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.

Highlights

  • In patients with diffuse large B-­cell lymphoma (DLBCL), the most common subtype of malignant lymphoma worldwide, bone marrow involvement (BMI) is known to be a poor prognostic factor for patient outcome

  • Large B-c­ell lymphoma aggregates were noted in 6.9% (n = 27), small cell B-­cell lymphoma aggregates in 1.3% (n = 5), and B-­cell aggregates of unknown biological potential in 3.8% (n = 15)

  • This study investigated the prognostic implications of the molecular detection of monoclonal immunoglobulin gene rearrangement in conjunction with the histologic detection of B-­cell aggregates in the pretreatment bone marrow of patients with diffuse large B-c­ ell lymphoma (DLBCL)

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Summary

Introduction

In patients with diffuse large B-­cell lymphoma (DLBCL), the most common subtype of malignant lymphoma worldwide, bone marrow involvement (BMI) is known to be a poor prognostic factor for patient outcome. Bone marrow biopsies and aspirations sampled from the iliac crest bone, which are the conventional means of BMI detection, are notorious for their high false-­negative rates [2, 3, 5]. To overcome this limitation, the usefulness of ancillary tests, including immunoglobulin gene rearrangement study, flow cytometry and immunohistochemistry, have been evaluated.

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