Endocrine Malignancies
Endocrine malignancies beyond the thyroid include adrenocortical carcinoma, neuroendocrine tumours, phaeochromocytoma and paraganglioma — a group in which hereditary predisposition is unusually frequent.
Disease categories
Major disease categories
- Adrenocortical carcinoma
- Neuroendocrine tumours
- Phaeochromocytoma and paraganglioma
- Parathyroid carcinoma
- Pituitary tumours
Molecular
Molecular considerations
SDHx alterations are central in phaeochromocytoma and paraganglioma. MEN1 and DAXX/ATRX alterations feature in pancreatic neuroendocrine tumours. TP53 and CTNNB1 alterations are described in adrenocortical carcinoma.
Markers commonly discussed in endocrine malignancies
- SDHx
- MEN1
- RET
- VHL
- DAXX / ATRX
- Ki-67 / grade
- 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
Entity-directed molecular testing, with germline assessment forming a large part of the discussion.
Germline
Germline considerations
A high proportion of phaeochromocytoma and paraganglioma cases carry a germline predisposition, making germline assessment a routine part of the discussion.
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 germline assessment been discussed, given the frequency of predisposition in this group?
- Is tumour grade documented for neuroendocrine tumours?
Resistance
Resistance and recurrence questions
- Has grade been reassessed where behaviour changes?
Trials
Clinical trial considerations
Entity, grade and molecular 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.