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Medullary Carcinoma

  • Living reference work entry
  • First Online:
Thyroid Diseases

Part of the book series: Endocrinology ((ENDOCR))

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Abstract

Medullary thyroid cancer (MTC) is a rare neuroendocrine tumor that can be either sporadic or familial. In both cases, the pathogenesis is due to constitutively activating mutations, somatic or germline, of RET oncogene. The familial form of MTC can be associated with other endocrine neoplasias such as pheochromocytoma (PHEO) and/or multiple adenomatosis of parathyroids (PTHAd). According to the phenotype, three different syndromes are distinguished: the multiple endocrine neoplasia (MEN) type 2A, characterized by the association of MTC, PHEO, and PTHAd; the MEN 2B in which MTC and PHEO are associated with other nonendocrine diseases such as multiple mucosal neuromas, marfanoid habitus, and megacolon; and the familial form of MTC (FMTC) with hereditary MTC not associated with other neoplasias. The familial form, but not the sporadic, can affect children, and the RET genetic screening is the only diagnostic tool able to identify gene carriers when the tumor is not yet developed. As all thyroid tumors, MTC clinical manifestation is represented by a thyroid nodule, either isolated or in the context of a multinodular goiter. The cytological diagnosis is not always straightforward and can be facilitated by the measurement of serum calcitonin (Ct) that when >100 pg/ml is the most specific and sensitive serum marker of MTC. An early diagnosis of MTC, when the tumor is still intrathyroid, is needed to definitively cure the patient with the first surgical treatment. The presence of distant metastases at diagnosis is, together with the presence of a somatic RET mutation in the tumor tissue, the most important prognostic factor for a poor outcome. If the first surgery will not be curative, other local or systemic therapies are currently available, and their use can have a positive impact on the progression-free survival of MTC patients. Since MTC is a rare tumor, with several peculiarities such as the possibility to be hereditary, the management of MTC patients should be performed in referral centers and by a multidisciplinary team.

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References

  • Abrahamsen B, Eiken P, et al. Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study. J Bone Miner Res. 2009;24(6):1095–102.

    Article  CAS  PubMed  Google Scholar 

  • Acar T, Ozbek SS, et al. Incidentally discovered thyroid nodules: frequency in an adult population during Doppler ultrasonographic evaluation of cervical vessels. Endocrine. 2014;45(1):73–8.

    Article  CAS  PubMed  Google Scholar 

  • Alam MJ. Chronic refractory diarrhoea: a manifestation of endocrine disorders. Dig Dis. 1994;12(1):46–61.

    Article  CAS  PubMed  Google Scholar 

  • Alevizaki M, Saltiki K. Primary hyperparathyroidism in MEN2 syndromes. Recent Results Cancer Res. 2015;204:179–86.

    Article  PubMed  Google Scholar 

  • Barakat MT, Meeran K, et al. Neuroendocrine tumours. Endocr Relat Cancer. 2004;11(1):1–18.

    Article  CAS  PubMed  Google Scholar 

  • Baudin E, Lumbroso J, et al. Comparison of octreotide scintigraphy and conventional imaging in medullary thyroid carcinoma. J Nucl Med. 1996;37(6):912–6.

    CAS  PubMed  Google Scholar 

  • Baudin E, Bidart JM, et al. Impact of chromogranin A measurement in the work-up of neuroendocrine tumors. Ann Oncol. 2001;12(Suppl 2):S79–82.

    Article  PubMed  Google Scholar 

  • Bible KC, Suman VJ, et al. A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H. J Clin Endocrinol Metab. 2014;99(5):1687–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biscolla RP, Ugolini C, et al. Medullary and papillary tumors are frequently associated in the same thyroid gland without evidence of reciprocal influence in their biologic behavior. Thyroid. 2004;14(11):946–52.

    Article  PubMed  Google Scholar 

  • Bodei L, Handkiewicz-Junak D, et al. Receptor radionuclide therapy with 90Y-DOTATOC in patients with medullary thyroid carcinomas. Cancer Biother Radiopharm. 2004;19(1):65–71.

    Article  CAS  PubMed  Google Scholar 

  • Boi F, Maurelli I, 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.

    Article  CAS  PubMed  Google Scholar 

  • Brauckhoff M, Gimm O, 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.

    Article  PubMed  Google Scholar 

  • Budiawan H, Salavati A, et al. Peptide receptor radionuclide therapy of treatment-refractory metastatic thyroid cancer using (90)Yttrium and (177)Lutetium labeled somatostatin analogs: toxicity, response and survival analysis. Am J Nucl Med Mol Imaging. 2013;4(1):39–52.

    PubMed  PubMed Central  Google Scholar 

  • Busnardo B, Girelli ME, et al. Nonparallel patterns of calcitonin and carcinoembryonic antigen levels in the follow-up of medullary thyroid carcinoma. Cancer. 1984;53(2):278–85.

    Article  CAS  PubMed  Google Scholar 

  • Ceccherini I, Romei C, et al. Identification of the Cys634→Tyr mutation of the RET proto-oncogene in a pedigree with multiple endocrine neoplasia type 2A and localized cutaneous lichen amyloidosis. J Endocrinol Investig. 1994;17(3):201–4.

    Article  CAS  Google Scholar 

  • Chen H, Roberts JR, et al. Effective long-term palliation of symptomatic, incurable metastatic medullary thyroid cancer by operative resection. Ann Surg. 1998;227(6):887–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheung K, Roman SA, et al. Calcitonin measurement in the evaluation of thyroid nodules in the United States: a cost-effectiveness and decision analysis. J Clin Endocrinol Metab. 2008;93:2173–80.

    Article  CAS  PubMed  Google Scholar 

  • Chi MS, Yang KL, et al. Comparing the effectiveness of combined external beam radiation and hyperthermia versus external beam radiation alone in treating patients with painful bony metastases: a phase 3 prospective, randomized, controlled trial. Int J Radiat Oncol Biol Phys. 2018;100(1):78–87.

    Article  PubMed  Google Scholar 

  • Ciampi R, Mian C, et al. Evidence of a low prevalence of RAS mutations in a large medullary thyroid cancer series. Thyroid. 2013;23(1):50–7.

    Article  CAS  PubMed  Google Scholar 

  • Ciampi R, Romei C, et al. Classical point mutations of RET, BRAF and RAS oncogenes are not shared in papillary and medullary thyroid cancer occurring simultaneously in the same gland. J Endocrinol Investig. 2017;40(1):55–62.

    Article  CAS  Google Scholar 

  • Colombo C, Minna E, et al. The modifier role of RET-G691S polymorphism in hereditary medullary thyroid carcinoma: functional characterization and expression/penetrance studies. Orphanet J Rare Dis. 2015;10:25.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cosci B, Vivaldi A, et al. In silico and in vitro analysis of rare germline allelic variants of RET oncogene associated with medullary thyroid cancer. Endocr Relat Cancer. 2011;18(5):603–12.

    Article  CAS  PubMed  Google Scholar 

  • Costante G, Meringolo D, et al. Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules. J Clin Endocrinol Metab. 2007;92(2):450–5.

    Article  CAS  PubMed  Google Scholar 

  • Cunliffe WJ, Hudgson P, et al. A calcitonin-secreting medullary thyroid carcinoma associated with mucosal neuromas, marfanoid features, myopathy and pigmentation. Am J Med. 1970;48(1):120–6.

    Article  CAS  PubMed  Google Scholar 

  • Deldycke A, Haenebalcke C, et al. Paraneoplastic Cushing syndrome, case-series and review of the literature. Acta Clin Belg. 2017; 1–7. http://www.tandfonline.com/loi/yacb20.

  • Donis-Keller H, Dou S, 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 

  • Eisele RM. Advances in local ablation of malignant liver lesions. World J Gastroenterol. 2016;22(15):3885–91.

    Article  PubMed  PubMed Central  Google Scholar 

  • Elisei R. Routine serum calcitonin measurement in the evaluation of thyroid nodules. Best Pract Res Clin Endocrinol Metab. 2008;22(6):941–53.

    Article  CAS  PubMed  Google Scholar 

  • Elisei R, Bottici V, et al. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. J Clin Endocrinol Metab. 2004a;89(1):163–8.

    Article  CAS  PubMed  Google Scholar 

  • Elisei R, Cosci B, et al. RET exon 11 (G691S) polymorphism is significantly more frequent in sporadic medullary thyroid carcinoma than in the general population. J Clin Endocrinol Metab. 2004b;89(7):3579–84.

    Article  CAS  PubMed  Google Scholar 

  • Elisei R, Romei C, 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 

  • Elisei R, Cosci B, et al. Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab. 2008;93(3):682–7.

    Article  CAS  PubMed  Google Scholar 

  • Elisei R, Romei C, et al. The timing of total thyroidectomy in RET gene mutation carriers could be personalized and safely planned on the basis of serum calcitonin: 18 years experience at one single center. J Clin Endocrinol Metab. 2012;97(2):426–35.

    Article  CAS  PubMed  Google Scholar 

  • Elisei R, Alevizaki M, et al. 2012 European thyroid association guidelines for genetic testing and its clinical consequences in medullary thyroid cancer. Eur Thyroid J. 2013a;1(4):216–31.

    Article  CAS  PubMed  Google Scholar 

  • Elisei R, Schlumberger MJ, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol. 2013b;31(29):3639–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Emmertsen KK, Nielsen HE, et al. Pentagastrin, calcium and whisky stimulated serum calcitonin in medullary carcinoma of the thyroid. Acta Radiol Oncol. 1980;19(2):85–9.

    Article  CAS  PubMed  Google Scholar 

  • Eng C, Smith DP, 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.

    Article  CAS  PubMed  Google Scholar 

  • Eng C, Clayton D, 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 

  • Erdogan MF, Gulec B, et al. Multiple endocrine neoplasia 2B presenting with Pseudo-Hirschsprung’s disease. J Natl Med Assoc. 2006;98(5):783–6.

    PubMed  PubMed Central  Google Scholar 

  • Essig Jr GF, Porter K, et al. Fine needle aspiration and medullary thyroid carcinoma: the risk of inadequate preoperative evaluation and initial surgery when relying upon FNAB cytology alone. Endocr Pract. 2013;19(6):920–7.

    Article  PubMed  Google Scholar 

  • Essig Jr GF, Porter K, et al. Multifocality in sporadic medullary thyroid carcinoma: an international multicenter study. Thyroid. 2016;26(11):1563–72.

    Article  CAS  PubMed  Google Scholar 

  • Farndon JR, Leight GS, et al. Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity. Br J Surg. 1986;73(4):278–81.

    Article  CAS  PubMed  Google Scholar 

  • Forrest CH, Frost FA, et al. Medullary carcinoma of the thyroid: accuracy of diagnosis of fine-needle aspiration cytology. Cancer. 1998;84(5):295–302.

    Article  CAS  PubMed  Google Scholar 

  • Fox E, Widemann BC, et al. Vandetanib in children and adolescents with multiple endocrine neoplasia type 2B associated medullary thyroid carcinoma. Clin Cancer Res. 2013;19(15):4239–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franc S, Niccoli-Sire P, et al. Complete surgical lymph node resection does not prevent authentic recurrences of medullary thyroid carcinoma. Clin Endocrinol. 2001;55(3):403–9.

    Article  CAS  Google Scholar 

  • Frank-Raue K, Raue F. Hereditary medullary thyroid cancer genotype-phenotype correlation. Recent Results Cancer Res. 2015;204:139–56.

    Article  PubMed  Google Scholar 

  • Fugazzola L. Stimulated calcitonin cut-offs by different tests. Eur Thyroid J. 2013;2(1):49–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fugazzola L, Pinchera A, et al. Disappearance rate of serum calcitonin after total thyroidectomy for medullary thyroid carcinoma. Int J Biol Markers. 1994;9(1):21–4.

    CAS  PubMed  Google Scholar 

  • Gawlik T, d’Amico A, et al. The prognostic value of tumor markers doubling times in medullary thyroid carcinoma – preliminary report. Thyroid Res. 2010;3(1):10.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gharib H, Papini E, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules – 2016 update. Endocr Pract. 2016;22(5):622–39.

    PubMed  Google Scholar 

  • Gimm O, Ukkat J, et al. Determinative factors of biochemical cure after primary and reoperative surgery for sporadic medullary thyroid carcinoma. World J Surg. 1998;22(6):562–7. discussion 567–568.

    Article  CAS  PubMed  Google Scholar 

  • Giovanella L, Crippa S, et al. Serum calcitonin-negative medullary thyroid carcinoma: role of CgA and CEA as complementary markers. Int J Biol Markers. 2008;23(2):129–31.

    Article  CAS  PubMed  Google Scholar 

  • Giraudet AL, Taieb D. PET imaging for thyroid cancers: current status and future directions. Ann Endocrinol (Paris). 2017;78(1):38–42.

    Article  Google Scholar 

  • Giraudet AL, Vanel D, 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 

  • Grozinsky-Glasberg S, Bloom AI, et al. The role of hepatic trans-arterial chemoembolization in metastatic medullary thyroid carcinoma: a specialist center experience and review of the literature. Eur J Endocrinol. 2017;176(4):461–8.

    Article  CAS  PubMed  Google Scholar 

  • Hahm JR, Lee MS, et al. Routine measurement of serum calcitonin is useful for early detection of medullary thyroid carcinoma in patients with nodular thyroid diseases. Thyroid. 2001;11(1):73–80.

    Article  CAS  PubMed  Google Scholar 

  • Hannah-Shmouni F, Stratakis CA, et al. Flushing in (neuro)endocrinology. Rev Endocr Metab Disord. 2016;17(3):373–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hegedus L. Clinical practice. The thyroid nodule. N Engl J Med. 2004;351(17):1764–71.

    Article  PubMed  Google Scholar 

  • Hegedus L, Bonnema SJ, et al. Management of simple nodular goiter: current status and future perspectives. Endocr Rev. 2003;24(1):102–32.

    Article  PubMed  Google Scholar 

  • Heilmann AM, Subbiah V, et al. Comprehensive genomic profiling of clinically advanced medullary thyroid carcinoma. Oncology. 2016;90(6):339–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jackson CE, Norum RA, et al. Clinical value of calcitonin and carcinoembryonic antigen doubling times in medullary thyroid carcinoma. Henry Ford Hosp Med J. 1987;35(2–3):120–1.

    CAS  PubMed  Google Scholar 

  • Jaffe BM. Prostaglandins and serotonin: nonpeptide diarrheogenic hormones. World J Surg. 1979;3(5):565–78.

    Article  CAS  PubMed  Google Scholar 

  • Johansson E, Andersson L, et al. Revising the embryonic origin of thyroid C cells in mice and humans. Development. 2015;142(20):3519–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaltsas G, Rockall A, et al. Recent advances in radiological and radionuclide imaging and therapy of neuroendocrine tumours. Eur J Endocrinol. 2004;151(1):15–27.

    Article  CAS  PubMed  Google Scholar 

  • Kameda Y, Nishimaki T, et al. Expression of the epithelial marker E-cadherin by thyroid C cells and their precursors during murine development. J Histochem Cytochem. 2007;55(10):1075–88.

    Article  CAS  PubMed  Google Scholar 

  • Kaserer K, Scheuba C, et al. C-cell hyperplasia and medullary thyroid carcinoma in patients routinely screened for serum calcitonin. Am J Surg Pathol. 1998;22(6):722–8.

    Article  CAS  PubMed  Google Scholar 

  • Keiser HR, Beaven MA, et al. Sipple’s syndrome: medullary thyroid carcinoma, pheochromocytoma, and parathyroid disease. Studies in a large family. NIH conference. Ann Intern Med. 1973;78(4):561–79.

    Article  CAS  PubMed  Google Scholar 

  • Khosla S, Burr D, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007;22(10):1479–91.

    Article  PubMed  Google Scholar 

  • King J, Quinn R, et al. Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer. 2008;113(5):921–9.

    Article  PubMed  Google Scholar 

  • Kodama T, Fujino M, et al. Identification of carcinoembryonic antigen in the C-cell of the normal thyroid. Cancer. 1980;45(1):98–101.

    Article  CAS  PubMed  Google Scholar 

  • Kraeber-Bodere F, Faivre-Chauvet A, et al. Pharmacokinetics and dosimetry studies for optimization of anti-carcinoembryonic antigen x anti-hapten bispecific antibody-mediated pretargeting of Iodine-131-labeled hapten in a phase I radioimmunotherapy trial. Clin Cancer Res. 2003;9(10 Pt 2):3973S–81S.

    CAS  PubMed  Google Scholar 

  • Kraft IL, Akshintala S, et al. Outcomes of children and adolescents with advanced hereditary medullary thyroid carcinoma treated with vandetanib. Clin Cancer Res. 2018;24:753–765.

    Google Scholar 

  • Lam ET, Ringel MD, et al. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol. 2010;28(14):2323–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lebeault M, Pinson S, et al. Nationwide French study of RET variants detected from 2003 to 2013 suggests a possible influence of polymorphisms as modifiers. Thyroid. 2017;27(12):1511–22.

    Article  CAS  PubMed  Google Scholar 

  • Lee S, Shin JH, et al. Medullary thyroid carcinoma: comparison with papillary thyroid carcinoma and application of current sonographic criteria. AJR Am J Roentgenol. 2010;194(4):1090–4.

    Article  PubMed  Google Scholar 

  • Lencioni R, Crocetti L, et al. Response to radiofrequency ablation of pulmonary tumours: a prospective, intention-to-treat, multicentre clinical trial (the RAPTURE study). Lancet Oncol. 2008;9(7):621–8.

    Article  PubMed  Google Scholar 

  • Libansky P, Adamek S, et al. Measurement of intact parathormone during operation for primary hyperparathyroidism. Bratisl Lek Listy. 2017;118(5):255–7.

    CAS  PubMed  Google Scholar 

  • LiVolsi VA. C cell hyperplasia/neoplasia. J Clin Endocrinol Metab. 1997;82(1):39–41.

    Article  CAS  PubMed  Google Scholar 

  • Locati LD, Licitra L, et al. Treatment of advanced thyroid cancer with axitinib: phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments. Cancer. 2014;120(17):2694–703.

    Article  CAS  PubMed  Google Scholar 

  • Lupoli GA, Fonderico F, et al. The role of somatostatin analogs in the management of medullary thyroid carcinoma. J Endocrinol Investig. 2003;26(8 Suppl):72–4.

    CAS  Google Scholar 

  • 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 

  • Machens A, Dralle H. Surgical treatment of medullary thyroid cancer. Recent Results Cancer Res. 2015;204:187–205.

    Article  PubMed  Google Scholar 

  • Machens A, Lorenz K, et al. Utility of serum procalcitonin for screening and risk stratification of medullary thyroid cancer. J Clin Endocrinol Metab. 2014;99(8):2986–94.

    Article  CAS  PubMed  Google Scholar 

  • Maiza JC, Grunenwald S, et al. Use of 131 I-MIBG therapy in MIBG-positive metastatic medullary thyroid carcinoma. Thyroid. 2012;22(6):654–5.

    Article  CAS  PubMed  Google Scholar 

  • Mathiesen JS, Habra MA, et al. Risk profile of the RET A883F germline mutation: an international collaborative study. J Clin Endocrinol Metab. 2017;102(6):2069–74.

    Article  PubMed  Google Scholar 

  • Matias-Guiu X. Mixed medullary and follicular carcinoma of the thyroid. On the search for its histogenesis. Am J Pathol. 1999;155(5):1413–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matrone A, Valerio L, et al. Protein kinase inhibitors for the treatment of advanced and progressive radiorefractory thyroid tumors: from the clinical trials to the real life. Best Pract Res Clin Endocrinol Metab. 2017;31(3):319–34.

    Article  CAS  PubMed  Google Scholar 

  • Meijer JA, le Cessie S, et al. Calcitonin and carcinoembryonic antigen doubling times as prognostic factors in medullary thyroid carcinoma: a structured meta-analysis. Clin Endocrinol. 2010;72(4):534–42.

    Article  CAS  Google Scholar 

  • Melvin KE, Tashjian Jr AH. The syndrome of excessive thyrocalcitonin produced by medullary carcinoma of the thyroid. Proc Natl Acad Sci U S A. 1968;59(4):1216–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Menko FH, van der Luijt RB, et al. Atypical MEN type 2B associated with two germline RET mutations on the same allele not involving codon 918. J Clin Endocrinol Metab. 2002;87(1):393–7.

    Article  CAS  PubMed  Google Scholar 

  • Mian C, Pennelli G, et al. Combined RET and Ki-67 assessment in sporadic medullary thyroid carcinoma: a useful tool for patient risk stratification. Eur J Endocrinol. 2011;164(6):971–6.

    Article  CAS  PubMed  Google Scholar 

  • Miccoli P, Minuto MN, et al. Clinically unpredictable prognostic factors in the outcome of medullary thyroid cancer. Endocr Relat Cancer. 2007;14(4):1099–105.

    Article  PubMed  Google Scholar 

  • 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 887–888.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moley JF, Debenedetti MK, et al. Surgical management of patients with persistent or recurrent medullary thyroid cancer. J Intern Med. 1998;243(6):521–6.

    Article  CAS  PubMed  Google Scholar 

  • Moura MM, Cavaco BM, et al. Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas. Br J Cancer. 2009;100(11):1777–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mucha L, Leidig-Bruckner G, et al. Phaeochromocytoma in multiple endocrine neoplasia type 2: RET codon-specific penetrance and changes in management during the last four decades. Clin Endocrinol. 2017;87(4):320–6.

    Article  CAS  Google Scholar 

  • Mulligan LM, Kwok JB, et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature. 1993;363(6428):458–60.

    Article  CAS  PubMed  Google Scholar 

  • Nashed C, Sakpal SV, et al. Medullary thyroid carcinoma metastatic to skin. J Cutan Pathol. 2010;37(12):1237–40.

    Article  PubMed  Google Scholar 

  • Nella AA, Lodish MB, et al. Vandetanib successfully controls medullary thyroid cancer-related Cushing syndrome in an adolescent patient. J Clin Endocrinol Metab. 2014;99(9):3055–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Niccoli P, Wion-Barbot N, et al. Interest of routine measurement of serum calcitonin: study in a large series of thyroidectomized patients. The French Medullary Study Group. J Clin Endocrinol Metab. 1997;82(2):338–41.

    Article  CAS  PubMed  Google Scholar 

  • Niederle B, Roka R, et al. The transplantation of parathyroid tissue in man: development, indications, technique, and results. Endocr Rev. 1982;3(3):245–79.

    Article  CAS  PubMed  Google Scholar 

  • Nieuwenhuijzen Kruseman AC, Bussemaker JK, et al. Radioiodine in the treatment of hereditary medullary carcinoma of the thyroid. J Clin Endocrinol Metab. 1984;59(3):491–4.

    Article  CAS  PubMed  Google Scholar 

  • Nikiforov Y, Biddinger P, Thompson LDR, editors. Diagnostic pathology and molecular genetics of the thyroid: a comprehensive guide for practicing thyroid pathology. In: Wolters Kluwer/Lippincott Williams & Wilkins (eds.), 2nd ed. 2012. Philadelphia PA 19103.

    Google Scholar 

  • Nilsson M, Williams D. On the origin of cells and derivation of thyroid cancer: C cell story revisited. Eur Thyroid J. 2016;5(2):79–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nocera M, Baudin E, et al. Treatment of advanced medullary thyroid cancer with an alternating combination of doxorubicin-streptozocin and 5 FU-dacarbazine. Groupe d’Etude des Tumeurs a Calcitonine (GETC). Br J Cancer. 2000;83(6):715–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nour-Eldin NA, Exner S, et al. Ablation therapy of non-colorectal cancer lung metastases: retrospective analysis of tumour response post-laser-induced interstitial thermotherapy (LITT), radiofrequency ablation (RFA) and microwave ablation (MWA). Int J Hyperth. 2017;33(7):820–9.

    Google Scholar 

  • Nusynowitz ML, Pollard E, et al. Treatment of medullary carcinoma of the thyroid with I-131. J Nucl Med. 1982;23(2):143–6.

    CAS  PubMed  Google Scholar 

  • Orita Y, Sugitani I, et al. Prospective evaluation of zoledronic acid in the treatment of bone metastases from differentiated thyroid carcinoma. Ann Surg Oncol. 2015;22(12):4008–13.

    Article  PubMed  Google Scholar 

  • Orlandi F, Caraci P, et al. Treatment of medullary thyroid carcinoma: an update. Endocr Relat Cancer. 2001;8(2):135–47.

    Article  CAS  PubMed  Google Scholar 

  • Ozgen AG, Hamulu F, et al. Evaluation of routine basal serum calcitonin measurement for early diagnosis of medullary thyroid carcinoma in seven hundred seventy-three patients with nodular goiter. Thyroid. 1999;9(6):579–82.

    Article  CAS  PubMed  Google Scholar 

  • Pacini F, Basolo F, et al. Medullary thyroid cancer. An immunohistochemical and humoral study using six separate antigens. Am J Clin Pathol. 1991;95(3):300–8.

    Article  CAS  PubMed  Google Scholar 

  • Pacini F, Fontanelli M, et al. Routine measurement of serum calcitonin in nodular thyroid diseases allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab. 1994;78(4):826–9.

    CAS  PubMed  Google Scholar 

  • Paepegaey AC, Cochand-Priollet B, et al. Long-term control of hypercortisolism by vandetanib in a case of medullary thyroid carcinoma with a somatic RET mutation. Thyroid. 2017;27(4):587–90.

    Article  CAS  PubMed  Google Scholar 

  • Papotti M, Kumar U, et al. Immunohistochemical detection of somatostatin receptor types 1–5 in medullary carcinoma of the thyroid. Clin Endocrinol. 2001;54(5):641–9.

    Article  CAS  Google Scholar 

  • Pelizzo MR, Boschin IM, et al. Natural history, diagnosis, treatment and outcome of medullary thyroid cancer: 37 years experience on 157 patients. Eur J Surg Oncol. 2007;33(4):493–7.

    Article  CAS  PubMed  Google Scholar 

  • Pellegriti G, Leboulleux S, et al. Long-term outcome of medullary thyroid carcinoma in patients with normal postoperative medical imaging. Br J Cancer. 2003;88(10):1537–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pitoia F, Bueno F, et al. Rapid response of hypercortisolism to vandetanib treatment in a patient with advanced medullary thyroid cancer and ectopic Cushing syndrome. Arch Endocrinol Metab. 2015;59(4):343–6.

    Article  PubMed  Google Scholar 

  • Randle RW, Balentine CJ, 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 

  • Raue F, Frank-Raue K. Genotype-phenotype relationship in multiple endocrine neoplasia type 2. Implications for clinical management. Hormones (Athens). 2009;8(1):23–8.

    Article  Google Scholar 

  • Raue F, Dralle H, et al. Long-term survivorship in multiple endocrine neoplasia type 2B diagnosed before and in the new millennium. J Clin Endocrinol Metab. 2018;103(1):235–43.

    Article  PubMed  Google Scholar 

  • Ravaud A, de la Fouchardiere C, et al. A multicenter phase II study of sunitinib in patients with locally advanced or metastatic differentiated, anaplastic or medullary thyroid carcinomas: mature data from the THYSU study. Eur J Cancer. 2017;76:110–7.

    Article  CAS  PubMed  Google Scholar 

  • Rieu M, Lame MC, et al. Prevalence of sporadic medullary thyroid carcinoma: the importance of routine measurement of serum calcitonin in the diagnostic evaluation of thyroid nodules. Clin Endocrinol. 1995;42(5):453–60.

    Article  CAS  Google Scholar 

  • Ringe KI, Panzica M, et al. Thermoablation of bone tumors. RoFo. 2016;188(6):539–50.

    Article  CAS  PubMed  Google Scholar 

  • Rohmer V, Vidal-Trecan G, et al. Prognostic factors of disease-free survival after thyroidectomy in 170 young patients with a RET germline mutation: a multicenter study of the Groupe Francais d’Etude des Tumeurs Endocrines. J Clin Endocrinol Metab. 2011;96(3):E509–18.

    Article  CAS  PubMed  Google Scholar 

  • Romei C, Cosci B, et al. RET genetic screening of sporadic medullary thyroid cancer (MTC) allows the preclinical diagnosis of unsuspected gene carriers and the identification of a relevant percentage of hidden familial MTC (FMTC). Clin Endocrinol. 2011;74(2):241–7.

    Article  CAS  Google Scholar 

  • Romei C, Casella F, et al. New insights in the molecular signature of advanced medullary thyroid cancer: evidence of a bad outcome of cases with double RET mutations. J Med Genet 2016a;53:729–734.

    Google Scholar 

  • Romei C, Ciampi R, et al. A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma. Nat Rev Endocrinol. 2016b;12(4):192–202.

    Article  CAS  PubMed  Google Scholar 

  • Rougier P, Calmettes C, et al. The values of calcitonin and carcinoembryonic antigen in the treatment and management of nonfamilial medullary thyroid carcinoma. Cancer. 1983;51(5):855–62.

    Article  CAS  PubMed  Google Scholar 

  • Salaun PY, Campion L, et al. Phase II trial of anticarcinoembryonic antigen pretargeted radioimmunotherapy in progressive metastatic medullary thyroid carcinoma: biomarker response and survival improvement. J Nucl Med. 2012;53(8):1185–92.

    Article  CAS  PubMed  Google Scholar 

  • Santarpia L, El-Naggar AK, et al. Four patients with cutaneous metastases from medullary thyroid cancer. Thyroid. 2008;18(8):901–5.

    Article  CAS  PubMed  Google Scholar 

  • Schlumberger MJ, Elisei R, et al. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol. 2009;27(23):3794–801.

    Article  CAS  PubMed  Google Scholar 

  • Schlumberger M, Bastholt L, et al. 2012 European thyroid association guidelines for metastatic medullary thyroid cancer. Eur Thyroid J. 2012a;1(1):5–14.

    Article  PubMed  PubMed Central  Google Scholar 

  • Schlumberger M, Bastholt L, Dralle H, Jarzab B, Pacini F, Smit JWA, the European Task Force. 2012 European Thyroid Association Guidelines for metastatic medullary thyroid cancer. Eur Thyroid J. 2012b;1:5–14.

    Article  PubMed  PubMed Central  Google Scholar 

  • Schlumberger M, Jarzab B, et al. A phase II trial of the multitargeted tyrosine kinase inhibitor lenvatinib (E7080) in advanced medullary thyroid cancer. Clin Cancer Res. 2016;22(1):44–53.

    Article  CAS  PubMed  Google Scholar 

  • Schlumberger M, Elisei R, et al. Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma. Ann Oncol. 2017;28(11):2813–9.

    Article  CAS  PubMed  Google Scholar 

  • Schmid KW. Histopathology of C cells and medullary thyroid carcinoma. Recent Results Cancer Res. 2015;204:41–60.

    Article  PubMed  Google Scholar 

  • Schuffenecker I, Ginet N, et al. Prevalence and parental origin of de novo RET mutations in multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma. Le Groupe d’Etude des Tumeurs a Calcitonine. Am J Hum Genet. 1997;60(1):233–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schwartz DL, Rana V, et al. Postoperative radiotherapy for advanced medullary thyroid cancer – local disease control in the modern era. Head Neck. 2008;30(7):883–8.

    Article  PubMed  Google Scholar 

  • Scollo C, Baudin E, et al. Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer. J Clin Endocrinol Metab. 2003;88(5):2070–5.

    Article  CAS  PubMed  Google Scholar 

  • Simbolo M, Mian C, et al. High-throughput mutation profiling improves diagnostic stratification of sporadic medullary thyroid carcinomas. Virchows Arch. 2014;465(1):73–8.

    Article  CAS  PubMed  Google Scholar 

  • Simoes-Pereira J, Macedo D, et al. Clinical outcomes of a cohort of patients with central nervous system metastases from thyroid cancer. Endocr Connect. 2016;5(6):82–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Skoura E. Depicting medullary thyroid cancer recurrence: the past and the future of nuclear medicine imaging. Int J Endocrinol Metab. 2013;11(4):e8156.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sletten K, Westermark P, et al. Characterization of amyloid fibril proteins from medullary carcinoma of the thyroid. J Exp Med. 1976;143(4):993–8.

    Article  CAS  PubMed  Google Scholar 

  • Tisell LE, Hansson G, et al. Reoperation in the treatment of asymptomatic metastasizing medullary thyroid carcinoma. Surgery. 1986;99(1):60–6.

    CAS  PubMed  Google Scholar 

  • Trimboli P, Giovanella L. Serum calcitonin negative medullary thyroid carcinoma: a systematic review of the literature. Clin Chem Lab Med. 2015;53(10):1507–14.

    Article  CAS  PubMed  Google Scholar 

  • Ukkat J, Gimm O, et al. Single center experience in primary surgery for medullary thyroid carcinoma. World J Surg. 2004;28(12):1271–4.

    Article  PubMed  Google Scholar 

  • van der Zee PA, de Boer A. Pheochromocytoma: a review on preoperative treatment with phenoxybenzamine or doxazosin. Neth J Med. 2014;72(4):190–201.

    PubMed  Google Scholar 

  • Valle LA, Kloos RT. The prevalence of occult medullary thyroid carcinoma at autopsy. J Clin Endocrinol Metab. 2011;96(1):E109–13.

    Article  CAS  PubMed  Google Scholar 

  • Verbeek HH, Meijer JA, et al. Fewer cancer reoperations for medullary thyroid cancer after initial surgery according to ATA guidelines. Ann Surg Oncol. 2015;22(4):1207–13.

    Article  PubMed  Google Scholar 

  • Vierhapper H, Raber W, et al. Routine measurement of plasma calcitonin in nodular thyroid diseases. J Clin Endocrinol Metab. 1997;82(5):1589–93.

    Article  CAS  PubMed  Google Scholar 

  • Viola D, Materazzi G, et al. Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study. J Clin Endocrinol Metab. 2015;100(4):1316–24.

    Article  CAS  PubMed  Google Scholar 

  • Vitale G, Fonderico F, et al. Pamidronate improves the quality of life and induces clinical remission of bone metastases in patients with thyroid cancer. Br J Cancer. 2001;84(12):1586–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weber T, Schilling T, et al. Impact of modified radical neck dissection on biochemical cure in medullary thyroid carcinomas. Surgery. 2001;130(6):1044–9.

    Article  CAS  PubMed  Google Scholar 

  • Wells Jr SA, Robinson BG, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30(2):134–41.

    Article  CAS  PubMed  Google Scholar 

  • Wells Jr SA, Pacini F, et al. Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: an update. J Clin Endocrinol Metab. 2013;98(8):3149–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wells Jr SA, Asa SL, 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 

  • Wertenbroek MW, Links TP, et al. Radiofrequency ablation of hepatic metastases from thyroid carcinoma. Thyroid. 2008;18(10):1105–10.

    Article  PubMed  Google Scholar 

  • Wilhelm SM, Wang TS, et al. The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. 2016;151(10):959–68.

    Article  PubMed  Google Scholar 

  • Wong RL, Kazaure HS, et al. Simultaneous medullary and differentiated thyroid cancer: a population-level analysis of an increasingly common entity. Ann Surg Oncol. 2012;19(8):2635–42.

    Article  PubMed  Google Scholar 

  • Wyon Y, Frisk J, et al. Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide. Maturitas. 1998;30(3):289–94.

    Article  CAS  PubMed  Google Scholar 

  • Xu JY, Murphy Jr WA, et al. Bone metastases and skeletal-related events in medullary thyroid carcinoma. J Clin Endocrinol Metab. 2016;101(12):4871–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zatelli MC, Tagliati F, et al. Somatostatin receptor subtype 1-selective activation reduces cell growth and calcitonin secretion in a human medullary thyroid carcinoma cell line. Biochem Biophys Res Commun. 2002;297(4):828–34.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Endocrine Unit, Department of Clinical and Experimental Medicine, University Hospital, University of Pisa, Pisa, Italy

    Rossella Elisei

  2. Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Institute – Cancer Center, Gliwice Branch, Gliwice, Poland

    Barbara Jarzab

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  1. Rossella Elisei
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  2. Barbara Jarzab
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Correspondence to Rossella Elisei .

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Editors and Affiliations

  1. Department of Endocrinology, University of Pisa, Pisa, Italy

    Paolo Vitti

  2. Department of Endocrinology and Metaboli, Odense Univeristy Hospital, Odense, Denmark

    Laszlo Hegedus

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Elisei, R., Jarzab, B. (2018). Medullary Carcinoma. In: Vitti, P., Hegedus, L. (eds) Thyroid Diseases. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-29195-6_22-1

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