Whether patients with PTMC should routinely undergo prophylactic central neck dissection (PCND) remains controversial17. On the one hand, some scholars believe that PCND can help reduce recurrence risk and avoid secondary operations complications18. What's more, it can help stage the tumor more accurately, which is beneficial for making postoperative supplementary treatment plans (such as I-131 treatment)19. On the other hand, there is no definite evidence to prove that PCND can improve the prognosis or prolong the survival of patients with thyroid cancer, and the expansion of the dissection scope will increase the incidence of postoperative complications19, 20. Lymph node macro-metastasis is a vital risk stratification factor for PTMC patients according to the 2015 ATA guidelines12, 21, 22. Therefore, preoperative identification of macro-CLNM can provide a certain reference for the management of PTMC patients.
The number and macro-metastasis rate of lymph nodes in PTMC patients are, from high to low, the right paratracheal, the left paratracheal, the pretracheal, and the prelaryngeal level. The right paratracheal level has more LNs and a higher macro-metastasis rate than the left side, which may relate to anatomy. The angle between the right RLN and the carotid artery is larger than the angle on the left side, where the RLN is parallel to the tracheoesophageal sulcus23.
This study demonstrated that the preoperative ultrasound had an extremely high false-negative rate for assessing macro-metastatic LNs in prelaryngeal-pretracheal sublevel, there were 14 macro-CLNM cases in pretracheal and prelaryngeal sublevel which were diagnosed as negative by HRUS. Among them, HRUS failed to detect any LN in 13 cases. The LNs cannot be observed by ultrasound because the prelaryngeal-pretracheal LNs are located between the anterior cervical muscles and the trachea. The relatively small space in this area makes the number and the size of lymph nodes small. There were only 1–2 prelaryngeal-pretracheal LNs per patient (Table 2); the average short-xis diameter of the prelaryngeal and pretracheal LNs was less than 3mm and 2-4mm, respectively (Table 5), and even the smallest nodule detected by HRUS is only 2-3mm24. The extremely low detective rate of HRUS in prelaryngeal-pretracheal LNs caused many false-negative cases, with the AUC of only 0.51–0.55 (Table 6). We suggested that preoperative HRUS did not help identify the macro-CLNM in prelaryngeal-pretracheal sublevel.
Compared with the prelaryngeal-pretracheal sublevel, dissection of LNs in the paratracheal levels is more likely to cause complications such as hoarseness and hypocalcemia common in post thyroid cancer operation because of the injury of recurrent laryngeal nerve and parathyroid19. Therefore, the preoperative diagnosis of the paratracheal LNs is of great significance. The diagnostic efficacy of HRUS for CLNM in paratracheal sublevels is low, with the AUC of only 0.51–0.54, which is consistent with the conclusions of other previous studies5, 14. For macro-CLNM, the AUC of the paratracheal sublevels has been significantly improved, with 0.80 on the left and 0.75 on the right. This is probably because the diameter of macro-CLNM is larger than that of the non-macro-CLNM (including no- and micro-CLNM) (Table 5), which is more easily to be detected by HRUS (Table 4). In addition, micro-CLNM has only pathological changes below 2 mm, which is difficult to distinguish by ultrasound, while cancer foci in macro-CLNM are larger than 2 mm, which are more likely to show abnormalities in ultrasound images. Moreover, the NPV of ultrasound diagnosis of macrometastasis in paratracheal sublevels reached 99% (left) and 95% (right). In other words, when the paratracheal sublevel is negative under HRUS, the probability of macrometastasis is extremely low, only 1%-5%. Therefore, this study believes that preoperative HRUS has an exclusive diagnostic effect on macrometastasis in paratracheal sublevels.
It is worth mentioning that macrometastasis in prelaryngeal-pretracheal sublevel is a high risk factor for paratracheal macrometastases, with an OR value of 9.1 (95% CI 2.8–29.2, P = 0.0002), And among the patients with macrometastases in prelaryngeal-pretracheal sublevel, nearly 40% of them accompanied by paratracheal macrometastases (6/15). As a result, macro-CLNM in prelaryngeal-pretracheal sublevel has a certain prompting effect on paratracheal LNs macrometastasis. If PTMC patients are found with prelaryngeal-pretracheal macro-CLNM during surgery, it is necessary to be alert to ipsilateral paratracheal macro-CLNM.
This study creatively analyzed the preoperative ultrasound and postoperative pathological results of patients with PTMC sublevel-by-sublevel, figuring out the number of LNs and macro-metastatic rate in each sublevel and discussing the diagnostic efficacy of ultrasound. Compared with the traditional rough analysis of central LNs, the ultrasound diagnostic performance obtained in this paper is more accurate and closer to the real situation. However, there are some limitations to our study. Firstly, in order to reduce the interference of contralateral central LN and lateral cervical LN to the analysis of ultrasound diagnostic performance in each sublevel, this retrospective study design only focus on unilateral PTMC, so there is an unavoidable selection bias. Secondly, this study can only analyze LNs sublevel-by-sublevel rather than single LN one-to-one. It remains a clinically significant topic that urgently needs research on whether combining with other imaging tests or artificial intelligence can improve diagnosis efficiency.