| BackgroundThyroid cancer,which although only 1%of the incidence of systemic cancer,is the most common head and neck cancer. Thyroid cancer currently accounts for the first systemic endocrine tumors, but its incidence is rising rapidly in recent years and rising to become one of the fastest growth in the incidence of malignant humantumors. Ultrasound has been Confirmed not only providing the mass number, size, shape, and to clear cystic mass and enelope complete.it is associated microcalcifications and organizational relationships and circumstances surrounding the neck lymph nodes and other features, conventional ultrasound could detect some clinical failure palpable mass and for the early detection of tumors.It have a certain value. High-resolution ultrasound has become the preferred laboratory examinations of thyroid nodular disease. However, there are some limitations of ultrasound in differentiating benign and malignant thyroid nodules, biopsy cytopathology was confirmed the most effective preoperative diagnostic method in current clinical suspicion of thyroid cancer patients.Thyroid biopsy cytology (fine-needle aspiration, FNA) as a screening tool, which is is recognized as a means to assess the nature of thyroid nodules Gold standard.It is easy to operate,safe, minimally invasive, rapid diagnostic accuracy and complications. Ultrasound-guided fine-needle aspiration biopsy (ultrasound-guided fine-needle aspiration US-FNA) is the use of fine 18G following ultrasound-guided aspiration interspersed repetitive method for thyroid nodules. FNA can get a cell or tissue smear or liquid-based cell was stored after production and then clear nodules under the microscope. There are large differences in thyroid FNA accuracy of data. Puncture level, cytology experience and other important factors affect the accuracy of FNA. Current research focus is to find an effective adjunct to assist clinical pathology. High-resolution ultrasound combined with biopsy and cytology antibody immunohistochemical markers for the differential diagnosis of thyroid cancer,lack of uniform standards. For thyroid cancer difficult to diagnose pathological cytological differential diagnosis typing is not clear. Currently less relevant reports.Objective1. To discuss high-resolution ultrasound combined with FNA immunohistochemical analysis methods of diagnosis and differential diagnostic value for benign and malignant thyroid nodules.2. To analysis cytokeratin (CK)-3、BRAF、HBME-1、the expression of TPO antibodies in particular diagnostic value of thyroid cancer-19, galectin (Galectin) for thyroid nodules.3. To discuss simple FNA diagnosis of not easy to diagnose thyroid cancer pathological joint new ideas typing.Materials and methods1. Patient sample38 patients with thyroid nodules diagnosed patients in Qilu Hospital of Shandong University (Qingdao) of Otolaryngology Head and Neck Surgery on October 2015 to February 2016 were enrolled in this study. The mean age of the patient sample were (36.7±9.6) years, ranging from 25 to 67years old. The mean diameter of the lesions were (8.1±10.2)mm, ranging from 5.0 to 18.2mm.38 patients with a total of 45 nodules. Where in two nodules have not achieved satisfactory number of organizations, not for immunohistochemistry, quit the study. Pathologically confirmed malignant nodules 25, where 22 cases of papillary thyroid carcinoma, undifferentiated carcinoma, follicular carcinoma in 2 cases; 18 cases of benign nodules, surgery in 14 cases,9 cases of nodular goiter,4 cases of adenoma, and 1 with Hashimoto fibrosis. The remaining four cases without surgery, regular follow-up. In this study, informed consent was obtained from all patients.2. Ultrasound scanning2.1 Ultrasound and FNA screening:2.1.1 Patient were scanned on a philips iU Eliter color Doppler ultrasonic diagnostic apparatus with a L12-5 linear array probe. Patient supine, fully exposed neck, carried horizontal, vertical, oblique multi-directional scanning. Case record lesions under conventional modes.lt include nodule number, size, shape, edge, border, aspect ratio, internal and rear echo characteristics, internal calcification, blood supply, surrounding tissue changes, the corresponding regional lymph nodes and so on.2.1.2 The latest guidelines from the American Thyroid Association (ATA) in 2014 pointed to FNA ultrasound screening has a very important role. According to the different characteristics of ultrasound ultrasound to assess the risk of malignant thyroid nodules. Nodules divided into five categories including highly malignant, intermediate grade, low grade and low index of suspicion as well as benign and malignant thus a corresponding probability of malignancy. This study FNA nodules greater than 5.0mm in diameter and not as high, medium and low grade.2.2 FNA examinationPatient with neck fully exposed supine hyperextended head and routine skin disinfection. Books about patients who were holding the needle and the probe in the ultrasound-guided thyroid nodule fine needle aspiration was performed twice. The first needle No.7 needle puncture made negative pressure tissue smear. Use the second needle biopsy needle attracted Japanese Hakko CL Type 23G x 50mm obtain tissue in formalin preservation solution.3.3 Immunohistochemical analysisGalactosidase lectin-3, CK19, BRAF, HBME-1, TPO immune expression was determined.①Immunohistochemical indicators cytologic diagnosis of benign and malignant cases as a reference only.②In cytological diagnosis of suspected immunohistochemical expression of Galectin-3, CK19, BRAF, HBME-1 in which three or more positive, TPO negative for malignant nodules are malignant or uncertain, when Galectin-3, CK19, BRAF,HBME-1 in which three or more negative, TPO positive were regarded as a benign diagnosis theory.4. Statistical analysisStatistical analysis were performed using SPSS 17.0 software. All measurement data were expressed as x±s. Student’s t tests, one-way ANOVA tests and χ2 tests were used for comparisons. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic performances of discriminating benign and malignant thyroid nodules.Z tests were used to compare the area under the curve (AUC). A P value<0.05 was considered statistically significant.Results1. Joint immunohistochemical cytologic diagnosis and postoperative pathology: Preoperative cytological diagnosis:17 cases of papillary carcinoma, undifferentiated carcinoma, follicular tumors (8 cases of suspected malignant), follicular lesions (seven cases of suspected benign). Cytological diagnosis of suspected malignant cases immunohistochemical antibody labeling. Where three cases of papillary carcinoma, follicular carcinoma. Pathological papillary carcinoma in 4 cases, follicular carcinoma. Benign cytological diagnosis of suspected cases in 7 cases, immunohistochemical antibody labeling,4 cases of malignant, pathological papillary carcinoma in 2 cases, follicular carcinoma. Finally, determine the pathology of papillary carcinoma in 22 cases, carcinoma, follicular undifferentiated carcinoma in 2 cases,4 cases of adenoma, nodular goiter 9 cases with Hashimoto fibrosis in 1 case.2. The diagnostic value of different immunohistochemical markers in thyroid cancer in comparison:Galectin-3 in thyroid cancer diagnosis sensitivity, specificity, accuracy, positive predictive value (positive predictive value, PPV), negative predictive value (negative predictive value, NPV) were 96.7%,90.9%,90.7%, 96.7%,76.9%. CK19 sensitivity in the diagnosis of thyroid cancer, specificity, accuracy, PPV, NPV were 100%,100%,93.0%,100%,78.6%. BRAF sensitivity in the diagnosis of thyroid cancer, specificity, accuracy, PPV, NPV were 100%,100%, 90.7%,100%,73.3%. HBME-1 in thyroid cancer diagnosis sensitivity, specificity, accuracy, PPV, NPV was 93.1%,81.8%,83.7%,93.1%,69.2%. TPO in thyroid cancer diagnosis sensitivity, specificity, accuracy, PPV, NPV was 93.7%,72.7%, 90.7%,86.1%and 100%. Joint-labeled antibody in the diagnosis of thyroid cancer sensitivity, specificity, accuracy, PPV, NPV was 90.6%,100%,93.0%,90.6%and 70%.3. The differential diagnostic value of high-resolution ultrasound, FNA, FNA combined with immunohistochemistry and in benign and malignant thyroid nodules in comparison:the sensitivity of high-resolution ultrasound differential diagnosis of benign and malignant thyroid nodules, specificity, PPV, NPV, accuracy, respectively 72.2%,74.5%,68.5%,69.5%,75.4%. FNA differential diagnosis of benign and malignant thyroid nodules sensitivity, specificity, PPV, NPV, accuracy were 75%, 78.7%,85.7%,73.5%,86.5%. FNA sensitivity joint immunohistochemistry in differential diagnosis of benign and malignant thyroid nodules, specificity, PPV, NPV, accuracy were 93.7%,90.9%,93.7%,77.8%and 93.0%. FNA FNA joint and immunohistochemistry for the identification of benign and malignant thyroid nodules sensitivity, specificity, PPV, NPV, accuracy are higher than conventional ultrasound; FNA combined with immunohistochemistry for the differential diagnosis of thyroid nodules sensitivity, PPV, NPV, accuracy was higher than FNA.4. High-frequency ultrasound, FNA, FNA Joint antibody immunohistochemical markers in the differential diagnosis of benign and malignant thyroid nodules The ROC curve analysis:High frequency ultrasound in differential diagnosis of benign and malignant thyroid nodules AUC was 0.807, FNA Kam diagnosis of benign and malignant thyroid nodules AUC was 0.930, FNA Joint antibody immunohistochemical markers in the differential diagnosis of benign and malignant thyroid nodules AUC 0.989.5. Differential diagnosis of benign and malignant thyroid nodules, FNA and high-frequency ultrasound ROC area under the curve, the difference was statistically significant (Z=2.70, P= 0.017); area under the ROC curve FNA Joint immunohistochemistry and high-frequency ultrasound Comparison the difference was statistically significant (Z=3.18, P=0.009); FNA FNA joint with immunohistochemistry for the differential diagnosis of benign and malignant thyroid nodules in the area under the ROC curve, the difference was not statistically significant (Z=1.23, P=0.083). Tips and FNA FNA Joint immunohistochemical differential diagnosis of benign and malignant thyroid nodules similar meaning, the smaller the difference, but FNA Joint immunohistochemistry sensitivity, specificity, PPV higher than FNA, but NPV is lower than pure FNA.6. High-resolution ultrasound diagnosis of follicular tumors prompted two cases. Wherein cytology positive case and negative in 1 case.Positive tips Galectin-3, CK19, BRAF, HBME-1 were positive.TPO negative cytology results still prompted follicular tumors and finally confirmed by pathology thyroid follicular carcinoma. But FNA negative in 1 case which immunohistochemistry also negative in the end still pathologically confirmed follicular thyroid cancer.ConclusionsFNA, FNA joint and antibody labeling immunohistochemistry for the diagnosis and differential diagnosis of benign and malignant thyroid nodules has important clinical value. Thyroid cancer coudle improve diagnostic sensitivity, positive predictive value, negative predictive value and accuracy. Galectin-3, CK19, BRAF, HBME-1 antibody for thyroid cancer diagnostic sensitivity, specificity, accuracy, PPV, NPV were high. The above antibodies can be used as a specific marker of thyroid cancer antibody. For follicular thyroid cancer difficult to diagnose simply FNA can provide new ideas and new diagnostic method of diagnosis. FNA occupy an important position, especially in the thyroid nodule accurate diagnosis of thyroid cancer. FNA combined with immunohistochemistry in the diagnosis of thyroid cancer show good prospects... |
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