Thyroid最新文献

{"title":"Biphasic Effect of Thyroid Hormone on Megakaryopoiesis and Platelet Production.","authors":"Baichuan Xu, Xianpeng Ye, Zhaoyang Wen, Jun Chen, Mo Chen, Mingqiang Shen, Yang Xu, Junping Wang, Shilei Chen","doi":"10.1089/thy.2024.0361","DOIUrl":"10.1089/thy.2024.0361","url":null,"abstract":"<p><p><b><i>Background:</i></b> Abnormal platelet counts are frequently observed in patients with thyroid dysfunction; however, the direct impact of thyroid hormones on thrombopoiesis remains largely undefined. <b><i>Methods:</i></b> This study elucidates the dose-response effect of the thyroid hormone triiodothyronine (T₃) on megakaryocyte (MK) development and thrombopoiesis using both a murine model of hyperthyroidism/hypothyroidism and <i>in vitro</i> cultures of human cord blood CD34⁺ cell-derived MKs. After the application of inhibitors to MKs, the examination of total and phosphorylated protein levels of the phosphoinositide 3-kinase (PI3K)/AKT pathway was utilized to assess the specific mechanisms of T₃ action. The use of autophagy dual-staining lentivirus and transmission electron microscopy was employed to evaluate the impact of T₃ on the autophagy flux in MKs. Mouse whole-body irradiation and bone marrow transplantation models are applied to assess the influence of T₃ on the recovery of MKs/platelets <i>in vivo</i>. <b><i>Results:</i></b> We found that physiological or slightly elevated thyroid hormone levels are essential for sustaining MK development and thrombopoiesis, primarily through the TRα-PI3K/AKT signaling pathway. In contrast, supraphysiological thyroid hormone concentrations induce MK apoptosis via excessive autophagy, thereby reducing platelet production. <b><i>Conclusions:</i></b> Here, we present evidence that the thyroid hormone influences MK development and platelet production in a concentration-dependent manner, exhibiting a dualistic role. Our discoveries shed new light on the intricate relationship between thyroid hormones and platelet formation, offering novel perspectives on the pathophysiological consequences of thyroid disorders.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"321-334"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ablative Versus Conservative Approach for Hyperthyroidism Treatment in Patients with Graves' Orbitopathy: A Retrospective Cohort Study.","authors":"Giada Cosentino, Giulia Lanzolla, Simone Comi, Maria Novella Maglionico, Chiara Posarelli, Dalì Antonia Ciampa, Francesca Menconi, Roberto Rocchi, Francesco Latrofa, Michele Figus, Ferruccio Santini, Michele Marinò","doi":"10.1089/thy.2024.0633","DOIUrl":"10.1089/thy.2024.0633","url":null,"abstract":"<p><p><b><i>Background:</i></b> Treatment for Graves' hyperthyroidism (GH) in patients with Graves' orbitopathy (GO) remains a topic of debate. This study aimed to investigate the outcome of GO following glucocorticoids, depending on the chosen thyroid treatment. <b><i>Methods:</i></b> This retrospective cohort study included 49 consecutive patients with GH and moderate-to-severe, active GO, as defined by the European Group on Graves' Orbitopathy guidelines. Twenty-four patients were treated with radioactive iodine (RAI) and 25 with methimazole (MMI). All patients were administered intravenous methylprednisolone. Follow-up visits occurred at weeks 24, 48, and 72. The primary endpoint was the overall outcome of GO at week 24. Response was defined as a change in at least two of the following eye features: reduction ≥1 point in clinical activity score; proptosis reduction ≥2 mm; eyelid aperture reduction ≥2 mm; increase in eye ductions ≥8 degrees. <b><i>Results:</i></b> Follow-up duration was 72 weeks for both groups (interquartile range 66-72 for RAI and 48-72 for MMI). The proportion of responders for week 24 overall GO outcome was greater in RAI (54.1% vs. 16%; odds ratio [OR] 6.2 [confidence interval (CI): 1.6-23.6], <i>p</i> = 0.0075), but it increased in MMI at weeks 48 and 72, with no differences between groups. There was a trend indicating a better response in RAI regarding individual eye features. Improvement in GO-specific quality of life questionnaire at week 24 was trendily more pronounced in RAI (responders 50% vs. 28% in MMI; OR = 2.5 [CI: 0.7-8.4], <i>p</i> = 0.11), although results were similar in both groups at later time points. At week 24, only one patient (4%) in RAI and three (12%) in MMI experienced worsening of GO. Fifty-nine adverse events were recorded among 36 patients, with no differences between groups, except for infections, which were more frequent in RAI (53.8% vs. 15.3% in MMI; OR = 6.41 [CI: 1.7-23.9], <i>p</i> = 0.0056). <b><i>Conclusions:</i></b> RAI appears to be associated with an earlier response of GO to intravenous glucocorticoids. In the long term, a conservative approach also seems to be effective. RAI appears to be relatively safe when patients are concurrently treated with glucocorticoids. However, randomized clinical trials are necessary to confirm these findings.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"298-306"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International Women's Day: An Occasion for a Tribute to Women Leaders in the American Thyroid Association.","authors":"Jacqueline Jonklaas","doi":"10.1089/thy.2025.0073","DOIUrl":"10.1089/thy.2025.0073","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"227-229"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid Nodule Sphericity Metrics Discriminate Benign and Malignant Follicular and Oncocytic Neoplasms.","authors":"Caitlin Bell, Samantha L White, Tracy Tylee, Manjiri Dighe, Amanda La Greca, Whitney Goldner, Sarah Mayson, Bryan R Haugen, Nikita Pozdeyev","doi":"10.1089/thy.2024.0670","DOIUrl":"10.1089/thy.2024.0670","url":null,"abstract":"<p><p><b><i>Background:</i></b> We investigated if thyroid nodule taller-than-wide (TTW) feature and sphericity metrics are helpful in separating benign neoplastic thyroid nodules (follicular and oncocytic adenomas) from follicular thyroid carcinomas (FTC) and oncocytic thyroid carcinomas (OCA). <b><i>Methods:</i></b> This is a retrospective study of TTW sonographic feature as reported by radiologists and nodule sphericity metrics at two academic health systems. Surgical pathology reports for benign and malignant follicular and oncocytic neoplasms, non-neoplastic nodules (hyperplastic and adenomatoid), and classic papillary thyroid cancers (PTC) were extracted from enterprise data warehouses. We independently reviewed each ultrasound and recorded nodule dimensions to identify nodules that were TTW and determine if the proportion of TTW nodules is different in benign and malignant thyroid nodules of various histologies. We also evaluated the sphericity index and sphericity ratio, two quantitative measures of how close the 3D shape of the nodule is to a sphere. <b><i>Results:</i></b> In total, 1110 nodules were analyzed: 209 non-neoplastic nodules (hyperplastic and adenomatoid), 398 benign neoplasms (follicular and oncocytic adenomas), and 503 malignant neoplasms (FTC, OCA, PTC, and follicular variant-PTC [FV-PTC]) and noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP). There was no statistical difference for the TTW feature when follicular and oncocytic adenomas were compared with FV-PTC, OCA, FTC, and NIFTP (χ², <i>p</i> = 0.08, sensitivity of 28% [confidence interval 23-24%]), when follicular adenoma was compared with FTC (χ², <i>p</i> = 0.64) or when oncocytic adenoma was compared with OCA (χ², <i>p</i> = 0.08). Benign and malignant neoplasms were more likely than non-neoplastic nodules to be TTW (χ², <i>p</i> = 0.02). In contrast, the sphericity index and sphericity ratio were significantly different in most comparisons of benign and malignant nodules (Wilcoxon, <i>p</i> < 0.03) except for oncocytic tumors. <b><i>Conclusions:</i></b> TTW shape has limited utility in distinguishing benign follicular and oncocytic neoplasms from malignancy. This sonographic feature was more common among all benign and malignant neoplasms when they were compared as a group to non-neoplastic nodules, which suggests this sonographic feature is an indicator of neoplastic growth (benign or malignant) but not cancer. Alternative methods, such as measures of sphericity, are needed to distinguish benign and malignant oncocytic and follicular neoplasms.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"291-297"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Response to the Letter:</i> Addressing Surgical Difficulty and Pathological Findings in Thyroidectomy Post-Thermal Ablation.","authors":"Ting-Chun Kuo, Ming-Hsun Wu","doi":"10.1089/thy.2025.0029","DOIUrl":"10.1089/thy.2025.0029","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"340-341"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Novel <i>SLC5A5</i> Variants (Q263L and G350D) Causing Congenital Hypothyroidism.","authors":"Kiyomi Abe, Mikiko Koizumi, Takahiko Kogai, Shinobu Ida, Chiho Sugisawa, Masanobu Kawai, Tomonobu Hasegawa, Satoshi Narumi","doi":"10.1089/thy.2024.0716","DOIUrl":"10.1089/thy.2024.0716","url":null,"abstract":"<p><p><i>SLC5A5</i> encodes sodium-iodide symporter (NIS), which transports inorganic iodide into thyroid cells. Biallelic loss-of-function variants in <i>SLC5A5</i> cause thyroid dyshormonogenesis due to iodide transport defect (ITD). We report a Japanese sibling with ITD carrying novel compound heterozygous <i>SLC5A5</i> variants (p. [Gln263Leu]; [Gly350Asp]). The elder brother was diagnosed with congenital hypothyroidism (CH) through newborn screening (NBS), while the younger brother, with a negative NBS result, developed CH-related symptoms at age 3 months. We characterized the two variant NIS proteins <i>in vitro</i> and negligible iodide transport capacity of both proteins. These findings provide unique evidence for the structure-function relationship of the NIS protein.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"335-337"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Thyrotropin and Clinically Relevant Depression: A Retrospective Cross-Sectional Study.","authors":"Balwinder Singh, Amanda V Bakian, Michael Newman, Vishnu Sundaresh","doi":"10.1089/thy.2024.0428","DOIUrl":"10.1089/thy.2024.0428","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Thyroid dysfunction and mood disorders are chronic health conditions with a significant impact on quality of life. This study aimed to investigate the association between thyrotropin (TSH) and clinically relevant depression (CRD) in patients with and without mood disorders, in a population-based sample. <b><i>Methods:</i></b> This retrospective cross-sectional study included all consecutive adults (≥18 years) who had TSH and completed the Patient Health Questionnaire (PHQ-9) within 6 months of the index visit, between October 2016 and May 2021, at the University of Utah Health. Data on demographics, hypothyroidism diagnoses, TSH, thyroid hormone replacement (THR), PHQ-9, antidepressant (AD) medications, and mood disorder diagnoses (using the International Classification of Diseases, 10th Revision, Clinical Modification codes; Major depressive disorder single episode-F32, recurrent-F33, persistent mood disorder-F34, bipolar disorder-F30+F31, and mood disorder not otherwise specified-F39) were extracted electronically. CRD was defined as PHQ-9 ≥ 10. <i>t</i>-Test and chi-square test were used to compare continuous and categorical variables, respectively. Logistic regression models were formulated to evaluate the association between TSH and CRD, after adjusting for covariates. <b><i>Results:</i></b> The cohort included 33,138 patients, mean age 42.41 ± 16.10 years, 80.67% Caucasian, 69.10% females, and mean PHQ-9 score 10.11 ± 6.94. A total of 45.23% (<i>n</i> = 14,989) patients had a diagnosis of mood disorders, and 49.70% had CRD. Patients with mood disorders were more likely to be female, Caucasian, non-Hispanic/Latino, on AD, had hypothyroidism diagnoses, on thyroid medications, had higher mean PHQ-9 scores, and had CRD. TSH level was associated with an increased odds of CRD (odds ratio [OR] = 1.01, confidence interval [CI], 1.01-1.02, <i>p</i> < 0.009) after adjusting for age, sex, body mass index, Charlson Comorbidity Index, and use of THR and AD. Both the low TSH and high TSH groups showed increased odds of CRD, with respective ORs of 1.19 (CI: 1.04-1.37) and 1.26 (CI: 1.13-1.40). <b><i>Conclusions:</i></b> Thyroid dysfunction is associated with an increase in the odds of depression. Future longitudinal cohort studies are recommended to investigate the association between thyroid function and incident depression.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"245-254"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytologic and Molecular Assessment of Isthmus Thyroid Nodules and Carcinomas.","authors":"Sina Jasim, Allan Golding, David Bimston, Mohammed Alshalalfa, Yang Chen, Ruochen Jiang, Yangyang Hao, Jing Huang, Joshua P Klopper, Richard T Kloos, Taylor C Brown","doi":"10.1089/thy.2024.0254","DOIUrl":"10.1089/thy.2024.0254","url":null,"abstract":"<p><p><b><i>Background:</i></b> Isthmic thyroid nodules are more likely to be malignant and isthmic differentiated thyroid cancer demonstrates less favorable behavior compared with lobar locations. The goal of this study was to assess molecular differences of thyroid nodules and carcinomas from the isthmus relative to the lobes. <b><i>Methods:</i></b> The Afirma thyroid nodule database (<i>n</i> = 177,227) was assessed for cytologic and molecular differences between isthmus and lobar nodules in this observational cohort study. Genome-wide differential expression analysis was conducted to decipher transcriptomic differences. Histopathology reports (<i>n</i> = 583) of papillary thyroid cancer (PTC) (<i>n</i> = 389) and infiltrative follicular subtype of PTC (IF-PTC) (<i>n</i> = 194) from Afirma discovery cohorts and from thyroid cancer patients managed at an integrative endocrine surgery community care practice were analyzed for molecular differences between isthmic and lobar cancers. <b><i>Results:</i></b> In the Afirma database, 8527 (4.8%) isthmus nodules were identified. Bethesda V-VI nodules were almost twice as prevalent from the isthmus as compared with the lobes (8.2% vs. 4.3%, <i>p</i> < 0.0001). Isthmus nodules had twice the frequency of <i>BRAFp.^V600E</i> (21% vs. 10.6%, <i>p</i> < 0.0001), an increased frequency of <i>ALK</i>/<i>NTRK</i>/<i>RET</i> fusions (4.6% vs. 2.5%, <i>p</i> < 0.0001) and <i>SPOP</i> variants (1.5% vs. 0.8%, <i>p</i> < 0.0001), and a lower frequency of <i>NRAS</i> mutations (7.8% vs. 13.2%, <i>p</i> < 0.0001), and <i>PAX8::PPARy</i> fusions (1.1% vs. 2.3%, <i>p</i> < 0.0001) than lobar nodules. Transcriptome analysis of molecular signatures and genome-wide analysis showed that isthmus nodules have higher <i>BRAF</i>-like scores, ERK activity, follicular mesenchymal transition scores (FMT), and lower inflammation activity scores. Pathway enrichment analysis revealed genes downregulated in isthmus tumors are enriched in immune response regulation. IF-PTC from the isthmus (<i>n</i> = 13) were more <i>BRAF</i>-like and had increased ERK and FMT scores compared with those from the lobes (<i>n</i> = 181) (<i>p</i> < 0.01 for all). <b><i>Conclusions:</i></b> These data suggest isthmic nodules are more likely to have malignant cytology and increased rates of higher risk molecular alterations compared with lobar nodules. IF-PTC from the isthmus is molecularly different compared with IF-PTC from the lobes. More data are needed to know if a change in surgical therapy is warranted in isthmic thyroid cancers relative to lobar cancers and if this molecular data should influence isthmic thyroid cancer management and monitoring.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"255-264"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Profiling of Medullary Thyroid Cancer Identifies CAPN1 as a Key Regulator of NF1 and RET Fueled Growth.","authors":"Eshan Khan, Hannah Hylton, Neel Rajan, Stephanie J Bouley, Jalal K Siddiqui, Swetha Rajasekaran, Ganesh R Koshre, Hayden Storts, Anisley Valenciaga, Misbah Khan, Sandya Liyanarachchi, Francisco Fernandez, Xuguang Zheng, John Phay, Priya H Dedhia, Jing Wang, James A Walker, Matthew D Ringel, Wayne O Miles","doi":"10.1089/thy.2024.0102","DOIUrl":"10.1089/thy.2024.0102","url":null,"abstract":"<p><p><b><i>Background:</i></b> Medullary thyroid cancer (MTC) is a frequently metastatic tumor of the thyroid that develops from the malignant transformation of C-cells. These tumors most commonly have activating mutations within the RET or RAS proto-oncogenes. Germline mutations within RET result in C-cell hyperplasia, and cause the MTC pre-disposition disorder, multiple endocrine neoplasia, type 2A (MEN2A). Single-agent therapies for MTC, including vandetanib (VAN) and cabozantinib for all MTCs and selpercatinib (SEL) for RET-mutated MTC, lead to partial responses but are not curative. <b><i>Methods:</i></b> To identify new therapeutic targets for MTC, we conducted proteomic profiling of normal C-cells, MTC cells, pre-malignant MEN2A patient samples, and MTC tumors. <b><i>Results:</i></b> From this analysis, we identified CAPN1, a member of the CALPAIN (CAPN) family endopeptidases, as widely upregulated in MTC samples. We found that short hairpin RNA-mediated depletion of CAPN1 or inhibitors of CAPN1 significantly reduced MTC cell growth, colony formation, and xenograft tumor growth <i>in vivo</i>. In addition, we show that CAPN1 inhibitors synergize with VAN and SEL <i>in vitro</i>, maximizing apoptosis. Mechanistic experiments implicate CAPN1 in inhibiting neurofibromin, encoded by NF1, and CAPN1 inhibitors stabilize NF1 protein levels and diminish downstream RAS/RET activation of AKT and ERK. <b><i>Conclusions:</i></b> Our data suggest that increased CAPN1 levels support RET and RAS-fueled growth by reducing NF1 levels. We find that combinatorial therapies between CAPN1 inhibitors and VAN or SEL show maximal efficacy in MTC cells.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"177-187"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Grade Follicular Cell-Derived Non-Anaplastic Thyroid Carcinoma: Correlating Extent of Invasion and Mutation Profile with Oncologic Outcome.","authors":"Daniel W Scholfield, Bin Xu, Helena Levyn, Alana Eagan, Ashok R Shaha, Jatin P Shah, R Michael Tuttle, James A Fagin, Richard J Wong, Snehal G Patel, Ronald Ghossein, Ian Ganly","doi":"10.1089/thy.2024.0499","DOIUrl":"10.1089/thy.2024.0499","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The 2022 World Health Organization classification introduced the term high-grade follicular cell-derived nonanaplastic thyroid carcinoma (HGFCTC) to define invasive/infiltrative nonanaplastic thyroid carcinoma with high-grade features, including poorly differentiated thyroid carcinoma and high-grade differentiated thyroid carcinoma. Our objectives were to compare clinicopathological characteristics, oncologic outcomes, and mutation profiles among HGFCTC subgroups to better inform prognostication and treatment. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In this single-center, retrospective cohort study of 252 patients who had surgery for HGFCTC from 1986 to 2020, we categorized HGFCTC and its related entity, \"encapsulated noninvasive neoplasms of follicular cells with high-grade features,\" into five subgroups: (A) encapsulated noninvasive, (B) encapsulated with capsular invasion only (minimally invasive), (C) encapsulated angioinvasive with focal vascular invasion (VI), (D) encapsulated angioinvasive with extensive VI, and (E) infiltrative tumors. Next-generation sequencing with Memorial Sloan Kettering Cancer Center-Integrated Mutation Profiling of Actionable Cancer Targets was available for 117/252 patients to investigate differences in mutation profiles. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The cohort comprised 50% infiltrative, 33% encapsulated angioinvasive, and 18% encapsulated noninvasive/minimally invasive tumors. No patients with encapsulated noninvasive or minimally invasive disease had regional or distant metastases at presentation. Patients with infiltrative tumors were significantly more likely to present with T3/T4 disease (71%), regional metastases (55%), and distant metastases (25%) (&lt;i&gt;p&lt;/i&gt; ≤ 0.003&lt;i&gt;).&lt;/i&gt; Five-year disease-specific survival was poorer in patients with infiltrative disease (67.7%), compared to encapsulated angioinvasive focal VI (90.4%), encapsulated angioinvasive extensive VI (88.1%), and encapsulated noninvasive/minimally invasive (100%) (&lt;i&gt;p =&lt;/i&gt; 0.0002) subgroups. Common mutations were &lt;i&gt;TERT&lt;/i&gt; (42%), &lt;i&gt;BRAF&lt;sup&gt;V600E&lt;/sup&gt;&lt;/i&gt; (29%), &lt;i&gt;NRAS&lt;/i&gt; (27%), &lt;i&gt;EIF1AX&lt;/i&gt; (11%), and &lt;i&gt;TP53&lt;/i&gt; (9%). Pathways altered included &lt;i&gt;RTK/RAS/RAF/MAPK&lt;/i&gt; (69%), &lt;i&gt;PI3K/AKT/MTOR&lt;/i&gt; (14%), histone methyltransferases (9%), and SWI/SNF chromatin remodeling complex (8%). Subgroup analysis showed the infiltrative subgroup was mainly &lt;i&gt;BRAF&lt;sup&gt;V600E&lt;/sup&gt;&lt;/i&gt;-driven, and the encapsulated angioinvasive and minimally invasive subgroups were &lt;i&gt;NRAS-&lt;/i&gt;driven. Encapsulated noninvasive tumors had a different mutation profile, with &lt;i&gt;DICER1&lt;/i&gt; as the main driver mutation. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; HGFCTC comprises different subgroups with different clinical behaviors determined by the extent of vascular invasion and degree of infiltration. Excellent recurrence and survival outcomes occur in encapsulated noninvasive and minimally invasive tumors compared to infiltrative tumors. Infiltrative tumors are largely \"&lt;i&gt;BRAF&lt;/","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":"35 2","pages":"153-165"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}