Non-CLL-like Monoclonal B-Cell Lymphocytosis in the General Population: Prevalence and Phenotypic/Genetic Characteristics

Background: Monoclonal B-cell lymphocytosis (MBL) indicates <5 x 10(9) peripheral blood (PB) clonal B-cells/L in healthy individuals. In most cases, MBL cells show similar phenotypic/genetic features to chronic lymphocytic leukemia cells-CLL-like MBL but little is known about non-CLL-like MBL. Methods: PB samples from 639 healthy individuals (46% men/54% women) >40 years old (62 +/- 13years) with normal lymphocyte counts (2.1 +/- 0.7 x 10(9)/L) were immunophenotyped using high-sensitive flow cytometry, based on 8-color stainings and the screening for >5 x 10(6) total PB leukocytes. Results: Thirteen subjects (2.0%; 9 males/4 females, aged 73 +/- 10 years; absolute lymphocyte count: 2.4 +/- 0.8 x 10(9)/L) showed a non-CLL-like clonal B-cell population, whose frequency clearly increased with age: 0.4%, 3%, and 5.4% of subjects aged 40-59, 60-79, and >= 80 years, respectively. One single B-cell clone was detected in 9/13 cases, while two B-cell clones were found in 4/13 (n = 17 MBL populations). Nine MBL cell populations showed a CD5(-) phenotype (usually overlapping with marginal zone-derived (MZL) or lymphoplasmacytic (LPL) non-Hodgkin lymphoma (NHL) B-cells, or an unclassifiable NHL), but CD-/+d (n = 3) and CD5(+) (n = 3 non-CLL-like MBL, consistent with a mantle-cell lymphoma (MCL)-like phenotype, and n = 2 CLL-like) MBL were also identified; iFISH supported the diagnosis in most cases. No preferential IGHV usage of B-cell receptor could be found. Twelve cases reevaluated at month +12 showed circulating clonal B-cells, at mean levels significantly higher than those initially detected. Conclusions: Non-CLL-like MBL cases frequently show biclonality, in association with MZL-, LPL-, MCL-like, or unclassifiable phenotypic profiles. As with CLL-like MBL, the frequency of non-CLL-like MBL increases with age, with a clear predominance of males. (C) 2010 International Clinical Cytornetry Society