Multifocal Papillary Thyroid Cancer Increases the Risk of Central Lymph Node Metastasis

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Abstract
Background - Papillary thyroid cancer (PTC) is the most common thyroid malignancy, with a strong predilection for lymph node metastasis, most commonly to the central neck compartment (level VI). Few studies have evaluated lymph node metastasis in multifocal PTC, and the role of level VI dissection in the management of PTC remains controversial. This retrospective analysis evaluated the rate of level VI lymph node positivity in multifocal PTC, as compared with unifocal disease, in order to better inform surgical decision-making. Methods - Patients with PTC who underwent total or hemi-thyroidectomy plus level VI lymph node dissection at our institution, between January 2008-June 2014, were included (total=227). We recorded the number and laterality of PTC foci, lympho-vascular invasion (LVI), extra-thyroidal extension (ETE) and positive/total number of level VI lymph nodes. Fisher exact test was used to determine univariate associations, and multivariate analysis was done by logistical regression. Results - There was an association between the number of PTC foci and level VI node positivity (p<0.001), with an odds ratio (OR) of 2.355 in patients with ≥ 3 tumor foci (p=0.026). The OR for central neck metastasis was 1.088 with each additional focus of PTC (p=0.018). The risk of level VI node positivity in the presence of 1-2 foci was only 19%, with no appreciable difference between 1 and 2 foci. This risk increased in the presence of 3-9 foci (38%), and 10 or more foci (88%). Level VI node positivity was associated with ETE (p<0.001), LVI (p<0.001), and size of the largest focus (p<0.001). There was no association between level VI lymph node positivity and male gender (p=0.089), bilaterality (p=0.276) or age (p=0.076). Conclusions - There is a significant association between multifocal PTC and level VI lymph node positivity, increasing proportionally with the number of foci. These findings recognize multifocality as a sign of tumor aggressiveness, as evidenced by a higher propensity for lymph node metastasis.

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