 中華病理學雜志, 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. 　農琳, 張爽, 李陽, 等. C型凝集素樣自然殺傷(NK)細胞受體在結外鼻型NK/T細胞淋巴瘤中表達及意義[J]. 中華病理學雜志, 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. 　馬林峰, 樊衛. 淋巴瘤病灶對18F-FDG攝取與不同病理亞型的關系[J]. 癌癥, 2009, 28(4): 425-430.

《華西醫學》

自然殺傷/T細胞淋巴瘤的生物學行為和臨床及診斷研究進展

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《華西醫學》

自然殺傷/T細胞淋巴瘤的生物學行為和臨床及診斷研究進展

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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