A comparative study of flow cytometric T cell receptor Vβ repertoire and T cell receptor gene rearrangement in the diagnosis of large granular lymphocytic lymphoproliferation

Abstract

Large granular lymphocytes (LGLs) are medium- to large-sized lymphocytes with azurophilic cytoplasmic granules. Reactive vs. neoplastic LGLs are usually morphologically indistinguishable. We investigated 25 consecutive cases of LGL lymphoproliferation using flow cytometric T cell receptor Vβ (FC-Vβ) repertoire and T cell receptor gene rearrangement (TCR-GR) in detecting clonality. Seventeen patients (68%) were T-LGL leukemia (T-LGLL) with a male predominance, a median age of 67, and a median absolute LGL count of 2.592 × 10(9) /L. All cases were clonal using the FC-Vβ analysis, and all but one (94%) was clonal by TCR-GR. Eight patients (32%) had reactive LGL lymphoproliferation. Two had EBV-associated infectious mononucleosis; one was clonal by both FC-Vβ and TCR-GR; and the other was clonal only by TCR-GR. The remaining six cases were polyclonal by both assays. Patients with reactive LGL lymphoproliferation were more frequently associated with an underlying/concurrent malignancy than those with T-LGLL (4/8 cases vs. 1/17; P = 0.023, Fisher's exact test). We compared the demographic, hemogram, and clonality data between these two groups and found that the only significant difference was the lower median platelet count in the LGL lymphocytosis group (201 × 10(9) /L vs. 223 × 10(9) /L; P = 0.031; Student's t-test). A literature review including the current study showed a high sensitivity of FC-Vβ analysis for T-LGLL (97.2%; 107/110 cases). FC-Vβ analysis was slightly more sensitive than TCR-GR for the detection of clonal T cell lymphoproliferation. However, we must interpret the laboratory findings with clinical context as clonal T cell lymphoproliferation may occur in patients with viral infection.