Introduction: Parathyroid carcinoma (PC) is a rare endocrine disorder, commonly causing severe primary hyperparathyroidism (PHPT). PC is mainly a sporadic disease, but it may occur in familial PHPT. Patients with PC usually present markedly elevated serum calcium and PTH. The clinical features are mostly due to the effects of the excessive secretion of PTH rather than to the spread of tumor. At times, the diagnosis can be difficult.
Purpose: The aim of this work is to review the available data on PC, and focus its molecular pathogenesis and the clinical utility of CDC73 genetic testing and immunostaining of its product, parafibromin. The pathological diagnosis of PC is restricted to lesions showing unequivocal growth into adjacent tissues or metastasis. Inactivating mutations of the cell division cycle 73 (CDC73) gene have been identified in up to 70 % of apparently sporadic PC and in one-third are germline. Loss of parafibromin immunostaining has been shown in most PC. The association of CDC73 mutations and loss of parafibromin predicts a worse clinical outcome and a lower overall 5- and 10-year survival.
Conclusions: The treatment of choice is the en bloc resection of the tumor. The course of PC is variable; most patients have local recurrences or distant metastases and die from unmanageable hypercalcemia.
Keywords: CDC73; HRPT2; Hyperparathyroidism-jaw tumor syndrome; PRUNE2; Parafibromin; Primary hyperparathyroidism.