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Nonnasal lymphoma expressing the natural killer cell marker CD56: a
clinicopathologic study of 49 cases of an uncommon aggressive neoplasm
JK Chan, VC Sin, KF Wong, CS Ng, WY Tsang, CH Chan, MM Cheung and WH Lau
Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong.
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.
Volume 89,
Issue 12,
pp. 4501-4513,
06/15/1997
Copyright © 1997 by The American Society of Hematology
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