Opinion statement
Parathyroid carcinoma is one of the rarest known malignancies that may occur sporadically or as a part of a genetic syndrome. It accounts for approximately 1% of patients with primary hyperparathyroidism. The majority (90%) of parathyroid cancer tumors are hormonally functional and hypersecrete parathyroid hormone (PTH). Thus, most patients exhibit strong symptomatology of hypercalcemia at presentation. Sometimes, it can be difficult to diagnose parathyroid cancer preoperatively due to clinical features shared with benign causes of hyperparathyroidism. Imaging techniques such as neck ultrasound and 99mTc sestamibi scan can help localize disease, but they are not useful in the assessment of malignancy potential. Fine needle aspiration (FNA) prior to initial operation is not recommended due to technical difficulty in differentiating benign and malignant disease on cytology specimens and the possible associated risk of tumor seeding from the needle track. Complete surgical resection with microscopically negative margins is the recommended treatment and offers the best chance of cure. Persistent or recurrent disease occurs in more than 50% of patients with parathyroid carcinoma. Surgical resection is also the primary mode of therapy for recurrence since it can offer significant palliation for the metabolic derangement caused by hyperparathyroidism and allows hypercalcemia to become more medically manageable. However, reoperation is rarely curative and eventual relapse is likely. Chemotherapy and external beam radiation treatments have been generally ineffective in the treatment of parathyroid carcinoma. Typically, these patients require repeated operations that predispose them to accumulated surgical risks with each intervention. In inoperable cases, few palliative treatment options exist, although treatment with calcimimetics can effectively control hypercalcemia in some patients. Most patients ultimately succumb to complications of hypercalcemia rather than from tumor burden or infiltration.
Similar content being viewed by others
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
Dudney WC, Bodenner D, Stack Jr BC. Parathyroid carcinoma. Otolaryngol Clin North Am. 2010;43(2):441–53. xi.
Kebebew E, Arici C, Duh QY, et al. Localization and reoperation results for persistent and recurrent parathyroid carcinoma. Arch Surg. 2001;136(8):878–85.
Kebebew E. Parathyroid carcinoma. Curr Treat Options Oncol. 2001;2(4):347–54.
Lee PK, Jarosek SL, Virnig BA, et al. Trends in the incidence and treatment of parathyroid cancer in the United States. Cancer. 2007;109(9):1736–41.
Givi B, Shah JP. Parathyroid carcinoma. Clin Oncol (R Coll Radiol). 2010;22(6):498–507.
Sandelin K, Auer G, Bondeson L, et al. Prognostic factors in parathyroid cancer: a review of 95 cases. World J Surg. 1992;16(4):724–31.
Levin KE, Galante M, Clark OH. Parathyroid carcinoma versus parathyroid adenoma in patients with profound hypercalcemia. Surgery. 1987;101(6):649–60.
Shane E. Clinical review 122: parathyroid carcinoma. J Clin Endocrinol Metab. 2001;86(2):485–93.
Hundahl SA, Fleming ID, Fremgen AM, et al. Two hundred eighty-six cases of parathyroid carcinoma treated in the U.S. between 1985–1995: a National Cancer Data Base Report. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1999;86(3):538–44.
Kebebew E. Parathyroid carcinoma, a rare but important disorder for endocrinologists, primary care physicians, and endocrine surgeons. Thyroid. 2008;18(4):385–6.
Sharretts JM, Simonds WF. Clinical and molecular genetics of parathyroid neoplasms. Best Pract Res Clin Endocrinol Metabol. 2010;24(3):491–502.
Khan MW, Worcester EM, Straus 2nd FH, et al. Parathyroid carcinoma in secondary and tertiary hyperparathyroidism. J Am Coll Surg. 2004;199(2):312–9.
Fallah M, Kharazmi E, Sundquist J, et al. Nonendocrine cancers associated with benign and malignant parathyroid tumors. J Clin Endocrinol Metab. 2011;96(7):E1108–14.
•• Harari A, Waring A, Fernandez-Ranvier G, et al. Parathyroid carcinoma: a 43-year outcome and survival analysis. J Clin Endocrinol Metabol. 2011; in press.
Goldfarb M, O’Neal P, Shih JL, et al. Synchronous parathyroid carcinoma, parathyroid adenoma, and papillary thyroid carcinoma in a patient with severe and long-standing hyperparathyroidism. Endocr Pract. 2009;15(5):463–8.
Schantz A, Castleman B. Parathyroid carcinoma. A study of 70 cases. Cancer. 1973;31(3):600–5.
Wilkins BJ, Lewis Jr JS. Non-functional parathyroid carcinoma: a review of the literature and report of a case requiring extensive surgery. Head Neck Pathol. 2009;3(2):140–9.
Gao WC, Ruan CP, Zhang JC, et al. Nonfunctional parathyroid carcinoma. J Cancer Res Clin Oncol. 2010;136(7):969–74.
Kebebew E, Clark OH. Parathyroid adenoma, hyperplasia, and carcinoma: localization, technical details of primary neck exploration, and treatment of hypercalcemic crisis. Surg Oncol Clin N Am. 1998;7(4):721–48.
Wynne AG, van Heerden J, Carney JA, et al. Parathyroid carcinoma: clinical and pathologic features in 43 patients. Medicine (Baltimore). 1992;71(4):197–205.
Busaidy NL, Jimenez C, Habra MA, et al. Parathyroid carcinoma: a 22-year experience. Head Neck. 2004;26(8):716–26.
Wu B, Haigh PI, Hwang R, et al. Underutilization of parathyroidectomy in elderly patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 2010;95(9):4324–30.
Sandelin K. Parathyroid carcinoma. In: Clark OH, Duh QY, Kebebew E, editors. Textbook of endocrine surgery. Philadelphia: Elsevier Saunders; 2005. p. 549–54.
Patel CN, Salahudeen HM, Lansdown M, et al. Clinical utility of ultrasound and 99mTc sestamibi SPECT/CT for preoperative localization of parathyroid adenoma in patients with primary hyperparathyroidism. Clin Radiol. 2010;65(4):278–87.
Hara H, Igarashi A, Yano Y, et al. Ultrasonographic features of parathyroid carcinoma. Endocr J. 2001;48(2):213–7.
Sidhu PS, Talat N, Patel P, et al. Ultrasound features of malignancy in the preoperative diagnosis of parathyroid cancer: a retrospective analysis of parathyroid tumours larger than 15 mm. Eur Radiol. 2011;21(9):1865–73.
Harari A, Zarnegar R, Lee J, et al. Computed tomography can guide focused exploration in select patients with primary hyperparathyroidism and negative sestamibi scanning. Surgery. 2008;144(6):970–6. discussion 976-9.
Kassahun WT, Jonas S. Focus on parathyroid carcinoma. Int J Surg. 2011;9(1):13–9.
Clark O. Parathyroid carcinoma. In: Doherty GM, Way LW, editors. Current surgical diagnosis and treatment. Michigan: McGraw-Hill Companies; 2006. p. 284–93.
Rodgers SE, Perrier ND. Parathyroid carcinoma. Curr Opin Oncol. 2006;18(1):16–22.
Smith JF, Coombs RR. Histological diagnosis of carcinoma of the parathyroid gland. J Clin Pathol. 1984;37(12):1370–8.
Obara T, Fujimoto Y, Hirayama A, et al. Flow cytometric DNA analysis of parathyroid tumors with special reference to its diagnostic and prognostic value in parathyroid carcinoma. Cancer. 1990;65(8):1789–93.
Shattuck TM, Valimaki S, Obara T, et al. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. 2003;349(18):1722–9.
Haven CJ, Howell VM, Eilers PH, et al. Gene expression of parathyroid tumors: molecular subclassification and identification of the potential malignant phenotype. Cancer Res. 2004;64(20):7405–11.
Fernandez-Ranvier GG, Khanafshar E, Tacha D, et al. Defining a molecular phenotype for benign and malignant parathyroid tumors. Cancer. 2009;115(2):334–44.
Munson ND, Foote RL, Northcutt RC, et al. Parathyroid carcinoma: is there a role for adjuvant radiation therapy? Cancer. 2003;98(11):2378–84.
Lefevre JH, Tresallet C, Leenhardt L, et al. Reoperative surgery for thyroid disease. Langenbecks Arch Surg. 2007;392(6):685–91.
Farrag TY, Agrawal N, Sheth S, et al. Algorithm for safe and effective reoperative thyroid bed surgery for recurrent/persistent papillary thyroid carcinoma. Head Neck. 2007;29(12):1069–74.
Ariyan CE, Sosa JA. Assessment and management of patients with abnormal calcium. Crit Care Med. 2004;32(4 Suppl):S146–54.
Binstock ML, Mundy GR. Effect of calcitonin and glutocorticoids in combination on the hypercalcemia of malignancy. Ann Intern Med. 1980;93(2):269–72.
Rodriguez A, Trujillo MJ, Herrero T, et al. Allergy to calcitonin. Allergy. 2001;56(8):801.
Calandra DB, Chejfec G, Foy BK, et al. Parathyroid carcinoma: biochemical and pathologic response to DTIC. Surgery. 1984;96(6):1132–7.
Bukowski RM, Sheeler L, Cunningham J, et al. Successful combination chemotherapy for metastatic parathyroid carcinoma. Arch Intern Med. 1984;144(2):399–400.
Chahinian AP, Holland JF, Nieburgs HE, et al. Metastatic nonfunctioning parathyroid carcinoma: ultrastructural evidence of secretory granules and response to chemotherapy. Am J Med Sci. 1981;282(2):80–4.
Chow E, Tsang RW, Brierley JD, et al. Parathyroid carcinoma–the Princess Margaret Hospital experience. Int J Radiat Oncol Biol Phys. 1998;41(3):569–72.
Warrell Jr RP, Issacs M, Alcock NW, et al. Gallium nitrate for treatment of refractory hypercalcemia from parathyroid carcinoma. Ann Intern Med. 1987;107(5):683–6.
Silverberg SJ, Rubin MR, Faiman C, et al. Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma. J Clin Endocrinol Metab. 2007;92(10):3803–8.
Betea D, Bradwell AR, Harvey TC, et al. Hormonal and biochemical normalization and tumor shrinkage induced by anti-parathyroid hormone immunotherapy in a patient with metastatic parathyroid carcinoma. J Clin Endocrinol Metab. 2004;89(7):3413–20.
Bradwell AR, Harvey TC. Control of hypercalcaemia of parathyroid carcinoma by immunisation. Lancet. 1999;353(9150):370–3.
Montenegro FL, Chammas MC, Juliano AG, et al. Ethanol injection under ultrasound guidance to palliate unresectable parathyroid carcinoma. Arq Bras Endocrinol Metabol. 2008;52(4):707–11.
Stratigis S, Stylianou K, Mamalaki E, et al. Percutaneous ethanol injection therapy: a surgery-sparing treatment for primary hyperparathyroidism. Clin Endocrinol (Oxf). 2008;69(4):542–8.
Mauz PS, Stiegler M, Holderried M, et al. Complications of ultrasound guided percutaneous ethanol injection therapy of the thyroid and parathyroid glands. Ultraschall Med. 2005;26(2):142–5.
Tochio M, Takaki H, Yamakado K, et al. A case report of 20 lung radiofrequency ablation sessions for 50 lung metastases from parathyroid carcinoma causing hyperparathyroidism. Cardiovasc Intervent Radiol. 2010;33(3):657–9.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wei, C.H., Harari, A. Parathyroid Carcinoma: Update and Guidelines for Management. Curr. Treat. Options in Oncol. 13, 11–23 (2012). https://doi.org/10.1007/s11864-011-0171-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11864-011-0171-3