Parathyroid carcinoma (PC) is an extremely rare malignant tumor of the parathyroid glands, accounting for less than 1% of primary hyperparathyroidism, commonly characterized by severe and unmanageable hypercalcemia, aggressive behavior, high metastatic potential, and poor prognosis. PC manifests prevalently as a sporadic tumor and only occasionally it is part of congenital syndromic and non-syndromic endocrine diseases. Molecular pathogenesis of this form of parathyroid tumor is not fully elucidated and it appears to be caused by multiple genetic and epigenetic drivers, differing among affected patients and not yet clearly stated in distinguishing PC from the benign parathyroid adenoma (PA). Congenital forms of PC have been prevalently associated with germline heterozygous loss-of-function mutations of the CDC73 tumor suppressor gene, both in the context of the hyperparathyroidism jaw-tumor syndrome (HPT-JT) and of the isolated familial hyperparathyroidism (FIPH). Currently, surgical en bloc resection of affected gland(s) and other involved structures is the elective therapy for both primary and recurrent PC. However, it usually results ineffective for advance and metastatic disease, and a high percentage of post-operative recurrence is reported. Targeted medical therapies for surgically untreatable PC, based on the molecular profile of PC samples, are, therefore, needed. The characterization of genetic and epigenetic alterations and deregulated pathways in PC samples will be of fundamental importance to tailor treatment for each patient. Here, we reviewed main findings on molecular pathogenetic aspects of PC, and the current state of the art of therapies.
Keywords: CDC73 gene; Epigenetic alterations; Gene mutation; Molecular therapeutic targets; Parathyroid carcinoma.
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.