Diagnostic Value Of CEUS Combined With BRAF^V600E Gene Mutation For Immunologically Ambiguous ACR-TIRADS 4 Thyroid Nodules

Background:With the advancement of social medical level and the improvement of people’s awareness of their own health,the detection rate of thyroid nodules（TN）is also increasing year by year.TN is a common thyroid disease.The diagnosis of TN mainly relies on thyroid ultrasound（Ultrasonography,US）.TN diagnosed by palpation also needs to be confirmed by thyroid US.It is necessary to further evaluate the benign and malignant nodules based on medical history,clinical manifestations and auxiliary examinations.The application of Thyroid Imaging Reporting and Data System（TI-RADS）makes the US assessment of TN more standardized.However,it cannot clarify the specific nature of TN,especially TI-RADS type 4 nodules.Therefore,it is necessary to further combine other auxiliary examinations to clarify its properties for targeted treatment.Ultrasound-guided fine needle aspiration biopsy（UG-FNAB）is a method with high accuracy before surgery,which is currently widely used to provide cytological specimens for TN.According to thyroid cytopathology Bethesda system,cytology reports can be divided into 6 categories,of which class I can not be diagnosed or unsatisfactory,Class III atypical or unspecified follicular lesions（AUS/FLUS）and class IV follicular tumors or suspected follicular tumors（FN/SFN）are classified as TN with unclear cytological type.V-raf murine sarcoma viral oncogene homolig B1（BRAF）is the BRAF gene.The BRAF^V600E gene mutation is considered as a specific molecular marker of differentiated thyroid carcinoma（DTC）,which is used to further analyze the nature of TN and determine the benign and malignant TN.Contrast enhanced ultra sound（CEUS）,also known as acoustic contrast,can show blood perfusion in TN by observing the flow of microbubble contrast agent,which has certain advantages in the identification and diagnosis of benign and malignant properties of TN.In clinical practice,the diagnostic value of CEUS and BRAF^V600E gene mutation detection in ACR-TIRADS class 4 TN with unclear cytological diagnosis deserves further exploration.Objective:This study explored the application value of CEUS combined with BRAF^V600E gene mutation detection in the differential diagnosis of benign and malignant ACR-TIRADS type 4 TN with unclear cytological diagnosis.Methods:A retrospective analysis of Northern Jiangsu People’s Hospital between 2017-06 and2022-10,a total of 124 patients with ACR-TIRADS 4 nodules diagnosed with Bethesda Ⅰ,Ⅲ and Ⅳ by preoperative FNAB at the same time after CEUS,BRAF^V600E gene mutation and surgical treatment.The patient’s general information,postoperative pathological results,CEUS reports,BRAF^V600E gene test results,thyroid function and antibodies data were analyzed.Postoperative pathology was used as the criterion,the following comparisons were made:（1）Analyze the differences in age,sex,thyroid function and antibodies,TN diameter and location among benign and malignant nodule groups;（2）Analyze the difference between US characteristics and CEUS features in benign and malignant nodules,and calculate the sensitivity（Se）,specificity（Sp）,positive predictive value（PPV）,negative predictive value（NPV）and accuracy of CEUS for the diagnosis of TN;（3）Analyze the Se,Sp,PPV,NPV and accuracy of Se,SP,PPV,NPV and TN diagnosed by BRAF^V600E gene mutation detection and combined with CEUS,construct receiver operating characteristic curve（ROC）,calculate the area under the curve（AUC）,and evaluate the effects of different examination methods on Bethesda I,III,Diagnostic value of ACR-TIRADS class 4 nodules in IV.Results:Among the 124 ACR-TIRADS class 4 nodules with preoperative FNAB diagnosed with Bethesda Ⅰ,Ⅲ and Ⅳ,there were no significant differences in age,thyroid function,antibody,location,diameter and size of patients with benign and malignant group nodules（P>0.05）.Among the US characteristics,there was a statistically significant difference between the two groups between>aspect ratios 1 and microcalcification（P<0.05）.Among the CEUS features,there were statistically significant differences between the two groups（P<0.05）in the six features of low enhancement,uneven reinforcement,abundant blood flow signal,rapid regression,mean time to increase（RT）and mean time to peak（TTP）.CEUS’s Se,Sp,PPV,NPV,accuracy and AUC for THESDA I,III,IV class4 TNs were 82.81%,66.67%,89.83%,52.17%,79.27%and 0.728,respectively.The accuracy and AUC of SE,SP,PPV,NPV,and AUC of ACR-TIRADS class 4 TN in Bethesda Ⅰ,Ⅲ and Ⅳ were 34.09%,100.00%,100.00%,38.30%,53.23%and 0.669,respectively.The Se,Sp,PPV,NPV,accuracy and AUC of CEUS combined with BRAF^V600E gene mutation detection for the diagnosis of SE,SP,PPV,NPV,87.4%and AUC of ACR-TIRADS class 4 TN in Bethesda Ⅰ,Ⅲ and Ⅳ were 83.82%,85.71%,96.61%,67.63%,87.42%and 0.950,respectively.Conclusion:1.In the ACR-TIRADS class 4 TN of Bethesda Ⅰ,Ⅲ and Ⅳ diagnosed by CEUS,malignant nodules were mainly characterized by low,unevenly enhanced,rich blood flow signals and rapid regression.In addition,the levels of RT and TTP were significantly higher than those of benign nodules;2.Compared with the application alone,CEUS combined with BRAFV600E gene mutation detection has higher Se,NPV and accuracy in diagnosing the ACR-TIRADS class 4 TN of Bethesda Ⅰ,Ⅲ and Ⅳ.