Cancer Dictionary · Blood and lymphatic

Lymphoma

Lymphomas are classified by cell of origin, morphology, immunophenotype and genetics. The same word covers indolent diseases that may be observed for years and aggressive diseases that are curable but require prompt treatment. Certain genetic findings, particularly rearrangements in diffuse large B-cell lymphoma, change the treatment discussion substantially.

Also called Hodgkin lymphoma, Non-Hodgkin lymphoma, DLBCL, Follicular lymphoma.

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The governing idea

Lymphoma is a family of more than sixty diagnoses whose behaviours range from needing no treatment to needing treatment within days, so the exact subtype, established by expert haematopathology, decides everything.

01Before any molecular question

How it usually presents

Usually established first: the precise subtype from an adequate biopsy, stage, and whether the disease is indolent or aggressive. An excisional or core biopsy is generally required; a fine needle aspirate is usually insufficient to subtype a lymphoma, and this is a common cause of delay.

Usually already established

Precise subtype from an adequate biopsy
Stage
Whether indolent or aggressive
Prognostic index score, where applicable

Major disease categories

The divisions below are not labels. Each one changes what the treatment discussion is actually about.

Hodgkin lymphoma

A distinct entity with a characteristic cell type and a high cure rate. Managed on its own pathway, with substantial attention to reducing long-term effects.

Diffuse large B-cell lymphoma

The most common aggressive lymphoma. Cell of origin and specific rearrangements shape the discussion.

Follicular lymphoma

Usually indolent, often not requiring immediate treatment, with transformation to aggressive lymphoma a recognised event.

Mantle cell lymphoma

Defined by CCND1 rearrangement, with variable behaviour and specific treatment approaches.

T-cell lymphomas

A diverse and less common group, generally with a different treatment landscape.

Primary CNS lymphoma

Arising in the brain, and managed entirely differently from systemic lymphoma.

03What is discussed

Molecular considerations

In diffuse large B-cell lymphoma, MYC, BCL2 and BCL6 rearrangements are assessed, and the combination of MYC with BCL2 or BCL6 defines high-grade B-cell lymphoma with rearrangements, which is a distinct entity rather than a variant. Cell of origin classification into germinal centre and activated B-cell types carries prognostic and increasingly therapeutic weight. CCND1 rearrangement defines mantle cell lymphoma; TP53 alteration within it carries substantial weight. In follicular lymphoma, BCL2 rearrangement is characteristic. EZH2 alterations are of therapeutic interest. In T-cell lymphomas, ALK status defines subgroups of anaplastic large cell lymphoma. Epstein-Barr virus association is relevant in several subtypes.

Biomarkers commonly discussed

MYC, BCL2, BCL6

Rearrangements assessed in diffuse large B-cell lymphoma. Their combination defines a distinct entity.

Cell of origin

Germinal centre versus activated B-cell type. Prognostic and increasingly therapeutic.

CCND1

Rearrangement defines mantle cell lymphoma.

TP53

Carries substantial weight in mantle cell and other lymphomas.

ALK

Defines subgroups of anaplastic large cell lymphoma.

CD19, CD20, CD30, CD79b

Surface markers relevant to targeted and immune-based approaches.

EBV

Relevant in several lymphoma subtypes.

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.

04What is tested, and from what

Testing, inherited risk and blood-based monitoring

Genomic testing considerations

An adequate biopsy is the foundation, and expert haematopathology review is important because subtype determines everything downstream. In diffuse large B-cell lymphoma, rearrangement testing for MYC, BCL2 and BCL6 is standard, because identifying high-grade B-cell lymphoma with rearrangements changes the treatment discussion. Comprehensive sequencing panels are used more in research and in relapsed disease than in routine first-line management.

Germline considerations

Most lymphoma is sporadic. Inherited immunodeficiency syndromes and conditions affecting DNA repair predispose to lymphoma, and there is familial clustering in some subtypes. Formal germline testing is not a routine part of the pathway unless the presentation is unusual, for example very young onset or a background of recurrent infections.

Cancer genetics and hereditary risk

ctDNA and liquid biopsy considerations

ctDNA is a well-developed research area in lymphoma, particularly in diffuse large B-cell lymphoma, where it is studied for baseline disease burden, early response assessment and detection of relapse. It is not yet routine practice in most settings, but this is one of the areas moving fastest.

When molecular information matters

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.

At biopsyAn adequate sample is essential. A fine needle aspirate is usually not enough to subtype a lymphoma, and repeating a biopsy costs time.
At diagnosisSubtype, stage and, in DLBCL, rearrangement testing establish the plan. In aggressive lymphoma this happens quickly.
In indolent lymphomaObservation may be appropriate for years, and explaining that clearly matters.
At transformationA rebiopsy is needed to confirm transformation rather than assuming it from clinical behaviour.
At relapseSurface marker expression and molecular characterisation inform immune-based options.

06Take these to your team

Questions worth raising

When a decision is being made

Questions worth raising with a treating team.

Was the biopsy adequate to subtype the lymphoma, since a fine needle aspirate usually is not?
Has expert haematopathology review been obtained, given how much follows from the exact subtype?
In diffuse large B-cell lymphoma, have MYC, BCL2 and BCL6 rearrangements been assessed?
In indolent lymphoma, has the case for observation been explained clearly?
Has the distinction between an indolent and an aggressive subtype been made explicit, since the urgency differs completely?

At progression, recurrence or resistance

The molecular picture at diagnosis is not always the molecular picture later.

Has a rebiopsy been done to confirm transformation rather than inferring it from clinical behaviour?
Has surface marker expression been reassessed, since target loss is a recognised resistance mechanism?
Has the subtype been reconsidered where behaviour does not match expectation?

07What shapes eligibility

Clinical trial considerations

Eligibility is written by precise subtype, prior therapy including specific immune-based agents, and surface marker expression. Because the subtypes are numerous and trials are usually subtype-specific, an imprecise diagnosis is a practical barrier to matching.

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Plain-language glossary for this entry (5 terms)

Term	What it means
Indolent versus aggressive	Slow-growing lymphoma that may need no treatment, versus fast-growing lymphoma that needs prompt treatment but is often curable.
Cell of origin	Which stage of normal B-cell development the lymphoma most resembles. Carries prognostic weight in DLBCL.
Double hit	An informal term for lymphoma with both MYC and BCL2 or BCL6 rearrangements. Now formally a distinct entity.
Transformation	When an indolent lymphoma changes into an aggressive one. Confirmed by biopsy.
Excisional biopsy	Removing a whole lymph node. Usually needed to subtype a lymphoma properly.

Where OnKommon fits

These are the services most often relevant to this cancer. Which of them applies is a clinical question, not an automatic one.

Signature B ALLProfiling for lymphoblastic leukaemia.See how it works Signature B AMLProfiling for myeloid leukaemia.See how it works SentinelSerial monitoring during active treatment.See how it works Blueprint CareThe decision report that reads the profile and ranks the options.See how it works

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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