Biophysical characterization of normal T-lymphocytes and Sézary cells

Abstract

Blood lymphocytes from 18 patients with cutaneous T-cell lymphoma (Sézary syndrome and mycosis fungoides) were characterized using multiparameter laser flow microfluorimetry (FMF) and automated image analysis (AIA) and the results correlated with routine blood smears, cytogenetic studies and observations made on PHA-stimulated normal T-lymphocytes in vitro. Specimens from all 9 patients with Sézary syndrome and 5 of 9 patients with mycosis fungoides contained one or more discrete subpopulations of neoplastic (Sézary) lymphocytes that were detected by FMF. Studies with AIA demonstrated that neoplastic T-lymphocytes are distinguished from normal quiescent (G0) lymphocytes not only by alterations in DNA content (aneuploidy) but also by chromatin structuring (increased chromatin dispersion), which may be a more sensitive index of neoplastic transformation than ploidy levels. In several patients, small and large Sézary cells were present with DNA-chromatin properties quite similar to normal cycling G1 and G2 lymphocytes respectively, but their presence was not explained by an increase in proliferative activity in the blood. These findings indicate that Sézary syndrome consists of a heterogeneous group of related disorders differing in terms of the Sézary cell population. The response to treatment and prognosis may differ accordingly.