From the Guidelines
Diffuse Large B-Cell Lymphoma (DLBCL) is characterized by a diffuse infiltrate of large cells expressing B-cell markers CD19 and CD20.
Clinical Features
The clinical features of DLBCL can be summarized as follows:
- Morphological diagnosis: confirmed by immunophenotypic investigations, either immunohistochemistry (IHC) or flow cytometry, or a combination of both techniques 1
- Immunohistochemical panel: includes CD20, CD79a, BCL6, CD10, MYC, BCL2, Ki67, IRF4, CyclinD1, CD5, and CD23 to confirm B-cell lineage and distinguish alternative diagnoses 1
- Cell of origin: determined by gene expression profiling (GEP) or IHC-based classification systems, with germinal centre B-cell (GCB) or activated B-cell subtypes having different clinical outcomes 1
- Prognostic factors: include cell of origin phenotype, with GCB subtype having a better clinical outcome than activated B-cell subtype 1
Diagnosis
Diagnosis of DLBCL should be carried out in a reference haematopathology laboratory with expertise in morphological interpretation and facilities to carry out phenotypic and molecular investigations 1. A surgical excision biopsy is the optimal method of diagnosis, allowing assessment of nodal architecture and providing adequate material for phenotypic and molecular studies 1.
Molecular Biology
Molecular analysis, such as gene expression profiling, can help determine the cell of origin and predict clinical outcome 1. IHC-based classification systems, such as the Hans algorithm, can also be used to classify DLBCL as GCB or non-GCB subtypes 1.
From the Research
Clinical Features of Diffuse Large B-Cell Lymphoma (DLBCL)
The clinical features of DLBCL are characterized by a heterogeneous group of diseases with variable outcomes, differentially characterized by clinical features, cell of origin (COO), molecular features, and frequently recurring mutations 2. The diagnosis of DLBCL is ideally made 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 2.
Key Clinical Features
- DLBCL is the most common type of aggressive non-Hodgkin lymphoma originating from the germinal center 2
- 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 2
- 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 2
- 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 2
Molecular Subtypes and Outcomes
- DLBCL can be classified into transcriptionally defined activated B cell (ABC) and germinal center B cell (GCB) subtypes, which are associated with distinct pathogenic mechanisms and outcomes 3
- Gene expression profiling has identified two distinct forms of DLBCL: activated B cell-like (ABC) and germinal center B-cell-like (GCB) types, with ABC DLBCL exhibiting a worse prognosis than GCB DLBCL by molecular diagnosis after R-CHOP therapy 4
Clinical Manifestations and Prognosis
- Clinical manifestations of DLBCL transformed from follicular lymphoma include extranodal involvement, anemia, and B symptoms, with a median age of 56 years old and a male-to-female ratio of 1:1 5
- The germinal center B-cell-like (GCB) subtype of DLBCL is observed in most cases, with an overall response rate of 80.0% and a complete response rate of 60.0% 5
- Factors affecting prognosis include OR rate, POD24, IPI score, B symptoms, and anemia, with IPI score being an independent prognostic factor for OS 5