CD56+/CD4+lymphomas and leukemias are morphologically, immunophenotypically, cytogenetically, and clinically diverse

CD56, a neural adhesion molecule, is a marker of natural killer (NK) lympho cytes as well as a subgroup of CD8+ T cells. Normal lymphocytes with a CD56 /CD4 phenotype are scarce. Physiologic increases may occur in patients with immunosuppression, chronic inflammation, and autoimmune disorders. We repo rt 4 cases of lymphomas/leukemias with the unusual CD56/CD4 phenotype. Two were of T-cell and 2 of true NK-cell origin. The T-cell lymphomas had large granular lymphocyte morphologic features and splenomeagaly. One patients h ad a benign course; the other died within months of the leukemia diagnosis. The 2 NK cell lymphomas had blastic morphologic features, initially involv ed skin, and had a very aggressive clinical course; 1 patient died of acute leukemia, and 1 had recurrence after bone marrow transplantation. Cytogene tic analyses did not show a consistent pattern of abnormalities. The NK lym phoma with acute leukemia had a t(2;5) but was CD30- and anaplastic lymphom a kinase negative. Although CD56+/CD4+ lymphomas/leukemias are a heterogene ous group, there may be a distinct subgroup of NK lymphoblastoid lymphomas of the skin, judging from our cases, as well as those previously reported.