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.
Keywords: Compartment-oriented lymph node dissection; Genotype-phenotype correlation; Lymph node metastases; Medullary thyroid cancer; Prophylactic thyroidectomy; RET proto-oncogene.