title: Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm.
abstract: Expression of the natural killer (NK) cell antigen CD56 is uncommon among lymphomas, and those that do are almost exclusively of non-B-cell lineage and show a predilection for the nasal and nasopharyngeal region. This study analyzes 49 cases of nonnasal CD56+ lymphomas, the largest series to date, to characterize the clinicopathologic spectrum of these rare neoplasms. All patients were Chinese. Four categories could be delineated. (1) Nasal-type NK/T cell lymphoma (n = 34) patients were adults 21 to 76 years of age (median, 50 years), including 25 men and 9 women. They presented with extranodal disease, usually in multiple sites. The commonest sites of involvement were skin, upper aerodigestive tract, testis, soft tissue, gastrointestinal tract, and spleen. Only 7 cases (21%) apparently had stage I disease. The neoplastic cells were often pleomorphic, with irregular nuclei and granular chromatin, and angiocentric growth was common. The characteristic immunophenotype was CD2+ CD3/Leu4- CD3epsilon+ CD56+, and 32 cases (94%) harbored Epstein-Barr virus (EBV). Follow-up information was available in 29 cases: 24 died at a median of 3.5 months; 3 were alive with relapse at 5 months to 2.5 years; and 2 were alive and well at 3 and 5 years, respectively. (2) Aggressive NK cell leukemia/lymphoma (n = 5) patients presented with hepatomegaly and blood/marrow involvement, sometimes accompanied by splenomegaly or lymphadenopathy. The neoplastic cells often had round nuclei and azurophilic granules in the pale cytoplasm. All cases exhibited an immunophenotype of CD2+ CD3/Leu4- CD56+ CD16- CD57- and all were EBV+. All of these patients died within 6 weeks. (3) In blastoid NK cell lymphoma (n = 2), the lymphoma cells resembled those of lymphoblastic or myeloid leukemia. One case studied for CD2 was negative and both cases were EBV-. One patient was alive with disease at 10 months and one was a recent case. (4) Other specific lymphoma types with CD56 expression (n = 8) included one case each of hepatosplenic gammadelta T-cell lymphoma and S100 protein+ T-cell lymphoproliferative disease and two cases each of T-chronic lymphocytic/prolymphocytic leukemia, lymphoblastic lymphoma, and true histiocytic lymphoma. All of these cases were EBV-. Six patients died at a median of 6.5 months. Nonnasal CD56+ lymphomas are heterogeneous, but all pursue a highly aggressive clinical course. The nasal-type NK/T-cell lymphoma and aggressive NK cell leukemia/lymphoma show distinctive clinicopathologic features and a very strong association with EBV. Blastoid NK cell lymphoma appears to be a different entity and shows no association with EBV.
authors.affiliation: Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong.
authors.forename: J K
authors.initials: JK
authors.lastname: Chan
authors.forename: V C
authors.initials: VC
authors.lastname: Sin
authors.forename: K F
authors.initials: KF
authors.lastname: Wong
authors.forename: C S
authors.initials: CS
authors.lastname: Ng
authors.forename: W Y
authors.initials: WY
authors.lastname: Tsang
authors.forename: C H
authors.initials: CH
authors.lastname: Chan
authors.forename: M M
authors.initials: MM
authors.lastname: Cheung
authors.forename: W H
authors.initials: WH
authors.lastname: Lau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis*; D019002:CD56 Antigen / Q000032:analysis*; D002648:Child; D018450:Disease Progression; D005260:Female; D006566:Herpesviridae Infections / Q000453:epidemiology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000472:pathogenicity; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007694:Killer Cells, Natural / Q000737:chemistry; D015993:Life Tables; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000453:epidemiology / Q000473:pathology* / Q000821:virology; D016399:Lymphoma, T-Cell / Q000145:classification / Q000453:epidemiology / Q000473:pathology / Q000821:virology; D016411:Lymphoma, T-Cell, Peripheral / Q000145:classification / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000453:epidemiology / Q000473:pathology / Q000821:virology; D012189:Retrospective Studies; D016019:Survival Analysis; D014412:Tumor Virus Infections / Q000453:epidemiology
chemical_list: D000951:Antigens, Neoplasm; D019002:CD56 Antigen