How I Diagnose Mature T-Cell Proliferations by Flow Cytometry

Objectives Mature T-cell neoplasms are a challenging area of diagnostic hematopathology. Flow cytometry has emerged as a useful technique for T-cell assessment. Methods We discuss the application of flow cytometry to the evaluation of mature T-cell proliferations, to include illustrative cases, theoretical framework, detailed review of normal and reactive T-cell subsets, and examination of diagnostic pitfalls. Results Immunophenotypic aberrancy can be construed as a direct expression of the neoplastic phenotype, in contrast to clonal expansion, which is seen in reactive and neoplastic T-cell proliferations. Major and minor T-cell subsets show characteristic patterns of antigen expression. Reactive states can manifest expansions of normal minor subsets and also show alterations of antigen expression on certain populations. However, some patterns of antigen expression are either never or very rarely encountered in reactive T cells. Flow cytometric tools are now available to directly assess clonality in specific T-cell populations. Technical and biological pitfalls may complicate the interpretation of T-cell flow cytometry. Conclusions Flow cytometry is a very useful tool in the diagnostic armamentarium for the assessment of mature T-cell proliferations, but it must be interpreted based on a thorough knowledge of the T-cell immune response, as well as an awareness of clinical context.