Neuroendocrine Tumours
Neuroendocrine tumours span an unusually wide range of behaviour, from indolent well-differentiated tumours followed for years to aggressive poorly-differentiated carcinoma. Grade and differentiation carry more weight here than primary site.
Disease categories
Major disease categories
- Well-differentiated neuroendocrine tumours (G1–G3)
- Poorly differentiated neuroendocrine carcinoma
- Pancreatic neuroendocrine tumours
- Small bowel neuroendocrine tumours
- Lung carcinoid
Molecular
Molecular considerations
MEN1, DAXX and ATRX alterations feature in pancreatic neuroendocrine tumours. Poorly differentiated neuroendocrine carcinoma frequently carries TP53 and RB1 alterations and behaves quite differently. Somatostatin receptor expression, assessed by imaging, is central to management discussion.
Markers commonly discussed in neuroendocrine tumours
- Ki-67 / grade
- Somatostatin receptor expression
- MEN1
- DAXX / ATRX
- TP53 / RB1
- Chromogranin A
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 disease and where behaviour is discordant with the assigned grade.
Germline
Germline considerations
MEN1, VHL, NF1 and tuberous sclerosis are considered where the clinical pattern suggests a syndrome.
Molecular monitoring
ctDNA and liquid biopsy considerations
Investigational; circulating transcript assays are an active research area.
Single-cell & computation
Single-cell and algorithmic approaches
In gastrointestinal and hepatobiliary disease, single-cell sequencing is used chiefly to characterise the tumour microenvironment and to resolve clonal structure in tumours that are heterogeneous between regions. Single-cell DNA analysis helps establish whether a RAS or driver alteration is clonal or subclonal, which bears directly on how much weight it should carry. Algorithm work here includes molecular residual disease detection from serial samples, mismatch repair classification from sequencing data, and pipelines that reconcile findings across multiple biopsy sites.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Is grade documented with the Ki-67 index, not just a descriptive label?
- Is the tumour well or poorly differentiated — the two behave very differently?
- Has somatostatin receptor imaging been performed?
Resistance
Resistance and recurrence questions
- Has grade been reassessed on re-biopsy, since it can increase over time?
- Is there discordance between sites suggesting heterogeneity?
Trials
Clinical trial considerations
Grade, differentiation and somatostatin receptor status 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.