Compared to individuals with sporadic PHPT, individuals with a CDC73 gene pathogenic variant have an increased risk of the following:
- larger parathyroid tumours which demonstrate distinctive morphological features
- synchronous or metachronous multiglandular disease
- local or distant recurrence
- postoperative hungry bones syndrome.
These factors should be considered when planning the surgical and post-surgical management of individuals with a CDC73 gene pathogenic variant and PHPT.
Biopsy of suspicious neck lesions in these patients is discouraged due to risk of seeding parathyroid cancer cells, the difficulty it creates in interpreting the pathology of excision specimen and the limited information it provides.r If there is a suspicion of parathyroid carcinoma (i.e. large tumour on imaging, palpable neck mass, clinical and biochemical evidence of severe hypercalcaemia) then “en bloc” resection is recommended of the affected gland, surrounding tissues, ipsilateral thyroid lobe, ipsilateral normal parathyroid and thymus. This is to reduce the risk of capsular spillage, local seeding and potential need for reoperation on the same side.r
Rare cases of non-functioning parathyroid carcinoma have been reported in individuals with a CDC73 gene pathogenic variant. Some authors recommend consideration of periodic neck ultrasound in addition to biochemical screening. However, the age of commencement and optimal interval of imaging has not been defined.
The youngest age of PHPT in HPT-JT is reported to be 7 years, while the youngest age of parathyroid carcinoma is reported to be 15 years.r
There is emerging evidence that CDC73 germline variants that disrupt the C-terminal domain are associated with an increased risk of parathyroid carcinoma.r These patients may benefit from closer monitoring for parathyroid carcinoma.
Ossifying fibroma/cemento-ossifying fibroma of the maxilla or mandible
There is currently insufficient available data to indicate whether there is an age at which jaw imaging can be ceased in individuals who have had serial normal imaging.
The lifetime risk of developing uterine tumours in females with a CDC73 pathogenic variant is approximately 45%.r The incidence of uterine leiomyomas in females with a CDC73 pathogenic variant is similar to that of the general population.r
While malignant uterine tumours have been reported in females with a CDC73 pathogenic variant, they appear to be rare. There is no evidence to support routine surveillance for uterine tumours. Females with a CDC73 pathogenic variant should be aware of the risk of uterine tumours and report any new symptoms to their General Practitioner. Menorrhagia and infertility have been reported in females with CDC73 pathogenic variants and may potentially indicate a uterine tumour. Further investigation should be undertaken if clinically indicated with pelvic ultrasound and then further imaging studies if needed.r
Wilms tumours have been reported in a small number of patients with CDC73 pathogenic variants from the age of 8 years. There is insufficient evidence to estimate the risk of Wilms tumour in the setting of a CDC73 pathogenic variant, but it is likely to be <1%, and the intensive surveillance that would be recommended in other conditions associated with Wilms tumours is not recommended. The current recommendation for 5-yearly ultrasound is predominantly to assess for renal cysts.rr