Skip to main content
SpringerLink
Log in

Medullary Thyroid Cancer

  • Chapter
  • First Online:
Neuroendocrine Tumors

  • 482 Accesses

Abstract

MTC is a rare thyroid malignancy that is associated with a worse prognosis than follicular-derived thyroid cancers. It can occur sporadically or as part of hereditary syndromes such as MEN2 with various clinical phenotypes dependent on the tumor genotype. The mainstays for treatment are early diagnosis and surgical removal of all disease. In the case of sporadic MTC, this is done with a total thyroidectomy and central lymph node dissection with a lateral dissection reserved for sonographic or biochemical evidence of disease. In patients with a hereditary form of MTC, the goal is for prophylactic surgery to improve future oncologic outcomes with the timing of surgery based on genotype and calcitonin level. For patients with advanced or metastatic disease, further work is being done to identify systemic therapies, such as novel tyrosine kinase inhibitors, that improve outcomes in those who cannot be cured with surgery alone.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hazard JB, Hawk WA, Crile G Jr. Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity. J Clin Endocrinol Metab. 1959;19:152–61.

    Article  CAS  PubMed  Google Scholar 

  2. Surveillance, Epidemiology, and End Results (SEER) Program Populations (1969–2018). www.seer.cancer.gov/popdata, National Cancer Institute, DCCPS, surveillance research program, released December 2019.

  3. Williams ED. Histogenesis of medullary carcinoma of the thyroid. J Clin Pathol. 1966;19:114–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pearse AG, Polak JM. Cytochemical evidence for the neural crest origin of mammalian ultimobranchial C cells. Histochemie. 1971;27(2):96–102.

    Article  CAS  PubMed  Google Scholar 

  5. Foster GV. Calcitonin (thyrocalcitonin). N Engl J Med. 1968;279(7):349–60.

    Article  CAS  PubMed  Google Scholar 

  6. Block MA, Jackson CE, Greenawald KA, Yott JB, Tashjian AH Jr. Clinical characteristics distinguishing hereditary from sporadic medullary thyroid carcinoma. Treatment implications. Arch Surg. 1980;115:142–8.

    Article  CAS  PubMed  Google Scholar 

  7. Santoro M, Rosati R, Grieco M, et al. The ret proto-oncogene is consistently expressed in human pheochromocytomas and thyroid medullary carcinomas. Oncogene. 1990;5(10):1595–8.

    CAS  PubMed  Google Scholar 

  8. Donis-Keller H, Dou S, Chi D, et al. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet. 1993;2(7):851–6.

    Article  CAS  PubMed  Google Scholar 

  9. Marsh DJ, Learoyd DL, Andrew SD, et al. Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinoma. Clin Endocrinol. 1996;44(3):249–57.

    Article  CAS  Google Scholar 

  10. Agrawal N, Jiao Y, Sausen M, et al. Exomic sequencing of medullary thyroid cancer reveals dominant and mutually exclusive oncogenic mutations in RET and RAS. J Clin Endocrinol Metab. 2013;98(2):E364–9.

    Article  CAS  PubMed  Google Scholar 

  11. Margraf RL, Crockett DK, Krautscheid PM, et al. Multiple endocrine neoplasia type 2 RET protooncogene database: repository of MEN2-associated RET sequence variation and reference for genotype/phenotype correlations. Hum Mutat. 2009;30(4):548–56.

    Article  CAS  PubMed  Google Scholar 

  12. Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Schilling T, Bürck J, Sinn HP, et al. Prognostic value of codon 918 (ATG-->ACG) RET proto-oncogene mutations in sporadic medullary thyroid carcinoma. Int J Cancer. 2001;95(1):62–6.

    Article  CAS  PubMed  Google Scholar 

  14. Romei C, Ugolini C, Cosci B, et al. Low prevalence of the somatic M918T RET mutation in micro-medullary thyroid cancer. Thyroid. 2012;22(5):476–81.

    Article  CAS  PubMed  Google Scholar 

  15. Moley JF. Medullary thyroid carcinoma: management of lymph node metastases. J Natl Compr Cancer Netw. 2010;8(5):549–56.

    Article  Google Scholar 

  16. Machens A, Hinze R, Thomusch O, Dralle H. Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg. 2002;26(1):22–8.

    Article  PubMed  Google Scholar 

  17. Ilias I, Torpy DJ, Pacak K, Mullen N, Wesley RA, Nieman LK. Cushing’s syndrome due to ectopic corticotropin secretion: twenty years’ experience at the National Institutes of Health. J Clin Endocrinol Metab. 2005;90(8):4955–62.

    Article  CAS  PubMed  Google Scholar 

  18. Steiner AL, Goodman AD, Powers SR. Study of a kindred with pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism and Cushing’s disease: multiple endocrine neoplasia, type 2. Medicine (Baltimore). 1968;47(5):371–409.

    Article  CAS  Google Scholar 

  19. Raue F, Frank-Raue K. Genotype-phenotype correlation in multiple endocrine neoplasia type 2. Clinics (Sao Paulo). 2012;67(Suppl 1):69–75.

    Article  Google Scholar 

  20. Eng C, Clayton D, Schuffenecker I, et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA. 1996;276(19):1575–9.

    Article  CAS  PubMed  Google Scholar 

  21. Dabir T, Hunter SJ, Russell CF, McCall D, Morrison PJ. The RET mutation E768D confers a late-onset familial medullary thyroid carcinoma – only phenotype with incomplete penetrance: implications for screening and management of carrier status. Familial Cancer. 2006;5(2):201–4.

    Article  PubMed  Google Scholar 

  22. Patócs A, Valkusz Z, Igaz P, et al. Segregation of the V804L mutation and S836S polymorphism of exon 14 of the RET gene in an extended kindred with familial medullary thyroid cancer. Clin Genet. 2003;63(3):219–23.

    Article  PubMed  Google Scholar 

  23. Gimm O, Marsh DJ, Andrew SD, et al. Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutation. J Clin Endocrinol Metab. 1997;82(11):3902–4.

    Article  CAS  PubMed  Google Scholar 

  24. Elisei R, Romei C, Cosci B, et al. RET genetic screening in patients with medullary thyroid cancer and their relatives: experience with 807 individuals at one center. J Clin Endocrinol Metab. 2007;92(12):4725–9.

    Article  CAS  PubMed  Google Scholar 

  25. Machens A, Dralle H. Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab. 2010;95(6):2655–63.

    Article  CAS  PubMed  Google Scholar 

  26. Gambardella C, Offi C, Patrone R, et al. Calcitonin negative medullary thyroid carcinoma: a challenging diagnosis or a medical dilemma? BMC Endocr Disord. 2019;19(Suppl 1):45. Published 2019 May 29

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Brutsaert EF, Gersten AJ, Tassler AB, Surks MI. Medullary thyroid cancer with undetectable serum calcitonin. J Clin Endocrinol Metab. 2015;100(2):337–41.

    Article  CAS  PubMed  Google Scholar 

  28. Giraudet AL, Vanel D, Leboulleux S, et al. Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels. J Clin Endocrinol Metab. 2007;92(11):4185–90.

    Article  CAS  PubMed  Google Scholar 

  29. Ong SC, Schöder H, Patel SG, et al. Diagnostic accuracy of 18F-FDG PET in restaging patients with medullary thyroid carcinoma and elevated calcitonin levels. J Nucl Med. 2007;48(4):501–7.

    Article  CAS  PubMed  Google Scholar 

  30. Treglia G, Tamburello A, Giovanella L. Detection rate of somatostatin receptor PET in patients with recurrent medullary thyroid carcinoma: a systematic review and a meta-analysis. Hormones (Athens). 2017;16(4):362–72.

    Google Scholar 

  31. Conry BG, Papathanasiou ND, Prakash V, et al. Comparison of 68Ga-DOTATATE and 18F-fluorodeoxyglucose PET/CT in the detection of recurrent medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2010;37:49.

    Article  CAS  PubMed  Google Scholar 

  32. Wolfe HJ, Melvin KE, Cervi-Skinner SJ, et al. C-cell hyperplasia preceding medullary thyroid carcinoma. N Engl J Med. 1973;289(9):437–41.

    Article  CAS  PubMed  Google Scholar 

  33. Machens A, Dralle H. Genotype-phenotype based surgical concept of hereditary medullary thyroid carcinoma. World J Surg. 2007;31(5):957–68.

    Article  PubMed  Google Scholar 

  34. Sosa JA, Tuggle CT, Wang TS, et al. Clinical and economic outcomes of thyroid and parathyroid surgery in children. J Clin Endocrinol Metab. 2008;93(8):3058–65.

    Article  CAS  PubMed  Google Scholar 

  35. Machens A, Schneyer U, Holzhausen HJ, Dralle H. Prospects of remission in medullary thyroid carcinoma according to basal calcitonin level. J Clin Endocrinol Metab. 2005;90(4):2029–34.

    Article  CAS  PubMed  Google Scholar 

  36. Klein GL, Wadlington EL, Collins ED, Catherwood BD, Deftos LJ. Calcitonin levels in sera of infants and children: relations to age and periods of bone growth. Calcif Tissue Int. 1984;36(6):635–8.

    Article  CAS  PubMed  Google Scholar 

  37. Zenaty D, Aigrain Y, Peuchmaur M, et al. Medullary thyroid carcinoma identified within the first year of life in children with hereditary multiple endocrine neoplasia type 2A (codon 634) and 2B. Eur J Endocrinol. 2009;160(5):807–13.

    Article  CAS  PubMed  Google Scholar 

  38. Laird AM, Gauger PG, Miller BS, Doherty GM. Evaluation of postoperative radioactive iodine scans in patients who underwent prophylactic central lymph node dissection. World J Surg. 2012;36(6):1268–73.

    Article  PubMed  Google Scholar 

  39. Moley JF, DeBenedetti MK. Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg. 1999;229(6):880–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. American Thyroid Association Surgery Working Group. American Association of Endocrine Surgeons, American Academy of Otolaryngology-Head and Neck Surgery; consensus statement on the terminology and classification of central neck dissection for thyroid cancer. Thyroid. 2009;19(11):1153–8.

    Article  Google Scholar 

  41. Stack BC Jr, Ferris RL, Goldenberg D, et al. American Thyroid Association consensus review and statement regarding the anatomy, terminology, and rationale for lateral neck dissection in differentiated thyroid cancer. Thyroid. 2012;22(5):501–8.

    Article  PubMed  Google Scholar 

  42. Miyauchi A, Matsuzuka F, Hirai K, et al. Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutations. World J Surg. 2002;26(8):1023–8.

    Article  PubMed  Google Scholar 

  43. Machens A, Dralle H. Benefit-risk balance of reoperation for persistent medullary thyroid cancer. Ann Surg. 2013;257(4):751–7.

    Article  PubMed  Google Scholar 

  44. Fialkowski E, DeBenedetti M, Moley J. Long-term outcome of reoperations for medullary thyroid carcinoma. World J Surg. 2008;32(5):754–65.

    Article  PubMed  Google Scholar 

  45. Modigliani E, Cohen R, Campos JM, et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC study group. Groupe d’étude des tumeurs à calcitonine. Clin Endocrinol. 1998;48(3):265–73.

    Article  CAS  Google Scholar 

  46. Howlader N, Noone AM, Krapcho M, et al (eds). SEER cancer statistics review, 1975–2016, National Cancer Institute, Bethesda, MD. https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission, posted to the SEER website, April 2019.

  47. Randle RW, Balentine CJ, Leverson GE, et al. Trends in the presentation, treatment, and survival of patients with medullary thyroid cancer over the past 30 years. Surgery. 2017;161(1):137–46.

    Article  PubMed  Google Scholar 

  48. Parghane RV, Naik C, Talole S, et al. Clinical utility of 177 Lu-DOTATATE PRRT in somatostatin receptor-positive metastatic medullary carcinoma of thyroid patients with assessment of efficacy, survival analysis, prognostic variables, and toxicity. Head Neck. 2020;42(3):401–16.

    Article  PubMed  Google Scholar 

  49. Wells SA Jr, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial [published correction appears in J Clin Oncol. 2013 Aug 20;31(24):3049]. J Clin Oncol. 2012;30(2):134–141.

    Google Scholar 

  50. Elisei R, Schlumberger MJ, Müller SP, et al. Cabozantinib in progressive medullary thyroid cancer [published correction appears in J Clin Oncol. 2014 Jun 10;32(17):1864]. J Clin Oncol. 2013;31(29):3639–3646.

    Google Scholar 

  51. Engelbach M, Görges R, Forst T, et al. Improved diagnostic methods in the follow-up of medullary thyroid carcinoma by highly specific calcitonin measurements. J Clin Endocrinol Metab. 2000;85(5):1890–4.

    CAS  PubMed  Google Scholar 

  52. Ismailov SI, Piulatova NR. Postoperative calcitonin study in medullary thyroid carcinoma. Endocr Relat Cancer. 2004;11(2):357–63.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Victor A. Gall

  2. Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA

    Amanda M. Laird

Authors
  1. Victor A. Gall
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amanda M. Laird
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amanda M. Laird .

Editor information

Editors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Jordan M. Cloyd

  2. Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Timothy M. Pawlik

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gall, V.A., Laird, A.M. (2021). Medullary Thyroid Cancer. In: Cloyd, J.M., Pawlik, T.M. (eds) Neuroendocrine Tumors. Springer, Cham. https://doi.org/10.1007/978-3-030-62241-1_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-62241-1_14

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-62240-4

  • Online ISBN: 978-3-030-62241-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation