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− CD3ε+ 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 γδ 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.

A long‐term study of patients with chronic natural killer cell lymphocytosis

“…The results of the present study complement previous observations about CNKL and provide additional data that con®rm the biological and clinical distinction between CNKL and NK lymphoma/leukaemia. The latter is characterized by a clinical course reminiscent of aggressive non-Hodgkin's lymphoma or acute leukaemia, with poor response to chemotherapy and a median survival time of <1 year (Chan et al, 1997;Kwong et al, 1997b). In contrast, the median survival time for the present series of patients with CNKL was not reached after a median follow-up of >5 years; only one of the 16 patients died, and death was due to an unrelated cause.…”

“…In this instance, NK cell excess is thought to represent either a reactive polyclonal process or a secondary monoclonal epiphenomenon (Bassan et al, 1988). However, NK cellderived aggressive non-Hodgkin's lymphoma, with or without a leukaemic phase, has been well described and includes angiocentric nasal and non-nasal lymphoma, NK lymphoma/leukaemia, and cutaneous lymphoma (Emile et al, 1996;Oshimi, 1996;Chan et al, 1997;Kwong et al, 1997a;Savoia et al, 1997). These lymphomas are frequently fatal and may be associated with a myriad of systemic manifestations, including fever, abnormal liver function tests, pancytopenia, haemophagocytosis and multiorgan in®ltration.…”

Cutaneous lymphomas other than mycosis fungoides in Singapore: a clinicopathological analysis using recent classification systems

“…3,14 European data, however, showed a predominance or higher frequency of B-cell phenotype of about 40%. 2,15 Apart from a real geographical difference, where subcutaneous panniculitis-like T-cell lymphoma and NK ⁄ T-cell lymphoma are mainly recognized in the U.S.A. and in the Asia-Pacific region, 7,[16][17][18][19][20][21][22] and Borreliarelated cutaneous B-cell lymphomas are more common in Europe, 23 these differences could also be contributed by selection or inclusion criteria, different classification systems and different antibody panels. The older classifications, for instance, the Kiel classification and Working formulation had no provision for lymphomatoid papulosis, while in the REAL classification, it was classified under the broad category of peripheral T-cell lymphomas, unspecified.…”

Maintenance and Characterization of an Epstein Barr Virus‐infected CD56‐negative T Cell Lymphoma

“…Epstein-Barr virus (EBV) is associated with various lymphoid malignancies, including Burkitt's lymphoma, 1) lymphoma occurring in immunocompromised patients, 2) Hodgkin's disease, 3) pyothorax-associated lymphoma, 4,5) nasal and nasal type T/Natural Killer (T/NK) cell lymphoma (NT/NKL), 6) NK cell leukemia/lymphomas, [7][8][9] Tcell lymphoma, 10) and a few other lymphoma subtypes. B cell lymphoma predominates in EBV-associated lymphomas, while some portions are reported to be of T and/or NK cell lineage.…”