Parathyroid Carcinoma Treatment & Management
- Author: Lawrence Kim, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC more...
No effective medical therapy for parathyroid carcinoma is known. Trials of chemotherapeutic agents have been generally disappointing with only anecdotal reports of success. This tumor is sufficiently rare that controlled trials are impossible.
Medical therapy is primarily geared toward management of the hypercalcemia that is often quite severe. Treatment is similar to hypercalcemia due to other causes. At initial presentation and for rapid treatment of severe hypercalcemia volume loading and diuresis with a calcium-wasting loop diuretic is the treatment of choice. The next line of therapy, used for chronic treatment, is the bisphosphonates. Detailed dosing information can be found below.
Hypercalcemia due to parathyroid cancer is often resistant to long-term medical management and is usually the cause of death in patients with metastatic disease.
At present, resection of the parathyroid cancer is the only effective treatment.
- Preoperative care
- Because the hypercalcemia caused by parathyroid cancer is often severe, preoperative medical intervention to control hypercalcemia is often required.
- Volume expansion with isotonic saline and diuresis with furosemide is often adequate.
- Take care to ensure that any volume contraction is corrected before the operation.
- Operative management
- The goal of the initial operation is to remove the tumor en bloc with any adherent tissue, the ipsilateral thyroid lobe, and any enlarged lymph nodes.
- Because the diagnosis of malignancy is usually uncertain before the operation, the initial approach is the same as for benign primary hyperparathyroidism.
- Make a standard collar incision. While approaching the parathyroid, be alert for evidence of invasion into surrounding tissue or gland firmness that might indicate malignancy.
- If any indication of malignancy is noted, perform an en bloc excision as described above.
- Regional lymph node metastases are uncommon ; however, if any regional lymph nodes are enlarged, perform a compartmental lymphadenectomy.
- Recommendations on the precise extent of the dissection cannot be made because of the rarity of this condition, but an en bloc excision with negative margins and removal of the involved lymph nodes is standard.
- Postoperative care
- Postoperative care is generally the same as for benign hyperparathyroidism.
- Bone hunger may be quite profound and require substantial doses of postoperative calcium.
- Resection of recurrence
- Reoperation for local and regional recurrence is indicated and may provide substantial palliation from hypercalcemia, in some cases for many years.
- Resection or ablation of pulmonary or hepatic metastases also may provide palliation.
- Long-term cure after a recurrence is virtually unknown.
See the list below:
- Experienced surgeon - Surgical removal is the mainstay of treatment.
- Medical endocrinologist - Medical care of the hypercalcemia can be difficult and complex.
- Interventional radiologist - Percutaneous ablation or embolization of metastatic lesions may provide palliation.
- Radiation oncologist - External beam radiation therapy (EBRT) is controversial. It may decrease local recurrence when used in the adjuvant setting postoperatively but the evidence for this is not strong. It may also be used in specific circumstances for treatment of a metastasis. In general, however, parathyroid carcinoma is relatively resistant to radiation therapy.
McClenaghan F, Qureshi YA. Parathyroid cancer. Gland Surg. 2015 Aug. 4 (4):329-38. [Medline].
Schaapveld M, Jorna FH, Aben KK, Haak HR, Plukker JT, Links TP. Incidence and prognosis of parathyroid gland carcinoma: A population-based study in The Netherlands estimating the preoperative diagnosis. Am J Surg. 2011 Aug 20. [Medline].
Mittendorf EA, McHenry CR. Parathyroid carcinoma. J Surg Oncol. 2005 Mar 1. 89(3):136-42.
Yip L, Seethala RR, Nikiforova MN, Nikiforov YE, Ogilvie JB, Carty SE, et al. Loss of heterozygosity of selected tumor suppressor genes in parathyroid carcinoma. Surgery. 2008 Dec. 144(6):949-55; discussion 954-5. [Medline].
van der Zwan JM, Mallone S, van Dijk B, Bielska-Lasota M, Otter R, Foschi R, et al. Carcinoma of endocrine organs: results of the RARECARE project. Eur J Cancer. 2012 Sep. 48(13):1923-31. [Medline].
Douglas L. Fraker. Chapter 44 - Cancer of the Endocrine System, Section 3: Parathyroid Tumors. Vincent T. DeVita, Jr., Theodore S. Lawrence, Steven A. Rosenberg. Cancer: Principles & Practice of Oncology. 8th. Philadelphia: Lippincott Williams & Wilkins; 2008. 1682-1690.
Wynne AG, van Heerden J, Carney JA. Parathyroid carcinoma: clinical and pathologic features in 43 patients. Medicine (Baltimore). 1992 Jul. 71(4):197-205. [Medline].
Busaidy NL, Jimenez C, Habra MA, Schultz PN, El-Naggar AK, Clayman GL, et al. Parathyroid carcinoma: a 22-year experience. Head Neck. 2004 Aug. 26(8):716-26. [Medline].
Wang CA, Gaz RD. Natural history of parathyroid carcinoma. Diagnosis, treatment, and results. Am J Surg. 1985 Apr. 149(4):522-7. [Medline].
Hakaim AG, Esselstyn CB Jr. Parathyroid carcinoma: 50-year experience at The Cleveland Clinic Foundation. Cleve Clin J Med. 1993 Jul-Aug. 60(4):331-5. [Medline].
Favia G, Lumachi F, Polistina F, D'Amico DF. Parathyroid carcinoma: sixteen new cases and suggestions for correct management. World J Surg. 1998 Dec. 22(12):1225-30. [Medline].
Flye MW, Brennan MF. Surgical resection of metastatic parathyroid carcinoma. Ann Surg. 1981 Apr. 193(4):425-35. [Medline].
Talat N, Schulte KM. Clinical presentation, staging and long-term evolution of parathyroid cancer. Ann Surg Oncol. 2010 Aug. 17(8):2156-74. [Medline].
Hundahl SA, Fleming ID, Fremgen AM, Menck HR. 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 Aug 1. 86(3):538-44. [Medline].
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 May 1. 109(9):1736-41. [Medline].
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 Nov. 202(5):590-7. [Medline].
Shattuck TM, Valimaki S, Obara T. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. 2003 Oct 30. 349(18):1722-9. [Medline].
Lim S, Elston MS, Gill AJ, Marsh DJ, Conaglen JV. Metastatic parathyroid carcinoma initially misdiagnosed as parathyroid adenoma: the role of parafibromin in increasing diagnostic accuracy. Intern Med J. 2011 Sep. 41(9):695-9. [Medline].
Sulaiman L, Haglund F, Hashemi J, Obara T, Nordenström J, Larsson C, et al. Genome-wide and locus specific alterations in CDC73/HRPT2-mutated parathyroid tumors. PLoS One. 2012. 7(9):e46325. [Medline]. [Full Text].
Vasef MA, Brynes RK, Sturm M, Bromley C, Robinson RA. Expression of cyclin D1 in parathyroid carcinomas, adenomas, and hyperplasias: a paraffin immunohistochemical study. Mod Pathol. 1999 Apr. 12(4):412-6. [Medline].
Woodard GE, Lin L, Zhang JH, Agarwal SK, Marx SJ, Simonds WF. Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression. Oncogene. 2005 Feb 10. 24(7):1272-6. [Medline].
Cryns VL, Thor A, Xu HJ. Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med. 1994 Mar 17. 330(11):757-61. [Medline].
Haven CJ, van Puijenbroek M, Tan MH, Teh BT, Fleuren GJ, van Wezel T, et al. Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas. Clin Endocrinol (Oxf). 2007 Sep. 67(3):370-6. [Medline].
Karakas E, Müller HH, Lyadov VK, Luz S, Schneider R, Rothmund M, et al. Development of a formula to predict parathyroid carcinoma in patients with primary hyperparathyroidism. World J Surg. 2012 Nov. 36(11):2605-11. [Medline].
van Baardwijk A, de Jong J, Arens A, Thimister P, Verseput G, Kremer B, et al. False-positive FDG-PET scan due to brown tumours. Eur J Nucl Med Mol Imaging. 2006 Mar. 33(3):393-4. [Medline].
Guarnieri V, Battista C, Muscarella LA, Bisceglia M, de Martino D, Baorda F, et al. CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors: clinical correlations in a single-centre patient cohort. Cell Oncol (Dordr). 2012 Dec. 35(6):411-22. [Medline].
Howell VM, Gill A, Clarkson A, Nelson AE, Dunne R, Delbridge LW, et al. Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma. J Clin Endocrinol Metab. 2009 Feb. 94(2):434-41. [Medline].
Erovic BM, Harris L, Jamali M, Goldstein DP, Irish JC, Asa SL, et al. Biomarkers of parathyroid carcinoma. Endocr Pathol. 2012 Dec. 23(4):221-31. [Medline].
Fang SH, Lal G. Parathyroid cancer. Endocr Pract. 2011 Mar-Apr. 17 Suppl 1:36-43. [Medline].
Schulte KM, Gill AJ, Barczynski M, Karakas E, Miyauchi A, Knoefel WT, et al. Classification of parathyroid cancer. Ann Surg Oncol. 2012 Aug. 19(8):2620-8. [Medline].
Schulte KM, Talat N, Miell J, Moniz C, Sinha P, Diaz-Cano S. Lymph node involvement and surgical approach in parathyroid cancer. World J Surg. 2010 Nov. 34(11):2611-20. [Medline].
Harari A, Waring A, Fernandez-Ranvier G, Hwang J, Suh I, Mitmaker E, et al. Parathyroid carcinoma: a 43-year outcome and survival analysis. J Clin Endocrinol Metab. 2011 Dec. 96(12):3679-86. [Medline].
Bergero N, De Pompa R, Sacerdote C. Galectin-3 expression in parathyroid carcinoma: immunohistochemical study of 26 cases. Hum Pathol. 2005 Aug. 36(8):908-14.
Cetani F, Ambrogini E, Viacava P, Pardi E, Fanelli G, Naccarato AG, et al. Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma?. Eur J Endocrinol. 2007 May. 156(5):547-54. [Medline].
DeLellis RA. Parathyroid carcinoma: an overview. Adv Anat Pathol. 2005 Mar. 12(2):53-61.
Fernandez-Ranvier GG, Jensen K, Khanafshar E, Quivey JM, Glastonbury C, Kebebew E, et al. Nonfunctioning parathyroid carcinoma: case report and review of literature. Endocr Pract. 2007 Nov-Dec. 13(7):750-7. [Medline].
Hunt JL, Carty SE, Yim JH. Allelic loss in parathyroid neoplasia can help characterize malignancy. Am J Surg Pathol. 2005 Aug. 29(8):1049-55.
Iacobone M, Lumachi F, Favia G. Up-to-date on parathyroid carcinoma: analysis of an experience of 19 cases. J Surg Oncol. 2004 Dec 15. 88(4):223-8. [Medline].
Iihara M, Okamoto T, Suzuki R, Kawamata A, Nishikawa T, Kobayashi M, et al. Functional parathyroid carcinoma: Long-term treatment outcome and risk factor analysis. Surgery. 2007 Dec. 142(6):936-43; discussion 943.e1. [Medline].
Kleinpeter KP, Lovato JF, Clark PB. Is parathyroid carcinoma indeed a lethal disease?. Ann Surg Oncol. 2005 Mar. 12(3):260-6.
Lin L, Czapiga M, Nini L, Zhang JH, Simonds WF. Nuclear localization of the parafibromin tumor suppressor protein implicated in the hyperparathyroidism-jaw tumor syndrome enhances its proapoptotic function. Mol Cancer Res. 2007 Feb. 5(2):183-93. [Medline].
Lumachi F, Basso SM, Basso U. Parathyroid cancer: etiology, clinical presentation and treatment. Anticancer Res. 2006 Nov-Dec. 26(6C):4803-7. [Medline].
Obara T, Fujimoto Y. Diagnosis and treatment of patients with parathyroid carcinoma: an update and review. World J Surg. 1991 Nov-Dec. 15(6):738-44. [Medline].
Rodgers SE, Perrier ND. Parathyroid carcinoma. Curr Opin Oncol. 2006 Jan. 18(1):16-22.
Sandelin K, Thompson NW, Bondeson L. Metastatic parathyroid carcinoma: dilemmas in management. Surgery. 1991 Dec. 110(6):978-86; discussion 986-8. [Medline].
Sandelin K, Tullgren O, Farnebo LO. Clinical course of metastatic parathyroid cancer. World J Surg. 1994 Jul-Aug. 18(4):594-8; discussion 599. [Medline].
van Heerden JA, Weiland LH, ReMine WH, Walls JT, Purnell DC. Cancer of the parathyroid glands. Arch Surg. 1979 Apr. 114(4):475-80. [Medline].
Vetto JT, Brennan MF, Woodruf J. Parathyroid carcinoma: diagnosis and clinical history. Surgery. 1993 Nov. 114(5):882-92. [Medline].
Yart A, Gstaiger M, Wirbelauer C. The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II. Mol Cell Biol. 2005 Jun. 25(12):5052-60.
Fountas A, Andrikoula M, Giotaki Z, Limniati C, Tsakiridou E, Tigas S, et al. The emerging role of denosumab in the long-term management of parathyroid carcinoma-related refractory hypercalcemia. Endocr Pract. 2015 May. 21 (5):468-73. [Medline].
Jumpertz von Schwartzenberg R, Elbelt U, Ventz M, Mai K, Kienitz T, Maurer L, et al. Palliative treatment of uncontrollable hypercalcemia due to parathyrotoxicosis: denosumab as rescue therapy. Endocrinol Diabetes Metab Case Rep. 2015. 2015:150082. [Medline].