The Impact of Metastatic Lymph Nodes on Risk Stratification in Differentiated Thyroid Cancer: Have We Reached a Higher Level of Understanding?

Background: The revised American Thyroid Association (ATA) management guidelines for differentiated thyroid cancer emphasize a variety of clinicopathologic features of metastatic lymph nodes in determining the risk of recurrence. The mere presence of a positive node is not sufficient to confer reliable prognostic significance. The number and size of lymph nodes, as well as the presence of extranodal extension (ENE), impact risk stratification. Moreover, the presence of clinically evident lymph nodes is important for determining risk of recurrence. A patient's place on the risk spectrum has ramifications for the management of differentiated thyroid cancer. However, there are inherent inconsistencies in the identification and characterization of metastatic lymph nodes. Moreover, the significance of ENE must be clarified. Summary: There are many obstacles to the consistent reporting of metastatic lymph nodes. What constitutes a "clinically evident" lymph node has not been well defined, lacks precision, and varies depending on clinical context, as well as the experience of the surgeon and the ultrasonographer. The number of lymph nodes sampled by surgeons and reported by pathologists may vary from institution to institution. The literature on ENE has been limited by the fact that the definition of ENE has not been standardized. Nevertheless, 17/19 manuscripts reviewed herein suggest that ENE confers a worse prognosis. The ATA risk stratification for metastatic lymph nodes published in the 2015 guidelines combines clinicopathological features that are variably identified and reported across institutions. This review brings into question the significance of the number of nodes with ENE, a factor that is used as an important stratifying variable in the latest guidelines. Conclusions: Metastatic lymph nodes do not all carry the same prognostic significance, but a risk assignment based on the ATA guidelines is limited by a lack of standardization in clinical and pathologic definitions, lymph node sampling, and reporting. This study reviews the limitations of prior studies on ENE and concludes that the body of the evidence reported in those studies suggests that ENE increases the risk of recurrence. The impact of ENE in lymph nodes in thyroid cancer risk stratification should be reconsidered.