Lymphoma
Lymphoma comprises many distinct diseases sharing a lymphoid origin. Accurate pathological classification is the single most consequential step, and expert haematopathology review is frequently discussed where the diagnosis is difficult.
Disease categories
Major disease categories
- Diffuse large B-cell lymphoma
- Follicular lymphoma
- Hodgkin lymphoma
- Mantle cell lymphoma
- Marginal zone lymphoma
- T-cell lymphomas
- Burkitt lymphoma
Molecular
Molecular considerations
MYC, BCL2 and BCL6 rearrangements define high-grade B-cell lymphoma with rearrangements. Cell-of-origin classification is discussed in diffuse large B-cell lymphoma. TP53 alteration carries weight across several entities. CD markers determined by immunophenotyping are integral to classification.
Markers commonly discussed in lymphoma
- MYC / BCL2 / BCL6 rearrangements
- Cell of origin
- TP53
- CD20
- CD30
- Ki-67
- EBV status
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
Immunophenotyping and fluorescence in situ hybridisation are core to diagnosis; sequencing panels are used in selected entities.
Germline
Germline considerations
Considered where family history or an immunodeficiency phenotype suggests it.
Molecular monitoring
ctDNA and liquid biopsy considerations
ctDNA is an active research area in lymphoma, including for measurable residual disease and for tracking clonal evolution.
Single-cell & computation
Single-cell and algorithmic approaches
Haematological malignancy is where single-cell analysis is most directly applicable, because the tissue is already a cell suspension. Single-cell DNA sequencing resolves whether co-occurring alterations sit in the same clone or in competing clones — a distinction bulk sequencing cannot make and which changes the interpretation substantially. Single-cell RNA analysis characterises differentiation state and microenvironmental interaction. Algorithm work includes measurable residual disease detection at high sensitivity, clonal phylogeny reconstruction across timepoints, and risk models built on combined cytogenetic and molecular features.
In practice
What a review of this disease typically surfaces
Diagnostic classification is where most value is added. Expert haematopathology review changes the entity more often than clinicians expect, and the entity determines everything downstream. Cases also arrive where MYC, BCL2 and BCL6 rearrangement testing was not performed in a large B-cell lymphoma, leaving high-grade disease unexcluded. At relapse, re-biopsy is frequently omitted where transformation is a real possibility.
Patterns observed across precision oncology case reviews. Every case differs; these are the questions worth checking, not conclusions about any individual patient.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has the diagnosis been confirmed by expert haematopathology review?
- Have MYC, BCL2 and BCL6 rearrangements been assessed where the entity warrants it?
- Is the immunophenotype complete?
Resistance
Resistance and recurrence questions
- Has re-biopsy been considered at relapse to confirm the entity and check for transformation?
Trials
Clinical trial considerations
Entity, prior lines of therapy and molecular features all shape eligibility.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.