Parathyroid Carcinoma
Parathyroid carcinoma is very rare and typically presents with severe hypercalcaemia. Distinguishing it from benign parathyroid disease can be genuinely difficult, and the distinction governs management.
Disease categories
Major disease categories
- Parathyroid carcinoma
- Atypical parathyroid tumour
- Recurrent or metastatic disease
Molecular
Molecular considerations
CDC73 alteration, with associated loss of parafibromin expression, is characteristic and is used to support the diagnosis. PRUNE2 and other alterations are described.
Markers commonly discussed in parathyroid carcinoma
- CDC73 / parafibromin
- PTH
- Serum calcium
- Ki-67
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
CDC73 assessment contributes to diagnosis as well as to germline risk assessment.
Germline
Germline considerations
Germline CDC73 testing is widely discussed, since hyperparathyroidism–jaw tumour syndrome carries 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:
- Has parafibromin immunohistochemistry or CDC73 testing been performed?
- Has germline CDC73 testing been discussed?
- Is hypercalcaemia being actively managed alongside oncological treatment?
Resistance
Resistance and recurrence questions
- Is calcium control deteriorating, and has recurrence been sought?
Trials
Clinical trial considerations
Very limited; international and basket-trial search is usually necessary.
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.