Parathyroid Cancer and the CDC73 Tumor Suppressor Gene

Abstract

Parathyroid carcinoma (PC) is a rare endocrine neoplasm, usually causing severe primary hyperparathyroidism, that frequently causes death from unmanageable hypercalcemia. PC is frequently associated with somatic inactivating mutations of the CDC73 gene (previously called HRPT2), a gene discovered in association with the familial hyperparathyroidism-jaw tumor syndrome. DNA analysis for CDC73 mutation should be performed on all patients with seemingly sporadic PC since some 25% will carry a germline mutation. It is often difficult to make a firm diagnosis of PC by histopathology alone. That diagnosis often depends on the presence of local tissue invasion or distant metastases. If PC is suspected, en bloc resection at initial surgery is recommended. Medical therapy with cinacalcet, bisphosphonates or denosumab may temporarily ameliorate the hypercalcemia of inoperable PC.