Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter study from Thailand

Diagnostic Pathology

Sanya Sukpanichnant³  Daisuke Niino¹  Fumiko Arakawa¹  Koichi Ohshima¹  Archrob Khuhapinant⁴  Anan Bedavanija⁵  Tanawan Kummalue²  Tawatchai Pongpruttipan³ 

[1] Department of Pathology, Kurume University School of Medicine, Japan;Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand;Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand;Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand;Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand

关键词: TCR gene rearrangement;    LMP-1 gene;    EBV;    immunophenotype;    pathology;    Extranodal NK/T-cell lymphoma;   

Others  :  808261
DOI  :  10.1186/1746-1596-6-79

 received in 2011-06-28, accepted in 2011-08-25,  发布年份 2011

【 摘 要 】

Background

Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is not common worldwide, but it is the most common T- and NK-cell lymphomas in many Asian countries. Immunophenotypic profiles were studied based on limited series. The authors, therefore, studied on ENKTL according to characterize immunophenotypic profiles as well as the distribution of EBV subtype and LMP-1 gene deletion.

Methods

By using tissue microarray (TMA), immunohistochemical study and EBV encoded RNA (EBER) in situ hybridization were performed. T-cell receptor (TCR) gene rearrangement, EBV subtyping, and LMP-1 gene deletion were studied on the available cases.

Results

There were 22 cases eligible for TMA. ENKTL were positive for CD3 (91%), CD5 (9%), CD7 (32%), CD4 (14%), CD56 (82%), TIA-1 (100%), granzyme B (95%), perforin (86%), CD45 (83%), CD30 (75%), Oct2 (25%), and IRF4/MUM1 (33%). None of them was positive for βF1, CD8, or CD57. TCR gene rearrangement was negative in all 18 tested cases. EBV was subtype A in all 15 tested cases, with 87% deleted LMP-1 gene. Cases lacking perforin expression demonstrated a significantly poorer survival outcome (p = 0.008).

Conclusions

The present study demonstrated TIA-1 and EBER as the two most sensitive markers. There were a few CD3 and/or CD56 negative cases noted. Interestingly, losses of CD45 and/or CD7 were not uncommon while Oct2 and IRF4/MUM1 could be positive in a subset of cases. Based on the present study in conjunction with the literature review, determination of PCR-based TCR gene rearrangement analysis might not be a useful technique for making diagnosis of ENKTL.

【 授权许可】

   
2011 Pongpruttipan et al; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW: World Health Organization Classification of Tumours. In Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008.
• [2]Aozasa K, Takakuwa T, Hongyo T, Yang WI: Nasal NK/T-cell lymphoma: epidemiology and pathogenesis. Int J Hematol 2008, 87(2):110-7.
• [3]Au WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Sng I, Vose J, Armitage JO, Liang R: Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project. Blood 2009, 113(17):3931-7.
• [4]Pongpruttipan T, Pongtongcharoen P, Sukpanichnant S: Mature T-cell and NK-cell lymphomas in Thailand: an analysis of 71 cases. J Med Assoc Thai 2011, 94(6):743-8.
• [5]Chan JKC, Quintanilla-Martinez L, Ferry JA, Peh S-C: Extranodal NK/T-cell lymphoma, nasal type. Edited by Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. France: IARC Press; 2008:285-8. World Health Organization Classification of Tumours Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues Lyon
• [6]Suzumiya J, Ohshima K, Takeshita M, Kanda M, Kawasaki C, Kimura N, Tamura K, Kikuchi M: Nasal lymphomas in Japan: a high prevalence of Epstein-Barr virus type A and deletion within the latent membrane protein gene. Leuk Lymphoma 1999, 35(5-6):567-78.
• [7]Nakamura S, Katoh E, Koshikawa T, Yatabe Y, Nagasaka T, Ishida H, Tokoro Y, Koike K, Kagami Y, Ogura M, Kojima M, Nara Y, Mizoguchi Y, Hara K, Kurita S, Seto M, Suchi T: Clinicopathologic study of nasal T/NK-cell lymphoma among the Japanese. Pathol Int 1997, 47(1):38-53.
• [8]Suzuki R, Takeuchi K, Ohshima K, Nakamura S: Extranodal NK/T-cell lymphoma: diagnosis and treatment cues. Hematol Oncol 2008, 26(2):66-72.
• [9]Dambaugh T, Hennessy K, Chamnankit L, Kieff E: U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear antigen 2. Proc Natl Acad Sci USA 1984, 81(23):7632-6.
• [10]Peh SC, Sandvej K, Pallesen G: Epstein-Barr virus (EBV) in Malaysian upper-aerodigestive-tract lymphoma: incidence and sub-type. Int J Cancer 1995, 61(3):327-32.
• [11]Tomita Y, Ohsawa M, Qiu K, Hashimoto M, Yang WI, Kim GE, Aozasa K: Epstein-Barr virus in lymphoproliferative diseases in the sino-nasal region: close association with CD56+ immunophenotype and polymorphic-reticulosis morphology. Int J Cancer 1997, 70(1):9-13.
• [12]Chiang AK, Wong KY, Liang AC, Srivastava G: Comparative analysis of Epstein-Barr virus gene polymorphisms in nasal T/NK-cell lymphomas and normal nasal tissues: implications on virus strain selection in malignancy. Int J Cancer 1999, 80(3):356-64.
• [13]Borisch B, Hennig I, Laeng RH, Waelti ER, Kraft R, Laissue J: Association of the subtype 2 of the Epstein-Barr virus with T-cell non-Hodgkin's lymphoma of the midline granuloma type. Blood 1993, 82(3):858-64.
• [14]Elenitoba-Johnson KS, Zarate-Osorno A, Meneses A, Krenacs L, Kingma DW, Raffeld M, Jaffe ES: Cytotoxic granular protein expression, Epstein-Barr virus strain type, and latent membrane protein-1 oncogene deletions in nasal T-lymphocyte/natural killer cell lymphomas from Mexico. Mod Pathol 1998, 11(8):754-61.
• [15]Gualco G, Domeny-Duarte P, Chioato L, Barber G, Natkunam Y, Bacchi CE: Clinicopathologic and Molecular Features of 122 Brazilian Cases of Nodal and Extranodal NK/T-Cell Lymphoma, Nasal Type, With EBV Subtyping Analysis. Am J Surg Pathol 2011, 35(8):1195-203.
• [16]Barrionuevo C, Zaharia M, Martinez MT, Taxa L, Misad O, Moscol A, Sarria G, Guerrero I, Casanova L, Flores C, Zevallos-Giampietri EA: Extranodal NK/T-cell lymphoma, nasal type: study of clinicopathologic and prognosis factors in a series of 78 cases from Peru. Appl Immunohistochem Mol Morphol 2007, 15(1):38-44.
• [17]Cabrera ME, Eizuru Y, Itoh T, Koriyama C, Tashiro Y, Ding S, Rey S, Akiba S, Corvalan A: Nasal natural killer/T-cell lymphoma and its association with type "i"/XhoI loss strain Epstein-Barr virus in Chile. J Clin Pathol 2007, 60(6):656-60.
• [18]Gaal K, Sun NC, Hernandez AM, Arber DA: Sinonasal NK/T-cell lymphomas in the United States. Am J Surg Pathol 2000, 24(11):1511-7.
• [19]Garcia-Cosio M, Santon A, Mendez MC, Rivas C, Martin C, Bellas C: Nasopharyngeal/nasal type T/NK lymphomas: analysis of 14 cases and review of the literature. Tumori 2003, 89(3):278-84.
• [20]van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL, Delabesse E, Davi F, Schuuring E, Garcia-Sanz R, van Krieken JH, Droese J, Gonzalez D, Bastard C, White HE, Spaargaren M, Gonzalez M, Parreira A, Smith JL, Morgan GJ, Kneba M, Macintyre EA: Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2003, 17(12):2257-317.
• [21]Pongpruttipan T, Treetipsatit J, Amornpichetkul K, Kummalue T, Chuphrom A, Khuhapinant A, Siritanaratkul N, Sukpanichnant S: EBV-positive diffuse large B-cell lymphoma of the elderly with dual genotype and aberrant TIA-1 expression: a case report and review of literature. J Hematopathol 2010, 3(2-3):83-9.
• [22]Ohshima K, Suzumiya J, Kanda M, Haraoka S, Kawasaki C, Shimazaki K, Kikuchi M: Genotypic and phenotypic alterations in Epstein-Barr virus-associated lymphoma. Histopathology 1999, 35(6):539-50.
• [23]Hudson GS, Bankier AT, Satchwell SC, Barrell BG: The short unique region of the B95-8 Epstein-Barr virus genome. Virology 1985, 147(1):81-98.
• [24]Al-Hakeem DA, Fedele S, Carlos R, Porter S: Extranodal NK/T-cell lymphoma, nasal type. Oral Oncol 2007, 43(1):4-14.
• [25]Sukpanichnant S: Analysis of 1983 cases of malignant lymphoma in Thailand according to the World Health Organization classification. Hum Pathol 2004, 35(2):224-30.
• [26]Lee MY, Tan TD, Feng AC, Liu MC: Clinicopathological analysis of 598 malignant lymphomas in Taiwan: seven-year experience in a single institution. Am J Hematol 2006, 81(8):568-75.
• [27]Yoon SO, Suh C, Lee DH, Chi HS, Park CJ, Jang SS, Shin HR, Park BH, Huh J: Distribution of lymphoid neoplasms in the Republic of Korea: analysis of 5318 cases according to the World Health Organization classification. Am J Hematol 2010, 85(10):760-4.
• [28]Gross SA, Zhu X, Bao L, Ryder J, Le A, Chen Y, Wang XQ, Irons RD: A prospective study of 728 cases of non-Hodgkin lymphoma from a single laboratory in Shanghai, China. Int J Hematol 2008, 88(2):165-73.
• [29]Au WY, Ma SY, Chim CS, Choy C, Loong F, Lie AK, Lam CC, Leung AY, Tse E, Yau CC, Liang R, Kwong YL: 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 10 years. Ann Oncol 2005, 16(2):206-14.
• [30]Aoki R, Karube K, Sugita Y, Nomura Y, Shimizu K, Kimura Y, Hashikawa K, Suefuji N, Kikuchi M, Ohshima K: Distribution of malignant lymphoma in Japan: analysis of 2260 cases, 2001-2006. Pathol Int 2008, 58(3):174-82.
• [31]Naresh KN, Agarwal B, Nathwani BN, Diebold J, McLennan KA, Muller-Hermelink KH, Armitage JO, Weisenburger DD: Use of the World Health Organization (WHO) classification of non-Hodgkin's lymphoma in Mumbai, India: a review of 200 consecutive cases by a panel of five expert hematopathologists. Leuk Lymphoma 2004, 45(8):1569-77.
• [32]Assanasen T, Wannakrairot P, Keelawat S, Ruangvejvorachai P, Pramprayoon N: Extranodal malignant lymphoma of the upper aerodigestive tract: prevalence of Epstien-Barr virus (EBV) infection in King Chulalongkorn Memorial Hospital. J Med Assoc Thai 2005, 88(Suppl 4):S266-73.
• [33]Kuwabara H, Tsuji M, Yoshii Y, Kakuno Y, Akioka T, Kotani T, Iwao N, Hanafusa T, Ikeda T, Mori H: Nasal-type NK/T cell lymphoma of the orbit with distant metastases. Hum Pathol 2003, 34(3):290-2.
• [34]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(10):2106-16.
• [35]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. Int J Surg Pathol 2004, 12(4):375-87.
• [36]Ng SB, Lai KW, Murugaya S, Lee KM, Loong SL, Fook-Chong S, Tao M, Sng I: Nasal-type extranodal natural killer/T-cell lymphomas: a clinicopathologic and genotypic study of 42 cases in Singapore. Mod Pathol 2004, 17(9):1097-107.
• [37]Emile JF, Boulland ML, Haioun C, Kanavaros P, Petrella T, Delfau-Larue MH, Bensussan A, Farcet JP, Gaulard P: CD5-CD56+ T-cell receptor silent peripheral T-cell lymphomas are natural killer cell lymphomas. Blood 1996, 87(4):1466-73.
• [38]Kwong YL, Chan AC, Liang R, Chiang AK, Chim CS, Chan TK, Todd D, Ho FC: CD56+ NK lymphomas: clinicopathological features and prognosis. Br J Haematol 1997, 97(4):821-9.
• [39]Karube K, Aoki R, Nomura Y, Yamamoto K, Shimizu K, Yoshida S, Komatani H, Sugita Y, Ohshima K: Usefulness of flow cytometry for differential diagnosis of precursor and peripheral T-cell and NK-cell lymphomas: analysis of 490 cases. Pathol Int 2008, 58(2):89-97.
• [40]Ohshima K, Suzumiya J, Shimazaki K, Kato A, Tanaka T, Kanda M, Kikuchi M: Nasal T/NK cell lymphomas commonly express perforin and Fas ligand: important mediators of tissue damage. Histopathology 1997, 31(5):444-50.
• [41]Ichimura K, Kagami Y, Suzuki R, Kojima M, Yoshino T, Ohshima K, Koike K, Kondo E, Taji H, Ogura M, Morishima Y, Akagi T, Takahashi T, Nakamura S: Phenotypic analysis of peripheral T/NK cell lymphoma: study of 408 Japanese cases with special reference to their anatomical sites. Pathol Int 2003, 53(6):333-44.
• [42]Ng CS, Lo ST, Chan JK, Chan WC: CD56+ putative natural killer cell lymphomas: production of cytolytic effectors and related proteins mediating tumor cell apoptosis? Hum Pathol 1997, 28(11):1276-82.
• [43]Griffiths GM, Mueller C: Expression of perforin and granzymes in vivo: potential diagnostic markers for activated cytotoxic cells. Immunol Today 1991, 12(11):415-9.
• [44]Salcedo TW, Azzoni L, Wolf SF, Perussia B: Modulation of perforin and granzyme messenger RNA expression in human natural killer cells. J Immunol 1993, 151(5):2511-20.
• [45]Huang Y, de Reynies A, de Leval L, Ghazi B, Martin-Garcia N, Travert M, Bosq J, Briere J, Petit B, Thomas E, Coppo P, Marafioti T, Emile JF, Delfau-Larue MH, Schmitt C, Gaulard P: Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type. Blood 2010, 115(6):1226-37.
• [46]d'Amore ES, Menin A, Bonoldi E, Bevilacqua P, Cazzavillan S, Donofrio V, Gambini C, Forni M, Gentile A, Magro G, Boldrini R, Pillon M, Rosolen A, Alaggio R: Anaplastic large cell lymphomas: a study of 75 pediatric patients. Pediatr Dev Pathol 2007, 10(3):181-91.
• [47]Saez AI, Artiga MJ, Sanchez-Beato M, Sanchez-Verde L, Garcia JF, Camacho FI, Franco R, Piris MA: Analysis of octamer-binding transcription factors Oct2 and Oct1 and their coactivator BOB.1/OBF.1 in lymphomas. Mod Pathol 2002, 15(3):211-20.
• [48]Gualco G, Weiss LM, Bacchi CE: MUM1/IRF4: A Review. Appl Immunohistochem Mol Morphol 2010, 18(4):301-10.
• [49]Wasco MJ, Fullen D, Su L, Ma L: The expression of MUM1 in cutaneous T-cell lymphoproliferative disorders. Hum Pathol 2008, 39(4):557-63.
• [50]Natkunam Y, Warnke RA, Montgomery K, Falini B, van De Rijn M: Analysis of MUM1/IRF4 protein expression using tissue microarrays and immunohistochemistry. Mod Pathol 2001, 14(7):686-94.
• [51]Ohsawa M, Nakatsuka S, Kanno H, Miwa H, Kojya S, Harabuchi Y, Yang WI, Aozasa K: Immunophenotypic and genotypic characterization of nasal lymphoma with polymorphic reticulosis morphology. Int J Cancer 1999, 81(6):865-70.
• [52]Chen YL, Su IJ, Cheng HY, Chang KC, Lu CC, Chow NH, Ho CL, Huang W: BIOMED-2 protocols to detect clonal immunoglobulin and T-cell receptor gene rearrangements in B- and T-cell lymphomas in southern Taiwan. Leuk Lymphoma 2010, 51(4):650-5.
• [53]Lin CW, Lee WH, Chang CL, Yang JY, Hsu SM: Restricted killer cell immunoglobulin-like receptor repertoire without T-cell receptor gamma rearrangement supports a true natural killer-cell lineage in a subset of sinonasal lymphomas. Am J Pathol 2001, 159(5):1671-9.
• [54]Mitarnun W, Suwiwat S, Pradutkanchana J: Epstein-Barr virus-associated extranodal non-Hodgkin's lymphoma of the sinonasal tract and nasopharynx in Thailand. Asian Pac J Cancer Prev 2006, 7(1):91-4.
• [55]Theriault C, Galoin S, Valmary S, Selves J, Lamant L, Roda D, Rigal-Huguet F, Brousset P, Delsol G, Al Saati T: PCR analysis of immunoglobulin heavy chain (IgH) and TcR-gamma chain gene rearrangements in the diagnosis of lymphoproliferative disorders: results of a study of 525 cases. Mod Pathol 2000, 13(12):1269-79.
• [56]Vergier B, Dubus P, Kutschmar A, Parrens M, Ferrer J, de Mascarel A, Merlio JP: Combined analysis of T cell receptor gamma and immunoglobulin heavy chain gene rearrangements at the single-cell level in lymphomas with dual genotype. J Pathol 2002, 198(2):171-80.
• [57]Sanchez I, San Miguel JF, Corral J, Martin C, Perez R, Gonzalez M, Canizo MC, Orfao A, Gonzalez-Sarmiento R: Gene rearrangement in acute non-lymphoblastic leukaemia: correlation with morphological and immunophenotypic characteristics of blast cells. Br J Haematol 1995, 89(1):104-9.
• [58]Tai YC, Peh SC: Feasibility of T-cell receptor gamma (TCRgamma) gene rearrangement on formalin-fixed, paraffin-embedded tissues by PCR assays. Singapore Med J 2003, 44(5):250-5.
• [59]Nagata H, Konno A, Kimura N, Zhang Y, Kimura M, Demachi A, Sekine T, Yamamoto K, Shimizu N: Characterization of novel natural killer (NK)-cell and gammadelta T-cell lines established from primary lesions of nasal T/NK-cell lymphomas associated with the Epstein-Barr virus. Blood 2001, 97(3):708-13.