PTC is the most common malignant tumor of the endocrine system, and the incidence rate has increased significantly in recent years. PTC usually has indolent behavior, with a good prognosis, however, some tumors may present with local recurrence and distant metastases. There are many factors associated with the prognosis of PTC, including older age, male gender, a large tumor size, multifocality, extrathyroidal extension, and the presence of LNM or distant metastases [12–16]. The isthmus locates directly in front of the trachea. It is the central part of the thyroid gland, connecting the left and right lobes. Although the incidence rate of PTC arising from isthmus is low, it has been reported to exhibit aggressive tumor characteristics[3, 17]. This present study showed that the incidence was 16.2% (133/823), which was similar with the result previously reported .
The sonographic features of PTC mainly included solid composition, hypo-echogenicity, aspect ratio ≥ 1, irregular margin, and microcalcifications[12, 18]. However, these features were mainly based on the studies of nodules in lateral lobe. To the best of our knowledge, this was the largest sample size study of sonographic characteristics of PTC arising from the isthmus. Our results showed that there were no differences in margin, echogenicity, homogeneity and halo between the isthmus and lateral lobe groups, however, there were significant differences in aspect ratio and microcalcification.
The aspect ratio of thyroid nodule is of great significance in distinguishing benign and malignant tumors. It is generally considered that aspect ratio ≥ 1 is an important feature of malignant nodule , and the aspect ratio reflects the variation index in thyroid nodule shape, which is closely related to the growth mode of the thyroid nodule. Due to a large intensive fibrosis, the compressibility of PTC was reduced, which resulted in its standing-like shape. In this study, it was a common sign in the lateral lobe group, and the proportion was as high as 51.7%, which was consistent with the results of previous studies. However, there was only 43 (32.3%) cases with aspect ratio ≥ 1 in the isthmus group, which indicated that it might not apply to PTC in the isthmus. This may be related to the unique location of the isthmus in the thyroid gland. The isthmus is usually thin, and the normal thickness is generally not more than 4mm. When PTC grows to a certain extent, its longitudinal growth rate slows down due to a limitation that is imposed by the thyroid capsule and external muscles, resulting in an increased transverse diameter of the nodule and an altered aspect ratio from ≥ 1 to < 1.
Microcalcifications also play an important role in the differential diagnosis of benign and malignant thyroid nodules, and it could be more commonly seen in PTCs. In this study, the incidences of microcalcification in the two groups were 43.6% and 57.8%, and the difference was statistically significant. Microcalcifications are usually manifested in round or concentric under the light microscope, which are mainly induced by psammoma bodies with a tiny diameter of 10 ~ 100 µm. Because the isthmus is more superficial than the lateral lobe, it might be more easily affected by the generation of intense echoes due to transducer reverberations. Reverberations is defined as equally spaced, bright linear echoes, which are produced by the repeated reflections from specular-type interfaces. This artifact is frequently seen in the superficial zone of the near field on a sonographic image.
This study also found that the incidence of extrathyroidal extension in the isthmus group was significantly higher than that in the lateral lobe group, which was consistent with previously published reports. The isthmus is composed of thin, small volume thyroid parenchyma. Therefore, the thyroid capsule is easier to be invaded or broken through, and even the surrounding tissues could also be invaded. Extrathyroidal extension is well known as a related factor of the presence of LNMs for differentiated thyroid carcinoma. Cervical lymph node metastasis is an important factor affecting the prognosis in PTC patients . In a large sample of a case-control study, Lundgren  et al showed that well-differentiated PTC with lymph node metastasis could increase the risk of disease-related death by as much as three-fold. In our study, central lymph node involvement was more commonly observed in the isthmus group, whereas lateral node involvement was similar for the two groups. The management of PTC confined to the thyroid isthmus has remained controversial. Huang et al suggested that an isthmusectomy or extended isthmusectomy was feasible for patients with well-differentiated thyroid carcinoma arising in the isthmus. An isthmusectomy does not require exploration of the tracheo-esophageal groove and identification of parathyroid glands and the recurrent laryngeal nerve, which could reduce the risk of postoperative complications. However, Song et al recommended that complete bilateral central neck dissection should be considered for PTC in the isthmus due to the high rate of bilateral central lymph node metastasis. Our results indicated that a total thyroidectomy and central neck dissection seemed to be more appropriate than a less-than-total thyroidectomy for PTC in the isthmus. However, a prophylactic lateral neck dissection may be not necessary for patients with clinically negative nodes.
LND is defined as the ratio of the number of positive lymph nodes to the total number of lymph nodes excised. It has been shown to play a predictive role for oral cavity, pancreatic, gastric, and colon, and be superior to conventional nodal staging, which could be potential useful in identifying patients with poorer outcome who might benefit from more aggressive adjuvant treatments[24–28]. As for thyroid cancers, a previous study investigated the utility of LND using large single-institute cohort. It showed that LND greater than 0.19 was independently related to an adverse disease-specific survival and overall survival . To the best of our knowledge, the LND of PTC between in isthmus and in lateral lobe has not been compared in the literatures. In this study, LND in isthmus group was significantly higher than that of the lateral group, which might indicate a relatively poor outcome and the importance of routine central compartment dissection.
There were some limitations in this study: first, not all patients underwent lymph node dissection in the central and lateral cervical regions during surgery, and it is possible that there might have been some bias in the LND value. Second, patients with multiple lesions were excluded in our study, however, multifocality might also be associated with the presence of LNMs. Third, it is theoretically possible that other malignancies or benign nodules also might have exhibited atypical features compared to PTCs, but only PTCs were included in our study. This might lessen the value of our results. Finally, this study was a retrospective study. The follow-up results were incomplete, and no analysis was performed.
In summary, our results showed that patients with PTCs arising from the isthmus had a higher incidence of extrathyroidal extension, central lymph node involvement and a tendency of higher LND, however, the sonographic appearance was not typical. Therefore, more careful ultrasound evaluation should be performed for the nodule and cervical lymph nodes.