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Virchows Archiv

, Volume 474, Issue 2, pp 219–226 | Cite as

Acute Epstein–Barr virus-positive cytotoxic T cell lymphoid hyperplasia in the upper aerodigestive tract, mimicking extranodal natural killer/T cell lymphoma, nasal type

  • Xie Jianlan
  • Huang Yuhua
  • Zheng Yuanyuan
  • Zhang Yanlin
  • Wei Ping
  • Liu Wei
  • Zhou XiaogeEmail author
  • Jin MulanEmail author
Original Article

Abstract

To describe the clinicopathological features of nine patients with acute Epstein–Barr virus (EBV)-positive cytotoxic T cell lymphoid hyperplasia (EBV+TLH) in the upper aerodigestive tract, in which initial findings led to a preliminary misdiagnosis of extranodal NK/T cell lymphoma, nasal type (ENKTL). A series of nine cases of EBV+TLH in one Chinese institution over a 9-year interval was retrospectively analyzed. Median age was 16 years (range 5–29 years) with a M:F ratio of 5:4. All patients were previously healthy with an acute onset period of < 1 month. Six patients (66%) presented with masses or polypoid protrusions in the upper aerodigestive tract. Nasopharyngeal symptoms, cervical lymphadenopathy, and fever were found in 89%, 78%, and 56% of patients, respectively. In seven cases, morphology mainly showed small-sized irregular cells and in two cases medium-to-large cells. In all cases, the cells diffusely expressed cytoplasmic CD3 and at least one marker for cytotoxic granules, but were negative for CD56. CD5 expression was detected in eight cases (8/9, 89%). In all cases, double staining for CD3 and EBER indicated that most T cells were infected with EBV. T cell receptor gene rearrangement was performed in five cases and all showed polyclonal results. All patients achieved complete remission within 1 month after diagnosis without any chemoradiotherapy and were followed up 19–124 months without recurrent disease. EBV+TLH in the upper aerodigestive tract is occasionally observed in China. The histopathologic features of EBV+TLH can mimic ENKTL. EBV+TLH should be taken into consideration as a potential diagnosis when the disease duration is short, spontaneous remission is achieved without intervention, and when histology shows infiltration with EBV-infected T lymphocytes.

Keywords

Extranodal NK/T cell lymphoma Human herpesvirus 4 Infectious mononucleosis Upper aerodigestive tract Immunophenotyping 

Notes

Acknowledgements

The authors thank Drs Sun Jirui and Ma Yin for providing clinical follow-up details, the technical staff of the immunohistochemistry laboratories at the Capital Medical University, the Beijing Friendship Hospital and the Beijing Chaoyang Hospital for performing additional double staining studies.

Funding information

This work was supported by grants from the Internal Start-up Science Foundation of Beijing Friendship Hospital, China (No. Yyqdkt2013-15) and by grants from the Internal Talent Development Foundation of Beijing Chaoyang Hospital, China (No. CYMY-2017-01).

Compliance with ethical standards

All patients provided written informed consent for use of tissue samples for research and were audited by the Medical Ethics Committee of Beijing Friendship Hospital, Capital Medical University (approval number 2017-P2-129-01).

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Epstein MA, Henle G, Achong BG, Barr YM (1965) Morphological and biological studies on a virus in cultured lymphoblasts from Burkitt’s lymphoma. J Exp Med 121:761–770CrossRefGoogle Scholar
  2. 2.
    Sun J, Yang Q, Lu Z, He M, Gao L, Zhu M, Sun L, Wei L, Li M, Liu C, Zheng J, Liu W, Li G, Chen J (2012) Distribution of lymphoid neoplasms in China: analysis of 4,638 cases according to the World Health Organization classification. Am J Clin Pathol 138:429–434CrossRefGoogle Scholar
  3. 3.
    Fujiwara S, Kimura H, Imadome K, Arai A, Kodama E, Morio T, Shimizu N, Wakiguchi H (2014) Current research on chronic active Epstein-Barr virus infection in Japan. Pediatr Int 56:159–166CrossRefGoogle Scholar
  4. 4.
    Nagata H, Numata T, Konno A, Mikata I, Kurasawa K, Hara S, Nishimura M, Yamamoto K, Shimizu N (2001) Presence of natural killer-cell clones with variable proliferative capacity in chronic active Epstein-Barr virus infection. Pathol Int 51:778–785CrossRefGoogle Scholar
  5. 5.
    He HL, Wang MC, Huang WT (2013) Infectious mononucleosis mimicking malignant T-cell lymphoma in the nasopharynx: a case report and review of the literature. Int J Clin Exp Pathol 6:105–109Google Scholar
  6. 6.
    Huang Y, Xie J, Ding Y, Zhou X (2016) Extranodal natural killer/T-cell lymphoma in children and adolescents: a report of 17 cases in China. Am J Clin Pathol 145:46–54CrossRefGoogle Scholar
  7. 7.
    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 (2003) 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 17:2257–2317CrossRefGoogle 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 58:209–217CrossRefGoogle Scholar
  9. 9.
    Au WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Sng I, Vose J, Armitage JO, Liang R (2009) 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 113:3931–3937CrossRefGoogle Scholar
  10. 10.
    McKelvie PA, Climent F, Krings G, Hasserjian RP, Abramson JS, Pilch BZ, Harris NL, Ferry JA, Zukerberg LR, Sohani AR (2016) Small-cell predominant extranodal NK/T cell lymphoma, nasal type: clinicopathological analysis of a series of cases diagnosed in a Western population. Histopathology 69:667–679CrossRefGoogle Scholar
  11. 11.
    Dunmire SK, Hogquist KA, Balfour HH (2015) Infectious mononucleosis. Curr Top Microbiol Immunol 390:211–240Google Scholar
  12. 12.
    Wang H, Li P, Zhang X, Xia Z, Lu Y, Huang H (2016) Histological vascular invasion is a novel prognostic indicator in extranodal natural killer/T-cell lymphoma, nasal type. Oncol Lett 12:825–836CrossRefGoogle Scholar
  13. 13.
    Pongpruttipan T, Sukpanichnant S, Assanasen T, Wannakrairot P, Boonsakan P, Kanoksil W, Kayasut K, Mitarnun W, Khuhapinant A, Bunworasate U, Puavilai T, Bedavanija A, Garcia-Herrera A, Campo E, Cook JR, Choi J, Swerdlow SH (2012) Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and alphabeta, gammadelta, and alphabeta/gammadelta T-cell origin: a comprehensive clinicopathologic and phenotypic study. Am J Surg Pathol 36:481–499CrossRefGoogle Scholar
  14. 14.
    Gualco G, Domeny-Duarte P, Chioato L, Barber G, Natkunam Y, Bacchi CE (2011) 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 35:1195–1203CrossRefGoogle Scholar
  15. 15.
    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 20:1472–1482CrossRefGoogle Scholar
  16. 16.
    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 119:673–686CrossRefGoogle Scholar
  17. 17.
    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 80:64–69CrossRefGoogle Scholar
  18. 18.
    Kato S, Miyata T, Takata K, Shimada S, Ito Y, Tomita A, Elsayed AA, Takahashi E, Asano N, Kinoshita T, Kimura H, Nakamura S (2013) Epstein-Barr virus-positive cytotoxic T-cell lymphoma followed by chronic active Epstein-Barr virus infection-associated T/NK-cell lymphoproliferative disorder: a case report. Hum Pathol 44:2849–2852CrossRefGoogle Scholar
  19. 19.
    Park S, Ko YH (2014) Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorders. J Dermatol 41:29–39CrossRefGoogle Scholar
  20. 20.
    Kimura H, Hoshino Y, Hara S, Sugaya N, Kawada J, Shibata Y, Kojima S, Nagasaka T, Kuzushima K, Morishima T (2005) Differences between T cell-type and natural killer cell-type chronic active Epstein-Barr virus infection. J Infect Dis 191:531–539CrossRefGoogle Scholar
  21. 21.
    Balfour HJ, Dunmire SK, Hogquist KA (2015) Infectious mononucleosis. Clin Transl Immunol 4:e33CrossRefGoogle Scholar
  22. 22.
    Tao Q, Srivastava G, Chan AC, Chung LP, Loke SL, Ho FC (1995) Evidence for lytic infection by Epstein-Barr virus in mucosal lymphocytes instead of nasopharyngeal epithelial cells in normal individuals. J Med Virol 45:71–77CrossRefGoogle Scholar
  23. 23.
    Fingeroth JD, Weis JJ, Tedder TF, Strominger JL, Biro PA, Fearon DT (1984) Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci U S A 81:4510–4514CrossRefGoogle Scholar
  24. 24.
    Anagnostopoulos I, Hummel M, Kreschel C, Stein H (1995) Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus. Blood 85:744–750Google Scholar
  25. 25.
    Strickler JG, Fedeli F, Horwitz CA, Copenhaver CM, Frizzera G (1993) Infectious mononucleosis in lymphoid tissue. Histopathology, in situ hybridization, and differential diagnosis. Arch Pathol Lab Med 117:269–278Google Scholar
  26. 26.
    Ha SY, An J, Park S (2013) Detection of Epstein-Barr virus-infected lymphoid cells in nasal mucosa or nasopharynx: appearances can be deceptive. Virchows Arch 462:391–397CrossRefGoogle Scholar
  27. 27.
    Balfour HJ, Verghese P (2013) Primary Epstein-Barr virus infection: impact of age at acquisition, coinfection, and viral load. J Infect Dis 207:1787–1789CrossRefGoogle Scholar
  28. 28.
    Abbott RJ, Quinn LL, Leese AM, Scholes HM, Pachnio A, Rickinson AB (2013) CD8+ T cell responses to lytic EBV infection: late antigen specificities as subdominant components of the total response. J Immunol 191:5398–5409CrossRefGoogle Scholar
  29. 29.
    Hislop AD, Kuo M, Drake-Lee AB, Akbar AN, Bergler W, Hammerschmitt N, Khan N, Palendira U, Leese AM, Timms JM, Bell AI, Buckley CD, Rickinson AB (2005) Tonsillar homing of Epstein-Barr virus-specific CD8+ T cells and the virus-host balance. J Clin Invest 115:2546–2555CrossRefGoogle Scholar
  30. 30.
    Fischer E, Delibrias C, Kazatchkine MD (1991) Expression of CR2 (the C3dg/EBV receptor, CD21) on normal human peripheral blood T lymphocytes. J Immunol 146:865–869Google Scholar
  31. 31.
    Chen BJ, Chapuy B, Ouyang J, Sun HH, Roemer MG, Xu ML, Yu H, Fletcher CD, Freeman GJ, Shipp MA, Rodig SJ (2013) PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res 19:3462–3473CrossRefGoogle Scholar
  32. 32.
    Zhou XG, Sandvej K, Li PJ, Ji XL, Yan QH, Zhang XP, Da JP, Hamilton-Dutoit SJ (2001) Epstein–Barr virus gene polymorphisms in Chinese Hodgkin’s disease cases and healthy donors: identification of three distinct virus variants. J Gen Virol 82:1157–1167CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Xie Jianlan
    • 1
  • Huang Yuhua
    • 2
    • 3
  • Zheng Yuanyuan
    • 1
  • Zhang Yanlin
    • 1
  • Wei Ping
    • 1
  • Liu Wei
    • 1
  • Zhou Xiaoge
    • 1
    Email author
  • Jin Mulan
    • 4
    Email author
  1. 1.Department of Pathology, Beijing Friendship HospitalCapital Medical UniversityBeijingPeople’s Republic of China
  2. 2.Department of PathologySun Yat-Sen University Cancer CenterGuangzhouPeople’s Republic of China
  3. 3.State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineGuangzhouPeople’s Republic of China
  4. 4.Department of Pathology, Beijing Chaoyang HospitalCapital Medical UniversityBeijingPeople’s Republic of China

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