Diagnostic Value Of UG-FNAB For Thyroid Nodules And Its Combination With Brafv600e Gene Detection For TI-RADS Type 4 Nodules

Background:With the improvement of clinical medical equipment and diagnosis and treatment and the people’s awareness of their own health,more and more thyroid nodules（Thyroid nodules,TN）have been discovered and diagnosed.Ultrasound examination is a routine screening method for TN.The Thyroid Imaging Reporting And Data System（TI-RADS）was proposed to standardize the ultrasound examination of TN,which initially assessed the malignant risk of TN,but could not accurately identify it.The nature of TN requires other tests to improve the accuracy of pathological diagnosis.Ultrasound-guided Fine Needle Aspiration Biopsy（UG-FNAB）examination is one of the most accurate preoperative examination items,and it is recommended by domestic and foreign guidelines to evaluate the pathological properties of TI-RADS type 3–5 nodules.However,there were many influencing factors for UG-FNAB,especially the large number of red blood cells under the microscope interfered with the pathological diagnosis,and the conclusions of different studies had great differences.Therefore,in this study,the advanced Thinprep cytology test,TCT)was used to process puncture samples to avoid the interference of red blood cells.Due to the existence of certain false-negative and false-positive results of UG-FNAB,in recent years,the detection of gene mutation in murine sarcoma viral oncohomologue B1（v-Rafmurine sarcoma viral oncogene homologue B1,BRAF）V600E（BRAFV600E）from puncture specimens has been used as an important molecular marker to further assist in the diagnosis of the nature of TN.It is well known that TI-RADS type 4 nodules are the most common among the benign and malignant TN that need to be further evaluated clinically,and the malignant risk of this type of nodule is the most controversial in the academic community.Objective:This study explored the diagnostic value of UG-FNAB for Ti-RADS type 3-5nodules by using advanced TCT method,and further studied the application value of UG-FNAB combined with BRAF^V600Egene detection in differential diagnosis of TI-RADS type 4 nodules.Methods:A retrospective analysis of Northern Jiangsu People’s Hospital between 2018-01-01and 2020-12-31,a total of 468 patients with TI-RADS type 3,4,and 5 nodules who underwent UG-FNAB and surgical treatment at the same time.All patients have the following complete clinical data:postoperative and UG-FNAB pathological conclusions,general data,thyroid function and antibodies,TI-RADS classification report,among them,of which 282 cases of TI-RADS type 4 nodules have also perfected BRAF^V600Egene mutation detection.Taking postoperative pathology as the gold standard,make the following comparisons:（1）The chi-square test was used to calculate the sensitivity（Se）,specificity（Sp）,positive predictive value（PPV）,negative predictive value（NPV）and accuracy rate of UG-FNAB for the diagnosis of 468 cases of TN.The Kappa value was used to compare the consistency of UG-FNAB cytopathological and postoperative histopathological results.Taking the postoperative histopathological results as the standard,construct the receiver operating characteristic curve（ROC curve）,calculate the area under the curve（AUC）,and evaluate the diagnostic value of UG-FNAB for TNs;（2）Compare the UG-FNAB cytological diagnosis results and postoperative pathological results of TI-RADS type 3,4,5 nodules,calculate the Se,Sp,PPV,NPV and accuracy of UG-FNAB in the diagnosis of TI-RADS type 3,4,5 nodules;（3）Select 282 cases of TI-RADS type 4 nodules that completed BRAF^V600Egene mutation detection,respectively calculate the Se,Sp,PPV,NPV and accuracy of UG-FNAB,BRAF^V600Egene mutations and the combination of the two diagnostic methods for TI-RADS type 4 nodules;construct ROC curves and calculate AUC,and evaluate the diagnostic value of different diagnostic methods for TI-RADS type 4nodules.Results:（1）A total of 468 TN patients were included in this study.The Se、Sp、PPV、NPV and accuracy of UG-FNAB diagnosis in 468 cases were 87.6%,93.8%,96.4%,80.0%and89.7%respectively;The cytological pathology of UG-FNAB is in good agreement with the postoperative pathology（Kappa=0.782）;Taking the postoperative histopathological results as the standard,the ROC curve was constructed,and the AUC was 0.907（95%CI:0.877～0.937）.（2）There were 43 cases of TI-RADS type 3 nodules,316 cases of TI-RADS type 4nodules and 109 cases of TI-RADS type 5 nodules.The diagnostic rates of Se,Sp,PPV,and NPV and the accuracy of UG-FNAB in the diagnosis of TI-RADS type 3 nodules were 77.8%,97.1%,85.5%,94.3%,and 93.0%,respectively.The diagnostic rates of Se,Sp,PPV,and NPV and the accuracy rate of UG-FNAB in the diagnosis of TI-RADS type 4 nodules were 84.5%,93.6%,96.2%,76.1%,and 87.8%,respectively.The diagnostic rates of Se,Sp,PPV,and NPV and the accuracy rate of UG-FNAB in the diagnosis of TI-RADS type 5 nodules were 95.6%,89.5%,97.7%,81.0%,and 94.5%,respectively.（3）282 cases of TI-RADS type 4 nodules which were simultaneously perfected in the detection of BRAF^V600Egene were screened out.The diagnostic rates of Se,Sp,PPV,and NPV and the accuracy of UG-FNAB in the diagnosis of TI-RADS type 4 nodules were 84.7%,95.7%,97.6%,75.4%,and 88.3%,respectively.The diagnostic rates of Se,Sp,PPV,and NPV and the accuracy of BRAF^V600Egene detection in the diagnosis of TI-RADS type 4 nodules were 70.0%,97.8%,98.6%,64.1%,and 81.2%,respectively.The combined diagnostic rates of Se,Sp,PPV,and NPV and the accuracy in the diagnosis of TI-RADS type 4 nodules were 95.8%,94.6%,97.3%,91.7%,and95.4%,respectively.The AUC of the three diagnostic methods from large to small was:UG-FNAB combined with BRAF ^V600Etest（AUC=0.952）,UG-FNAB（AUC=0.902）and BRAF^V600Egenetic test（AUC=0.865）.Conclusion:1.UG-FNAB has high diagnostic value in differentiating benign and malignant nodules of TI-RADS type 3～5 nodules,and the cytological pathology of UG-FNAB is consistent with postoperative pathology,but the negative predictive value of diagnosis of TI-RADS type 4 nodules is low,and it is easy to miss some malignant nodules.2.Compared with UG-FNAB alone,UG-FNAB combined with BRAFV600E gene detection can significantly improve its sensitivity,accuracy and negative predictive value for the diagnosis of TI-RADS type 4 nodules.