Context: There is no histopathological or radiological information on the natural course of tumor growth and lymph node metastasis in medullary thyroid cancer (MTC). Objective: This investigation aimed at determining annual rates of tumor growth and lymph node metastasis in hereditary MTC at the surgical pathology level. Design: This was a retrospective analysis. Setting: The setting was a tertiary referral center. Patients: Included were 172 carriers of American Thyroid Association (ATA) class C (95 patients) and class A rearranged during transfection (RET) mutations (77 patients) with MTC. Intervention: The intervention was compartment-oriented surgery. Main Outcome Measures: Comparisons of means between index and nonindex patients yielded incremental primary tumor diameter and incremental number of lymph node metastases, which were divided by incremental patient age at tissue diagnosis. Results: Annual primary tumor growth was 0.4-0.5 mm in node-negative carriers of ATA class A and C mutations. In node-positive carriers, annual primary tumor growth was 2.6 mm (ATA class C mutations) and 1.2 mm (ATA class A mutations), more than 6-fold (2.6 vs 0.4 mm) and more than 2-fold greater (1.2 vs 0.5 mm) than in their node-negative peers. Node-positive carriers revealed an annual rate of lymph node metastasis of 0.6-0.7 nodes independent of ATA class. Conclusions: Small MTCs may take longer than 10 years to become big enough to visualize on imaging. These slow growth rates highlight the importance of following up on patients for very long time periods to uncover at least some tumoral sources of persistent calcitonin production.
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