Presentation: Patient with parathyroid carcinoma

A 28-year-old male is referred to you with presumed primary hyperparathyroidism with a corrected serum calcium of 3.62mmol/l (normal range 2.15mmol/l to 2.55mmol/l) and parathyroid hormone (PTH) of 87pmol/l (normal range 1.6pmol/l to 6.9pmol/l). A palpable neck lump has been found on examination and a pre-operative ultrasound imaging has indicated a likely 3cm enlarged right inferior parathyroid gland. Following surgical resection, the pathology report has indicated histological features in keeping with parathyroid carcinoma.

If a patient’s tumour and any similar tumours in their family have been confirmed as parathyroid carcinoma, the patient should be considered for genomic testing.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria, which provides information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• For patients who meet test directory eligibility criteria and do not have a personal or family history of a genetic variant in a parathyroid carcinoma gene (for example, CDC73), select the following:
  • R226: Inherited parathyroid carcinoma panel for patients with parathyroid carcinoma. This involves CDC73 single gene testing.
• Similar or overlapping tests include:
  • R151: Familial hyperparathyroidism or familial hypocalciuric hypercalcaemia (FHH). This panel currently comprises the following genes: AP2S1, CASR, CDC73, CDKN1B, GCM2, GNA11, MEN1 and RET. It involves small gene panel sequencing and exon-level copy number variation (CNV) detection by multiplex ligation-dependent probe amplification (MLPA) or equivalent.
  • R217 and R218: Endocrine neoplasia and multiple endocrine neoplasia type 2 respectively. These panels should be used if the patient presents with clinical features, including hypercalcaemia, of a wider multiple endocrine neoplasia syndrome (for example, multiple endocrine neoplasia types 1, 2 and 4 (MEN1, MEN2 and MEN4, respectively) and hyperparathyroidism-jaw tumour syndrome).
    • The R217 panel currently comprises the following genes: AIP, CDC73, CDKN1B, MEN1, PRKAR1A, RET and VHL. This involves small gene panel sequencing and exon-level CNV detection by MLPA or equivalent.
    • The R218 panel involves RET single gene testing.
• For patients with a high clinical suspicion of a hereditary cause but no detectable likely pathogenic or pathogenic variants in a parathyroid carcinoma predisposition gene, further discussion with the clinical genetics team may identify additional genomic testing strategies.
• For patients presenting with hereditary parathyroid carcinoma in whom a genetic diagnosis in a relevant predisposition gene (for example, CDC73) has been established in another family member, single gene testing for that specific variant should be considered. R240 Diagnostic testing for known mutation(s) could be selected, if the close family member’s pathogenic variant report is available and testing was performed in an accredited laboratory.
• These tests do not include whole genome sequencing, so you should use your local Genomic Laboratory Hub test order and consent (record of discussion) forms.
• These tests are DNA based, and an EDTA sample (purple-topped tube) is required. The sample is best stored at four degrees Celsius until it can be posted to the genomic laboratory.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• MedlinePlus: Hyperparathyroidism-jaw tumor syndrome
• NHS England: National Genomic Test Directory

For patients

• Macmillan Cancer Support: Parathyroid cancer
• Parathyroid UK