Practical Management of Thyroid Cancer: A Multidisciplinary Approach-Medullary Thyroid Cancer

  • Anna I. Kaleva
  • Ashok R. Shaha
  • Iain J. Nixon


Medullary thyroid cancer (MTC) is one of the less common histological types of thyroid malignancy, only accounting for 1–2% of thyroid cancers [1]. It was first recognised as an entity in 1906 by Jaquet and subsequently described in more definitive detail by Hazard and Crile [2]. In practical terms its biology differs from the more common papillary cancer and as such, requires a different therapeutic approach. This chapter describes the current understanding of the biology of this thyroid cancer type and practical considerations useful for the multi-disciplinary care of these patients.


  1. 1.
    Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610.CrossRefGoogle Scholar
  2. 2.
    Hazard JB, Hawk WA, Crile G Jr. Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity. J Clin Endocrinol Metab. 1959;19(1):152–61.CrossRefGoogle Scholar
  3. 3.
    Donis-Keller H, Dou S, Chi D, Carlson KM, Toshima K, Lairmore TC, et al. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet. 1993;2(7):851–6.CrossRefGoogle Scholar
  4. 4.
    Mulligan LM, Kwok JB, Healey CS, Elsdon MJ, Eng C, Gardner E, et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature. 1993;363(6428):458–60.CrossRefGoogle Scholar
  5. 5.
    Carlson KM, Dou S, Chi D, Scavarda N, Toshima K, Jackson CE, et al. Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B. Proc Natl Acad Sci U S A. 1994;91(4):1579–83.CrossRefGoogle Scholar
  6. 6.
    Hofstra RM, Landsvater RM, Ceccherini I, Stulp RP, Stelwagen T, Luo Y, et al. A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature. 1994;367(6461):375–6.CrossRefGoogle Scholar
  7. 7.
    Eng C, Smith DP, Mulligan LM, Nagai MA, Healey CS, Ponder MA, et al. Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours. Hum Mol Genet. 1994;3(2):237–41.CrossRefGoogle Scholar
  8. 8.
    Marsh DJ, McDowall D, Hyland VJ, Andrew SD, Schnitzler M, Gaskin EL, et al. The identification of false positive responses to the pentagastrin stimulation test in RET mutation negative members of MEN 2A families. Clin Endocrinol. 1996;44(2):213–20.CrossRefGoogle Scholar
  9. 9.
    Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86(12):5658–71.CrossRefGoogle Scholar
  10. 10.
    Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, American Thyroid Association Guidelines Task Force, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19(6):565–612.CrossRefGoogle Scholar
  11. 11.
    Leenhardt L, Erdogan MF, Hegedus L, Mandel SJ, Paschke R, Rago T, et al. 2013 European thyroid association guidelines for cervical ultrasound scan and ultrasound-guided techniques in the postoperative management of patients with thyroid cancer. Eur Thyroid J. 2013;2(3):147–59.CrossRefGoogle Scholar
  12. 12.
    Schroder S, Bocker W, Baisch H, Burk CG, Arps H, Meiners I, et al. Prognostic factors in medullary thyroid carcinomas. Survival in relation to age, sex, stage, histology, immunocytochemistry, and DNA content. Cancer. 1988;61(4):806–16.CrossRefGoogle Scholar
  13. 13.
    Papaparaskeva K, Nagel H, Droese M. Cytologic diagnosis of medullary carcinoma of the thyroid gland. Diagn Cytopathol. 2000;22(6):351–8.CrossRefGoogle Scholar
  14. 14.
    Rios A, Rodriguez JM, Febrero B, Acosta Ortega JM, Torregrosa N, Balsalobre M, et al. Histological and immunohistochemical profile of sporadic and familial medullary thyroid carcinoma. Endocrinol Nutr. 2011;58(10):521–8.CrossRefGoogle Scholar
  15. 15.
    Algeciras-Schimnich A, Preissner CM, Theobald JP, Finseth MS, Grebe SK. Procalcitonin: a marker for the diagnosis and follow-up of patients with medullary thyroid carcinoma. J Clin Endocrinol Metab. 2009;94(3):861–8.CrossRefGoogle Scholar
  16. 16.
    Walter MA, Meier C, Radimerski T, Iten F, Kranzlin M, Muller-Brand J, et al. Procalcitonin levels predict clinical course and progression-free survival in patients with medullary thyroid cancer. Cancer. 2010;116(1):31–40.PubMedGoogle Scholar
  17. 17.
    Weber T, Schilling T, Frank-Raue K, Colombo-Benkmann M, Hinz U, Ziegler R, et al. Impact of modified radical neck dissection on biochemical cure in medullary thyroid carcinomas. Surgery. 2001;130(6):1044–9.CrossRefGoogle Scholar
  18. 18.
    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.CrossRefGoogle Scholar
  19. 19.
    Moley JF, DeBenedetti MK. Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg. 1999;229(6):880–7. discussion 7–8CrossRefGoogle Scholar
  20. 20.
    McMullen C, Rocke D, Freeman J. Complications of bilateral neck dissection in thyroid cancer from a single high-volume center. JAMA Otolaryngol Head Neck Surg. 2017;143:376–81.CrossRefGoogle Scholar
  21. 21.
    Machens A, Dralle H. Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab. 2010;95(6):2655–63.CrossRefGoogle Scholar
  22. 22.
    Brierley J, Tsang R, Simpson WJ, Gospodarowicz M, Sutcliffe S, Panzarella T. Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control. Thyroid. 1996;6(4):305–10.CrossRefGoogle Scholar
  23. 23.
    Orlandi F, Caraci P, Berruti A, Puligheddu B, Pivano G, Dogliotti L, et al. Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid cancer. Ann Oncol. 1994;5(8):763–5.CrossRefGoogle Scholar
  24. 24.
    Petursson SR. Metastatic medullary thyroid carcinoma. Complete response to combination chemotherapy with dacarbazine and 5-fluorouracil. Cancer. 1988;62(9):1899–903.CrossRefGoogle Scholar
  25. 25.
    Nixon IJ, Shaha AR, Tuttle MR. Targeted therapy in thyroid cancer. Curr Opin Otolaryngol Head Neck Surg. 2013;21(2):130–4.CrossRefGoogle Scholar
  26. 26.
    Brauckhoff M, Gimm O, Weiss CL, Ukkat J, Sekulla C, Brauckhoff K, et al. Multiple endocrine neoplasia 2B syndrome due to codon 918 mutation: clinical manifestation and course in early and late onset disease. World J Surg. 2004;28(12):1305–11.CrossRefGoogle Scholar
  27. 27.
    Frank-Raue K, Buhr H, Dralle H, Klar E, Senninger N, Weber T, et al. Long-term outcome in 46 gene carriers of hereditary medullary thyroid carcinoma after prophylactic thyroidectomy: impact of individual RET genotype. Eur J Endocrinol. 2006;155(2):229–36.CrossRefGoogle Scholar
  28. 28.
    Engelbach M, Gorges R, Forst T, Pfutzner A, Dawood R, Heerdt S, 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.PubMedGoogle Scholar
  29. 29.
    Barbet J, Campion L, Kraeber-Bodere F, Chatal JF, Group GTES. Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab. 2005;90(11):6077–84.CrossRefGoogle Scholar
  30. 30.
    Boi F, Maurelli I, Pinna G, Atzeni F, Piga M, Lai ML, et al. Calcitonin measurement in wash-out fluid from fine needle aspiration of neck masses in patients with primary and metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab. 2007;92(6):2115–8.CrossRefGoogle Scholar
  31. 31.
    Kudo T, Miyauchi A, Ito Y, Takamura Y, Amino N, Hirokawa M. Diagnosis of medullary thyroid carcinoma by calcitonin measurement in fine-needle aspiration biopsy specimens. Thyroid. 2007;17(7):635–8.CrossRefGoogle Scholar
  32. 32.
    Pellegriti G, Leboulleux S, Baudin E, Bellon N, Scollo C, Travagli JP, et al. Long-term outcome of medullary thyroid carcinoma in patients with normal postoperative medical imaging. Br J Cancer. 2003;88(10):1537–42.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Anna I. Kaleva
    • 1
  • Ashok R. Shaha
    • 2
  • Iain J. Nixon
    • 3
  1. 1.Ipswich Hospital NHS TrustIpswichUK
  2. 2.Memorial Sloan Kettering Cancer CenterNew YorkUSA
  3. 3.NHS LothianEdinburghUK

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