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Epstein–Barr Virus: Epidemiology and Clinical Features of Related Cancer

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Viruses and Human Cancer

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Abstract

Epstein–Barr virus, one of the most ubiquitous viruses on earth, with a worldwide seroprevalence rate of about 90 %, has devised a clever strategy to assure its survival and lifelong persistence in the human host. In the vast majority of infected hosts, EBV remains in a nearly silent latent state that remains asymptomatic throughout life. In contrast, in the immunodeficient host, EBV infection can lead to severe disease ranging from organ failure to cancer. Infrequently, EBV-associated cancers also develop sporadically in patients with no apparent immunodeficiency. Some EBV-associated cancers are found in geographically distinct regions. Endemic Burkitt lymphoma occurs in subequatorial Africa and New Guinea in areas plagued by holoendemic falciparum malaria. Nasopharyngeal carcinoma most often occurs in Southeast Asians and native North Americans, with exposure to potentially tumor-promoting substance in food and the environment. Many EBV-related T/NK tumors occur most commonly in East Asia. The increased risk of EBV-related disease in these populations is likely multifactorial, including both genetic and environmental factors.

Patients with primary and acquired immunodeficiency are at significantly increased risk of EBV-positive lymphoma. The variety of EBV-positive human malignant tumors in both immunocompromised and immunocompetent hosts of all ages includes seven subtypes of B cell lymphoma, five subtypes of T/NK cell lymphoma, four subtypes of immunodeficiency-associated lymphoma, two sarcomas, and lymphoepithelial carcinoma from at least nine primary sites. Given the restricted pattern of EBV gene expression in these tumors it is clear that EBV latency genes and microRNA likely contribute to tumor formation and growth.

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References

  1. Kangro HO, Osman HK, Lau YL, Heath RB, Yeung CY, Ng MH. Seroprevalence of antibodies to human herpesviruses in England and Hong Kong. J Med Virol. 1994;43:91–6.

    CAS  PubMed  Google Scholar 

  2. Dowd JB, Palermo T, Brite J, McDade TW, Aiello A. Seroprevalence of Epstein-Barr virus infection in U.S. children ages 6–19, 2003–2010. PLoS One. 2013;8:e64921.

    CAS  PubMed Central  PubMed  Google Scholar 

  3. de-Thé G, Day N, Geser A, et al. Sero-epidemiology of the Epstein-Barr virus: preliminary analysis of an international study—a review. IARC Sci Publ. 1975;11(Pt 2):3–16.

    PubMed  Google Scholar 

  4. Niederman JC. Infectious mononucleosis: observations on transmission. Yale J Biol Med. 1982;55:259–64.

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Ikuta K, Satoh Y, Hoshikawa Y, Sairenji T. Detection of Epstein-Barr virus in salivas and throat washings in healthy adults and children. Microbes Infect. 2000;2:115–20.

    CAS  PubMed  Google Scholar 

  6. Mbulaiteye SM, Walters M, Engels EA, et al. High levels of Epstein-Barr virus DNA in saliva and peripheral blood from Ugandan mother-child pairs. J Infect Dis. 2006;193:422–6.

    PubMed  Google Scholar 

  7. Godshall SE, Kirchner JT. Infectious mononucleosis. Complexities of a common syndrome. Postgrad Med. 2000;107:175–9, 183–4, 186.

    CAS  PubMed  Google Scholar 

  8. Luzuriaga K, Sullivan JL. Infectious mononucleosis. N Engl J Med. 2010;362:1993–2000.

    CAS  PubMed  Google Scholar 

  9. Sixbey JW, Nedrud JG, Raab-Traub N, Hanes RA, Pagano JS. Epstein-Barr virus replication in oropharyngeal epithelial cells. N Engl J Med. 1984;310:1225–30.

    CAS  PubMed  Google Scholar 

  10. Kurth J, Spieker T, Wustrow J, et al. EBV-infected B cells in infectious mononucleosis: viral strategies for spreading in the B cell compartment and establishing latency. Immunity. 2000;13:485–95.

    CAS  PubMed  Google Scholar 

  11. Joseph AM, Babcock GJ, Thorley-Lawson DA. Cells expressing the Epstein-Barr virus growth program are present in and restricted to the naive B-cell subset of healthy tonsils. J Virol. 2000;74:9964–71.

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Chaganti S, Heath EM, Bergler W, et al. Epstein-Barr virus colonization of tonsillar and peripheral blood B-cell subsets in primary infection and persistence. Blood. 2009;113:6372–81.

    PubMed  Google Scholar 

  13. Hudnall SD, Ge Y, Wei L, Yang NP, Wang HQ, Chen T. Distribution and phenotype of Epstein-Barr virus-infected cells in human pharyngeal tonsils. Mod Pathol. 2005;18:519–27.

    PubMed  Google Scholar 

  14. Joseph AM, Babcock GJ, Thorley-Lawson DA. EBV persistence involves strict selection of latently infected B cells. J Immunol. 2000;165:2975–81.

    CAS  PubMed  Google Scholar 

  15. Hadinoto V, Shapiro M, Sun CC, Thorley-Lawson DA. The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output. PLoS Pathog. 2009;5:e1000496.

    PubMed Central  PubMed  Google Scholar 

  16. Hudnall SD, Patel J, Schwab H, Martinez J. Comparative immunophenotypic features of EBV-positive and EBV-negative atypical lymphocytosis. Cytometry B Clin Cytom. 2003;55:22–8.

    PubMed  Google Scholar 

  17. Maia DM, Peace-Brewer AL. Chronic, active Epstein-Barr virus infection. Curr Opin Hematol. 2000;7:59–63.

    CAS  PubMed  Google Scholar 

  18. Shibata D, Weiss LM. Epstein-Barr virus-associated gastric adenocarcinoma. Am J Pathol. 1992;140:769–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Imai S, Koizumi S, Sugiura M, et al. Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein-Barr virus latent infection protein. Proc Natl Acad Sci U S A. 1994;91:9131–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Chan JK, Yip TT, Tsang WY, Poon YF, Wong CS, Ma VW. Specific association of Epstein-Barr virus with lymphoepithelial carcinoma among tumors and tumorlike lesions of the salivary gland. Arch Pathol Lab Med. 1994;118:994–7.

    CAS  PubMed  Google Scholar 

  21. Kingma DW, Shad A, Tsokos M, et al. Epstein-Barr virus (EBV)-associated smooth-muscle tumor arising in a post-transplant patient treated successfully for two PT-EBV-associated large-cell lymphomas. Case report. Am J Surg Pathol. 1996;20:1511–9.

    CAS  PubMed  Google Scholar 

  22. McClain KL, Leach CT, Jenson HB, et al. Association of Epstein-Barr virus with leiomyosarcomas in children with AIDS. N Engl J Med. 1995;332:12–8.

    CAS  PubMed  Google Scholar 

  23. Anagnostopoulos I, Hummel M. Epstein-Barr virus in tumours. Histopathology. 1996;29:297–315.

    CAS  PubMed  Google Scholar 

  24. Tatsumi E, Purtilo D. Epstein-Barr virus (EBV) and X-linked lymphoproliferative syndrome (XLP). AIDS Res. 1986;2 Suppl 1:S109–13.

    PubMed  Google Scholar 

  25. Rezaei N, Mahmoudi E, Aghamohammadi A, Das R, Nichols KE. X-linked lymphoproliferative syndrome: a genetic condition typified by the triad of infection, immunodeficiency and lymphoma. Br J Haematol. 2011;152:13–30.

    CAS  PubMed  Google Scholar 

  26. Niedobitek G, Young LS, Lau R, et al. Epstein-Barr virus infection in oral hairy leukoplakia: virus replication in the absence of a detectable latent phase. J Gen Virol. 1991;72(Pt 12):3035–46.

    PubMed  Google Scholar 

  27. Cohen JI. Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency. Medicine (Baltimore). 1991;70:137–60.

    CAS  Google Scholar 

  28. Parvaneh N, Filipovich AH, Borkhardt A. Primary immunodeficiencies predisposed to Epstein-Barr virus-driven haematological diseases. Br J Haematol. 2013;162:573–86.

    CAS  PubMed  Google Scholar 

  29. Li X, Fasano R, Wang E, Yao KT, Marincola FM. HLA associations with nasopharyngeal carcinoma. Curr Mol Med. 2009;9:751–65.

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2006;15:1765–77.

    CAS  PubMed  Google Scholar 

  31. Chan SH, Day NE, Kunaratnam N, Chia KB, Simons MJ. HLA and nasopharyngeal carcinoma in Chinese—a further study. Int J Cancer. 1983;32:171–6.

    CAS  PubMed  Google Scholar 

  32. Yu MC, Ho JH, Lai SH, Henderson BE. Cantonese-style salted fish as a cause of nasopharyngeal carcinoma: report of a case-control study in Hong Kong. Cancer Res. 1986;46:956–61.

    CAS  PubMed  Google Scholar 

  33. Yu MC, Huang TB, Henderson BE. Diet and nasopharyngeal carcinoma: a case-control study in Guangzhou, China. Int J Cancer. 1989;43:1077–82.

    CAS  PubMed  Google Scholar 

  34. Armstrong RW, Armstrong MJ, Yu MC, Henderson BE. Salted fish and inhalants as risk factors for nasopharyngeal carcinoma in Malaysian Chinese. Cancer Res. 1983;43:2967–70.

    CAS  PubMed  Google Scholar 

  35. West S, Hildesheim A, Dosemeci M. Non-viral risk factors for nasopharyngeal carcinoma in the Philippines: results from a case-control study. Int J Cancer. 1993;55:722–7.

    CAS  PubMed  Google Scholar 

  36. Poirier S, Ohshima H, de-Thé G, Hubert A, Bourgade MC, Bartsch H. Volatile nitrosamine levels in common foods from Tunisia, south China and Greenland, high-risk areas for nasopharyngeal carcinoma (NPC). Int J Cancer. 1987;39:293–6.

    CAS  PubMed  Google Scholar 

  37. Ito Y, Ohigashi H, Koshimizu K, Yi Z. Epstein-Barr virus-activating principle in the ether extracts of soils collected from under plants which contain active diterpene esters. Cancer Lett. 1983;19:113–7.

    CAS  PubMed  Google Scholar 

  38. Yu WM, Hussain SS. Incidence of nasopharyngeal carcinoma in Chinese immigrants, compared with Chinese in China and South East Asia: review. J Laryngol Otol. 2009;123:1067–74.

    CAS  PubMed  Google Scholar 

  39. Fedder M, Gonzalez MF. Nasopharyngeal carcinoma. Brief review. Am J Med. 1985;79:365–9.

    CAS  PubMed  Google Scholar 

  40. Shanmugaratnam K. Histological typing of nasopharyngeal carcinoma. IARC Sci Publ. 1978;(20):3–12.

    Google Scholar 

  41. Pathmanathan R, Prasad U, Chandrika G, Sadler R, Flynn K, Raab-Traub N. Undifferentiated, nonkeratinizing, and squamous cell carcinoma of the nasopharynx. Variants of Epstein-Barr virus-infected neoplasia. Am J Pathol. 1995;146:1355–67.

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Niedobitek G, Agathanggelou A, Nicholls JM. Epstein-Barr virus infection and the pathogenesis of nasopharyngeal carcinoma: viral gene expression, tumour cell phenotype, and the role of the lymphoid stroma. Semin Cancer Biol. 1996;7:165–74.

    CAS  PubMed  Google Scholar 

  43. Niedobitek G, Hansmann ML, Herbst H, et al. Epstein-Barr virus and carcinomas: undifferentiated carcinomas but not squamous cell carcinomas of the nasopharynx are regularly associated with the virus. J Pathol. 1991;165:17–24.

    CAS  PubMed  Google Scholar 

  44. Raab-Traub N, Flynn K, Pearson G, et al. The differentiated form of nasopharyngeal carcinoma contains Epstein-Barr virus DNA. Int J Cancer. 1987;39:25–9.

    CAS  PubMed  Google Scholar 

  45. Young LS, Dawson CW, Clark D, et al. Epstein-Barr virus gene expression in nasopharyngeal carcinoma. J Gen Virol. 1988;69(Pt 5):1051–65.

    CAS  PubMed  Google Scholar 

  46. Gilligan KJ, Rajadurai P, Lin JC, et al. Expression of the Epstein-Barr virus BamHI A fragment in nasopharyngeal carcinoma: evidence for a viral protein expressed in vivo. J Virol. 1991;65:6252–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Yoshizaki T, Kondo S, Wakisaka N, et al. Pathogenic role of Epstein-Barr virus latent membrane protein-1 in the development of nasopharyngeal carcinoma. Cancer Lett. 2013;337:1–7.

    CAS  PubMed  Google Scholar 

  48. Dawson CW, Rickinson AB, Young LS. Epstein-Barr virus latent membrane protein inhibits human epithelial cell differentiation. Nature. 1990;344:777–80.

    CAS  PubMed  Google Scholar 

  49. Murono S, Inoue H, Tanabe T, et al. Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells. Proc Natl Acad Sci U S A. 2001;98:6905–10.

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Kusano S, Raab-Traub N. An Epstein-Barr virus protein interacts with Notch. J Virol. 2001;75:384–95.

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Hoebe EK, Hutajulu SH, van Beek J, et al. Purified hexameric Epstein-Barr virus-encoded BARF1 protein for measuring anti-BARF1 antibody responses in nasopharyngeal carcinoma patients. Clin Vaccine Immunol. 2011;18:298–304.

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Chang MS, Kim DH, Roh JK, et al. Epstein-Barr virus-encoded BARF1 promotes proliferation of gastric carcinoma cells through regulation of NF-κB. J Virol. 2013;87:10515–23.

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Pan ZG, Kashuba VI, Liu XQ, et al. High frequency somatic mutations in RASSF1A in nasopharyngeal carcinoma. Cancer Biol Ther. 2005;4:1116–22.

    CAS  PubMed  Google Scholar 

  54. Cheng Y, Poulos NE, Lung ML, et al. Functional evidence for a nasopharyngeal carcinoma tumor suppressor gene that maps at chromosome 3p21.3. Proc Natl Acad Sci U S A. 1998;95:3042–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Lo KW, Kwong J, Hui AB, et al. High frequency of promoter hypermethylation of RASSF1A in nasopharyngeal carcinoma. Cancer Res. 2001;61:3877–81.

    CAS  PubMed  Google Scholar 

  56. Yi HM, Li H, Peng D, et al. Genetic and epigenetic alterations of LTF at 3p21.3 in nasopharyngeal carcinoma. Oncol Res. 2006;16:261–72.

    CAS  PubMed  Google Scholar 

  57. Lu QL, Elia G, Lucas S, Thomas JA. Bcl-2 proto-oncogene expression in Epstein-Barr-virus-associated nasopharyngeal carcinoma. Int J Cancer. 1993;53:29–35.

    CAS  PubMed  Google Scholar 

  58. Qin HD, Shugart YY, Bei JX, et al. Comprehensive pathway-based association study of DNA repair gene variants and the risk of nasopharyngeal carcinoma. Cancer Res. 2011;71:3000–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Xiao M, Zhang L, Zhu X, et al. Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population. BMC Cancer. 2010;10:147.

    PubMed Central  PubMed  Google Scholar 

  60. Shao JY, Cao Y, Miao XP, et al. A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is closely associated with high risk of nasopharyngeal carcinoma in Cantonese from southern China. Chin J Cancer. 2011;30:620–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  61. Lee JM, Kim H, Noh SH, Lee WY, Kim SJ, Park JH. Expression of Epstein-Barr virus gene and clonality of infiltrated T lymphocytes in Epstein-Barr virus-associated gastric carcinoma. Immune Netw. 2011;11:50–8.

    PubMed Central  PubMed  Google Scholar 

  62. Chetty R. Gastrointestinal cancers accompanied by a dense lymphoid component: an overview with special reference to gastric and colonic medullary and lymphoepithelioma-like carcinomas. J Clin Pathol. 2012;65:1062–5.

    PubMed  Google Scholar 

  63. Rowlands DC, Ito M, Mangham DC, et al. Epstein-Barr virus and carcinomas: rare association of the virus with gastric adenocarcinomas. Br J Cancer. 1993;68:1014–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Oda K, Tamaru J, Takenouchi T, et al. Association of Epstein-Barr virus with gastric carcinoma with lymphoid stroma. Am J Pathol. 1993;143:1063–71.

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Cho HJ, Kim JY, Yoo J, Lee SS. Gastric carcinoma with lymphoid stroma: incidence of EBV and Helicobacter pylori infection. Appl Immunohistochem Mol Morphol. 2003;11:149–52.

    PubMed  Google Scholar 

  66. Fukayama M. Epstein-Barr virus and gastric carcinoma. Pathol Int. 2010;60:337–50.

    CAS  PubMed  Google Scholar 

  67. Iizasa H, Nanbo A, Nishikawa J, Jinushi M, Yoshiyama H. Epstein-Barr Virus (EBV)-associated gastric carcinoma. Viruses. 2012;4:3420–39.

    PubMed Central  PubMed  Google Scholar 

  68. Osato T, Imai S. Epstein-Barr virus and gastric carcinoma. Semin Cancer Biol. 1996;7:175–82.

    CAS  PubMed  Google Scholar 

  69. Fukayama M, Ushiku T. Epstein-Barr virus-associated gastric carcinoma. Pathol Res Pract. 2011;207:529–37.

    CAS  PubMed  Google Scholar 

  70. Kida Y, Miyauchi K, Takano Y. Gastric adenocarcinoma with differentiation to sarcomatous components associated with monoclonal Epstein-Barr virus infection and LMP-1 expression. Virchows Arch A Pathol Anat Histopathol. 1993;423:383–7.

    CAS  PubMed  Google Scholar 

  71. Tang W, Morgan DR, Meyers MO, et al. Epstein-Barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile. Infect Agent Cancer. 2012;7:21.

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Song HJ, Srivastava A, Lee J, et al. Host inflammatory response predicts survival of patients with Epstein-Barr virus-associated gastric carcinoma. Gastroenterology. 2010;139:84–92.e2.

    PubMed  Google Scholar 

  73. McGuire LJ, Huang DP, Teoh R, Arnold M, Wong K, Lee JC. Epstein-Barr virus genome in thymoma and thymic lymphoid hyperplasia. Am J Pathol. 1988;131:385–90.

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Lanier AP, Clift SR, Bornkamm G, Henle W, Goepfert H, Raab-Traub N. Epstein-Barr virus and malignant lymphoepithelial lesions of the salivary gland. Arctic Med Res. 1991;50:55–61.

    CAS  PubMed  Google Scholar 

  75. Gaffey MJ, Frierson HF, Mills SE, et al. Medullary carcinoma of the breast. Identification of lymphocyte subpopulations and their significance. Mod Pathol. 1993;6:721–8.

    CAS  PubMed  Google Scholar 

  76. Tseng CJ, Pao CC, Tseng LH, et al. Lymphoepithelioma-like carcinoma of the uterine cervix: association with Epstein-Barr virus and human papillomavirus. Cancer. 1997;80:91–7.

    CAS  PubMed  Google Scholar 

  77. Chen PC, Pan CC, Hsu WH, Ka HJ, Yang AH. Epstein-Barr virus-associated lymphoepithelioma-like carcinoma of the esophagus. Hum Pathol. 2003;34:407–11.

    CAS  PubMed  Google Scholar 

  78. Chen CJ, Jeng LB, Huang SF. Lymphoepithelioma-like hepatocellular carcinoma. Chang Gung Med J. 2007;30:172–7.

    PubMed  Google Scholar 

  79. Jeng YM, Chen CL, Hsu HC. Lymphoepithelioma-like cholangiocarcinoma: an Epstein-Barr virus-associated tumor. Am J Surg Pathol. 2001;25:516–20.

    CAS  PubMed  Google Scholar 

  80. Aoki R, Mitsui H, Harada K, et al. A case of lymphoepithelioma-like carcinoma of the skin associated with Epstein-Barr virus infection. J Am Acad Dermatol. 2010;62:681–4.

    PubMed  Google Scholar 

  81. Terada T. Epstein-Barr virus associated lymphoepithelial carcinoma of the esophagus. Int J Clin Exp Med. 2013;6:219–26.

    PubMed Central  PubMed  Google Scholar 

  82. Chen PC, Pan CC, Yang AH, Wang LS, Chiang H. Detection of Epstein-Barr virus genome within thymic epithelial tumours in Taiwanese patients by nested PCR, PCR in situ hybridization, and RNA in situ hybridization. J Pathol. 2002;197:684–8.

    CAS  PubMed  Google Scholar 

  83. Shimoyama Y, Oyama T, Asano N, et al. Senile Epstein-Barr virus-associated B-cell lymphoproliferative disorders: a mini review. J Clin Exp Hematop. 2006;46:1–4.

    PubMed  Google Scholar 

  84. Oyama T, Ichimura K, Suzuki R, et al. Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol. 2003;27:16–26.

    PubMed  Google Scholar 

  85. Oyama T, Yamamoto K, Asano N, et al. Age-related EBV-associated B-cell lymphoproliferative disorders constitute a distinct clinicopathologic group: a study of 96 patients. Clin Cancer Res. 2007;13:5124–32.

    CAS  PubMed  Google Scholar 

  86. Iuchi K, Aozasa K, Yamamoto S, et al. Non-Hodgkin’s lymphoma of the pleural cavity developing from long-standing pyothorax. Summary of clinical and pathological findings in thirty-seven cases. Jpn J Clin Oncol. 1989;19:249–57.

    CAS  PubMed  Google Scholar 

  87. Nakatsuka S, Yao M, Hoshida Y, Yamamoto S, Iuchi K, Aozasa K. Pyothorax-associated lymphoma: a review of 106 cases. J Clin Oncol. 2002;20:4255–60.

    PubMed  Google Scholar 

  88. Aozasa K, Takakuwa T, Nakatsuka S. Pyothorax-associated lymphoma: a lymphoma developing in chronic inflammation. Adv Anat Pathol. 2005;12:324–31.

    PubMed  Google Scholar 

  89. Petitjean B, Jardin F, Joly B, et al. Pyothorax-associated lymphoma: a peculiar clinicopathologic entity derived from B cells at late stage of differentiation and with occasional aberrant dual B- and T-cell phenotype. Am J Surg Pathol. 2002;26:724–32.

    PubMed  Google Scholar 

  90. Takakuwa T, Ham MF, Luo WJ, Nakatsuka S, Daibata M, Aozasa K. Loss of expression of Epstein-Barr virus nuclear antigen-2 correlates with a poor prognosis in cases of pyothorax-associated lymphoma. Int J Cancer. 2006;118:2782–9.

    CAS  PubMed  Google Scholar 

  91. Hummel M, Anagnostopoulos I, Korbjuhn P, Stein H. Epstein-Barr virus in B-cell non-Hodgkin’s lymphomas: unexpected infection patterns and different infection incidence in low- and high-grade types. J Pathol. 1995;175:263–71.

    CAS  PubMed  Google Scholar 

  92. Park S, Lee J, Ko YH, et al. The impact of Epstein-Barr virus status on clinical outcome in diffuse large B-cell lymphoma. Blood. 2007;110:972–8.

    CAS  PubMed  Google Scholar 

  93. Beltran BE, Morales D, Quiñones P, Medeiros LJ, Miranda RN, Castillo JJ. EBV-positive diffuse large b-cell lymphoma in young immunocompetent individuals. Clin Lymphoma Myeloma Leuk. 2011;11:512–6.

    PubMed  Google Scholar 

  94. Wada N, Ikeda J, Hori Y, et al. Epstein-Barr virus in diffuse large B-Cell lymphoma in immunocompetent patients in Japan is as low as in Western Countries. J Med Virol. 2011;83:317–21.

    PubMed  Google Scholar 

  95. Morales D, Beltran B, De Mendoza FH, et al. Epstein-Barr virus as a prognostic factor in de novo nodal diffuse large B-cell lymphoma. Leuk Lymphoma. 2010;51:66–72.

    CAS  PubMed  Google Scholar 

  96. Cohen M, De Matteo E, Narbaitz M, Carreño FA, Preciado MV, Chabay PA. Epstein-Barr virus presence in pediatric diffuse large B-cell lymphoma reveals a particular association and latency patterns: analysis of viral role in tumor microenvironment. Int J Cancer. 2013;132:1572–80.

    CAS  PubMed  Google Scholar 

  97. White RE, Rämer PC, Naresh KN, et al. EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors. J Clin Invest. 2012;122:1487–502.

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Myers JL, Kurtin PJ, Katzenstein AL, et al. Lymphomatoid granulomatosis. Evidence of immunophenotypic diversity and relationship to Epstein-Barr virus infection. Am J Surg Pathol. 1995;19:1300–12.

    CAS  PubMed  Google Scholar 

  99. Jaffe ES, Wilson WH. Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications. Cancer Surv. 1997;30:233–48.

    CAS  PubMed  Google Scholar 

  100. Roschewski M, Wilson WH. Lymphomatoid granulomatosis. Cancer J. 2012;18:469–74.

    CAS  PubMed  Google Scholar 

  101. Delecluse HJ, Anagnostopoulos I, Dallenbach F, et al. Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection. Blood. 1997;89:1413–20.

    CAS  PubMed  Google Scholar 

  102. Castillo J, Pantanowitz L, Dezube BJ. HIV-associated plasmablastic lymphoma: lessons learned from 112 published cases. Am J Hematol. 2008;83:804–9.

    PubMed  Google Scholar 

  103. Sarode SC, Sarode GS, Patil A. Plasmablastic lymphoma of the oral cavity: a review. Oral Oncol. 2010;46:146–53.

    PubMed  Google Scholar 

  104. Valera A, Balagué O, Colomo L, et al. IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas. Am J Surg Pathol. 2010;34:1686–94.

    PubMed Central  PubMed  Google Scholar 

  105. Nador RG, Cesarman E, Chadburn A, et al. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi’s sarcoma-associated herpes virus. Blood. 1996;88:645–56.

    CAS  PubMed  Google Scholar 

  106. Komanduri KV, Luce JA, McGrath MS, Herndier BG, Ng VL. The natural history and molecular heterogeneity of HIV-associated primary malignant lymphomatous effusions. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;13:215–26.

    CAS  PubMed  Google Scholar 

  107. Patel S, Xiao P. Primary effusion lymphoma. Arch Pathol Lab Med. 2013;137:1152–4.

    PubMed  Google Scholar 

  108. Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med. 1995;332:1186–91.

    CAS  PubMed  Google Scholar 

  109. Asou H, Tasaka T, Said JW, Daibata M, Kamada N, Koeffler HP. Co-infection of HHV-6 and HHV-8 is rare in primary effusion lymphoma. Leuk Res. 2000;24:59–61.

    CAS  PubMed  Google Scholar 

  110. Fassone L, Bhatia K, Gutierrez M, et al. Molecular profile of Epstein-Barr virus infection in HHV-8-positive primary effusion lymphoma. Leukemia. 2000;14:271–7.

    CAS  PubMed  Google Scholar 

  111. Jiang Y, Xu D, Zhao Y, Zhang L. Mutual inhibition between Kaposi’s sarcoma-associated herpesvirus and Epstein-Barr virus lytic replication initiators in dually-infected primary effusion lymphoma. PLoS One. 2008;3:e1569.

    PubMed Central  PubMed  Google Scholar 

  112. Xu D, Coleman T, Zhang J, et al. Epstein-Barr virus inhibits Kaposi’s sarcoma-associated herpesvirus lytic replication in primary effusion lymphomas. J Virol. 2007;81:6068–78.

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Spadavecchia S, Gonzalez-Lopez O, Carroll KD, Palmeri D, Lukac DM. Convergence of Kaposi’s sarcoma-associated herpesvirus reactivation with Epstein-Barr virus latency and cellular growth mediated by the notch signaling pathway in coinfected cells. J Virol. 2010;84:10488–500.

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Marcu KB, Harris LJ, Stanton LW, Erikson J, Watt R, Croce CM. Transcriptionally active c-myc oncogene is contained within NIARD, a DNA sequence associated with chromosome translocations in B-cell neoplasia. Proc Natl Acad Sci U S A. 1983;80:519–23.

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Dalla-Favera R, Martinotti S, Gallo RC, Erikson J, Croce CM. Translocation and rearrangements of the c-myc oncogene locus in human undifferentiated B-cell lymphomas. Science. 1983;219:963–7.

    CAS  PubMed  Google Scholar 

  116. Polack A, Hörtnagel K, Pajic A, et al. c-myc activation renders proliferation of Epstein-Barr virus (EBV)-transformed cells independent of EBV nuclear antigen 2 and latent membrane protein 1. Proc Natl Acad Sci U S A. 1996;93:10411–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  117. Raab-Traub N, Flynn K. The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation. Cell. 1986;47:883–9.

    CAS  PubMed  Google Scholar 

  118. Rowe M, Lear AL, Croom-Carter D, Davies AH, Rickinson AB. Three pathways of Epstein-Barr virus gene activation from EBNA1-positive latency in B lymphocytes. J Virol. 1992;66:122–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  119. Bell AI, Groves K, Kelly GL, et al. Analysis of Epstein-Barr virus latent gene expression in endemic Burkitt’s lymphoma and nasopharyngeal carcinoma tumour cells by using quantitative real-time PCR assays. J Gen Virol. 2006;87:2885–90.

    CAS  PubMed  Google Scholar 

  120. Pratt ZL, Kuzembayeva M, Sengupta S, Sugden B. The microRNAs of Epstein-Barr Virus are expressed at dramatically differing levels among cell lines. Virology. 2009;386:387–97.

    CAS  PubMed Central  PubMed  Google Scholar 

  121. Bornkamm GW. Epstein-Barr virus and its role in the pathogenesis of Burkitt’s lymphoma: an unresolved issue. Semin Cancer Biol. 2009;19:351–65.

    CAS  PubMed  Google Scholar 

  122. Choy EY, Siu KL, Kok KH, et al. An Epstein-Barr virus-encoded microRNA targets PUMA to promote host cell survival. J Exp Med. 2008;205:2551–60.

    CAS  PubMed Central  PubMed  Google Scholar 

  123. Hemann MT, Zilfou JT, Zhao Z, Burgess DJ, Hannon GJ, Lowe SW. Suppression of tumorigenesis by the p53 target PUMA. Proc Natl Acad Sci U S A. 2004;101:9333–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  124. Brady G, Macarthur GJ, Farrell PJ. Epstein-Barr virus and Burkitt lymphoma. Postgrad Med J. 2008;84:372–7.

    CAS  PubMed  Google Scholar 

  125. Morrow RH. Epidemiological evidence for the role of falciparum malaria in the pathogenesis of Burkitt’s lymphoma. IARC Sci Publ. 1985;(60):177–86.

    Google Scholar 

  126. Burkitt D. A children’s cancer dependent on climatic factors. Nature. 1962;194:232–4.

    CAS  PubMed  Google Scholar 

  127. Pope JH, Achong BG, Epstein MA, Biddulph J. Burkitt lymphoma in New Guinea: establishment of a line of lymphoblasts in vitro and description of their fine structure. J Natl Cancer Inst. 1967;39:933–45.

    CAS  PubMed  Google Scholar 

  128. Moormann AM, Heller KN, Chelimo K, et al. Children with endemic Burkitt lymphoma are deficient in EBNA1-specific IFN-gamma T cell responses. Int J Cancer. 2009;124:1721–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  129. Snider CJ, Cole SR, Chelimo K, et al. Recurrent Plasmodium falciparum malaria infections in Kenyan children diminish T-cell immunity to Epstein Barr virus lytic but not latent antigens. PLoS One. 2012;7:e31753.

    CAS  PubMed Central  PubMed  Google Scholar 

  130. Chattopadhyay PK, Chelimo K, Embury PB, et al. Holoendemic malaria exposure is associated with altered Epstein-Barr virus-specific CD8(+) T-cell differentiation. J Virol. 2013;87:1779–88.

    CAS  PubMed Central  PubMed  Google Scholar 

  131. Magrath I. Epidemiology: clues to the pathogenesis of Burkitt lymphoma. Br J Haematol. 2012;156:744–56.

    CAS  PubMed  Google Scholar 

  132. Andersson M, Klein G, Zeigler JL, Henle W. Association of Epstein-Barr viral genomes with American Burkitt lymphoma. Nature. 1976;260:357–9.

    CAS  PubMed  Google Scholar 

  133. Shiramizu B, Barriga F, Neequaye J, et al. Patterns of chromosomal breakpoint locations in Burkitt’s lymphoma: relevance to geography and Epstein-Barr virus association. Blood. 1991;77:1516–26.

    CAS  PubMed  Google Scholar 

  134. Roithmann S, Toledano M, Tourani JM, et al. HIV-associated non-Hodgkin’s lymphomas: clinical characteristics and outcome. The experience of the French Registry of HIV-associated tumors. Ann Oncol. 1991;2:289–95.

    CAS  PubMed  Google Scholar 

  135. Tran H, Nourse J, Hall S, Green M, Griffiths L, Gandhi MK. Immunodeficiency-associated lymphomas. Blood Rev. 2008;22:261–81.

    PubMed  Google Scholar 

  136. Gross TG, Savoldo B, Punnett A. Posttransplant lymphoproliferative diseases. Pediatr Clin North Am. 2010;57:481–503, table of contents.

    PubMed  Google Scholar 

  137. Tsao L, Hsi ED. The clinicopathologic spectrum of posttransplantation lymphoproliferative disorders. Arch Pathol Lab Med. 2007;131:1209–18.

    PubMed  Google Scholar 

  138. Nalesnik MA. Clinicopathologic characteristics of post-transplant lymphoproliferative disorders. Recent Results Cancer Res. 2002;159:9–18.

    PubMed  Google Scholar 

  139. Swerdlow SH. Classification of the posttransplant lymphoproliferative disorders: from the past to the present. Semin Diagn Pathol. 1997;14:2–7.

    CAS  PubMed  Google Scholar 

  140. Starzl TE, Penn I, Halgrimson CG. Immunosuppression and malignant neoplasms. N Engl J Med. 1970;283:934.

    CAS  PubMed  Google Scholar 

  141. Penn I. Cancer is a complication of severe immunosuppression. Surg Gynecol Obstet. 1986;162:603–10.

    CAS  PubMed  Google Scholar 

  142. Penn I. Post-transplant malignancy: the role of immunosuppression. Drug Saf. 2000;23:101–13.

    CAS  PubMed  Google Scholar 

  143. Ho M, Jaffe R, Miller G, et al. The frequency of Epstein-Barr virus infection and associated lymphoproliferative syndrome after transplantation and its manifestations in children. Transplantation. 1988;45:719–27.

    CAS  PubMed Central  PubMed  Google Scholar 

  144. Walker RC. Pretransplant assessment of the risk for posttransplant lymphoproliferative disorder. Transplant Proc. 1995;27:41.

    CAS  PubMed  Google Scholar 

  145. Morrison VA, Dunn DL, Manivel JC, Gajl-Peczalska KJ, Peterson BA. Clinical characteristics of post-transplant lymphoproliferative disorders. Am J Med. 1994;97:14–24.

    CAS  PubMed  Google Scholar 

  146. Cleary ML, Warnke R, Sklar J. Monoclonality of lymphoproliferative lesions in cardiac-transplant recipients. Clonal analysis based on immunoglobulin-gene rearrangements. N Engl J Med. 1984;310:477–82.

    CAS  PubMed  Google Scholar 

  147. Hanto DW, Birkenbach M, Frizzera G, Gajl-Peczalska KJ, Simmons RL, Schubach WH. Confirmation of the heterogeneity of posttransplant Epstein-Barr virus-associated B cell proliferations by immunoglobulin gene rearrangement analyses. Transplantation. 1989;47:458–64.

    CAS  PubMed  Google Scholar 

  148. Katz BZ, Raab-Traub N, Miller G. Latent and replicating forms of Epstein-Barr virus DNA in lymphomas and lymphoproliferative diseases. J Infect Dis. 1989;160:589–98.

    CAS  PubMed  Google Scholar 

  149. Locker J, Nalesnik M. Molecular genetic analysis of lymphoid tumors arising after organ transplantation. Am J Pathol. 1989;135:977–87.

    CAS  PubMed Central  PubMed  Google Scholar 

  150. Knowles DM, Cesarman E, Chadburn A, et al. Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders. Blood. 1995;85:552–65.

    CAS  PubMed  Google Scholar 

  151. Beral V, Peterman T, Berkelman R, Jaffe H. AIDS-associated non-Hodgkin lymphoma. Lancet. 1991;337:805–9.

    CAS  PubMed  Google Scholar 

  152. Levine AM. Hodgkin’s disease in the setting of HIV infection. Ann Oncol. 1993;4:621–2.

    CAS  PubMed  Google Scholar 

  153. Carbone A, Cesarman E, Spina M, Gloghini A, Schulz TF. HIV-associated lymphomas and gamma-herpesviruses. Blood. 2009;113:1213–24.

    CAS  PubMed  Google Scholar 

  154. Roschewski M, Wilson WH. EBV-associated lymphomas in adults. Best Pract Res Clin Haematol. 2012;25:75–89.

    PubMed Central  PubMed  Google Scholar 

  155. Gloghini A, Dolcetti R, Carbone A. Lymphomas occurring specifically in HIV-infected patients: from pathogenesis to pathology. Semin Cancer Biol. 2013;23:457–67.

    CAS  PubMed  Google Scholar 

  156. Menke DM, Griesser H, Moder KG, et al. Lymphomas in patients with connective tissue disease. Comparison of p53 protein expression and latent EBV infection in patients immunosuppressed and not immunosuppressed with methotrexate. Am J Clin Pathol. 2000;113:212–8.

    CAS  PubMed  Google Scholar 

  157. Hasserjian RP, Chen S, Perkins SL, et al. Immunomodulator agent-related lymphoproliferative disorders. Mod Pathol. 2009;22:1532–40.

    CAS  PubMed  Google Scholar 

  158. Bagg A, Dunphy CH. Immunosuppressive and immunomodulatory therapy-associated lymphoproliferative disorders. Semin Diagn Pathol. 2013;30:102–12.

    PubMed  Google Scholar 

  159. Gutensohn N, Cole P. Epidemiology of Hodgkin’s disease. Semin Oncol. 1980;7:92–102.

    CAS  PubMed  Google Scholar 

  160. Glaser SL, Jarrett RF. The epidemiology of Hodgkin’s disease. Baillieres Clin Haematol. 1996;9:401–16.

    CAS  PubMed  Google Scholar 

  161. Anastasi J, Bitter MA, Vardiman JW. The histopathologic diagnosis and subclassification of Hodgkin’s disease. Hematol Oncol Clin North Am. 1989;3:187–204.

    CAS  PubMed  Google Scholar 

  162. Küppers R. Molecular biology of Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program 2009:491–6.

    Google Scholar 

  163. Weiss LM, Strickler JG, Warnke RA, Purtilo DT, Sklar J. Epstein-Barr viral DNA in tissues of Hodgkin’s disease. Am J Pathol. 1987;129:86–91.

    CAS  PubMed Central  PubMed  Google Scholar 

  164. Anagnostopoulos I, Herbst H, Niedobitek G, Stein H. Demonstration of monoclonal EBV genomes in Hodgkin’s disease and Ki-1-positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization. Blood. 1989;74:810–6.

    CAS  PubMed  Google Scholar 

  165. Sandvej K, Munch M, Hamilton-Dutoit S. Mutations in the Epstein-Barr virus latent membrane protein-1 (BNLF-1) gene in spontaneous lymphoblastoid cell lines: effect on in vitro transformation associated parameters and tumorigenicity in SCID and nude mice. Clin Mol Pathol. 1996;49:M290–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  166. Hummel M, Anagnostopoulos I, Dallenbach F, Korbjuhn P, Dimmler C, Stein H. EBV infection patterns in Hodgkin’s disease and normal lymphoid tissue: expression and cellular localization of EBV gene products. Br J Haematol. 1992;82:689–94.

    CAS  PubMed  Google Scholar 

  167. Niedermeyer H, Fellbaum C, Hansmann ML, et al. [Influence of Epstein-Barr virus genome on patient survival in Hodgkin’s disease]. Verh Dtsch Ges Pathol. 1992;76:173–6.

    CAS  PubMed  Google Scholar 

  168. Diepstra A, van Imhoff GW, Schaapveld M, et al. Latent Epstein-Barr virus infection of tumor cells in classical Hodgkin’s lymphoma predicts adverse outcome in older adult patients. J Clin Oncol. 2009;27:3815–21.

    PubMed  Google Scholar 

  169. McAllister SC, Shedd D, Mueller NE, Chang ET, Miller G, Bhaduri-McIntosh S. Serum IgA to Epstein-Barr virus Early Antigen-Diffuse identifies Hodgkin’s lymphoma. J Med Virol. 2013. doi:10.1002/jmv.23761.

    PubMed  Google Scholar 

  170. Jarrett RF, Gallagher A, Jones DB, et al. Detection of Epstein-Barr virus genomes in Hodgkin’s disease: relation to age. J Clin Pathol. 1991;44:844–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  171. Khan G, Norton AJ, Slavin G. Epstein-Barr virus in Hodgkin disease. Relation to age and subtype. Cancer. 1993;71:3124–9.

    CAS  PubMed  Google Scholar 

  172. Ambinder RF, Browning PJ, Lorenzana I, et al. Epstein-Barr virus and childhood Hodgkin’s disease in Honduras and the United States. Blood. 1993;81:462–7.

    CAS  PubMed  Google Scholar 

  173. Jarrett AF, Armstrong AA, Alexander E. Epidemiology of EBV and Hodgkin’s lymphoma. Ann Oncol. 1996;7 Suppl 4:5–10.

    PubMed  Google Scholar 

  174. Lin AY, Kingma DW, Lennette ET, et al. Epstein-Barr virus and familial Hodgkin’s disease. Blood. 1996;88:3160–5.

    CAS  PubMed  Google Scholar 

  175. Hjalgrim H, Askling J, Rostgaard K, et al. Characteristics of Hodgkin’s lymphoma after infectious mononucleosis. N Engl J Med. 2003;349:1324–32.

    CAS  PubMed  Google Scholar 

  176. Hjalgrim H. On the aetiology of Hodgkin lymphoma. Dan Med J. 2012;59:B4485.

    PubMed  Google Scholar 

  177. Goldacre MJ, Wotton CJ, Yeates DG. Associations between infectious mononucleosis and cancer: record-linkage studies. Epidemiol Infect. 2009;137:672–80.

    CAS  PubMed  Google Scholar 

  178. Sleckman BG, Mauch PM, Ambinder RF, et al. Epstein-Barr virus in Hodgkin’s disease: correlation of risk factors and disease characteristics with molecular evidence of viral infection. Cancer Epidemiol Biomarkers Prev. 1998;7:1117–21.

    CAS  PubMed  Google Scholar 

  179. Rosdahl N, Larsen SO, Clemmesen J. Hodgkin’s disease in patients with previous infectious mononucleosis: 30 years’ experience. Br Med J. 1974;2:253–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  180. Muñoz N, Davidson RJ, Witthoff B, Ericsson JE, De-Thé G. Infectious mononucleosis and Hodgkin’s disease. Int J Cancer. 1978;22:10–3.

    PubMed  Google Scholar 

  181. Kvåle G, Høiby EA, Pedersen E. Hodgkin’s disease in patients with previous infectious mononucleosis. Int J Cancer. 1979;23:593–7.

    PubMed  Google Scholar 

  182. Chang ET, Zheng T, Lennette ET, et al. Heterogeneity of risk factors and antibody profiles in Epstein-Barr virus genome-positive and -negative Hodgkin lymphoma. J Infect Dis. 2004;189:2271–81.

    PubMed  Google Scholar 

  183. Alexander FE, Jarrett RF, Lawrence D, et al. Risk factors for Hodgkin’s disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents. Br J Cancer. 2000;82:1117–21.

    CAS  PubMed Central  PubMed  Google Scholar 

  184. Frisan T, Sjöberg J, Dolcetti R, et al. Local suppression of Epstein-Barr virus (EBV)-specific cytotoxicity in biopsies of EBV-positive Hodgkin’s disease. Blood. 1995;86:1493–501.

    CAS  PubMed  Google Scholar 

  185. Herbst H, Foss H, Samol J, et al. Frequent expression of interleukin-10 by Epstein-Barr virus-harboring tumor cells of Hodgkin’s disease. Blood. 1996;87:2918–29.

    CAS  PubMed  Google Scholar 

  186. Hudnall SD, Betancourt E, Barnhart E, Patel J. Comparative flow immunophenotypic features of the inflammatory infiltrates of Hodgkin lymphoma and lymphoid hyperplasia. Cytometry B Clin Cytom. 2008;74:1–8.

    PubMed  Google Scholar 

  187. Thangavelu M, Le Beau MM. Chromosomal abnormalities in Hodgkin’s disease. Hematol Oncol Clin North Am. 1989;3:221–36.

    CAS  PubMed  Google Scholar 

  188. Su IJ, Hsieh HC. Clinicopathological spectrum of Epstein-Barr virus-associated T cell malignancies. Leuk Lymphoma. 1992;7:47–53.

    CAS  PubMed  Google Scholar 

  189. Suzuki R, Suzumiya J, Nakamura S, et al. Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells. Leukemia. 2004;18:763–70.

    CAS  PubMed  Google Scholar 

  190. Chan JK. Natural killer cell neoplasms. Anat Pathol. 1998;3:77–145.

    CAS  PubMed  Google Scholar 

  191. Lima M. Aggressive mature natural killer cell neoplasms: from epidemiology to diagnosis. Orphanet J Rare Dis. 2013;8:95.

    PubMed Central  PubMed  Google Scholar 

  192. Cheuk W, Chan JK, Shek TW, et al. Inflammatory pseudotumor-like follicular dendritic cell tumor: a distinctive low-grade malignant intra-abdominal neoplasm with consistent Epstein-Barr virus association. Am J Surg Pathol. 2001;25:721–31.

    CAS  PubMed  Google Scholar 

  193. 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.

    CAS  PubMed  Google Scholar 

  194. 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 10 years. Ann Oncol. 2005;16:206–14.

    PubMed  Google Scholar 

  195. Au WY, Law MF, Tung Y, Shek TW. Concomitant EBV encoded RNA positive cutaneous nasal-type natural killer-cell lymphoma and EBV encoded RNA negative nasopharyngeal carcinoma. Leuk Lymphoma. 2009;50:1543–4.

    CAS  PubMed  Google Scholar 

  196. Ho FC, Srivastava G, Loke SL, et al. Presence of Epstein-Barr virus DNA in nasal lymphomas of B and ‘T’ cell type. Hematol Oncol. 1990;8:271–81.

    CAS  PubMed  Google Scholar 

  197. Chiang AK, Tao Q, Srivastava G, Ho FC. Nasal NK- and T-cell lymphomas share the same type of Epstein-Barr virus latency as nasopharyngeal carcinoma and Hodgkin’s disease. Int J Cancer. 1996;68:285–90.

    CAS  PubMed  Google Scholar 

  198. Fox CP, Haigh TA, Taylor GS, et al. A novel latent membrane 2 transcript expressed in Epstein-Barr virus-positive NK- and T-cell lymphoproliferative disease encodes a target for cellular immunotherapy. Blood. 2010;116:3695–704.

    CAS  PubMed Central  PubMed  Google Scholar 

  199. Wong KF, Chan JK, Kwong YL. Identification of del(6)(q21q25) as a recurring chromosomal abnormality in putative NK cell lymphoma/leukaemia. Br J Haematol. 1997;98:922–6.

    CAS  PubMed  Google Scholar 

  200. Suzuki R. NK/T-cell lymphomas: pathobiology, prognosis and treatment paradigm. Curr Oncol Rep. 2012;14:395–402.

    CAS  PubMed  Google Scholar 

  201. Suzuki R, Suzumiya J, Yamaguchi M, et al. Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type. Ann Oncol. 2010;21:1032–40.

    CAS  PubMed  Google Scholar 

  202. Quintanilla-Martinez L, Kimura H, Jaffe ES. EBV-positive T cell lymphoproliferative disorders of childhood. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, 2008:278–280.

    Google Scholar 

  203. Quintanilla-Martinez L, Kumar S, Fend F, et al. Fulminant EBV(+) T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome. Blood. 2000;96:443–51.

    CAS  PubMed  Google Scholar 

  204. Kanegane H, Nomura K, Miyawaki T, Tosato G. Biological aspects of Epstein-Barr virus (EBV)-infected lymphocytes in chronic active EBV infection and associated malignancies. Crit Rev Oncol Hematol. 2002;44:239–49.

    PubMed  Google Scholar 

  205. Kimura H. Pathogenesis of chronic active Epstein-Barr virus infection: is this an infectious disease, lymphoproliferative disorder, or immunodeficiency? Rev Med Virol. 2006;16:251–61.

    PubMed  Google Scholar 

  206. Okano M, Gross TG. Epstein-Barr virus-associated hemophagocytic syndrome and fatal infectious mononucleosis. Am J Hematol. 1996;53:111–5.

    CAS  PubMed  Google Scholar 

  207. Yoshioka M, Kikuta H, Ishiguro N, Endo R, Kobayashi K. Latency pattern of Epstein-Barr virus and methylation status in Epstein-Barr virus-associated hemophagocytic syndrome. J Med Virol. 2003;70:410–9.

    CAS  PubMed  Google Scholar 

  208. Barrionuevo C, Anderson VM, Zevallos-Giampietri E, et al. Hydroa-like cutaneous T-cell lymphoma: a clinicopathologic and molecular genetic study of 16 pediatric cases from Peru. Appl Immunohistochem Mol Morphol. 2002;10:7–14.

    PubMed  Google Scholar 

  209. Rodríguez-Pinilla SM, Barrionuevo C, Garcia J, et al. EBV-associated cutaneous NK/T-cell lymphoma: review of a series of 14 cases from peru in children and young adults. Am J Surg Pathol. 2010;34:1773–82.

    PubMed  Google Scholar 

  210. Quintanilla-Martinez L, Ridaura C, Nagl F, et al. Hydroa vacciniforme-like lymphoma: a chronic EBV+ lymphoproliferative disorder with risk to develop a systemic lymphoma. Blood. 2013;122:3101–10.

    CAS  PubMed  Google Scholar 

  211. Iwatsuki K, Xu Z, Takata M, et al. The association of latent Epstein-Barr virus infection with hydroa vacciniforme. Br J Dermatol. 1999;140:715–21.

    CAS  PubMed  Google Scholar 

  212. Iwatsuki K, Xu Z, Ohtsuka M, Kaneko F. Cutaneous lymphoproliferative disorders associated with Epstein-Barr virus infection: a clinical overview. J Dermatol Sci. 2000;22:181–95.

    CAS  PubMed  Google Scholar 

  213. Hirai Y, Yamamoto T, Kimura H, et al. Hydroa vacciniforme is associated with increased numbers of Epstein-Barr virus-infected γδT cells. J Invest Dermatol. 2012;132:1401–8.

    CAS  PubMed  Google Scholar 

  214. Ishihara S, Yabuta R, Tokura Y, Ohshima K, Tagawa S. Hypersensitivity to mosquito bites is not an allergic disease, but an Epstein-Barr virus-associated lymphoproliferative disease. Int J Hematol. 2000;72:223–8.

    CAS  PubMed  Google Scholar 

  215. Yachie A, Kanegane H, Kasahara Y. Epstein-Barr virus-associated T-/natural killer cell lymphoproliferative diseases. Semin Hematol. 2003;40:124–32.

    PubMed  Google Scholar 

  216. Asada H. Hypersensitivity to mosquito bites: a unique pathogenic mechanism linking Epstein-Barr virus infection, allergy and oncogenesis. J Dermatol Sci. 2007;45:153–60.

    CAS  PubMed  Google Scholar 

  217. Lee WI, Lin JJ, Hsieh MY, et al. Immunologic difference between hypersensitivity to mosquito bite and hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus infection. PLoS One. 2013;8:e76711.

    CAS  PubMed Central  PubMed  Google Scholar 

  218. Dogan A, Attygalle AD, Kyriakou C. Angioimmunoblastic T-cell lymphoma. Br J Haematol. 2003;121:681–91.

    PubMed  Google Scholar 

  219. Tan BT, Warnke RA, Arber DA. The frequency of B- and T-cell gene rearrangements and Epstein-Barr virus in T-cell lymphomas: a comparison between angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified with and without associated B-cell proliferations. J Mol Diagn. 2006;8:466–75. quiz 527.

    CAS  PubMed Central  PubMed  Google Scholar 

  220. Anagnostopoulos I, Hummel M, Finn T, et al. Heterogeneous Epstein-Barr virus infection patterns in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type. Blood. 1992;80:1804–12.

    CAS  PubMed  Google Scholar 

  221. Zettl A, Lee SS, Rüdiger T, et al. Epstein-Barr virus-associated B-cell lymphoproliferative disorders in angloimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified. Am J Clin Pathol. 2002;117:368–79.

    PubMed  Google Scholar 

  222. Attygalle AD, Kyriakou C, Dupuis J, et al. Histologic evolution of angioimmunoblastic T-cell lymphoma in consecutive biopsies: clinical correlation and insights into natural history and disease progression. Am J Surg Pathol. 2007;31:1077–88.

    PubMed  Google Scholar 

  223. Ha SY, Sung J, Ju H, et al. Epstein-Barr virus-positive nodal peripheral T cell lymphomas: clinicopathologic and gene expression profiling study. Pathol Res Pract. 2013;209:448–54.

    PubMed  Google Scholar 

  224. Dupuis J, Emile JF, Mounier N, et al. Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified: A Groupe d’Etude des Lymphomes de l’Adulte (GELA) study. Blood. 2006;108:4163–9.

    CAS  PubMed  Google Scholar 

  225. Chen CL, Sadler RH, Walling DM, Su IJ, Hsieh HC, Raab-Traub N. Epstein-Barr virus (EBV) gene expression in EBV-positive peripheral T-cell lymphomas. J Virol. 1993;67:6303–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  226. Geissinger E, Odenwald T, Lee SS, et al. Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert’s) variant are often derived from CD8(+) cytotoxic T-cells. Virchows Arch. 2004;445:334–43.

    PubMed  Google Scholar 

  227. Anagnostopoulos I, Hummel M, Tiemann M, Korbjuhn P, Parwaresch MR, Stein H. Frequent presence of latent Epstein-Barr virus infection in lymphoepithelioid cell lymphoma (Lennert’s lymphoma). Histopathology. 1994;25:331–7.

    CAS  PubMed  Google Scholar 

  228. Cheng AL, Su IJ, Chen YC, Uen WC, Wang CH. Characteristic clinicopathologic features of Epstein-Barr virus-associated peripheral T-cell lymphoma. Cancer. 1993;72:909–16.

    CAS  PubMed  Google Scholar 

  229. Su IJ, Hsu YH, Lin MT, Cheng AL, Wang CH, Weiss LM. Epstein-Barr virus-containing T-cell lymphoma presents with hemophagocytic syndrome mimicking malignant histiocytosis. Cancer. 1993;72:2019–27.

    CAS  PubMed  Google Scholar 

  230. Yamamoto T, Shirakawa A, Kawaguchi M, Masuda A, Nishikawa T, Kobayashi M. Lytic infection of Epstein-Barr virus (EBV) in hemophagocytic syndrome associated with EBV-induced lymphoproliferative disorder. Ann Hematol. 2004;83:127–32.

    CAS  PubMed  Google Scholar 

  231. Chandrakasan S, Filipovich AH. Hemophagocytic lymphohistiocytosis: advances in pathophysiology, diagnosis, and treatment. J Pediatr. 2013;163:1253–9.

    PubMed  Google Scholar 

  232. Su IJ, Wang CH, Cheng AL, Chen RL. Hemophagocytic syndrome in Epstein-Barr virus-associated T-lymphoproliferative disorders: disease spectrum, pathogenesis, and management. Leuk Lymphoma. 1995;19:401–6.

    CAS  PubMed  Google Scholar 

  233. Cho JH, Kim HS, Ko YH, Park CS. Epstein-Barr virus infected natural killer cell lymphoma in a patient with hypersensitivity to mosquito bite. J Infect. 2006;52:e173–6.

    PubMed  Google Scholar 

  234. Konuma T, Uchimaru K, Sekine R, et al. Atypical hypersensitivity to mosquito bites without natural killer cell proliferative disease in an adult patient. Int J Hematol. 2005;82:441–4.

    PubMed  Google Scholar 

  235. Roh EJ, Chung EH, Chang YP, et al. A case of hypersensitivity to mosquito bite associated with Epstein-Barr viral infection and natural killer cell lymphocytosis. J Korean Med Sci. 2010;25:321–3.

    PubMed Central  PubMed  Google Scholar 

  236. Zhang Z, Shi Q, An X, et al. NK/T-cell lymphoma in a child with hypersensitivity to mosquito bites. J Pediatr Hematol Oncol. 2009;31:855–7.

    PubMed  Google Scholar 

  237. Cho KH, Lee SH, Kim CW, et al. Epstein-Barr virus-associated lymphoproliferative lesions presenting as a hydroa vacciniforme-like eruption: an analysis of six cases. Br J Dermatol. 2004;151:372–80.

    PubMed  Google Scholar 

  238. Cohen JI, Kimura H, Nakamura S, Ko YH, Jaffe ES. 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. 2009;20:1472–82.

    CAS  PubMed Central  PubMed  Google Scholar 

  239. Wang M, Wang S, Yang QP, et al. Hydroa vacciniforme-like lymphoma of an adult: a case report with review of the literature. Diagn Pathol. 2013;8:72.

    PubMed Central  PubMed  Google Scholar 

  240. Shek TW, Ho FC, Ng IO, Chan AC, Ma L, Srivastava G. Follicular dendritic cell tumor of the liver. Evidence for an Epstein-Barr virus-related clonal proliferation of follicular dendritic cells. Am J Surg Pathol. 1996;20:313–24.

    CAS  PubMed  Google Scholar 

  241. Perez-Ordoñez B, Rosai J. Follicular dendritic cell tumor: review of the entity. Semin Diagn Pathol. 1998;15:144–54.

    PubMed  Google Scholar 

  242. Arber DA, Weiss LM. Inflammatory pseudotumor and follicular dendritic cell tumor. Am J Surg Pathol. 2001;25:1558–9.

    CAS  PubMed  Google Scholar 

  243. Arber DA, Weiss LM, Chang KL. Detection of Epstein-Barr Virus in inflammatory pseudotumor. Semin Diagn Pathol. 1998;15:155–60.

    CAS  PubMed  Google Scholar 

  244. Selves J, Meggetto F, Brousset P, et al. Inflammatory pseudotumor of the liver. Evidence for follicular dendritic reticulum cell proliferation associated with clonal Epstein-Barr virus. Am J Surg Pathol. 1996;20:747–53.

    CAS  PubMed  Google Scholar 

  245. Timmons CF, Dawson DB, Richards CS, Andrews WS, Katz JA. Epstein-Barr virus-associated leiomyosarcomas in liver transplantation recipients. Origin from either donor or recipient tissue. Cancer. 1995;76:1481–9.

    CAS  PubMed  Google Scholar 

  246. Purgina B, Rao UN, Miettinen M, Pantanowitz L. AIDS-related EBV-associated smooth muscle tumors: a review of 64 published cases. Patholog Res Int. 2011;2011:561548.

    PubMed Central  PubMed  Google Scholar 

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  1. Department of Pathology and Laboratory Medicine, Director, Division of Hematopathology, Yale University School of Medicine, 310 Cedar Street, BML116B, New Haven, CT, 06520-8023, USA

    S. David Hudnall M.D., F.C.A.P.

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  1. Pathology and Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA

    S. David Hudnall

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Hudnall, S.D. (2014). Epstein–Barr Virus: Epidemiology and Clinical Features of Related Cancer. In: Hudnall, S. (eds) Viruses and Human Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0870-7_3

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