The Value Of C-TIRADS,Contrast-Enhanced Ultrasound And BRAF^V600E Gene In Preoperative Diagnosis Of TBSRTC Type Ⅲ Thyroid Nodules

Objective:1.To investigate the diagnostic value of contrast-enhanced ultrasound（CEUS）,China Thyroid Imaging Reporting and Data System（C-TIRADS）,and BRAF ^V600Egene in thyroid cytopathology reporting system（TBSRTC）class Ⅲ nodules.2.To compare the diagnostic efficacy of C-TIRADS,CEUS and BRAF^V600Egene in predicting benign and malignant TBSRTC Type Ⅲ nodules.3.To compare the diagnostic value of C-TIRADS and CEUS alone or in combination in predicting benign and malignant BRAF^V600Emutation-negative nodules in TBSRTC Class Ⅲ nodules.Methods:From August 2018 to December 2021,120 patients（120 in total）with thyroid nodules diagnosed as TBSRTC Ⅲ by preoperative fine needle aspiration cytopathology were selected from Daping Hospital of the Army Military Medical University.When patients have multiple thyroid nodules,the highest risk of malignancy is selected as the target nodule.Thyroid ultrasound examination was performed on all nodules.Five malignant indicators（solid,very low echo,microcalcification,verticality,blurred edges or irregularity or external thyroid invasion）and one benign indicator（comet tail sign artifacts）were classified by C-TIRADS according to the ultrasonic image features of nodules based on counting method.In this study,C-TIRADS 4B and above were classified as malignant,and C-TIRADS 4A and below were classified as benign.At the same time,the nodules were examined by contrast-enhanced ultrasound（CEUS）.According to the diagnostic criteria of CEUS,it was diagnosed as malignant by the ultrasonographic manifestations of uneven or low enhancement,centripetal filling,interrupted capsular membrane of nodules near the thyroid edge,etc.,and benign by the ultrasonographic manifestations of high or equal enhancement,complete annular enhancement,and no enhancement.Ultrasound-guided fine-needle aspiration biopsy cytology of thyroid nodules was performed on and BRAF^V600Egene was detected on puncture extract.Finally,surgical pathological results were used as the gold standard to compare the diagnostic efficacy of single or combined C-TIRADS,CEUS and BRAF^V600Egene detection for TBSRTC Type Ⅲ nodules.At the same time,the diagnostic efficacy of C-TIRADS and CEUS alone or combined in the diagnosis of BRAF^V600Enegative TBSRTCⅢnodules was compared.Results:1.Postoperative pathology:In this study,there were 120 TBSRTC Class Ⅲ nodules and 79 malignant tumors,including 74 papillary carcinoma,4 follicular carcinoma and 1 diffuse large B lymphoma;There were 41 benign nodules,including 26 nodular goiters,6 follicular tumors,4 adenomas,2 Hashimoto’s thyroiditis,1 subacute thyroiditis,and 2 glial cysts.2.In this study of 120 thyroid nodules,78 cases were diagnosed malignant by C-TIRADS before surgery,70 cases were confirmed malignant by pathology after surgery,and 8 cases were benign.Preoperative diagnosis of C-TIRADS was benign in 42 cases,postoperative pathology confirmed that 33 cases were benign and 9 cases were malignant.Preoperative CEUS diagnosis was malignant in 67 cases,postoperative pathology confirmed malignant in 58 cases and benign in 9 cases.Preoperative CEUS diagnosis was benign in 53 cases,postoperative pathology confirmed that 32 cases were benign and 21 cases were malignant.61 nodules with BRAF^V600Egene mutation extracted by fine needle extraction before surgery were malignant,59 nodules had no mutation by gene detection,41 cases were benign tumors and 18 cases were malignant tumors.3.The sensitivity,specificity,accuracy and area under the curve of single method were 88.61%,80.49%,85.83%and 0.845 for C-TIRADS in the diagnosis of TBSRTC Type Ⅲ thyroid nodules,respectively.CEUS 73.42%,78.05%,75.00%,0.757;BRAF^V600Egene was detected 77.22%,100%,85.00%and 0.886.The diagnostic sensitivity and accuracy of C-TIRADS were higher than those of CEUS,with statistical significance（P<0.05）.The diagnostic sensitivity and accuracy of C-TIRADS were higher than those of BRAF^V600Egene,but the differences were not statistically significant（P>0.05）.The specificity of BRAF^V600Egene was higher than that of CEUS and C-TIRADS,and the differences were statistically significant（P<0.05）.Comparison of AUC:BRAF^V600Egene>C-TIRADS>CEUS.4.The sensitivity,specificity,accuracy and area under the curve（AUC）for C-TIRADS+BRAF^V600Egene,C-TIRADS+CEUS and CEUS+BRAF^V600Egene in diagnosing TBSRTC Type Ⅲ thyroid nodules were 98.73%,90.24%,95.83%,0.945,88.61%,70.73%,82.50%,0.797,and 87.34%,70.73%,81.67%,0.790,respectively.In pairwise comparison,the diagnostic sensitivity,specificity and accuracy of C-TIRADS+BRAF^V600Egene were higher than those of C-TIRADS+CEUS and CEUS+BRAF^V600Egene,the differences were statistically significant（P<0.05）,and the AUC of C-TIRADS+BRAF^V600Egene was the highest among them.5.The sensitivity,specificity,accuracy and area under the curve（AUC）of the three methods for the combined diagnosis of TBSRTC type Ⅲ thyroid nodules were 98.73%,73.17%,90.00%and 0.860 respectively;The diagnostic sensitivity was improved,but the specificity was significantly reduced.6.In this study of 120 thyroid nodules,there were 59 nodules with negative BRAF^V600Egene mutation before surgery,18 were pathologically malignant and41 were pathologically benign.25 patients were diagnosed malignant by C-TIRADS before surgery,17 were malignant and 8 were benign by pathology after surgery.34 cases were diagnosed benign by C-TIRADS before surgery,33cases were benign and 1 case was malignant by pathology after surgery.Preoperative CEUS diagnosis was malignant in 24 cases,postoperative pathology confirmed that 12 cases were malignant,12 cases were benign.Preoperative CEUS diagnosis was benign in 35 cases,postoperative pathology confirmed benign in 29 cases and malignant in 6 cases.The sensitivity,specificity,accuracy and area under the curve（AUC）of C-TIRADS,CEUS and CEUS in the diagnosis of TBSRTC Type Ⅲ nodules were 94.44%,84.49%,84.75%,0.875,respectively.CEUS 66.67%,70.73%,69.49%,0.687;C-TIRAD+CEUS 94.44%,68.29%,76.27%,0.814;The diagnostic sensitivity,specificity and accuracy of C-TIRADS were higher than those of CEUS and the combined diagnosis of the two methods,and the accuracy difference was statistically significant（P<0.05）.AUC of C-TIRADS was the highestamong them.Conclusion:1.Single application of C-TIRADS,CEUS and BRAF^V600Egene diagnostic methods has high diagnostic value for TBSRTC Type Ⅲ nodules.2.The combination of C-TIRADS and BRAF^V600Egene can maximize the diagnostic efficacy in differentiating benign and malignant TBSRTC Type Ⅲ nodules.3.The combined application of C-TIRADS,CEUS and BRAF^V600Ein the diagnosis of benign and malignant TBSRTC Type Ⅲ nodules increased the sensitivity,but the specificity decreased significantly,and the diagnostic efficacy did not improve effectively.4.Comparing the diagnostic efficacy of C-TIRADS,CEUS and the combination of the two methods for BRAF^V600Emutage-negative TBSRTC Type Ⅲ nodules,the diagnostic value of CEUS is limited,C-TIRADS has higher diagnostic accuracy and efficacy than CEUS and the combination of the two methods.