Synchronous papillary and follicular thyroid carcinomas: the first retrospective cohort study and literature review.

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

Persistence of primary hyperparathyroidism: a single-center experience.

BACKGROUND: Parathyroidectomy is the only definitive treatment for primary hyperparathyroidism (PHPT). Precise localization of abnormal glands is a key to a successful surgery. Most patients are expected to be successfully treated with focused parathyroidectomy. However, this approach is associated with a risk of existing multiglandular disease which may lead to the postoperative persistence of PHPT. METHODS: Eight hundred ten patients who underwent an initial surgery for PHPT at SPBU Hospital in 2017-2018 were included in the study. Preoperative imaging results were evaluated. Multivariate logistic regressions were calculated to estimate predictive values of preoperative data for the risk of postoperative persistence and risk of MGD. RESULTS: Multiglandular disease was found to be a leading cause of persistent hyperparathyroidism. An anamnesis of thyroid surgery was found to be a significant risk factor for the persistence of hyperparathyroidism. The rate of persistence did not differ significantly between groups with bilateral neck exploration and focused parathyroidectomy. Age, sex, body mass index as well as negative results of preoperative US, MIBI, and 4D CT were not independently associated with a higher risk of MGD. All preoperative imaging modalities showed from low to moderate sensitivity for the detection of MGD. The frequency of cases of a missed second adenoma did not differ significantly between patients with concordant and discordant preoperative data. There were 7 cases with previously unsuspected second adenomas found solely due to bilateral neck exploration. CONCLUSIONS: None of the combination of preoperative visualization modalities was able to rule out the MGD and reliably identify patients for focused parathyroidectomy. Additional preoperative visualization failed to improve overall results. Bilateral neck exploration appeared to have a slight benefit for the patients with concordant preoperative imaging results.

Next-Generation Sequencing Enhances the Diagnosis Efficiency in Thyroid Nodules.

BACKGROUND: Though fine-needle aspiration (FNA) improved the diagnostic methods of thyroid nodules, there are still parts of nodules that cannot be determined according to cytology. In the Bethesda system for reporting thyroid cytopathology, there are two uncertain cytology results. Thanks to the development of next-generation sequencing technology, it is possible to gain the genetic background of pathological tissue efficiently. Therefore, a combination of the cytology and genetic background may enhance the accuracy of diagnosis in thyroid nodules. METHODS: DNA from 73 FNA samples of thyroid nodules belonging to different cytology types was extracted and exome sequencing was performed by the ThyroLead panel. Test for BRAF mutation was also performed by ARMS-qPCR. Information including age, sex, preoperative cytology, BRAF mutation status tested by ARMS-qPCR, and surgical pathology was collected in electronic medical record system. RESULTS: A total of 71 single nucleotide variants, three fusion gene, and two microsatellite instability-high status were detected in 73 FNA samples. BRAF V600E mutation is the most common mutation in these malignant thyroid nodules. After combining the cytology and genetic background detected by next-generation sequencing, the diagnosis sensitivity was increased from 0.582 (95% CI: 0.441-0.711) to 0.855 (95% CI: 0.728-0.930) (P < 0.001) in our group, while the specificity, 1,000 (95% CI: 0.732-1.000) compared to 0.857 (95% CI: 0.562-0.975) (P = 0.25), did not get affected. CONCLUSIONS: Next-generation sequencing in thyroid nodules can enhance the preoperative diagnosis sensitivity by fine-needle aspiration alone. It can also provide genetic background for direction of medication. It is possible for clinicians to combine cytology with genetic alterations for a more precise diagnosis strategy of thyroid nodules.

Arms-qPCR Improves Detection Sensitivity of Earlier Diagnosis of Papillary Thyroid Cancers With Worse Prognosis Determined by Coexisting BRAF V600E and Tert Promoter Mutations.

OBJECTIVE: The coexistence of BRAF V600E and the telomerase reverse transcriptase (TERT) promoter mutation C228T/C250T is extensively associated with thyroid cancer prognosis. Our study aimed to establish a sensitive method for mutation detection and explore the correlation in detail. METHODS: The BRAF and TERT promoter mutation status of 250 papillary thyroid cancers was determined using amplification-refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR) and Sanger sequencing to compare the sensitivity of the 2 methods. Associations between the mutation status and clinicopathological features were then analyzed. RESULTS: ARMS-qPCR was more sensitive than Sanger sequencing (BRAF V600E: 75.2% [188 of 250] vs 52.4% [131 of 250], P < .001; TERT promoter C228T/C250T mutation: 12.0% [30 of 250] vs 3.6% [9 of 250], P = .001; comutation: 9.6% [24 of 250] vs 3.2% [8 of 250], P = .005). Both ARMS-qPCR and Sanger sequencing indicated that patients with coexisting BRAF V600E and TERT promoter mutations had an older diagnosis age, higher recurrence rate, and were associated with a more advanced TNM stage and higher metastasis, age, completeness of resection, invasion, and size score. Moreover, ARMS-qPCR helped identify an earlier group stage, which was younger and had smaller tumors and a lower recurrence rate, compared with the group with coexisting BRAF V600E and TERT promoter mutations identified by Sanger sequencing. The newly identified group had a lower metastasis, age, completeness of resection, invasion, and size score and TNM stage. CONCLUSION: Patients with coexisting BRAF V600E and TERT promoter mutations had a worse prognosis. ARMS-qPCR, the more sensitive method, can be used to identify patients who have a potentially worse prognosis earlier.

Transcutaneous laryngeal ultrasonography (TLUS) as an alternative to direct flexible laryngoscopy (DFL) in the perioperative evaluation of the vocal cord mobility in thyroid surgery.

PURPOSE: Direct flexible laryngoscopy (DFL) is the golden standard to evaluate the vocal cord (VC) function in thyroid and parathyroid surgery pre- and postoperatively. Transcutaneous laryngeal ultrasonography (TLUS) could represent an alternative to the DFL and has been evaluated in the present study comparing the results of both methods performed at two referral centers for endocrine pathologies. METHODS: In the setting of a retrospective study, 668 patients (560 female, 118 male; mean age 50.3 ± 14.2) were included from two tertiary referral centers of endocrine surgery. In all patients, TLUS was performed pre- and postoperatively prior to transnasal DFL, which served as a golden standard. TLUS was performed by B-scan (probe 5-13 MHz, aperture 40 mm). RESULTS: Preoperative visualization of the vocal cords by TLUS was possible in 526 patients (78.7%). Due to the frequent thyroid cartilage calcification (TCC) in male patients, a significant difference in the visualization rate was found between female and male (88.7% vs. 26.8%) [p < 0.0001]. Additionally, the visualization rate was inversely related to the patient's age [p < 0.001]. The sensitivity of preoperative TLUS was found to be 66.7%, the specificity 100%. DFL confirmed a postoperative palsy in 34 out of 40 patients with supposed abnormal vocal cord mobility at TLUS and demonstrated a palsy in four more cases with supposed regular mobility at TLUS. Therefore, the sensitivity of postoperative TLUS was 86%, the specificity of 99.1%, positive predictive value 89.4%, negative predictive value 98.7%. CONCLUSIONS: TLUS could represent an alternative for the evaluation of vocal cords mobility. This method has the potential to replace the DFL in the majority of cases, especially in female patients. Nevertheless, DFL is still necessary in about 20% of the patients with failed visualization at TLUS.