Thyroid nodules in pediatric patients are less common than in adults but show a higher malignancy rate. Accordingly, the management of thyroid nodules in pediatric patients is more complex the younger the patient is, needing careful evaluation by physicians. In adult patients, specific ultrasound (US) features have been associated with an increased risk of malignancy (ROM) in thyroid nodules. Moreover, several US risk stratification systems (RSSs) combining the US features of the nodule were built to define the ROM. RSSs are developed for the adult population and their use has not been fully validated in pediatric patients. This study aimed to evaluate the available data about US features of thyroid nodules in pediatric patients and to provide a summary of the evidence regarding the performance of RSS in predicting malignancy. Moreover, insights into the management of thyroid nodules in pediatric patients will be provided.

BACKGROUND: BRAFV600E and TERT promoter mutations in papillary thyroid carcinoma (PTC) have a synergistic effect on prognosis. This effect is believed to arise from MAPK activation triggered by BRAFV600E, leading to the upregulation of ETS transcription factors that bind to the mutant TERT promoter.
OBJECTIVE: To explore the role of ETS factors in relation to clinical features, BRAFV600E and TERT promoter mutations in PTC.
METHODS: Transcriptomic data for 28 ETS factors were analyzed in the PTC cohort of The Cancer Genome Atlas (TCGA, n=399) and subsequently validated in a local cohort (n=93). In vitro experiments were performed to investigate the regulatory role in relation to BRAFV600E and TERT expression.
RESULTS: TCGA identified ETS1, ERG, FLI1, GABPA, EHF, ETV6 and SPDEF as differentially expressed genes between stages I+II and III+IV. In both cohorts, EHF was consistently associated with adverse clinical features, BRAFV600E and TERT promoter mutation/expression. Notably, in BRAFV600E mutated PTC, high EHF expression was associated with shorter disease-free survival. Cases harboring concurrent BRAFV600E, TERT promoter mutations and high EHF expression exhibited the shortest disease-free survival. In cells harboring concurrent BRAFV600E and TERT promoter mutation, over-expression of EHF significantly increased TERT expression while knockdown or pharmacological inhibition of BRAF significantly decreased both EHF and TERT expression. In addition, ChIP-qPCR analysis suggested a potential binding of EHF in TERT promoter mutant cells but not in TERT promoter wild-type cells.
CONCLUSIONS: The ETS transcription factor EHF is associated with poor prognosis in PTC. This is potentially mediated by BRAF-induced upregulation of EHF which in turn increases TERT expression in TERT promoter mutated cells.

As the most common endocrine cancer, thyroid cancer (TC) has sharply increased globally over the past three decades. The growing incidence of TC might be counted by genetics, radiation, iodine, autoimmune disease, and exposure to environmental endocrine-disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs), being typical EDCs, have been widely utilized in plastics, electronics, furniture, and textiles as flame retardants since the 1980s, and research has indicated a significant correlation between their exposure and the risk of TC. Even so, PBDEs exposure impact on the metabolic signature for TC remains unexplored. In this study, eight congeners of PBDEs were determined in serum from 111 patents with papillary thyroid cancer (PTC) and 111 healthy participants based on case-control epidemiology using gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (GC-APCI-MS/MS). Based on the tertile distribution of total PBDEs concentrations in 59 participants, metabolomics analysis was further performed by ultra-high performance liquid chromatography coupled to hybrid quadrupole-Orbitrap MS. In the partial correlation analysis, the 29 identified metabolites were correlated with PBDEs exposure (P < 0.05). In addition, PBDEs disrupted the metabolism of glycerophospholipids, sphingolipids, taurine, and hypotaurine, indicating that neurotransmitters, oxidative stress, and inflammation are the vulnerable pathways affected in PTC. Furthermore, (±)-octopamine and 5-hydroxyindole, both of which modulate the actions of neurotransmitters, emerged as potential disturbed metabolite markers for TC following exposure to PBDEs. This study analyzed the impact of PBDEs on PTC in terms of the metabolic changes and further explored possible biomarkers, which helped us have a deep understanding of the possible mechanism of the effects of PBDEs on TC.

Medullary thyroid carcinoma is a rare neuroendocrine tumor derived from parafollicular C-cells. It can be inherited as part of syndromes, such as familial medullary thyroid cancer (FMTC) and multiple endocrine neoplasia type 2 (MEN 2), or it can arise sporadically. We herein report a unique case of medullary thyroid carcinoma in a 50-year-old male who presented with a neck mass. Fine needle aspiration cytology (FNAC) of the thyroid and histopathological examination revealed a diagnosis of medullary thyroid carcinoma. Both carcinoembryonic antigen (CEA) and calcitonin are the key serum markers utilized in the diagnosis and monitoring of medullary thyroid cancer (MTC). Thorough evaluation, prompt identification, and efficient treatment constitute the pivotal measures for ensuring favorable survival outcomes.

UNASSIGNED: Hyperspectral imaging (HSI) is an emerging imaging modality for oncological applications and can improve cancer detection with digital pathology.
UNASSIGNED: The study aims to highlight the increased accuracy and sensitivity of detecting the margin of thyroid carcinoma in hematoxylin and eosin (H&E)-stained histological slides using HSI and data augmentation methods.
UNASSIGNED: Using an automated microscopic imaging system, we captured 2599 hyperspectral images from 65 H&E-stained human thyroid slides. Images were then preprocessed into 153,906 image patches of dimension 250 × 250 × 84   pixels . We modified the TimeSformer network architecture, which used alternating spectral attention and spatial attention layers. We implemented several data augmentation methods for HSI based on the RandAugment algorithm. We compared the performances of TimeSformer on HSI against the performances of pretrained ConvNext and pretrained vision transformers (ViT) networks on red, green, and blue (RGB) images. Finally, we applied attention unrolling techniques on the trained TimeSformer network to identify the biological features to which the network paid attention.
UNASSIGNED: In the testing dataset, TimeSformer achieved an accuracy of 90.87%, a weighted F 1 score of 89.79%, a sensitivity of 91.50%, and an area under the receiving operator characteristic curve (AU-ROC) score of 97.04%. Additionally, TimeSformer produced thyroid carcinoma tumor margins with an average Jaccard score of 0.76 mm. Without data augmentation, TimeSformer achieved an accuracy of 88.23%, a weighted F 1 score of 86.46%, a sensitivity of 85.53%, and an AU-ROC score of 94.94%. In comparison, the ViT network achieved an 89.98% accuracy, an 88.14% weighted F 1 score, an 84.77% sensitivity, and a 96.17% AU-ROC. Our visualization results showed that the network paid attention to biological features.
UNASSIGNED: The TimeSformer model trained with hyperspectral histological data consistently outperformed conventional RGB-based models, highlighting the superiority of HSI in this context. Our proposed augmentation methods improved the accuracy, the F 1 score, and the sensitivity score.

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Background: Diagnostic classification of thyroid malignancy is primarily accomplished through examination of histomorphological features and may be substantiated and clarified by molecular data. Individual molecular drivers show relatively robust and specific associations with histological subtypes of thyroid malignancy, including BRAF sequence variants and kinase gene fusions in papillary thyroid carcinoma, predominantly RAS variants in follicular-patterned neoplasia, and additional \"late\" mutations affecting TERT promoter, TP53, and the PI3K/AKT/PTEN pathway in high-grade malignancies. Given the oncogenic role of FGFR, particularly FGFR1-3, the goal of this study was to explore the role of FGFR in thyroid carcinoma biology. Methods: We completed a multicenter retrospective observational study for thyroid carcinomas with pathogenic alterations in the FGFR gene family. We performed this study by querying the molecular data accumulated for thyroid carcinomas from each center. Results: Overall, 5030 sequenced thyroid malignancies were reviewed, yielding 17 tumors with FGFR alterations, including 11 where FGFR was the primary molecular driver and 6 where FGFR was a secondary pathogenic alteration, with a subset for which there was available clinical follow-up data. Of the 11 carcinomas with an FGFR driver, 9 were gene fusions involving FGFR2:VCL (4 tumors), TG::FGFR1 (3 tumors), FGFR2::CIT, and FGFR2::SHTN1, and the remaining 2 were driven by FGFR1 amplification. In the 6 tumors where a canonical driver of thyroid neoplasia was present (5 cases) or no clear primary driver was detected (1 case), sequencing detected secondary FGFR2 p.W290C, p.Y375C, and p.N549K, as well as FGFR1 p.N546K in the respective tyrosine kinase domains, some at subclonal variant allele frequencies. Conclusions: This study presents the first description of a collection of thyroid carcinomas grouped by primary driver alterations in FGFR, as well as a cohort of thyroid tumors with secondary alterations that potentially lead to tumor progression or resistance to targeted therapy. Given the availability of small molecular inhibitors targeting oncogenic FGFR, this study emphasizes the significant implications for patients from identification of FGFR alterations as they are currently under-recognized in the literature and, most importantly, have potential novel treatment options.

BACKGROUND: Technology allows us to predict a histopathological diagnosis, but the high costs prevent the large-scale use of these possibilities. The current liberal indication for surgery in benign thyroid conditions led to a rising frequency of incidental thyroid carcinoma, especially low-risk papillary micro-carcinomas.
METHODS: We selected a cohort of 148 patients with thyroid nodules by ultrasound characteristics and investigated them by fine needle aspiration cytology (FNAC)and prospective BRAF collection for 70 patients. Also, we selected 44 patients with thyroid nodules using semi-quantitative functional imaging with an oncological, 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) radiotracer.
RESULTS: Following a correlation with final histopathological reports in patients who underwent thyroidectomy, we introduced the results in a machine learning program (AI) in order to obtain a pattern. For semi-quantitative functional visual pattern imaging, we found a sensitivity of 33%, a specificity of 66.67%, an accuracy of 60% and a negative predicting value (NPV) of 88.6%. For the wash-out index (WOind), we found a sensitivity of 57.14%, a specificity of 50%, an accuracy of 70% and an NPV of 90.06%.The results of BRAF in FNAC included 87.50% sensitivity, 75.00% specificity, 83.33% accuracy, 75.00% NPV and 87.50% PPV. The prevalence of malignancy in our small cohort was 11.4%.
CONCLUSIONS: We intend to continue combining preoperative investigations such as molecular detection in FNAC, 99mTc-MIBI scanning and AI training with the obtained results on a larger cohort. The combination of these investigations may generate an efficient and cost-effective diagnostic tool, but confirmation of the results on a larger scale is necessary.

UNASSIGNED: Total thyroidectomy (TT) and central neck dissection (CND) had a significant effect on the reduction of local recurrence compared with TT alone. Lateral Neck Dissection (LND) was performed in all the cases with therapeutic intent. The suspicion of nodal recurrence is provided by the appearance of one or more enlarged nodes in the central and/or laterocervical compartment during the follow up period.
UNASSIGNED: From January 2018 to November 2023, 16 patients at the University General Surgery unit of the Polyclinic of Foggia underwent reoperation due to nodal recurrence after previously undergoing total thyroidectomy with central and lateral cervical dissection.
UNASSIGNED: All surgical interventions were approached with intraoperative ultrasound performed by the operating surgeon. In all cases, ultrasound identification of the suspicious lymph node led to histological confirmation of malignancy. In only two cases it was necessary to carry out an extemporaneous intraoperative histological examination. No complications were recorded during the operations.
UNASSIGNED: Surgical reintervention in patients with nodal recurrence is challenging and requires an assessment by members of the interdisciplinary team. The ideal method should be economically convenient, easy to practice, with a quick learning curve, easily reproducible, and safe for patients. Intraoperative, ultrasound-guided, is a safe and effective technique. It facilitates tumor localization and removal, especially in patients requiring re-operative neck surgery.

BACKGROUND: Thyroid nodules are unusual in children, but when present, they carry a higher risk for malignancy, as compared to adults. Several guidelines have been created to address the risk stratification for malignancy of thyroid nodules in adults, but none has been completely validated in children. A few authors have proposed lowering the size threshold to the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS™) management guidelines to decrease missed carcinomas at presentation in children; however, little information is known regarding their accuracy.
OBJECTIVE: To assess the performance of proposed modifications of the ACR TI-RADS™ size criteria to guide management decisions in pediatric thyroid nodules and to assess the associated increase in number of fine needle aspiration (FNA) and follow-up exams.
METHODS: This is a retrospective study of children under 18 years old who underwent ultrasound assessment of a thyroid nodule at a tertiary care pediatric institution between January 2006 and August 2021. The largest dimension, maximum ACR TI-RADS™ score, and final thyroid nodules\' diagnoses were documented. The course of action based on the adult ACR TI-RADS™ and after modifying the size threshold for management recommendations was documented and compared. Statistics included descriptive analysis, weighted Kappa statistics, sensitivity, specificity, accuracy, and positive/negative predictive values of the ACR TI-RADS™ presented with 95% confidence intervals (CI) using either Clopper-Pearson or standard logit methods.
RESULTS: Of 116 nodules, 18 (15.5%) were malignant. Most malignant nodules (94.4%, n = 17) were ACR TI-RADS™ 4 and ACR TI-RADS™ 5 categories. Based on the adult ACR TI-RADS™ criteria, 24 (24.5%) benign and 15 (83.3%) malignant nodules would have undergone FNA; 14 (14.3%) benign and 3 (16.7%) malignant nodules would have been followed up; and 60 (61.2%) benign and none of malignant nodules would have been dismissed. Three (16.7%) malignant nodules would not have been recommended FNA at presentation, delaying their diagnoses. By lowering the size-threshold criteria of the ACR TI-RADS™ guidelines, no malignancy would have been missed at presentation, but this also resulted in a higher number of FNA from 24 (24.5%) to 36 (36.7%) and follow-up ultrasound exams from 14 (14.3%) to 62 (63.3%).
CONCLUSIONS: Applying potential modifications to the ACR TI-RADS™ guideline lowering the size threshold criteria of the thyroid nodule to guide management decisions for pediatric thyroid nodules can lead to early detection of malignant nodules in children, but at the cost of a significantly increased number of biopsies or ultrasound exams. Further tailoring of the guideline with larger multicentric studies is needed, before warranting its acceptance and general use in the pediatric population.