T-cell clones of uncertain significance are highly prevalent and show close resemblance to T-cell large granular lymphocytic leukemia. Implications for laboratory diagnostics

Min Shi, Horatiu Olteanu, Dragan Jevremovic, Rong He, David Viswanatha, Heidi Corley, Pedro Horna

Research output: Contribution to journalArticle

Abstract

Benign clonal T-cell expansions in reactive immune responses often complicate the laboratory diagnosis T-cell neoplasia. We recently introduced a novel flow cytometry assay to detect T-cell clones in blood and bone marrow, based on the identification of a monophasic T-cell receptor (TCR) β chain constant region-1 (TRBC1) expression pattern within a phenotypically distinct TCRαβ T-cell subset. In routine laboratory practice, T-cell clones of uncertain significance (T-CUS) were detected in 42 of 159 (26%) patients without T-cell malignancy, and in 3 of 24 (13%) healthy donors. Their phenotype (CD8+/CD4: 78%, CD4/CD8: 12%, CD4+/CD8+: 9%, or CD4+/CD8: 2%) closely resembled that of 26 cases of T-cell large granular lymphocytic leukemia (T-LGLL) studied similarly, except for a much smaller clone size (p < 0.0001), slightly brighter CD2 and CD7, and slightly dimmer CD3 expression (p < 0.05). T-CUS was not associated with age, gender, comorbidities, or peripheral blood counts. TCR-Vβ repertoire analysis confirmed the clonality of T-CUS, and identified additional clonotypic CD8-positive subsets when combined with TRBC1 analysis. We hereby report the phenotypic features and incidence of clonal T-cell subsets in patients with no demonstrable T-cell neoplasia, providing a framework for the differential interpretation of T-cell clones based on their size and phenotypic properties.

Original languageEnglish (US)
JournalModern Pathology
DOIs
StateAccepted/In press - 2020

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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