Mature T-cell leukemia/lymphoma with an NK-like immunophenotype: A report of 7 cases

Distinguishing T-cell from NK-cell neoplasms can occasionally be challenging, as neoplastic T cells can lose T-cell markers such as surface CD3 (sCD3) and CD5 while acquiring NK-cell markers such as CD16, CD56, and CD94. In this study, we present a series of 7 mature T-cell lymphoma/leukemia cases with NK-like immunophenotypes to clarify diagnostic approaches for lineage determination. The cohort included 3 cases of peripheral T-cell lymphoma, not otherwise specified, 2 cases of T-large granular lymphocytic leukemia, and 2 cases of hepatosplenic T-cell lymphoma. In all cases, flow cytometry immunophenotypic analysis showed that the neoplastic cells exhibited an NK-like immunophenotype characterized by expression of CD56 and CD94 in all 7 cases, with 4 cases also positive for CD16. Concurrently, the neoplastic cells in all cases were negative for the T-cell markers, including sCD3, CD4, CD5, TCRαβ, TCRγδ, and TRBC1 by flow cytometry. These immunophenotypic features mimicked NK cells. But in T-cell receptor (TCR) gene rearrangement analysis, all 7 cases had monoclonal TRG rearrangements, and 4 cases also showed concurrent TRB rearrangements. Immunohistochemical analysis showed that all 6 tested cases were positive for BCL11B, and 1 case was positive for TCRαβ. Additionally, 2 of 3 cases assessed using a T-cell-specific CD3 antibody were positive for cytoplasmic CD3 by flow cytometry. In summary, this study illustrates that neoplastic T cells can show an NK-like immunophenotype. Features useful for supporting T-lineage in this context include cytoplasmic CD3 expression assessed using a T-cell-specific CD3 antibody, clonal TCR gene rearrangement, BCL11B expression, and detection of TCRαβ, TCRγδ, or TRBC by immunohistochemistry.