Diffuse large B‐cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment

Abstract

Disease Overview: Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma originating from the germinal center, and it represents a heterogeneous group of diseases with variable outcomes that are differentially characterized by clinical features, cell of origin (COO), molecular features, and most recently, frequently recurring mutations. Diagnosis: DLBCL is ideally diagnosed from an excisional biopsy of a suspicious lymph node, which shows sheets of large cells that disrupt the underlying structural integrity of the follicle center and stain positive for pan-B-cell antigens, such as CD20 and CD79a. COO is determined by immunohistochemical stains, while molecular features such as double-hit or triple-hit disease are determined by fluorescent in situ hybridization analysis. Commercial tests for frequently recurring mutations are currently not routinely used to inform treatment. Risk Stratification: Clinical prognostic systems for DLBCL, including the rituximab International Prognostic Index, age-adjusted IPI, and NCCN-IPI, use clinical factors for the risk stratification of patients, although this does not affect the treatment approach. Furthermore, DLBCL patients with non-germinal center B-cell (GCB)-like DLBCL (activated B-cell like and unclassifiable) have a poorer response to up-front chemoimmunotherapy (CI) compared to patients with GCB-like DLBCL. Those with c-MYC-altered disease alone and in combination with translocations in BCL2 and/or BCL6 (particularly when the MYC translocation partner is immunoglobulin) respond poorly to up-front CI and salvage autologous stem cell transplant at relapse.Risk-Adapted Therapy: This review will focus on differential treatment of DLBCL up-front and at the time of relapse by COO and molecular features.

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

“…Diffuse large B-cell lymphoma (DLBCL) is the most common class of aggressive non-Hodgkin lymphoma originating from the germinal center. It is a heterogeneous group of diseases with variable outcomes that are characterized by clinical features, origin, molecular characteristics, and mutations [16]. DLBCL is a malignancy of large B cells and its incidence is increasing 3 to 4% each year in the US [17].…”

Risk Stratification Using Multivariable Fractional Polynomials in Diffuse Large B-Cell Lymphoma

“…Diffuse large B-cell lymphoma (DLBCL) is an aggressive and the most prevalent subtype of non-Hodgkin lymphoma (NHL) (1,2). Despite the improvement of overall outcomes with up-front immunochemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]), ∼40% of patients with DLBCL fail to achieve remission and ultimately succumb to death (3)(4)(5).…”

Ancillary Studies in the Diagnostic Evaluation of Large B-Cell Lymphoma

“…In general studies have shown MYC rearrangements to be an adverse prognostic finding, including lower response to standard R-CHOP therapy. 17 While there is a worse prognosis associated with MYC rearrangements in DLBCL, the prognosis is not as poor as when MYC is seen in association with either BCL2 or BCL6 rearrangement (''double-/triple-hit'' lymphomas). 3 Investigation on the rearrangement partner involved in MYC translocations has shown that MYC rearrangements involving immunoglobulin (Ig) genes (IgH, IgK [Ig kappa], or IgL [Ig lambda]) are more likely to be associated with this adverse prognostic risk than rearrangements involving other non-Ig gene partners.…”

“…12 Associations with an increased risk of central nervous system relapse and lower rates of overall survival have been reported. 17,19 Given the lack of a standardized algorithm to define this double-expresser subgroup, the clinical utility of MYC and BCL2 expression by immunohistochemistry is uncertain and likely depends on institutional validation. 11 While polymerase chain reaction (PCR) clonality assessment is not routinely required for the diagnosis of most DLBCLs, a pitfall in this type of analysis includes the presence of clonal T-cell receptor (TCR) rearrangements in up to 33% of DLBCLs due to lineage infidelity.…”

“…2 Of note, relapsed DLBCL may benefit from FISH analysis for these gene rearrangements as well, given their negative impact on prognosis in this clinical setting. 17 Large B-Cell Lymphoma With IRF4 Rearrangement This is a new category in the 2016 WHO classification that defines a group of predominantly pediatric large B-cell lymphomas of germinal center B-cell origin that show strong expression of MUM-1/IRF4 by immunohistochemistry and are characterized by IRF4 gene rearrangements ( Figure 6, C and D). 2,6 IRF4 is a transcription factor located on the short arm of chromosome 6.…”