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Diffuse large B-cell lymphoma grows quickly and is curable in a majority of cases with first-line treatment. Testing for MYC, BCL2 and BCL6 rearrangements at diagnosis is standard, because the combination defines a distinct and more aggressive entity rather than a variant. Central nervous system risk is assessed separately.
Also called DLBCL, High-grade B-cell lymphoma.
Start here
DLBCL is aggressive and frequently curable, which makes it one of the few cancers where moving quickly is itself part of the treatment, and where rearrangement testing at diagnosis changes what that treatment should be.
Diffuse large B-cell lymphoma grows quickly and is curable in a majority of cases with first-line treatment. Testing for MYC, BCL2 and BCL6 rearrangements at diagnosis is standard, because the combination defines a distinct and more aggressive entity rather than a variant. Central nervous system risk is assessed separately.
Before any molecular question
Usually established first: the diagnosis from an adequate biopsy, the stage, a prognostic index score, and CNS risk. This disease can progress over weeks, so the interval between presentation and starting treatment is itself clinically significant.
Usually already established
The divisions below are not labels. Each one changes what the treatment discussion is actually about.
DLBCL, not otherwise specified
The large majority. Cell of origin classification into germinal centre and activated B-cell types carries prognostic and increasingly therapeutic weight.
High-grade B-cell lymphoma with rearrangements
Carrying MYC together with BCL2 or BCL6. A distinct entity under current classification, not a subtype of DLBCL, and managed differently.
Primary CNS lymphoma
Arising in the brain. Managed on an entirely separate pathway, because most systemic treatment does not reach the central nervous system.
Transformed lymphoma
Arising from a previously indolent lymphoma. Confirmed by biopsy rather than assumed from clinical behaviour.
Relapsed or refractory disease
Where cellular therapy, bispecific antibodies and antibody-drug conjugates dominate the discussion, and where surface marker expression becomes central.
What is discussed
MYC, BCL2 and BCL6 rearrangements are tested at diagnosis, usually by fluorescence in situ hybridisation, because MYC together with either of the others defines high-grade B-cell lymphoma with rearrangements. Cell of origin classification separates germinal centre from activated B-cell type. Genetic subtypes defined by mutation clusters, involving genes such as MYD88, CD79B, EZH2, TP53 and CREBBP, are an active research classification moving toward clinical use. CD19, CD20 and CD79b expression underpins the immune-based treatment classes and can be lost under treatment pressure.
MYC, BCL2, BCL6
Rearrangements tested at diagnosis. The combination defines a distinct entity.
Cell of origin
Germinal centre versus activated B-cell type. Prognostic, and increasingly therapeutic.
TP53
Alteration carries adverse weight, as it does across the lymphoid malignancies.
CD19, CD20, CD79b
Surface markers underpinning immune and antibody-based treatment. Loss is a recognised resistance mechanism.
MYD88 and CD79B
Defining a genetic subtype, and particularly relevant in primary CNS lymphoma.
ctDNA
A well-developed research area here, for baseline burden, early response and relapse detection.
This is not an exhaustive list, and which markers are relevant depends on the individual case. Not every marker listed is assessed in every patient.
What is tested, and from what
An adequate biopsy comes first: an excisional or generous core sample, not a fine needle aspirate. Rearrangement testing for MYC, BCL2 and BCL6 is standard at diagnosis. Comprehensive sequencing panels are used more in relapsed disease and in research than in routine first-line management. Because the disease moves quickly, turnaround on the rearrangement result is part of the clinical question.
Most cases are sporadic. Inherited immunodeficiency and conditions affecting DNA repair predispose to lymphoma, and very young onset or a background of recurrent infection is a reasonable prompt to consider one. Germline testing is not part of the routine pathway.
Cancer genetics and hereditary riskDLBCL is one of the diseases where ctDNA research is furthest advanced. It is studied for measuring baseline disease burden, for assessing response after one or two cycles, and for detecting relapse before imaging. It is not yet routine in most settings, but this is moving quickly.
More on ctDNA monitoringThe timing question
Testing that arrives after the decision it was meant to inform has already been made is a common and avoidable problem. This is the sequence in which molecular information tends to become relevant.
Take these to your team
When a decision is being made
Questions worth raising with a treating team.
At progression, recurrence or resistance
The molecular picture at diagnosis is not always the molecular picture later.
What shapes eligibility
Eligibility is written around prior therapy, particularly which immune-based agents have been used, and around surface marker expression. Because the treatment classes in relapsed disease are numerous and sequential, the exact prior agents matter more than the number of lines.
| Term | What it means |
|---|---|
| Double hit | Informal term for lymphoma carrying MYC together with BCL2 or BCL6. Now formally a distinct entity. |
| Cell of origin | Which stage of normal B-cell development the lymphoma most resembles. |
| CNS prophylaxis | Treatment directed at the central nervous system, given because standard treatment does not reach it well. |
| Excisional biopsy | Removing a whole lymph node. Usually needed to subtype a lymphoma properly. |
| Target loss | When a cancer stops expressing the surface marker a treatment was aimed at. |
These are the services most often relevant to this cancer. Which of them applies is a clinical question, not an automatic one.
This entry is educational. It describes what is commonly discussed in this cancer, not what should happen for any individual. Which of it applies depends on the specific diagnosis, stage, prior treatment and the person themselves. Nothing here is a recommendation, and no list of biomarkers here is exhaustive. Decisions belong with a treating team who know the whole case.
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