Parathyroid Carcinoma: Current Understanding and New Insights into Gene Expression and Intraoperative Parathyroid Hormone Kinetics

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to: Discuss the association of parathyroid cancers with severe hypercalcemia and markedly elevated parathyroid hormone levels.Describe the effect of the risk factors, clinical presentation, and gene expression on diagnosis of parathyroid cancers.Analyze the probability of cure for parathyroid cancers with treatment by aggressive surgery with en bloc resection and lymph node dissection. CME This article is available for continuing medical education credit at CME.TheOncologist.com Parathyroid carcinoma is an indolent but ultimately life-threatening malignancy. Due to the lack of definitive diagnostic markers and overlapping clinical features of benign primary hyperparathyroidism (PHPT), this disease is often misdiagnosed as parathyroid adenoma. Therefore, a high index of suspicion preoperatively and early intraoperative recognition with en bloc surgical resection are crucial for favorable outcome. Owing to the rarity of the disease, little is known about the molecular pathogenesis of parathyroid carcinoma. Here, we review the literature to present current understanding of the disease and provide new information on gene expression and use of intraoperative parathyroid hormone (PTH) monitoring in the surgical management of this rare malignancy. Specifically, using microarray transcriptome analysis of an unequivocal case of parathyroid carcinoma and a biopsy from the same patient's normal parathyroid gland, we identify APP, CDH1, KCNJ16, and UCHL1 as differentially expressed genes in parathyroid carcinoma. Further, using case records from four cases of unequivocal parathyroid carcinoma, we compared intraoperative PTH kinetics of these patients to 475 patients with benign PHPT, and show that intraoperative PTH monitoring is accurate in predicting postoperative normocalcemia in initial en bloc operations for parathyroid carcinoma.