NK cells

NK cells represent a third lineage of lymphoid cells. They account for 10-15% of circulating lymphocytes in adults, more in cord blood. They are also found in the spleen but almost none in lymph nodes, thymus or other lymphoid organs. They differentiated in bone marrow and do not require the thymus for their maturation. They have the ability to lyse tumour cells, virus-infected cells and certain normal target cells without prior sensitization or activation.

Morphologically, they are medium to large lymphocytes with abundant cytoplasm containing azurophilic granules and an indented or kidney-shaped nucleus (not all large granulocytic lymphocytes possess NK activity).

Immunophenotypically, they are a heterogeneous cell population which shares surface and cytoplasmic molecules expressed by macrophages, granulocytes and T cells. All NK cells express CD16 and CD56. The vast majority express CD11b. The TCR and Ig genes are in germline configuration.

The cytoplasmic granules contain perforin and granzymes.

NK cells carry receptors:

C-type lectin-like receptors of CD94 with associated NKG-2 proteins result in NK cell activation and cytotoxicity
The ability of NK cells to destroy target cells is mediated by a number of cell surface receptors, including the killer immunoglobulin-like receptors (KIRs), acting in concert with co-receptors including CD2445.

Non-neoplastic NK proliferations:

NK-cell lymphoproliferative disorder5 (NK-cell large granular lymphocytosis): this is a benign NK proliferation, which may be chronic. It may represent a response to a viral infection. It closely resembles T-cell large granular lymphocytic leukaemia. However, there is no lymphadenopathy, hepatosplenomegaly or neutropenia.
NK cells are seen in creased numbers after bone marrow transplantation5.

NK cell neoplasms (WHO classification)

extranodal NK/T lymphoma, nasal type
Aggressive NK-cell leukaemia, possibly the leukaemic counterpart of the above.
blastic NK-cell lymphoma: this variant is not associated with EBV4.

References

1Chan, J. K. Peripheral T-cell and NK-cell neoplasms: an integrated approach to diagnosis. Mod Pathol 1999;12:177-99.

2Jaffe, E. S., Chan, J. K., Su, I. J., Frizzera, G., Mori, S., Feller, A. C., Ho, F. C. Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology. Am J Surg Pathol 1996;20:103-11.

3Chan, J. K., Yip, T. T., Tsang, W. Y. Detection of Epstein-Barr viral RNA in malignant lymphomas of the upper aerodigestive tract. Am J Surg Pathol 1994;18:938-46.

4Chan, J. K., Sin, V. C., Wong, K. F. Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood 1997;89:4501-13.

5Nava VE,Jaffe ES The pathology of NK-cell lymphomas and leukemias. Adv Anat Pathol 2005; 12:27-34

This page last revised 8.6.2002.