The prognostic significance of monoclonal immunoglobulin gene rearrangement in conjunction with histologic B-cell aggregates in the bone marrow of patients with diffuse large B-cell lymphoma

Cancer Med. 2016 Jun;5(6):1066-73. doi: 10.1002/cam4.679. Epub 2016 Feb 29.

Abstract

Bone marrow involvement (BMI) is a well-known poor prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL). This study robustly investigated the significance of monoclonal immunoglobulin gene rearrangement combined with histologic B-cell aggregates in bone marrow (BM) in the detection of a poor prognostic group. Pretreatment BM samples of 394 DLBCL patients were analyzed via the immunoglobulin gene rearrangement study and the microscopic examination. Monoclonal immunoglobulin gene rearrangement was detected in 25.4% of cases. Histologic B-cell aggregates with the features of large B-cell lymphoma aggregates, small cell B-cell lymphoma aggregates, or B-cell aggregates of unknown biological potential were observed in 12% of cases (6.9%, 1.3%, and 3.8%, respectively). Histologic B-cell aggregates were more associated with monoclonality than polyclonality. Cases with both monoclonality and histologic B-cell aggregates demonstrated close association with poor prognostic factors such as a higher International Prognostic Index score and showed an inferior overall survival rate when compared to cases with only monoclonality or only histologic B-cell aggregates. From the findings, a combination of monoclonality and histologic B-cell aggregates within the bone marrow was highly associated with poor prognosis and could be used to determine high-risk DLBLC patients with greater sensitivity and specificity than conventional microscopic examination or immunoglobulin gene rearrangement study alone.

Keywords: Bone marrow; diffuse large B-cell lymphoma; immunoglobulin genes; lymphoid aggregates; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology*
  • Biomarkers
  • Bone Marrow / pathology*
  • Cell Aggregation
  • Female
  • Gene Rearrangement, B-Lymphocyte*
  • Genes, Immunoglobulin*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models

Substances

  • Biomarkers