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Parathyroid Carcinoma: Current Concepts

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Evidence-Based Endocrine Surgery

Abstract

Parathyroid cancer is a rare tumor accounting for less than 1% of primary hyperparathyroidism. De Quervain in 1904 described the first case of parathyroid carcinoma which was nonfunctioning. Parathyroid carcinoma is a rare malignancy whose recognition requires a high index of suspicion. Best opportunity to cure parathyroid carcinoma is to diagnose it before or at the time of surgery for the tumor to be completely removed at the time of initial operation. Histological diagnosis can be difficult and nonspecific but immune histochemical markers (PF, galectin-3, PGP 9.5) can be used as a complement to histological diagnosis. En bloc excision reduces soft-tissue recurrence and, even though evidence base for LN involvement by parathyroid cancer is sparse, a systematic central LN resection may improve outcomes. Thus failure to perform oncological surgery (en bloc resection) predicts higher recurrence and death rates.The morbidity and mortality of parathyroid cancer are mainly related to hypersecretion of PTH and the resulting hypercalcemia, rather than the tumor itself. Cinacalcet and bisphosphonates are the most effective treatments for hypercalcemia.

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References

  1. Fraker DL. Parathyroid tumors. In: DeVita Jr VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 6th ed. Philadelphia: Lippincott Williams and Wilkins; 2001. p. 1763–9.

    Google Scholar 

  2. Sharretts JM, Simonds WF. Clinical and molecular genetics of parathyroid neoplasms. Best Pract Res Clin Endocrinol Metab. 2010;24(3):491–502.

    Article  CAS  Google Scholar 

  3. Gill AJ. Understanding the genetic basis of parathyroid carcinoma. Endocr Pathol. 2014;25(1):30–4.

    Article  CAS  Google Scholar 

  4. Goswamy J, Lei M, Simo R. Parathyroid carcinoma. Curr Opin Otolaryngol Head Neck Surg. 2016;24(2):155–62.

    Article  Google Scholar 

  5. Shi Y, Hogue J, Dixit D, Koh J, Olson JA Jr. Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia. Proc Natl Acad Sci U S A. 2014;111(8):3092–7.

    Article  CAS  Google Scholar 

  6. Friedman E, Sakaguchi K, Bale AE, Falchetti A, Streeten E, Zimering MB, et al. Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1. N Engl J Med. 1989;321(4):213–8.

    Article  CAS  Google Scholar 

  7. Shattuck TM, Kim TS, Costa J, Yandell DW, Imanishi Y, Palanisamy N, et al. Mutational analyses of RB and BRCA2 as candidate tumour suppressor genes in parathyroid carcinoma. Clin Endocrinol. 2003;59(2):180–9.

    Article  CAS  Google Scholar 

  8. Arnold A. The cyclin D1/PRAD1 oncogene in human neoplasia. J Investig Med. 1995;43(6):543–9.

    CAS  PubMed  Google Scholar 

  9. Simonds WF, Robbins CM, Agarwal SK, Hendy GN, Carpten JD, Marx SJ. 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):96–102.

    Article  CAS  Google Scholar 

  10. Cetani F, Pardi E, Borsari S, Viacava P, Dipollina G, Cianferotti L, 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):5583–91.

    Article  CAS  Google Scholar 

  11. Cryns VL, Thor A, Xu HJ, Hu SX, Wierman ME, Vickery AL Jr, et al. Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med. 1994;330(11):757–61.

    Article  CAS  Google Scholar 

  12. Talat N, Schulte KM. Clinical presentation, staging andlong-term evolution of parathyroid cancer. Ann Surg Oncol. 2010;17:2156–74.

    Article  Google Scholar 

  13. Holmes EC, Morton DL, Ketcham AS. Parathyroid carcinoma: a collective review. Ann Surg. 1969;169(4):631–40.

    Article  CAS  Google Scholar 

  14. Schaapveld M, Jorna FH, Aben KK, et al. Incidence and prognosis of parathyroid gland carcinoma: a population-based study in The Netherlands estimating the preoperative diagnosis. Am J Surg. 2011;202(5):590–7.

    Article  Google Scholar 

  15. Harari A, Waring A, Fernandez-Ranvier G, et al. Parathyroid carcinoma: a 43-year outcome and survival analysis. J Clin Endocrinol Metab. 2011;96(12):3679–86.

    Article  CAS  Google Scholar 

  16. Robert JH, Trombetti A, Garcia A, et al. Primary hyperparathyroidism: can parathyroid carcinoma be anticipated on clinical and biochemical grounds? Report of nine cases and review of the literature. Ann Surg Oncol. 2005;12(7):526–32.

    Article  Google Scholar 

  17. Iihara M, Okamoto T, Suzuki R, et al. Functional parathyroid carcinoma: longterm treatment outcome and risk factor analysis. Surgery. 2007;142(6):936–43; discussion 943.e1

    Article  Google Scholar 

  18. Rubin MR, Bilezikian JP, Birken S, et al. Human chorionic gonadotropin measurements in parathyroid carcinoma. Eur J Endocrinol. 2008;159(4):469–74.

    Article  CAS  Google Scholar 

  19. Koea JB, Shaw JH. Parathyroid cancer: biology and management. Surg Oncol. 1999;8:155–65l.

    Article  CAS  Google Scholar 

  20. Singh DN, Gupta SK, Kumari N, Krishnani N, Chand G, Mishra A, Agarwal G, Verma AK, Mishra SK, Agarwal A. Primary hyperparathyroidism presenting as hypercalcemic crisis: twenty-year experience. Indian J Endocrinol Metab. 2015;19(1):100–5.

    Article  CAS  Google Scholar 

  21. Shane E. Clinical review 122: parathyroid carcinoma. J Clin Endocrinol Metab. 2001;86(2):485–93.

    Article  CAS  Google Scholar 

  22. Levin KE, Galante M, Clark OH. Parathyroid carcinoma versus parathyroid adenoma in patients with profound hypercalcemia. Surgery. 1987;101(6):649–60.

    CAS  PubMed  Google Scholar 

  23. Shaha AR, Shah JP. Parathyroid carcinoma: a diagnostic and therapeutic challenge. Cancer. 1999;86(3):378–80.

    Article  CAS  Google Scholar 

  24. Shaha AR, Ferlito A, Rinaldo A. Distant metastases from thyroid and parathyroid cancer. ORL J Otorhinolaryngol Relat Spec. 2001;63(4):243–9.

    Article  CAS  Google Scholar 

  25. Fang SH, Lal G. Parathyroid cancer. Endocr Pract. 2011;17(Suppl 1):36–43.

    Article  Google Scholar 

  26. 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.

    Article  Google Scholar 

  27. Hara H, Igarashi A, Yano Y, et al. Ultrasonographic features of parathyroid carcinoma. Endocr J. 2001;48(2):213–7.

    Article  CAS  Google Scholar 

  28. Edmonson GR, Charboneau JW, James EM, et al. Parathyroid carcinoma: highfrequency sonographic features. Radiology. 1986;161(1):65–7.

    Article  CAS  Google Scholar 

  29. Tamler R, Lewis MS, LiVolsi VA, et al. Parathyroid carcinoma: ultrasonographic and histologic features. Thyroid. 2005;15(7):744–5.

    Article  Google Scholar 

  30. Spinelli C, Bonadio AG, Berti P, et al. Cutaneous spreading of parathyroid carcinoma after fine needle aspiration cytology. J Endocrinol Invest. 2000;23(4):255–7.

    Article  CAS  Google Scholar 

  31. Kumari N, Mishra D, Pradhan R, Agarwal A, Krishnani N. Utility of fine-needle aspiration cytology in the identification of parathyroid lesions. J Cytol. 2016;33:17–21.

    Article  Google Scholar 

  32. Agarwal A, Gupta SK, Sukumar R. Hyperparathyroidism and malnutrition with severe Vitamin D deficiency. World J Surg. 2009;33(11):2303–13.

    Article  Google Scholar 

  33. Smith JF, Coombs RR. Histological diagnosis of carcinoma of the parathyroid gland. J Clin Pathol. 1984;37(12):1370–8.

    Article  CAS  Google Scholar 

  34. Delellis RA. Challenging lesions in the differential diagnosis of endocrine tumors: parathyroid carcinoma. Endocr Pathol. 2008;19(4):221–5.

    Article  CAS  Google Scholar 

  35. 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.

    Article  CAS  Google Scholar 

  36. Cohn K, Silverman M, Corrado J, et al. Parathyroid carcinoma: the Lahey Clinic experience. Surgery. 1985;98(6):1095–100.

    CAS  PubMed  Google Scholar 

  37. Schantz A, Castleman B. Parathyroid carcinoma. A study of 70 cases. Cancer. 1973;31(3):600–5.

    Article  CAS  Google Scholar 

  38. McKeown PP, McGarity WC, Sewell CW. Carcinoma of the parathyroid gland: is it overdiagnosed? A report of three cases. Am J Surg. 1984;147:292–7.

    Article  CAS  Google Scholar 

  39. Bondeson L, Sandelin K, Grimelius L. Histopathological variables and DNA cytometry in parathyroid carcinoma. Am J Surg Pathol. 1993;17:820–9.

    Article  CAS  Google Scholar 

  40. Okamoto T, Iihara M, Obara T, Tsukada T. Parathyroid carcinoma: etiology, diagnosis, and treatment. World J Surg. 2009;33:2343–54.

    Article  Google Scholar 

  41. Obara T, Okamoto T, Kanbe M, et al. Functioning parathyroid carcinoma: clinicopathologic features and rational treatment. Semin Surg Oncol. 1997;13(2):134–41.

    Article  CAS  Google Scholar 

  42. Chang YJ, Mittal V, Remine S, et al. Correlation between clinical and histological findings in parathyroid tumors suspicious for carcinoma. Am Surg. 2006;72(5):419–26.

    PubMed  Google Scholar 

  43. Fujimoto Y, Obara T. How to recognize and treat parathyroid carcinoma. Surg Clin North Am. 1987;67:343–57.

    Article  CAS  Google Scholar 

  44. Holck S, Pedersen N. Carcinoma of the parathyroid gland. A light and electron microscopic study. Acta Pathol Microbiol Scand. 1981;89:297–302.

    CAS  Google Scholar 

  45. Levin K, Chew K, Ljung B, Mayall B, Siperstein A, Clark O. Deoxyribonucleic acid flow cytometry helps identify parathyroid carcinomas. J Clin Endocrinol Metab. 1988;67:779–84.

    Article  CAS  Google Scholar 

  46. Mallette LE. DNA quantitation in the study of parathyroid lesions. A review. Am J Clin Pathol. 1992;98:305–11.

    Article  CAS  Google Scholar 

  47. Cryns VL, Rubio MP, Thor AD, Louis DN, Arnold A. p53 abnormalities in human parathyroid carcinoma. J Clin Endocrinol Metab. 1994;78:1320–4.

    CAS  PubMed  Google Scholar 

  48. Cetani F, Pardi E, ViacavaP Pollina GD, Fanelli G, Picone A, Borsari S, Gazzerro E, Miccoli P, Berti P, Pinchera A, Marcocci C. A reappraisal of the Rb1 gene abnormalities in the diagnosis of parathyroid cancer. Clin Endocrinol. 2004;60:99–10.

    Article  CAS  Google Scholar 

  49. Lloyd RV, Carney JA, Ferreiro JA, Jin L, Thompson GB, Van Heerden JA, Grant CS, Wollan PC. Immunohistochemical analysis of the cell cycle-associated antigens Ki-67 and retinoblastoma protein in parathyroid carcinomas and adenomas. Endocr Pathol. 1995;6(4):279–87.

    Article  Google Scholar 

  50. Juhlin CC, Nilsson IL, Johansson K, Haglund F, Villablanca A, Höög A, Larsson C. Parafibromin and APC as screening markers for malignant potential in atypical parathyroid adenomas. Endocr Pathol. 2010;21(3):166–77.

    Article  CAS  Google Scholar 

  51. Bergero N, De Pompa R, Sacerdote C, Gasparri G, Volante M, Bussolati G, Papotti M. Galectin-3 expression in parathyroid carcinoma: immunohistochemical study of 26 cases. Hum Pathol. 2005;36(8):908–14.

    Article  CAS  Google Scholar 

  52. Tezel E, Hibi K, Nagasaka T, Nakao A. PGP9.5 as a prognostic factor in pancreatic cancer. Clin Cancer Res. 2000;6(12):4764–7.

    CAS  PubMed  Google Scholar 

  53. Takano T, Miyauchi A, Matsuzuka F, Yoshida H, Nakata Y, Kuma K, Amino N. PGP9.5 mRNA could contribute to the molecular-based diagnosis of medullary thyroid carcinoma. Eur J Cancer. 2004;40(4):614–618 27.

    Article  CAS  Google Scholar 

  54. Yamazaki T, Hibi K, Takase T, Tezel E, Nakayama H, Kasai Y, Ito K, Akiyama S, Nagasaka T, Nakao A. PGP9.5 as a marker for invasive colorectal cancer. Clin Cancer Res. 2002;8(1):192–5.

    CAS  PubMed  Google Scholar 

  55. Tan MH, Morrison C, Wang P, Yang X, Haven CJ, Zhang C, Zhao P, Tretiakova MS, Korpi-Hyovalti E, Burgess JR, Soo KC, Cheah WK, Cao B, Resau J, Morreau H, Teh BT. Loss of parafibromin immunoreactivity is a distinguishing feature of parathyroid carcinoma. Clin Cancer Res. 2004;10:6629–37.

    Article  CAS  Google Scholar 

  56. Gill AJ, Clarkson A, Gimm O, Keil J, Dralle H, Howell VM, Marsh DJ. Loss of nuclear expression of parafibromin distinguishes parathyroid carcinomas and hyperparathyroidismjaw tumor (HPT-JT) syndrome related adenomas from sporadic parathyroid adenomas and hyperplasias. Am J Surg Pathol. 2006;30(9):1140–9.

    Article  Google Scholar 

  57. Agarwal A, Pradhan R, Kumari N, Krishnani N, Shukla P, Gupta SK, Chand G, Mishra A, Agarwal G, Verma AK, Mishra SK. Molecular characteristics of large parathyroid adenomas. World J Surg. 2016;40(3):607–14.

    Article  Google Scholar 

  58. Farnebo F, Svensson A, Thompson NW, et al. Expression of matrix metalloproteinase gelatinase A messenger ribonucleic acid in parathyroid carcinomas. Surgery. 1999;126:1183–7.

    Article  CAS  Google Scholar 

  59. Villar-del-Moral J, Jimenez-Garcıa A, Salvador-Egea P, Martos-Martınez JM, Nuño-Vazquez-Garza JM, Serradilla-Martın M, Gómez-Palacios A, Moreno-Llorente P, Ortega-Serrano J, de la Quintana-Basarrate A. Prognostic factors and staging systems in parathyroid cancer: a multicenter cohort study. Surgery. 2014;156:1132–44.

    Article  Google Scholar 

  60. Medas F, et al. Controversies in the management of parathyroid carcinoma: a case series and review of the literature. Int J Surg. 2015;28:S94. https://doi.org/10.1016/j.ijsu.2015.12.040

    Article  Google Scholar 

  61. Christine J, Chan O’NC, Symons J, Learoyd DL, Sidhu SB, Delbridge LW, Gill A, Sywak MS. Parathyroid carcinoma encountered after minimally invasive focused parathyroidectomy may not require further radical surgery. World J Surg. 2011;35:147–53.

    Article  Google Scholar 

  62. Lee PK, Jarosek SL, Virnig BA, Evasovich M, Tuttle TM. Trends in the incidence and treatment of parathyroid cancer in the United States. Cancer. 2007;109:1736–41.

    Article  Google Scholar 

  63. Enomoto K, Uchino S, Ito A, et al. The surgical strategy and the molecular analysis of patients with parathyroid cancer. World J Surg. 2010;34:2604–10.

    Article  Google Scholar 

  64. Kameyama K, Takami H. Double parathyroid carcinoma. Endocr J. 2003;50:477–9.

    Article  Google Scholar 

  65. Busaidy NL, Jimenez C, Habra MA, Schultz PN, El-Naggar AK, Clayman GL, Asper JA, Diaz EM Jr, Evans DB, Gagel RF, Garden A, Hoff AO, Lee JE, Morrison WH, Rosenthal DI, Sherman SI, Sturgis EM, Waguespack SG, Weber RS, Wirfel K, Vassilopoulou-Sellin R. Parathyroid carcinoma: a 22-year experience. Head Neck. 2004;26(8):716–26.

    Article  Google Scholar 

  66. Kebebew E, et al. Localization and reoperation results for persistent and recurrent parathyroid carcinoma. Arch Surg. 2001;136:878–85.

    Article  CAS  Google Scholar 

  67. Mohebati A, Shaha A, Shah J. Parathyroid carcinoma: challenges in diagnosis and treatment. Hematol Oncol Clin North Am. 2012;26(6):1221–38.

    Article  Google Scholar 

  68. Sandelin K, Auer G, Bondeson L, Grimelius L, Farnebo LO. Prognostic factors in parathyroid cancer: a review of 95 cases. World J Surg. 1992;16(4):724–31.

    Article  CAS  Google Scholar 

  69. Sadler C, Gow KW, Beierle EA, Doski JJ, Langer M, Nuchtern JG, Vasudevan SA, Goldfarb M. Parathyroid carcinoma in more than 1,000 patients: a population-level analysis. Surgery. 2014;156(6):1622–9.

    Article  Google Scholar 

  70. Munson ND, Foote RL, Northcutt RC, et al. Parathyroid carcinoma: is there a role for adjuvant radiation therapy? Cancer. 2003;98(11):2378–84.

    Article  Google Scholar 

  71. 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.

    Article  CAS  Google Scholar 

  72. Bukowski RM, Sheeler L, Cunningham J, et al. Successful combination chemotherapy for metastatic parathyroid carcinoma. Arch Intern Med. 1984;144(2):399–400.

    Article  CAS  Google Scholar 

  73. Chahinian AP. Chemotherapy for metastatic parathyroid carcinoma. Arch Intern Med. 1984;144(9):1889.

    Article  CAS  Google Scholar 

  74. Wang CA, Gaz RD. Natural history of parathyroid carcinoma. Diagnosis, treatment, and results. Am J Surg. 1985;149:522–7.

    Article  CAS  Google Scholar 

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Pradhan, R., Mayilvaganan, S., Agarwal, A. (2018). Parathyroid Carcinoma: Current Concepts. In: Parameswaran, R., Agarwal, A. (eds) Evidence-Based Endocrine Surgery. Springer, Singapore. https://doi.org/10.1007/978-981-10-1124-5_24

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