Abstract
Medullary thyroid cancer (MTC) can vary in tumor biology and progression. The most important indicator of distant metastases, determining clinical outcome, is lymph node metastasis to the neck and mediastinum. Surgical cure is within reach in node-negative tumors or node-positive tumors with fewer than 10 lymph node metastases. From a surgical point of view, compartment-oriented lymph node dissection, clearing gross, and occult metastases are important for locoregional tumor control. The discovery of missense germline mutations in the RET proto-oncogene and the close genotype-phenotype correlation in hereditary MTC promoted the worldwide breakthrough of prophylactic thyroidectomy. The best approach to hereditary MTC affords the DNA-based/biochemical concept, which is geared at limiting prophylactic surgery to total thyroidectomy at minimal surgical morbidity before the tumor can spread beyond the thyroid capsule. To improve outcome, routine calcitonin screening in nodular thyroid disease and DNA-based screening of the offspring in RET families are effective interventions.
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Barbosa SLS, Rodien P, Leboulleux S, Niccoli-Sire P, Kraimps JL, Caron P, Archambeaud-Mouveroux F, Conte-Devolx B, Rohmer V; Groupe d’Etude des Tumeurs Endocrines (2005) Ectopic adrenocortico-tropic hormone-syndrome in medullary carcinoma of the thyroid: a retrospective analysis and review of the literature. Thyroid 15:618–623
Basuyau JP, Mallet E, Leroy M, Brunelle P (2004) Reference intervals for serum calcitonin in men, women, and children. Clin Chem 50:1828–1830
Ben M, Gardet P, Roche A (1989) Value of venous catheterization and calcitonin studies in the treatment and management of clinically inapparent medullary thyroid carcinoma. Cancer 63:133–138
Billroth Th (1869) Chirurgische Erfahrungen. Zürich 1860–1867. Langenbecks Arch Klin Chir 10:158–171
Brauckhoff M, Gimm O, Weiss CL, Ukkat J, Sekulla C, Brauckhoff K, Nguyen Thanh P, Dralle H (2004) Multiple endocrine neoplasia 2B syndrome due to codon 918 mutation: clinical manifestation and course in early and late onset disease. World J Surg 28:1305–1311
Brauckhoff M, Machens A, Hess S, Lorenz K, Gimm O, Brauckhoff K, Sekulla C, Dralle H (2008) Premonitory symptoms preceding metastatic medullary thyroid cancer in MEN 2B: an exploratory analysis. Surgery 144:1044–1051
Brauckhoff M, Machens A, Lorenz K, Bjøro T, Varhaug JE, Dralle H (2014) Surgical curability of medullary thyroid cancer in multiple endocrine neoplasia 2B: a changing perspective. Ann Surg 259:800–806
Burk W (1901) Über einen Amyloidtumor mit Metastasen. Inaugural-Dissertation, Tübingen
Chambon G, Alovisetti C, Idoux-Louche C, Reynaud C, Rodier M, Guedj AM, Chapuis H, Lallemant JG, Lallemant B (2011) The use of preoperative routine measurement of basal serum thyrocalcitonin in candidates for thyroidectomy due to nodular thyroid disorders: results from 2733 consecutive patients. J Clin Endocrinol Metab 96:75–81
Chen H, Roberts JR, Ball DW, Eisele DW, Baylin SB, Udelsman R, Bulkley GB (1998) Effective long-term palliation of symptomatic, incurable metastatic medullary thyroid cancer by operative resection. Ann Surg 227:887–895
Copp DH (1962) Evidence for calcitonin: new hormone from parathyroid that lowers blood calcium. Endocrinology 70:638–649
Donis-Keller H, Dou S, Chi D, Carlson KM, Toshima K, Lairmore TC, Howe JR, Moley JF, Goodfellow P, Wells SA (1993) Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet 7:851–856
Doyle P, Duren C, Nerlich K, Verburg FA, Grelle I, Jahn H, Fassnacht M, Mäder U, Reiners C, Luster M (2009) Potency and tolerance of calcitonin stimulation with high-dose calcium versus pentagastrin in normal adults. J Clin Endocrinol Metab 94:2970–2974
Dralle H (2002) Lymph node dissection and medullary thyroid carcinoma. Br J Surg 89:1073–1075
Dralle H, Machens A (2013) Surgical management of the lateral neck compartment for metastatic thyroid cancer. Curr Opin Oncol 25:20–26
Dralle H, Damm I, Scheumann GFW, Kotzerke J, Kupsch E, Geerlings H, Pichlmayr R (1994) Compartment-oriented microdissection of regional lymph nodes in medullary thyroid carcinoma. Surg Today 24:112–121
Dralle H, Gimm O, Simon D, Frank-Raue K, Görtz G, Niederle B, Wahl RA, Koch B, Walgenbach S, Hampel R, Ritter MM, Spelsberg F, Heiss A, Hinze R, Höppner W (1998) Prophylactic thyroidectomy in 75 children and adolescents with hereditary medullary thyroid carcinoma—The German and Austrian experience. World J Surg 22:744–751
Dralle H, Machens A, Brauckhoff M (2013a) Syndromic medullary thyroid carcinoma: MEN 2A and MEN 2B. In: Randolph GW (ed) Surgery of the thyroid and parathyroid glands 2nd edn. Saunders, pp 225–236
Dralle H, Musholt TJ, Schabram J, Steinmüller T, Frilling A, Simon D, Goretzki PE, Niderle B, Scheuba C, Clerici T, Hermann M, Kußmann J, Lorenz K, Nies C, Schabram P, Trupka A, Zielke A, Karges W, Luster M, Schmid KW, Vordermark D, Schmoll HJ, Mühlenberg R, Schober O, Rimmele H, Machens A for the German Societies of General and Visceral Surgery; Endocrinology; Nuclear Medicine; Pathology; Radiooncology; Oncological Hematology; and the German Thyroid Cancer Patient Support Organization (2013b) German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors. Langenbecks Arch Surg 398:347–375
Elisei R, Bottici V, Luchetti F, Di Coscio G, Romei C, Grasso L, Miccoli P, Iacconi P, Basolo F, Pinchera A, Pacini F (2004) Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorder. J Clin Endocrinol Metab 89:163–168
Elisei R, Romei C, Renzini G, Bottici V, Cosci B, Molinaro E, Agate L, Cappagli V, Miccoli P, Berti P, Faviana P, Ugolini C, Basolo F, Vitti P, Pinchera A (2012) 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 97:426–435
Elisei R, Alevizaki M, Conte-Devolx B, Frank-Raue K, Leite V, Williams GR (2013) 2012 European Thyroid Association Guidelines for genetic testing and its clinical consequences in medullary thyroid cancer. Eur Thyroid J 1:216–231
Esfandiari NH, Hughes DT, Yin H, Banerjee M, Haymart MR (2014) The effect of extent of surgery and number of lymph node metastases on overall survival in patients with medullary thyroid cancer. J Clin Endocrinol Metab 99:448–454
Esik O, Tusnady G, Tron L, Boer A, Szentirmay Z, Szabolcs I, Racz K, Lengyle E, Szekely J, Kasler M (2002) Markov model-based estimation of individual survival probability for medullary thyroid cancer patients. Pathol Oncol Res 8:93–104
Foster GV, McIntyre I, Pearse AGE (1964) Thyroid origin of calcitonin. Nature 202:1303–1305
Frank-Raue K, Raue F, Buhr HJ (1992) Localization of occult persisting medullary thyroid carcinoma before microsurgical reoperation: high sensitivity of selective venous catheterisation. Thyroid 2:113–117
Frank-Raue K, Machens A, Leidig-Bruckner G, Rondot S, Haag C, Schulze E, Lorenz A, Kreissl MC, Dralle H, Raue F, Schmid KW (2013) Prevalence and clinical spectrum of nonsecretory medullary thyroid carcinoma in a series of 839 patients with sporadic medullary thyroid carcinoma. Thyroid 23:294–300
Gurlt E (1861) Bericht über die Leistungen und Fortschritte auf dem Gebiet der Chirurgie im Jahre 1859. Langenbecks Arch Klin Chir 1:184–187
Hazard JB, Hawk WA, Crile G (1959) Medullary (solid) carcinoma of the thyroid, a clinicopathologic entity. J Clin Endocrinol Metab 19:152–161
Horn RC (1951) Carcinoma of the thyroid. Description of a distinctive morphological variant and report of seven cases. Cancer 4:697–707
Jacquet J (1906) Ein Fall von metastasierenden Amyloidtumoren (Lymphosarkom). Virchows Arch 185:251–268
Karges W, Dralle H, Raue F, Mann K, Reiners C, Grussendorf M, Hüfner M, Niederle B, Brabant G, German Society for Endocrinology (DGE)—Thyroid Section (2004) Calcitonin measurement to detect medullary thyroid carcinoma in nodular goiter: German evidence-based consensus recommendation. Exp Clin Endocrinol Diabetes 112:52–58
Kratzsch J, Petzold A, Raue F, Reinhardt W, Bröcker-Preuβ M, Görges R, Mann K, Karges W, Morgenthaler N, Luster M, Reiners C, Thiery J, Dralle H, Fuhrer D (2011) Basal and stimulated calcitonin and procalcitonin by various assays in patients with and without medullary thyroid cancer. Clin Chem 57:467–474
Lips C, Landsvater RM, Hoppener J, Geerdink RA, Blijham G, van Veen JMJS, van Gils A, de Wit MJ, Zewald RA, Berends M, Beemer FA, Brouwers-Smalbraak J, Jansen R, van Amstel HKP, van Vroonhoven T, Vroom TM (1994) Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 331:828–835
Lorenz K, Brauckhoff M, Behrmann C, Sekulla C, Ukkat J, Brauckhoff K, Gimm O, Dralle H (2005) Selective arterial chemoembolization for hepatic metastases from medullary thyroid carcinoma. Surgery 138:986–993
Lorenz K, Abuazab M, Sekulla C, Nguyen Thanh P, Brauckhoff M, Dralle H (2010) Management of lymph fistulas in thyroid surgery. Langenbeck’s Arch Surg 395:911–917
Machens A, Niccoli-Sire P, Hoegel J, Frank-Raue K, Vroonhoven v T J, Roeher H D, Wahl R A, Lamesch P, Raue F, Conte-Devolx B, Dralle H, for the European Multiple Endocrine Neoplasia (EUROMEN) Study Group (2003) Early malignant progression of hereditary medullary thyroid cancer. N Engl J Med 349:1517–1523
Machens A, Dralle H (2009) Prophylactic thyroidectomy in RET carriers at risk for hereditary medullary thyroid cancer. Thyroid 19:551–554
Machens A, Dralle H (2010a) Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab 95:2655–2663
Machens A, Dralle H (2010b) Decreasing tumor size of thyroid cancer in Germany: institutional experience 1995–2009. Eur J Endocrinol 163:111–119
Machens A, Dralle H (2013a) Prognostic impact of N staging in 715 medullary thyroid cancer patients: proposal for a revised staging system. Ann Surg 257:323–329
Machens A, Dralle H (2013b) Benefit-risk balance of reoperation for persistent medullary thyroid cancer. Ann Surg 257:751–757
Machens A, Gimm O, Ukkat J, Sutter T, Dralle H (1999) Repeat mediastinal lymph node dissection for palliation in advanced medullary thyroid carcinoma. Langenbeck’s Arch Surg 384:271–286
Machens A, Gimm O, Ukkat J, Hinze R, Schneyer U, Dralle H (2000a) Improved prediction of calcitonin normalization in medullary thyroid carcinoma patients by quantitative lymph node analysis. Cancer 88:1909–1915
Machens A, Haedicke J, Hinze R, Thomusch O, Schneyer U, Dralle H (2000b) Hypercalcitoninemia in a sporadic asymptomatic neuroendocrine tumor of the pancreatic tail. Dig Surg 17:522–524
Machens A, Haedecke J, Holzhausen HJ, Thomusch O, Schneyer U, Dralle H (2000c) Differential diagnosis of calcitonin-secreting neuroendocrine carcinoma of the foregut by pentagastrin stimulation. Langenbeck’s Arch Surg 385:398–401
Machens A, Hinze R, Dralle H (2001a) Surgery on the cervicovisceral axis for invasive thyroid cancer. Langenbeck’s Arch Surg 386:318–323
Machens A, Hinze R, Lautenschläger C, Thomusch O, Dralle H (2001b) Thyroid carcinoma invading the cervicovisceral axis: routes of invading and clinical implications. Surgery 129:23–28
Machens A, Holzhausen HJ, Dralle H (2004) Prediction of mediastinal lymph node metastasis in medullary thyroid carcinoma. Br J Surg 91:709–712
Machens A, Brauckhoff M, Holzhausen HJ, Nguyen Thanh P, Lehnert H, Dralle H (2005a) Codon-specific development of pheochromocytoma in multiple endocrine neoplasia Type 2. J Clin Endocrinol Metab 90:3999–4003
Machens A, Schneyer U, Holzhausen HJ, Dralle H (2005b) Prospects of remission in medullary thyroid carcinoma according to basal calcitonin level. J Clin Endcrinol Metab 90:2029–2034
Machens A, Hauptmann S, Dralle H (2007a) Increased risk of lymph node metastasis in multifocal hereditary and sporadic medullary thyroid cancer. World J Surg 31:1960–1965
Machens A, Hofmann C, Hauptmann S, Dralle H (2007b) Locoregional recurrence and death from medullary thyroid carcinoma in a contemporaneous series: five-year results. Eur J Endocrinol 157:85–93
Machens A, Hoffmann F, Sekulla C, Dralle H (2009a) Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer. Endocr Relat Cancer 16:1291–1298
Machens A, Lorenz K, Dralle H (2009b) Individualization of lymph node dissection in RET (rearranged during transfection) carriers at risk for medullary thyroid cancer. Ann Surg 250:305–310
Machens A, Lorenz K, Dralle H (2013) Peak incidence of pheochromocytoma and primary hyperparathyroidism in multiple endocrine neoplasia 2: need for age-adjusted biochemical screening. J Clin Endocinol Metab 98:E336–E345
Machens A, Lorenz K, Dralle H (2014a) Progression of medullary thyroid cancer in RET carriers of ATA class A and C mutations. J Clin Endocinol Metab 99:E286–E292
Machens A, Lorenz K, Dralle H (2014b) Utility of serum procalcitonin for screening and risk stratification of medullary thyroid cancer. J Clin Endocinol Metab 99:2986–2994
Manning PC, Molnar GD, Black BM, Priestley JT, Woolner LB (1963) Pheochromocytoma, hyperparathyroidism and thyroid carcinoma occurring coincidentally—report of a case. N Engl J Med 268:68–72
Milone F, Ramundo V, Chiofalo MG, Severino R, Paciolla I, Pezzullo L, Lombardi G, Colao A, Faggiano A (2010) Predictive value of pentagastrin test for preoperative differential diagnosis between C-cell hyperplasia and medullary thyroid carcinoma in patients with moderately elevated basal calcitonin levels. Clin Endocrinol 73:85–88
Mirallié E, Vuilez JP, Bardet T, Frampas E, Dupas B, Ferrer L, Faivre-Chauvet A, Murat A, Charbonnel B, Barbet J, Goldenberg DM, Chatal JF, Kraeber-Bodéré F (2005) High frequency of bone/bone marrow involvement in advanced medullary thyroid cancer. J Clin Endocrinol Metab 90:779–788
Miyauchi A, Matsuzuka F, Kuma K, Takai S, Nakamoto K, Nakamura K, Nanjo S, Maeda M (1988) Evaluation of surgical results and prediction of prognosis in patient with medullary thyroid carcinoma by analysis of serum calcitonin levels. World J Surg 12:610–615
Miyauchi A, Matsuzuka F, Hirai K, Yokozawa T, Kobayashi K, Ito Y, Nakano K, Kuma K, Futami H, Yamaguchi K (2002) Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutations. World J Surg 26:1023–1028
Moley JF, DeBenedetti MK (1999) Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg 229:880–887
Mulligan LM, Kwok JBJ, Healey CS, Elsdon MJ, Eng C, Gardner E, Love DR, Mole SE, Moore JK, Papi L, Ponder MA, Telenius HK, Tunnacliffe A, Ponder BA (1993) Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 363:458–460
Pearse AGE, Polak JM (1971) Cytochemical evidence for the neural crest origin of mammalian ultimobranchial C-cells. Histochemistry 27:96–102
Pellegriti G, Leboulieux S, Baudin E, Ballon N, Scollo C, Travagli JP, Schlumberger M (2003) Long-term outcome of medullary thyroid carcinoma in patients with normal postoperative medical imaging. Br J Cancer 88:1537–1542
Scollo C, Baudin E, Travagli JP, Caillou B, Bellon N, Leboulleux S, Schlumberger M (2003) Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer. J Clin Endocrinol Metab 88:2070–2075
Sipple JH (1961) The association of pheochromocytoma with carcinoma of the thyroid gland. Am J Med 31:163–166
Skinner MA, Moley JA, Dilley WG, Owzar K, DeBenedetti MK, Wells SA (2005) Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med 353:1105–1113
Stoffel E (1910) Lokales Amyloid der Schilddrüse. Virchows Arch 201:245–252
Szavcsur P, Gödeny M, Bajzik G, Lengyel E, Repa I, Trón L, Boér A, Vincze B, Póti Z, Szabolcs I, Esik O (2005) Angiography-proven liver metastases explain low efficacy of lymph node dissections in medullary thyroid cancer patients. Eur J Surg Oncol 31:183–190
Tashjian AH Jr, Melvin EW (1968) Medullary carcinoma of the thyroid gland. Studies of thyrocalcitonin in plasma and tumor extracts. N Engl J Med 279:279–283
Tashjian AH Jr, Howland BG, Melvin KEW, Hill CS Jr (1970) Immunoassay of human calcitonin: clinical measurement, relation to serum calcium and studies in patients with medullary thyroid carcinoma. N Eng J Med 283:890–895
Tisell L, Hansson G, Jansson S, Salander H (1986) Reoperation in the treatment of asymptomatic metastasizing medullary thyroid carcinoma. Surgery 99:60–66
Tung WS, Vesely TM, Moley JF (1995) Laparoscopic detection of hepatic metastases in patients with residual or recurrent medullary thyroid cancer. Surgery 118:1024–1030
Wells SA, Chi DD, Toshima K, Dehner LP, Coffin CM, Dowton B, Ivanovich JL, DeBenedetti MK, Dilley WG, Moley JF, Norton JA, Donis-Keller H (1994) Predictive DNA testing and prophylactic thyroidectomy in patients at risk for multiple endocrine neoplasia type 2A. Ann Surg 200:237–250
Wells SA Jr., Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, Lee N, Machens A, Moley JF, Pacini F, Raue F, Frank-Raue K, Robinson B, Rosenthal MS, Santoro M, Schlumberger M, Shah M, Waguespack SG (2015) Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma. Thyroid 25:567–610
Williams ED (1965) A review of 17 cases of carcinoma of the thyroid and phaeochromocytoma. J Clin Path 18:288–292
Wölfer A (1883) Über die Entwicklung und den Bau des Kropfes. Arch Klin Chir 29:1–97 and 754–866
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Machens, A., Dralle, H. (2015). Surgical Treatment of Medullary Thyroid Cancer. In: Raue, F. (eds) Medullary Thyroid Carcinoma. Recent Results in Cancer Research, vol 204. Springer, Cham. https://doi.org/10.1007/978-3-319-22542-5_9
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