NONNASAL LYMPHOMA EXPRESSING THE NATURAL-KILLER-CELL MARKER CD56 - A CLINICOPATHOLOGICAL STUDY OF 49 CASES OF AN UNCOMMON AGGRESSIVE NEOPLASM

Expression of the natural killer (NK) cell antigen CD56 is uncommon am ong lymphomas, and those that do are almost exclusively of non-B-cell lineage and show a predilection for the nasal and nasopharyngeal regio n. This study analyzes 49 cases of nonnasal CD56(+) lymphomas, the lar gest series to date, to characterize the clinicopathologic spectrum of these rare neoplasms. All patients were Chinese. Four categories coul d be delineated. (1) Nasal-type NK/T cell lymphoma (n = 34) patients w ere adults 21 to 76 years of age (median, 50 years), including 25 men and 9 women, They presented with extranodal disease, usually in multip le sites, The commonest sites of involvement were skin, upper aero-dig estive tract, testis, soft tissue, gastrointestinal tract, and spleen. Only 7 cases (21%) apparently had stage I disease. The neoplastic cel ls were often pleomorphic, with irregular nuclei and granular chromati n, and angiocentric growth was common. The characteristic immunophenot ype was CD2(+) CD3/Leu4(-) CD3 epsilon(+) 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 rel apse at 5 months to 2.5 years; and 2 were alive and well at 3 and 5 ye ars, respectively. (2) Aggressive NK cell leukemia/lymphoma (n = 5) pa tients presented with hepatomegaly and blood/marrow involvement, somet imes accompanied by splenomegaly or lymphadenopathy. The neoplastic ce lls often had round nuclei and azurophilic granules in the pale cytopl asm. All cases exhibited an immunophenotype of CD2(+) CD3/Leu4(-) CD56 (+) CD16(-) CD57(-) and all were EBV+. All of these patients died with in 6 weeks. (3) In blastoid NK cell lymphoma (n = 2), the lymphoma cel ls resembled those of lymphoblastic or myeloid leukemia. One case stud ied for CD2 was negative and both cases were EBV-. One patient was ali ve with disease at 10 months and one was a recent case. (4) Other spec ific lymphoma types with CD56 expression (n = 8) included one case eac h of hepatosplenic gamma delta T-cell lymphoma and S100 protein(+) T-c ell lymphoproliferative disease and two cases each of T-chronic lympho cytic/prolymphocytic leukemia, lymphoblastic lymphoma, and true histio cytic lymphoma. All of these cases were EBV-. Six patients died at a m edian of 6.5 months. Nonnasal CD56(+) lymphomas are heterogeneous, but all pursue a highly aggressive clinical course. The nasal-type NK/T-c ell lymphoma and aggressive NK cell leukemia/lymphoma show distinctive clinicopathologic features and a very strong association with EBV. Bl astoid NK cell lymphoma appears to be a different entity and shows no association with EBV. (C) 1997 by The American Society of Hematology.