Clinical and Pathological Differences between Nasal and Nasal-Type NK/T Cell Lymphomas: A Summary of 136 Cases from the International T Cell Lymphoma (ITCL) Project.

Background: Due to their lower incidence, pathological heterogeneity and varied geographical distribution, the clinicopathological features and prognostic factors in mature T/NK cell lymphomas have not been comprehensively studied in international studies.

Materials and methods: Consecutive adult new cases of mature T cell neoplasms from 1990–2002 from 21 clinical centers in 13 countries were reviewed. NK/T nasal/nasal type lymphoma was defined by standard WHO criteria after central review.

Results: Among 1159 cases of proven T cell lymphomas, 136 cases (11.7%) of NK/T lymphomas were registered (nasal 68%, nasal-type 26%, aggressive or unclassified 6%). Its incidence among T cell lymphoma was higher in Oriental (22%) than in Western countries (4%) and in Continental Asia (43%) than in Japan (11%, 19% excluding ATLL), where nasal-type subcategory is particularly uncommon (6% vs 42%). The median age was 49 years with male to female ratio of 2:1. The nasal-type cases had higher stage (p=0.0002) and LDH (p=0.01), more B symptoms (p=0.042), bulky disease (p=0.026) and poorer performance status (p<0.001) than nasal ones. Compared to nasal-type cases, more nasal patients received treatment (98% vs 80%, p=0.0009), including anthracycline (89% vs 76%, p=0.08) and radiotherapy (RT, 52% vs 24% p=0.018). The inclusion of RT to early stage nasal cases yielded survival benefit (p=0.045). The median overall survival (OS) was inferior in nasal-type than nasal cases for both early (0.36 vs 2.96 yr, p<0.001) and late stage diseases (0.28 vs 0.8 yrs, p=0.031). The event free and overall survival curves tend to overlap, signifying poor salvage efficacy for relapses. Among nasal disease, prognostic value for OS was confirmed for all three published indices: IPI (Schipp et al, p=0.0057), T-IPI (Went et al, p=0.044) and NK/T PI (Lee et al, p<0.001). In addition, Ki67 staining >50% (p=0.05), transformed T cell >40% (p=0.022), raised CRP (p=0.025), hemoglobin <11g/dl (p=0.0038), platelet count <150×10⁹/l (p=0.0092), B symptoms (p=0.042) were associated with poorer OS on univariate analysis. Their prognostic values were retained on multivariate analysis, after controlling for factors used for the IPI, T-IPI and NK/T PI. However, none of the histological or clinical prognostic factors or prognostic indices was significant for nasal-type disease.

Conclusion: The prognosis of nasal/nasal-type lymphoma is distinctly worse than other categories of peripheral T cell lymphomas. The clinical feature, treatment response and epidemiology of nasal type lymphoma is different from that of nasal NK lymphoma and the poor response preclude the finding of any favorable prognostic factors. There are still grounds for developing a better prognostic model for nasal cases to triage patients to more aggressive or novel treatment.