Abstract

Background. Aggressive natural killer cell leukemia (ANKL) is rare and difficult to diagnose in early stages, with no standard treatment and a poor prognosis.

Case presentation. Two adolescents with ANKL presented with hemophagocytic lymphohistiocytosis (HLH), with Case-1 presenting as refractory HLH and Case-2 with lung involvement. The morphology of bone marrow showed an increase in unidentified cells, which mainly expressed CD56. Cytogenetic analysis showed complex karyotypes. Both patients received intensive combined chemotherapy based on pegaspargase and anthracyclines. Case-1 died of tumor lysis syndrome. Case-2 underwent hematopoietic stem cell transplantation and is currently alive and disease-free.

Conclusions. HLH can serve as the initial manifestation of ANKL. Leukemia cells of ANKL have significant variations in the morphology and mainly express CD56. Intensive combination chemotherapy based on pegaspargase and anthracyclines may be considered for ANKL.

Keywords: aggressive NK cell leukemia, asparaginase, anthracyclines, hemophagocytic lymphohistiocytosis

Supplementary materials
Supplementary Tables

Copyright and license

Copyright © 2024 The Author(s). This is an open access article distributed under the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.

How to cite

1.
Ni Y, Li L, Wang Y, Sun L. Clinicopathological features and treatment of aggressive natural killer cell leukemia: case series and literature review. Turk J Pediatr 2024; 66: 481-489. https://doi.org/10.24953/turkjpediatr.2024.5072

References

  1. Chan JKC, Jaffe ES, Ko YH. Aggressive NK-cell leukaemia. In: Swerdlow SH, Campo E, Harris NL, et al, editors. WHO Classifification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th ed. IARC: Lyon; 2017: 353-354.
  2. Hue SS, Oon ML, Wang S, Tan SY, Ng SB. Epstein-Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach. Pathology 2020; 52: 111-127. https://doi.org/10.1016/j.pathol.2019.09.011
  3. Lepe-Zuniga JL, Jeronimo-Lopez FJ, Hernandez-Orantes JG, Mendez-Cigarroa AO. Non-EBV-related aggressive NK-Cell leukemia: an oncohematological great imitator. J Hematol 2018; 7: 163-166. https://doi.org/10.14740/jh462
  4. Jin C, Bandovic J, Brody J, Hsu P, Sheikh-Fayyaz S, Zhang X. Aggressive natural killer cell leukemia mimicking interstitial lung diseases with the activation of the mitogen-activated protein kinase pathway. Int J Clin Exp Pathol 2018; 11: 5502-5508.
  5. Qian WS, Shen L, Wulipan F, et al. Clinical characteristics and prognosis of patients with aggressive NK cell leukemia. Zhonghua Xue Ye Xue Za Zhi 2022; 43: 424-426. https://doi.org/10.3760/cma.j.issn.0253-2727.2022.05.013
  6. Tang YT, Wang D, Luo H, et al. Aggressive NK-cell leukemia: clinical subtypes, molecular features, and treatment outcomes. Blood Cancer J 2017; 7: 660. https://doi.org/10.1038/s41408-017-0021-z
  7. Fujimoto A, Ishida F, Izutsu K, et al. Allogeneic stem cell transplantation for patients with aggressive NK-cell leukemia. Bone Marrow Transplant 2021; 56: 347-356. https://doi.org/10.1038/s41409-020-01009-8
  8. Rey-Helo E, Pérez-Velásquez RD, Cortés-Alva D. Agressive NK-cell leukemia in a pediatric patient. Bol Med Hosp Infant Mex 2019; 76: 188-192. https://doi.org/10.24875/BMHIM.19000089
  9. Syrykh C, Péricart S, Lamaison C, Escudié F, Brousset P, Laurent C. Epstein-Barr virus-associated T- and NK-Cell lymphoproliferative diseases: a review of clinical and pathological features. Cancers (Basel) 2021; 13: 3315. https://doi.org/10.3390/cancers13133315
  10. Ishida F. Aggressive NK-Cell leukemia. Front Pediatr 2018; 6: 292. https://doi.org/10.3389/fped.2018.00292
  11. Guerreiro M, Príncipe F, Teles MJ, et al. CD56-negative aggressive NK cell leukemia relapsing as multiple cranial nerve palsies: case report and literature review. Case Rep Hematol 2017; 2017: 3724017. https://doi.org/10.1155/2017/3724017
  12. Wang LP, Yu YP, Mei JG, Song P, An ZM, Zhou XG. Clinical and pathological characteristics of aggressive natural killer cell leukemia patients. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021; 29: 1093-1100. https://doi.org/10.19746/j.cnki.issn.1009-2137.2021.04.012
  13. Yang CF, Hsu CY, Ho DM. Aggressive natural killer (NK)-cell leukaemia and extranodal NK/T-cell lymphoma are two distinct diseases that differ in their clinical presentation and cytogenetic findings. Histopathology 2018; 72: 955-964. https://doi.org/10.1111/his.13463
  14. Li Y, Wei J, Mao X, et al. Flow cytometric immunophenotyping is sensitive for the early diagnosis of de novo aggressive natural killer cell leukemia (ANKL): a multicenter retrospective analysis. PLoS One 2016; 11: e0158827. https://doi.org/10.1371/journal.pone.0158827
  15. Gu Y, Guo FL, Yang L, Ma L. A case of natural killer cell leukemia with perineal mass as the main manifestation. J Leuk Lymph 2008; 17: 378-379. https://doi.org/10.3760/cma.j.issn.1009-9921.2008.05.023
  16. Chen DD, Yu ZH, Guo Z, Chen HR, He XP. Aggressive NK cell leukemia: a case report and literature review. Chin J Clinicians (Electronic Edition) 2010; 4: 222-225. https://doi.org/10.3969/j.issn.1674-0785.2010.02.025
  17. Liu ZQ, Liu R, Shi XD. Aggressive NK cell leukemia: a case report. Chin J Hematol 2010; 31: 359. https://doi.org/10.3760/cma.j.issn.0253-2727.2010.05.022
  18. Zhu RM, Yang J. A case of childhood acute aggressive NK cell leukemia. Shenyang Budui Yiyao 2011; 24: 83.
  19. Ma SX, Zhao K, Zhang Y. A case of childhood aggressive NK cell leukemia with rash as the main manifestation. Shandong Medical Journal 2012; 52: 102.
  20. Wang XC, Ding KY, Wang ZH, Wang J, Wang XQ, Li Q. Clinical characteristics of five cases of aggressive NK cell leukemia. Shandong Medical Journal 2017; 57: 98-101. https://doi.org/10.3969/j.issn.1002-266X.2017.30.032
  21. Wei XY, Huang KK, Huang HY, Cui LY, Zhang MJ. Two cases of aggressive NK cell leukemia complicated with multiple organ dysfunction syndrome. Guangdong Medical Journal 2017; 38: 1949. https://doi.org/10.3969/j.issn.1001-9448.2017.12.046
  22. Skorupa A, Chaudhary UB, Lazarchick J. Cold agglutinin induced autoimmune hemolytic anemia and NK-cell leukemia: a new association. Am J Hematol 2007; 82: 668-671. https://doi.org/10.1002/ajh.20876
  23. Petterson TE, Bosco AA, Cohn RJ. Aggressive natural killer cell leukemia presenting with hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2008; 50: 654-657. https://doi.org/10.1002/pbc.21358
  24. Huang J, Ni W, Wang L, Zhou W, Jin J. A rare case of co-existent aggressive natural killer cell and acute monocytic leukemia with cytomegalovirus infection. Int J Hematol 2008; 87: 553-556. https://doi.org/10.1007/s12185-008-0078-3
  25. Patel AP, Ghatak SB, Patel JA. Long term survival in aggressive NK cell leukemia. Indian Pediatr 2010; 47: 807-808. https://doi.org/10.1007/s13312-010-0108-0
  26. Yadav SP, Kharya G. Aggressive natural cell leukemia in an infant with bilateral testicular mass. Indian Pediatr 2011; 48: 79-80.
  27. Park JA, Jun KR, Nam SH, Ghim TT. Favorable outcome in a child with EBV-negative aggressive NK cell leukemia. Int J Hematol 2013; 97: 673-676. https://doi.org/10.1007/s12185-013-1319-7
  28. Kim BK, Hong KT, Kang HJ, et al. Successful treatment of pediatric Epstein-Barr virus-positive aggressive natural killer-cell leukemia. J Pediatr Hematol Oncol 2019; 41: e336-e337. https://doi.org/10.1097/MPH.0000000000001237
  29. Pan M, Huang JX, Wu Q, et al. Misdiagnosis of invasive NK cell leukemia in children: a case report. J China Pediatr Blood Cancer 2020; 25: 236-238. https://doi.org/10.3969/j.issn.1673-5323.2020.04.013
  30. Gao LM, Zhao S, Liu WP, et al. Clinicopathologic characterization of aggressive natural killer cell leukemia involving different tissue sites. Am J Surg Pathol 2016; 40: 836-846. https://doi.org/10.1097/PAS.0000000000000634
  31. Fang H, Wang W, Kadia TM, El Hussein S, Wang SA, Khoury JD. CD94 expression patterns in reactive and neoplastic T-cell and NK-cell proliferations. Leuk Res 2021; 108: 106614. https://doi.org/10.1016/j.leukres.2021.106614
  32. Freud AG, Zhao S, Wei S, et al. Expression of the activating receptor, NKp46 (CD335), in human natural killer and T-cell neoplasia. Am J Clin Pathol 2013; 140: 853-866. https://doi.org/10.1309/AJCPWGG69MCZOWMM
  33. 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: 763-770. https://doi.org/10.1038/sj.leu.2403262