Prediction of cervical lymph node metastasis with contrast-enhanced ultrasound and association between presence of BRAF^V600E and extrathyroidal extension in papillary thyroid carcinoma

Abstract

Objective: This study aimed to evaluate the correlation between cervical lymph node metastasis (CLNM) and each of the ultrasound features, immunohistochemical factors, and B-type Raf (BRAFV600E) mutation. Methods: A retrospective analysis was performed on 405 patients with single papillary thyroid carcinoma (PTC) nodules, all of whom underwent preoperative sonographic examinations, including gray-scale ultrasound, color Doppler ultrasound, and contrast-enhanced ultrasound (CEUS). All PTC patients were evaluated using 14 clinical and sonographic features, eight immunohistochemical factors, and BRAFV600E. Multivariate analyses were performed to identify the risk factors for CLNM, and an equation for CLNM was established. The diagnostic value of each modality was compared with a receiver operating characteristic (ROC) curve. Results: Among the 405 PTC nodules removed surgically, CLNM was confirmed in 138 patients, whereas extrathyroidal extension was confirmed in 185 patients. Multivariate analyses indicated significant differences between CLNM and non-CLNM groups in three conventional ultrasound features ( p < 0.05), whereas other sonographic features, eight immunohistochemical factors, and BRAFV600E did not indicate significant differences. A ROC curve of 0.757 in the equation exhibited a significant difference compared with the solo factors ( p < 0.05 for all). Hyper or isoechoic enhancement at peak time on CEUS was associated with CLNM, whereas the presence of the BRAFV600E mutation was associated with extrathyroidal extensions although BRAF appeared to be uncorrelated with CLNM in the present study. Conclusion: Intensity at peak time, homogeneity, and size are the three most significant features in predicting CLNM in PTC patients, and the presence of the BRAFV600E mutation was associated with extrathyroidal extensions when PTCs showed a hyper or isoechoic enhancement at peak time in CEUS.

Ultrasound and Contrast-Enhanced Ultrasound Characteristics Associated With cN1 and Microscopic pN1 in Papillary Thyroid Carcinoma

“…In our study, hyper-enhancement on CEUS was correlated with cN1 rather than with microscopic pN1. The similar conclusion was drawn by other studies ( 7 , 10 ) that hyper-enhancement on CEUS suggested a high risk of LNMs. In these studies, the LNMs included both cN1 and microscopic pN1.…”

“…Some investigations ( 7 – 13 ) have explored the PTC’s US and CEUS features associated with LNMs and confirmed their values in predicting LNMs. However, LNMs could be stratified into clinical N1 (cN1, observed on US) and microscopic pN1 (pathological N1), which might bear different biological behavior and prognostic values.…”

Analysis of the Relevance of the Ultrasonographic Features of Papillary Thyroid Carcinoma and Cervical Lymph Node Metastasis on Conventional and Contrast-Enhanced Ultrasonography

“…Previous studies found that the enhancement patterns of PTC on CEUS are a useful tool to predict CLNM ( 29 , 30 ). Hong ( 31 ) et al.…”

Value of Combining Clinical Factors, Conventional Ultrasound, and Contrast-Enhanced Ultrasound Features in Preoperative Prediction of Central Lymph Node Metastases of Different Sized Papillary Thyroid Carcinomas

“…19,20 Several studies have shown that CEUS could assess the biological behavior of thyroid nodules. [21][22][23] To our knowledge, few studies have included CEUS for preoperative prediction CLNM of different sized PTC.…”