# Skip metastases in papillary thyroid carcinoma: evidence from a multicenter European retrospective study

## TL;DR

This study finds that skip metastases in thyroid cancer are linked to less aggressive tumors and a higher occurrence of a specific cancer type.

## Contribution

The study provides new insights into the clinicopathological features of skip metastases in papillary thyroid carcinoma using a large European cohort.

## Key findings

- Skip metastases were associated with older age, smaller tumors, and less aggressive features like fewer positive lymph nodes.
- The follicular variant of thyroid cancer was more common in skip metastases compared to non-skip cases.
- Central nodal yield and lymphovascular invasion were significant predictors of non-skip metastases.

## Abstract

Papillary thyroid carcinoma (PTC) frequently involves cervical lymph nodes. Lateral nodal involvement without central compartment disease (Skip Metastasis, SM) poses diagnostic and staging challenges. We aimed to characterize clinicopathological features of SM in a large multicenter European cohort comparing SM+ (lateral only) and SM- (central + lateral) disease.

We conducted a retrospective study across four high-volume European centers (01/2020-12/2022). Adults with histologically proven PTC, confirmed lateral cervical metastases, and both central (level VI) and lateral (levels II–IV) dissections were included. Additional subanalyses among pT1a and cases with >2 central nodes retrieved were employed to control for confounders.

Among 283 patients, 48 (17.0%) were SM +. SM+ patients were older (47 vs 39 years, p=0.006) and had smaller primaries (12 vs 16 mm, p=0.008), fewer microfoci (2 vs 3, p=0.013), fewer lateral nodes retrieved (22 vs 25, p=0.004), fewer positive nodes (2 vs 4, p<0.001), and smaller largest metastatic node (14.5 vs 18.5 mm, p=0.010). Follicular variant was prevalent in SM+ (18.8% vs 4.3%; p=0.001). Features of aggressiveness were less frequent in SM+: multifocality (62.5% vs 74.9%, p=0.016), bilaterality (37.5% vs 52.8%, p=0.024), microscopic ETE (33.3% vs 52.3%, p=0.016), LVI (14.6% vs 47.7%, p<0.001), and extranodal extension (8.3% vs 20.4%, p=0.043). Findings persisted in different subanalyses (>2 central nodes; n=252. pT1a tumors n=73). In multivariable analysis, central nodal yield (OR 1.13, p=0.003) and LVI (OR 6.5, p=0.005) were associated with SM-, whereas follicular variant was inversely associated (OR 0.24, p=0.028).

SM were not uncommon and associated with a less aggressive clinicopathologic profile and increased proportion of follicular variant. While limited central nodal yield may pose false positive risks, key associations persisted after adjustment. Prospective studies are warranted to refine risk stratification and surgical planning.