Current Understanding and Management of Parathyroid Carcinoma
Journal of Cancer Treatment and Research
Volume 5, Issue 3, May 2017, Pages: 51-61
Received: Mar. 30, 2017; Accepted: Apr. 19, 2017; Published: May 31, 2017
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Rodrigo Arrangoiz, Department of Surgical Oncology, American British Cowdray Medical Center, Mexico City, Mexico
Fernando Cordera, Department of Surgical Oncology, American British Cowdray Medical Center, Mexico City, Mexico
David Caba, Department of Surgical Oncology, American British Cowdray Medical Center, Mexico City, Mexico
Manuel Muñoz Juarez, Department of Surgical Oncology, American British Cowdray Medical Center, Mexico City, Mexico
Eduardo Moreno, Department of Surgical Oncology, American British Cowdray Medical Center, Mexico City, Mexico
Enrique Luque de Leon, Department of Surgical Oncology, American British Cowdray Medical Center, Mexico City, Mexico
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Parathyroid adenomas are a very common endocrine entity, whereas parathyroid carcinomas (PC) are extremely rare. With an estimated incidence of 0.015 per 100,000 population and an estimated prevalence of 0.005% in the United States, parathyroid cancer is one of the rarest of all human malignancies. PC is an extremely rare cause of primary hyperparathyroidism (PHPT). Men and women are equally affected, usually in the fourth or fifth decade of life. The exact etiology has not been identified, but mutations in the CDC73 gene appear to have a critical role in its pathogenesis. The morbidity and mortality of PC is secondary to the hypercalcemia resulting from tumor overproduction of PTH. The primary management objectives are complete removal of the cancer and prevention of recurrences. This review will talk about the epidemiology, etiology, clinical manifestations, and management of PC.
Parathyroid Cancer, Hyperparathyroidism, Hypercalcemia, Parathyroid Carcinoma
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Rodrigo Arrangoiz, Fernando Cordera, David Caba, Manuel Muñoz Juarez, Eduardo Moreno, Enrique Luque de Leon, Current Understanding and Management of Parathyroid Carcinoma, Journal of Cancer Treatment and Research. Vol. 5, No. 3, 2017, pp. 51-61. doi: 10.11648/j.jctr.20170503.15
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Rahbari R, K. E., Parathyroid tumors. 9th ed. ed. Cancer: Principles and Practice of Oncology, ed. L. T. DeVita VT Jr, Rosenberg SA:. 2011, Philadelphia, Pa: Lippincott Williams & Wilkins.
Hundahl SA, F. I., 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): p. 538-44.
Lee, P. K., et al., Trends in the incidence and treatment of parathyroid cancer in the United States. Cancer, 2007. 109(9): p. 1736-41.
Arrangoiz R, C. F., et al., Current Thinking on Primary Hyperparathyroidism.. JSM Head Neck Cancer Cases 2016. Rev 1(1) (1002): p. 1-15.
Fraker, D. L., Update on the management of parathyroid tumors. Curr Opin Oncol, 2000. 12(1): p. 41-8.
Favia, G., et al., Parathyroid carcinoma: sixteen new cases and suggestions for correct management. World J Surg, 1998. 22(12): p. 1225-30.
Shane, E., Clinical review 122: Parathyroid carcinoma. J. Clin Endocrinol Metab, 2001. 86(2): p. 485-93.
Arrangoiz R, R. J., Parathyroid Carcinoma. Textbook of Uncommon Cancer, ed. C.D.B. Derek Raghavan, David H. Johnson, Paul L. Moots, Gregory H. Reaman, Peter G. Rose, Mikkael A. Sekeres. 2012: John Wiley and Sons.
Fujimoto, Y., et al., Surgical treatment of ten cases of parathyroid carcinoma: importance of an initial en bloc tumor resection. World J Surg, 1984. 8(3): p. 392-400.
Singh Ospina N, S. T., Thompson GB, et al., Prevalence of parathyroid carcinoma in 348 patients with multiple endocrine neoplasia type 1 - case report and review of the literature.. Clin Endocrinol (Oxf) 2014.
Hamill, J., et al., Familial parathyroid carcinoma in a child. J Paediatr Child Health, 2002. 38(3): p. 314-7.
Koea, J. B. and J. H. Shaw, Parathyroid cancer: biology and management. Surg Oncol, 1999. 8(3): p. 155-65.
Waun., H. B. L. S. B. R. H. K., Head and Neck Cancer: A multidisciplinary Approach. Edition 2009 ed., Philadelphia: Lippincott Williams and Wilkins.
Mallette, L. E., et al., Parathyroid carcinoma in familial hyperparathyroidism. Am J Med, 1974. 57(4): p. 642-8.
Dionisi, S., et al., Concurrent parathyroid adenomas and carcinoma in the setting of multiple endocrine neoplasia type 1: presentation as hypercalcemic crisis. Mayo Clin Proc, 2002. 77(8): p. 866-9.
Wassif, W. S., et al., Familial isolated hyperparathyroidism: a distinct genetic entity with an increased risk of parathyroid cancer. J Clin Endocrinol Metab, 1993. 77(6): p. 1485-9.
Khan, M. W., et al., Parathyroid carcinoma in secondary and tertiary hyperparathyroidism. J Am Coll Surg, 2004. 199(2): p. 312-9.
Mittendorf, E. A. and C. R. McHenry, Parathyroid carcinoma. J Surg Oncol, 2005. 89(3): p. 136-42.
Woodard, G. E., et al., Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression. Oncogene, 2005. 24(7): p. 1272-6.
Szabo, J., et al., Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2 maps to chromosome 1q21-q31. Am J Hum Genet, 1995. 56(4): p. 944-50.
Carpten, J. D., et al., HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet, 2002. 32(4): p. 676-80.
Fernandez-Ranvier, G. G., et al., Defining a molecular phenotype for benign and malignant parathyroid tumors. Cancer, 2009. 115(2): p. 334-44.
Howell, V. M., et al., HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. J Med Genet, 2003. 40(9): p. 657-63.
Cetani, F., et al., Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab, 2004. 89(11): p. 5583-91.
Simonds, W. F., et al., Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome. J Clin Endocrinol Metab, 2004. 89(1): p. 96-102.
Shattuck, T. M., et al., Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med, 2003. 349(18): p. 1722-9.
Fang, S. H. and G. Lal, Parathyroid cancer. Endocr Pract, 2011. 17 Suppl 1: p. 36-43.
Cryns, V. L., et al., Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med, 1994. 330(11): p. 757-61.
Cryns, V. L., et al., p53 abnormalities in human parathyroid carcinoma. J Clin Endocrinol Metab, 1994. 78(6): p. 1320-4.
Shattuck, T. M., et al., Mutational analyses of RB and BRCA2 as candidate tumour suppressor genes in parathyroid carcinoma. Clin Endocrinol (Oxf), 2003. 59(2): p. 180-9.
Sinha, S., A. Sinha, and G. A. McPherson, Synchronous sporadic carcinoma and primary hyperplasia of the parathyroid glands: A case report and review of the literature. Int J Surg Pathol, 2006. 14(4): p. 336-9.
Hunt, J. L., et al., Allelic loss in parathyroid neoplasia can help characterize malignancy. Am J Surg Pathol, 2005. 29(8): p. 1049-55.
Svedlund, J., et al., Aberrant WNT/beta-catenin signaling in parathyroid carcinoma. Mol Cancer, 2010. 9: p. 294.
Haven, C. J., et al., Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas. Clin Endocrinol (Oxf), 2007. 67(3): p. 370-6.
Perrier, N. D., Asymptomatic hyperparathyroidism: a medical misnomer? Surgery, 2005. 137(2): p. 127-31.
Schoretsanitis, G., et al., Parathyroid carcinoma: clinical presentation and management. Am J Otolaryngol, 2009. 30(4): p. 277-80.
Quinn, C. E., et al., Modern experience with aggressive parathyroid tumors in a high-volume New England referral center. J Am Coll Surg, 2015. 220(6): p. 1054-62.
Obara, T. and Y. Fujimoto, Diagnosis and treatment of patients with parathyroid carcinoma: an update and review. World J Surg, 1991. 15(6): p. 738-44.
Shane, E. and J. P. Bilezikian, Parathyroid carcinoma: a review of 62 patients. Endocr Rev, 1982. 3(2): p. 218-26.
Wynne, A. G., et al., Parathyroid carcinoma: clinical and pathologic features in 43 patients. Medicine (Baltimore), 1992. 71(4): p. 197-205.
Holmes, E. C., D. L. Morton, and A. S. Ketcham, Parathyroid carcinoma: a collective review. Ann Surg, 1969. 169(4): p. 631-40.
Iacobone, M., F. Lumachi, and G. Favia, Up-to-date on parathyroid carcinoma: analysis of an experience of 19 cases. J Surg Oncol, 2004. 88(4): p. 223-8.
Busaidy, N. L., et al., Parathyroid carcinoma: a 22-year experience. Head Neck, 2004. 26(8): p. 716-26.
Schantz, A. and B. Castleman, Parathyroid carcinoma. A study of 70 cases. Cancer, 1973. 31(3): p. 600-5.
Stojadinovic, A., et al., Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis. Hum Pathol, 2003. 34(1): p. 54-64.
Kleinpeter, K. P., et al., Is parathyroid carcinoma indeed a lethal disease? Ann Surg Oncol, 2005. 12(3): p. 260-6.
Messerer, C. L., et al., Normocalcemic parathyroid carcinoma: an unusual clinical presentation. World J Surg Oncol, 2006. 4: p. 10.
Wang, L., et al., Non-functional parathyroid carcinoma: a case report and review of the literature. Cancer Biol Ther, 2015. 16(11): p. 1569-76.
Fernandez-Ranvier, G. G., et al., Nonfunctioning parathyroid carcinoma: case report and review of literature. Endocr Pract, 2007. 13(7): p. 750-7.
Sandelin, K., et al., Prognostic factors in parathyroid cancer: a review of 95 cases. World J Surg, 1992. 16(4): p. 724-31.
Adam, M. A., B. R. Untch, and J. A. Olson, Jr., Parathyroid carcinoma: current understanding and new insights into gene expression and intraoperative parathyroid hormone kinetics. Oncologist, 2010. 15(1): p. 61-72.
Singhal, T., M. Jacobs, and J. C. Mantil, Tc-99m pertechnetate/sestamibi subtraction scan in a case of parathyroid carcinoma. Clin Nucl Med, 2008. 33(3): p. 196-7.
Al-Sobhi, S., L. H. Ashari, and S. Ingemansson, Detection of metastatic parathyroid carcinoma with Tc-99m sestamibi imaging. Clin Nucl Med, 1999. 24(1): p. 21-3.
Chen, C. C., et al., Comparison of parathyroid imaging with technetium-99m-pertechnetate/sestamibi subtraction, double-phase technetium-99m-sestamibi and technetium-99m-sestamibi SPECT. J Nucl Med, 1997. 38(6): p. 834-9.
Hara, H., et al., Ultrasonographic features of parathyroid carcinoma. Endocr J, 2001. 48(2): p. 213-7.
Weber, A. L., G. Randolph, and F. G. Aksoy, The thyroid and parathyroid glands. CT and MR imaging and correlation with pathology and clinical findings. Radiol Clin North Am, 2000. 38(5): p. 1105-29.
Clark, P., et al., Providing optimal preoperative localization for recurrent parathyroid carcinoma: a combined parathyroid scintigraphy and computed tomography approach. Clin Nucl Med, 2004. 29(11): p. 681-4.
Arslan, N. and B. Rydzewski, Detection of a recurrent parathyroid carcinoma with FDG positron emission tomography. Clin Nucl Med, 2002. 27(3): p. 221-2.
Kemps, B., et al., Brown tumors simulating metastases on FDG PET in a patient with parathyroid carcinoma. Eur J Nucl Med Mol Imaging, 2008. 35(4): p. 850.
Wei, C. H. and A. Harari, Parathyroid carcinoma: update and guidelines for management. Curr Treat Options Oncol, 2012. 13(1): p. 11-23.
Brown, J. J., et al., Primary hyperparathyroidism secondary to simultaneous bilateral parathyroid carcinoma. Ear Nose Throat J, 2002. 81(6): p. 395-8, 400-1.
Marcocci, C., et al., Parathyroid carcinoma. J Bone Miner Res, 2008. 23(12): p. 1869-80.
Flye, M. W. and M. F. Brennan, Surgical resection of metastatic parathyroid carcinoma. Ann Surg, 1981. 193(4): p. 425-35.
Clayman, G. L., et al., Parathyroid carcinoma: evaluation and interdisciplinary management. Cancer, 2004. 100(5): p. 900-5.
Bondeson, L., K. Sandelin, and L. Grimelius, Histopathological variables and DNA cytometry in parathyroid carcinoma. Am J Surg Pathol, 1993. 17(8): p. 820-9.
Sharretts, J. M., E. Kebebew, and W. F. Simonds, Parathyroid cancer. Semin Oncol, 2010. 37(6): p. 580-90.
Howell, V. M., et al., Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma. J Clin Endocrinol Metab, 2009. 94(2): p. 434-41.
Gill, A. J., et al., Loss of nuclear expression of parafibromin distinguishes parathyroid carcinomas and hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from sporadic parathyroid adenomas and hyperplasias. Am J Surg Pathol, 2006. 30(9): p. 1140-9.
Zhao, L., et al., Copy number variation in CCND1 gene is implicated in the pathogenesis of sporadic parathyroid carcinoma. World J Surg, 2014. 38(7): p. 1730-7.
Truran, P. P., et al., Parafibromin, galectin-3, PGP9.5, Ki67, and cyclin D1: using an immunohistochemical panel to aid in the diagnosis of parathyroid cancer. World J Surg, 2014. 38(11): p. 2845-54.
Thompson, S. D. and A. J. Prichard, The management of parathyroid carcinoma. Curr Opin Otolaryngol Head Neck Surg, 2004. 12(2): p. 93-7.
Shaha, A. R. and J. P. Shah, Parathyroid carcinoma: a diagnostic and therapeutic challenge. Cancer, 1999. 86(3): p. 378-80.
Talat, N. and K. M. Schulte, Clinical presentation, staging and long-term evolution of parathyroid cancer. Ann Surg Oncol, 2010. 17(8): p. 2156-74.
Schulte, K. M., et al., Classification of parathyroid cancer. Ann Surg Oncol, 2012. 19(8): p. 2620-8.
Chow, E., et al., Parathyroid carcinoma--the Princess Margaret Hospital experience. Int J Radiat Oncol Biol Phys, 1998. 41(3): p. 569-72.
Kebebew, E., Parathyroid carcinoma. Curr Treat Options Oncol, 2001. 2(4): p. 347-54.
McKeown, P. P., W. C. McGarity, and C. W. Sewell, Carcinoma of the parathyroid gland: is it overdiagnosed? A report of three cases. Am J Surg, 1984. 147(2): p. 292-8.
Shortell, C. K., et al., Carcinoma of the parathyroid gland: a 30-year experience. Surgery, 1991. 110(4): p. 704-8.
Hoelting, T., et al., Surgical treatment of parathyroid carcinoma (Review). Oncol Rep, 2001. 8(4): p. 931-4.
Givi, B. and J. P. Shah, Parathyroid carcinoma. Clin Oncol (R Coll Radiol), 2010. 22(6): p. 498-507.
Kebebew, E. and O. H. Clark, 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): p. 721-48.
Kebebew, E., et al., Localization and reoperation results for persistent and recurrent parathyroid carcinoma. Arch Surg, 2001. 136(8): p. 878-85.
Harari, A., et al., Parathyroid carcinoma: a 43-year outcome and survival analysis. J Clin Endocrinol Metab, 2011. 96(12): p. 3679-86.
Fujimoto, Y., et al., Localization and surgical resection of metastatic parathyroid carcinoma. World J Surg, 1986. 10(4): p. 539-47.
Obara, T., et al., Surgical and medical management of patients with pulmonary metastasis from parathyroid carcinoma. Surgery, 1993. 114(6): p. 1040-8; discussion 1048-9.
Hundley, J. C., et al., Resection of pulmonary metastasis from parathyroid carcinoma. Am Surg, 2003. 69(9): p. 779-83.
Cohn, K., et al., Parathyroid carcinoma: the Lahey Clinic experience. Surgery, 1985. 98(6): p. 1095-100.
Munson, N. D., et al., Parathyroid carcinoma: is there a role for adjuvant radiation therapy? Cancer, 2003. 98(11): p. 2378-84.
Calandra, D. B., et al., Parathyroid carcinoma: biochemical and pathologic response to DTIC. Surgery, 1984. 96(6): p. 1132-7.
Bukowski, R. M., et al., Successful combination chemotherapy for metastatic parathyroid carcinoma. Arch Intern Med, 1984. 144(2): p. 399-400.
Chahinian, A. P., et al., Metastatic nonfunctioning parathyroid carcinoma: ultrastructural evidence of secretory granules and response to chemotherapy. Am J Med Sci, 1981. 282(2): p. 80-4.
Chahinian, A. P., Chemotherapy for metastatic parathyroid carcinoma. Arch Intern Med, 1984. 144(9): p. 1889.
Owen, R. P., et al., Parathyroid carcinoma: a review. Head Neck, 2011. 33(3): p. 429-36.
Pacini, F., et al., Telomerase and the endocrine system. Nat Rev Endocrinol, 2011. 7(7): p. 420-30.
Falchetti, A., et al., Azidothymidine induces apoptosis and inhibits cell growth and telomerase activity of human parathyroid cancer cells in culture. J Bone Miner Res, 2005. 20(3): p. 410-8.
Betea, D., 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): p. 3413-20.
Mohebati, A., A. Shaha, and J. Shah, Parathyroid carcinoma: challenges in diagnosis and treatment. Hematol Oncol Clin North Am, 2012. 26(6): p. 1221-38.
Silverberg, S. J., et al., Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma. J Clin Endocrinol Metab, 2007. 92(10): p. 3803-8.
Vellanki, P., et al., Denosumab for management of parathyroid carcinoma-mediated hypercalcemia. J Clin Endocrinol Metab, 2014. 99(2): p. 387-90.
Tong, C. V., et al., Use of denosumab in parathyroid carcinoma with refractory hypercalcemia. QJM, 2015. 108(1): p. 49-50.
Nadarasa, K., et al., Denosumab for management of refractory hypercalcaemia in recurrent parathyroid carcinoma. Eur J Endocrinol, 2014. 171(3): p. L7-8.
Erovic, B. M., et al., Parathyroid cancer: outcome analysis of 16 patients treated at the Princess Margaret Hospital. Head Neck, 2013. 35(1): p. 35-9.
Obara, T., et al., Flow cytometric DNA analysis of parathyroid tumors. Implication of aneuploidy for pathologic and biologic classification. Cancer, 1990. 66(7): p. 1555-62.
Giessler, G. A. and D. J. Beech, Nonfunctional parathyroid carcinoma. J Natl Med Assoc, 2001. 93(7-8): p. 251-5.
Asare, E. A., et al., Parathyroid Carcinoma: An Update on Treatment Outcomes and Prognostic Factors from the National Cancer Data Base (NCDB). Ann Surg Oncol, 2015. 22(12): p. 3990-5.
Sadler, C., et al., Parathyroid carcinoma in more than 1,000 patients: A population-level analysis. Surgery, 2014. 156(6): p. 1622-9; discussion 1629-30.
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