Parathyroid carcinoma

Parathyroid carcinoma is a malignant neoplasm of parathyroid chief cells that presents with severe primary hyperparathyroidism: calcium and parathyroid hormone far above adenoma levels, bone disease, kidney stones and renal impairment, and often a palpable neck mass, in contrast to the mild disease of parathyroid adenoma. About a quarter of sporadic cases and nearly all cases in the hyperparathyroidism-jaw tumour syndrome carry inactivating mutations in CDC73 (HRPT2), whose product parafibromin is lost on immunohistochemistry; germline testing is recommended for all patients because of the syndromic association. Preoperative distinction from adenoma is unreliable, so the diagnosis is often made at surgery or pathology.

The only curative treatment is en bloc resection of the tumour with the ipsilateral thyroid lobe and any adherent tissue, avoiding capsular rupture; incomplete initial surgery is the main cause of recurrence, which is usually loco-regional and can be re-resected repeatedly. Radiotherapy and chemotherapy have little proven activity. Because morbidity and death come from hypercalcaemia rather than tumour mass, medical control matters: cinacalcet (a calcimimetic, approved for hypercalcaemia of parathyroid carcinoma), denosumab or bisphosphonates for bone resorption, hydration and, in crisis, dialysis. Rare durable responses to PD-1 inhibitors have been reported in tumours with high mutation burden, and case series describe activity of multikinase inhibitors, but there is no approved systemic anticancer therapy.

Open problems are pre-operative recognition (parafibromin and PGP9.5 staining, calcium and PTH thresholds), the lack of trials, and effective therapy for metastatic disease beyond calcium control.