Risk factors for lung metastasis in children and adolescent patients with papillary thyroid cancer: A retrospective cohort study

Pediatric papillary thyroid cancer (pPTC) exhibits a higher incidence of lung metastasis (LM) compared to its adult counterpart. This study supplements the gap in pediatric management guidelines by exploring factors associated with LM in pPTC and characterizing relevant genetic alterations. We retrospectively analyzed pPTC patients under 20 years who underwent initial surgery at our center between December 2008 and December 2022. Clinicopathological features, treatment approaches, outcomes, and target-gene sequencing were reviewed to identify risk factors and genetic variations. Among 114 pPTC cases, 17 developed LM. Risk factors associated with LM included younger age, male gender, larger tumor size, multifocality, extrathyroidal extension, lymphatic invasion, and the number of metastatic lymph nodes (NMLNs), with NMLNs > 14 identified as an independent predictor (OR = 18.20, p = 0.037). Treatment responses with radioiodine related to postoperative stimulated thyroglobulin (sTg) levels (p = 0.003). Genomic analysis identified 1007 somatic mutations, including in the BRAF, APC, RET, and ATM genes, with RET-NCOA4 fusions observed in the LM subgroup. LM is common in pPTC, and NMLNs > 14 is a critical risk indicator. The genetic profile, particularly RET mutations, highlights potential therapeutic targets. Further large-scale studies are needed to validate these findings.