| Objective To learn the incidence of bilateral well-differentiated thyroid carcinoma (BWDTC) which were found in the pathology results of total or near total thyroidectomy and investigate the pathoclinical characteristics of BWDTC in order to find the optimal pocedure. Analyze the pathological and genetic features of multicentricity papillaty thytoid carcinoma to evaluate the clonal origins of different tumors, and to figure out the relationship between bilateral thyroid carcinoma and the underlying thyroid diseases.Methods The medical records of121cases which had underwent total or near total thyroidectomy were reviewed, retrospectively. Fourteen items selected from both the unilateral thyroid carcinoma group and bilateral thyroid carcinoma group were adopted to undergo a univariate analysis and logistic regression analysis. The pathological sections of33bilateral papillary thyroid carcinoma cases were reexamined in order to determine the histological variants by the experienced pathologists. According to the histological variants of the tumors located in two lobes, the tumors’clonal origins could be determined in the first step. Spectial pathological sections for microdissection of23cases whose paraffin blocks were in excellent state of preservation were made. There were62tumors in total, including50focus and12metastatic lymph nodes. The tumor tissue was obtained using laser capture microdissection technology. Genomic DNA was extracted from the formalin fixed and paraffin embedded tissues via the digestion by the proteinase K and extraction with phenol/chloroform. BRAFV600E mutation was detected by means of polymerase chain reation and DNA sequencing assays.Results There were33.06%BWDTC in the pathological results of total or near total thyroidectomy. Logistic regression analysis showed that patient’s age under50s, bilateral nodules based on ultrasound and the diameter of the first nodule over 2cm were independent risk factors of BWDTC(P<0.05).In the33papillary thyroid carcinoma cases, there were37(37/82,45.12%) focus of papillary thyroid microcarcinoma(PTMC) and26(26/33,78.79%) cases of PTMC.24cases showed conconcordant histological variants of tumors from both thyroid lobes, while9(9/33,27.27%) cases showed disconcordant variants in the bilateral tumors(one was conventional variant but the other one was follicular variant of papillary carcinoma) which could arise from different clonal origin. In these cases, combining with Hashimoto’thyroiditis showed significant difference in the bilateral papillary thyroid carcinoma cases which have different disconcordant variants in two lobes(P＜0.05).After the successful microdissection and extraction of the genomic DNA from FFPET of all the cases,51(51/62,82.26%) tumors were screened for BRAFV600E mutation. There were18cases whose tumors from both lobes were successfully amplified. The result of direct DNA sequencing showed15cases (15/18,83.33%) were positive for this common mutation (the missense T to A transversion at nucleotide1799).16(16/18,88.89%) cases showed conconcordant BRAF gene status in tumors from both thyroid lobes, being either BRAF mutation positive (13cases) or BRAF mutation negative (3cases), indicating that these tumors might be of monoclonal origin.86.67%cases with BRAFV600E mutation had concordant BRAF gene status, which meant BRAFV600E mutation could promote the intrathyroid spread. While the other2cases (2/18,11.11%) showed disconcordant BRAF gene status in tumors from both thyroid lobes. These11.11%PTCs might arise independently. All the10lymph nodes shared the same BRAF gene status with the tumors located in the same lobe. Such the lymph nodes metastasis might be the result of intrathyroidal spread originating from a single tumor mass. In the18cases which had been successfully amplified and screened for BRAFV600E mutation, PTCs combining with nodular goiter had a high BRAFV600E mutation rate which also had statistical difference(P＜0.05).Conclusion The incidence of BWDTC increased more than expected. In the premise of a malignant first nodule found in the preoperative examinations, BWDTC should be highly considered if the patient is under50years old, has bilateral nodules found by preoperative ultrasound and the diameter of the first nodule which is also the malignant one is over2cm. PTMC accourts for the main part of tumors of bilateral thyroid carcinoma, which should be placed a high value by doctors to avoid missed diagnosis. From both the pathology and BRAF mutation aspects, the bilateral tumors of most multicentricity papillary thyroid carcinoma may be the result of intrathyroid spread of one clonal origin. But there is still a certain number of multiple PTCs arise independently. The patient who has Hashimoto’ thyroiditis may have a great chance to combine with multiple PTCs which could arise independently in the form of bilateral focus with different histological variants. The bilateral thyroid papillary carcinoma may have a high BRAFV600E mutation rate, so does the multiple PTCs combining with nodular goiter. BRAFv600E mutation may promote the intrathyroid spread. |
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