Thyroid carcinomas are the most common endocrine malignancy and commonly have alterations in the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K)/AKT signaling pathways in well-differentiated tumors. Alternative molecular alterations driving thyroid carcinomas have been identified rarely in the literature and are more likely to occur in poorly differentiated or anaplastic cases. In this study, uncommon genetic alterations such as MLH1, MSH2, NSD3::NUTM1, RET::SPECC1L, and G3BP2::FGFR2 were identified in patients with papillary thyroid carcinoma, poorly differentiated thyroid carcinoma, and differentiated high-grade thyroid carcinoma. Most of these tumors demonstrated an aggressive biological behavior. Atypical driver mutations in thyroid carcinomas can occur in patients with cancer predisposition syndromes as demonstrated by an NTRK1::TPM3 fusion in a patient with Li Fraumeni syndrome. In these settings of more aggressive disease, molecular testing targeting actionable fusions and mutations is important. As demonstrated in our case cohort, 100% of cases diagnosed as high-grade follicular-derived thyroid carcinoma had a mutation or fusion that is associated with worse prognosis, has a germline syndrome association requiring further work up, or an actionable mutation. This high yield seen in this cohort for molecular testing in patients with high-grade follicular-derived thyroid carcinoma suggests more routine molecular testing in this population would be a beneficial clinical practice.

BACKGROUND: The relationship between genomic profile and prognosis of advanced thyroid carcinoma requiring drug therapy has not been reported.
OBJECTIVE: To evaluate the treatment period and overall survival time for each genetic alteration in advanced thyroid carcinoma that requires drug therapy.
METHODS: We conducted a retrospective observational study using a national database in Japan, which included 552 cases of thyroid carcinoma out of 53,543 patients in the database.
RESULTS: The database included anaplastic thyroid carcinoma (23.6%), poorly differentiated thyroid carcinoma (10.0%), and differentiated thyroid carcinoma (66.4%). The most common genetic abnormalities were TERT promoter (66.3%), BRAF (56.7%), and TP53 (32.2%). The typical driver genes were BRAF V600E (55.0%), RAS (18.5%), RET fusion (4.7%), NTRK fusion (1.6%), and ALK fusion (0.4%). The most common regimen was lenvatinib, and the time to treatment failure was not different despite the presence of BRAF or RAS mutations. In differentiated thyroid carcinoma and poorly differentiated thyroid carcinoma, TP53 alterations independently predicted worse overall survival (hazard ratio = 2.205, 95% confidence interval: 1.135-4.283). In anaplastic thyroid carcinoma, no genetic alterations were associated with overall survival.
CONCLUSIONS: Genetic abnormalities with treatment options were found in 62.7% of advanced thyroid carcinomas. TP53 abnormality was an independent poor prognostic factor for overall survival in differentiated thyroid carcinoma. The time to treatment failure for lenvatinib was not different based on genetic profile.

BACKGROUND: Circulating tumor cell (CTC) detection is one form of liquid biopsy. It is a novel technique that is beginning to be applied in the field of thyroid cancer. The present study was designed to evaluate the diagnostic value of CTCs in patients with thyroid cancer.
METHODS: A total of 1478 patients were retrospectively analyzed and divided into malignant group (n = 747) and benign group (n = 731). Peripheral blood was collected, and CTCs were enriched and quantified before surgery. The baseline data of the two groups were matched by Propensity Score Matching (PSM). Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficiency of different indicators for thyroid cancer. The malignant group before PSM was further divided into subgroups according to the BRAF V600E mutation and lymphatic metastasis (N stage), and the number of CTCs in different subgroups was compared.
RESULTS: After 1:1 PSM, baseline characteristics of the malignant group and benign group were matched and assigned 315 cases in each group. The number of CTCs and the TPOAb values were comparable in the two groups (p > 0.05). The TgAb values [1.890 (1.110 - 16.010) vs 1.645 (1.030 - 7.073) IU/mL, p = 0.049] were significantly higher in the malignant group than in the benign group. After PSM, ROC analyses showed that the areas under the curve (AUCs) of CTC, TgAb and ultrasound were 0.537 (sensitivity 65.6%, specificity 45.8%), 0.546 (sensitivity 40.0%, specificity 70.8%) and 0.705 (sensitivity 77.1%, specificity 63.2%), respectively. The AUCs of the combined detection of \'CTC + ultrasound\' (combine 1) and the combined detection of \'CTC + TgAb + ultrasound\' (combine 2) were 0.718 (sensitivity 79.3%, specificity 61.7%) and 0.724 (sensitivity 78.0%, specificity 63.3%), respectively. The AUC of ultrasound was significantly higher than CTC (p < 0.001). There was no statistically significant difference in AUC between combination 1 and ultrasound, and between combination 2 and ultrasound (p > 0.05). The number of CTCs between the N0 and N1 subgroups, and between the BRAF mutant and BRAF wild subgroups was comparable (p > 0.05).
CONCLUSIONS: As an emerging and noninvasive testing tool, the efficacy of CTCs in diagnosing thyroid cancer is limited.

UNASSIGNED: To evaluate potential improvements in the diagnosis of thyroid nodules when conventional ultrasound (US) is combined with contrast-enhanced US (CEUS).
UNASSIGNED: We recruited 515 participants with 323 malignant and 192 benign nodules, who underwent both US and CEUS examinations at 8 different medical centers in China between October 2020 and October 2021. We assessed the malignancy of thyroid nodules in US using the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TIRADS). Diagnostic criteria for US and US + CEUS were developed by investigators based on evaluations of sonographic features. Using multivariate logistic regression and receiver operating characteristic (ROC) analysis, we compared diagnostic performance between the 2 methods based on criteria identified by investigators and via statistical models.
UNASSIGNED: On the basis of diagnostic criteria identified by investigators, we measured statistically significant differences in area under the curve (AUC) values between ACR TIRADS (0.83) and CEUS TIRADS (0.87; P < .001). On the basis of diagnostic regression models, we found statistically significant differences in AUC values between US (0.76) and US + CEUS (0.84; P = .001). Models based on US + CEUS outperformed those based on US alone (Akaike information criterion of 347.7 and significant improvement in integrated discrimination). These results were confirmed by similar analyses applied to a validation cohort.
UNASSIGNED: The accuracy of conventional US for differentiating between benign and malignant thyroid nodules can be improved by combining this approach with CEUS.

BACKGROUND: There is ongoing debate about whether intraoperative parathyroid autotransplantation effectively prevents permanent hypoparathyroidism after thyroidectomy. This study aims to examine its impact on postoperative parathyroid function and determine the best autotransplantation strategy.
METHODS: A retrospective analysis was conducted on 194 patients who underwent total thyroidectomy with central lymph node dissection (CLND) for papillary thyroid carcinoma (PTC). Patients were divided into four groups based on the number of parathyroid autotransplants during surgery: Group 1 (none, n = 43), Group 2 (1 transplant, n = 60), Group 3 (2 transplants, n = 67), and Group 4 (3 transplants, n = 24). Various clinical parameters were collected and compared among the groups.
RESULTS: Parathyroid autotransplantation was identified as a risk factor for temporary hypoparathyroidism (OR: 1.74; 95% CI: 1.27-2.39, P = 0.001) and a protective factor for permanent hypoparathyroidism (OR: 0.27; 95% CI: 0.14-0.55, P < 0.001). At 12 months postoperative, systemic parathyroid hormone (PTH) levels increased progressively from Groups 1 to 4, with significant differences observed only between Group 1 and Group 2 (P < 0.02). Difference values in systemic PTH levels between Month 1 and Day 1 postoperative increased progressively from Groups 1 to 4, with statistically significant differences observed between adjacent groups (P < 0.02). The number of dissected positive lymph nodes increased progressively across the four groups, showing statistical differences (P < 0.02).
CONCLUSIONS: Parathyroid autotransplantation can prevent permanent hypoparathyroidism. Additionally, we recommend preserving parathyroids in situ whenever possible. If autotransplantation is required, it should involve no more than two glands.

OBJECTIVE: Sentinel lymph node (SLN) biopsy is rarely used for thyroid carcinoma staging. This is due to challenges associated with conventional Tc-99m-labeled tracers, often producing a large hotspot at the injection site, potentially hiding nearby SLNs (shine-through effect). The aim of this study was to demonstrate the feasibility and effectiveness of SLN visualization using the new PET tracer [68Ga]Ga-tilmanocept.
METHODS: Patients with thyroid carcinoma underwent ultrasound-guided peritumoral injection of [68Ga]Ga-tilmanocept and ICG-[99mTc]Tc-nanocolloid. [68Ga]Ga-tilmanocept PET/CT scans were conducted at 15 min and 60 min post-injection to visualize the SLNs. SLN biopsy was performed using ICG-[99mTc]TC-nanocolloid for intraoperative identification. The corresponding lymph node level was resected for reference.
RESULTS: Seven differentiated thyroid carcinoma (DTC) and 3 medullary thyroid carcinoma (MTC) patients were included, of which 6 were clinically node-negative. The median number of SLNs detected on [68Ga]Ga-tilmanocept PET/CT and resected was 3 (range 1-4) and 3 (range 1-5), respectively. Eight SLNs were found on PET/CT in the central compartment and 19 in the lateral compartment. The SLN procedure detected (micro)metastases in all patients except one. Seventeen of 27 pathologically assessed SLNs were positive, 8 negative, and 2 did not contain lymph node tissue, which led to upstaging in 5 out of 6 clinically node-negative patients.
CONCLUSIONS: [68Ga]Ga-tilmanocept PET/CT identified SLNs in all patients, mainly in the lateral neck. The SLNs were successfully surgically detected and resected using ICG-[99mTc]Tc-nanocolloid. This technique has the potential to improve neck staging, enabling more personalized treatment of thyroid cancer according to the lymph node status.
BACKGROUND: 2021-002470-42 (EudraCT).

There is limited evidence for mapping clinical tools to preference-based generic tools in the Chinese thyroid cancer patient population. The current study aims to map the FACT-H&N (Functional Assessment of Cancer Therapy-Head and Neck Cancer) to the SF-6D (Short Form Six-Dimension), which will inform future cost-utility analyses related to thyroid cancer treatment.
A total of 1050 participants who completed the FACT-H&N and SF-6D questionnaires were included in the analysis. Four methods of direct and indirect mapping were estimated: OLS regression, Tobit regression, ordered probit regression, and beta mixture regression. We evaluated the predictive performance in terms of root mean square error (RMSE), mean absolute error (MAE), concordance correlation coefficient (CCC), Akaike information criterion (AIC) and Bayesian information criterion (BIC) and the correlation between the observed and predicted SF-6D scores.
The mean value of SF-6D was 0.690 (SD = 0.128). The RMSE values for the fivefold cross-validation as well as the 30% random sample validation for multiple models in this study were 0.0833-0.0909, MAE values were 0.0676-0.0782, and CCC values were 0.6940-0.7161. SF-6D utility scores were best predicted by a regression model consisting of the total score of each dimension of the FACT-H&N, the square of the total score of each dimension, and covariates including age and gender. We proposed to use direct mapping (OLS regression) and indirect mapping (ordered probit regression) to establish a mapping model of FACT-H&N to SF-6D. The mean SF-6D and cumulative distribution functions simulated from the recommended mapping algorithm generally matched the observed ones.
In the absence of preference-based quality of life tools, obtaining the health status utility of thyroid cancer patients from directly mapped OLS regression and indirectly mapped ordered probit regression is an effective alternative.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma, and Hashimoto\'s thyroiditis (HT) has been postulated to have a relationship with PTC. This study aims to assess clinical and pathological characteristics of patients with papillary thyroid carcinoma coexisting with Hashimoto\'s thyroiditis.
METHODS: A retrospective study was conducted in a cohort of patients with thyroid carcinoma at the Department of Surgery, Shanghai General Hospital from January 2017 to December 2018. Medical records of patients who had PTC with or without HT were reviewed and clinical and histopathological characteristics of these patients were analyzed.
RESULTS: A total of 632 patients with thyroid carcinoma were identified. Among them, 614 (97.15%) had PTC and 120/614 (19.0%) harbored PTC together with HT. PTC was significantly associated with HT, as compared with other histological subtypes (P < .001). Patients with coexisting PTC and HT (PTC + HT group) were significantly younger than patients with PTC alone (PTC group) (P = .008). There were more women in the PTC + HT group than in the PTC group (88.3% vs. 73.1%, P < .001). TSH, TGAb, and TPOAb levels were significantly higher in the PTC + HT group than in the PTC group (P ≤ .001). In addition, tumor diameter was smaller in the PTC + HT group than in the PTC group (P = .034). The PTC + HT group showed a significant better recurrence-free survival than the PTC group. Furthermore, immunohistochemical analysis revealed that patients in the PTC + HT group had a higher positive rate and higher expression intensity of Ki67 than patients in the PTC group.
CONCLUSIONS: Our study revealed that patients with coexisting PTC and HT were younger, had smaller tumor diameters, a better prognosis, and higher positive rates and expression intensity of Ki67, than did patients with PTC alone.

OBJECTIVE: Microwave ablation (MWA) has achieved excellent long-term efficacy in treating unifocal papillary thyroid microcarcinoma (UPTMC). The therapeutic effect of this treatment on multifocal papillary thyroid microcarcinoma (MPTMC) is unknown. Therefore, we evaluated the long-term efficacy of MWA for low-risk MPTMC and to provide evidence-based medicine for the revision of clinical guidelines.
METHODS: This study included 66 MPTMC patients with a total of 158 lesions, all of whom received MWA. We collected and retrospectively analyzed the patients\' follow-up data before MWA, at 1, 3, 6, and 12 months posttreatment and every 6 months thereafter until 5 years posttreatment. We evaluated the MWA complication rate, technical success rate (TSR), lesion volume reduction rate (VRR), and complete disappearance rate (CDR) during follow-up and in those patients with tumor progression and delayed surgery.
RESULTS: After 60 months of follow-up, all 158 lesions disappeared in 66 patients, and the volume was reduced from 43.82 mm3 to 0.00 mm3. The TSR and VRR were both 100%. The CDRs at 1 year, 2 years, and 3 years were 57.59%, 93.67%, and 100%, respectively. The complication rate was 3.03% (2/66), and the incidence of tumor progression was 3.03% (2/66), including one new intrathyroidal lesion and one cervical lymph node metastasis (LNM). These lesions were retreated with MWA, and the lesions disappeared during the follow-up period.
CONCLUSIONS: Ultrasound-guided MWA for low-risk MPTMC is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance (AS).
CONCLUSIONS: This study concludes that ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance.
CONCLUSIONS: • Ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective. • During 5 years of follow-up, multifocal papillary thyroid microcarcinoma patients treated with microwave ablation had a favorable prognosis. • To provide evidence-based medicine for the revision of clinical guidelines.

OBJECTIVE: The aim of this study was to evaluate the clinical value of preoperative thyroid autoantibodies with reference to the post-thyroidectomy patient pathology.
METHODS: A retrospective cohort study.
METHODS: Two tertiary care academic hospitals.
METHODS: A total of (n = 473) subjects who underwent thyroidectomy from 2009 to 2019 were included. Preoperative serum thyroid autoantibodies (anti-thyroglobulin [anti-Tg] and anti-thyroperoxidase [anti-TPO]) were measured, and the potential predictors of postoperative pathological diagnosis (age, gender, and thyroid autoantibodies) were assessed using multivariable regression models.
RESULTS: Patients with positive thyroid autoantibodies were more likely to have malignant disease than benign disease; adjusted odds ratio (AOR) = 1.6 (1.3-2.7, p = 0.002) for anti-Tg, and AOR = 1.6 (1.1-2.5, p = 0.027) for anti-TPO. A subset analysis of the same predictors performed on patients with cancer (malignant vs. microcarcinoma) showed that patients with ages ≥40 were more likely to develop microcarcinoma as opposed to malignant disease; AOR = 1.8 (1.1-3.1, p = 0.03) for anti-TPO, and AOR = 1.7 (1.0-2.9, p = 0.04) for anti-Tg.
CONCLUSIONS: Preoperative thyroid autoantibodies could be used clinically to predict the risk of malignancy in thyroid nodules, thus helping guide treatment decisions in patients with thyroid nodules and speeding up the decision to undergo surgical intervention.