{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:02:01Z","timestamp":1790334121225,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytometry Part B Clinical"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Natural killer (NK) cell neoplasms span indolent to highly aggressive entities, and flow cytometric immunophenotyping is central to their detection and classification. However, distinguishing reactive from neoplastic NK cell expansions can be challenging because NK cells lack somatically recombined antigen receptors, and reactive states may produce restricted phenotypes that mimic clonality. This best\u2010practices manuscript outlines a practical, flow cytometry\u2010based approach to NK cell analysis that integrates (i) robust lineage definition and gating, (ii) subset\u2010aware interpretation of CD16\/CD56 patterns, (iii) inference of clonality using killer cell immunoglobulin\u2010like receptor (KIR; CD158) repertoire restriction and other NK cell receptors. We highlight key pitfalls\u2014particularly the limited utility of KIR\u2010based clonality inference in CD56\n                    <jats:sup>bright<\/jats:sup>\n                    CD16\n                    <jats:sup>\u2212<\/jats:sup>\n                    NK cells and the potential for adaptive NK cell expansions to appear KIR\u2010restricted\u2014and propose an operational reflex algorithm triggered by NK cell expansion and\/or defined immunophenotypic abnormalities in screening tubes. Case\u2010based examples illustrate common scenarios, including NK\u2010large granular lymphocytic leukemia, extranodal NK\/T\u2010cell lymphoma with circulating CD56\n                    <jats:sup>bright<\/jats:sup>\n                    CD16\n                    <jats:sup>\u2212<\/jats:sup>\n                    cells, reactive adaptive NK cell expansions, and concurrent neoplastic and reactive NK clones. This framework supports standardized, reproducible NK cell assessment and improves specificity of flow\u2010based clonality inference in routine clinical practice.\n                  <\/jats:p>","DOI":"10.1002\/cyto.b.70076","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:11:38Z","timestamp":1790331098000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A practical difference from the normal approach to evaluate natural killer (NK) cells and NK cell neoplasms by flow cytometry"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1430-5852","authenticated-orcid":false,"given":"Aaron J.","family":"Wilk","sequence":"first","affiliation":[{"name":"Department of Pathology Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Shameli","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Ames","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Fromm","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0075-688X","authenticated-orcid":false,"given":"Bartosz","family":"Grzywacz","sequence":"additional","affiliation":[{"name":"Department of Pathology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Hematopathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sindhu","family":"Cherian","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5220-4628","authenticated-orcid":false,"given":"Jean","family":"Oak","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University School of Medicine  Stanford California 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