Thyroid Cancer
Most differentiated thyroid cancer has an excellent outlook, and the principal risk in discussion is over-treatment. The molecular conversation matters most in radioiodine-refractory, poorly differentiated and anaplastic disease.
Disease categories
Major disease categories
- Papillary thyroid carcinoma
- Follicular thyroid carcinoma
- Medullary thyroid carcinoma
- Anaplastic thyroid carcinoma
- Poorly differentiated thyroid carcinoma
Molecular
Molecular considerations
BRAF V600E and RET fusions are frequent in papillary carcinoma. RET alterations define medullary thyroid carcinoma, including hereditary forms. NTRK fusions occur in a minority. Anaplastic carcinoma frequently carries TP53 and TERT promoter alterations.
Markers commonly discussed in thyroid cancer
- BRAF V600E
- RET fusions / alterations
- NTRK fusions
- TERT promoter
- RAS
- Thyroglobulin
- Calcitonin (medullary)
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 is discussed in advanced, radioiodine-refractory and anaplastic disease, and in indeterminate nodule assessment.
Germline
Germline considerations
Germline RET testing is central in medullary thyroid carcinoma, with direct implications for relatives.
Molecular monitoring
ctDNA and liquid biopsy considerations
Investigational.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell analysis in endocrine malignancy is used to characterise cellular composition and differentiation state, particularly where a tumour's behaviour is discordant with its assigned grade. Single-cell DNA sequencing contributes to clonal questions in tumours with a long natural history. Algorithm work includes hormone-pathway expression analysis, grade refinement from molecular features, and germline–somatic integration given how frequently these tumours are syndromic.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Is the histological subtype clearly established?
- For medullary carcinoma, has germline RET testing been discussed?
- In radioiodine-refractory disease, has molecular profiling been considered?
Resistance
Resistance and recurrence questions
- Has dedifferentiation been considered where behaviour changes?
Trials
Clinical trial considerations
Molecular alteration status shapes eligibility in advanced 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.