Critical Insights into Parathyroid Cancer

Parathyroid carcinoma (PC) is a rare endocrine malignancy accounting for less than 1% of primary hyperparathyroidism cases. It carries significant morbidity due to severe hypercalcemia and a high rate of recurrence post-resection. This literature review synthesizes current evidence on the diagnostic challenges, surgical management, and outcomes associated with parathyroid carcinoma. Diagnosis of parathyroid carcinoma remains difficult due to a large overlap with parathyroid adenoma in clinical presentation, laboratory findings, and imaging characteristics. However, markedly elevated serum calcium and parathyroid hormone levels, palpable neck mass, and evidence of local invasion may raise suspicion for malignancy. Definitive diagnosis relies on histopathologic features such as capsular, vascular, or perineural invasion. Also, many immunohistochemical markers are currently under review, including mutation of the CDC73 gene, loss of parafibromin, and elevated Ki-67, which support the diagnosis. Complete en bloc resection at the initial operation represents the most critical determinant of long-term outcomes. Achieving negative margins significantly reduces recurrence rates and improves survival, while limited resection and capsular disruption are associated with increased risk of locoregional recurrence. While lymph node involvement is relatively uncommon, selective rather than routine lymph node dissection is recommended. Adjuvant therapies, including radiation and systemic treatments, play a limited and largely palliative role, particularly in advanced or unresectable disease. Parathyroid carcinoma commonly recurs, requiring multiple reoperations, with morbidity primarily driven by persistent hypercalcemia. Long-term surveillance with serial biochemical monitoring is essential due to the risk of late recurrence. Overall, evidence consistently demonstrates that outcomes are contingent on the adequacy of the initial surgical resection, highlighting the importance of early recognition and complete en bloc resection.