Cytoplasmic Expression of CD3ϵ Heterodimers by Flow Cytometry Rapidly Distinguishes between Mature T-Cell and Natural Killer-Cell Neoplasms

Min Shi, Phuong Nguyen, Michael M. Timm, Gregory E. Otteson, Pedro Horna, Horatiu Olteanu, Dragan Jevremovic

Research output: Contribution to journalArticlepeer-review

Abstract

Distinguishing between T-cell and natural killer (NK)-cell neoplasms could be difficult given their overlapping immunophenotype. In this study, we investigated whether a flow cytometry assay with cytoplasmic staining for CD3 could be used for this purpose. Methods: Flow cytometry immunophenotyping was performed on 19 surface CD3 (sCD3)-negative mature T-cell neoplasms, 10 sCD3-positive mature T-cell neoplasms, 13 mature NK-cell neoplasms, and 19 normal controls. In addition to routine antibody panels (CD2, sCD3, CD4, CD5, CD7, CD8, CD16, CD45, CD56, CD57, CD94, CD158a, CD158b, CD158e, NKG2A TCRγ/δ), cytoplasmic staining for a monoclonal CD3 antibody (clone SK7/Leu-4) was assessed in all cases. A molecular study for T-cell receptor (TCR) gene rearrangement and an immunohistochemical study for TCRβ were performed. Results: Our data showed all T-cell neoplasms were uniformly positive for cytoplasmic CD3 (cCD3) regardless of sCD3 expression, whereas 85% of NK-cell neoplasms completely lacked cCD3 expression. The 2 cases with classic NK-cell immunophenotype but partial cCD3 expression showed no molecular genetic features of T-cell lineage by TCR gene rearrangement studies. Conclusions: Uniform cCD3 positivity and homogeneous cCD3 negativity highly suggest T-cell and NK lineage, respectively. When partial cCD3 expression is encountered, additional confirmatory studies should be pursued for the most accurate lineage assignment.

Original languageEnglish (US)
Pages (from-to)683-691
Number of pages9
JournalAmerican journal of clinical pathology
Volume154
Issue number5
DOIs
StatePublished - Nov 1 2020

Keywords

  • Cytoplasmic CD3
  • Flow cytometry
  • NK-cell neoplasm
  • T-cell neoplasm

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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