With the application of high frequency ultrasound, the incidence of thyroid lesions in adults can be up to 60 ~ 70% . Fine-needle aspiration (FNA) has been the most effective diagnostic method for benign and malignant thyroid neoplasms recently . However, regular observation is one of the choices for most benign nodules, even malignant nodules, especially malignant nodules < 1cm or selected patients with contraindications for surgical procedure [12–13]. Therefore, the standardization of thyroid ultrasonographic images by ti-rads can effectively improve the differential diagnosis of thyroid nodules.
PTC is the most common malignant thyroid tumour, lymph node metastasis of which were associated with the diameter, location, number and invasive growth of primary tumour [14–15]. The sensitivity of ultrasound for the evaluation of central and lateral compartment lymph nodes is around 60% , in this study, compared with cN1 and pN1, the detection rate of cervical lymph node metastases was 64.8% (280/432). CLNM in PTC generally first occurs in the central region and then to the lateral region , which is more common in area VI, followed by area III and IV . However, not all PTC lymph node metastases follow this pattern, with some skip metastasis where lymph node metastasis occurs in the lateral neck region and no metastasis in the ipsilateral central region . Some studies have reported that the rate of lymph node skip metastasis was 3 ~ 21.8% . Due to only unifocal PTC included in this study, the lymph node skip metastasis rate was 4.0% (54/432).
TI-RADS was mainly adopted in the differential diagnosis of benign and malignant thyroid neoplasms. The consistent conclusion of the association between sex, age and sonographic features and lymph node metastasis was difficult to achieve [20–22]. This study only included unifocal PTC and conducted a stratified study to comprehensively evaluate the risks of CLNM in PTC combined with clinical information, ultrasonographic measurements and TI-RADS to obtain a more complete and effective result.
PTC can occur in any part of thyroid, including bilateral lobes and isthmus. For isthmus, the incidence of thyroid cancer is about 2.5%~9.2% . Studies have found that isthmus PTC was more likely to invade thyroid capsule and surrounding tissues, compared with the lateral lobe PTC [24–25]. This is mainly because the area of the isthmus tumour in contact with thyroid capsule is relatively large, which is easy to invade the capsule or break through the capsule and invade the surrounding tissues, thus CLNM would happen. Previous studies [25–26] have suggested that when the tumour was located in the middle or lower pole of thyroid, the risk of CLNM was increased. In this study, the incidence of PTC lymph node metastasis in isthmus was larger than in the left and right lobes (51.2%(42/82)vs 29.9%༈177/591༉vs 32.2%༈213/662༉), and the lobes were stereolocated by the upper and lower, anterior and posterior, inside and outside, 43.8% (28/64) of lymph node metastasis occurred in the lower, anterior and outside location, which were consistent with previous studies [25–26]. We recommend principle of stereo-position for lesions, in one hand, we can assess the clearer location of the lesion, in other hand, for isthmus and lower lesion, we should check the neck carefully for CLNM. However, more data should be provided to promote and confirm the result.
Aspect ratio ≥ 1 is a highly specific index for the diagnosis of malignant thyroid nodules [27–28]. According to previous literature, the results of association between aspect ratio and CLNM in PTC were not consistent. Part of literature [29–30] suggested that it was prone to occur CLNM when aspect ratio > 1, and CLNM was the risk factor. The study  reported that no statistical significance could be seen in the prediction of lateral cervical lymph node metastasis in the case of aspect ratio ≥ 1. In this study, aspect ratio had statistical significance in univariate analysis, while we used the binary logistical analysis, there was no significant difference, the main reason was that PTMC patients were 65.5% (874/1335) in the study, just 20.7% (181/874) were in the positive group. In addition, according to the morphology of the thyroid lesion, it could be divided into cross-sectional aspect ratio and longitudinal section aspect ratio. We compared cross-sectional aspect ratio and longitudinal section aspect ratio for PTMC and PTC patients excluding PTMC, it could be concluded that cross-sectional aspect ratio had a better predictive value for CLNM in PTC excluding PTMC, compared with the longitudinal aspect ratio. There was less relevant literature with the association between cross-sectional and longitudinal section aspect ratios in predicting cervical LN metastasis, especially for PTC patients excluding PTMC. We will collect more data for further research in the future.
Malignant tumour grows rapidly, the cancer cells continue to invade outward, then the incidence of lymph node metastasis is relatively increased [32–33]. Margin is one of the invasive characteristics of the tumour. The nodules with high invasiveness showed irregular and lobulated boundaries, while smooth boundaries generally indicate low invasiveness and slow growth . In this study, univariate analysis and logistic regression analysis both showed a good association between margin and CLNM in PTC, the lesions with lobular/irregular or extension more occurred CLNM than smooth or ill-defined (60.4% (261/432) vs 39.6% (171/432)). This is consistent with the results reported in the literature [21, 26]. Margin had statistical significance (P < 0.001) between only central lymph node metastasis group and only lateral lymph node metastasis group, between only central lymph node metastasis group and both metastatic group by ANOVA variance analysis.
Echogenic foci are divided into micro-calcification, macro-calcification and ring calcification around the nodules on the basis of 1mm . Micro-calcification can reflect the psammoma bodies in pathology, which results from calcification and necrosis of cancer cells and is a specific indicator for the diagnosis of PTC , and it is significantly related to lymph node metastasis. Continuous follow-up studies found that CLNM was more likely to occur in PTC with micro-calcification . In this study, the patients with peripheral calcification or punctate echogenic foci had more CLNM, compared with none or large comet-tail artifacts (57.9% (250/432) vs 42.1% (182/432)). When ANOVA variance analysis was executed, echogenic foci also had significant difference (P < 0.001). Therefore, ultrasonography can better predict the risk of CLNM in PTC for the different types of calcifications.
Ti-rads comprehensively evaluated the tumour according to sonographic features of thyroid nodules. Its scoring and grading system were used for the differential diagnosis of benign and malignant nodules, it would be great value for further determination of diagnosis and treatment protocols. In this study, sex, age, ultrasonographic measurements and features were included for logistic regression analysis to establish a prediction model for CLNM, with a specificity of 72.8% and a sensitivity of 75.0%. Sun et al.  reported that they used sex, age, max diameter and number of nodules, cervical lymph node detected by ultrasound as covariates, CLNM as a dependent variable, a prediction model was acquired with a specificity of 80.8% and a sensitivity of 59.8%. The result had reference value. It also demonstrates the importance of comprehensive evaluation of ultrasound in clinical practice.
Heaton et al.  reported that women and elderly patients were at risk of PTC, while men and younger patients were at risk of CLNM. In this study, CLNM occurred in 42.5% (127/299) of male patients, and occurred in only 29.4% (305/1036) of female patients, which also suggests that male patients have a higher risk of lymph node metastasis. We used 55 years as the threshold in this study according to the TNM staging system for thyroid cancer , and 35.4% (371/1048) of patients who were younger than 55 years had CLNM, and among those who were 55 years or older, lymph node metastases occurred in only 21.2% (61/287) of patients in this study.
The maximum tumor diameter is an important reference index for PTC treatment protocols and the range of surgery . The results demonstrated that the average maximum tumor diameter in the positive group was about 1.7 times (14.4mm vs 8.36mm) that in the negative group. The tumor seemed to be ellipsoid, and the volume as the evaluation parameter made the result more objective and scientific. The average tumor volume in the positive group was about 3.7 times (2.05ml vs 0.55ml) that in the negative group. For larger tumors, cervical lymph nodes should be examined in order to improve the detection rate of CLNM. In particular, in patients with large tumors, central or both central and lateral lymph node metastasis should be determined in advance.
Limitations of this study: 1. It was a single-center retrospective study including unifocal PTC and lymph node dissection performed in the central area, which may cause selection bias. 2. Cases with metastases in lateral location were not adequate, large samples are required to study the cervical metastases in different parts. For skip lateral lymph node metastases, more effective preoperative assessment should be adopted. 3. This is our preliminary study for large sample size of PTC patients, we will add detailed clinical and pathological staging, subdivided pathological types, machine learning models for further research.