Abstract
Background
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.
Methods
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.
Results
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).
Conclusion
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.
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References
Machens A, Niccoli-Sire P, Hoegel J, et al. (2003) Early malignant progression of hereditary medullary thyroid cancer. N Engl J Med 349:1517–1525
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 25:1245–1251
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 88:1909–1915
Weber T, Schilling T, Frank-Raue K, et al. (2001) Impact of modified radical neck dissection on biochemical cure in medullary thyroid carcinomas. Surgery 130:1044–1049
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 88:2070–2075
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 90:2029–2034
Beressi N, Campos JM, Beressi JP, et al. (1998) Sporadic medullary microcarcinoma of the thyroid: a retrospective analysis of eighty cases. Thyroid 8:1039–1044
Röher HD, Simon D, Goretzki PE (1997) Guidelines in oncologic surgery: malignant thyroid tumors. Langenbecks Arch Surg 114 (Suppl 2):142
Machens A, Hinze R, Thomusch O, et al. (2002) Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg 26:22–28
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 433:203–208
Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481
Cox DR (1972) Regression models and life tables. J R Stat Soc 34:187–220
Tamagnini P, Iacobone M, Sebag F, et al. (2005) Lymph node involvement in macroscopic medullary thyroid carcinoma. Br J Surg 92:449–453
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 26:1023–1028
Raffel A, Cupisti K, Krausch M, et al. (2004) Incidentally found medullary thyroid cancer: Treatment rationale for small tumors. World J Surg 28:397–401
Fleming JB, Lee JE, Bouvet M, et al. (1999) Surgical strategy for the treatment of medullary thyroid carcinoma. Ann Surg 230:697–707
Moley JF, DeBenedetti MK (1999) Patterns of nodal metastases in palpable medullary thyroid carcinoma. Recommendations for extent of node dissection. Ann Surg 229:880–888
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Machens, A., Hauptmann, S. & Dralle, H. Increased Risk of Lymph Node Metastasis in Multifocal Hereditary and Sporadic Medullary Thyroid Cancer. World J Surg 31, 1960–1965 (2007). https://doi.org/10.1007/s00268-007-9185-1
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DOI: https://doi.org/10.1007/s00268-007-9185-1