All PTC are developed from PTMC, and the central lymph node metastasis rate of PTMC has been reported to be 32%-48% [3-4]. Central lymph node metastasis often develops into lateral neck lymph node metastasis and distant metastasis. Accurate assessment of central lymph node metastasis and dissection of central and lateral neck lymph node metastasis can stop the progression of the disease, reduce the risk of recurrence and metastasis, and avoid surgical complications. Preoperative ultrasonography can detect enlarged lymph nodes in the central region of PTMC, but due to the limitations of anatomical site and puncture technique, the positive rate is low, and the diagnosis can only be confirmed by pathological examination after intraoperative lymph node dissection. In this study, the risk factors of CLNM in PTMC patients were analysed to evaluate the risk of CLNM in PTMC patients as early as possible. The rate of central lymph node metastasis in this study was 47.2%, which was consistent with literature reports. It was found that the male gender with maximum tumor diameter≥0.75cm, multifocal and capsular immersion were the risk factors for CLNM in PTMC. However, there was no significant difference between PTMC with HT and nodular goiter metastasis group and non-metastasis group.
Most studies have found that the CLNM rate in male patients is significantly higher than that in female patients, and being male is considered to be a risk factor for CLNM in cN0 PTMC [5-6], which is consistent with the conclusion of this study. However, some studies have reached the opposite conclusion [7-8], which may be related to the small sample size, low proportion of male patients, study inclusion criteria and differences in surgical methods. This study showed that the proportion of CLNM in PTMC patients aged ≤30 years was higher than that in other age groups. At present, it is generally believed that age< 45 years is a risk factor for CLNM in PTMC patients [9]. Oh et al. [10] divided 239 patients with cN0 PTMC into 3 groups according to age < 40 years old, 40-50 years old and ≥50 years old. The incidence of CLNM in each group was 86.9%, 46.6% and 66.5%, respectively, suggesting that age < 40 years old was a risk factor for lymph node metastasis. In a prospective study, 1235 PTMC patients were divided into three groups according to age < 40 years, 40-59 years, and ≥60 years, and similar conclusions were obtained [11]. Younger age is an independent risk factor for predicting CLNM in patients with PTMC, but there is no standard cut-off age. In this study, 26.5 years old is the cut-off age for predicting central cervical lymph node metastasis in PTMC, which is basically consistent with the above studies. It is well established that the larger the tumor diameter, the higher the risk of CLNM. Some scholars believe that the optimal critical value of CLNM for PTMC is 0.6cm based on tumour diameter. Tumour diameter > 0.6cm is significantly correlated with CLNM [12]. Further studies by Lee et al. [13] found that the occurrence of CLNM in PTMC patients was significantly correlated with tumour diameter > 0.7cm. At present, more and more studies tend to take 0.7cm as the cut-off value and confirm that tumour diameter greater than 0.7cm is the risk of CLNM in PTMC patients. In this study, it was found that the maximum tumour diameter ≥0.75cm was the cut-off value for CLNM in PTMC patients. However, prospective, large-sample studies are needed to determine the optimal cut-off value of tumour size for predicting CLNM in PTMC patients. Some scholars have found that multifocal tumour is a risk factor for CLNM in PTMC patients [14-15], which is consistent with the conclusion of this study. At present, whether the multifocal origin of PTMC is intra glandular spread or independent occurrence has not been determined. In addition, intra glandular metastasis may be completed through the rich lymphatic system between the glandular lobe and isthmus. This study shows that thyroid capsule invasion is a risk factor for CLNM, which is consistent with most studies [16-17]. Clinical observation and follow-up are often adopted for PTMC patients with low risk factors. As the tumour continues to grow, the scope of immersion is also expanded accordingly, which leads to a high proportion of capsule immersion in surgical cases, and the proportion of lymph node tissue invasion along the capsule is also increased.
Some studies have shown that the CLNM rate is lower in PTMC patients with HT [10], but this study and other studies have shown that HT is not correlated with CLNM [6,18]. A multicenter study with a larger sample size is needed to further evaluate the effect of HT on CLNM in PTMC patients. Clinically, many patients with PTMC combined with HT have more enlarged central cervical lymph nodes [19], but the metastasis rate is not high, so it is neither necessary nor appropriate to remove central lymph nodes. Recent studies have found that v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation is the most common and critical genetic event in the process of PTC. In addition, BRAF V600E mutation is only found in PTC and undifferentiated carcinoma obviously derived from PTC, and is not present in normal thyroid tissues, thyroid follicles and other types of thyroid tumours [20]. Many studies have found that this mutation is associated with routinely known clinicopathological features of PTC that predict tumour progression and recurrence, including advanced age, extrathyroid invasion, lymph node metastasis, and advanced tumour stage. In addition, a direct association between BRAFV600E mutation and clinical progression, recurrence, and treatment failure of PTC has been demonstrated. At present, there are few CLNM studies on BRAFV600E mutation and PTMC. A Meta-analysis showed that BRAFV600E mutation is an independent risk factor for PTMC central cervical lymph node metastasis. However, because only 5 studies with 559 patients were included, and all of them were retrospective studies, the conclusion was not convincing [21]. In this study, a total of 85 out of 375 PTMC patients underwent BRAF gene testing, and 79 of them were found to have BRAF gene mutation, with a mutation rate of 93%. However, the sample size of BRAF gene testing in this study was too small, and it is necessary to expand the sample size of BRAF gene testing for further study to obtain more accurate conclusions.
At present, the specific treatment of PTMC is still controversial. Surgery has always been the traditional cornerstone of the treatment of PTMC. However, scholars both in China and abroad have been controversial about the necessity and scope of PTMC surgery. Currently, it is generally believed that the removal of affected side adenoidectomy plus isthmus resection and reasonable cervical lymph node should be recommended for PTMC patients with low risk factors [22]. In this study, male gender, age ≤26.5 years, maximum tumour diameter ≥0.75cm, multifocal tumour and capsule invasion were considered as risk factors for CLNM. Preventive central lymph node dissection should be performed when formulating surgical strategies. In recent years, thermal ablation has been gradually used in some low-risk PTMC patients, and has achieved good therapeutic effects [23]. Thermal ablation is also a safe and effective treatment for low-risk PTMC patients who are unwilling to undergo surgical treatment [23].
Active surveillance (AS) has been used in patients with PTMC for the past 10 years. AS as a treatment strategy for low-risk PTMC was first proposed in Japan, and the 2015 American Thyroid Association (ATA) guidelines included AS as a management strategy for patients with low-risk PTMC [24]. The efficacy of AS in patients with low-risk PTMC mainly depends on the accurate assessment of the patient's risk. Clinicians can take measures such as dynamic monitoring, risk stratification and personal follow-up plan to reduce the potential risk.