Comparative clinical and molecular profiling of papillary thyroid carcinomas with unilateral and bilateral lateral lymph node metastasis: a retrospective cohort study.

PURPOSE: Studies on pathological and genetic features related to lateral lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remain limited. This study aimed to elucidate these features.

METHODS

A total of 135 patients with PTC who underwent total thyroidectomy with lateral neck dissection between 2000 and 2021 were retrospectively analyzed. Next-generation sequencing-based mutation panel analysis was conducted for 26 cases with unilateral or bilateral LNM.

RESULTS

Contralateral central LNM ratio (P = 0.001) and extrathyroidal extension (P = 0.04) were significantly associated with contralateral lateral LNM. The cutoff value of central LNM ratio for predicting contralateral lateral LNM was 0.59 in total cases and 0.34 in contralateral cases. Receiver operating characteristic analysis demonstrated statistically significant but modest discrimination, with relatively low specificity. The bilateral group showed a broader distribution of genomic alterations, including copy number losses (e.g., FCGR2B, APOBEC3B) and enriched signaling pathways (RTK/RAS, Hippo, Notch). One bilateral case had a CCDC6::RET fusion.

CONCLUSION

Bilateral LNM cases showed higher nodal burden and a broader distribution of genomic alterations in this limited cohort. These findings suggest potential biological heterogeneity in PTC with lateral LNM and warrant validation in larger studies.