Skin Cancer
Non-melanoma skin cancer is the most common malignancy overall. Most is managed straightforwardly; the discussion becomes more complex in locally advanced, recurrent or metastatic disease and in immunosuppressed patients.
Disease categories
Major disease categories
- Basal cell carcinoma
- Cutaneous squamous cell carcinoma
- Merkel cell carcinoma
- Dermatofibrosarcoma protuberans
Molecular
Molecular considerations
Hedgehog pathway alterations characterise basal cell carcinoma. Cutaneous squamous cell carcinoma typically carries a very high mutational burden. Merkel cell polyomavirus status is relevant in Merkel cell carcinoma.
Markers commonly discussed in skin cancer
- PTCH1 / SMO
- TMB
- PD-L1
- Merkel cell polyomavirus
- COL1A1-PDGFB (DFSP)
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
Profiling is discussed in advanced and treatment-refractory disease.
Germline
Germline considerations
Basal cell naevus syndrome and xeroderma pigmentosum are considered where the pattern suggests them.
Molecular monitoring
ctDNA and liquid biopsy considerations
Investigational.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell sequencing in skin malignancy is used to characterise immune infiltration and exhaustion states, which bear directly on how these tumours behave. Single-cell DNA analysis resolves clonal structure in tumours with very high mutational burden, where bulk calls can be difficult to attribute. Algorithm work includes mutational signature deconvolution, neoantigen prediction pipelines, and models of resistance emergence under targeted therapy.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Is the histological subtype and its extent clearly documented?
- Is immunosuppression status recorded, given its effect on behaviour?
Resistance
Resistance and recurrence questions
- Has the diagnosis been reviewed in refractory disease?
Trials
Clinical trial considerations
Relevant chiefly in advanced or refractory disease.
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.