Background: Although cervical lymphatic metastasis (LM) of thyroid carcinoma (TC) occurs most frequently in children, adolescents, and young adults (CAYA), this population exhibits the most favorable prognosis. This study aimed to clarify the characteristics of LM in CAYA TC patients from immunobiological and epidemiological perspectives.

Methods: The collected preoperative clinical data included serum levels of inflammatory and immunobiological markers. The two-tailed t-test or the Mann–Whitney U test was used to compare variables. To control the false discovery rate (FDR), the Benjamini-Hochberg procedure was applied. Categorical variables were analyzed with the chi-squared test. Correlations between continuous variables were identified by Spearman analysis. Receiver operating characteristic (ROC) curve analysis and binary logistic regression were performed to evaluate the association of these factors with LM. Bootstrap resampling (1000 replicates) was used to correct for optimism and assess model stability.

Results: This study was ultimately limited to 487 CAYA participants, including 317 (65.1%) with cervical LM. The LM rate was higher in CAYA males (71.9%) than in CAYA females (62.4%) (p = 0.045). Patients with LM exhibited elevated levels of monocyte ratio (MOR) (q = 0.038), thyroglobulin (Tg) (q = 0.008), and tumor necrosis factor-alpha (TNF-α) (q = 0.04) (q-values representing FDR-adjusted p-values). Young age (OR = 0.79, 95% CI: 0.70–0.91, p = 0.001) and larger tumor size (OR = 1.43, 95% CI: 1.05–1.96, p = 0.02) were independent risk factors for LM. The ROC curve revealed that age (area under the curve (AUC) = 0.63, 95% CI: 0.56–0.70), tumor size (AUC = 0.66, 95% CI: 0.59–0.74), Tg (AUC = 0.58, 95% CI: 0.51–0.66), and TNF-α (AUC = 0.61, 95% CI: 0.53–0.68) were predictive of LM. The combination of four indicators (age, tumor size, Tg, and TNF-α) enhanced predictive performance, achieving an AUC of 0.70 (95% CI: 0.63–0.76). In the N1 subgroup, significant sex differences were observed in markers, including Tg, interleukin (IL)-6, IL-4, MOR, natural killer cells, lymphocyte ratio, antithyroglobulin antibody, neutrophil ratio, platelet and Th/Ts (all q < 0.05).

Conclusion: This study identified younger age and larger tumor size as independent risk factors for LM in CAYA TC patients, and preoperative immune-inflammatory markers were associated with LM. Additionally, patients with LM displayed distinct sex-specific immune-inflammatory features.