Treatment of Parathyroid Cancer: Current Status and Near-Term Prospects
- Authors: Kim E.I.1, Krupinova J.A.1, Belousov P.V.1, Trutneva K.А.1, Mokrysheva N.G.1
-
Affiliations:
- Endocrinology Research Centre
- Issue: Vol 77, No 5 (2022)
- Pages: 362-370
- Section: ENDOCRINOLOGY: CURRENT ISSUES
- URL: https://vestnikramn.spr-journal.ru/jour/article/view/2132
- DOI: https://doi.org/10.15690/vramn2132
Cite item
Abstract
Parathyroid cancer (PС) is a rare malignant neoplasm of the endocrine system, characterized by a severe course due to the development of life-threatening hypercalcemia. Despite a relatively high survival rate, recurrence occurs about half the time. The aggressive course of PС is associated with both local spread of the process and distant metastasis. With the exception of isolated cases, cytotoxic chemo- and radiotherapy are inefficacious, and treatment protocols have not been developed. Therefore the only effective way is the surgical removal of secondary lesions, which is not always technically feasible and is associated with a high risk of postoperative complications. The literature describes individual cases of successful use of targeted therapy, as well as immunotherapy in the form of therapeutic vaccination to induce an immune response against parathyroid hormone (PTH) and block immune checkpoint. A promising direction of study is the tumor immunoenvironment, which has both diagnostic and prognostic value in relation to the likelihood of the spread of the tumor process. In this review, we describe the main directions in the treatment of PC, including disseminated forms, the possibilities of immunotherapy will be considered in details.
Keywords
Full Text

About the authors
Ekaterina I. Kim
Endocrinology Research Centre
Author for correspondence.
Email: kat-alex2007@mail.ru
ORCID iD: 0000-0001-7879-8495
SPIN-code: 1628-2139
MD, PhD Student
Russian Federation, MoscowJulia A. Krupinova
Endocrinology Research Centre
Email: j.krupinova@gmail.com
ORCID iD: 0000-0001-7963-5022
SPIN-code: 6279-8247
MD, PhD
Russian Federation, MoscowPavel V. Belousov
Endocrinology Research Centre
Email: belousp@gmail.com
ORCID iD: 0000-0002-8216-517X
SPIN-code: 5531-6435
Senior Research Associate
Russian Federation, MoscowKseniya А. Trutneva
Endocrinology Research Centre
Email: trutneva-k@mail.ru
ORCID iD: 0000-0003-4748-6362
Researcher, PhD in Biology
Russian Federation, MoscowNatalya G. Mokrysheva
Endocrinology Research Centre
Email: mokrisheva.natalia@endocrincentr.ru
ORCID iD: 0000-0002-9717-9742
SPIN-code: 5624-3875
MD, PhD, Professor
Russian Federation, MoscowReferences
- 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):538–544. doi: https://doi.org/10.1002/(SICI)1097-0142(19990801)86:3<538::AID-CNCR25>3.0.CO;2-k
- 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):1736–1741. doi: https://doi.org/10.1002/cncr.22599
- Fraser WD. Hyperparathyroidism. Lancet. 2009;374(9684):145–158. doi: https://doi.org/10.1016/S0140-6736(09)60507-9
- Obregón LM, Taylor MF, Mir G, et al. Parathyroidectomy for parathyroid carcinoma in renal transplantation. Transplant Proc. 2005;37(2):973–976. doi: https://doi.org/10.1016/j.transproceed.2004.12.305
- Machado NN, Wilhelm SM. Parathyroid cancer: A review. Cancers (Basel). 2019;11(11):1676. doi: https://doi.org/10.3390/cancers11111676
- Ryhänen EM, Leijon H, Metso S, et al. A nationwide study on parathyroid carcinoma. Acta Oncol. 2017;56(7):991–1003. doi: https://doi.org/10.1080/0284186X.2017.1306103
- Brown S, O’Neill C, Suliburk J, et al. Parathyroid carcinoma: Increasing incidence and changing presentation. ANZ J Surg. 2011;81(7–8):528–532. doi: https://doi.org/10.1111/j.1445-2197.2010.05594.x
- Van der Zwan JM, Mallone S, van Dijk B, et al. Carcinoma of endocrine organs : Results of the RARECARE project. Eur J Cancel. 2012;48(13):1923–1931. doi: https://doi.org/10.1016/j.ejca.2012.01.029
- Sadler C, Gow KW, Beierle EA, et al. Parathyroid carcinoma in more than 1,000 patients: A population-level analysis. Surgery. 2014;156(6):1622–1630. doi: https://doi.org/10.1016/j.surg.2014.08.069
- Sandelin K, Auer G, Bondeson L, et al. Prognostic factors in parathyroid cancer: A review of 95 cases. World J Surg. 1992;16(4):724–731. doi: https://doi.org/10.1007/BF02067369
- Busaidy NL, Jimenez C, Habra MA, et al. Parathyroid carcinoma: A 22-year experience. Head Neck. 2004;26(8):716–726. doi: https://doi.org/10.1002/hed.20049
- Iacobone M, Lumachi F, Favia G. Up-to-date on parathyroid carcinoma: Analysis of an experience of 19 cases. J Surg Oncol. 2004;88(4):223–228. doi: https://doi.org/10.1002/jso.20152
- Rodrigo JP, Hernandez-Prera JC, Randolph GW, et al. Parathyroid cancer : An update. Cancer Treat Rev. 2020;86:102012. doi: https://doi.org/10.1016/j.ctrv.2020.102012
- Kebebew E. Parathyroid carcinoma. Curr Treat Options Oncol. 2001;2(4):347–354. doi: https://doi.org/10.1007/s11864-001-0028-2
- Shifrin A, LiVolsi V, Shifrin-Douglas S, et al. Primary and metastatic parathyroid malignancies: A rare or underdiagnosed condition? J Clin Endocrinol Metab. 2015;100(3):E478–E481. doi: https://doi.org/10.1210/jc.2014-2760
- Salcuni AS, Cetani F, Guarnieri V, et al. Parathyroid carcinoma. Best Pract Res Clin Endocrinol Metab. 2018;32(6):877–889. doi: https://doi.org/10.1016/j.beem.2018.11.002
- Erickson LA, Mete O, Juhlin CC, et al. Overview of the 2022 WHO Classification of Parathyroid Tumors. Endocr Pathol. 2022;33(1):64–89. doi: https://doi.org/10.1007/s12022-022-09709-1
- Cetani F, Marcocci C, Torregrossa L, et al. Atypical parathyroid adenomas: challenging lesions in the differential diagnosis of endocrine tumors. Endocr Relat Cancer. 2019;26(7):R441–R464. doi: https://doi.org/10.1530/ERC-19-0135
- Erickson LA, Mete O. Immunohistochemistry in Diagnostic Parathyroid Pathology. Endocr Pathol. 2018;29(2):113–129. doi: https://doi.org/10.1007/s12022-018-9527-6
- Juhlin CC, Nilsson IL, Lagerstedt-Robinson K, et al. Parafibromin immunostainings of parathyroid tumors in clinical routine: a near-decade experience from a tertiary center. Mod Pathol. 2019;32(8):1082–1094. doi: https://doi.org/10.1038/s41379-019-0252-6
- Xue S, Chen H, Lv C, et al. Preoperative diagnosis and prognosis in 40 Parathyroid Carcinoma Patients. Clin Endocrinol (Oxf). 2016;85(1):29–36. doi: https://doi.org/10.1111/cen.13055
- Asare EA, Sturgeon C, Winchester DJ, 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):3990–3995. doi: https://doi.org/10.1245/s10434-015-4672
- Hsu KT, Sippel RS, Chen H, et al. Is central lymph node dissection necessary for parathyroid carcinoma? Surgery. 2014;156(6):1336–1341. doi: https://doi.org/10.1016/j.surg.2014.08.005
- Perrier ND, Arnold A, Costa-Guda J, et al. Hereditary endocrine tumours: Current state-of-the-art and research opportunities: New and future perspectives for parathyroid carcinoma. Endocr Relat Cancer. 2020;27(8):T53–T63. doi: https://doi.org/10.1530/ERC-20-0018
- Lenschow C, Schrägle S, Kircher S, et al. Clinical Presentation, Treatment, and Outcome of Parathyroid Carcinoma: Results of the NEKAR Retrospective International Multicenter Study. Ann Surg. 2022;275(2):e479–e487. doi: https://doi.org/10.1097/SLA.0000000000004144
- Leonard-Murali S, Ivanics T, Kwon DS, et al. Local resection versus radical surgery for parathyroid carcinoma: A National Cancer Database analysis. Eur J Surg Oncol. 2021;47(11):2768–2773. doi: https://doi.org/10.1016/j.ejso.2021.06.026
- Shane E. Clinical review 122: Parathyroid Carcinoma. J Clin Endocrinol Metab. 2001;86(2):485–493. doi: https://doi.org/10.1210/jcem.86.2.7207
- Cetani F, Pardi E, Marcocci C. Update on parathyroid carcinoma. J Endocrinol Invest. 2016;39(6):595–606. doi: https://doi.org/10.1007/s40618-016-0447-3
- Storvall S, Ryhänen E, Bensch FV, et al. Recurrent Metastasized Parathyroid Carcinoma-Long-Term Remission after Combined Treatments with Surgery, Radiotherapy, Cinacalcet, Zoledronic Acid, and Temozolomide. JBMR Plus. 2019;3(4):e10114. doi: https://doi.org/10.1002/jbm4.10114
- Christakis I, Silva AM, Williams MD, et al. Postoperative local-regional radiation therapy in the treatment of parathyroid carcinoma: The MD Anderson experience of 35 years. Pract Radiat Oncol. 2017;7(6):e463–e470. doi: https://doi.org/10.1016/j.prro.2017.05.009
- Erovic BM, Goldstein DP, Kim D, et al. Parathyroid cancer: Outcome analysis of 16 patients treated at the princess margaret hospital. Head Neck. 2013;35(1):35–39. doi: https://doi.org/10.1002/hed.22908
- Calandra DB, Chejfec G, Foy BK, et al. Parathyroid carcinoma: biochemical and pathologic response to DTIC. Surgery. 1984;96(6):1132–1137.
- Bukowski RM, Sheeler L, Cunningham J, et al. Successful Combination Chemotherapy for Metastatic Parathyroid Carcinoma. Arch Intern Med. 1984;144(2):399–400. doi: https://doi.org/10.1001/archinte.1984.00350140229032
- 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):80–84. doi: https://doi.org/10.1097/00000441-198109000-00005
- DasGupta R, Shetty S, Keshava SN, et al. Metastatic parathyroid carcinoma treated with radiofrequency ablation: A novel therapeutic modality. Australas Med J. 2014;7(9):372–375. doi: https://doi.org/10.4066/AMJ.2014.2084
- Singh RR, Patel KP, Routbort MJ, et al. Clinical validation of a next-generation sequencing screen for mutational hotspots in 46 cancer-related genes. J Mol Diagn. 2013;15(5):607–622. doi: https://doi.org/10.1016/j.jmoldx.2013.05.003
- Kutahyalioglu M, Nguyen HT, Kwatampora L, et al. Genetic profiling as a clinical tool in advanced parathyroid carcinoma. J Cancer Res Clin Oncol. 2019;145(8):1977–1986. doi: https://doi.org/10.1007/s00432-019-02945-9
- Knudson AG. Two genetic hits (more or less) to cancer. Nat Rev Cancer. 2001;1(2):157–162. doi: https://doi.org/10.1038/35101031
- Hsieh JJ, Chen D, Wang PI, et al. Genomic Biomarkers of a Randomized Trial Comparing First-Line Everolimus and Sunitinib in Patients with Metastatic Renal Cell Carcinoma. Eur Urol. 2017;71(3):405–414. doi: https://doi.org/10.1016/j.eururo.2016.10.007
- Rozhinskaya L, Pigarova E, Sabanova E, et al. Diagnosis and treatment challenges of parathyroid carcinoma in a 27-year-old woman with multiple lung metastases. Endocrinol Diabetes Metab Case Rep. 2017;2017:16-0113. doi: https://doi.org/10.1530/EDM-16-0113
- Schott M, Feldkamp J, Schaltenberg D, et al. Dendritic cell immune-therapy in disseminated parathyroid carcinoma. Lancet. 1999;353(9159):1188–1189. doi: https://doi.org/10.1016/S0140-6736(05)74412-3
- Bradwell AR, Harvey TC. Control of hypercalcaemia of parathyroid carcinoma by immunisation. Lancet. 1999;353(9150):370–373. doi: https://doi.org/10.1016/S0140-6736(98)06469-1
- 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):3413–3420. doi: https://doi.org/10.1210/jc.2003-031911
- Sarquis M, Marx SJ, Beckers A, et al. Long-term remission of disseminated parathyroid cancer following immunotherapy. Endocrine. 2020;67(1):204–208. doi: https://doi.org/10.1007/s12020-019-02136-z
- Dudley JC, Lin M-T, Le DT, et al. Microsatellite Instability as a Biomarker for PD-1 Blockade. Clin Cancer Res. 2016;22(4):813–820. doi: https://doi.org/10.1158/1078-0432.CCR-15-1678
- Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012;24(2):207–212. doi: https://doi.org/10.1016/j.coi.2011.12.009
- Hino R, Kabashima K, Kato Y, et al. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer. 2010;116(7):1757–1766. doi: https://doi.org/10.1002/cncr.24899
- Cancer Research Institute. Timeline of progress. Available from: https://www.cancerresearch.org/immunotherapy/timeline-of-progress (accessed: 22.09.2019).
- Park D, Airi R, Sherman M. Microsatellite instability driven metastatic parathyroid carcinoma managed with the anti-PD1 immunotherapy, pembrolizumab. BMJ Case Rep. 2020;13(9):e235293. doi: https://doi.org/10.1136/bcr-2020-235293
- Lenschow C, Fuss CT, Kircher S, et al. Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management. Front Endocrinol (Lausanne). 2021;12:643328. doi: https://doi.org/10.3389/fendo.2021.643328
- Galon J, Lanzi A. Immunoscore and its introduction in clinical practice. Q J Nucl Med Mol Imaging. 2020;64(2):152–161. doi: https://doi.org/10.23736/S1824-4785.20.03249-5
- Hu Y, Cui M, Bi Y, et al. Immunocyte density in parathyroid carcinoma is correlated with disease relapse. J Endocrinol Invest. 2020;43(10):1453–1461. doi: https://doi.org/10.1007/s40618-020-01224-6
- Mirrakhimov A.E. Hypercalcemia of Malignancy: An Update on Pathogenesis and Management. N Am J Med Sci. 2015;7(11):483–493. doi: https://doi.org/10.4103/1947-2714.170600
- Hu MI, Glezerman IG, Leboulleux S, et al. Denosumab for treatment of hypercalcemia of malignancy. J Clin Endocrinol Metab. 2014;99(9):3144–3152. doi: https://doi.org/10.1210/jc.2014-1001
- 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):3803–3808. doi: https://doi.org/10.1210/jc.2007-0585
- Koyano H, Shishiba Y, Shimizu T, et al. Successful Treatment by Surgical Removal of Bone Metastasis Producing PTH: New Approach to the Management of Metastatic Parathyroid Carcinoma. Intern Med. 1994;33(11):697–702. doi: https://doi.org/10.2169/internalmedicine.33.697
- Iguchi T, Yasui K, Hiraki T, et al. Radiofrequency ablation of functioning lung metastases from parathyroid carcinoma. J Vasc Interv Radiol. 2008;19(3):462–464. doi: https://doi.org/10.1016/j.jvir.2007.12.440
- 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):657–659. doi: https://doi.org/10.1007/s00270-009-9730-4
- Artinyan A, Guzman E, Maghami E, et al. Metastatic parathyroid carcinoma to the liver treated with radiofrequency ablation and transcatheter arterial embolization. J Clin Oncol. 2008;26(24):4039–4041. doi: https://doi.org/10.1200/JCO.2007.15.9038
- 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):707–711. doi: https://doi.org/10.1590/s0004-27302008000400019
Supplementary files
There are no supplementary files to display.
