Revisión Integral del Carcinoma Paratiroideo a Propósito de un caso

Revisión Integral del Carcinoma Paratiroideo a Propósito de un caso: Patogénesis, Diagnóstico y Estrategias Terapéuticas

Comprehensive Review of Parathyroid Carcinoma: A Case Report. Pathogenesis, Diagnosis, and Therapeutic Strategies

Almudena Martínez-Pozuelo*, Carmen Sánchez García*, Julia Bernal Tirapo*, Francisco Javier Guadarrama González*,
Pedro Yuste García*

* Unidad de Cirugía Endocrina. Servicio de Cirugía General, Aparato Digestivo y Trasplante de Órganos Abdominales.
     Hospital Universitario 12 de Octubre. Madrid. España.

DOI: https://doi.org/10.14679/5185

Resumen:

Introducción: El carcinoma paratiroideo es una neoplasia endocrina rara de difícil diagnóstico, cuyo único tratamiento curativo es la resección en bloque con márgenes libres, a pesar del cual, presenta una alta tasa de recurrencia, ya que las terapias adyuvantes no son eficaces. Se presenta una revisión de la entidad a partir de un caso clínico.
Caso clínico: Mujer de 48 años diagnosticada de hiperparatiroidismo primario y una masa paratiroidea sospechosa en pruebas de imagen. Se realiza cirugía con resección en bloque, con evolución postoperatoria favorable.
Resultados: El estudio anatomopatológico confirma carcinoma paratiroideo. Tras dos años de seguimiento no se evidencia recidiva.
Discusión: El carcinoma paratiroideo supone el 0,5-1% del hiperparatiroidismo primario y una fracción mínima de los cánceres. Se asocia a factores de riesgo como radiación cervical, enfermedad renal crónica y síndromes hereditarios. Se caracteriza por hipercalcemia severa y elevación marcada de PTH. El diagnóstico preoperatorio es complejo y se basa en hallazgos clínicos, bioquímicos e imagen, aunque la confirmación definitiva es histológica. La inmunohistoquímica ayuda al diagnóstico diferencial. La extirpación en bloque es el único tratamiento curativo, evitando la rotura capsular, lo cual es clave para reducir recurrencias. El control de la hipercalcemia es fundamental, mientras que terapias sistémicas están en investigación para enfermedad avanzada. El seguimiento prolongado es imprescindible debido a la alta tasa de recurrencia.
Conclusión: Carcinoma paratiroideo es infrecuente, asociado a factores de riesgo y con diagnóstico complejo. Provoca hipercalcemia y PTH elevadas. La cirugía en bloque curativa. El control hipercalcemia es esencial. El seguimiento debe ser prolongado por la alta recurrencia.
Palabras Clave: Carcinoma paratiroides, parafibromina, hipercalcemia, diagnóstico, resección en bloque, recurrencia.

Abstract:

Introduction: Parathyroid carcinoma is a rare endocrine neoplasm difficult to diagnose. Its only curative treatment is en bloc resection with clear margins, despite which it has a high recurrence rate, as adjuvant therapies are ineffective. A review of this entity is presented based on a clinical case.
Clinical case: A 48-year-old woman diagnosed with primary hyperparathyroidism and a suspicious parathyroid mass on imaging studies. She underwent surgery with en bloc resection, with a favorable postoperative course.
Results: Histopathological study confirmed parathyroid carcinoma. After two years of follow-up, no recurrence was observed.
Discussion: Parathyroid carcinoma accounts for 0.5-1% of primary hyperparathyroidism and a small fraction of overall cancers. It is associated with risk factors such as cervical radiation, chronic kidney disease, and hereditary syndromes. It is characterized by severe hypercalcemia and marked elevation of PTH. Preoperative diagnosis is complex and based on clinical, biochemical, and imaging findings, although definitive confirmation is histological. Immunohistochemistry aids in differential diagnosis. En bloc resection is the only curative treatment, avoiding capsular rupture, which is key to reducing recurrence. Control of hypercalcemia is essential, while systemic therapies are under investigation for advanced disease. Long-term follow-up is mandatory due to the high recurrence rate.

Key words: Parathyroid carcinoma, parafibromina, hipercalcemia, diagnosis, en bloc resection, recurrence.

Bibliografía

1. 1. 1. Pia Roser, Bianca M Leca, Claudia Coelho, Klaus-Martin Schulte, Jackie Gilbert, Eftychia E Drakou. Diagnosis and Management of Parathyroid Carcinoma: A State-of-the-Art Review. Endocrine-Related Cancer. 2023 Mar 22;30(4).
      2. Fingeret AL. Contemporary Evaluation and Management of Parathyroid Carcinoma. JCO Oncol Pract. 2021 Jan;17(1):17-21.
      3. Bilezikian JP, Bandeira L, Khan A, Cusano NE. Hyperparathyroidism. Lancet. 2018. Lancet. 2018 Jan 13;391(10116):168-178.
      4. Parathyroid cancer. 2017. National Library of Medicine (MedlinePlus)
      5. Cardoso L, Stevenson M, Thakker RV. Molecular Genetics of Syndromic and Non-Syndromic Forms of Parathyroid Carcinoma. Hum Mutat. 2017 Dec;38(12):1621-1648.
      6. Salcuni AS, Cetani F, Guarnieri V, Nicastro V, Romagnoli E, Danilo de Martino D. Parathyroid Carcinoma. Best Pract Res Clin Endocrinol Metab. 2018 Dec;32(6):877-889.
      7. Gill AJ, Lim G, Cheung VKY, Juliana Andrici J, Perry-Keene JL, Julie Paik J. Parafibromin-Deficient (HPT-JT Type, CDC73 Mutated) Parathyroid Tumors Demonstrate Distinctive Morphologic Features. Am J Surg Pathol.2019 Jan;43(1):35-46
      8. Li Y, Simonds WF, Chen H. A Comparative Genomic Analysis of Parathyroid Adenomas and Carcinomas Harboring Heterozygous Germline CDC73 Mutations. J Clin Endocrinol Metab. 2025 Jan 21;110(2):429-440.
      9. Li Y, Zhang J, Adikaram PR, Adikaram PR, Welch J, Guan B, Weinstein LS. Genotype of CDC73 Germline Mutation Determines Risk of Parathyroid Cancer. Endocr Relat Cancer. 2020 Sep;27(9):483-494.
      10. Zhu R, Wang Z, Hu Y. Prognostic Role of Parafibromin Staining and CDC73 Mutation in Patients With Parathyroid Carcinoma: A Systematic Review and Meta-Analysis Based on Individual Patient Data. Clin Endocrinol. 2020 Apr;92(4):295-302.
      11. Marini F, Giusti F, Palmini G, Perigli G, Santoro R, Brandi ML. Genetics and Epigenetics of Parathyroid Carcinoma. Front Endocrinol. 2022 Feb 24:13:834362.
      12. Kang H, Pettinga D, Schubert AD, Landenson PW, Ball DW, Chung JH. Genomic Profiling of Parathyroid Carcinoma Reveals Genomic Alterations Suggesting Benefit From Therapy. Oncologist. 2019 Jun;24(6):791-797.
      13. Cui M, Hu Y, Bi Y, Wang W, Wang M, Zhang X. Preliminary Exploration of Potential Molecular Therapeutic Targets in Recurrent and Metastatic Parathyroid Carcinomas. Int J Cancer. 2019 Feb 1;144(3):525-532.
      14. Simescu R, Piciu A, Muntean V, Mester A, Leucuta DC, Piciu D. Diagnostic and Surgical Challenges in Parathyroid Neoplasia: An Extensive Analysis of a Single Endocrine Surgery Center Cohort of Patients. Cancers. 2025 May 26;17(11):1783.
      15. Miao XY, Wang XL, Lyu ZH, Ba JM, Pei Y, Dou JT. Parathyroid Carcinoma: Report of 10 Patients and Literature Review. Neuro Endocrinol Lett. 2022 Nov 30;43(4):233-238.
      16. Zelano L, Locantore P, Rota CA, Policola C, Corsello A, Rossi ED. Parathyroid Carcinoma All-in-One, a Rare Life-Threatening Case With Multiple Systemic Manifestations: Case Report and Review of the Literature. Front Endocrinol. 2022 Jul 7:13:881225.
      17. Çalış H, Vural V, Özen A, Olgunçelik K, Yılmaz N, Ramazan Sarı R. A Rare Endocrine Malignancy: Retrospective Analysis of Parathyroid Cancer. Cancer Invest. 2025 Nov;43(10):872-881.
      18. Kawai Y, Kishimoto Y, Tamaki H, Fujiwara T, Asato R, Ushiro K. Parathyroid Carcinoma: Impact of Preoperative Diagnosis on the Choice of Surgical Procedure. Endocr J. 2023 Oct 30;70(10):969-976.
      19. Chen Z, Fu J, Shao Q, Zhou B, Wang F. 99mTc-Mibi Single Photon Emission Computed Tomography/Computed Tomography for the Incidental Detection of Rare Parathyroid Carcinoma. Medicine. 2018 Oct;97(40).
      20. Lu G, Shih WJ, Xiu JY. Technetium-99m MIBI Uptake in Recurrent Parathyroid Carcinoma and Brown Tumors. J Nucl Med: Official Publication, Society of Nuclear Medicine. 1995;36(5):811-3.
      21. Stack BC, Tolley NS, Bartel TB, Bilezikian JP, Bodenner D, Camacho P. AHNS Series: Do You Know Your Guidelines? Optimizing Outcomes in Reoperative Parathyroid Surgery: Definitive Multidisciplinary Joint Consensus Guidelines of the American Head and Neck Society and the British Association of Endocrine and Thyroid Surgeons. Head & Neck. 2018;40(8):1617-1629.
      22. Whitman J, Allen IE, Bergsland EK, Suh I, Hope TA. Assessment and Comparison of 18f-Fluorocholine PET and 99mTc-Sestamibi Scans in Identifying Parathyroid Adenomas: A Metaanalysis. J Nucl Med. 2021 Sep 1;62(9):1285-1291.
      23. Neumann DR, Esselstyn CB, Kim EY. Recurrent Postoperative Parathyroid Carcinoma: FDG-PET and Sestamibi-Spect Findings. J Nucl Med. 1996 Dec;37(12):2000-1.
      24. Viswanath A, Drakou EE, Lajeunesse-Trempe F, Grossman AB, Dimitriadis GK.Parathyroid Carcinoma: New Insights. Best Pract Res Clin Endocrinol Metab. 2025 Mar;39(2):101966.
      25. Christakis I, Vu T, Chuang HH, Fellman B, Silva Figueroa AM, Williams MD. The Diagnostic Accuracy of Neck Ultrasound, 4d-Computed Tomographyand Sestamibi Imaging in Parathyroid Carcinoma. Eur J Radiol.2017 Oct:95:82-88.
      26. Wilhelm SM, Wang TS, Ruan DT, Lee JA, Asa SL, Duh OY. The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism. JAMA Surg. 2016 Oct 1;151(10):959-968.
      27. Barale M, Nervo A, Craparo A, Pusterla A, Retta F, Maiorino F. Recurrence and Mortality Rate in an Italian Multi-Center Case Series of Parathyroid Atypical Adenomas and Carcinomas. Front Endocrinol (Lausanne). 2023 May 8:14:1158474.
      28. Goswamy J, Lei M, Simo R. Parathyroid Carcinoma. Curr Opin Otolaryngol Head Neck Surg. 2016 Apr;24(2):155-62.
      29. Schulte KM, Talat N, Galatá G. Margin Free Resection Achieves Excellent Long Term Outcomes in Parathyroid Cancer. Cancers. 2022 Dec 29;15(1):199.
      30. Talat N, Schulte KM. Clinical Presentation, Staging and Long-Term Evolution of Parathyroid Cancer. Ann Surg Oncol. 2010 Aug;17(8):2156-74.
      31. Young S, Wu JX, Li N, Yeh MW, Livhits MJ. More Extensive Surgery May Not Improve Survival Over Parathyroidectomy Alone in Parathyroid Carcinoma. Ann Surg Oncol. 2016 Sep;23(9):2898-904
      32. Jin S, Cho WC, Yang J, Xia K, Zhou C. Comparison of Prognosis After Partial and Total Surgical Resection for Parathyroid Carcinoma: An Inverse Probability of Treatment Weighting Analysis of the SEER Database. Front Endocrinol. 2023 Oct 16:14:1167508.
      33. Armstrong VL, Vaghaiwalla TM, Saghira C, Chen CB, Wang Y, Anantharaj J. A >50% Intraoperative Parathyroid Hormone Level Decrease Into Normal Reference Range Predicts Complete Excision of Malignancy in Patients With Parathyroid Carcinoma. J Surg Res. 2024 Aug:300:567-573.
      34. Lenschow C, Schrägle S, Kircher S, Lorenz K, Machens A, Dralle H. Clinical Presentation, Treatment, and Outcome of Parathyroid Carcinoma: Results of the NEKAR Retrospective International Multicenter Study. Ann Surg. 2022 Feb 1;275(2):e479-e487
      35. Harari A, Waring A, Fernandez-Ranvier G, Hwang J, Suh I, Mitmaker E. Parathyroid Carcinoma: A 43-Year Outcome and Survival Analysis. J Clin Endocrinol Metab. 2011 Dec;96(12):3679-86.
      36. Lazzaro A, Zhao GQ, Kulke M. Diagnosis and Management of Parathyroid Carcinoma. Clin Pharmacol Ther. 2024 Dec;116(6):1496-1505.
      37. Teleanu MV, Fuss CT, Paramasivam N, Pirmann S, Mock A, Terkamp C. Targeted Therapy of Advanced Parathyroid Carcinoma Guided by Genomic and Transcriptomic Profiling. Mol Oncol. 2023 Jul;17(7):1343-1355.
      38. Yu Z, Zhou J, Li F, Xie X, Hu L, Chen L. Efficacy of Surufatinib in the Treatment of Advanced Parathyroid Carcinoma: A Case Report. Heliyon. 2024 Aug 22;10(17):e36656.
      39. El-Hajj Fuleihan G, Clines GA, Hu MI, Marcocci C, Murad MH, Piggott T. Treatment of Hypercalcemia of Malignancy in Adults: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2023 Feb 15;108(3):507-528.
      40. Guise TA, Wysolmerski JJ. Cancer-Associated Hypercalcemia. N Engl J Med. 2022 Apr 14;386(15):1443-1451.
      41. Vellanki P, Lange K, Elaraj D, Kopp PA, El Muayed M. Denosumab for Management of Parathyroid Carcinoma-Mediated Hypercalcemia. J Clin Endocrinol Metab. 2014 Feb;99(2):387-90.
      42. Cunha C, Pinheiro SL, Donato S, Tavares Bello C, Simões H, Silva TN. Parathyroid Carcinoma: Single Centre Experience. Clin Endocrinol. 2022 Sep;97(3):250-257.
      43. Rodrigo JP, Hernandez-Prera JC, Randolph GW, Zafereo ME, Hartl DM, Silver CE. Parathyroid Cancer: An Update. Cancer Treat Rev. 2020 Jun:86:102012.
      44. Kim E, Lavreniuk A, Spasskaya O, Eremkina A, Salimkhanov R, Urusova L. Case Report: Relapse of Intrathyroidal Parathyroid Carcinoma in a Patient With Novel Variants in MET and CDKN1C Genes. Front Oncol. 2025 Jan 16:14:1441083.
      45. Wei B, Zhao T, Shen H, Mulan Jin M, Zhou Q, Liu X. Extended en Bloc Reoperation for Recurrent or Persistent Parathyroid Carcinoma: Analysis of 31 Cases in a Single Institute Experience. Ann Surg Oncol. 2022 Feb;29(2):1208-1215.