Parathyroid Carcinoma: From Molecular Pathogenesis to Multidisciplinary Management

Area of Science:

• Endocrinology
• Oncology
• Molecular Biology

Background:

• Parathyroid carcinoma (PC) is a rare endocrine malignancy, representing less than 1% of primary hyperparathyroidism cases.
• Understanding its molecular drivers is crucial for improving diagnosis and treatment.
• Current knowledge on PC pathogenesis, diagnosis, imaging, management, and prognosis is synthesized in this review.

Purpose of the Study:

• To review the current understanding of parathyroid carcinoma.
• To highlight key aspects of its molecular pathogenesis, diagnosis, imaging, management, and prognosis.
• To emphasize the importance of multidisciplinary care for optimizing patient outcomes.

Main Methods:

• Literature review summarizing current knowledge on parathyroid carcinoma.
• Analysis of molecular pathogenesis, including genetic mutations and pathway alterations.
• Evaluation of diagnostic criteria, imaging modalities, and treatment strategies.
• Review of prognostic factors and follow-up recommendations.

Main Results:

• PC is primarily driven by CDC73 mutations, affecting parafibromin expression, with involvement of PI3K/AKT/mTOR and Wnt pathways.
• Diagnosis is challenging, requiring clinical suspicion based on severe hypercalcemia, elevated PTH, neck mass, or nerve palsy.
• Imaging like ultrasound, 99mTc-sestamibi, 4D-CT, and PET/CT aids localization and metastasis detection.
• En bloc resection with thyroid lobectomy is standard; medical therapies manage calcium, while radiotherapy/chemotherapy have limited roles.
• Recurrence rates are high (23-65%), necessitating lifelong follow-up.
• Prognostic factors include surgical approach, remission, Ki-67, parafibromin, and mTOR status.

Conclusions:

• Parathyroid carcinoma diagnosis and management require a high index of suspicion and specialized multidisciplinary care.
• While surgery is the primary treatment, targeted therapies show potential for advanced disease.
• Effective management hinges on accurate diagnosis, surgical expertise, and vigilant long-term follow-up.