Merkel Cell Carcinoma
Merkel cell carcinoma is a rare, aggressive neuroendocrine skin cancer. It arises through two distinct routes — polyomavirus-associated and ultraviolet-associated — which differ molecularly.
Disease categories
Major disease categories
- Merkel cell polyomavirus-positive disease
- Polyomavirus-negative, UV-associated disease
- Merkel cell carcinoma of unknown primary
Molecular
Molecular considerations
Polyomavirus-positive tumours carry low mutational burden with integrated viral DNA. Virus-negative tumours carry very high UV-associated mutational burden with RB1 and TP53 alterations. PD-L1 expression is commonly assessed.
Markers commonly discussed in merkel cell carcinoma
- Merkel cell polyomavirus status
- TMB
- PD-L1
- RB1
- TP53
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
Viral status and immune marker assessment are the principal molecular questions.
Germline
Germline considerations
Not routinely indicated; immunosuppression status is clinically important.
Molecular monitoring
ctDNA and liquid biopsy considerations
Antibody titres against viral oncoproteins are used in research and practice discussion for surveillance in virus-positive disease.
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:
- Has polyomavirus status been assessed?
- Is immunosuppression status documented?
- Has the extent of nodal disease been established?
Resistance
Resistance and recurrence questions
- Has the disease been re-characterised on progression?
Trials
Clinical trial considerations
Viral status and prior immunotherapy exposure 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.