SOHO State of the Art Updates and Next Questions: High incidence of clonal CD8+ T-cell proliferation in non-malignant conditions may reduce the significance of T-cell clonality assay for differential diagnosis in oncohematology

Abstract Background PCR analysis of rearranged T-cell receptor (TCR) genes is a valuable diagnostic tool for differential diagnosis of T-cell large granular lymphocytic (T-LGL) leukemia and reactive lymphocytosis. Age-related narrowing of T-cells repertoire, expansion of immune or autoimmune clones may lead to false positive results. The objective of this study was to evaluate specificity and positive predictive value of PCR-based clonality assessment for a differential diagnostics of T-LGL leukemia. Patients and methods Rearrangements of TCRG and TCRB genes using BIOMED-2 protocol were assessed in healthy individuals including the elderly (n-62), patients with rheumatic diseases (n-14), transitory reactive CD8+ lymphocytosis (n-17) and T-LGL leukemia (n-42). Results Monoclonal TCRG/TCRB rearrangements in blood were identified in 11.3%/4.8% of healthy individuals (7/3 of 62); 21.4%/14.3% of patients with rheumatic diseases (3/2 of 14) and 17.6%/11.8% of patients with reactive lymphocytosis (3/2 of 17). Immunomagnetic selection of lymphocytes in healthy individuals (31 of 33) revealed that clonal T-cells belong to CD8+ and CD57+ population. No clonal Vβ-Jβ TCRB rearrangements were found in control group, only Dβ-Jβ TCRB and TCRG. Given the high detectability of Vβ-Jβ TCRB monoclonal rearrangements (96.7%) in patients with αβ-T-LGL leukemia, this marker had the greatest specificity and positive predictive value (100%; 99.2%). Conclusions The presence of clonal CD8+CD57+ cells in blood is common for healthy individuals and patients with reactive conditions and may not associate with any malignancy. Different specificity of TCRG/ Dβ-Jβ TRB/ Vβ-Jβ TCRB PCR reactions should be taken into account for T-cell clonality data interpretation.