Salivary Gland Cancer
Salivary gland tumours comprise many histological entities with markedly different behaviour, several defined by characteristic gene fusions. Precise subtyping is the decisive step, and it is frequently difficult.
Disease categories
Major disease categories
- Adenoid cystic carcinoma
- Mucoepidermoid carcinoma
- Salivary duct carcinoma
- Acinic cell carcinoma
- Secretory carcinoma
Molecular
Molecular considerations
MYB and MYBL1 fusions characterise adenoid cystic carcinoma. CRTC1-MAML2 fusion defines mucoepidermoid carcinoma. Secretory carcinoma carries an ETV6-NTRK3 fusion. Salivary duct carcinoma frequently expresses androgen receptor and may carry HER2 amplification.
Markers commonly discussed in salivary gland cancer
- MYB / MYBL1 fusions
- CRTC1-MAML2
- ETV6-NTRK3
- Androgen receptor
- HER2
- PD-L1
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
Fusion-capable testing is important here, since several defining alterations are fusions a sequence-only panel would miss.
Germline
Germline considerations
Not routinely indicated.
Molecular monitoring
ctDNA and liquid biopsy considerations
Investigational.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell sequencing in head and neck cancer is used to characterise immune exclusion and the stromal compartment, both of which vary substantially between tumours that look similar histologically. Single-cell DNA analysis contributes to field-change questions — whether a second lesion is a recurrence or an independent primary, which clonal analysis can often settle. Algorithm work includes HPV integration site analysis, deconvolution of immune composition from bulk expression, and viral circulating-DNA trajectory modelling.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has the histological subtype been confirmed by a head and neck pathologist?
- Has fusion testing been performed where the subtype suggests it?
- For salivary duct carcinoma, have androgen receptor and HER2 been assessed?
Resistance
Resistance and recurrence questions
- Has the diagnosis been reviewed where behaviour is atypical?
Trials
Clinical trial considerations
Subtype and fusion status largely determine the relevant trial set.
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.