This entity has been renamed “CD4+’CD56+ hematodermic neoplasm” and is now recognized as a malignancy of immature dendritic cells. As such, it is discussed with other dendritic cell neoplasms in Chapter 22.

NK-cell acute leukemia has rarely been reported, usually as a biphenotypic leukemia with evidence of myeloid or B-cell antigen expression (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16). It occurs de novo and has been reported as a blast crisis in chronic myeloid leukemia and as a relapse in T-cell acute lymphoblastic leukemia.

Patients present with cytopenias, lymphadenopathy, hepatosplenomegaly, and systemic symptoms. Skin lesions may or may not be present. The clinical course is aggressive. Relapses may show a change from the initial NK-cell immunophenotype to a myeloid’NK-cell or T-cell immunophenotype.

Peripheral blood and bone marrow specimens show blasts with agranular cytoplasm, resembling lymphoblasts or monoblasts. Rarely, cells have been described as pleomorphic and bizarre.

Immunophenotyping shows expression of cytoplasmic CD3ε, CD45, CD56, and terminal deoxynucleotidyl transferase. CD7, CD34, and CD57 may be expressed The blasts do not express surface CD3, CD4, CD16, CD19, CD33, or myeloperoxidase (MPO). Epstein-Barr virus antigens are not present. Killer cell immunoglobulin-like receptor (KIR) may be expressed. T-cell receptor genes and immunoglobulin genes show no rearrangements.

In some cases, CD13, CD33, and’or MPO expression has been reported. These cases have been considered as myeloid’NK-cell acute leukemia.

In other cases, CD10 and CD19 expression has been reported, with rearranged T-cell receptor and immunoglobulin genes. These cases have been considered as B-cell’NK-cell acute leukemia.

Still other cases have been reported with coexpression of NK-cell, T-cell, and B-cell antigens; and with coexpression of NK-cell, myeloid, and dendritic cell (CD123) antigens.

The differential diagnosis includes other types of acute leukemia, blast crisis of chronic myeloid leukemia, and CD4+’CD56+ hematodermic neoplasm.

Chronic lymphoproliferative disorder of NK-cells. (NK-cell large granular lymphocytic leukemia, chronic NK-cell lymphocytosis) is essentially the NK-cell equivalent of chronic lymphocytic leukemia (Figs. 27.1 and 27.2) (17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33). This entity represents a minor component of large granular lymphocytic leukemia, the major component being T-cell large granular lymphocytic leukemia.