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Thyroid cancer is increasing globally, with anaplastic thyroid carcinoma (ATC) being the most aggressive type and having a poor prognosis. Current clinical treatments for thyroid cancer present numerous challenges, including invasiveness and the necessity of lifelong medication. Furthermore, a significant portion of patients with ATC experience cancer recurrence and metastasis. To overcome this dilemma, we developed a pH-responsive biomimetic nanocarrier (CLP@HP-A) through the incorporation of Chlorin e6 (Ce6) and Lenvatinib (Len) within hollow polydopamine nanoparticles (HP) that were further modified with platinum nanoparticles (Pt), enabling synergistic chemotherapy and sonodynamic therapy. The CLP@HP-A nanocarriers exhibited specific binding with galectin-3 receptors, facilitating their internalization through receptor-mediated endocytosis for targeted drug delivery. Upon exposure to ultrasound (US) irradiation, Ce6 rapidly generated reactive oxygen species (ROS) to induce significant oxidative stress and trigger apoptosis in tumor cells. Additionally, Pt not only alleviated tumor hypoxia by catalyzing the conversion of H2O2 to oxygen (O2) but also augmented intracellular ROS levels through the production of hydroxyl radicals (â¢OH), thereby enhancing the efficacy of sonodynamic therapy. Moreover, Len demonstrated a potent cytotoxic effect on thyroid cancer cells through the induction of apoptosis. Transcriptomics analysis findings additionally corroborated that CLP@HP-A effectively triggered cancer cell apoptosis, thereby serving as a crucial mechanism for its cytotoxic effects. In conclusion, the integration of sonodynamic/chemo combination therapy with targeted drug delivery systems offers a novel approach to the management of malignant tumors.
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Clorofilidas , Indoles , Platino (Metal) , Polímeros , Porfirinas , Neoplasias de la Tiroides , Microambiente Tumoral , Terapia por Ultrasonido , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/metabolismo , Humanos , Línea Celular Tumoral , Microambiente Tumoral/efectos de los fármacos , Indoles/química , Terapia por Ultrasonido/métodos , Porfirinas/química , Porfirinas/farmacología , Polímeros/química , Animales , Platino (Metal)/química , Platino (Metal)/uso terapéutico , Platino (Metal)/farmacología , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Apoptosis/efectos de los fármacos , Nanopartículas/química , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Ratones , Quinolinas/farmacología , Quinolinas/química , Ratones Desnudos , Portadores de Fármacos/químicaRESUMEN
Introduction: The risk factors linked to hand osteoarthritis (OA) that contribute to its distinct symptoms and clinical presentation are not thoroughly understood. This study aimed to examine whether the autoimmune thyroid disease (AITD) autoantibodies, anti-thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TgAb), associate with hand OA and symptomatic hand OA in the Third National Health and Nutrition Examination Survey (NHANES III). Materials and methods: We included 2,429 persons from NHANES III ≥60 years of age. Data on hand OA or symptomatic hand OA were examined with respect to their associations with TPOAb and TgAb. Log-binomial and modified Poisson regression models were fit to examine the associations between the anti-thyroid autoantibodies and hand OA or symptomatic hand OA. Results: Higher levels of TPOAb were associated with a higher prevalence of symptomatic hand OA in the unadjusted (PR = 1.182, p = 0.024) and adjusted models after controlling for age, gender, and diabetes (PR = 1.174, p = 0.039). This association was no longer significant when positive TPOAb was considered a categorical variable with four levels and compared with negative TPOAb. TgAb showed a trend toward being positively associated with symptomatic hand OA (p < 0.10). When positive TgAb was considered a categorical variable with four levels and compared with negative TgAb, the highest quartile was associated with a higher prevalence of symptomatic hand OA than negative TgAb in the unadjusted (PR = 2.242, p = 0.008) and adjusted models (PR = 2.045, p = 0.038). There was no significant association between TPOAb or TgAb and hand OA. Conclusion: Higher levels of TPOAb may be associated with the presence of symptomatic hand OA in persons ≥60 years old. Persons ≥60 years old with the highest quartile levels of TgAb may be more likely to present with symptomatic hand OA.
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Thyroid tissue in teleosts is located mainly in the pharyngeal region, usually reaching other adjacent anatomical locations. Herein, a nodular lesion located in the left operculum of a Senegal seabream (Diplodus bellottii) was surgically excised and sent for microscopical evaluation. Microscopically, the lesion presented irregular borders and consisted in columnar epithelial cells arranged in a tubulopapillary pattern, surrounding a central lumen filled with acellular, acidophilic and homogeneous, material ('colloid'). To determine the lesion's histogenesis, immunohistochemistry was performed employing antibodies for AE1/AE3, CK7, thyroglobulin and vimentin. The neoplastic cells presented low mitotic index and positive immunolabelling for CK7 and thyroglobulin. Therefore, a diagnosis of ectopic thyroid adenoma was made. Herein, the successful employment of antibodies classically used in mammals for accurate diagnosis of thyroid disorders is described. Proliferation of thyroid tissue in fish may reflect environmental and physiological imbalances, making the study and correct diagnosis of these tumours in this species important.
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PURPOSE: This updated systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT for the detection of recurrent disease in patients with differentiated thyroid cancer (DTC) who have negative 131I whole body scintigraphy and increased antithyroglobulin antibodies (TgAb) levels. METHODS: The current systematic review was carried out following a preset protocol, and the "Preferred Reporting Items for a Systematic Review and Meta-Analysis" served as a guideline for its development and reporting. A comprehensive research of the PubMed/MEDLINE, Embase and Cochrane library databases was conducted until June 2024. RESULTS: Between 2002 and 2023, 13 studies (608 patients) published on this topic were selected. The pooled sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 2-[18F]FDG PET or PET/CT were 84% (95%CI: 78-87%), 82% (95%CI: 78-86%), 72% (95%CI: 67-76%), 90% (95%CI: 87-93%) and 83% (95%CI: 79%-86%) respectively. The pooled positive and negative likelihood ratios (LR+ and LR - ) and the diagnostic odds ratio (DOR) were 0.180 (95%CI: 0.128-0.253), 3.214 (95%CI: 2.357-4.383), and 17.863 (95%CI: 10.475-30.462), respectively. No statistically significant heterogeneity among the studies was found for all the metrics evaluated (I2 < 50%). CONCLUSIONS: 2-[18F]FDG PET/CT demonstrated a good diagnostic performance in patients with DTC and increased TgAb. Although more studies are warranted, the provided evidence-based data should support the integration of 2-[18F]FDG PET/CT in clinical and diagnostic guidelines on DTC patients with increased TgAb.
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BACKGROUND: Thyroid cancer (TC) is a highly prevalent malignant tumor of the head and neck. Papillary thyroid carcinoma (PTC) is the primary pathological type of TC, accounting for more than 80% of all TCs. BRAF mutations are closely associated with PTC. However, the relationship among HT, PTC, and BRAF mutations has not yet been clarified. We aimed to investigate the BRAF mutation in Hashimoto's thyroiditis (HT) with PTC. METHODS: A total of 72 patients with multifocal PTC were included and grouped based on surgical pathology examination. Group A (n = 32) had pure multifocal PTC and Group B (n = 40) had HT with multifocal PTC. Various features were compared: BRAF mutation, multifactorial analysis of BRAF mutations, pathological features in patients with HT and multifocal PTC, and multifactorial analysis of factors affecting HT with multifocal PTC. RESULTS: Significant differences were seen in thyroid peroxidase antibody levels, central lymph node metastasis, extra-thyroidal invasion, main and non-main lesion diameters, and BRAF mutation positivity (P < 0.05). Patients with the BRAF mutation had significantly higher rates of extra-thyroidal invasion and lymph node metastasis than those without the BRAF mutation (P < 0.05). Logistic regression analysis showed that BRAF mutation and main lesion nodule diameter were independent risk factors affecting extra-thyroidal invasion and central lymph node metastasis in patients with HT and multifocal PTC (P < 0.05). DISCUSSION: BRAF mutations were more prevalent and closely associated with extra-thyroidal invasion and central lymph node metastasis in patients with HT and multifocal PTC.
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OBJECTIVES: TERT promoter mutations are not infrequently encountered in thyroid carcinomas; however, it is unclear if additional molecular alterations may play a role in determining tumor behavior. METHODS: Fine-needle aspiration (FNA) specimens from 32 patients with TERT promoter mutations detected by ThyroSeq v3 from 4 institutions were included in the study. FNA diagnoses, molecular results, and surgical follow-up were retrospectively reviewed and analyzed. RESULTS: There were 5 benign and 27 malignant neoplasms, including 7 high-grade thyroid carcinomas (HGCs) on histopathologic follow-up. Of 4 cases with an isolated TERT mutation, 3 (75%) cases were malignant. Of 17 cases harboring a co-occurring TERT mutation with 1 additional molecular alteration, 13 (76%) displayed malignancy on histopathologic follow-up. All 11 cases with TERT mutations plus 2 or more additional molecular alterations were malignant on follow-up. Furthermore, HGC was not seen in cases with an isolated TERT mutation, while 80% of cases harboring TERT mutations plus 3 additional molecular alterations showed HGC. CONCLUSIONS: TERT promoter mutations are commonly associated with malignancy, particularly HGCs, when multiple co-occurring molecular alterations are present. However, TERT promoter mutations may occasionally be detected in benign thyroid neoplasms when encountered in isolation or with fewer than 2 additional molecular alterations.
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INTRODUCTION: Differentiated thyroid cancer (DTC), the most common endocrine malignancy is subdivided into papillary (the most common) and follicular type. Generally, DTC has a good prognosis with standard treatments such as surgery and, in some cases, radioactive iodine (RAI). Post-treatment follow-up includes thyroglobulin (Tg) and anti-thyroglobulin antibody (TgAb) measurement and imaging to assess treatment success and detect recurrence. However, TgAb can interfere with Tg measurements, making it essential to measure TgAb at different times (months). Aim of the study: The aim of this study was to evaluate the changes in TgAb level in DTC patients after thyroidectomy and its association with recurrence. METHODS: This was a retrospective cohort study done at the Faiha Specialized Diabetes, Endocrine, and Metabolism Center (FDEMC), Basrah, Iraq, for individuals diagnosed with DTC between 2008 and 2023. The data collected were analyzed using IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States). The categories were classified according to the TgAb level as: (i) elevated (>115 IU/ml) and (ii) normal (<115 IU/ml), where TgAb levels measured at 0-6 months, 6-12 months, 24-36 months, 36-48 months, and beyond 48 months. RESULTS: The mean age at diagnosis of the study population (n=108) was 40.15 years with a female-to-male ratio of 4:1. Among these individuals, 52.8% (n=57) were found to be obese. Total thyroidectomy was performed on 84.3% (n=91). Papillary thyroid cancer was diagnosed in 69.5% (n=75). TgAb levels were influenced by body mass index (BMI); higher BMI (>30kg/m2) was associated with less consistent TgAb normalization, particularly beyond 48 months (P = 0.04). The study found no significant differences in TgAb normalization based on gender, age, BMI, type of surgery, type of cancer, American Thyroid Association (ATA) risk of recurrence, or radioactive iodine (RAI) treatment. CONCLUSION: Factors including gender, age, type of surgery, type of cancer, ATA risk of recurrence, and RAI treatment did not significantly affect TgAb normalization in DTC individuals over the study period. However, higher BMI is associated with less consistent TgAb normalization in the long term.
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Background: Hashimoto's thyroiditis (HT) is a thyroid autoimmune disease characterized by lymphocytic infiltration and thyroid destruction. Prunella vulgaris (PV) is a traditional Chinese herbal medicine with documented clinical efficacy in treating HT. We previously reported an immunoregulatory effect of PV in thyrocytes; however, the bioactive components of PV remained unclear. This study aimed to elucidate key components of PV for treating HT and their acting mechanisms. Methods: Network pharmacology was used to predict key PV components for HT. The predicted components were tested to determine whether they could exert an immunoregulatory effect of PV in human thyrocytes. Limited proteolysis-mass spectrometry (Lip-MS) was used to explore interacting proteins with PV components in human thyrocytes. Microscale thermophoresis binding assay was used to evaluate the affinity of PV components with the target protein. Results: Eleven PV components with 192 component targets and 3415 HT-related genes were gathered from public databases. With network pharmacology, a 'component-target-disease' network was established wherein four flavonoids including quercetin, luteolin, kaempferol, morin, and a phytosterol, ß-sitosterol were predicted as key components in PV for HT. In stimulated primary human thyrocytes or Nthy-ori-31 cells, key components inhibited gene expressions of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interferon-ß (IFN-ß), cellular apoptosis, and activation of nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3). Heat shock protein 90 alpha, class A, member 1 (HSP90AA1), was identified to interact with flavonoids in PV by Lip-MS. Morin had the highest affinity with HSP90AA1 (KD = 122.74 µM), followed by kaempferol (KD = 168.53 µM), luteolin (KD = 293.94 µM), and quercetin (KD = 356.86 µM). Conclusion: Quercetin, luteolin, kaempferol, morin, and ß-sitosterol reproduced an anti-inflammatory and anti-apoptosis effect of PV in stimulated human thyrocytes, which potentially contributed to the treatment efficacy of PV in HT.
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The hypometabolism induced by fasting has great potential in maintaining health and improving survival in extreme environments, among which thyroid hormone (TH) plays an important role in the adaptation and the formation of new energy metabolism homeostasis during long-term fasting. In the present review, we emphasize the potential of long-term fasting to improve physical health and emergency rescue in extreme environments, introduce the concept and pattern of fasting and its impact on the body's energy metabolism consumption. Prolonged fasting has more application potential in emergency rescue in special environments. The changes of THs caused by fasting, including serum biochemical characteristics, responsiveness of the peripheral and central hypothalamus-pituitary-thyroid (HPT) axis, and differential changes of TH metabolism, are emphasized in particular. It was proposed that the variability between brain and liver tissues in THs uptake, deiodination activation and inactivation is the key regulatory mechanism for the cause of peripheral THs decline and central homeostasis. While hypothalamic tanycytes play a pivotal role in the fine regulation of the HPT negative feedback regulation during long-term fasting. The study progress of tanycytes on thyrotropin-releasing hormone (TRH) release and deiodination is described in detail. In conclusion, the combination of the decrease of TH metabolism in peripheral tissues and stability in the central HPT axis maintains the basal physiological requirement and new energy metabolism homeostasis to adapt to long-term food scarcity. The molecular mechanisms of this localized and differential regulation will be a key research direction for developing measures for hypometabolic applications in extreme environment.
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Metabolismo Energético , Ayuno , Hormonas Tiroideas , Humanos , Ayuno/metabolismo , Ayuno/fisiología , Hormonas Tiroideas/metabolismo , Animales , Metabolismo Energético/fisiología , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Glándula Tiroides/metabolismo , Glándula Tiroides/fisiología , HomeostasisRESUMEN
OBJECTIVES: In this study, the effects of sex and birth type on growth performance, withers height (WH), radiographic measurements and selected hormone profiles in Gurcu goat kids were investigated. METHODS: Twenty kids (single female = 5, single male = 5, twin female = 5, twin male = 5) were included in the study. Body weight (BW), WH, radiographic measurements (humerus length [HL], radius length [RL], proximal humerus epiphyseal plate width [HEP] and distal ulna epiphyseal plate width [UEP]) and biochemical analysis (for serum calcitonin, free triiodothyronine [FT3], free thyroxine [FT4], growth hormone [GH] and insulin-like growth factor-I [IGF-I]) were performed at 1, 3, 5, 7, 9 and 12 months of age. RESULTS: BW was significantly higher in males starting from the seventh month compared to females (p < 0.05). HL was higher in males at seventh (p = 0.009) and ninth (p = 0.033) months, whereas RL was lower in twins at the third month (p = 0.021). UEP was wider in males at seventh (p = 0.008) and ninth (p = 0.036) months. Closure of HEP was observed in 65% of kids by the 12th month. Calcitonin was lower in twins at third (p = 0.045) and fifth (p = 0.006) months, with changes observed due to group and time effects (p < 0.05), whereas other hormones only changed with time (p < 0.05). Positive correlations were observed between BW, WH, HL, RL and IGF-I. There was a negative correlation between BW, WH, HL, RL, IGF-I and HEP, UEP, calcitonin, FT3, FT4, GH. CONCLUSION: Sex and birth type in Gurcu goat kids may have an impact on growth performance, radiographic measurements and certain hormonal profiles.
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Cabras , Animales , Femenino , Masculino , Cabras/fisiología , Cabras/crecimiento & desarrollo , Placa de Crecimiento , Factores Sexuales , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/análisis , Húmero/crecimiento & desarrollo , Cúbito/crecimiento & desarrollo , Cúbito/diagnóstico por imagen , Radio (Anatomía)/diagnóstico por imagen , Hormona del Crecimiento/sangreRESUMEN
A 37-year-old, never-smoker, pregnant woman diagnosed with Graves' disease who had stable thyroid eye disease (TED) before pregnancy presented with aggravated proptosis and eyelid swelling at 13 weeks of pregnancy. Despite the administration of local triamcinolone and 3 cycles of corticosteroid pulse therapy from 25 to 28 weeks, the patient's visual acuity decline necessitated postpartum orbital decompression surgery. Although TSH receptor antibody (TRAb) levels decreased during the mid- to late term of pregnancy, the TED worsened. This finding suggests that factors other than anti-TSH receptor antibodies may have a significant effect on disease severity.
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Depressive disorder exhibits heterogeneity in clinical presentation, progression, and treatment outcomes. While conventional antidepressants based on the monoamine hypothesis benefit many patients, a significant proportion remains unresponsive or fails to fully recover. An individualized integrative treatment approach, considering diverse pathophysiologies, holds promise for these individuals. The endocrine system, governing physiological regulation and organ homeostasis, plays a pivotal role in central nervous system functions. Dysregulations in endocrine system are major cause of depressive disorder due to other medical conditions. Subtle endocrine abnormalities, such as subclinical hypothyroidism, are associated with depression. Conversely, depressive disorder correlates with endocrine-related biomarkers. Fluctuations in sex hormone levels related to female reproduction, elevate depression risk in susceptible subjects. Consequently, extensive research has explored treatment strategies involving the endocrine system. Treatment guidelines recommend tri-iodothyronine augmentation for resistant depression, while allopregnanolone analogs have gained approval for postpartum depression, with ongoing investigations for broader depressive disorders. This book chapter will introduce the relationship between the endocrine system and depressive disorders, presenting clinical findings on neuroendocrinological treatments for depression.
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Antidepresivos , Trastorno Depresivo , Humanos , Antidepresivos/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/metabolismo , Sistema Endocrino/efectos de los fármacos , Sistema Endocrino/metabolismo , Femenino , Triyodotironina/uso terapéutico , Triyodotironina/metabolismoRESUMEN
Background: The coexistence of tuberculosis (TB) and malignancy within the same lymph node is a rare, if not exceptional, pathology, with only a few cases reported. Methods: We collected patients who presented concomitant TB and malignancy within the same cervical lymph node diagnosed during the period (2010-2023). Results: Ten patients were included. They received or were receiving treatment for cancer or TB in 7 cases. All patients presented with recurrent or new lymph nodes despite being under treatment. The 3 remaining patients did not have a history of cancer or TB. Histopathological examination confirmed the coexistence of TB and malignancy within the same lymph node. Histological types of diagnosed cancers included laryngeal squamous cell carcinoma, papillary thyroid carcinoma, nasopharyngeal carcinoma, medullary carcinoma of the thyroid gland, Hodgkin lymphoma, and non-Hodgkin lymphoma. All patients received treatment for TB and cancer. Two patients died from septic complication in 1 case and from pulmonary complication due to miliary TB in 1 case. Conclusions: Concomitant TB and malignancy are possible, especially in countries with a high incidence of TB. Immunocompromised states related to cancer, and its treatments can add the risk of flare-up of a latent infection.
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A 28-year-old female patient developed a 5.5â¯cm progressive thyroid nodule that was surgically removed due to local symptoms. Histologically, a solitary fibrous tumor (SFT) in a thyroid adenoma was diagnosed. The tumor had a specific NAB2-STAT6 fusion.Solitary fibrous tumors rarely occur in the thyroid gland and are described as both primary and secondary manifestations. The diagnosis, prognosis assessment and treatment decision are carried out analogously to SFT of other localizations.
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Concepts in thyroid diagnostics are evolving. As cytopathologists, we benefit from understanding the changes taking place in cytopathology practice as well as intersecting areas that may have implications for us. In this review, we discuss recent changes to 1. Classification systems, 2. Ancillary molecular testing modalities, and 3. Key metrics that affect thyroid cytopathology. The recent World Health Organization, Bethesda Thyroid Cytopathology, and American Joint Committee on Cancer classification systems have aspects that are designed to harmonize the clinical, cytopathologic, histomorphologic, and molecular findings for improved communication and patient management. New terminologies such as thyroid follicular nodular disease and low-risk follicular cell-derived thyroid neoplasms are introduced to reflect the subtle biologic nuances involving benign non-neoplastic and low-grade neoplastic conditions. The Bethesda Thyroid Cytopathology System has simplified its terminology, updated risk of malignancy estimates, and expanded the discussions on molecular testing, clinical and imaging assessments, and pediatric cytopathology. There is now a single term for each of the 6 diagnostic categories. The American Joint Committee on Cancer has refined the staging criteria to provide improved stratification of patient prognostication. Molecular testing using next-generation technology now offers large panels of markers that are sensitive for detecting the wide range of thyroid neoplasms. These panels were developed in North America and whether other regions of the world will choose similar tests remain to be seen. Finally, metrics such as molecular-derived risk of malignancy and molecular risk group may be viewed as surrogates of resection information and used to complement diagnostics, management, and quality assurance.
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Background: The diagnosis of thyroid neoplasms necessitates the identification of distinct histological features. Various education/hospital centers located in cities across Indonesia likely result in discordances among pathologists when diagnosing thyroid neoplasms. Methods: This study examined the concordance among Indonesian pathologists in assessing nuclear features and capsular and vascular invasion of thyroid tumors. Fifteen pathologists from different centers independently assessed the same 14 digital slides of thyroid tumor specimens. All the specimens were thyroid neoplasms with known BRAFV600E and RAS mutational status, from a single center. We evaluated the pre- and post-training agreement using the Fleiss kappa. The significance of the training was evaluated using a paired T-test. Results: Baseline agreement on nuclear features was slight to fair based on a 3-point scoring system (k = 0.14 to 0.28) and poor to fair based on an eight-point system (k = -0.02 to 0.24). Agreements on vascular (κ = 0.35) and capsular invasion (κ = 0.27) were fair, whereas the estimated molecular type showed substantial agreement (κ = 0.74). Following the training, agreement using the eight-point system significantly improved (p = 0.001). Conclusions: The level of concordance among Indonesian pathologists in diagnosing thyroid neoplasm was relatively poor. Consensus in pathology assessment requires ongoing collaboration and education to refine diagnostic criteria.
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Background: Radioiodine (RI) ablation following thyroid-stimulating hormone suppression is an effective treatment for papillary thyroid cancer (PTC), typically leading to favorable outcomes. However, RI-refractory tumors exhibit aggressive behavior and poor prognoses. Recent studies highlight the role of genetic abnormalities in PTC signaling pathways, including the activation of telomerase reverse transcriptase (TERT), and the correlation of mutations with adverse outcomes. Methods: This study analyzed mutations in BRAF V600E and the TERT-promoter genes, comparing clinicopathological features between RI-refractory and RI-responsive PTCs. Among 82 RI-refractory patients, formalin-fixed, paraffin-embedded tissues from initial surgeries were available for 26. Another 89 without distant metastasis over 5 years formed a matched RI-responsive control group. Results: Histopathologically, RI-refractory PTCs showed increased frequencies of small tumor clusters without fibrovascular cores, hobnail features, and a high height-to-width ratio of tumor cells. These tumors were more likely to exhibit necrosis, mitosis, lymph node metastasis, extrathyroidal extension, and involvement of resection margins. TERT-promoter mutations were statistically significantly associated with these aggressive clinicopathologic features. Immunohistochemically, decreased expression of sodium iodide symporter and thyroglobulin stimulating hormone receptor proteins was common in RI-refractory PTCs, along with lower levels of oncogenic proteins such as vascular endothelial cell growth factor, vascular endothelial cell growth factor receptor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells. Total loss of PTEN expression was occasionally observed. In contrast, all cases tested positive for cytoplasmic ß-catenin. Conclusions: RI-refractory PTCs are linked to TERT mutations and exhibit specific aggressive histopathologic features, particularly in tumor centers.
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INTRODUCTION: Thyroid cytopathology cases with suspicious for malignancy (SFM) diagnosis often result in resection. However, molecular testing offers details that may provide additional insights. In this study, the molecular profiles of SFM cases from two institutions that routinely used ThyroSeq v3 (TSV3) were examined. MATERIALS AND METHODS: Following institutional review board approval, SFM thyroid cytopathology cases with TSV3 results were retrieved from the databases of two institutions. Molecular information including molecular-derived risk of malignancy (MDROM), cytologic-histologic correlation data, and other related parameters were calculated. Statistical comparisons were made with a p <.05 considered significant. RESULTS: The core data set comprised 114 SFM cases that passed TSV3 quality assurance. All TSV3 results were reported as positive or negative for genomic alterations and all except five cases provided a probability of malignancy estimate. The overall combined baseline MDROM of 75.7% (95% CI, 70.0-81.4) was comparable to the risk of malignancy (74%) published in the Bethesda System. There was a statistically significant difference between the combined MDROMs of resected and unresected cohorts (79.0% vs 58.6%; p = .0153). Interestingly, the MDROMs of the resected cohorts from the two institutions were statistically different (75.0% vs 85.3%; p = .020). Cytologic-histologic correlation revealed malignant outcome in 88.5% of resected cases. CONCLUSIONS: Molecular analyses of SFM cases demonstrated higher risk genomic alterations that were associated with histologically overt neoplasms, resulting in increased malignancy outcome compared to baseline. MDROM analysis revealed differences in the cytopathologic practice patterns regarding follicular-patterned neoplasms at the two institutions.
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BACKGROUND: Oncocytic thyroid carcinoma (OTC) is a rare subtype of thyroid cancer known for its distinctive morphology and high likelihood of recurrence, setting it apart from follicular thyroid carcinoma (FTC). Despite this, there is limited research comparing the clinicopathological characteristics and outcomes of OTC and FTC. METHODS: We retrospectively searched through the Surveillance, Epidemiology, and End-Results (SEER) database (2004-2015) for histologically diagnosed OTC and FTC patients. Kaplan-Meier analysis, propensity score matching (PSM), univariate Cox proportional risk regression model, and subgroup analysis were employed to investigate the prognostic effect of clinicopathological features and treatment regimens on survival outcomes of OTC and FTC patients. RESULTS: 2329 OTC patients and 5679 FTC patients were included in the study. OTC patients were prone to older age, white race, lymph node metastasis, distal metastasis, extension and multiple primary tumors compared with FTC patients. After using a 1:1 PSM matching ratio, there were no significant differences in demographic and clinicopathological characteristics between the matched groups. Further Cox regression analysis showed that OTC patients had lower overall survival (OS) and cancer-specific survival (CSS) in contrast with FTC patients. Subgroup survival analysis suggested that the OTC patients were related to lower OS in subgroups including those over 55 years old, male sex, white ethnicity, extrathyroidal extension, single primary tumor, surgery and without chemotherapy compared with the FTC patients in these subgroups. In addition, the OTC patients were connected with lower CSS in subgroups including male sex, white ethnicity, married status, tumor size is less than 20 mm or more than 40 mm, N0 stage, localized stage, single primary tumor, surgery, radiotherapy, and without chemotherapy compared with the FTC patients in these subgroups. Meanwhile, the OTC patients had lower CSS compared to FTC patients regardless of age and extrathyroidal extension. CONCLUSIONS: The results suggested that OTC patients have unique clinical features and poorer prognoses compared to FTC patients. Surgical resection and radioactive iodine therapy are recommended for OTC patients and FTC patients. It is worth noting that the prognosis of OTC relies largely on the selection of treatment strategies. Therefore, our results highlighted the clinical significance of the early distinguishment and the correct choice of treatment in OTC patients.
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Simultaneous imaging of the SPECT tracer 131I and PET tracer 18F is important in the diagnosis of high- and low-grade thyroid cancers because high-grade thyroid cancers have high 18F-FDG and low 131I uptake, while low-grade thyroid cancers have high 131I and low 18F-FDG uptake. In this study, Na131I and 18F-FDG were simultaneously imaged using the Compton-PET system, in vivo. The angular resolution and sensitivity of the Compton camera with 356 keV gamma ray measured using a 133Ba point source were 12.3° and 2 × 10-5, respectively. The spatial resolution and sensitivity of PET were measured with a 22Na point source. The transaxial and axial spatial resolutions of the PET at the center of the FOV were 1.15 mm and 2.04 mm, respectively. Its sensitivity was 1.2 × 10-4. In-vivo images of the 18F and 131I isotopes were simultaneously acquired from mice. These showed that 18F-FDG was active in the heart, brown fat, and brain, while Na131I was active in the thyroid, stomach, and bladder. Artifacts were found in the Compton camera images when the activity of 131I was much lower than that of 18F. This study demonstrates the potential of simultaneous clinical imaging of 18F and 131I.