Projecting long-term clinical outcomes with larotrectinib compared with immune checkpoint inhibitors in metastatic nonsmall cell lung cancer and differentiated thyroid cancer.

BACKGROUND: Larotrectinib is approved for patients with advanced NTRK gene fusion-positive solid tumors. Prior studies demonstrated promising results with larotrectinib compared with other systemic therapy. However, comparisons to checkpoint inhibitors, such as nivolumab or pembrolizumab, have not been done. OBJECTIVE: To estimate and compare expected life-years (LYs) and quality-adjusted LYs (QALYs) for patients with nonsmall cell lung cancer (NSCLC) eligible for larotrectinib vs patients with unknown NTRK gene fusion status on nivolumab or pembrolizumab. We also assessed patients with metastatic differentiated thyroid cancer (DTC), as pembrolizumab may be considered in certain circumstances. METHODS: We developed partitioned survival models to project long-term comparative effectiveness of larotrectinib vs nivolumab or pembrolizumab. Larotrectinib survival data were derived from an updated July 2021 analysis of 21 adult patients (≥18 years of age) with metastatic NTRK gene fusion-positive NSCLC and 21 with DTC. Survival inputs for nivolumab and pembrolizumab were obtained from published articles. Progression-free and overall survival were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Log-normal). Exponential fits were chosen based on goodness-of-fit and clinical plausibility. RESULTS: In NSCLC, larotrectinib resulted in gains of 5.87 and 5.91 LYs compared to nivolumab and pembrolizumab, respectively, which translated to gains of 3.53 and 3.56 QALYs. In DTC, larotrectinib resulted in a gain of 5.23 LYs and 4.24 QALYs compared to pembrolizumab. CONCLUSIONS: In metastatic NSCLC and DTC, larotrectinib may produce substantial life expectancy and QALY gains compared to immune checkpoint inhibitors. Additional data with longer follow-up will further inform this comparison.

MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma: potential therapeutic targets and diagnostic/prognostic markers and web based tools.

This review aimed to describe the inculpation of microRNAs (miRNAs) in thyroid cancer (TC) and its subtypes, mainly medullary thyroid carcinoma (MTC), and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC. Additionally, the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed. This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes, mainly MTC. Additionally, web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described. MiRNAs can perform as oncomiRs or antioncoges, relying on the target mRNAs they regulate. MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases, particularly in cancer. MiRNAs are involved in the modulation of fundamental pathways related to cancer, resembling cell cycle checkpoints and DNA repair pathways. MiRNAs are also rather stable and can reliably be detected in different types of biological materials, rendering them favorable diagnosis and prognosis biomarkers as well. MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets. The contribution of miRNAs in thyroid cancer, particularly MTC, is an active area of research, and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

Risk factors for secondary thyroid cancer in patients with breast cancer: a propensity­matched SEER analysis.

With the rapid development of imaging technology and comprehensive treatment in modern medicine, the early diagnosis rate of breast cancer is constantly improving, and the prognosis is also improving; As breast cancer patients survive longer, the risk of developing second primary cancers increases. Since both breast and thyroid are Hormone receptor sensitive organs, which are regulated by hypothalamus pituitary target gland endocrine axis, changes in body endocrine status may lead to the occurrence of these two diseases in succession or simultaneously. This study extracted clinical data and survival outcomes of breast cancer patients registered in the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2019. After matching the case and controls with propensity scores, the selected patients were randomly split into training and test datasets at a ratio of 7:3. Univariate and multivariate COX proportional regression analysis is used to determine independent risk factors for secondary thyroid cancer and construct a column chart prediction model. Age, ethnicity, whether radiotherapy, tumor primary location, N stage, M stage were identified by Cox regression as independent factors affecting secondary thyroid cancer in patients with breast cancer patients, and a risk factor nomogram was established to predict patients' 3 and 5 year survival probabilities. The AUC values for 3 and 5 years in the training set were 0.713, 0.707, and the c-index was 0.693 (95% CI 0.67144, 0.71456), and the AUC values for 3 and 5 years in the validation set were 0.681, 0.681, and the c-index was 0.673 (95% CI 0.64164, 0.70436), respectively.

Diagnostic value of combined ultrasound contrast and elastography for differentiating benign and malignant thyroid nodules: a meta-analysis.

The diagnostic value of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules is still controversial, so we used meta-analysis to seek controversial answers. The PubMed, OVID, and CNKI databases were searched according to the inclusion and exclusion criteria. The literature was selected from the establishment of each database to February 2024. The QUADAS-2 tool assessed diagnostic test accuracy. SROC curves and Spearman's correlation coefficient were made by Review Manager 5.4 software to assess the presence of threshold effects in the literature. Meta-Disc1.4 software was used for Cochrane-Q and χ2 tests, which be used to evaluate heterogeneity, with P-values and I2 indicating heterogeneity levels. The appropriate effect model was selected based on the results of the heterogeneity test. Stata18.0 software was used to evaluate publication bias. The diagnostic accuracy of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules was evaluated by calculating the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, DOR, and area under the SROC curve. A total of 31 studies included 3811 patients with 4718 nodules were analyzed. There is no heterogeneity caused by the threshold effect, but there is significant non-threshold heterogeneity. Combined diagnostic metrics were: sensitivity = 0.93, specificity = 0.91, DOR = 168.41, positive likelihood ratio = 10.60, and negative likelihood ratio = 0.07. The SROC curve area was 0.97. Contrast-enhanced ultrasound and elastography show high diagnostic accuracy for thyroid nodules, offering a solid foundation for early diagnosis and treatment.Trial registration. CRD42024509462.

Feasibility and safety of modified en-bloc resection in endoscopic thyroid surgery via bilateral areolar approach - long-term institutional analysis ten years after surgery.

Purpose: This study aimed to introduce a new modified en-bloc resection method and evaluate its feasibility and safety in endoscopic thyroid surgery via bilateral areolar approach (BAA). Methods: Papillary thyroid carcinoma (PTC) patients who underwent lobectomy and ipsilateral central node dissection (CND) via the BAA approach were retrospectively reviewed. Their clinical characteristics and outcomes were evaluated, including operative duration, lymph node yield (LNY), surgical complications, recurrence rate, and metastasis rate, over a ten-year follow-up period. Simultaneous lobectomy and CND were performed in the modified en-bloc group, whereas lobectomy was performed first, followed by CND in the conventional group. Results: The study included 108 patients in the modified en-bloc group and 213 in the conventional group. There were no significant differences in gender, age, tumor locations, tumor dominant nodule size, or the incidence of concomitant Hashimoto thyroiditis when comparing clinicopathologic characteristics. The comparison of operative duration (P = 0.14), blood loss (P = 0.13), postoperative hospital stay (P = 0.58), incidence of transient vocal cord paralysis (P = 0.90) and hypocalcemia (P = 0.60) did not show any differences. The mean LNY achieved in the central compartment of the modified en-bloc group (7.5 ± 4.5) was significantly higher than that in the conventional group (5.6 ± 3.6). Two patients in the modified en-bloc group and two in the conventional group experienced metastasis after surgery during the ten-year follow-up (1.8% vs. 0.9%, P = 0.60). The learning curve analysis showed a significant decrease in operative duration after the 25-35th cases for modified en-bloc resection. Conclusions: The modified en-bloc resection method in endoscopic thyroid surgery via BAA is a technically feasible and safe procedure with excellent cosmetic outcomes for selective PTC patients.

Changes in thyroid cytology reporting in the 3rd edition of the Bethesda system.

Reporting fine-needle aspiration of thyroid nodules in the Bethesda classification is a practice widely used internationally and by us. The revised third edition of the Bethesda System of Reporting Thyroid Cytopathology brings changes in terminology, content, and new chapters. In terms of terminology, an obvious change is the removal of the two-word names of three categories while maintaining the six diagnostic categories of the previous versions - new: BI - non-diag- nostic, BIII - atypia of undetermined significance, BIV - follicular neoplasia. In the detailed description of the findings within the individual categories, the ter- minological changes adopted by the fifth edition of the WHO classification of thyroid neoplasia are respected - in particular, the recommended name follicular thyroid nodular disease for the most frequently represented category BII - benign. In the evaluation itself, the diagnostic specifications accepted by the current WHO classification of histopathological findings are reflected in the individual categories - if they are applicable at the cytological level. Targeted attention will need to be paid to high grade features. The revised version brings new chapters dedicated to molecular testing and evaluation of the paediatric population.

Score based on contrast-enhanced ultrasound predict central lymph node metastasis in papillary thyroid cancer.

Objectives: To investigate the association between contrast-enhanced ultrasound (CEUS) features of PTC and central lymph node metastasis (CLNM) and to develop a predictive model for the preoperative identification of CLNM. Methods: This retrospective study evaluated 750 consecutive patients with PTC from August 2020 to April 2023. Conventional ultrasound and qualitative CEUS features were analyzed for the PTC with or without CLNM using univariate and multivariate logistic regression analysis. A nomogram integrating the predictors was constructed to identify CLNM in PTC. The predictive nomogram was validated using a validation cohort. Results: A total of 684 patients were enrolled. The 495 patients in training cohort were divided into two groups according to whether they had CLNM (pCLNM, n= 191) or not (nCLNM, n= 304). There were significant differences in terms of tumor size, shape, echogenic foci, enhancement direction, peak intensity, and score based on CEUS TI-RADS between the two groups. Independent predictive US features included irregular shape, larger tumor size (≥ 1.0cm), and score. Nomogram integrating these predictive features showed good discrimination and calibration in both training and validation cohort with an AUC of 0.72 (95% CI: 0.68, 0.77) and 0.79 (95% CI: 0.72, 0.85), respectively. In the subgroup with larger tumor size, age ≤ 35 years, irregular shape, and score > 6 were independent risk factors for CLNM. Conclusion: The score based on preoperative CEUS features of PTC may help to identify CLNM. The nomogram developed in this study provides a convenient and effective tool for clinicians to determine an optimal treatment regimen for patients with PTC.

Prognostic value of postoperative anti-thyroglobulin antibody in patients with differentiated thyroid cancer.

Purpose: Postoperative thyroglobulin (Tg) generally serves as a biomarker to monitor the recurrence or persistence of differentiated thyroid cancer (DTC), whereas it constrains to interference from anti-thyroglobulin antibody (TgAb). This study aimed to determine the value of postoperative TgAb as a surrogate for monitoring tumor status in DTCs with positive TgAb after successful radioactive iodine (RAI) remnant ablation. Methods: We retrospectively enrolled DTC patients with positive (≥40 IU/mL, Roche) postoperative TgAb measurements. An index of TgAb change (ΔTgAb) was defined to describe the TgAb decrease rate. DTC status was defined as either no evidence of disease (NED) or persistent/recurrent disease (PRD). Univariate and multivariate binary logistic analyses were used to identify the independent risk factors of PRD. Receiver operating characteristic (ROC) curves were performed to determine the optimal cutoff values of each risk factor, and DeLong's test was conducted to compare their predictive powers. Kaplan-Meier curves were used to assess the impact of different TgAb trends in the first year on progression-free survival. Results: Of the 232 patients enrolled, the median diagnosis age was 34 years (range, 18-62 years), with a male-to-female ratio of 1:4.66 (41/191). Among them, after a median follow-up of 44 months (range, 4-128 months),183 (78.87%) patients were evaluated as NED, while the other 49 (21.12%) had either persistent (n = 25) or recurrent disease (n = 24). Multivariate regression showed that ΔTgAb (P < 0.001) and lymph node metastasis (LNM) rate (P = 0.009) were independently relevant to the presence of PRD, with optimal cutoff values of 47.0% and 35.1%, respectively. It is important to note that there is a high negative predictive value (96.93%) of ΔTgAb with the cutoff of 47.0%. DeLong's test showed that ΔTgAb alone and the combination of ΔTgAb and LNM rate were significantly greater than the isolated LNM rate (both P < 0.001) in predicting NED, while there was no statistical difference of the predictive power between ΔTgAb and the combination (P = 0.203). Additionally, patients with ΔTgAb >47.0% had longer progression-free survival than those with ΔTgAb ≤47.0% (not reached vs. 50 months, P < 0.001), and those with ΔTgAb >47.0% or negative conversion within the first year after RAI ablation had longer progression-free survival. Conclusion: Our study suggested that ΔTgAb could serve as a valuable indicator of disease status in DTC patients with positive TgAb. A ΔTgAb of >47.0% is conducive to identify those with NED and may help to obviate their overtreatment. The decrease rate and negative conversion of TgAb in the first year were good predictors of disease-free survival in patients.

Differential diagnosis of thyroid nodules using heterogeneity quantification software on ultrasound images: correlation with the Bethesda system and surgical pathology.

Ultrasonography (US)-guided fine-needle aspiration cytology (FNAC) is the primary modality for evaluating thyroid nodules. However, in cases of atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), supplemental tests are necessary for a definitive diagnosis. Accordingly, we aimed to develop a non-invasive quantification software using the heterogeneity scores of thyroid nodules. This cross-sectional study retrospectively enrolled 188 patients who were categorized into four groups according to their diagnostic classification in the Bethesda system and surgical pathology [II-benign (B) (n = 24); III-B (n = 52); III-malignant (M) (n = 54); V/VI-M (n = 58)]. Heterogeneity scores were derived using an image pixel-based heterogeneity index, utilized as a coefficient of variation (CV) value, and analyzed across all US images. Differences in heterogeneity scores were compared using one-way analysis of variance with Tukey's test. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristic (AUROC) curve. The results of this study indicated significant differences in mean heterogeneity scores between benign and malignant thyroid nodules, except in the comparison between III-M and V/VI-M nodules. Among malignant nodules, the Bethesda classification was not observed to be associated with mean heterogeneity scores. Moreover, there was a positive correlation between heterogeneity scores and the combined diagnostic category, which was based on the Bethesda system and surgical cytology grades (R = 0.639, p < 0.001). AUROC for heterogeneity scores showed the highest diagnostic performance (0.818; cut-off: 30.22% CV value) for differentiating the benign group (normal/II-B/III-B) from the malignant group (III-M/V&VI-M), with a diagnostic accuracy of 72.5% (161/122). Quantitative heterogeneity measurement of US images is a valuable non-invasive diagnostic tool for predicting the likelihood of malignancy in thyroid nodules, including AUS or FLUS.

Homogentisic acid metabolism inhibits papillary thyroid carcinoma proliferation through ROS and p21-induced cell cycle arrest.

Thyroid cancer is one of the most common primary endocrine malignancies worldwide, and papillary thyroid carcinoma (PTC) is the predominant histological type observed therein. Although PTC has been studied extensively, our understanding of the altered metabolism and metabolic profile of PTC tumors is limited. We identified that the content of metabolite homogentisic acid (HGA) in PTC tissues was lower than that in adjacent non-cancerous tissues. We evaluated the potential of HGA as a novel molecular marker in the diagnosis of PTC tumors, as well as its ability to indicate the degree of malignancy. Studies have further shown that HGA contributes to reactive oxygen species (ROS) associated oxidative stress, leading to toxicity and inhibition of proliferation. In addition, HGA caused an increase in p21 expression levels in PTC cells and induced G1 arrest. Moreover, we found that the low HGA content in PTC tumors was due to the low expression levels of tyrosine aminotransferase (TAT) and p-hydroxyphenylpyruvate hydroxylase (HPD), which catalyze the conversion of tyrosine to HGA. The low expression levels of TAT and HPD are strongly associated with a higher probability of PTC tumor invasion and metastasis. Our study demonstrates that HGA could be used to diagnose PTC and provides mechanisms linking altered HGA levels to the biological behavior of PTC tumors.

Metabolomic screening of radioiodine refractory thyroid cancer patients and the underlying chemical mechanism of iodine resistance.

Radioiodine refractory (RAIR) patients do not benefit from iodine-131 therapy. Thus, timely identification of RAIR patients is critical for avoiding ineffective radioactive iodine therapy. In addition, determining the causes of iodine resistance will facilitate the development of novel treatment strategies. This study was comprised of 20 RAIR and 14 non-radioiodine refractory (non-RAIR) thyroid cancer patients. Liquid chromatography-mass spectrometry was used to identify differences in the serum metabolites of RAIR and non-RAIR patients. In addition, chemical assays were performed to determine the effects of the differential metabolites on iodine uptake. Metabolic pathway enrichment analysis of the differential metabolites revealed significant differences in the phenylalanine and tyrosine metabolic pathways. Notably, quinate and shikimic acid, metabolites of the tyrosine pathway, were significantly increased in the RAIR group. In contrast, the phenylalanine pathway metabolites, hippuric acid and 2-phenylacetamide, were markedly decreased in the RAIR group. Thyroid peroxidase plays an important role in catalyzing the iodination of tyrosine residues, while the ionic state of iodine promotes the iodination reaction. Quinate, shikimic acid, hippuric acid, and 2-phenylacetamide were found to be involved in the iodination of tyrosine, which is a key step in thyroid hormone synthesis. Specifically, quinate and shikimic acid were found to inhibit iodination, while hippuric acid and 2-phenylacetamide promoted iodination. Abnormalities in phenylalanine and tyrosine metabolic pathways are closely associated with iodine resistance. Tyrosine is required for thyroid hormone synthesis and could be a potential cause of iodine resistance.

CLIP170 inhibits the metastasis and EMT of papillary thyroid cancer through the TGF-ß pathway.

Metastasis poses a significant challenge in combating tumors. Even in papillary thyroid cancer (PTC), which typically exhibits a favorable prognosis, high recurrence rates are attributed to metastasis. Cytoplasmic linker protein 170 (CLIP170) functions as a classical microtubule plus-end tracking protein (+TIP) and has shown close association with cell migration. Nevertheless, the specific impact of CLIP170 on PTC cells remains to be elucidated. Our analysis of the GEO and TCGA databases unveiled an association between CLIP170 and the progression of PTC. To explore the impact of CLIP170 on PTC cells, we conducted various assays. We evaluated its effects through CCK-8, wound healing assay, and transwell assay after knocking down CLIP170. Additionally, the influence of CLIP170 on the cellular actin structure was examined via immunofluorescence; we further investigated the molecular expressions of epithelial-mesenchymal transition (EMT) and the transforming growth factor-ß (TGF-ß) signaling pathways through Western blotting and RT-qPCR. These findings were substantiated through an in vivo nude mouse model of lung metastasis. We observed a decreased expression of CLIP170 in PTC in contrast to normal thyroid tissue. Functionally, the knockdown of CLIP170 (CLIP170KD) notably enhanced the metastatic potential and EMT of PTC cells, both in vitro and in vivo. Mechanistically, CLIP170KD triggered the activation of the TGF-ß pathway, subsequently promoting tumor cell migration, invasion, and EMT. Remarkably, the TGF-ß inhibitor LY2157299 effectively countered TGF-ß activity and significantly reversed tumor metastasis and EMT induced by CLIP170 knockdown. In summary, these findings collectively propose CLIP170 as a promising therapeutic target to mitigate metastatic tendencies in PTC.

Conformal thyroidectomy is a feasible option in papillary thyroid microcarcinoma: a retrospective cohort study with 10-year follow-up results.

BACKGROUND: In recent years, there has been an increasing prevalence of patients with papillary thyroid microcarcinoma (PTMC) without lymph node involvement in medical centers worldwide. For patients who are unable to undergo active surveillance (AS) and are afraid of postoperative complications, conformal thyroidectomy may be a suitable option to ensure both preservation of function and complete removal of the tumor. METHODS: The patients in the cohort during 2010 to 2015 were retrospectively enrolled strictly following the inclusion and exclusion criteria. The observation and control groups were defined based on the surgical approach, with patients in the observation group undergoing conformal thyroidectomy and patients in the control group undergoing lobectomy. Event-free survival (EFS), the interval from initial surgery to the detection of recurrent or metastatic disease, was defined as the primary observation endpoint. RESULTS: A total of 319 patients were included in the study, with 124 patients undergoing conformal thyroidectomy and 195 patients undergoing lobectomy. When compared to lobectomy, conformal thyroidectomy demonstrated reduced hospital stays, shorter operative times, and lower rates of vocal cord paralysis and hypoparathyroidism. Furthermore, the mean bleeding volume during the operation and the rate of permanent hypothyroidism were also lower in the conformal thyroidectomy group than in the lobectomy group. However, there was no statistically significant difference observed in the 5- and 10-year EFS between the two groups. CONCLUSIONS: Conformal thyroidectomy had advantages in perioperative management and short-term complication rates, with an EFS that was not inferior to that of lobectomy. Thus, conformal thyroidectomy is a feasible option for low-risk PTMC patients.

Timing and Ideal Patient for an Appropriate Search for Somatic RET Mutation in Medullary Thyroid Cancer.

RET somatic mutation analysis in sporadic MTC should be guided by postoperative evaluation results.

Spontaneous and Treatment-Related Changes of Serum Calcitonin in Medullary Thyroid Cancer: Long-Term Experience in a Patient With Multiple Endocrine Neoplasia Type 2B.

PURPOSE: Medullary thyroid carcinoma (MTC) in MEN2B syndrome is associated with germline RET mutation. Patients harboring de novo mutations are usually diagnosed at more advanced disease stages. We present a young woman with Met918Th mutation diagnosed with stage IV MTC at age 10 years. METHODS: The disease progressed despite total thyroidectomy and multiple surgical interventions for cervical lymph node recurrences, leading to distant metastases in the fifth year after the initial diagnosis. Subsequently, she underwent five different types of tyrosine kinase inhibitor (TKI) treatments. The 17-year disease course was divided into periods defined by four surgical interventions and sequential treatment intervals with four multikinase (sunitinib, vandetanib, cabozantinib, and lenvatinib) and one RET-selective TKI (selpercatinib). Tumor growth for different phases of spontaneous development and drug treatment intervals was characterized by changes in serial log-transformed calcitonin measurements (n = 114). RESULTS: Three operations (one for calcitonin-producing adrenal pheochromocytoma) were associated with drops in calcitonin levels. All of the nonselective TKIs were stopped due to adverse effects. As reflected by the negative calcitonin doubling rate, the best treatment response was observed with selpercatinib, which was associated with an initial large drop followed by a decreasing calcitonin trajectory over 514 days without any major side effects. CONCLUSION: This case of MEN2B medullary thyroid cancer with long-term survival presents how the effectiveness of different treatment modalities can be estimated using log-transformed calcitonin levels. Furthermore, our experience supports the view that serial calcitonin measurements may be more sensitive than radiological follow-up in advanced MTC. Our patient also represents a new case of rarely reported calcitonin-producing pheochromocytomas.

Uncommon molecular alterations in follicular-derived thyroid carcinoma: A single institution study.

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.