Non‐CLL‐like monoclonal B‐cell lymphocytosis in the general population: Prevalence and phenotypic/genetic characteristics

Background: Monoclonal B‐cell lymphocytosis (MBL) indicates <5 × 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 × 10 9 /L) were immunophenotyped using high‐sensitive flow cytometry, based on 8‐color stainings and the screening for >5 × 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 × 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 CD5 −/+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. © 2010 International Clinical Cytometry Society