title: NK and NK-like T-cell lymphoma in extranasal sites: a comparative clinicopathological study according to site and EBV status.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pathology, Sungkyunkwan University, Samsung Medical Center, Seoul, Korea. yhko@smc.samsung.co.kr
authors.forename: Y H
authors.initials: YH
authors.lastname: Ko
authors.forename: E-Y
authors.initials: EY
authors.lastname: Cho
authors.forename: J-E
authors.initials: JE
authors.lastname: Kim
authors.forename: S-S
authors.initials: SS
authors.lastname: Lee
authors.forename: J-R
authors.initials: JR
authors.lastname: Huh
authors.forename: H-K
authors.initials: HK
authors.lastname: Chang
authors.forename: W-I
authors.initials: WI
authors.lastname: Yang
authors.forename: C-W
authors.initials: CW
authors.lastname: Kim
authors.forename: S-W
authors.initials: SW
authors.lastname: Kim
authors.forename: H J
authors.initials: HJ
authors.lastname: Ree
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019002:CD56 Antigen / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D015321:Gene Rearrangement; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D017403:In Situ Hybridization; D007694:Killer Cells, Natural; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000473:pathology; D010307:Parotid Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D039102:Poly(A)-Binding Proteins; D011379:Prognosis; D011506:Proteins / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis; D016601:RNA-Binding Proteins; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D016019:Survival Analysis; D000074019:T-Cell Intracellular Antigen-1; D013736:Testicular Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology
chemical_list: D019002:CD56 Antigen; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human