NK and NK-like T-cell lymphoma in extranasal sites: a comparative clinicopathological study according to site and EBV status

Aims: To analyse the clinicopathological findings of extranasal CD56+ cytotoxic T- or NK-cell lymphomas in different organs and to compare Epstein-Barr virus (EBV)+ and EBV- lymphoma of non-blastoid cytomorphology. Methods and results: Fifty-one cases of cCD3+ T-cell intracellular antigen (TIA-1)+ CD56+ lymphomas of extranodal/extranasal origin were included in the study. The primary sites of the CD56+ tumours were soft tissue (n=10), the gastrointestinal (GI) tract (n=13), the skin (n=15), upper aerodigestive tract excluding nasal and nasopharyngeal regions (n=11), the testis (n=1), and parotid gland (n=1). TCR gene rearrangement was detected in seven of 47 cases examined (16%). EBV was positive in 39 of 51 cases (76%). The positive rate of EBV was higher in tumours of soft tissue (80%), GI tract (92%), and skin (80%), and lowest in the upper aerodigestive tract excluding the nasal and nasopharyngeal region (50%). Tumours of the soft tissue and the upper aerodigestive tract tended to present with localized disease (P=0.002). The 2-year survival rate was lowest for tumours of the GI tract (P=0.0256). EBV- TCR- lymphoma showed less necrosis (P=0.0133) and a better 2-year survival rate (P=0.0066) than EBV+ TCR- lymphoma. Patients with EBV+ TCR+ lymphomas tended to present with localized disease, more often than EBV+ TCR- lymphoma (P=0.0186). Significant prognostic factors in all CD56+ lymphomas were the site (P=0.0256), EBV status (P=0.0026), necrosis with or without perforation (P=0.0338) and the presence of pleomorphic large tumour cells (P=0.0428). Cox's regression analysis adjusting for other pathological parameters showed EBV status to be the only independent prognostic factor (P=0.018). Conclusions: Extranodal CD56+ EBV- lymphoma at extranasal sites is a clinically less aggressive malignancy and displays less necrosis than CD56+ EBV+ lymphoma. Because CD56+ EBV+ TCR+ lymphomas show similar pathological and clinical findings to CD56+ EBV+ TCR- lymphomas, nasal-type NK/T-cell lymphomas at extranasal sites should be diagnosed as such on the basis of EBV+, cytotoxic T or NK phenotype irrespective of the genotype determined by molecular study.