Mesothelioma
Mesothelioma arises from the mesothelial lining, most often the pleura, and is strongly associated with prior asbestos exposure. Diagnosis is genuinely difficult and expert pathology review is a recurring theme in its management.
Disease categories
Major disease categories
- Pleural mesothelioma
- Peritoneal mesothelioma
- Epithelioid subtype
- Sarcomatoid subtype
- Biphasic subtype
Molecular
Molecular considerations
BAP1, NF2, CDKN2A and TP53 alterations are the most frequently described. Loss of BAP1 expression and CDKN2A deletion are used to support the diagnosis where it is in doubt.
Markers commonly discussed in mesothelioma
- BAP1
- CDKN2A deletion
- NF2
- PD-L1
- Calretinin and other mesothelial markers
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
Molecular testing contributes to diagnosis as well as to treatment discussion, which is unusual among solid tumours.
Germline
Germline considerations
Germline BAP1 assessment is discussed where there is a young presentation, multiple BAP1-associated tumours, or a suggestive family history.
Molecular monitoring
ctDNA and liquid biopsy considerations
Largely investigational in this disease.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell analysis in thoracic malignancy is used to study resistance as it emerges — separating a resistant subclone from the bulk population before it dominates, and characterising the immune contexture that bulk profiling obscures. Single-cell DNA sequencing can establish whether a resistance alteration is present in a minority of cells at baseline rather than acquired later. Algorithmic work includes fusion detection from RNA, subclonal reconstruction across serial samples, and classifiers that distinguish histological transformation from acquired resistance.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Is the histological subtype documented, since epithelioid and sarcomatoid disease behave differently?
- Has expert pathology review been obtained?
- Has occupational exposure history been recorded?
Resistance
Resistance and recurrence questions
- Has the diagnosis been reviewed if the clinical course is atypical for the stated subtype?
Trials
Clinical trial considerations
Subtype and BAP1 status are both relevant to the trial landscape.
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.