As previously reported, MTC is a rare thyroid malignant tumor with an incidence of 0.11/100,000 in the population, which can be divided into sporadic and genetic types[10]. The C cells of MTC can secrete many kinds of substances, among which serum calcitonin is a valuable tumor marker of MTC. MTC is more aggressive than PTC, and it is prone to distant metastases including lung, liver, bone, and adrenal glands. Weber et al. reported that LNM-MTCs could be found in 75% patients who underwent total thyroidectomy and modified radical neck dissections[11]. Cervical lymph node dissection had certain complications, such as thoracic duct leak, injury to the recurrent laryngeal nerve, and hypoparathyroidism, and repeated operations were very traumatic to patients. Therefore, accurate preoperative diagnosis of LNM is of great significance for surgical plans.
In our study, there was no difference in gender between the two groups, however, patients with LNM-MTC were older than those with LNM-PTC. Similar results have also been reported in primary thyroid cancer. A previous study showed that patients with MTC were older than those with PTC[12]. No difference was observed in the location between LNM-MTC and LNM-PTC groups. However, more LNMs were located at the lateral region in both groups. LNMs of thyroid cancer usually spread to the central region first, followed by the lateral region[13], and central LNs dissection are routinely performed. Moreover, due to the poor US window and small size of LNs in the central region, the sensitivity of US in the detection of central LNMs was low[4]. Thus, many LNs in the central region might not be recognized, and FNA was not performed.
US is important for distinguishing benign and malignant LNs. The related ultrasonographic indicators of LN include size, L/S, shape, border, hilum, echogenicity, calcifications, cystic change and vascularization. LNMs of thyroid carcinoma are mainly manifested as microcalcifications, hyperechogenicity, cystic change and abnormal vascularization.[6] However, these features were commonly seen in LNM-PTC[14, 15], and they were rarely reported in LNM-MTC. To the best of our knowledge, the ultrasonic features of LNM-MTC have not been well documented in the literatures. In our study, no differences were observed in L/S, shape, border, echogenicity, cystic change and vascularity pattern between LNM-MTC and LNM-PTC groups. However, long-axis and short-axis diameter, hilum and calcifications were statistically different between these two groups.
In our study, the mean long-axis and short-axis diameter in LNM-MTC were 16.43 ± 10.36mm and 8.53 ± 5.79mm, both larger than those of LNM-PTC. Compared with PTC, MTC had a higher degree of malignancy and invasion[12, 16], which might be the reason for larger sizes of LNs. Normal LNs usually have an echogenic hilum, while metastatic LNs usually present with absence of hilum.[7, 14, 17] The metastases of the tumor initially appear in the peripheral area of LN, but as the size of metastases become larger, the normal nodal tissue destroyed. When LNs were filled with tumor cells, hilum could not be recognized[18]. However, absence of hilum may be without significance in distinguishing LNM-PTC from normal LNs[6]. Due to its indolent nature, PTC usually develops slowly. When the medullary lymphatic sinuses have not been completely destroyed by tumor cells, hilum also exists in early LNMs[19]. The results in our study showed that absence of hilum was more commonly detected in LNM-MTC than in LNM-PTC. MTC is a moderate malignancy, and the tumor cells commonly grow with invasion. The difference might be due to the more aggressive biological behavior.
Nodal calcification plays an important role in differentiating benign and malignant LNs. It is also an important indicator of primary thyroid carcinoma[20]. Li et al revealed that macrocalcification was more frequent in MTC, while microcalcification was more common in PTC[1]. Microcalcifications are usually round or concentric under the light microscope, with a tiny diameter of 10 to 100 µm, which correspond to the psammoma bodies on pathology. In MTC, macrocalcifications are associated with amyloid deposits [21]. Calcification in LNMs is generally rare, but it is common in LNM from thyroid cancer. Kim et al. found that there was no significant difference in calcifications between PTCs and MTCs[22]. To the best of our knowledge, calcification in metastatic LNs has not been compared between the two tumors. Our results showed that the incidence of calcifications in LNM-MTC group was significantly lower than that in LNM-PTC group (P < 0.05). In the LNM-PTC group, calcification was found in 58.6% (139/237) LNs, with a relatively high incidence. However, in LNM-MTC group, the incidence of calcifications was not high in LNM-MTC group, and it was detected in only 21.2% (11/52) cases. Due to the low prevalence, calcifications were not further subdivided into coarse and fine calcifications. The difference between the two groups indicated that although calcification was regarded as an ultrasonic feature of LNM-PTC, this sign may not be applied to LNM-MTC.
Hyperechogenicity and cystic change are also the characteristic manifestations of PTC-LNMs, and there were no differences between LNM-MTC and LNM-PTC in our study. The typical echogenicity of LNM from thyroid cancer is hyperechoic in the cortex compared to skeletal muscle[9]. This may be due to the deposition of thyroglobulin and clustering of the tumor cells in the LNs [9, 23]. LNM should also be suspected in patients with suspicious thyroid nodules when cystic change existed. The mechanism of cystic change in LNM may be related to necrosis[24]. Our results suggested that hyperechogenicity and cystic change can also be applied to LNM-MTC. Normal LNs usually had hilar flow, while metastatic LNs often showed peripheral flow or mixed flow, which was usually considered as abnormal flow[9]. Peripheral flow was a meaningful feature of LNM from thyroid cancer[25], which was caused by tumor angiogenesis or recruitment of capsular vessels[23]. In our study, abnormal flow was more frequent in LNM-MTC than in LNM-PTC, but the difference was not significant(P༞0.05).
It was reported that the ultrasonographic characteristics of LNM-PTC in the central and cervical groups were different[26]. The high frequency of malignant US characteristics in the lateral LNMs included partial cystic component, microcalcifications and diffusely increased echogenicity, however, these ultrasound findings may not apply to the central group. It was suggested that the taller-than-wide type was only malignant US feature in the central LNMs[26]. Previous studies also suggested that the sensitivity of US in central LNMs was lower than that of lateral cervical LNM in PTC, because the lymph nodes in the central region lacked characteristic sonographic appearances[4, 26]. The comparison of ultrasound images between the central and lateral LNs in LNM-MTC group was performed in our study, however, there were no differences in other indicators except the long-axis diameter. According to the results of our study, we suggested that the US features of LNM-MTC could also be applicable to the central LNMs.
There were several limitations in this study: First, due to the retrospective nature of this study, it is likely to have selection bias and restricted quality of images and data. Second, the sample size of LNM-MTC group was small, and a further study with a larger sample size should be performed.