In recent decades, the incidence of thyroid cancer has increased significantly. According to the Global Cancer Statistics 2020, thyroid cancer is now the ninth most common cancer worldwide (1). Among all malignant tumors, thyroid cancer exhibits the highest growth rate, with an annual increase of approximately 6% (2). Papillary thyroid carcinoma (PTC) is the most common primary thyroid malignancy, accounting for approximately 85–90% of all cases (3). Cervical lymph node metastasis is a frequent biological feature of PTC, occurring in 40–90% of cases (4). Cervical lymph node metastasis is classified into central lymph node metastasis (level VI) and lateral lymph node metastasis (LLNM) (levels II–V). According to the American Thyroid Association (ATA) guidelines, ipsilateral lobectomy is recommended for small, unifocal tumors without extrathyroidal extension or LNM, due to the indolent nature of PTC (5). In contrast, therapeutic lateral lymph node dissection (LLND) is advised for patients with clinically evident LLNM (5). LLNM is associated with a higher rate of regional recurrence than central LNM, leading to a poorer prognosis. Therefore, accurate preoperative identification of LLNM is critical for optimal staging, personalized treatment planning, and prognosis assessment.

International guidelines recommend therapeutic LLND for PTC patients with LLNM confirmed by preoperative imaging and pathology (6). Prophylactic LLND may be performed in patients with suspected but unconfirmed metastasis. However, LLND may constitute overtreatment in low-risk cases. Considering the complexity of neck anatomy, patients undergoing LLND carries risks such as bleeding, nerve injury, and lymphatic leakage (7). Hence, a systematic preoperative evaluation of LLNM is essential to determine the appropriate surgical strategy and extent.

Currently, suspicious lymph nodes are primarily assessed by ultrasound (US), computed tomography (CT), and fine-needle aspiration biopsy (FNAB) (8). FNAB is widely regarded as the gold standard for diagnosing LLNM (9). However, it is invasive and technically challenging when lymph nodes are small or located near critical anatomical structures. US is the first-line imaging modality for evaluating cervical lymph nodes (10). Its diagnostic accuracy is highly operator-dependent and can be limited by adjacent structures such as adipose tissue, the thyroid gland, and the trachea. The sensitivity of US for detecting LLNM ranges from only 20% to 40% (11). CT, which provides detailed anatomical visualization, is recommended as a complementary tool to US (12). Although CT is not the primary imaging modality for diagnosing PTC, it can offer advantages over US in identifying lymph node metastases in certain cases. For instance, Lee et al. found that CT outperforms US in detecting LLNM in patients with papillary thyroid microcarcinoma (13). Despite these advancements, accurately identifying LLNM remains clinically challenging. Improved prediction of LLNM risk would help clinicians and patients make more informed surgical decisions.

Several studies have developed LLNM risk prediction models for PTC (8, 14, 15). However, many rely solely on univariate and multivariate analyses, which are limited in addressing multicollinearity. LASSO regression, not widely applied in PTC research, can improve model performance by applying a penalty function to select relevant predictors. In this study, we integrate LASSO regression for variable selection with logistic regression for modeling and visualization, enabling more interpretable results. We aim to construct a new risk prediction model for LLNM in PTC patients using detailed preoperative examination results, thereby facilitating personalized clinical decision-making.

In recent years, the incidence of PTC has steadily increased (1). Although the prognosis of PTC is generally favorable, the rate of LLNM remains relatively high (2). Conventional wisdom suggests that the presence of LLNM in PTC patients is often associated with poor prognosis and an increased risk of local recurrence (3). Recent studies suggest that many intermediate-risk patients have favorable prognoses, supporting the trend toward less extensive surgical intervention. For instance, a study involving 946 patients with unilateral PTC and ipsilateral clinically apparent lateral neck metastases (cN1b) reported similar recurrence-free survival (RFS) outcomes between those who underwent lobectomy and those who underwent total thyroidectomy (19). Similarly, a 2025 study published in JAMA Otolaryngology demonstrated comparable survival and recurrence outcomes in intermediate-risk cN1b PTC patients treated with either lobectomy plus ipsilateral neck dissection or total thyroidectomy plus ipsilateral dissection (20). The 2021 ATA guidelines explicitly discourage prophylactic LLND, emphasizing that LLND should be performed for therapeutic rather than preventive purposes (5). Prophylactic LLND in patients with only suspected LLNM has not been shown to improve prognosis and may result in postoperative complications and visible cervical scarring, adversely affecting patients’ quality of life (21). Therefore, accurate preoperative assessment of cervical lymph node status is essential for selecting an appropriate treatment strategy. Enhancing the predictive accuracy for LLNM using current technologies has become a key issue in clinical practice. The nomogram developed in this study aims to identify patients truly at high risk for LLNM, thereby achieving a balance between minimizing unnecessary surgical intervention and reducing the risk of recurrence. Numerous studies have explored the risk factors associated with LLNM, but the findings remain inconsistent (22, 23). Liang et al. identified several key risk factors contributing to the development of LLNM in thyroid cancer, including central lymph node metastasis, extrathyroidal extension, multifocality, male sex, tumor location in the upper thyroid pole, tumor volume, lymph vascular invasion, and bilateral tumor presence (22). Similarly, Lai et al. reported that tumor size, location, microcalcification of lymph nodes, lymph node size, and patient age were significant predictors of LLNM (23). Although prophylactic LLND is not routinely recommended, preoperative imaging may reveal suspected lateral lymph node metastases, necessitating surgical intervention. In our cohort, patients in the LLNM-negative group showed suspicious metastases on imaging, but no metastases were confirmed by postoperative pathology. This finding suggests a potential false-positive rate in preoperative imaging, underscoring the critical importance of accurate preoperative assessment in guiding surgical decision-making. In this study, we identified tumor diameter, multifocality, tumor location, invasion, maximum diameter of suspicious LN on US, multiregionality suspicious LN on US, CT reported LN status, calcification of LN on CT, enhanced types of LN on CT and TG as significant risk factors for LLNM in PTC. All these variables were incorporated into the clinical prediction model. Nomogram was used to estimate the individual risk of LLNM in PTC patients, thereby helping clinicians determine whether LLND is needed.

In our study, the incidence rates of LLNM were 64.8% and 67.6% in the two groups, which was higher than previous reports (35.2-44.5%) (24, 25). This study only included PTC patients whose preoperative examinations highly suspected LLNM, which might explain the higher LLNM rate observed in our study than in previous studies. Previous studies have found that tumor size larger than 1.0 cm is significantly associated with LLNM (22). Larger tumor size is not only associated with a higher risk of LLNM (26), but also an independent predictor of LLNM recurrence (27). In our research cohort, tumor size was associated with LLNM in PTC.

Studies have shown that both bilateral and multifocal tumor characteristics are independent risk factors for LLNM in thyroid cancer (28). Liu et al. demonstrated a significant association between unilateral multifocality and LLNM, suggesting that multifocality increases the likelihood of lymphatic metastasis in thyroid cancer (29). In our study, we confirmed that tumor multifocality was an independent risk factor for LLNM, whereas laterality was not.

Previous studies have demonstrated that the location of thyroid cancer is closely associated with LLNM (30). Research by Jee indicates that nodules located in the upper pole or in the upper to middle third of the thyroid gland are significantly more prone to LLNM compared to those in the middle pole (31). This increased risk is primarily due to the similarity between the lymphatic and venous drainage systems of the thyroid, which collect lymph from the upper and middle poles (32). Lai et al. also reported that tumors located in the upper pole exhibit a significantly higher risk of LLNM (23). Therefore, we recommend that the preoperative assessment of thyroid nodules in the upper and middle poles should include careful assessment of the lateral cervical lymph nodes.

Extraglandular and capsular invasion of thyroid cancer are indicative of increased tumor aggressiveness. Huang et al. identified extraglandular invasion as a strong predictor of LLNM (33). Similarly, Yang et al. found that patients with capsular infiltration had a higher risk of LLNM than those without (34). Additional studies have shown that the proximity of the tumor to the thyroid capsule correlates with lateral cervical lymph node metastasis (35). Specifically, the closer a nodule is to the capsule, the greater the likelihood of LLNM.

Metastatic lymph nodes typically exhibit features such as calcification, cystic necrosis, hyperechogenicity, round shape, peripheral or mixed vascularity, and absence of an echogenic hilum. US is the primary non-invasive imaging modality for the preoperative evaluation of lymph node status. Accordingly, in this study, we focused on the US characteristics of cervical lymph nodes to assess their predictive value for LLNM in PTC. The size of lymph nodes is a critical factor in assessing lymph node status. Various studies have proposed different thresholds for defining suspicious lymph nodes. Generally, a diameter of 10 mm is considered the standard cutoff for identifying potential metastasis (36). Mack et al. found that spherical lymph nodes larger than 10 mm are more likely to indicate malignancy (37). Additionally, studies have shown that the likelihood of metastasis is 25.46 times higher in regions with multiple suspicious lymph nodes compared to regions with a single suspicious node (8). In our study, both the maximum diameter and multiregionality of suspicious lymph nodes on US were significantly associated with LLNM in PTC patients.

CT has demonstrated advantages in the evaluation of LLNM, as it effectively visualizes lymph nodes and delineates their spatial relationships with adjacent blood vessels (38). Morphological CT features—such as lymph node size >10 mm, irregular shape, ill-defined margins, calcification, and heterogeneous enhancement—are commonly used as predictive indicators of metastasis (39). Liu et al. reported a correlation between the degree of lymph node enhancement and metastatic involvement (40). Zhao et al. highlighted shape, margin, calcification, and cystic changes as key morphological characteristics of metastatic lymph nodes (41). In our study, we found significant differences in calcification and enhancement patterns between suspicious lymph nodes, but no differences in shape or margin between LLNM-negative and LLNM-positive groups. We propose that this discrepancy may be attributed to the subjectivity and variability inherent in morphological assessments.

TG, secreted by thyroid follicular epithelial cells, serves as a precursor for the synthesis of thyroid hormones. The American Thyroid Association recommends routine monitoring of serum TG levels in patients undergoing thyroid cancer surgery (5). Postoperative serum TG levels, particularly following thyroidectomy and radioactive iodine ablation are commonly used as indicators of residual thyroid tissue or metastatic disease (42). Elevated preoperative TG levels may also raise suspicion of cervical lymph node involvement (43). We found that elevated serum TG was associated with an increased risk of LLNM in PTC.

In the ongoing debate over LLND in PTC, our model offers a valuable reference for selecting personalized surgical approaches through non-invasive preoperative assessment. While numerous predictive models for diagnosing LLNM have been developed, they primarily rely on logistic regression for variable selection and model construction (8, 14, 15). These models often suffer from limitations such as small sample sizes, incomplete evaluation methodologies, and a lack of internal or external validation.

To address these limitations, we constructed a personalized and quantitative nomogram to predict the probability of LLNM in PTC patients using LASSO regression and multivariate logistic regression analysis. The study cohort was randomly divided into a training set for model development and a validation set for internal validation. ROC curves, calibration plots, and DCA were employed to assess the model’s accuracy and robustness. Although the model demonstrated excellent discrimination (AUC > 0.95) in both the training and validation cohorts, current evidence does not support its use in expanding surgical indications. Studies have shown that while prophylactic LLND can detect occult metastases in approximately 40% of patients, it does not improve oncologic outcomes (19, 20). Therefore, even when the model predicts a high probability of LLNM, central lymph node dissection (CLND) remains the standard surgical approach, unless cN1b disease is confirmed through preoperative fine-needle aspiration or intraoperative frozen section analysis (44). The primary value of this model lies in its utility for postoperative risk stratification. For patients with a high predicted probability (total score >75; LLNM risk >65%), more intensive postoperative surveillance—such as neck ultrasound every 3–6 months and dynamic serum Tg monitoring—is recommended to facilitate early detection of late lateral neck recurrence. Conversely, for patients with a low predicted probability (total score <60; LLNM risk <20%), extended follow-up intervals may be appropriate, thereby reducing unnecessary imaging and lowering the healthcare burden.

However, our study has several limitations. First, the nomogram was developed using data from a single-center study, which may introduce selection bias. While internal validation results are promising, external validation is essential to confirm the model’s generalizability. Future studies will incorporate data from multiple centers to evaluate its applicability across diverse patient populations. Second, as this study is based on a retrospective cohort, the model requires further prospective validation prior to clinical application. Finally, some imaging features are subjectively assessed and may vary between observers. To minimize interobserver variability, a third radiologist was consulted during final evaluations.

In summary, tumor diameter, multifocality, tumor location, invasion, maximum diameter of suspicious LN on US, multiregionality suspicious LN on US, CT reported LN status, calcification of LN on CT, enhanced types of LN on CT and TG are risk factors for predicting LLNM in PTC patients. The nomogram constructed from these variables demonstrated strong predictive performance and holds potential as a practical tool for individualized LLNM risk assessment, aiding clinicians in risk stratification and postoperative follow-up planning.