Skip to main content
Top
Published in: Annals of Surgical Oncology 9/2016

01-09-2016 | Endocrine Tumors

Differentiating Atypical Parathyroid Neoplasm from Parathyroid Cancer

Authors: Ioannis Christakis, MD, PhD, Naifa Bussaidy, MD, Callisia Clarke, MD, Lily Joy Kwatampora, MD, Carla L. Warneke, MD, Angelica M. Silva, MD, Michelle D. Williams, MD, Elizabeth Gardner Grubbs, MD, Jeffrey E. Lee, MD, Nancy D. Perrier, MD, FACS

Published in: Annals of Surgical Oncology | Issue 9/2016

Login to get access

Abstract

Introduction

The differentiation of benign parathyroid gland atypia and true parathyroid carcinoma (PC) can be challenging. In some instances, patients are classified as having ‘atypical parathyroid neoplasms’ (APNs), explicitly acknowledging that the distinction between benign and malignant disease appears impossible to determine. This ‘grey area’ diagnosis makes rendering an accurate prognosis difficult, and clouds clinical management and treatment planning.

Methods

We performed a retrospective chart review of all patients undergoing operation for primary hyperparathyroidism in our institution (2000–2014). Patients with a histopathological diagnosis of PC or APN were included. Demographics, clinical characteristics, and survival rates were analyzed, and analysis was conducted using SAS 9.4 (SAS Institute, Inc., Cary, NC, USA).

Results

Fifty-four patients were included in the study—31 (57.41 %) with PC and 23 (42.59 %) with APN. PC versus APN was associated with higher parathyroid hormone (PTH) (p = 0.005) and with males (p = 0.002). Five-year overall survival (OS) from diagnosis was 82.64 % [95 % confidence interval (CI) 59.82–93.17] for the PC group and 93.33 % (95 % CI 61.26–99.03) for the APN group, while the 5-year recurrence-free survival rate was 59.63 % (95 % CI 36.32–76.81) in the PC group and 90.91 % (95 % CI 50.81–98.67) in the APN group.

Conclusion

PC and APN are distinct clinical entities with differences in tumor biology reflected in overall recurrence rates, disease-free survival, and OS. APNs present with a less accentuated biochemical profile and demonstrate an indolent clinical course compared with PCs. Efforts to improve categorization and staging of PC and APN are needed.
Appendix
Available only for authorised users
Literature
2.
go back to reference Mazeh H, Sippel RS, Chen H. The role of gender in primary hyperparathyroidism: same disease, different presentation. Ann Surg Oncol. 2012;19(9):2958–962.CrossRefPubMed Mazeh H, Sippel RS, Chen H. The role of gender in primary hyperparathyroidism: same disease, different presentation. Ann Surg Oncol. 2012;19(9):2958–962.CrossRefPubMed
3.
go back to reference Clark OH. How should patients with primary hyperparathyroidism be treated? J Clin Endocrinol Metab. 2003;88(7):3011–014.CrossRefPubMed Clark OH. How should patients with primary hyperparathyroidism be treated? J Clin Endocrinol Metab. 2003;88(7):3011–014.CrossRefPubMed
4.
go back to reference Mohebati A, Shaha A, Shah J. Parathyroid carcinoma: challenges in diagnosis and treatment. Hematol Oncol Clin North Am. 2012;26(6):1221–38.CrossRefPubMed Mohebati A, Shaha A, Shah J. Parathyroid carcinoma: challenges in diagnosis and treatment. Hematol Oncol Clin North Am. 2012;26(6):1221–38.CrossRefPubMed
5.
go back to reference Wang CA, Gaz RD. Natural history of parathyroid carcinoma. Diagnosis, treatment, and results. Am J Surg. 1985;149(4):522–27.CrossRefPubMed Wang CA, Gaz RD. Natural history of parathyroid carcinoma. Diagnosis, treatment, and results. Am J Surg. 1985;149(4):522–27.CrossRefPubMed
6.
go back to reference Obara T, Fujimoto Y. Diagnosis and treatment of patients with parathyroid carcinoma: an update and review. World J Surg. 1991;15(6):738–44.CrossRefPubMed Obara T, Fujimoto Y. Diagnosis and treatment of patients with parathyroid carcinoma: an update and review. World J Surg. 1991;15(6):738–44.CrossRefPubMed
7.
go back to reference Schulte KM, Gill AJ, Barczynski M, et al. Classification of parathyroid cancer. Ann Surg Oncol. 2012;19(8):2620–28.CrossRefPubMed Schulte KM, Gill AJ, Barczynski M, et al. Classification of parathyroid cancer. Ann Surg Oncol. 2012;19(8):2620–28.CrossRefPubMed
8.
9.
go back to reference Wynne AG, van Heerden J, Carney JA, Fitzpatrick LA. Parathyroid carcinoma: clinical and pathologic features in 43 patients. Medicine (Baltimore). 1992;71(4):197–205.CrossRef Wynne AG, van Heerden J, Carney JA, Fitzpatrick LA. Parathyroid carcinoma: clinical and pathologic features in 43 patients. Medicine (Baltimore). 1992;71(4):197–205.CrossRef
10.
go back to reference Kebebew E, Arici C, Duh QY, Clark OH. Localization and reoperation results for persistent and recurrent parathyroid carcinoma. Arch Surg. 2001;136(8):878–85.CrossRefPubMed Kebebew E, Arici C, Duh QY, Clark OH. Localization and reoperation results for persistent and recurrent parathyroid carcinoma. Arch Surg. 2001;136(8):878–85.CrossRefPubMed
11.
go back to reference Hakaim AG, Esselstyn CB, Jr. Parathyroid carcinoma: 50-year experience at The Cleveland Clinic Foundation. Cleve Clin J Med. 1993;60(4):331–5.CrossRefPubMed Hakaim AG, Esselstyn CB, Jr. Parathyroid carcinoma: 50-year experience at The Cleveland Clinic Foundation. Cleve Clin J Med. 1993;60(4):331–5.CrossRefPubMed
12.
go back to reference 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):3990–5.CrossRefPubMed 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):3990–5.CrossRefPubMed
13.
go back to reference Quinn CE, Healy J, Lebastchi AH, et al. Modern experience with aggressive parathyroid tumors in a high-volume New England referral center. J Am Coll Surg. 2015;220(6):1054–62.CrossRefPubMed Quinn CE, Healy J, Lebastchi AH, et al. Modern experience with aggressive parathyroid tumors in a high-volume New England referral center. J Am Coll Surg. 2015;220(6):1054–62.CrossRefPubMed
14.
go back to reference Ippolito G, Palazzo FF, Sebag F, De Micco C, Henry JF. Intraoperative diagnosis and treatment of parathyroid cancer and atypical parathyroid adenoma. Br J Surg. 2007;94(5):566–70.CrossRefPubMed Ippolito G, Palazzo FF, Sebag F, De Micco C, Henry JF. Intraoperative diagnosis and treatment of parathyroid cancer and atypical parathyroid adenoma. Br J Surg. 2007;94(5):566–70.CrossRefPubMed
15.
go back to reference Fernandez-Ranvier GG, Khanafshar E, Jensen K, et al. Parathyroid carcinoma, atypical parathyroid adenoma, or parathyromatosis? Cancer. 2007;110(2):255–64.CrossRefPubMed Fernandez-Ranvier GG, Khanafshar E, Jensen K, et al. Parathyroid carcinoma, atypical parathyroid adenoma, or parathyromatosis? Cancer. 2007;110(2):255–64.CrossRefPubMed
16.
go back to reference Kruijff S, Sidhu SB, Sywak MS, Gill AJ, Delbridge LW. Negative parafibromin staining predicts malignant behavior in atypical parathyroid adenomas. Ann Surg Oncol. 2014;21(2):426–33.CrossRefPubMed Kruijff S, Sidhu SB, Sywak MS, Gill AJ, Delbridge LW. Negative parafibromin staining predicts malignant behavior in atypical parathyroid adenomas. Ann Surg Oncol. 2014;21(2):426–33.CrossRefPubMed
17.
go back to reference McCoy KL, Seethala RR, Armstrong MJ, et al. The clinical importance of parathyroid atypia: is long-term surveillance necessary? Surgery. 2015;158(4):929–35; discussion 935–926.CrossRefPubMed McCoy KL, Seethala RR, Armstrong MJ, et al. The clinical importance of parathyroid atypia: is long-term surveillance necessary? Surgery. 2015;158(4):929–35; discussion 935–926.CrossRefPubMed
18.
go back to reference Villar-del-Moral J, Jimenez-Garcia A, Salvador-Egea P, et al. Prognostic factors and staging systems in parathyroid cancer: a multicenter cohort study. Surgery. 2014;156(5):1132–44.CrossRefPubMed Villar-del-Moral J, Jimenez-Garcia A, Salvador-Egea P, et al. Prognostic factors and staging systems in parathyroid cancer: a multicenter cohort study. Surgery. 2014;156(5):1132–44.CrossRefPubMed
19.
go back to reference Stojadinovic A, Hoos A, Nissan A, et al. Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis. Hum Pathol. 2003;34(1):54–64.CrossRefPubMed Stojadinovic A, Hoos A, Nissan A, et al. Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis. Hum Pathol. 2003;34(1):54–64.CrossRefPubMed
20.
go back to reference Chen Q, Kaji H, Nomura R, et al. Trial to predict malignancy of affected parathyroid glands in primary hyperparathyroidism. Endocr J. 2003;50(5):527–34.CrossRefPubMed Chen Q, Kaji H, Nomura R, et al. Trial to predict malignancy of affected parathyroid glands in primary hyperparathyroidism. Endocr J. 2003;50(5):527–34.CrossRefPubMed
21.
go back to reference Marzouki HZ, Chavannes M, Tamilia M, et al. Location of parathyroid adenomas: 7-year experience. J Otolaryngol Head Neck Surg. 2010;39(5):551–4.PubMed Marzouki HZ, Chavannes M, Tamilia M, et al. Location of parathyroid adenomas: 7-year experience. J Otolaryngol Head Neck Surg. 2010;39(5):551–4.PubMed
22.
go back to reference Moreno MA, Callender GG, Woodburn K, et al. Common locations of parathyroid adenomas. Ann Surg Oncol. 2011;18(4):1047–51.CrossRefPubMed Moreno MA, Callender GG, Woodburn K, et al. Common locations of parathyroid adenomas. Ann Surg Oncol. 2011;18(4):1047–51.CrossRefPubMed
23.
go back to reference Mazeh H, Stoll SJ, Robbins JB, Sippel RS, Chen H. Validation of the “Perrier” parathyroid adenoma location nomenclature. World J Surg. 2012;36(3):612–6.CrossRefPubMed Mazeh H, Stoll SJ, Robbins JB, Sippel RS, Chen H. Validation of the “Perrier” parathyroid adenoma location nomenclature. World J Surg. 2012;36(3):612–6.CrossRefPubMed
24.
go back to reference Debruyne F, Ostyn F, Delaere P. Distribution of the solitary adenoma over the parathyroid glands. J Laryngol Otol. 1997;111(5):459–60.PubMed Debruyne F, Ostyn F, Delaere P. Distribution of the solitary adenoma over the parathyroid glands. J Laryngol Otol. 1997;111(5):459–60.PubMed
25.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
26.
27.
go back to reference Busaidy NL, Jimenez C, Habra MA, et al. Parathyroid carcinoma: a 22-year experience. Head Neck. 2004;26(8):716–26.CrossRefPubMed Busaidy NL, Jimenez C, Habra MA, et al. Parathyroid carcinoma: a 22-year experience. Head Neck. 2004;26(8):716–26.CrossRefPubMed
29.
go back to reference 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;86(3):538–44.CrossRefPubMed 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;86(3):538–44.CrossRefPubMed
30.
go back to reference 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(9):1736–41.CrossRefPubMed 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(9):1736–41.CrossRefPubMed
31.
go back to reference Fountas A, Andrikoula M, Giotaki Z, et al. The emerging role of denosumab in the long-term management of parathyroid carcinoma-related refractory hypercalcemia. Endocr Pract. 2015;21(5):468–73.CrossRefPubMed Fountas A, Andrikoula M, Giotaki Z, et al. The emerging role of denosumab in the long-term management of parathyroid carcinoma-related refractory hypercalcemia. Endocr Pract. 2015;21(5):468–73.CrossRefPubMed
32.
go back to reference Betea D, Potorac I, Beckers A. Parathyroid carcinoma: challenges in diagnosis and treatment. Ann Endocrinol (Paris). 2015;76(2):169–77.CrossRef Betea D, Potorac I, Beckers A. Parathyroid carcinoma: challenges in diagnosis and treatment. Ann Endocrinol (Paris). 2015;76(2):169–77.CrossRef
33.
go back to reference Anderson BJ, Samaan NA, Vassilopoulou-Sellin R, Ordonez NG, Hickey RC. Parathyroid carcinoma: features and difficulties in diagnosis and management. Surgery. 1983;94(6):906–15.PubMed Anderson BJ, Samaan NA, Vassilopoulou-Sellin R, Ordonez NG, Hickey RC. Parathyroid carcinoma: features and difficulties in diagnosis and management. Surgery. 1983;94(6):906–15.PubMed
34.
go back to reference Calandra DB, Chejfec G, Foy BK, Lawrence AM, Paloyan E. Parathyroid carcinoma: biochemical and pathologic response to DTIC. Surgery. 1984;96(6):1132–37.PubMed Calandra DB, Chejfec G, Foy BK, Lawrence AM, Paloyan E. Parathyroid carcinoma: biochemical and pathologic response to DTIC. Surgery. 1984;96(6):1132–37.PubMed
35.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
36.
go back to reference Arima Y, Matsueda S, Yano H, Harada M, Itoh K. Parathyroid hormone-related protein as a common target molecule in specific immunotherapy for a wide variety of tumor types. Int J Oncol. 2005;27(4):981–8.PubMed Arima Y, Matsueda S, Yano H, Harada M, Itoh K. Parathyroid hormone-related protein as a common target molecule in specific immunotherapy for a wide variety of tumor types. Int J Oncol. 2005;27(4):981–8.PubMed
37.
go back to reference Falchetti A, Cavalli L, Cavalli T, et al. Molecular diagnosis of parathyroid carcinoma: a reality in the near future. Expert Opin Med Diagn. 2012;6(1):27–37.CrossRefPubMed Falchetti A, Cavalli L, Cavalli T, et al. Molecular diagnosis of parathyroid carcinoma: a reality in the near future. Expert Opin Med Diagn. 2012;6(1):27–37.CrossRefPubMed
38.
go back to reference Levin KE, Galante M, Clark OH. Parathyroid carcinoma versus parathyroid adenoma in patients with profound hypercalcemia. Surgery. 1987;101(6):649–60.PubMed Levin KE, Galante M, Clark OH. Parathyroid carcinoma versus parathyroid adenoma in patients with profound hypercalcemia. Surgery. 1987;101(6):649–60.PubMed
Metadata
Title
Differentiating Atypical Parathyroid Neoplasm from Parathyroid Cancer
Authors
Ioannis Christakis, MD, PhD
Naifa Bussaidy, MD
Callisia Clarke, MD
Lily Joy Kwatampora, MD
Carla L. Warneke, MD
Angelica M. Silva, MD
Michelle D. Williams, MD
Elizabeth Gardner Grubbs, MD
Jeffrey E. Lee, MD
Nancy D. Perrier, MD, FACS
Publication date
01-09-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 9/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5248-6

Other articles of this Issue 9/2016

Annals of Surgical Oncology 9/2016 Go to the issue