From the Guidelines
Prominent NK/T cells on flow cytometry are most likely caused by NK/T cell lymphomas, reactive lymphocytosis, viral infections, chronic inflammatory conditions, or certain medications that alter immune function, as evidenced by recent studies 1. When evaluating prominent NK/T cells, it is essential to consider the underlying cause, as treatment approaches vary significantly depending on whether the cause is reactive or neoplastic.
- NK/T cell lymphomas, including extranodal NK/T cell lymphoma and aggressive NK cell leukemia, directly involve proliferation of these cells and typically show clonal expansion with aberrant marker expression.
- Viral infections, such as EBV, CMV, and HIV, can trigger a reactive increase in NK cells as part of the immune response.
- Chronic inflammatory conditions can lead to persistent immune activation with expanded NK cell populations.
- Certain immunomodulatory drugs like IL-2, lenalidomide, and checkpoint inhibitors can stimulate NK cell proliferation. Further workup should include clinical correlation, additional immunophenotyping, molecular studies for clonality (particularly EBV integration in lymphoma cases), and possibly tissue biopsy, as recommended by the NCCN guidelines 1. The distinction between reactive and neoplastic causes is crucial, as treatment approaches differ dramatically from observation or targeted anti-viral therapy for reactive causes to chemotherapy regimens like SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) for confirmed lymphomas, highlighting the importance of accurate diagnosis and management 1.
From the Research
Causes of Prominent Natural Killer (NK) Cells/T Cells in Flow Cytometry
- Prominent NK cells/T cells in flow cytometry can be caused by various conditions, including:
- T/NK-cell lymphoproliferative disorders 2
- Natural killer cell neoplasms, such as malignant NK cell lymphoma and aggressive NK cell lymphoma/leukemia 3
- Autoimmune lymphoproliferative syndrome with germline FAS mutation, which can lead to accumulation of mature T-cell receptor alpha/beta positive, CD4 and CD8 double-negative T cells 4
- Post-transplantation lymphoproliferative disease of natural killer cell lineage, which can occur after solid organ and bone marrow transplantation 5
- Iatrogenic immunodeficiency-associated Epstein-Barr virus (EBV) -negative natural killer cell lymphoproliferative disorder, which can develop in patients undergoing immunosuppressive therapy for conditions such as rheumatoid arthritis 6
Characteristics of NK Cells/T Cells in Flow Cytometry
- NK cells/T cells can exhibit various immunophenotypic features, including:
- CD56-expressing, larger forward scatter (FSC) and more usually CD7- and CD16-missing in malignant NK cell lymphoma and aggressive NK cell lymphoma/leukemia 3
- Abnormal CD56-expressing, which can be negative or partially/dimly expressed in chronic lymphoproliferative disorder of NK cell (CLPD-NK) 3
- CD2+, CD3-, CD3epsilon+, CD56+, CD94+, CD158a- and CD158b- in post-transplantation lymphoproliferative disease of natural killer cell lineage 5
- CD56 and T cell intracytoplasmic antigen positive, but CD3 and Epstein-Barr virus (EBV) -encoded RNA negative in iatrogenic immunodeficiency-associated EBV-negative natural killer cell lymphoproliferative disorder 6