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International Journal of Hematology
Published in: International Journal of Hematology 5/2010

01-12-2010 | Progress in Hematology

Natural killer cell neoplasm: biology and pathology

Authors: Maria Francisca Ham, Young-Hyeh Ko

Published in: International Journal of Hematology | Issue 5/2010

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Abstract

Natural killer (NK) cell neoplasm is a heterogeneous disease group. In the latest World Health Organization (WHO) classification of tumours of hematopoietic and lymphoid tissues (2008), disease entities considered as NK-cell derivation include NK-lymphoblastic leukemia/lymphoma, chronic lymphoproliferative disorders of NK cells, aggressive NK-cell leukemia, and extranodal NK-cell lymphoma, nasal-type. Despite recent advances in NK-cell research, which have expanded our understanding of the biology of NK-cell neoplasm, it cannot yet be sharply delineated from myeloid neoplasms and T-cell neoplasms even in some “well-known” entity, such as extranodal NK/T-cell lymphoma. This review describes current knowledge of the biology of NK cells and pathology of NK neoplasms as classified in the 2008 WHO classification of tumours of hematopoietic and lymphoid tissues.
Literature
1.
Phillips JH, Hori T, Nagler A, Bhat N, Spits H, Lanier LL. Ontogeny of human natural killer (NK) cells: fetal NK cells mediate cytolytic function and express cytoplasmic CD3 epsilon, delta proteins. J Exp Med. 1992;175:1055–66.PubMedCrossRef
2.
Stewart CA, Walzer T, Robbins SH, Malissen B, Vivier E, Prinz I. Germ-line and rearranged Tcrδ transcription distinguish bona fide NK cells and NK-like gd T cell. Eur J Immunol. 2007;37:1442–52.PubMedCrossRef
3.
4.
Cullen SP, Brunet M, Martin SJ. Granzymes in cancer and immunity. Cell Death Differ. 2010;17:616–23.PubMedCrossRef
5.
Nagler A, Lanier L, Cwirla S, Phillips J. Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol. 1989;143:3183–91.PubMed
6.
Lanier LL, Le AM, Civin CI, Loken MR, Phillips JH. The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 1986;136:4480–6.PubMed
7.
Farag S, VanDeusen J, Fehniger T, Caligiuri M. Biology and clinical impact of human natural killer cells. Int J Hematol. 2003;78:7–17.PubMedCrossRef
8.
Poli A, Michel T, Theresine M, Andres E, Hentges F, Zimmer J. CD56bright natural killer (NK) cells: an important NK cell subset. Immunology. 2009;126:458–65.PubMedCrossRef
9.
Cooper MA, Fehniger TA, Turner SC, Chen KS, Ghaheri BA, Ghayur T, et al. Human natural killer cells: a unique innate immunoregulatory role for the CD56bright subset. Blood. 2001;97:3146–51.PubMedCrossRef
10.
Berahovich RD, Lai NL, Wei Z, Lanier LL, Schall TJ. Evidence for NK cell subsets based on chemokine receptor expression. J Immunol. 2006;177:7833–40.PubMed
11.
Matos ME, Schnier GS, Beecher MS, Ashman LK, William DE, Caligiuri MA. Expression of a functional c-kit receptor on a subset of natural killer cells. J Exp Med. 1993;178:1079–84.PubMedCrossRef
12.
Carson WE, Fehniger TA, Caligiuri MA. CD56bright natural killer cell subsets: characterization of distinct functional responses to interleukin-2 and the c-kit ligand. Eur J Immunol. 1997;27:354–60.PubMedCrossRef
13.
Maghazachi AA. Role of chemokines in the biology of natural killer cells. Curr Top Microbiol Immunol. 2010;870:37–58.CrossRef
14.
Hanna J, Bechtel P, Zhai Y, Youssef F, McLachlan K, Mandelboim O. Novel insights on human NK cells’ immunological modalities revealed by gene expression profiling. J Immunol. 2004;173:6547–63.PubMed
15.
Wendt K, Wilk E, Buyny S, Buer J, Schmidt RE, Jacobs R. Gene and protein characteristics reflect functional diversity of CD56dim and CD56bright NK cells. J Leukoc Biol. 2006;80:1529–41.PubMedCrossRef
16.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. World Health Organization classification of hematopoietic and lymphoid tissues. Lyon: IARC Press; 2008.
17.
Liang X, Greffe B, Garrington T, Graham DK. Precursor natural killer cell leukemia. Pediatr Blood Cancer. 2008;50:876–8.PubMedCrossRef
18.
Dubois SG, Etzell JE, Matthay KK, Robbins E, Banerjee A. Pediatric acute blastic natural killer cell leukemia. Leuk Lymphoma. 2002;43:901–6.PubMedCrossRef
19.
Hyakuna N, Toguchi S, Higa T, Okudaira T, Taira N, Masuda M, et al. Childhood blastic NK cell leukemia successfully treated with l-asparaginase and allogeneic bone marrow transplantation. Pediatr Blood Cancer. 2004;42:631–4.PubMedCrossRef
20.
Matano S, Nakamura S, Nakamura S, Annen Y, Hattori N, Kobayashi K, et al. Monomorphic granular natural killer cell lymphoma/leukemia with no Epstein-Barr virus association. Acta Haematol. 1999;101:206–8.PubMedCrossRef
21.
Tamura H, Ogata K, Mori S, An E, Tajika K, Sugisaki Y, et al. Lymphoblastic lymphoma of natural killer cell origin, presenting as pancreatic tumour. Histopathology. 1998;32:508–11.PubMed
22.
23.
Lin CW, Liu TY, Chen SU, Wang KT, Medeiros LJ, Hsu SM. CD94 1A transcripts characterize lymphoblastic lymphoma/leukemia of immature natural killer cell origin with distinct clinical features. Blood. 2005;106:3567–74.PubMedCrossRef
24.
Bareau B, Rey J, Hamidou M, Donadieu J, Morcet J, Reman O, et al. Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases. Hematologica. 2010;95:1534–41.CrossRef
25.
26.
Oshimi K, Yamada O, Kaneko T, Nishinarita S, Iizuka Y, Urabe A, et al. Laboratory findings and clinical courses of patients with granular lymphocyte-proliferative disorders. Leukemia. 1993;7:782–8.PubMed
27.
Tefferi A, Li C-Y, Witzig TE, Dhodapkar MV, Okuno SH, Phyliky RL, et al. Chronic natural killer cell lymphocytosis: a descriptive clinical study. Blood. 1994;84:2721–5.PubMed
28.
Morice WG, Kurtin PJ, Leibson PJ, Tefferi A, Hanson CA. Demonstration of aberrant T-cell and natural killer-cell antigen expression in all cases of granular lymphocytic leukaemia. Br J Haematol. 2003;120(6):1026–36.PubMedCrossRef
29.
Zambello R, Semenzato G. Natural killer receptors in patients with lymphoproliferative diseases of granular lymphocytes. Semin Hematol. 2003;40:201–31.PubMedCrossRef
30.
Epling-Burnette PK, Painter JS, Chaurasia P, Bai F, Wei S, Djeu JY, et al. Dysregulated NK receptor expression in patients with lymphoproliferative disease of granular lymphocytes. Blood. 2004;103:3431–9.PubMedCrossRef
31.
Nash R, McSweeney P, Zambello R, Semenzato G, Loughran TP Jr. Clonal studies of CD3− lymphoproliferative disease of granular lymphocytes. Blood. 1993;81:2363–8.PubMed
32.
Tefferi A, Greipp PR, Leibson PJ, Thibodeau SN. Demonstration of clonality, by X-linked DNA analysis, in chronic natural killer cell lymphocytosis and successful therapy with oral cyclophosphamide. Leukemia. 1992;6:477–80.PubMed
33.
Kelly A, Richards SJ, Sivakumaran M, Shiach C, Stewart AD, Roberts BE, et al. Clonality of CD3 negative large granular lymphocyte proliferations determined by PCR based X-inactivation studies. J Clin Pathol. 1994;47:399–404.PubMedCrossRef
34.
Ryder J, Wang X, Bao L, Gross SA, Hua F, Irons RD. Aggressive natural killer cell leukemia: report of a Chinese series and review of the literature. Int J Hematol. 2007;85:18–25.PubMedCrossRef
35.
Ko YH, Park S, Kim K, Kim SJ, Kim WS. Aggressive natural killer cell leukemia: is Epstein-Barr virus negativity an indicator of a favorable prognosis? Acta Haematol. 2008;120:199–206.PubMedCrossRef
36.
Oshimi K. Progress in understanding and managing natural killer-cell malignancies. Br J Haematol. 2007;139:532–44.PubMedCrossRef
37.
Suzuki R, Suzumiya J, Nakamura S, Aoki S, Notoya A, Ozaki S, NK-cell Tumor Study Group, et al. Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells. Leukemia. 2004;18(4):763–70.PubMedCrossRef
38.
Kluin PM, Feller A, Gaulard P, Jaffe ES, Meijer CJLM, Muller-Hermelink HK, et al. Peripheral T/NK-cell lymphoma: a report of the IXth Workshop of the European Association for Haematopathology. Histopathology. 2001;38:250–70.PubMedCrossRef
39.
Mori N, Yamashita Y, Tsuzuki T, Nakayama A, Nakazawa M, Hasegawa Y, et al. Lymphomatous features of aggressive NK cell leukaemia/lymphoma with massive necrosis, haemophagocytosis and EB virus infection. Histopathology. 2000;37:363–71.PubMedCrossRef
40.
Yoo EH, Kim HJ, Lee ST, Kim WS, Kim SH. Frequent CD7 antigen loss in aggressive natural killer-cell leukemia: a useful diagnostic marker. Korean J Lab Med. 2009;29:491–6.PubMedCrossRef
41.
Makishima H, Ito T, Momose K, Nakazawa H, Shimodaira S, Kamijo Y, et al. Chemokine system and tissue infiltration in aggressive NK-cell leukemia. Leuk Res. 2007;31:1237–45.PubMedCrossRef
42.
Nakashima Y, Tagawa H, Suzuki R, Karnan S, Karube K, Ohshima K, et al. Genome-wide array-based comparative genomic hybridization of natural killer cell lymphoma/leukemia: different genomic alteration patterns of aggressive NK-cell leukemia and extranodal NK/T-cell lymphoma, nasal type. Genes Chromosomes Cancer. 2005;44:247–55.PubMedCrossRef
43.
Chan JK, Sin VC, Wong KF, et al. Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood. 1997;89:4501–13.PubMed
44.
Ko YH, Cho EY, Kim JE, Lee SS, Huh JR, Chang HK, et al. NK and NK-like T-cell lymphoma in extranasal sites: a comparative clinicopathological study according to site and EBV status. Histopathology. 2004;44:480–9.PubMedCrossRef
45.
Ng SB, Khoury JD. Epstein-Barr in lymphoproliferative process. An update for diagnostic pathologist. Adv Anat Pathol. 2009;16:40–55.PubMedCrossRef
46.
Zeglaoui I, Belcadhi M, Sriha B, Bouzouita K. Nasal NK/T-cell lymphoma in the paediatric population. Two case reports. B-ENT. 2009;5:119–23.PubMed
47.
Zhang Z, Shi Q, An X, Ma H, Zhou H, Ma J, et al. NK/T-cell lymphoma in a child with hypersensitivity to mosquito bites. J Pediatr Hematol Oncol. 2009;31:855–7.PubMedCrossRef
48.
Pellier I, N’Golet L, Rachieru P, Rousselet MC, Geneviève F, Moles MP, et al. Disseminated nasal-type natural killer/T-cell lymphoma in a child: a case report. J Pediatr Hematol Oncol. 2009;31:362–6.PubMedCrossRef
49.
Chen X, Pepper S, De V, Arrand JR. Prevalence of A and B types of Epstein–Barr virus DNA in nasopharyngeal carcinoma biopsies from South China. J Gen Virol. 1992;73:463–6.PubMedCrossRef
50.
Peh SC, Sardves K, Pallesen G. Epstein–Barr virus (EBV) in Malaysian upper-aerodigestive-tract lymphoma: incidence and subtype. Int J Cancer. 1995;61:327–32.PubMedCrossRef
51.
Aozasa K, Takakuwa T, Hongyo T, Yang WI. Nasal NK/T-cell lymphoma: epidemiology and pathogenesis. Int J Hematol. 2008;87:110–7.PubMedCrossRef
52.
Martin C, Carrasco C, Sotomayor C, Otth C. Prevalence of Epstein-Barr virus associated with nasal lymphoma in patients attending the regional hospital of Valdivia, Chile, between 1987 and 2005. J Med Virol. 2010;82:825–8.PubMedCrossRef
53.
Kanno H, Kojya S, Li T, Ohsawa M, Nakatsuka S, Miyaguchi M, et al. Low frequency of HLA-A*0201 allele in patients with Epstein–Barr virus-positive nasal lymphomas with polymorphic reticulosis morphology. Int J Cancer. 2000;87:195–9.PubMedCrossRef
54.
Li T, Hongyo T, Syaifudin M, Nomura T, Dong Z, Shingu N, et al. Sequence variations of Epstein-Barr virus LMP1 gene in nasal NK/T-cell lymphoma. Virus Genes. 2007;34:47–54.CrossRef
55.
Harabuchi Y, Takahara M, Kishibe K, Moriai S, Nagato T, Ishii H. Nasal natural killer (NK)/T-cell lymphoma: clinical, histological, virological, and genetic features. Int J Clin Oncol. 2009;14:181–90.PubMedCrossRef
56.
Lee J, Suh C, Huh J, Jun HJ, Kim K, Jung C, 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;13:3250–4.PubMedCrossRef
57.
Chim CS, Ma ES, Loong F, Kwong YL. Diagnostic clues for natural killer cell lymphoma: primary nodal presentation and the role of in situ hybridization for Epstein–Barr virus encoded early small RNA in detecting occult bone marrow involvement. J Clin Pathol. 2005;58:443–5.PubMedCrossRef
58.
Li T, Zhang B, Ye Y, Yin H. Immunohistochemical and genetic analysis of Chinese nasal natural killer/T-cell lymphomas. Hum Pathol. 2006;37:54–60.PubMedCrossRef
59.
Ng SB, Lai KW, Murugaya S, Lee KM, Loong SL, Fook-Chong S, et al. Nasal-type extranodal natural killer/T-cell lymphomas: a clinicopathologic and genotypic study of 42 cases in Singapore. Mod Pathol. 2004;17:1097–107.PubMedCrossRef
60.
Kurniawan AN, Hongyo T, Hardjolukito ES, Ham MF, Takakuwa T, Kodariah R, et al. Gene mutation analysis of sinonasal lymphomas in Indonesia. Oncol Rep. 2006;15:1257–63.PubMed
61.
Hoshida Y, Hongyo T, Jia X, He Y, Hasui K, Dong Z, et al. Analysis of p53, K-ras, c-kit, and beta-catenin gene mutations in sinonasal NK/T cell lymphoma in northeast district of China. Cancer Sci. 2003;94:297–301.PubMedCrossRef
62.
Hongyo T, Hoshida Y, Nakatsuka S, Syaifudin M, Kojya S, Yang WI. p53, K-ras, c-kit and beta-catenin gene mutations in sinonasal NK/T-cell lymphoma in Korea and Japan. Oncol Rep. 2005;13:265–71.PubMed
63.
Shen L, Liang ACT, Lu L, Au WY, Kwong YL, Liang RHS, et al. Frequent deletion of Fas gene sequences encoding death and transmembrane domains in nasal natural killer/T-cell lymphoma. Am J Pathol. 2002;161:2123–31.PubMed
64.
Takakuwa T, Dong Z, Nakatsuka S, Kojya S, Harabuchi Y, Yang WI, et al. Frequent mutation of Fas gene in nasal NK/T cell lymphoma. Oncogene. 2002;21:4702–5.PubMedCrossRef
65.
Huang Y, de Reyniès A, de Leval L, Ghazi B, Martin-Garcia N, Travert M, et al. Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type. Blood. 2010;115:1226–37.PubMedCrossRef
66.
Iqbal J, Weisenburger DD, Chowdhury A, Tsai MY, Srivastava G, Greiner TC, et al., The International Peripheral T-cell Lymphoma Project. Natural killer cell lymphoma shares strikingly similar molecular features with a group of non hepatosplenic gd t-cell lymphoma and is highly sensitive to a novel aurora kinase a inhibitor in vitro. Leukemia. 2010. doi:10.​1038/​leu.​2010.​255.
67.
Au WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Sng I, et al. Clinical differences between nasal and extranasal NK/T-cell lymphoma: a study of 136 cases from the International Peripheral T-cell Lymphoma Project. Blood. 2009;113:3931–7.PubMedCrossRef
68.
Kostal M, Kostalova M, Belada D, Laco J. Cutaneous natural killer (NK)/T-cell lymphoma: nasal type with extensive facial destruction. Int J Dermatol. 2009;48:1338–42.CrossRef
69.
Chia HY, Tey HL, Tan KB, Chong WS. Nasal-type extranodal natural killer/T-cell lymphoma presenting with extensive leg ulcers. Clin Exp Dermatol. 2009;34:693–5.CrossRef
70.
Fernández-Torres R, Del Pozo J, Alvarez A, Mazaira M, Varela C, Almagro M, et al. Extranodal NK/T-cell lymphoma, nasal type presenting as a pyogenic granuloma-like on a fingertip. Eur J Dermatol. 2009;19:79–80.PubMed
71.
Kim JH, Lee JH, Lee J, Oh SO, Chang DK, Rhee PL, et al. Primary NK-/T-cell lymphoma of the gastrointestinal tract: clinical characteristics and endoscopic findings. Endoscopy. 2007;39:156–60.PubMedCrossRef
72.
Takahashi E, Asano N, Li C, Tanaka T, Shimada K, Shimada S, et al. Nodal T/NK-cell lymphoma of nasal type: a clinicopathological study of six cases. Histopathology. 2008;52:585–96.PubMedCrossRef
73.
Chang SS, Liao YL, Lin SH, Chuang SS. NK-cell lymphoma with nodal presentation and expression of cutaneous lymphocyte-associated antigen. Pathol Res Pract. 2010;206:463–6.PubMedCrossRef
Metadata
Title
Natural killer cell neoplasm: biology and pathology
Authors
Maria Francisca Ham
Young-Hyeh Ko
Publication date
01-12-2010
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 5/2010
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-010-0738-y

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