Response: Prognosis of stage I/II nonnasal extranodal NK/T cell lymphoma

Response

We thank Suzuki et al for comparing the clinical outcome of their 10 patients with localized (stage I/II) nonnasal, extranodal NK/T cell lymphoma (ENKL) from a Japanese multicenter collection (3-year overall survival; 41%), to the 18 cases with similar disease from our international study (3-year overall survival; 12%).¹  They suggest that low-stage extranasal ENKL may carry a more favorable prognosis.

Due to differences in case selection criteria, it is difficult to resolve this discrepancy in a retrospective fashion. The small number of cases of low-stage extranasal ENKL in both studies means that this is a rare clinical presentation. From our understanding, most of the Japanese cases were dermatologic referrals. This category of cases was not submitted to our retrospective study. Indeed; none of our 18 stage I/II extranasal cases come from the 4 Japanese centers that participated in our study.¹  In contrast, only 2 of the 18 stage I/II cases from our study were cutaneous ENKL. The majority affected the alimentary tract (n = 7) and muscles (n = 5). Such bias may have led to the omission of a Japanese subcategory of limited stage cutaneous ENKL with a good prognosis, that is either not seen or missed in other parts of the world.²  It is also possible that with more meticulous staging, that is, Epstein-Barr virus (EBV)– encoded early small RNA (EBER) staining of marrow³  and whole body positive emission tomography (PET) scanning,⁴  apparent low-stage extranasal ENKL cases with a poor outcome would actually be upstaged. Given these uncertainties, the prognosis for bona fide low-stage extranasal ENKL (cutaneous and noncutaneous) remains unclear. In this setting, other ancillary variables; such as the size and number of lesions, biochemical and hematologic factors, and EBV DNA load, may also help to predict outcome. Future prospective studies of a larger number of well-characterized cases are needed to resolve this issue.