Parathyroid carcinoma is a rare malignant neoplasm of the parathyroid causing parathyroid hormone (PTH)–dependent hypercalcemia. Diagnosis is difficult so a high level of suspicion must be maintained, particularly in patients with markedly elevated serum calcium levels, local symptoms, and elevated PTH levels. Presence of these or clinical suspicion at surgery should allow consideration for a more aggressive surgical resection at the initial surgery. In this chapter we review current information on genetics and features of parathyroid carcinoma, and treatment options in the perioperative period.
Parathyroid carcinoma arises from parenchymal cells of the parathyroid. It is a rare neoplasm with an incidence of 5.73 per 10 million, that is, <1% of the population.1-3 It accounted for 0.005% of all cancers in the National Cancer Database from 1985 to 1995.4 A review of the Surveillance, Epidemiology, and End Results (SEER) cancer registry identifying patients with parathyroid carcinoma from 1988 to 2003 in the United States demonstrated a 60% rise in incidence of parathyroid carcinoma from 3.58 to 5.73 per 10 million.2 A review of the European Cancer registry from 1995 to 2002 demonstrated an incidence of 0.02% per 10 million among 27 European countries, emphasizing the rarity of this cancer.5 Approximately 1% of hyperparathyroidism is attributed to parathyroid carcinoma, and retrospective studies have demonstrated an even distribution between men and women.4 Benign parathyroid disease has a female predominance (3–4:1), occurring a decade later than parathyroid carcinoma which usually manifests at an average age of 48 years.1,3,6 Parathyroid carcinoma rarely occurs in children.7,8
Risk factors associated with the occurrence of parathyroid carcinoma include membership in kindred of familial parathyroid carcinoma or hyperparathyroidism-jaw tumor (HPT-JT) syndrome.1 HPT-JT syndrome is an autosomal dominant disorder due to HRPT2 gene mutation, with predisposition for multiglandular parathyroid neoplasms coupled with the presence of fibro-osseous lesions of the mandible and maxilla and renal lesions. Fifteen percent of HPT-JT syndrome patients develop parathyroid carcinoma.1,9
Parathyroid carcinoma has been seen in several patients exposed to chronic parathyroid stimulation in secondary hyperparathyroidism, especially from chronic renal failure, suggesting that this persistent stimulation results in malignant transformation of hyperplastic parathyroid cells and the development of parathyroid carcinoma.1,10-13
In a review by Koea and Shaw,14 a history of neck radiation was found in 1.4% of their parathyroid carcinoma cases. This review also demonstrated a possible geographic distribution with an incidence of 1% in the United States and 5% in Japan and Italy of all patients with hyperparathyroidism;15 however, it is unclear if the higher incidence in Japan and Italy is due to differentiation of disease susceptibility or due to a different diagnosing criteria.4