Parathyroid Carcinoma: From Molecular Pathogenesis to Multidisciplinary Management

Parathyroid carcinoma (PC) is a rare malignancy accounting for <1% of primary hyperparathyroidism cases. This review summarizes current knowledge on its molecular pathogenesis, diagnosis, imaging, management and prognosis. PC is driven primarily by CDC73 mutations with loss of parafibromin expression, with emerging roles for PI3 K/AKT/mTOR and Wnt pathway alterations. Its diagnosis remains challenging. Clinical suspicion should arise with marked hypercalcemia, elevated PTH, palpable neck mass or recurrent laryngeal nerve palsy. Imaging modalities including cervical ultrasound, 99ᵐTc-sestamibi, 4D-CT, and [18F]fluorocholine PET/CT aid localization and metastasis detection. En bloc resection with ipsilateral thyroid lobectomy is the standard approach. Traditional medical therapies are helpful in reducing serum calcium level. Radiotherapy and chemotherapy have limited efficacy. Targeted therapies and immunotherapy show promise in advanced disease, however, the such evidence is weak. Recurrence rates of 23-65% mandate lifelong follow-up. Prognostic factors include surgical approach, postoperative remission, Ki-67 index, as well as parafibromin status and mTOR activation. Multidisciplinary management in specialized centers is critical for optimizing outcomes.