Appendiceal Cancer
Appendiceal tumours are rare, frequently found incidentally at appendicectomy, and span a wide behavioural range from indolent mucinous neoplasms to aggressive adenocarcinoma. Accurate pathological classification governs everything that follows.
Disease categories
Major disease categories
- Low-grade appendiceal mucinous neoplasm
- Appendiceal adenocarcinoma
- Goblet cell adenocarcinoma
- Appendiceal neuroendocrine tumours
- Pseudomyxoma peritonei
Molecular
Molecular considerations
KRAS and GNAS alterations are characteristic of mucinous appendiceal neoplasms. TP53 and SMAD4 alterations are associated with more aggressive behaviour.
Markers commonly discussed in appendiceal cancer
- KRAS
- GNAS
- TP53
- SMAD4
- MMR / MSI
- CEA
- CA 19-9
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 particularly where the disease behaves more aggressively than the histology predicted.
Germline
Germline considerations
Considered where the clinical picture or family history suggests it.
Molecular monitoring
ctDNA and liquid biopsy considerations
Investigational; mucinous tumours are generally low shedders, which limits interpretation.
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:
- Has specialist pathology review been obtained, given how consequential grading is here?
- Is the peritoneal disease burden documented?
- Has referral to a peritoneal surface malignancy centre been considered?
Resistance
Resistance and recurrence questions
- Has the grade been reassessed on recurrent disease?
Trials
Clinical trial considerations
Trials are concentrated at specialist peritoneal malignancy centres.
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.