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Long-Term Outcomes of Parathyroidectomy in Hyperparathyroidism-Jaw Tumor Syndrome: Analysis of Five Families with CDC73 Mutations

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Abstract

Background

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare disease caused by CDC73 germline mutations, with familial primary hyperparathyroidism (pHPT), ossifying jaw tumors, genito-urinary neoplasms. The present study was aimed at determining the long-term postoperative outcome of parathyroidectomy in HPT-JT.

Methods

A retrospective analysis of a single-center series of 20 patients from five unrelated HPT-JT families undergoing parathyroid surgery was performed.

Results

Pathology confirmed a single-gland involvement in 95% of cases at onset. Parathyroid carcinoma occurred in three patients undergoing en-bloc parathyroidectomy and thyroid lobectomy: parathyroid benign lesions in 17 patients undergoing subtotal parathyroidectomy for evident multiglandular involvement (n = 1) or selective parathyroidectomy for single-gland involvement (n = 16), during bilateral (n = 13) or targeted unilateral neck exploration (n = 7). At a median overall follow-up of 16 years (range 2.5–42), patients with parathyroid carcinoma had a persistent/recurrent disease in 66.6%; patients with benign lesions had recurrent pHPT in 23.5% after a prolonged disease-free period; recurrent benign pHPT occurred slightly more often in cases of discordant preoperative localization (60% vs 9%; p = 0.06).

Conclusion

pHPT in HPT-JT is generally characterized by a benign and single-gland involvement, with a relatively increased risk of malignancy (15%). Parathyroid carcinoma needs extensive surgery because of high risk of permanent/recurrent disease (66.6%). In benign involvement, targeted unilateral exploration with selective parathyroidectomy may be effective in cases of concordant single-gland localization at preoperative localization imaging techniques. Bilateral neck exploration with subtotal parathyroidectomy might be preferred in cases of negative or discordant preoperative localization, because of the increased risk of multiglandular involvement and long-term recurrences (23.5%).

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References

  1. Carling T, Udelsman R (2005) Parathyroid surgery in familial hyperparathyroid disorders. J Intern Med 257:27–37

    Article  CAS  Google Scholar 

  2. Bradley KJ, Hobbs MR, Buley ID et al (2005) Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome. J Intern Med 257:18–26

    Article  CAS  Google Scholar 

  3. Iacobone M, Barzon L, Porzionato A et al (2007) Parafibromin expression, single-gland involvement, and limited parathyroidectomy in familial isolated hyperparathyroidism. Surgery 142(6):984–991

    Article  Google Scholar 

  4. Iacobone M, Masi G, Barzon L et al (2009) Hyperparathyroidism jaw tumor syndrome: a report of three large kindred. Langenbecks Arch Surg 394:817–825

    Article  Google Scholar 

  5. Masi G, Barzon L, Iacobone M et al (2008) Clinical, genetic, and histopathologic investigation of CDC73-related familial hyperparathyroidism. Endocr Relat Cancer 15:1115–1126

    Article  CAS  Google Scholar 

  6. Masi G, Iacobone M, Sinigaglia A et al (2014) Characterization of a new CDC73 missense mutation that impairs Parafibromin expression and nucleolar localization. PLoS One 9(5):e97994

    Article  Google Scholar 

  7. Iacobone M, Barzon L, Porzionato A et al (2009) The extent of parathyroidectomy for HRPT2-related hyperparathyroidism. Surgery 145:250–251

    Article  Google Scholar 

  8. Sarquis MS, Silveira LG, Pimenta FJ et al (2008) Familial hyperparathyroidism: surgical outcome after 30 years of follow up in three families with germline HRPT2 mutations. Surgery 143:630–640

    Article  Google Scholar 

  9. Mehta A, Patel D, Rosenberg A et al (2014) Hyperparathyroidism-jaw tumor syndrome: results of operative management. Surgery 156:1315–1325

    Article  Google Scholar 

  10. Li Y, Simonds WF (2015) Endocrine neoplasms in familial syndromes of hyperparathyroidism. Endocr Relat Cancer 23(6):R229–R247

    Article  Google Scholar 

  11. Lloyd RV, Osamura RY, Klőpper G, Rosai J (2017) WHO classification of tumours of endocrine organs, 4th edn. IARC Press, Lyon

    Google Scholar 

  12. Iacobone M, Lumachi F, Favia G (2004) Up-to-date on parathyroid carcinoma: analysis of an experience of 19 cases. J Surg Oncol 88:223–228

    Article  Google Scholar 

  13. Iacobone M, Ruffolo C, Lumachi F, Favia G (2005) Results of iterative surgery for persistent and recurrent parathyroid carcinoma. Langenbecks Arch Surg 390:385–390

    Article  Google Scholar 

  14. Iacobone M, Carnaille B, Palazzo F, Vriens M (2015) Hereditary hyperparathyroidism—a consensus report of the European Society of Endocrine Surgeons (ESES). Langenbecks Arch Surg 400:867–886

    Article  Google Scholar 

  15. Carpten JD, Robbins CM, Villablanca A et al (2002) HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet 32:676–680

    Article  CAS  Google Scholar 

  16. Shattuck TM, Valimaki S, Obara T et al (2003) Somatic and germline mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med 349:1722–1729

    Article  CAS  Google Scholar 

  17. Howell VM, Haven CJ, Kahnoski K et al (2003) HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. J Med Genet 40:657–663

    Article  CAS  Google Scholar 

  18. Bradley KJ, Cavaco BM, Bowl MR et al (2006) Parafibromin mutations in hereditary hyperparathyroidism syndromes and parathyroid tumours. Clin Endocrinol (Oxf) 64(3):299–306

    Article  CAS  Google Scholar 

  19. Juhlin C, Larsson C, Yakoleva T et al (2006) Loss of parafibromin expression in a subset of parathyroid adenomas. Endocr Relat Cancer 13:509–523

    Article  CAS  Google Scholar 

  20. Guarnieri V, Scillitani A, Muscarella LA et al (2006) Diagnosis of parathyroid tumors in familial isolated hyperparathyroidism with HRPT2 mutation: implications for cancer surveillance. J Clin Endocrinol Metab 91:2827–2832

    Article  CAS  Google Scholar 

  21. Porzionato A, Macchi V, Barzon L et al (2006) Immunohistochemical assessment of parafibromin in mouse and human tissues. J Anat 209:817–827

    Article  CAS  Google Scholar 

Download references

Funding

The study was supported by a Grant from University of Padua to Maurizio Iacobone (BIRD172205).

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Authors and Affiliations

  1. Endocrine Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, 35128, Padua, Italy

    Maurizio Iacobone, Costantino Pagetta, Eric Casal Ide & Francesca Torresan

  2. Endocrinogy Unit, Department of Medicine, University of Padua, Via Giustiniani 2, 35128, Padua, Italy

    Valentina Camozzi & Caterina Mian

  3. Pathology Unit, Department of Medicine, University of Padua, Via Giustiniani 2, 35128, Padua, Italy

    Gianmaria Pennelli

  4. Department of Molecular Medicine, University of Padua, Via Gabelli 63, 35128, Padua, Italy

    Giulia Masi

  5. Familial Tumor Unit, Veneto Institute of Oncology, (IOV)-IRCCS, Via Gattamelata, 64, 35128, Padua, Italy

    Stefania Zovato

Authors
  1. Maurizio Iacobone
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  2. Valentina Camozzi
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  3. Caterina Mian
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  4. Gianmaria Pennelli
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  5. Costantino Pagetta
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  6. Eric Casal Ide
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  7. Giulia Masi
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  8. Stefania Zovato
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  9. Francesca Torresan
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Corresponding author

Correspondence to Maurizio Iacobone.

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The authors declare that they have no conflict of interest.

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The study has been approved by the Institution review board.

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Informed consent was obtained from all individual participants included in the study.

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Iacobone, M., Camozzi, V., Mian, C. et al. Long-Term Outcomes of Parathyroidectomy in Hyperparathyroidism-Jaw Tumor Syndrome: Analysis of Five Families with CDC73 Mutations. World J Surg 44, 508–516 (2020). https://doi.org/10.1007/s00268-019-05156-y

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  • DOI: https://doi.org/10.1007/s00268-019-05156-y

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