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

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.

Next-generation sequencing for MRD monitoring in B-lineage malignancies: from bench to bedside

“…Several studies have also noted the selection pressure between remission and relapse, such as that resulting from treatments and antigens [68,[71][72][73]. Other IG repertoire-associated factors influencing the prognosis included monoclonality, the length of the HCDR3, and the abnormal ratio of functional IGK/IGL rearrangements [56,69,74,75].…”

Occurrence of MYD88L265P and CD79B mutations in diffuse large b cell lymphoma with bone marrow infiltration: A case report

“…Cox et al [ 12 ] analyzed 151 patients with DLBCL and found that 17 cases (11.2%) had a serum monoclonal IgM component, although none were associated with MYD88L265P mutations, which indicates there is no necessary connection between monoclonal IgM and MYD88L265P. Cho et al [ 13 ] studied the relationship between the clonal status of monoclonal immunoglobulin gene rearrangement and histological B cell aggregation in the BM. The results showed that of the 394 patients with DLBCL, 32 patients had BM invasion, and only two patients with large B-cell lymphoma had no gene rearrangement detected[ 13 ].…”

“…Cho et al [ 13 ] studied the relationship between the clonal status of monoclonal immunoglobulin gene rearrangement and histological B cell aggregation in the BM. The results showed that of the 394 patients with DLBCL, 32 patients had BM invasion, and only two patients with large B-cell lymphoma had no gene rearrangement detected[ 13 ]. This suggests that patients with BM invasion were more likely to have monoclonal immunoglobulin gene rearrangements.…”

“…This suggests that patients with BM invasion were more likely to have monoclonal immunoglobulin gene rearrangements. However, there is no correlation with the COO[ 13 ]. Although BM infiltration was found in our case, it showed a histological inconsistency compared with the immunohistochemistry of the peripheral lymph nodes.…”

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“…Bone marrow biopsies are slowly being replaced by other methods for staging. Cho et al [ 41 ] investigated pretreatment BM samples of 394 DLBCL patients with clonality testing in addition to microscopic examination. Monoclonal immunoglobulin gene rearrangement was detected in 25 % of cases.…”