Clonal B-cell lymphocytosis exhibiting immunophenotypic features consistent with a marginal-zone origin: is this a distinct entity?

Blood. 2014 Feb 20;123(8):1199-206. doi: 10.1182/blood-2013-07-515155. Epub 2013 Dec 3.

Abstract

The biological and clinical significance of a clonal B-cell lymphocytosis with an immunophenotype consistent with marginal-zone origin (CBL-MZ) is poorly understood. We retrospectively evaluated 102 such cases with no clinical evidence to suggest a concurrent MZ lymphoma. Immunophenotyping revealed a clonal B-cell population with Matutes score ≤2 in all cases; 19/102 were weakly CD5 positive and all 35 cases tested expressed CD49d. Bone marrow biopsy exhibited mostly mixed patterns of small B-lymphocytic infiltration. A total of 48/66 (72.7%) cases had an abnormal karyotype. Immunogenetics revealed overusage of the IGHV4-34 gene and somatic hypermutation in 71/79 (89.8%) IGHV-IGHD-IGHJ gene rearrangements. With a median follow-up of 5 years, 85 cases remain stable (group A), whereas 17 cases (group B) progressed, of whom 15 developed splenomegaly. The clonal B-cell count, degree of marrow infiltration, immunophenotypic, or immunogenetic findings at diagnosis did not distinguish between the 2 groups. However, deletions of chromosome 7q were confined to group A and complex karyotypes were more frequent in group B. Although CBL-MZ may antedate SMZL/SLLU, most cases remain stable over time. These cases, not readily classifiable within the World Heath Organization classification, raise the possibility that CBL-MZ should be considered as a new provisional entity within the spectrum of clonal MZ disorders.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / pathology*
  • Cell Lineage / genetics
  • Cell Lineage / immunology*
  • Chromosome Banding
  • Clone Cells / pathology
  • Disease Progression
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain / genetics
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain / immunology
  • Humans
  • Immunophenotyping
  • Lymphocytosis / classification
  • Lymphocytosis / genetics
  • Lymphocytosis / pathology*
  • Lymphoma, B-Cell, Marginal Zone / classification
  • Lymphoma, B-Cell, Marginal Zone / genetics
  • Lymphoma, B-Cell, Marginal Zone / pathology*
  • Male
  • Middle Aged
  • Retrospective Studies