World Journal of Surgery

, Volume 31, Issue 10, pp 1960–1965

Increased Risk of Lymph Node Metastasis in Multifocal Hereditary and Sporadic Medullary Thyroid Cancer

  • Andreas Machens
  • Steffen Hauptmann
  • Henning Dralle



In sporadic and hereditary medullary thyroid cancer, tumor multifocality may constitute an independent risk factor of lymph node metastasis on top of primary tumor size when the diameter of the largest primary tumor is the same.


Included in this institutional cohort study were 232 consecutive patients operated on at our institution for hitherto untreated medullary thyroid cancer. Associations of clinicopathologic variables with lymph node metastasis were investigated simultaneously using multivariate Cox regression analysis.


On univariate analysis, multifocal cancers developed lymph node metastases significantly more often (p ≤ 0.005) than unifocal cancers, in both the sporadic (90% vs. 41%) and the hereditary setting (48% vs. 14%). On multivariate Cox regression analysis on lymph node metastasis as a function of primary tumor diameter, only multifocal (vs. unifocal) tumor growth was significantly associated with lymph node metastasis (odds ratio [OR] = 2.5; p = 0.01). When multifocal growth was removed as an independent variable from the Cox model, heredity became the only significant predictor (OR = 3.1; p < 0.0001).


The excess risk of lymph node metastasis of 34%-49% in multifocal medullary thyroid cancer seems to be caused by concurrent smaller thyroid cancers. A diagnosis of more than one medullary thyroid cancer signifies a higher risk of lymph node metastasis, warranting systematic lymph node dissection.


  1. 1.
    Machens A, Niccoli-Sire P, Hoegel J, et al. (2003) Early malignant progression of hereditary medullary thyroid cancer. N Engl J Med 349:1517–1525PubMedCrossRefGoogle Scholar
  2. 2.
    Kaserer K, Scheuba C, Neuhold N, et al. (2001) Sporadic versus familial medullary thyroid microcarcinoma: a histopathologic study of 50 consecutive patients. Am J Surg Pathol 25:1245–1251PubMedCrossRefGoogle Scholar
  3. 3.
    Machens A, Gimm O, Ukkat J, et al. (2000) Improved prediction of calcitonin normalization in medullary thyroid carcinoma patients by quantitative lymph node analysis. Cancer 88:1909–1915PubMedCrossRefGoogle Scholar
  4. 4.
    Weber T, Schilling T, Frank-Raue K, et al. (2001) Impact of modified radical neck dissection on biochemical cure in medullary thyroid carcinomas. Surgery 130:1044–1049PubMedCrossRefGoogle Scholar
  5. 5.
    Scollo C, Baudin E, Travagli JP, et al. (2003) Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer. J Clin Endocrinol Metab 88:2070–2075PubMedCrossRefGoogle Scholar
  6. 6.
    Machens A, Schneyer U, Holzhausen HJ, et al. (2005) Prospects of remission in medullary thyroid carcinoma according to basal calcitonin level. J Clin Endocrinol Metab 90:2029–2034PubMedCrossRefGoogle Scholar
  7. 7.
    Beressi N, Campos JM, Beressi JP, et al. (1998) Sporadic medullary microcarcinoma of the thyroid: a retrospective analysis of eighty cases. Thyroid 8:1039–1044PubMedCrossRefGoogle Scholar
  8. 8.
    Röher HD, Simon D, Goretzki PE (1997) Guidelines in oncologic surgery: malignant thyroid tumors. Langenbecks Arch Surg 114 (Suppl 2):142Google Scholar
  9. 9.
    Machens A, Hinze R, Thomusch O, et al. (2002) Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg 26:22–28PubMedCrossRefGoogle Scholar
  10. 10.
    Hinze R, Holzhausen HJ, Gimm O, et al. (1998) Primary hereditary medullary thyroid carcinoma - C-cell morphology and correlation with preoperative calcitonin levels. Virchows Arch 433:203–208PubMedCrossRefGoogle Scholar
  11. 11.
    Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRefGoogle Scholar
  12. 12.
    Cox DR (1972) Regression models and life tables. J R Stat Soc 34:187–220Google Scholar
  13. 13.
    Tamagnini P, Iacobone M, Sebag F, et al. (2005) Lymph node involvement in macroscopic medullary thyroid carcinoma. Br J Surg 92:449–453PubMedCrossRefGoogle Scholar
  14. 14.
    Miyauchi A, Matsuzuka F, Hirai K, et al. (2002) Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutations. World J Surg 26:1023–1028PubMedCrossRefGoogle Scholar
  15. 15.
    Raffel A, Cupisti K, Krausch M, et al. (2004) Incidentally found medullary thyroid cancer: Treatment rationale for small tumors. World J Surg 28:397–401PubMedCrossRefGoogle Scholar
  16. 16.
    Fleming JB, Lee JE, Bouvet M, et al. (1999) Surgical strategy for the treatment of medullary thyroid carcinoma. Ann Surg 230:697–707PubMedCrossRefGoogle Scholar
  17. 17.
    Moley JF, DeBenedetti MK (1999) Patterns of nodal metastases in palpable medullary thyroid carcinoma. Recommendations for extent of node dissection. Ann Surg 229:880–888PubMedCrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2007

Authors and Affiliations

  • Andreas Machens
    • 1
  • Steffen Hauptmann
    • 2
  • Henning Dralle
    • 1
  1. 1.Department of General, Visceral and Vascular SurgeryMartin-Luther-University Halle-WittenbergHalle/SaaleGermany
  2. 2.Department of PathologyMartin-Luther-University Halle-WittenbergHalle/SaaleGermany

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