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

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 < or = 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.