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Lymphoma

Staging challenges in extranasal and juvenile extranodal NK/T-cell lymphoma

Leukemia volume 34, pages 3428–3431 (2020)Cite this article

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With great interest, we read the article published in Leukemia by Dr. Hong et al. [1]. We highly appreciated that they constructed a novel staging system, CA staging system (CASS), for extranodal NK/T-cell lymphoma (ENKTL). Among early-stage patients of the Ann Arbor staging system (AASS), the authors identified patients with nasal lesions without local invasiveness have better overall survival (OS) than the rest. For late-stage patients, the authors combined those with similar survival rates. Those modifications make CASS better in discriminating patients’ survival than AASS, which is confirmed in a large external cohort. However, since most of the patients in their study were nasal type, whether CASS could be used in extranasal patients needs further investigations. Moreover, juvenile ENKTL is recently identified as a rare subtype that is more aggressive than the adult counterpart [2, 3]. Whether CASS could be applied to juveniles remains unclear since most cases were adults in their study. Staging extranasal and juvenile ENKTL is essential clinically but challenging due to the heterogeneity and rareness. Therefore, whether physicians could transfer staging systems from general ENKTL to those subtypes is an important question. In this paper, we investigate the ability of AASS and CASS in depicting and discriminating survival by two large datasets extracted from literature specifically for extranasal and juvenile ENKTL [4] (Supplementary Methods and Table S1); we also summarize the clinical challenges and propose some suggestions aiming to improve the staging system better.

As ENKTL involving different regions cause various impacts, we conducted exploratory subgroup analysis. Overall, no statistically significant difference was found in discrimination abilities between AASS and CASS. The regions with the highest discrimination abilities were laryngeal and orbit, followed by skin, gastrointestinal (GI) tract, testis, and lung. For ENKTL originate from orbit, lung, and testis, most of the patients were classified into stage II/IV in CASS (stage I/IV in AASS), which limits precise risk-identification [5]. Particularly, patients with ENKTL of central nerve system (CNS) in early-stage (AASS stage I) had a 5-year OS rate of 13% [6]; the staging did not reflect the prognosis accurately. Those phenomena reflect the limited consideration of both systems in extranasal regions. Besides, for primary GI tract lesions, the Lugano staging system (LGSS) was widely used. Compared with LGSS, CASS had a similar discrimination ability (LGSS: CASS, AUC = 0.63:0.64). When extending the inclusion criteria including patients undergoing enterotomy, LGSS showed superior AUC to CASS (LGSS: CASS, AUC = 0.60:0.56), although the difference was not significant. Enterotomy is a common therapy for treating GI lymphoma and has been proved to be effective in improving the prognosis. Therefore, patients receiving enterotomy should be included when constructing new systems. Moreover, for primary laryngeal lesions, CASS displayed a trend of higher discrimination ability than AASS (AASS: CASS, AUC = 0.70:0.76). Although primary laryngeal ENKTL is considered as an extranasal type and demonstrates some pathological peculiarities [7], it belongs to the upper aerodigestive tract, the most frequently involved area of ENKTL; it might be a transition between nasal and extranasal ENKTL. Thereby satisfying results were achieved by CASS.

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Fig. 1: Comparison between AASS and CASS in extranasal and juvenile ENKTL.

References

  1. Hong H, Li Y, Lim ST, Liang C, Huang H, Yi P, et al. A proposal for a new staging system for extranodal natural killer T-cell lymphoma: a multicenter study from China and Asia Lymphoma Study Group. Leukemia. 2020. https://doi.org/10.1038/s41375-020-0740-1. [published online ahead of print]

  2. Guan P, Chen Z, Chu L, Zhen L, Zhang L, Pan L, et al. Extranodal NK/T-cell lymphoma in adolescents: imaging findings of a consecutive 7-year case series. J Int Med Res. 2019;47:1210–20.

    Article  Google Scholar 

  3. Takahashi E, Ohshima K, Kimura H, Hara K, Suzuki R, Kawa K, et al. Clinicopathological analysis of the age-related differences in patients with Epstein-Barr virus (EBV)-associated extranasal natural killer (NK)/T-cell lymphoma with reference to the relationship with aggressive NK cell leukaemia and chronic active EBV infection-associated lymphoproliferative disorders. Histopathology. 2011;59:660–71.

    Article  Google Scholar 

  4. Chen Z, Guan P, Shan T, Ye Y, Gao L, Wang Z, et al. CD30 expression and survival in extranodal NK/T-cell lymphoma: a systematic review and meta-analysis. Oncotarget. 2018;9:16547–56.

    Article  Google Scholar 

  5. Huang Y, Shi X, Zhong P, Wang Y, Xiao H, Zhou X, et al. De novo testicular extranodal NK/T-cell lymphoma: a clinicopathologic study of 21 cases with review of additional 18 cases in the literature. Am J Surg Pathol. 2019;43:549–58.

    Article  Google Scholar 

  6. Miyata-Takata T, Takata K, Kato S, Hu LM, Noujima-Harada M, Chuang SS, et al. Clinicopathological analysis of primary central nervous system NK/T cell lymphoma: rare and localized aggressive tumour among extranasal NK/T cell tumours. Histopathology. 2017;71:287–95.

    Article  Google Scholar 

  7. Xiang CX, Chen ZH, Zhao S, Gao LM, Tao Q, Zuo Z, et al. Laryngeal extranodal nasal-type natural killer/t-cell lymphoma: a clinicopathologic study of 31 cases in china. Am J Surg Pathol. 2019;43:995–1004.

    Article  Google Scholar 

  8. Chen Z, Guan P. Rethinking the elusive boundaries of EBV-associated T/NK-cell lymphoproliferative disorders. Haematologica. 2019;104:e124–5.

    Article  Google Scholar 

  9. Chen Z, Liu W, Zhang W, Ye Y, Guan P, Gao L, et al. Chronic active Epstein-Barr virus infection of T/NK-Cell type mimicking classic hodgkin lymphoma: clinicopathologic and genetic features of 8 cases supporting a variant with “Hodgkin/Reed-Sternberg-like” cells of NK phenotype. Am J Surg Pathol. 2019;43:1611–21.

    PubMed  Google Scholar 

  10. Chen Z, Wang M, Guan P, Zhao S, Zhang W, Gao L, et al. Comparison of systemic EBV-positive T-cell and NK-cell lymphoproliferative diseases of childhood based on classification evolution: new classification, old problems. Am J Surg Pathol. 2020. https://doi.org/10.1097/PAS.0000000000001495. [published online ahead of print]

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81900195 to ZHC), and Post-Doctor Research Project, West China Hospital, Sichuan University (2019HXBH067 to ZHC). We would like to thank Prof. Weiping Liu, Prof. Wenyan Zhang, and Prof. Ling Pan. The author PJG has moved to MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences.

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  1. These authors contributed equally: Pujun Guan, Tian Dong

Authors and Affiliations

  1. Department of Pathology, West China Hospital, Sichuan University, Chengdu, China

    Pujun Guan, Sha Zhao & Zihang Chen

  2. Department of Radiology, West China Hospital, Sichuan University, Chengdu, China

    Pujun Guan & Rongbo Liu

  3. Department of Hematology, West China Hospital, Sichuan University, Chengdu, China

    Tian Dong & Li Zhang

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  1. Pujun Guan
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Correspondence to Rongbo Liu or Zihang Chen.

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Guan, P., Dong, T., Zhang, L. et al. Staging challenges in extranasal and juvenile extranodal NK/T-cell lymphoma. Leukemia 34, 3428–3431 (2020). https://doi.org/10.1038/s41375-020-0975-x

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