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

自然殺傷（NK）/T細(xì)胞淋巴瘤（NKTCL）作為非霍奇金淋巴瘤（NHL）的獨(dú)立類型，在亞洲、拉丁美洲地區(qū)發(fā)病率明顯高于西方國(guó)家。其發(fā)病與EB病毒（EBV）感染關(guān)系密切，而遺傳因素、農(nóng)藥、化學(xué)溶劑等與其發(fā)病有一定相關(guān)性。病理組織學(xué)上以血管中心和多形淋巴網(wǎng)狀內(nèi)皮細(xì)胞的破壞性浸潤(rùn)為特征，表達(dá)T或NK細(xì)胞抗原，以及T細(xì)胞內(nèi)抗原-1、粒酶B、穿孔素等細(xì)胞毒顆粒相關(guān)蛋白，組織標(biāo)本中絕大部分EBV編碼的小分子RNA檢測(cè)陽(yáng)性。臨床上以中軸區(qū)受累為多見(jiàn)，早期病變常局限，進(jìn)展期則呈侵襲性生長(zhǎng)、少數(shù)可發(fā)生遠(yuǎn)處轉(zhuǎn)移。目前診斷主要依靠組織標(biāo)本的病理學(xué)檢查，CD2+、CD3ε+及CD56+可作為診斷該腫瘤較特異的免疫組織化學(xué)標(biāo)記；同時(shí)，EBV相關(guān)成分及白介素-9、白介素-10和γ-干擾素等相關(guān)細(xì)胞因子和蛋白的檢出對(duì)診斷具有積極幫助，卟啉鈣黏蛋白15則可望成為診斷NK細(xì)胞來(lái)源腫瘤的新的重要標(biāo)記。近年來(lái)，影像學(xué)檢查、尤其18氟標(biāo)記脫氧葡萄糖正電子發(fā)射型計(jì)算機(jī)斷層掃描顯像儀對(duì)診斷的價(jià)值更加受到重視，有利于與B細(xì)胞來(lái)源淋巴瘤鑒別，并對(duì)NKTCL的分期及預(yù)后判斷有一定價(jià)值。

引用本文： 王雪梅,程佳漢,徐才剛. 自然殺傷/T細(xì)胞淋巴瘤的生物學(xué)行為和臨床及診斷研究進(jìn)展. 華西醫(yī)學(xué), 2012, 27(3): 455-458. doi: 復(fù)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(guó)人淋巴瘤不同病理學(xué)類型的分布特點(diǎn)分析. 第十一屆中國(guó)抗癌協(xié)會(huì)全國(guó)淋巴瘤學(xué)術(shù)大會(huì)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(guān)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(wèi)平, 李甘地, 等. 西南地區(qū)鼻和鼻型NK/T細(xì)胞淋巴瘤的臨床病理特征及預(yù)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(cè)的臨床病理學(xué)意義[J]. 中華病理學(xué)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(nóng)琳, 張爽, 李陽(yáng), 等. C型凝集素樣自然殺傷(NK)細(xì)胞受體在結(jié)外鼻型NK/T細(xì)胞淋巴瘤中表達(dá)及意義[J]. 中華病理學(xué)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(wèi). 淋巴瘤病灶對(duì)18F-FDG攝取與不同病理亞型的關(guān)系[J]. 癌癥, 2009, 28(4): 425-430.
  1. 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. 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. 3. 　李敏, 劉翠苓, 黃欣, 等. 中國(guó)人淋巴瘤不同病理學(xué)類型的分布特點(diǎn)分析. 第十一屆中國(guó)抗癌協(xié)會(huì)全國(guó)淋巴瘤學(xué)術(shù)大會(huì)教育論文集[C]. 2009: 455-456.
  4. 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. 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(guān)系[J]. 癌癥, 2007, 26(11): 1170-1176.
  6. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 17. 　唐瓊蘭, 劉衛(wèi)平, 李甘地, 等. 西南地區(qū)鼻和鼻型NK/T細(xì)胞淋巴瘤的臨床病理特征及預(yù)后分析[J]. 腫瘤, 2003, 23(5): 411-413.
  18. 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. 19. 　Kwong YL. Natural killer-cell malignancies: diagnosis and treatment[J]. Leukemia, 2005, 19(12): 2186-2194.
  20. 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. 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. 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. 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. 24. 　Ianka GE. Hemophagocytic syndromes[J]. Blood Rev, 2007, 21(5): 245-253.
  25. 25. 　周小鴿. EB病毒小RNA檢測(cè)的臨床病理學(xué)意義[J]. 中華病理學(xué)雜志, 2006, 35(6): 321-323.
  26. 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. 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. 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. 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. 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. 31. 　農(nóng)琳, 張爽, 李陽(yáng), 等. C型凝集素樣自然殺傷(NK)細(xì)胞受體在結(jié)外鼻型NK/T細(xì)胞淋巴瘤中表達(dá)及意義[J]. 中華病理學(xué)雜志, 2010, 39(5): 319-324.
  32. 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. 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. 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. 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. 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. 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. 38. 　馬林峰, 樊衛(wèi). 淋巴瘤病灶對(duì)18F-FDG攝取與不同病理亞型的關(guān)系[J]. 癌癥, 2009, 28(4): 425-430.