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The thyroid gland is an essential endocrine organ that secretes hormones to regulate homeostasis across multiple organ systems throughout the body. It is actively regulated by the hypothalamic-pituitary-thyroid (HPT) axis, where negative feedback modulates the amounts of active hormone being released; thus, lesions that disrupt the proper functioning of this gland or its regulatory mechanisms can be destructive. Toxic thyroid adenomas are usually singular benign functioning nodules in the thyroid gland that cause thyrotoxicosis. Hyperthyroidism is commonly clinically silent, however, in most symptomatic cases, patients will be diagnosed based on abnormal laboratory findings and typical hyperthyroid symptoms. This case report examines an 81-year-old male with an extensive medical history who presented with complaints of new-onset generalized fatigue coupled with bilateral lower extremity muscle cramps. A positron emission tomography (PET) scan for other medical conditions incidentally noted mildly increased uptake in the thyroid gland, prompting a further investigation that resulted in a diagnosis of toxic thyroid adenoma. The patient responded well to treatment with methimazole and has remained in a euthyroid state.

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The classification of thyroid nodules, particularly those with a follicular growth pattern, has significantly evolved. These tumors, enriched with RAS or RAS-like mutations, remain challenging for pathologists due to variables such as nuclear atypia, invasion, mitotic activity, and tumor necrosis. This review addresses the histological correlates of benign, low-risk, and malignant RAS-mutant thyroid tumors, as well as some difficult-to-classify follicular nodules with worrisome features. One prototypical RAS-mutant nodule is non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The assessment of nuclear characteristics in encapsulated/well-demarcated non-invasive RAS-mutant follicular-patterned tumors helps distinguish between follicular thyroid adenoma (FTA) and NIFTP. Despite this straightforward concept, questions about the degree of nuclear atypia necessary for the diagnosis of NIFTP are common in clinical practice. The nomenclature of follicular nodules lacking clear invasive features with increased mitotic activity, tumor necrosis, and/or high-risk mutations (e.g., TERT promoter or TP53) remains debated. Invasion, particularly angioinvasion, is the current hallmark of malignancy in RAS-mutant follicular-patterned neoplasms, with follicular thyroid carcinoma (FTC) as the model. Assessing the tumor interface is critical, though full capsule evaluation can be challenging. Multiple levels and NRASQ61R-specific immunohistochemistry can aid in identifying invasion. Controversies around vascular invasion persist, with ancillary stains like CD31, ERG, and CD61 aiding in its evaluation. Moreover, the review highlights that invasive encapsulated follicular variant papillary thyroid carcinoma (IEFVPTC) is closely associated with FTC, suggesting the need for better nomenclature. The concept of "high-grade" differentiated carcinomas, applicable to FTC or IEFVPTC with necrosis and/or high mitotic activity, is also discussed.

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Cardiac glycosides, known as inhibitors of Na+,K+-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na+,K+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells.

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INTRODUCTION: The objective was to investigate the correlation between Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection in the development of benign thyroid lesions. MATERIAL AND METHODS: 29 cases of Hashimoto's thyroiditis (HT), 133 cases of thyroid adenoma, and 34 cases of HT with thyroid adenoma paraffin embedded tissue samples were used for EBV and HPV quantitative detection. RESULTS: None of the tissue samples carried HPV DNA. In HT tissue samples, the positive rate of EBV was 55.2% (16/29). In thyroid adenoma tissue samples, the positive rate was 37.6% (50/133). In HT combined with thyroid adenoma tissue samples, the positive rate of EBV was 67.6% (23/34). There was no correlation between EBV infection and clinical features such as age and gender. CONCLUSION: The occurrence and development of benign thyroid lesions are closely related to EBV infection. HT combined with thyroid adenoma may be more susceptible to EBV infection than simple HT and thyroid adenoma, which provides a new idea for the diagnosis and treatment of benign thyroid lesions.

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OBJECTIVES: Fetal and neonatal hyperthyroidism are most commonly seen in patients whose mothers have Graves' disease. Rarely, it can be caused by non-autoimmune conditions. As these conditions are rare, the workup and treatment is not uniform and can lead to persistent symptoms and long-term negative health effects. CASE PRESENTATION: This report describes a patient with congenital hyperthyroidism from a toxic adenoma presenting with fetal tachycardia. The patient was initially managed medically after birth, but was eventually treated with thyroidectomy. CONCLUSIONS: This case report highlights an additional, important, differential diagnosis for fetal hyperthyroidism when maternal Graves' disease has been ruled out.

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Complete deficiency of thyroxin-binding globulin (TBG-CD) is not commonly associated with clinical symptoms, and little is known about thyroid tumors associated with TBG-CD. We present a case report of an asymptomatic follicular adenoma that spontaneously shrank in a patient with TBG-CD. A previously healthy 13-yr-old male presented with a diffusely swollen thyroid gland. Thyroid function tests revealed low total thyroxin and TBG concentrations, indicating a TBG deficiency. Ultrasonography revealed a mildly swollen thyroid gland with a nodule (14 × 12 × 19 mm) in the left lobe. Genetic analysis of peripheral blood revealed a previously reported SERPINA7 variant, which resulted in complete loss of TBG function. The nodule was identified as a follicular adenoma using fine-needle aspiration. Subsequently, the adenoma shrank without treatment. This pubertal case suggests that careful observation with ultrasonography is warranted for follicular adenoma in patients with TBG deficiency and that treatment may not be required.

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This multi-institutional study investigated non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) frequency and its diagnostic significance in Japan. We reviewed 4008 thyroid nodules resected in six institutions before NIFTP was proposed. Overall, 26 cases diagnosed as non-invasive encapsulated follicular variant of papillary thyroid carcinoma (PTC) and 145 cases of follicular thyroid adenoma (FTA) were included. Of these nodules, 80.8% and 31.0%, respectively, were NIFTPs. In five institutions, NIFTPs were more commonly found in FTA than in PTC nodules. When NIFTP was included with PTC, the overall prevalence was 2.3%, with rates in five institutions below 5.0% (0.8%-4.4%). One NIFTP case with nuclear score 3 revealed nodal metastasis 2.5 years post-resection, and the carcinoma cells were immunohistochemically positive for BRAF. FTAs or NIFTPs with nuclear score 2 did not metastasize. NIFTP was more common among FTA than among PTC nodules, possibly due to underdiagnosis of PTC on nuclear findings. Considering the clinical findings, molecular pathogenesis, and therapeutic strategy in Japan, NIFTP with nuclear score 2 is not different from FTA, and use of this entity terminology is not meaningful. In contrast, NIFTP with nuclear score 3 has potential for metastasis and BRAFV600E mutation. Therefore, in NIFTP cases, nuclear scores 2 and 3 should be separately reported.

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Background: Thyroid cancer cell lines have been of great value for the study of thyroid cancer. However, the availability of benign thyroid adenoma cell lines is limited. Methods: Cell lines were established from thyroid adenomatous nodules that developed in mice treated with the goitrogen amitrole. Expression of epithelial, mesenchymal, and thyroid markers of these established cell lines was determined, and the effect of lentivirus-transduced overexpression of NKX2-1, a master regulator of thyroid development, on the thyroid marker expression was examined. Signal transduction and cell proliferation were evaluated after treatment with insulin-like growth factor-I (IGF-I) and the selective IGF-I receptor (IGF-IR) inhibitor NVP-ADW742. Xenograft studies were performed to examine tumorigenicity of the cells in mice. Whole-genome sequencing (WGS) was used to comprehensively determine the genetic mutations in the established two cell lines. Results: Five mouse thyroid adenomatous nodules-derived cell lines named CAT (cells from amitrole-treated thyroids) were established. Among these, two cell lines, CAT458/458s (CAT458s: a subline of CAT458) and CAT459, were found to be positive for epithelial markers and negative for a mesenchymal marker. NKX2-1-positive CAT459 cells showed higher messenger RNA (mRNA) expression of some thyroid differentiation markers than NKX2-1-negative CAT458s cells, and NKX2-1 overexpression increased and/or induced their expression. IGF-I signaling was transduced in thyrotropin receptor (Tshr)-negative CAT458s and 459 cells, and NVP-ADW742 suppressed their proliferation. No tumors developed in mice after subcutaneous injection of CAT458s or 459 cells. The WGS analysis revealed the presence of missense mutations in the tumor suppressor genes such as Polk (encoding DNA polymerase kappa) and Tgfb1 (encoding transforming growth factor beta 1), while no mutations were found in the prominent thyroid cancer-related genes Braf, Trp53 (encoding p53), and Tert (encoding telomerase reverse transcriptase). Conclusions: Two mouse thyroid adenomatous nodule-derived cell lines with different thyroid differentiation marker expression were established. NKX2-1 induced partial differentiation of these cell lines. They lacked tumorigenicity and prominent gene mutations involved in thyroid cancer development, while missense mutations were found in some tumor suppressors as revealed by WGS. The CAT458s and 459 provide a new tool to further clarify the process of thyroid multistep carcinogenesis and differentiation.

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Introduction: Thyroid cancer is the most common endocrine tumor in humans. Follicular adenoma/carcinoma is the second most common subtype. Multiple histological patterns have been identified. Follicular adenoma with bizarre nuclei is one of the patterns associated with p53 mutation and has an unclear clinical prognosis. Case report: A 74-year-old female presented with incidental findings of elevated TSH levels and normal thyroid markers. Ultrasound was performed and revealed multiple bilateral thyroid nodules measuring up to 1.9 cm. Fine needle aspiration was performed, and cytology showed one Bethesda category 5 nodule. Total thyroidectomy with neck dissection was performed, and the pathology showed follicular adenoma with bizarre nuclei. Based on the results of immunohistochemistry, the neoplastic cells exhibited staining for wild-type p53 and low levels of the proliferation index Ki-67. Conclusions: We report a rare case of thyroid follicular adenoma with bizarre nuclei. In contrast to previous reports of this tumor, our patient showed a p53 wild-type pattern using immunohistochemistry. More studies are needed to better understand the etiology and clinical prognosis of this tumor.

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STUDY QUESTION: Was polycystic ovary syndrome (PCOS), which impairs fertility and adheres to the evolutionary paradox, subject to evolutionary selection during ancestral times and did rapidly diminish in prevalence? SUMMARY ANSWER: This study strengthened the hypothesis that positive selection of genetic variants occurred and may account for the high prevalence of PCOS observed today. WHAT IS KNOWN ALREADY: PCOS is a complex endocrine disorder characterized by both reproductive and metabolic disturbances. As a heritable disease that impairs fertility, PCOS should diminish rapidly in prevalence; however, it is the most common cause of female subfertility globally. Few scientific genetic studies have attempted to provide evidence for the positive selection of gene variants underlying PCOS. STUDY DESIGN, SIZE, DURATION: We performed an evolutionary analysis of 2,504 individuals from 14 populations of the 1000 Genomes Project. PARTICIPANTS/MATERIALS, SETTING, METHODS: We tested the signature of positive selection for 37 single-nucleotide polymorphisms (SNPs) associated with PCOS in previous genome-wide association studies using six parameters of positive selection. MAIN RESULTS AND THE ROLE OF CHANCE: Analyzing the evolutionary indices together, there was obvious positive selection at the PCOS-related SNPs loci, especially within the original evolution window of humans, demonstrated by significant Tajima's D values. Compared to the genome background, six of the 37 SNPs in or close to five genes (DENN domain-containing protein 1A: DENND1A, chromosome 9 open reading frame 3: AOPEP, aminopeptidase O: THADA, diacylglycerol kinase iota: DGKI, and netrin receptor UNC5C: UNC5C) showed significant evidence of positive selection, among which DENND1A, AOPEP, and THADA represent the set of most established susceptibility genes for PCOS. LIMITATIONS, REASONS FOR CAUTION: First, only well-documented SNPs were selected from well-designed experiments. Second, it is difficult to determine which hypothesis of PCOS evolution is at play. After considering the most significant functions of these genes, we found that they had a wide variety of functions with no obvious association between them. WIDER IMPLICATIONS OF THE FINDINGS: Our findings provide additional evidence for the positive evolution of PCOS. Our analyses require confirmation in a larger study with more evolutionary indicators and larger data range. Further research to identify the roles of the DENND1A, AOPEP, THADA, DGKI, and UNC5C genes is also necessary. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2021YFC2700400 and 2021YFC2700701), Basic Science Center Program of NSFC (31988101), CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), National Natural Science Foundation of China (82192874, 31871509, and 82071606), Shandong Provincial Key Research and Development Program (2020ZLYS02), Taishan Scholars Program of Shandong Province (ts20190988), and Fundamental Research Funds of Shandong University. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

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A pararectal mass' specific diagnosis can be challenging as a broad range of both benign and malignant tumors are possible. Many of these lesions are congenital and do not require treatment, if asymptomatic. Special attention is to be paid when imaging findings are not typical. In such cases, definitive diagnostic can require surgical excision. To this day, ectopic thyroid tissue was not part of known differential diagnosis. This is the first reported case of thyroid adenoma found in the perirectal area. Ectopic thyroid gland can progress over time and include malignant transformation, although rare. It needs to be considered when managing these cases, especially in unusual locations. This case report offers a systematic approach to the atypical pararectal tumor. It shares new specific clinical experience in managing a case  of pararectal ectopic thyroid adenoma, from both a surgical and a histopathological point of view.

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OBJECTIVE: To explore the diagnostic performance of the currently used ultrasound-based thyroid nodule risk stratification systems (K-TIRADS, ACR -TIRADS, and C-TIRADS) in differentiating follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC). METHODS: Clinical data and preoperative ultrasonographic images of 269 follicular thyroid neoplasms were retrospectively analyzed. All of them were detected by Color Doppler ultrasound instruments equipped with high-frequency liner array probes (e.g. Toshiba Apoli500 with L5-14MHZ; Philips IU22 with L5-12MHZ; GE LOGIQ E9 with L9-12MHZ and MyLab Class C with L9-14MHZ). The diagnostic performance of three TIRADS classifications for differentiating FTA from FTC was evaluated by drawing the receiver operating characteristic (ROC) curves and calculating the cut-off values. RESULTS: Of the 269 follicular neoplasms (mean size, 3.67±1.53 cm), 209 were FTAs (mean size, 3.56±1.38 cm) and 60 were FTCs (mean size, 4.07±1.93 cm). There were significant differences in ultrasound features such as margins, calcifications, and vascularity of thyroid nodules between the FTA and FTC groups (P < 0.05). According to the ROC curve comparison analysis, the diagnostic cut-off values of K-TIRADS, ACR-TIRADS, and C-TIRADS for identifying FTA and FTC were K-TR4, ACR-TR4, and C-TR4B, respectively, and the areas under the curves were 0.676, 0.728, and 0.719, respectively. The difference between ACR-TIRADS and K-TIRADS classification was statistically significant (P = 0.0241), whereas the differences between ACR-TIRADS and C-TIRADS classification and between K-TIRADS and C-TIRADS classification were not statistically significant (P > 0.05). CONCLUSION: The three TIRADS classifications were not conducive to distinguishing FTA from FTC. It is necessary to develop a novel malignant risk stratification system specifically for the identification of follicular thyroid neoplasms.

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Background: Alterations in DNA methylation are stable epigenetic events that can serve as clinical biomarkers. The aim of this study was to analyze methylation patterns among various follicular cell-derived thyroid neoplasms to identify disease subtypes and help understand and classify thyroid tumors. Methods: We employed an unsupervised machine learning method for class discovery to search for distinct methylation patterns among various thyroid neoplasms. Our algorithm was not provided with any clinical or pathological information, relying exclusively on DNA methylation data to classify samples. We analyzed 810 thyroid samples (n = 256 for discovery and n = 554 for validation), including benign and malignant tumors, as well as normal thyroid tissue. Results: Our unsupervised algorithm identified that samples could be classified into three subtypes based solely on their methylation profile. These methylation subtypes were strongly associated with histological diagnosis (p < 0.001) and were therefore named normal-like, follicular-like, and papillary thyroid carcinoma (PTC)-like. Follicular adenomas, follicular carcinomas, oncocytic adenomas, and oncocytic carcinomas clustered together forming the follicular-like methylation subtype. Conversely, classic papillary thyroid carcinomas (cPTC) and tall cell PTC clustered together forming the PTC-like subtype. These methylation subtypes were also strongly associated with genomic drivers: 98.7% BRAFV600E-driven cancers were PTC like, whereas 96.0% RAS-driven cancers had a follicular-like methylation pattern. Interestingly, unlike other diagnoses, follicular variant PTC (FVPTC) samples were split into two methylation clusters (follicular like and PTC like), indicating a heterogeneous group likely to be formed by two distinct diseases. FVPTC samples with a follicular-like methylation pattern were enriched for RAS mutations (36.4% vs. 8.0%; p < 0.001), whereas FVPTC- with PTC-like methylation patterns were enriched for BRAFV600E mutations (52.0% vs. 0%, Fisher exact p = 0.004) and RET fusions (16.0% vs. 0%, Fisher exact p = 0.003). Conclusions: Our data provide novel insights into the epigenetic alterations of thyroid tumors. Since our classification method relies on a fully unsupervised machine learning approach for subtype discovery, our results offer a robust background to support the classification of thyroid neoplasms based on methylation patterns.

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Objective: To investigate the feasibility and value of histogram analysis based on two-dimensional gray-scale ultrasonography in the differential diagnosis of medullary thyroid carcinoma (MTC) and thyroid adenoma (TA). Methods: The preoperative ultrasound images of 86 newly diagnosed MTC patients and 100 TA patients treated in the Cancer Hospital of Chinese Academy of Medical Sciences from January 2015 to October 2021 were collected. Histograms were performed based on the regions of interest (ROIs) delineated manually by two radiologists, thereafter, mean, variance, skewness, kurtosis, percentiles (1st, 10th, 50th, 90th, 99th) were generated. The histogram parameters between the MTC group and the TA group were compared, and the independent predictors were screened by multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to compare the individual diagnostic efficacy and joint diagnostic efficacy of independent predictors. Results: Multivariate regression analysis showed that mean, skewness, kurtosis and 50th percentile were independent factors. The skewness and kurtosis in the MTC group were significantly higher than those in the TA group, and the mean and 50th percentile were significantly lower than those in the TA group. The area under the individual ROC curve of mean, skewness, kurtosis and 50th percentile is 0.654-0.778. The area under the combined ROC curve is 0.826. Conclusion: Histogram analysis based on two-dimensional gray-scale ultrasonography is a promising tool to distinguish MTC from TA, in which the joint diagnosis value of mean, skewness, kurtosis and 50th percentile is the highest.

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Pre- and postsurgical differentiation between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC) represents a significant diagnostic challenge. Furthermore, it remains unclear whether they share a common or distinct background and what the mechanisms underlying follicular thyroid lesions malignancy are. The study aimed to compare FTA and FTC by the comprehensive microarray and to identify recurrent regions of loss of heterozygosity (LOH). We analyzed formalin-fixed paraffin-embedded (FFPE) samples acquired from 32 Caucasian patients diagnosed with FTA (16) and FTC (16). We used the OncoScan™ microarray assay (Affymetrix, USA), using highly multiplexed molecular inversion probes for single nucleotide polymorphism (SNP). The total number of LOH was higher in FTC compared with FTA (18 vs. 15). The most common LOH present in 21 cases, in both FTA (10 cases) and FTC (11 cases), was 16p12.1, which encompasses many cancer-related genes, such as TP53, and was followed by 3p21.31. The only LOH present exclusively in FTA patients (56% vs. 0%) was 11p11.2-p11.12. The alteration which tended to be detected more often in FTC (6 vs. 1 in FTA) was 12q24.11-q24.13 overlapping FOXN4, MYL2, PTPN11 genes. FTA and FTC may share a common genetic background, even though differentiating rearrangements may also be detected.

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Objective: To investigate the feasibility and value of histogram analysis based on two-dimensional gray-scale ultrasonography in the differential diagnosis of medullary thyroid carcinoma (MTC) and thyroid adenoma (TA). Methods: The preoperative ultrasound images of 86 newly diagnosed MTC patients and 100 TA patients treated in the Cancer Hospital of Chinese Academy of Medical Sciences from January 2015 to October 2021 were collected. Histograms were performed based on the regions of interest (ROIs) delineated manually by two radiologists, thereafter, mean, variance, skewness, kurtosis, percentiles (1st, 10th, 50th, 90th, 99th) were generated. The histogram parameters between the MTC group and the TA group were compared, and the independent predictors were screened by multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to compare the individual diagnostic efficacy and joint diagnostic efficacy of independent predictors. Results: Multivariate regression analysis showed that mean, skewness, kurtosis and 50th percentile were independent factors. The skewness and kurtosis in the MTC group were significantly higher than those in the TA group, and the mean and 50th percentile were significantly lower than those in the TA group. The area under the individual ROC curve of mean, skewness, kurtosis and 50th percentile is 0.654-0.778. The area under the combined ROC curve is 0.826. Conclusion: Histogram analysis based on two-dimensional gray-scale ultrasonography is a promising tool to distinguish MTC from TA, in which the joint diagnosis value of mean, skewness, kurtosis and 50th percentile is the highest.

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Objective:To evaluate the value of ultrasonographic features and classification defined by the Chinese-Thyroid Imaging Reporting and Data System (C-TIRADS) in differentiating follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA) .Methods:Data of 87 patients who underwent thyroid nodule-related surgery at Tianjin Medical University General Hospital from Jan. 2019 to Feb. 2023 and whose postoperative pathology confirmed FTC or FTA was divided into FTC group (26 cases) and FTA group (61 cases) were retrospectively analyzed. The differences of general data, pathological diagnosis, surgical methods, ultrasonographic features of thyroid nodules and C-TIRADS classification between the two groups were compared. Multivariate Logistic regression analysis was used to screen the independent predictors related to the occurrence of FTC, a regression model was established based on the independent predictors and a nomogram was drawn. Bootstrap method was used to verify the nomogram internally, and ROC curve and calibration curve were drawn to evaluate the diagnostic efficiency and predictive ability of the nomogram.Results:There were statistically significant differences between orientation, echo, composition, calcification, margin, halo and C-TIRADS classification between groups (all P<0.05) ; maximum diameter, echotexture, blood flow, general data, pathological diagnosis and surgical methods had no statistically significant differences between groups (all P>0.05) .Single-factor logistic regression analysis showed taller-than-wide, peripheral calcification, blurred/irregular edges or external invasion, C-TIRADS 4B/4C class were candidate variables for predicting the occurrence of FTC ( OR=10.909, 19.059, 19.259, 49.333, all P<0.05). Multivariate logistic regression analysis showed that peripheral calcification, blurry/irregular edges or extra-thyroid invasion, C-TIRADS 4B/4C class were independent predictors for the occurrence of FTC ( OR=33.731, 11.620, 22.794, all P<0.05) .The nomogram of FTC occurrence was constructed based on the above three independent predictors, and the AUC was 0.920 (95% CI=0.854-0.986), which showed that the nomogram had high diagnostic efficacy, and the optimal diagnostic threshold determined by the Youden index was 0.23 (corresponding to the total score of the nomogram is about 52 points), the sensitivity was 88.5%, and the specificity was 82.0%. The calibration curve drawn by internal verification was close to the reference line, suggesting that the nomogram had a high predictive ability. Conclusions:The nomogram prediction model for FTC occurrence based on the ultrasonographic features and classification defined by C-TIRADS has high diagnostic efficiency and predictive ability, and can help in the preoperative identification of FTC and FTA.

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Follicular neoplasms of the thyroid include follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). However, the differences in cytological findings between FTC and FTA remain undetermined. Here, we aimed to evaluate the accumulation of lipid droplets (LDs) and the expression of adipophilin (perilipin 2/ADRP/ADFP), a known LD marker, in cultured FTC cells. We also immunohistochemically compared adipophilin expression in the FTC and FTA of resected human thyroid tissues. Cultured FTC (FTC-133 and RO82W-1) possessed increased populations of LDs compared to thyroid follicular epithelial (Nthy-ori 3-1) cells. In vitro treatment with phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling inhibitors (LY294002, MK2206, and rapamycin) in FTC-133 cells downregulated the PI3K/Akt/mTOR/sterol regulatory element-binding protein 1 (SREBP1) signaling pathway, resulting in a significant reduction in LD accumulation. SREBP1 is a master transcription factor that controls lipid metabolism. Fluorescence immunocytochemistry revealed adipophilin expression in the LDs of FTC-133 cells. Immunohistochemical analysis of surgically resected human thyroid tissues revealed significantly increased expression of adipophilin in FTC compared with FTA and adjacent non-tumorous thyroid epithelia. Taken together, LDs and adipophilin were abundant in cultured FTC; the evaluation of adipophilin expression can help distinguish FTC from FTA in surgical specimens.

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It is crucial for doctors to decide whether a thyroid nodule is benign or malignant when a patient presents with one, as it will significantly impact how the patient is managed in the future. However, it is not as straightforward to determine between the two; even a physical examination, thyroid function test, ultrasonography, and biopsy have been well performed. It can be more stressful if a patient has an increased risk of malignancy, such as age (below 20- and above 60-year-old), solid nodule, rapid growth, hoarseness, lymphadenopathy, and microcalcifications on the ultrasonography. The aim of this case was to present the management of a giant thyroid nodule with malignancy presentation and a benign biopsy finding. A 41-year-old male complained of a palpable neck mass, hoarseness, and dysphagia. The thyroid function test was normal. Ultrasonography revealed suspicion of malignancy with category 4 of American College of Radiology-Thyroid Imaging Reporting and Data System (ACR-TIRADS). The biopsy revealed follicular neoplasm, and was classified as Bethesda IV. The patient underwent a total thyroidectomy due to the large tumor size and symptoms. Histopathological findings post-surgery revealed a follicular thyroid adenoma. This case highlights a complex diagnosis and management of follicular thyroid neoplasm due to their potential for both benign and malignant. Comprehensive pre- and post-operative care is essential to determine the nature of nodules. Post-operative follow-up care might improve the patient's outcome and prevent complications.

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Oxidative stress (OS) can have an impact in the pathogenesis and in the progression of thyroid cancer. We investigated the levels of reactive oxygen species (ROS) in 50 malignant and benign thyroid lesions and 41 normal tissues, and correlated them with the thyroid differentiation score-TDS and the clinico-pathologic features. NOX4 expression, GPx activity and the genetic pattern of tumors were evaluated. In malignant and benign lesions, ROS generation and NOX4 protein expression were higher than in normal tissues. Follicular (FTCs) and anaplastic/poorly differentiated cancers had increased OS relative to papillary tumors (PTCs). Moreover, OS in FTCs was higher than in follicular adenomas. Mutated PTCs showed increased OS compared with non-mutated PTCs. In malignant tumors, OS was inversely correlated with TDS, and directly correlated with tumor stage and ATA risk. GPx activity was increased in tumors compared with normal tissues, and inversely correlated to OS. In conclusion, our data indicate that thyroid tumors are exposed to higher OS compared with normal tissues, while showing a compensative increased GPx activity. OS correlates with tumor aggressiveness and mutations in the MEK-ERK pathway in PTC. The inverse correlation between OS and TDS suggests that ROS may repress genes involved in thyroid differentiation.