Chapter 8: Management of aggressive forms of primary HPT: Parathyroid carcinoma and atypical parathyroid tumor

Parathyroid carcinoma is extremely rare, affecting 1% of cases of primary hyperparathyroidism. For this reason, management is poorly codified and requires expertise in specialized center. PC is genetically determined in a quarter to a third of cases, notably involving the CDC73 gene coding for parafibromin. Since 2004, malignancy has been diagnosed on both macroscopic and microscopic invasion criteria, as set out in the WHO 2022 histopathological classification. Surgery is an essential part of treatment. Resection must be oncological, after prior medical treatment for hypercalcemia that are often severe, and be supported by imaging studies to guide the surgical procedure. After incomplete resection with no possibility of reoperation, adjuvant external radiotherapy should be discussed, given the high risk of local recurrence, even if its value is debated. The recurrence rate for PC is 30–67%. Overall 5-year survival ranges from 60 to 95%. In cases of localized or oligometastatic recurrence, locoregional treatments are preferred. There is no standard treatment for metastatic disease, but the literature review suggests possible benefit from targeted anti-angiogenic therapy. Extensive tumor genotyping is recommended to screen for targetable alterations in driver genes. All parathyroid carcinoma cases should be reviewed in a specialized tumor board. Patients operated on for atypical parathyroid tumors or parathyroid tumors with loss of immunohistochemical expression of parafibromin also require long-term monitoring.