Review Article
Free Access
Extranodal NK/T-cell lymphoma: diagnosis and treatment cues
Ritsuro Suzuki,
Kengo Takeuchi,
Koichi Ohshima,
Shigeo Nakamura,
Corresponding Author
Ritsuro Suzuki
Department of HSCT Data Management, Nagoya University, School of Medicine, Nagoya, Japan
Department of HSCT Data Management, Nagoya University, School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-0047 Japan.Search for more papers by this authorKengo Takeuchi
Department of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, Japan
Search for more papers by this authorKoichi Ohshima
Department of Pathology, Kurume University, School of Medicine, Fukuoka, Japan
Search for more papers by this authorShigeo Nakamura
Department of Pathology, Nagoya University, School of Medicine, Nagoya, Japan
Search for more papers by this authorRitsuro Suzuki,
Kengo Takeuchi,
Koichi Ohshima,
Shigeo Nakamura,
Corresponding Author
Ritsuro Suzuki
Department of HSCT Data Management, Nagoya University, School of Medicine, Nagoya, Japan
Department of HSCT Data Management, Nagoya University, School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-0047 Japan.Search for more papers by this authorKengo Takeuchi
Department of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, Japan
Search for more papers by this authorKoichi Ohshima
Department of Pathology, Kurume University, School of Medicine, Fukuoka, Japan
Search for more papers by this authorShigeo Nakamura
Department of Pathology, Nagoya University, School of Medicine, Nagoya, Japan
Search for more papers by this authorAbstract
Extranodal NK/T-cell lymphoma, nasal type (ENKL) is mostly endemic to East Asia. It predominantly occurs in the nasal or paranasal areas and less frequently in the skin. Most of the tumours show NK-cell, but rarely T-cell, phenotypes. The Epstein–Barr virus (EBV) genome can be usually detected in lymphoma cells. Geographic localization of ENKL matches the endemic distribution of EBV, suggesting that EBV plays an important role in lymphomagenesis. Originally, NK-cell and T-cell types were believed to present the same clinicopathologic characteristics, but recent data suggest more aggressive characteristics for the NK-cell phenotype. Although ENKL is sensitive to radiotherapy, it shows a poorer response to chemotherapeutic agents than other lymphomas due to expression of p-glycoprotein. Therefore, new therapeutic approaches must be considered. Several new clinical trials are now being conducted in East Asia. Copyright © 2008 John Wiley & Sons, Ltd.
References
- 1 Chan JKC, Jaffe ES, Ralfkiaer E. Extranodal NK/T-cell lymphoma, nasal type. In World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, ES Jaffe, NL Harris, H Stein, JW Vardiman (eds). IARC Press: Lyon, France, 2001; 204–207.
- 2 Jaffe ES. Classification of natural killer (NK) cell and NK-like T-cell malignancies. Blood 1996; 87: 1207–1210.
- 3 Oshimi K. Leukemia and lymphoma of natural killer lineage cells. Int J Hematol 2003; 78: 18–23.
- 4 Lymphoma Study Group of Japanese Pathologists. The World Health Organization classification of malignant lymphomas in Japan: incidence of recently recognized entities. Pathol Int 2000; 50: 696–702.
- 5 Chen CY, Yao M, Tang JL, et al. Chromosomal abnormalities of 200 Chinese patients with non-Hodgkin's lymphoma in Taiwan: with special reference to T-cell lymphoma. Ann Oncol 2004; 15: 1091–1096.
- 6 Au WY, Ma SY, Chim CS, et al. Clinicopathologic features and treatment outcome of mature T-cell and natural killer cell lymphomas diagnosed according to the World Health Organization classification scheme: a single center experience of ten years. Ann Oncol 2005; 16: 206–214.
- 7
Ko YH,
Kim CW,
Park CS, et al.
REAL classification of malignant lymphomas in the Republic of Korea: incidence of recently recognized entities and changes in clinicopathologic features.
Cancer
1998;
83:
806–812.
10.1002/(SICI)1097-0142(19980815)83:4<806::AID-CNCR26>3.0.CO;2-V CAS PubMed Web of Science® Google Scholar
- 8 Hercend T, Schmidt RE. Characteristics and uses of natural killer cells. Immunol Today 1998; 9: 291–293.
- 9 Robertson MJ, Ritz J. Biology and clinical relevance of human natural killer cells. Blood 1990; 76: 2421–2438.
- 10 Sanchez MJ, Muench MO, Roncarolo MG, Lanier LL, Phillips JH. Identification of a common T/natural killer cell progenitor in human fetal thymus. J Exp Med 1994; 180: 569–576.
- 11 Shibuya A, Nagayoshi K, Nakamura K, Nakauchi H. Lymphokine requirement for the generation of natural killer cells from CD34+ hematopoietic progenitor cells. Blood 1995; 85: 3538–3546.
- 12
Ishii Y,
Yamanaka N,
Ogawa K, et al.
Nasal T-cell lymphoma as a type of so-called “lethal midline granuloma”.
Cancer
1982;
50:
2336–2344.
10.1002/1097-0142(19821201)50:11<2336::AID-CNCR2820501120>3.0.CO;2-C CAS PubMed Web of Science® Google Scholar
- 13 Chan JK, Ng CS, Lau WH, Lo ST. Most nasal/nasopharyngeal lymphomas are peripheral T-cell neoplasms. Am J Surg Pathol 1987; 11: 418–429.
- 14 Ng CS, Chan JK, Lo ST. Expression of natural killer cell markers in non-Hodgkin's lymphomas. Hum Pathol 1987; 18: 1257– 1262.
- 15 Suzuki R, Yamamoto K, Seto M, et al. CD7+ and CD56+ myeloid/natural killer cell precursor acute leukemia: A distinct hematolymphoid disease entity. Blood 1997; 90: 2417–2428.
- 16 Suzuki R, Murata M, Kami M, et al. Prognostic significance of CD7+ CD56+ phenotype and chromosome 5 abnormalities for acute myeloid leukemia M0. Int J Hematol 2003; 77: 482–489.
- 17 Suzuki R, Nakamura S. Malignancies of natural killer (NK) cell precursor: myeloid/NK cell precursor acute leukemia and blastic NK cell lymphoma/leukemia. Leuk Res 1999; 23: 615–624.
- 18 Suzuki R, Nakamura S, Suzumiya J, et al. Blastic natural killer cell lymphoma/leukemia (CD56-positive blastic tumor): prognostication and categorization according to anatomic sites of involvement. Cancer 2005; 104: 1022–1031.
- 19 Feuillard J, Jacob MC, Valensi F, et al. Clinical and biologic features of CD4+ CD56+ malignancies. Blood 2002; 99: 1556–1563.
- 20 Petrella T, Comeau MR, Maynadie M, et al. ‘Agranular CD4+ CD56+ hematodermic neoplasm’ (blastic NK-cell lymphoma) originates from a population of CD56+ precursor cells related to plasmacytoid monocytes. Am J Surg Pathol 2002; 26: 852–862.
- 21 Chan JKC, Wong KF, Jaffe ES, Ralfkiaer E. Aggressive NK-cell leukemia. In World Health Organization classification of tumors. Pathology and genetics of tumours of haematopoietic and lymphoid tissues, ES Jaffe, NL Harris, H Stein, JW Vardiman (eds). IARC Press: Lyon, France, 2001; 198–200.
- 22 Suzuki R, Suzumiya J, Nakamura S, et al. Aggressive natural killer (NK)-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells. Leukemia 2004; 18: 763–770.
- 23 Suzuki R, Suzumiya J, Nakamura S, Yamaguchi M, Kawa K, Oshimi K. Natural killer (NK)-cell neoplasms: aggressive NK-cell leukemia and extranodal NK-cell lymphoma, nasal type. Ann Oncol 2005; 16 (Suppl. 5): v129–v130 [Abstract # 315].
- 24 Liang R, Todd D, Chan TK, et al. Treatment outcome and prognostic factors for primary nasal lymphoma. J Clin Oncol 1995; 13: 666–670.
- 25 Emile J-F, Boulland M-L, Haioun C, et al. CD5- CD56+ T-cell receptor silent peripheral T-cell lymphomas are natural killer cell lymphomas. Blood 1996; 87: 1466–1473.
- 26 Nakamura S, Katoh E, Koshikawa T, et al. Clinicopathologic study of nasal T/NK-cell lymphoma among the Japanese. Pathol Int 1997; 47: 38–53.
- 27 Kwong YL, Chan ACL, Liang R, et al. CD56+ NK lymphomas: clinicopathological features and prognosis. Br J Haematol 1997; 97: 821–829.
- 28
Logsdon MD,
Ha CS,
Kavadi VS,
Cabanillas F,
Hess MA,
Cox JD.
Lymphoma of the nasal cavity and paranasal sinuses: improved outcome and altered prognostic factors with combined modality therapy.
Cancer
1997;
80:
477–488.
10.1002/(SICI)1097-0142(19970801)80:3<477::AID-CNCR16>3.0.CO;2-U CAS PubMed Web of Science® Google Scholar
- 29 Cheung MMC, Chan JK, Lau WH, et al. Primary non-Hodgkin's lymphoma of the nose and nasopharynx: clinical features, tumor immunophenotype, and treatment outcome in 113 patients. J Clin Oncol 1998; 16: 70–77.
- 30
Ko YH,
Ree HJ,
Kim WS,
Choi WH,
Moon WS,
Kim SW.
Clinicopathologic and genotypic study of extranodal nasal-type natural killer/T-cell lymphoma and natural killer precursor lymphoma among Koreans.
Cancer
2000;
89:
2106–2116.
10.1002/1097-0142(20001115)89:10<2106::AID-CNCR11>3.0.CO;2-G CAS PubMed Web of Science® Google Scholar
- 31 Li CC, Tien HF, Tang JL, et al. Treatment outcome and pattern of failure in 77 patients with sinonasal natural killer/T-cell or T-cell lymphoma. Cancer 2004; 100: 366–375.
- 32 Chim CS, Ma SY, Au WY, et al. Primary nasal natural killer cell lymphoma: long-term treatment outcome and relationship with the international prognostic index. Blood 2004; 103: 216–221.
- 33 You JY, Chi KH, Yang MH, et al. Radiation therapy versus chemotherapy as initial treatment for localized nasal natural killer (NK)/T-cell lymphoma: a single institute survey in Taiwan. Ann Oncol 2004; 15: 618–625.
- 34 Kim TM, Park YH, Lee SY, et al. Local tumor invasiveness is more predictive of survival than International Prognostic Index in stage IE/IIE extranodal NK/T-cell lymphoma, nasal type. Blood 2005; 106: 3785–3790.
- 35 Lee J, Suh C, Park YH, et al. Extranodal natural killer T-cell lymphoma, nasal-type: a prognostic model from a retrospective multicenter study. J Clin Oncol 2006; 24: 612–618.
- 36
Suzuki R.
Leukemia and lymphoma of natural killer cells.
J Clin Exp Hematop
2005;
45:
51–70.
10.3960/jslrt.45.51 Google Scholar
- 37 Ohshima K, Suzumiya J, Shimazaki K, et al. Nasal T/NK cell lymphomas commonly express perforin and Fas ligand: important mediators of tissue damage. Histopathology 1997; 31: 444–450.
- 38 Jaffe ES, Chan JKC, Su I-J, et al. Report of the workshop on nasal and related extranodal angiocentric T/natural killer cell lymphomas. definitions, differential diagnosis, and epidemiology. Am J Surg Pathol 1996; 20: 103–111.
- 39 Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994; 84: 1361–1392.
- 40 Wong KF, Chan JKC, Cheung MMC, So JC. Bone marrow involvement by nasal NK cell lymphoma at diagnosis is uncommon. Am J Clin Pathol 2001; 115: 266–270.
- 41 Lee J, Suh C, Huh J, et al. Effect of positive bone marrow EBV in situ hybridization in staging and survival of localized extranodal natural killer/T-cell lymphoma, nasal-type. Clin Cancer Res 2007; 13: 3250–3254.
- 42 Suzumiya J, Takeshita M, Kimura N, et al. Expression of adult and fetal natural killer cell markers in sinonasal lymphomas. Blood 1994; 83: 2255– 2260.
- 43 Yamaguchi M, Ohno T, Oka K, et al. Discordant reaction of Leu4 and rabbit anti-human CD3 epsilon in sinonasal ‘T’-cell lymphoma. Int J Hematol 1993; 59: 25–30.
- 44 Mori N, Yatabe Y, Oka K, et al. Expression of perforin in nasal lymphoma. Am J Pathol 1996; 149: 699–705.
- 45 Chan JKC, Tsang WY, Pau MY. Discordant CD3 expression in lymphomas when studied on frozen and paraffin sections. Hum Pathol 1995; 26: 1139–1143.
- 46 Kim GE, Koom WS, Yang WI, et al. Clinical relevance of three subtypes of primary sinonasal lymphoma characterized by immunophenotypic analysis. Head Neck 2004; 26: 584–593.
- 47 Seymour JF, Pierce SA, Kantarjian HM, Keating MI, Estey EH. Investigation of karyotypic, morphologic and clinical features in patients with acute myeloid leukemia blast cells expressing the neural cell adhesion molecule (CD56). Leukemia 1994; 8: 823–826.
- 48 Miller TP, Dahlberg S, Cassady JR, et al. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med 1998; 339: 21–26.
- 49 Kim WS, Song SY, Ahn YC, et al. CHOP followed by involved field radiation: is it optimal for localized nasal natural killer/T-cell lymphoma? Ann Oncol 2001; 12: 349–352.
- 50
Yamaguchi M,
Ogawa S,
Nomoto Y, et al.
Treatment outcome of nasal NK-cell lymphoma: a report of 12 consecutively-diagnosed cases and a review of the literature.
J Clin Exp Hematop
2001;
41:
93–99.
10.3960/jslrt.41.93 Google Scholar
- 51
Yamaguchi M,
Kita K,
Miwa H, et al.
Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells.
Cancer
1995;
76:
2351–2356.
10.1002/1097-0142(19951201)76:11<2351::AID-CNCR2820761125>3.0.CO;2-1 CAS PubMed Web of Science® Google Scholar
- 52 Egashira M, Kawamata N, Sugimoto K, Kaneko T, Oshimi K. P-glycoprotein expression on normal and abnormally expanded natural killer cells and inhibition of P-glycoprotein function by cyclosporin A and its analogue, P SC83. Blood 1999; 93: 599–606.
- 53 Kim GE, Cho JH, Yang WI, et al. Angiocentric lymphoma of the head and neck: patterns of systemic failure after radiation treatment. J Clin Oncol 2000; 18: 54–63.
- 54 Isobe K, Uno T, Tamaru J, et al. Extranodal natural killer/T-cell lymphoma, nasal type: the significance of radiotherapeutic parameters. Cancer 2006; 106: 609–615.
- 55 Ribrag V, Ell Hajj M, Janot F, et al. Early locoregional high-dose radiotherapy is associated with long-term disease control in localized primary angiocentric lymphoma of the nose and nasopharynx. Leukemia 2001; 15: 1123–1126.
- 56 Li YX, Yao B, Jin J, et al. Radiotherapy as primary treatment for stage IE and IIE nasal natural killer/T-cell lymphoma. J Clin Oncol 2006; 24: 181–189.
- 57 Aviles A, Neri N, Fernandez R, Calva A, Huerta-Guzman J, Nambo MJ. Nasal NK/T-cell lymphoma with disseminated disease treated with aggressive combined therapy. Med Oncol 2003; 20: 13–17.
- 58 Nagafuji K, Fujisaki T, Arima F, Ohshima K. L-asparaginase induced durable remission of relapsed nasal NK/T-cell lymphoma after autologous peripheral blood stem cell transplantation. Int J Hematol 2001; 74: 447–450.
- 59 Obama K, Tara M, Niina K. L-asparaginase-based induction therapy for advanced extranodal NK/T-cell lymphoma. Int J Hematol 2003; 78: 248–250.
- 60 Matsumoto Y, Nomura K, Kanda-Akano Y, et al. Successful treatment with Erwinia L-asparaginase for recurrent natural killer/T cell lymphoma. Leuk Lymphoma 2003; 44: 879–882.
- 61 Pinheiro JP, Boos J. The best way to use asparaginase in childhood acute lymphatic leukaemia–still to be defined? Br J Haematol 2004; 125: 117–127.
- 62 Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med 2006; 354: 166–178.
- 63 Yong W, Zheng W, Zhang Y, et al. L-asparaginase-based regimen in the treatment of refractory midline nasal/nasal-type T/NK-cell lymphoma. Int J Hematol 2003; 78: 163–167.
- 64 Yamaguchi M, Suzuki R, Kwong YL, et al. Phase I study of SMILE chemotherapy for advanced-stage or relapsed/refractory extranodal NK/T-cell lymphoma/leukemia. Cancer Sci 2008 (in press).
- 65 Au WY, Lie AK, Liang R, et al. Autologous stem cell transplantation for nasal NK/T-cell lymphoma: a progress report on its value. Ann Oncol 2003; 14: 1673–1676.
- 66 Suzuki R, Suzumiya J, Nakamura S, et al. Hematopoietic stem cell transplantation for natural killer-cell lineage neoplasms. Bone Marrow Transplant 2006; 37: 425–431.
- 67 Kim HJ, Bang SM, Lee J, et al. High-dose chemotherapy with autologous stem cell transplantation in extranodal NK/T-cell lymphoma: a retrospective comparison with non-transplantation cases. Bone Marrow Transplant 2006; 37: 819–824.
- 68 Murashige N, Kami M, Kishi Y, et al. Allogeneic haematopoietic stem cell transplantation as a promising treatment for natural killer-cell neoplasms. Br J Haematol 2005; 130: 561–567.
- 69 Harabuchi Y, Yamanaka N, Kataura A, et al. Epstein–Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma. Lancet 1990; 335: 128–130.
- 70 Chan JK, Yip TT, Tsang WY, et al. Detection of Epstein–Barr viral RNA in malignant lymphomas of the upper aerodigestive tract. Am J Surg Pathol 1994; 18: 938–946.
- 71 Chan KCA, Zhang J, Chan ATC, et al. Molecular characterization of circulating EBV DNA in the plasma of nasopharyngeal carcinoma and lymphoma patients. Cancer Res 2003; 63: 2028–2032.
- 72 Lei KIK, Chan LYS, Chan W-Y, Johnson PJ, Dennis Lo YM. Diagnostic and prognostic implications of circulating cell-free Epstein–Barr virus DNA in natural killer/T-cell lymphoma. Clin Cancer Res 2002; 8: 29–34.
- 73 Au WY, Pang A, Choy C, Chim CS, Kwong YL. Quantification of circulating Epstein–Barr virus (EBV) DNA in the diagnosis and monitoring of natural killer cell and EBV-positive lymphomas in immunocompetent patients. Blood 2004; 104: 243–249.
- 74 Stevens SJC, Pronk I, Middeldorp JM. Toward standardization of Epstein–Barr virus DNA load monitoring: unfractionated whole blood as preferred clinical specimen. J Clin Microbiol 2001; 39: 1211–1216.
Citing Literature
