Adrenocortical Carcinoma
Adrenocortical carcinoma is rare and frequently aggressive. Many of these tumours are hormonally active, so endocrine assessment sits alongside oncological staging from the outset.
Disease categories
Major disease categories
- Functioning adrenocortical carcinoma
- Non-functioning adrenocortical carcinoma
- Paediatric adrenocortical tumours
Molecular
Molecular considerations
TP53, CTNNB1 and ZNRF3 alterations are frequently described. IGF2 overexpression is characteristic. Ki-67 index carries prognostic weight.
Markers commonly discussed in adrenocortical carcinoma
- TP53
- CTNNB1
- ZNRF3
- IGF2
- Ki-67
- Steroid profile
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, where the actionable yield is limited but the diagnostic contribution can be useful.
Germline
Germline considerations
Li-Fraumeni syndrome is an important consideration, particularly in paediatric and young adult presentations. Lynch syndrome is also described.
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:
- Has full hormonal assessment been performed?
- Is the Ki-67 index documented?
- Has germline TP53 testing been discussed, particularly in younger patients?
Resistance
Resistance and recurrence questions
- Has hormonal activity been reassessed as disease progresses?
Trials
Clinical trial considerations
Trials are concentrated at specialist adrenal 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.