Exceptionality of Distant Metastasis in Node-Negative Hereditary and Sporadic Medullary Thyroid Cancer: Lessons Learned.

Abstract

Risk factors of lymph node and distant metastases have rarely been analyzed in hereditary and sporadic medullary thyroid cancer (MTC) using large genetic-clinical data sets. This comprehensive investigation aimed to explore risk factors of lymph node and distant metastases and interdependencies between age at thyroidectomy, primary tumor size, lymph node metastasis, and distant metastasis in patients with hereditary and sporadic MTC. We performed comparative analyses of risk factors of metastasis, stratified by hereditary MTC (4 mutational risk categories) and sporadic MTC. There were 1115 patients with hereditary MTC (307 patients) or sporadic MTC (808 patients). Age at thyroidectomy increased proportionately from 12.2, 22.7, 34.3, and 49.8 years for patients with decreasing mutational risk, compared with 52.1 years for patients with sporadic MTC. Metastatic primary tumors overall were 10.7 to 19.4 mm larger in node-positive patients and 15.9 to 19.3 mm larger in distant metastatic patients at thyroidectomy than nonmetastatic tumors. Distant metastases were noted in 13% to 50% of node-positive vs 0% of node-negative hereditary MTC, and in 23.5% of node-positive vs 1.7% of node-negative sporadic MTC. In multivariable logistic regression analysis for sporadic MTC, lymph node metastasis contributed to distant metastasis (odds ratio 12.4) more than primary tumor size (odds ratios of 7.8, 5.5, and 2.4 for tumors measuring >60, 41-60, and 21-40 mm, respectively). When thyroidectomy is performed before lymph node metastases have developed, distant metastases are exceptional, both in patients with hereditary MTC (irrespective of mutational risk level) and patients with sporadic MTC.