Journal of Hematopathology

, Volume 5, Issue 4, pp 319–324 | Cite as

EBV-associated T and NK cell lymphoproliferative disorders: consensus report of the 4th Asian Hematopathology Workshop

  • Young-Hyeh Ko
  • Hyun-Jung Kim
  • Young-Ha Oh
  • Geongsin Park
  • Seung-Sook Lee
  • Jooryung Huh
  • Chul-Woo Kim
  • Insun Kim
  • Siok-Bian Ng
  • Soo-Young Tan
  • Shih-Sung Chuang
  • Naoya Nakamura
  • Tadashi Yoshino
  • Shigeo Nakamura
  • Hiroshi Kimura
  • Koichi Ohshima
Review Article

Abstract

T and NK cell proliferative diseases associated with acute and chronic Epstein–Barr virus (EBV) infection are uncommon and raise several clinical issues regarding diagnostic criteria and terminology. This is a summary report of the consensus meeting held in the 4th Asian Hematopathology Workshop. The umbrella term “EBV-positive T/NK lymphoproliferative disease in childhood-type” covers the entire spectrum of EBV-associated lesions in childhood, ranging from reactive to neoplastic processes. Systemic T/NK cell lymphoproliferative disease (LPD) of childhood type is defined as a fulminant disease associated with the proliferation of polyclonal, oligoclonal, or monoclonal T or NK cells and includes aggressive NK cell-associated leukemia in children. Chronic active EBV disease-type T/NK cell LPD is divided into three groups—polymorphic/polyclonal, polymorphic/monoclonal, and monomorphic/monoclonal—based on the histology and clonality of T or NK cells. A monoclonal EBV-positive T/NK cell type of proliferation with the clinical features of chronic active EBV disease rather than the fulminant course of systemic EBV-positive T/NK cell LPD of childhood is considered “chronic active EBV disease-type T/NK cell LPD”. Hydroa vacciniforme (HV)-like T cell LPD is defined as a spectrum of EBV-infected T cell proliferative diseases with homing to the skin and is further classified into a classic type, a severe type, and malignant lymphoma. Criteria to define each category of HV-like T cell LPD remain to be clarified.

Keywords

EBV Lymphoproliferative disease Chronic active infection Hemophagocytosis Hydroa vacciniforme 

References

  1. 1.
    Iwatsuki K, Yamamoto T, Tsuji K, Suzuki D, Fujii K, Matsuura H, Oono T (2004) A spectrum of clinical manifestations caused by host immune responses against Epstein–Barr virus infections. Acta Med Okayama 58:169–180PubMedGoogle Scholar
  2. 2.
    Cohen JI, Kimura H, Nakamura S, Ko YH, Jaffe ES (2009) Epstein–Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8–9 September 2008. Ann Oncol 20:1472–1482PubMedCrossRefGoogle Scholar
  3. 3.
    Jones JF, Ray CG, Minnich LL, Hicks MJ, Kibler R, Lucas DO (1985) Evidence for active Epstein–Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies. Ann Intern Med 102:1–7PubMedGoogle Scholar
  4. 4.
    Chan JKC, Jaffe ES, Ralfkiaer E, Ko YH (2008) Aggressive NK-cell leukaemia. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. International Agency for Research on Cancer, Lyon, pp 276–277Google Scholar
  5. 5.
    Chan JKC, Quintanilla-Martinez L, Ferry JA, Peh SC (2008) Extranodal NK/T-cell lymphoma, nasal type. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. International Agency for Research on Cancer, Lyon, pp 285–288Google Scholar
  6. 6.
    Kimura H (2006) Pathogenesis of chronic active Epstein–Barr virus infection: is this an infectious disease, lymphoproliferative disorder, or immunodeficiency? Rev Med Virol 16:251–261PubMedCrossRefGoogle Scholar
  7. 7.
    Shibata Y, Hoshino Y, Hara S, Yagasaki H, Kojima S, Nishiyama Y, Morishima T, Kimura H (2006) Clonality analysis by sequence variation of the latent membrane protein 1 gene in patients with chronic active Epstein–Barr virus infection. J Med Virol 78:770–779PubMedCrossRefGoogle Scholar
  8. 8.
    Ohshima K, Kimura H, Yoshino T, Kim CW, Ko YH, Lee SS, Peh SC, Chan JK (2008) Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder (LPD) in children and young adults: overlap with chronic active EBV infection and infantile fulminant EBV T-LPD. Pathol Int 58:209–217PubMedCrossRefGoogle Scholar
  9. 9.
    Okano M, Kawa K, Kimura H, Yachie A, Wakiguchi H, Maeda A, Imai S, Ohga S, Kanegane H, Tsuchiya S, Morio T, Mori M, Yokota S, Imashuku S (2005) Proposed guidelines for diagnosing chronic active Epstein–Barr virus infection. Am J Hematol 80:64–69PubMedCrossRefGoogle Scholar
  10. 10.
    Ohshima K, Suzumiya J, Sugihara M, Nagafuchi S, Ohga S, Kikuchi M (1998) Clinicopathological study of severe chronic active Epstein–Barr virus infection that developed in association with lymphoproliferative disorder and/or hemophagocytic syndrome. Pathol Int 48:934–943PubMedCrossRefGoogle Scholar
  11. 11.
    Kimura H, Hoshino Y, Kanegane H, Tsuge I, Okamura T, Kawa K, Morishima T (2001) Clinical and virologic characteristics of chronic active Epstein–Barr virus infection. Blood 98:280–286PubMedCrossRefGoogle Scholar
  12. 12.
    Quintanilla-Martinez L, Kimura H, Jaffe ES (2008) EBV-positive T-cell lymphoproliferative disorders of childhood. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. International Agency for Research on Cancer, Lyon, pp 278–280Google Scholar
  13. 13.
    Quintanilla-Martinez L, Kumar S, Fend F, Reyes E, Teruya-Feldstein J, Kingma DW, Sorbara L, Raffeld M, Straus SE, Jaffe ES (2000) Fulminant EBV(+) T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome. Blood 96:443–451PubMedGoogle Scholar
  14. 14.
    Chuang HC, Lay JD, Chuang SE, Hsieh WC, Chang Y, Su IJ (2007) Epstein–Barr virus (EBV) latent membrane protein-1 down-regulates tumor necrosis factor-alpha (TNF-alpha) receptor-1 and confers resistance to TNF-alpha-induced apoptosis in T cells: implication for the progression to T-cell lymphoma in EBV-associated hemophagocytic syndrome. Am J Pathol 170:1607–1617PubMedCrossRefGoogle Scholar
  15. 15.
    Lay JD, Tsao CJ, Chen JY, Kadin ME, Su IJ (1997) Upregulation of tumor necrosis factor-alpha gene by Epstein–Barr virus and activation of macrophages in Epstein–Barr virus-infected T cells in the pathogenesis of hemophagocytic syndrome. J Clin Invest 100:1969–1979PubMedCrossRefGoogle Scholar
  16. 16.
    Su IJ, Wang CH, Cheng AL, Chen RL (1995) Hemophagocytic syndrome in Epstein–Barr virus-associated T-lymphoproliferative disorders: disease spectrum, pathogenesis, and management. Leuk Lymphoma 19:401–406PubMedCrossRefGoogle Scholar
  17. 17.
    Fox CP, Shannon-Lowe C, Gothard P, Kishore B, Neilson J, O’Connor N, Rowe M (2010) Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in adults characterized by high viral genome load within circulating natural killer cells. Clin Infect Dis 51:66–69PubMedCrossRefGoogle Scholar
  18. 18.
    Imashuku S, Hibi S, Tabata Y, Itoh E, Hashida T, Tsunamoto K, Ishimoto K, Kawano F (2000) Outcome of clonal hemophagocytic lymphohistiocytosis: analysis of 32 cases. Leuk Lymphoma 37:577–584PubMedCrossRefGoogle Scholar
  19. 19.
    Magana M, Sangueza P, Gil-Beristain J, Sanchez-Sosa S, Salgado A, Ramon G, Sangueza OP (1998) Angiocentric cutaneous T-cell lymphoma of childhood (hydroa-like lymphoma): a distinctive type of cutaneous T-cell lymphoma. J Am Acad Dermatol 38:574–579PubMedCrossRefGoogle Scholar
  20. 20.
    Wu YH, Chen HC, Hsiao PF, Tu MI, Lin YC, Wang TY (2007) Hydroa vacciniforme-like Epstein–Barr virus-associated monoclonal T-lymphoproliferative disorder in a child. Int J Dermatol 46:1081–1086PubMedCrossRefGoogle Scholar
  21. 21.
    Oono T, Arata J, Masuda T, Ohtsuki Y (1986) Coexistence of hydroa vacciniforme and malignant lymphoma. Arch Dermatol 122:1306–1309PubMedCrossRefGoogle Scholar
  22. 22.
    Iwatsuki K, Ohtsuka M, Akiba H, Kaneko F (1999) Atypical hydroa vacciniforme in childhood: from a smoldering stage to Epstein–Barr virus-associated lymphoid malignancy. J Am Acad Dermatol 40:283–284PubMedCrossRefGoogle Scholar
  23. 23.
    Cho KH, Lee SH, Kim CW, Jeon YK, Kwon IH, Cho YJ, Lee SK, Suh DH, Chung JH, Yoon TY, Lee SJ (2004) Epstein–Barr virus-associated lymphoproliferative lesions presenting as a hydroa vacciniforme-like eruption: an analysis of six cases. Br J Dermatol 151:372–380PubMedCrossRefGoogle Scholar
  24. 24.
    Kasahara Y, Yachie A, Takei K, Kanegane C, Okada K, Ohta K, Seki H, Igarashi N, Maruhashi K, Katayama K, Katoh E, Terao G, Sakiyama Y, Koizumi S (2001) Differential cellular targets of Epstein–Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection. Blood 98:1882–1888PubMedCrossRefGoogle Scholar
  25. 25.
    Kimura H, Ito Y, Kawabe S, Gotoh K, Takahashi Y, Kojima S, Naoe T, Esaki S, Kikuta A, Sawada A, Kawa K, Ohshima K, Nakamura S (2012) EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases. Blood 119:673–686PubMedCrossRefGoogle Scholar
  26. 26.
    Ahn JS, Rew SY, Shin MG, Kim HR, Yang DH, Cho D, Kim SH, Bae SY, Lee SR, Kim YK, Kim HJ, Lee JJ (2010) Clinical significance of clonality and Epstein–Barr virus infection in adult patients with hemophagocytic lymphohistiocytosis. Am J Hematol 85:719–722PubMedCrossRefGoogle Scholar
  27. 27.
    Matsuda K, Nakazawa Y, Yanagisawa R, Honda T, Ishii E, Koike K (2011) Detection of T-cell receptor gene rearrangement in children with Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis using the BIOMED-2 multiplex polymerase chain reaction combined with GeneScan analysis. Clin Chim Acta 412:1554–1558PubMedCrossRefGoogle Scholar
  28. 28.
    Gu H, Chang B, Qian H, Li G (1996) A clinical study on severe hydroa vacciniforme. Chin Med J (Engl) 109:645–647Google Scholar
  29. 29.
    Iwatsuki K, Satoh M, Yamamoto T, Oono T, Morizane S, Ohtsuka M, Xu ZG, Suzuki D, Tsuji K (2006) Pathogenic link between hydroa vacciniforme and Epstein–Barr virus-associated hematologic disorders. Arch Dermatol 142:587–595PubMedCrossRefGoogle Scholar
  30. 30.
    Gupta G, Man I, Kemmett D (2000) Hydroa vacciniforme: a clinical and follow-up study of 17 cases. J Am Acad Dermatol 42:208–213PubMedCrossRefGoogle Scholar
  31. 31.
    Cho KH, Kim CW, Lee DY, Sohn SJ, Kim DW, Chung JH (1996) An Epstein–Barr virus-associated lymphoproliferative lesion of the skin presenting as recurrent necrotic papulovesicles of the face. Br J Dermatol 134:791–796PubMedCrossRefGoogle Scholar
  32. 32.
    Barrionuevo C, Anderson VM, Zevallos-Giampietri E, Zaharia M, Misad O, Bravo F, Caceres H, Taxa L, Martinez MT, Wachtel A, Piris MA (2002) Hydroa-like cutaneous T-cell lymphoma: a clinicopathologic and molecular genetic study of 16 pediatric cases from Peru. Appl Immunohistochem Mol Morphol 10:7–14PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Young-Hyeh Ko
    • 1
  • Hyun-Jung Kim
    • 2
  • Young-Ha Oh
    • 3
  • Geongsin Park
    • 4
  • Seung-Sook Lee
    • 5
  • Jooryung Huh
    • 6
  • Chul-Woo Kim
    • 7
  • Insun Kim
    • 8
  • Siok-Bian Ng
    • 9
  • Soo-Young Tan
    • 10
  • Shih-Sung Chuang
    • 11
  • Naoya Nakamura
    • 12
  • Tadashi Yoshino
    • 13
  • Shigeo Nakamura
    • 14
  • Hiroshi Kimura
    • 15
  • Koichi Ohshima
    • 16
  1. 1.Department of Pathology, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  2. 2.Department of PathologyInje University, Sanggye Paik HospitalSeoulSouth Korea
  3. 3.Department of PathologyHanyang University Guri HospitalGuri-siSouth Korea
  4. 4.Catholic University St. Mary’s HospitalSeoulSouth Korea
  5. 5.Department of Pathology, Korea Cancer Center HospitalKorea Institute of Radiological and Medical SciencesSeoulSouth Korea
  6. 6.Department of Pathology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea
  7. 7.Department of PathologySeoul National University HospitalSeoulSouth Korea
  8. 8.Department of PathologyKorea University College of MedicineSeoulSouth Korea
  9. 9.Department of PathologyNational University Health SystemSingaporeSingapore
  10. 10.Department of PathologySingapore General HospitalSingaporeSingapore
  11. 11.Department of PathologyChi-Mei Medical CentreTainanTaiwan
  12. 12.Department of PathologyTokai University School of MedicineIseharaJapan
  13. 13.Department of PathologyOkayama University Graduate School of MedicineOkayamaJapan
  14. 14.Department of PathologyNagoya UniversityNagoyaJapan
  15. 15.Department of VirologyNagoya UniversityNagoyaJapan
  16. 16.Department of Pathology, School of MedicineKurume UniversityKurumeJapan

Personalised recommendations