Columnar Cell Thyroid Carcinoma: A Heterogeneous Entity Demonstrating Overlap Between Papillary Thyroid Carcinoma and Follicular Neoplasms.

BACKGROUND: Columnar cell papillary thyroid carcinoma (CC-PTC) is a morphologic subtype of papillary thyroid carcinoma with a variable prognosis. It is characterized by neoplastic thyroid follicular-derived cells with pseudostratified columnar morphology arranged in papillary or follicular structures with supranuclear or subnuclear vacuoles. The molecular profile of this subtype has only recently come under scrutiny, with mixed results. The aim of this study is to further explore the morphologic, immunohistochemical, and genetic profile of CC-PTC, as well as to correlate these features with clinical outcomes. METHODS: CC-PTC cases were identified from 3 institutions. Immunohistochemistry (ER, CDX2) and molecular testing (DNA and RNA sequencing) were performed. Clinicopathologic parameters and patient outcomes were recorded. RESULTS: Twelve cases (2006-2023) were identified, all in adults (age 45-91). Two presented with disease outside the thyroid gland (neck and mediastinum) and two presented with distant metastasis. Four were high-grade differentiated thyroid carcinomas (necrosis or mitoses), one of which died of disease. Four were noninvasive or minimally invasive, one of which locally recurred. Three patients had lymph node metastases. ER and CDX2 were positive in 73% and 50%, respectively. Pathogenic mutations were found in TERT promoter (n = 3), RAS (n = 2), ATM, NOTCH1, APC, and ESR1, along with cases bearing AGK::BRAF fusion (n = 1), BRAF VE1 expression (n = 1), and NF2 loss (n = 1). CONCLUSIONS: This study represents the largest molecularly defined cohort of non-oncocytic thyroid carcinomas with columnar cell morphology. These tumors represent a genetically and behaviorally heterogeneous group of neoplasms, some of which have RAS-like or follicular neoplasm-like genetics, some of which have BRAF-p.V600E-like or classic papillary thyroid carcinoma-like genetics, and some of which remain unclear. Noninvasive or minimally invasive tumors showed an indolent course compared to those with angioinvasion, gross extrathyroidal growth, or high-grade morphology. Consideration could be given to reclassification of this neoplasm outside of the subtyping of papillary thyroid carcinoma in light of its genetic diversity, distinct morphology, and clinical behavior more closely aligned with follicular thyroid neoplasms.

WHO 2022 updates on follicular cell and c-cell derived thyroid neoplasm.

The latest edition of the WHO Classification of thyroid tumors was released in 2022 and incorporates novel concepts vital to patient management. Thyroid follicular nodular disease is a term used to collectively represent a wide variety of benign and non-neoplastic lesions, including both clonal and non-clonal proliferations that manifest clinically as multinodular goiter. Thyroid neoplasms develop from follicular cells and can be either benign, low-risk, or malignant. To avoid classifying all lesions under 1 cm in diameter as low-risk illnesses, the new classification method highlights the need for subtyping papillary thyroid cancer based on histomorphologic indicators rather than tumor size. Formerly known as the cribriform-morular variety of papillary thyroid carcinoma, this tumor is now more commonly referred to by its more accurate name, cribriform-morular thyroid carcinoma. Its histogenesis is unknown. Similar to the traditional definition of 'poorly differentiated thyroid carcinoma' according to the Turin criteria, the newly defined 'differentiated high-grade thyroid carcinoma' encompasses papillary thyroid cancer, follicular thyroid carcinomas, and oncocytic carcinomas with high-grade characteristics linked to worse prognosis. The squamous cell subtype of anaplastic thyroid cancer has also recently been characterized as a distinct morphologic pattern. In this article, we will discuss the latest revision to the World Health Organization's classification system for thyroid cancer.

Incidentally detected follicular thyroid carcinoma mimicking parathyroid adenoma on Tc-99m MIBI scan: A case report.

RATIONALE: Primary hyperparathyroidism, though relatively prevalent among endocrine disorders, affecting 1% of the general population, often presents diagnostic challenges. Given its potential to precipitate severe complications including nephrolithiasis and fractures, timely diagnosis, and effective management are crucial. PATIENT CONCERNS: A 38-year-old woman with hypercalcemia was referred to the Department of Nuclear Medicine for a Tc-99m MIBI scan. DIAGNOSES: Tc-99m MIBI scan showed focal increased uptake in the left thyroid gland area, initially suggesting a parathyroid adenoma. Further examination using SPECT/CT revealed a nodular lesion within the left thyroid gland showing high Tc-99m MIBI uptake. INTERVENTIONS: Left thyroid lumpectomy confirmed the lesion as follicular thyroid carcinoma. On the second Tc-99m MIBI scan conducted after total thyroidectomy, a parathyroid adenoma was eventually detected in the right lower area, enabling the subsequent appropriate treatment, a right lower parathyroidectomy. OUTCOMES: Thirteen days after the parathyroidectomy, serum levels of total calcium and parathyroid hormone returned to normal. Furthermore, bone mineral density evaluated using DEXA remained within the expected range for her age even after 14 months. LESSONS: When interpreting the Tc-99m MIBI scan, it is essential to keep in mind that various tumors rich in mitochondria, such as thyroid carcinoma, could show a high uptake of Tc-99m MIBI.

[Interpretation of the pathological diagnostic criteria and characteristics of high-grade thyroid follicular-derived carcinoma in the 5th edition WHO classification].

The 5th edition WHO classification of thyroid tumors proposed high-grade non-anaplastic thyroid carcinoma, which includes traditional poorly differentiated thyroid carcinoma (PDTC) and differentiated high-grade thyroid carcinoma (DHGTC), with a prognosis between highly differentiated thyroid carcinoma and anaplastic thyroid carcinoma (ATC), in which about 50% of patients do not take radioactive iodine. Therefore, this classification is of great clinical significance. This article interprets the diagnostic criteria and genetic features of high-grade non-anaplastic thyroid carcinoma in 5th edition WHO classification, comparing with ATC.

Follow-up and Outcomes of 186 Patients With Follicular Cell-Derived Thyroid Cancer Seen at a Referral Center by One Thyroidologist in 2015.

OBJECTIVE: To study the profile, management, and outcomes of follicular cell-derived thyroid cancer (FCDTC) before publication of the 2016 American Thyroid Association guidelines recommending less-aggressive thyroid cancer procedures. METHODS: Patients with FCDTC were seen by one thyroidologist at Mayo Clinic during the 2015 calendar year. Patients underwent surgical procedures for FCDTC in 2015 or earlier at Mayo Clinic or another institution. Follow-up data were collected from January 1, 2016, through July 20, 2022. Outcomes measured included tumor characteristics, treatment methods, adverse effects, diagnostic imaging methods, and primary tumor/metastasis status at the last follow-up. RESULTS: Of 186 included patients, 85 had total or near-total thyroidectomy. Bilateral disease was present in 35.5% of these patients, and contralateral involvement would have been missed by lobectomy for 9 (10%) patients with low-risk thyroid cancer. Additionally, 57% had positive neck lymph nodes identified during their surgical procedure, 25% (21% in central compartment) of which were undetected by preoperative ultrasonography. At the last follow-up, 65.6% of patients had no evidence of disease and 10.7% had distant metastases. CONCLUSION: This report outlines the profile and outcomes of patients with FCDTC who were treated at a referral center before the revised 2016 American Thyroid Association guidelines. Lobectomy for low-risk FCDTC may miss some cancer in the contralateral lobe. However, the clinical importance of these missed microcarcinomas is unclear. Preoperative ultrasonography effectively predicts lateral, but not central compartment, nodal metastases.

The value of a neural network based on multi-scale feature fusion to ultrasound images for the differentiation in thyroid follicular neoplasms.

OBJECTIVE: The objective of this research was to create a deep learning network that utilizes multiscale images for the classification of follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) through preoperative US. METHODS: This retrospective study involved the collection of ultrasound images from 279 patients at two tertiary level hospitals. To address the issue of false positives caused by small nodules, we introduced a multi-rescale fusion network (MRF-Net). Four different deep learning models, namely MobileNet V3, ResNet50, DenseNet121 and MRF-Net, were studied based on the feature information extracted from ultrasound images. The performance of each model was evaluated using various metrics, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, F1 value, receiver operating curve (ROC), area under the curve (AUC), decision curve analysis (DCA), and confusion matrix. RESULTS: Out of the total nodules examined, 193 were identified as FTA and 86 were confirmed as FTC. Among the deep learning models evaluated, MRF-Net exhibited the highest accuracy and area under the curve (AUC) with values of 85.3% and 84.8%, respectively. Additionally, MRF-Net demonstrated superior sensitivity and specificity compared to other models. Notably, MRF-Net achieved an impressive F1 value of 83.08%. The curve of DCA revealed that MRF-Net consistently outperformed the other models, yielding higher net benefits across various decision thresholds. CONCLUSION: The utilization of MRF-Net enables more precise discrimination between benign and malignant thyroid follicular tumors utilizing preoperative US.

A comparison of the WHO 2004 and WHO 2017 thyroid tumor classifications.

INTRODUCTION: The category of borderline malignancy or unknown malignant potential was added to the WHO's 2017 classification of thyroid tumours. A new histological variety of papillary tumours and Hurthle cell tumours was given as a separate entity. The classification has also adopted the Turin criteria for histological diagnosis of poorly differentiated cancer (PDC). SETTINGS AND DESIGN: Descriptive study. METHODS AND MATERIAL: From July 2018 to June 2022, 200 thyroid neoplasm patients at a tertiary care facility in western Maharashtra were participated in the prospective research over a period of 4 years. STATISTICAL ANALYSIS USED: The descriptive statistics were used to analyse the collected data. AIM: This study was undertaken to compare the old (2004) and new (2016) WHO classifications and their importance in the treatment of thyroid malignancies. RESULTS: Out of 200 cases, the age range of 31 to 40 years had the greatest number of cases. The ratio of females to males was 5:1. In our study, according to the WHO 2004 classification, malignant tumours comprised 57.5% of the cases, while benign tumours 42.5% of the cases. When tumours were subcategorized, the most frequent benign tumour was follicular adenoma (43.5%) and malignant tumour was papillary thyroid carcinoma (37%). Malignant tumours made up 47.5% of the cases when the tumours were reclassified using the revised WHO 2017 classification, followed by borderline tumours with 27.5% of the cases and benign tumours with 25% of the cases. The most frequent borderline tumour was NIFTP (Noninvasive follicular thyroid neoplasm with papillary-like nuclear features) (17.5%), the most prevalent malignant tumour was papillary carcinoma (including its variant) (32%), and the most frequent benign tumour was follicular adenoma (27%). CONCLUSION: We concluded that the inclusion of the Boderline Category in the new WHO classification significantly improved thyroid cancer management. WHO 2017 classification prevents under diagnosis (in the case of benign tumors) and over diagnosis (in the case of malignant tumors).

Uptake of 99m Tc-DTPA in Bone Metastases From Follicular Thyroid Carcinoma.

ABSTRACT: A 53-year-old man with follicular thyroid carcinoma (FTC) was referred for renal scintigraphy using 99m Tc-DTPA to assess the kidney function. Unexpectedly, the images showed an abnormal uptake of radiotracer in the right pelvic region. It corresponded to the site of metastasis in the right ilium revealed on 131 I SPECT/CT images. The biopsy pathology of the ilium lesion demonstrated follicular thyroid cancer.

Differentiating BRAF V600E- and RAS-like alterations in encapsulated follicular patterned tumors through histologic features: a validation study.

Differentiating BRAF V600E- and RAS-altered encapsulated follicular-patterned thyroid tumors based on morphology remains challenging. This study aimed to validate an 8-score scale nuclear scoring system and investigate the importance of nuclear pseudoinclusions (NPIs) in aiding this differentiation. A cohort of 44 encapsulated follicular-patterned tumors with varying degrees of nuclear atypia and confirmed BRAF V600E or RAS alterations was studied. Nuclear parameters (area, diameter, and optical density) were analyzed using a deep learning model. Twelve pathologists from eight Asian countries visually assessed 22 cases after excluding the cases with any papillae. Eight nuclear features were applied, yielding a semi-quantitative score from 0 to 24. A threshold score of 14 was used to distinguish between RAS- and BRAF V600E-altered tumors. BRAF V600E-altered tumors typically demonstrated higher nuclear scores and notable morphometric alterations. Specifically, the nuclear area and diameter were significantly larger, and nuclear optical density was much lower compared to RAS-altered tumors. Observer accuracy varied, with two pathologists correctly identifying genotype of all cases. Observers were categorized into proficiency groups, with the highest group maintaining consistent accuracy across both evaluation methods. The lower group showed a significant improvement in accuracy upon utilizing the 8-score scale nuclear scoring system, with notably increased sensitivity and negative predictive value in BRAF V600E tumor detection. BRAF V600E-altered tumors had higher median total nuclear scores. Detailed reevaluation revealed NPIs in all BRAF V600E-altered cases, but in only 2 of 14 RAS-altered cases. These results could significantly assist pathologists, particularly those not specializing in thyroid pathology, in making a more accurate diagnosis.

Impact of fine-needle aspiration cytology in thyroidectomy extent and associated surgical morbidity in thyroid cancer.

PURPOSE: To assess the impact of fine-needle aspiration cytology (FNAC) in the extent of surgery in patients with thyroid cancer (TC) and the associated surgical morbidity in primary and completion setting. METHODS: A Swedish nationwide cohort of patients having surgery for TC (n = 2519) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal surgery between 2004 and 2013 was obtained. Data was validated through scrutinizing FNAC and histology reports. RESULTS: Among the 2519 cases operated for TC, the diagnosis was substantiated and validated through the histology report in 2332 cases (92.6%). Among these, 1679 patients (72%) were female, and the median age at TC diagnosis was 52.3 years (range 18-94.6). Less than total thyroidectomy (LTT) was undertaken in 944 whereas total thyroidectomy (TT) in 1388 cases. The intermediate FNAC categories of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/ FLUS), as well as suspicion for follicular neoplasm (SFN) lesions were more often encountered in LTT (n = 314, 33.3%) than TT (n = 63, 4.6%), whereas FNACs suspicion for malignancy and/or malignancy were overrepresented in TT (n = 963, 69.4%). Completion thyroidectomies were undertaken in 553 patients out of 944 that initially had LTT. In 201 cases with cancer lesions > 1 cm, other than FTC (Follicular TC)/ HTC (Hürthle cell TC) subjected to primary LTT, inadequate procedures were undertaken in 81 due to absent, Bethesda I or II FNAC categories, preoperatively. Complications at completion of surgery in this particular setting were 0.5% for RLN palsy (n = 1) and 1% (n = 2) for hypoparathyroidism 6 months postoperatively. The overall postoperative complication rate was higher in primary TT vs. LTT for RLN palsy (4.8% [n = 67] vs. 2.4% [n = 23]; p = 0.003) and permanent hypoparathyroidism (6.8% [n = 95] vs. 0.8% [n = 8]; p < 0.0001). CONCLUSIONS: FNAC results appear to affect surgical planning in TC as intermediate FNAC categories lead more often to LTT. Overall, inadequate procedures necessitating completion surgery are encountered in up to 15% of TC patients subjected to LTT due to absent, inconclusive, or misleading FNAC, preoperatively. However, completion of thyroidectomy in this setting did not yield significant surgical morbidity. Primary LTT is a safer primary approach compared to TT in respect of RLN palsy and permanent hypoparathyroidism complication rates; therefore, primary TT should probably be reserved for lesions > 1 cm or even larger with suspicion for malignancy or malignant FNAC.

Thyroid Cancer: A Review.

Importance: Approximately 43 720 new cases of thyroid carcinoma are expected to be diagnosed in 2023 in the US. Five-year relative survival is approximately 98.5%. This review summarizes current evidence regarding pathophysiology, diagnosis, and management of early-stage and advanced thyroid cancer. Observations: Papillary thyroid cancer accounts for approximately 84% of all thyroid cancers. Papillary, follicular (≈4%), and oncocytic (≈2%) forms arise from thyroid follicular cells and are termed well-differentiated thyroid cancer. Aggressive forms of follicular cell-derived thyroid cancer are poorly differentiated thyroid cancer (≈5%) and anaplastic thyroid cancer (≈1%). Medullary thyroid cancer (≈4%) arises from parafollicular C cells. Most cases of well-differentiated thyroid cancer are asymptomatic and detected during physical examination or incidentally found on diagnostic imaging studies. For microcarcinomas (≤1 cm), observation without surgical resection can be considered. For tumors larger than 1 cm with or without lymph node metastases, surgery with or without radioactive iodine is curative in most cases. Surgical resection is the preferred approach for patients with recurrent locoregional disease. For metastatic disease, surgical resection or stereotactic body irradiation is favored over systemic therapy (eg, lenvatinib, dabrafenib). Antiangiogenic multikinase inhibitors (eg, sorafenib, lenvatinib, cabozantinib) are approved for thyroid cancer that does not respond to radioactive iodine, with response rates 12% to 65%. Targeted therapies such as dabrafenib and selpercatinib are directed to genetic mutations (BRAF, RET, NTRK, MEK) that give rise to thyroid cancer and are used in patients with advanced thyroid carcinoma. Conclusions: Approximately 44 000 new cases of thyroid cancer are diagnosed each year in the US, with a 5-year relative survival of 98.5%. Surgery is curative in most cases of well-differentiated thyroid cancer. Radioactive iodine treatment after surgery improves overall survival in patients at high risk of recurrence. Antiangiogenic multikinase inhibitors and targeted therapies to genetic mutations that give rise to thyroid cancer are increasingly used in the treatment of metastatic disease.

Incidental thyroid carcinoma in an endemic goiter area in Italy: histopathological features and predictors of a common finding.

PURPOSE: The occurrence and histopathological features of incidental thyroid carcinoma (ITC) vary considerably among populations from different geographical regions. The aim of this study is to assess the prevalence and histopathological characteristics of ITC in patients who underwent thyroid surgery for apparently benign thyroid diseases in an endemic goiter area in Italy. METHODS: A total of 649 consecutive patients (531 females and 118 males; mean age, 52.9 ± 11.0 years), who underwent thyroid surgery at the Endocrine Surgery Unit of the tertiary care "Renato Dulbecco" University Hospital (Catanzaro, Italy) in the period between years 2017 and 2022, were included in this retrospective study. A comprehensive histopathological examination was performed on surgically excised thyroid tissue. Logistic regression analysis was employed to identify potential predictors of ITC. RESULTS: The histopathological examination revealed the presence of ITC in 81 patients, accounting for 12.5% of the total study population. The female to male ratio was found to be 6.4 to 1. Among the patients with ITC, 72 had papillary carcinoma (PTC), with 53 of these tumors being microcarcinomas (microPTC). Additionally, 5 patients had follicular thyroid carcinoma, 2 patients had low-risk follicular cell-derived thyroid neoplasms, 1 patient had an oncocytic carcinoma, and 1 patient had a medullary thyroid carcinoma. Logistic regression analysis demonstrated a significant association between female sex and incidental microPTC. CONCLUSIONS: These findings provide further evidence of the common occurrence of ITC, typically in the form of microPTC, among individuals who undergo thyroid surgery for apparently benign thyroid diseases.

Circulating small extracellular vesicle-based miRNA classifier for follicular thyroid carcinoma: a diagnostic study.

BACKGROUND: The diagnosis of follicular thyroid carcinoma (FTC) prior to surgery remains a major challenge in the clinic. METHODS: This multicentre diagnostic study involved 41 and 150 age- and sex-matched patients in the training cohort and validation cohort, respectively. The diagnostic properties of circulating small extracellular vesicle (sEV)-associated and cell-free RNAs were compared by RNA sequencing in the training cohort. Subsequently, using a quantitative real-time polymerase chain reaction (qRT‒PCR) assay, high-quality candidates were identified to construct an RNA classifier for FTC and verified in the validation cohort. The parallel expression, stability and influence of the RNA classifier on surgical strategy were also investigated. RESULTS: The diagnostic properties of sEV long RNAs, cell-free long RNAs and sEV microRNAs (miRNAs) were comparable and superior to those of cell-free miRNAs in RNA sequencing. Given the clinical application, the circulating sEV miRNA (CirsEV-miR) classifier was developed from five miRNAs based on qRT‒PCR data, which could well identify FTC patients (area under curve [AUC] of 0.924 in the training cohort and 0.844 in the multicentre validation cohort). Further tests revealed that the CirsEV-miR score was significantly correlated with the tumour burden, and the levels of sEV miRNAs were also higher in sEVs from the FTC cell line, organoid and tissue. Additionally, circulating sEV miRNAs remained constant after different treatments, and the addition of the CirsEV-miR classifier as a biomarker improves the current surgical strategy. CONCLUSIONS: The CirsEV-miR classifier could serve as a noninvasive, convenient, specific and stable auxiliary test to help diagnose FTC following ultrasonography.

A Comprehensive Approach to the Thyroid Bethesda Category III (AUS) in the Transition Zone Between 2nd Edition and 3rd Edition of The Bethesda System for Reporting Thyroid Cytopathology: Subcategorization, Nuclear Scoring, and More.

Significant interobserver variabilities exist for Bethesda category III: atypia of undetermined significance (AUS) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Thus, subcategorization of AUS including AUS "nuclear" and AUS "other" is proposed in the recent 3rd edition of TBSRTC. This study investigated the impact of the nuclear features/architectural features/nuclear score (NS) (3-tiered)/subcategories and subgroups on risk of malignancy (ROM) in thyroid fine-needle aspirations (FNA). 6940 FNAs were evaluated. 1224 (17.6%) cases diagnosed as AUS were reviewed, and 240 patients (initial FNAs of 260 nodules and 240 thyroidectomies) were included. Subcategories and subgroups were defined according to TBSRTC 2nd and 3rd editions. Histological diagnostic groups included nonneoplastic disease, benign neoplasm, low-risk neoplasm, and malignant neoplasm. Overall, ROM was 30.7%. ROM was significantly higher in FNAs with nuclear overlapping (35.5%), nuclear molding (56.9%), irregular contours (42.1%), nuclear grooves (74.1%), chromatin clearing (49.4%), and chromatin margination (57.7%), and these features were independent significant predictors for malignancy. FNAs with NS3 had significantly higher ROM (64.2%). Three-dimensional groups were significantly more frequent in malignant neoplasms (35.7%). ROM was significantly higher in AUS-nuclear subcategory (48.2%) and in AUS-nuclear and architectural subcategory (38.3%). The highest ROM was detected in AUS-nuclear1 subgroup (65.2%). ROM was significantly higher in the group including AUS-nuclear and AUS-nuclear and architectural subcategories, namely "high-risk group" than the group including other subcategories, namely "low-risk group" (42.0%vs 13.9%). In conclusion, subcategorization may not be the end point, and nuclear scoring and evaluation of architectural patterns according to strict criteria may provide data for remodeling of TBSRTC categories.

The Role of 5-Hydroxymethylcytosine as a Potential Epigenetic Biomarker in a Large Series of Thyroid Neoplasms.

Cytosine modifications at the 5-carbon position play a critical role in gene expression regulation and have been implicated in cancer development. 5-Hydroxymethylcytosine (5hmC), arising from 5-methylcytosine (5-mC) oxidation, has shown promise as a potential malignancy marker due to its depletion in various human cancers. However, its significance in thyroid tumors remains underexplored, primarily due to limited data. In our study, we evaluated 5hmC expression levels by immunohistochemistry in a cohort of 318 thyroid tumors. Our analysis revealed significant correlations between 5hmC staining extension scores and nodule size, vascular invasion, and oncocytic morphology. Nuclear 5hmC staining intensity demonstrated associations with focality, capsule status, extrathyroidal extension, vascular invasion, and oncocytic morphology. Follicular/oncocytic adenomas exhibited higher 5hmC expression than uncertain malignant potential (UMP) or noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), as well as malignant neoplasms, including papillary thyroid carcinomas (PTCs), oncocytic carcinomas (OCAs), follicular thyroid carcinomas (FTCs), and invasive encapsulated follicular variants of PTC (IEFV-PTC). TERT promoter mutation cases showed notably lower values for the 5hmC expression, while RAS (H, N, or K) mutations, particularly HRAS mutations, were associated with higher 5hmC expression. Additionally, we identified, for the first time, a significant link between 5hmC expression and oncocytic morphology. However, despite the merits of these discoveries, we acknowledge that 5hmC currently cannot segregate minimally invasive from widely invasive tumors, although 5hmC levels were lower in wi-FPTCs. Further research is needed to explore the potential clinical implications of 5hmC in thyroid tumors.

Diagnostic models for predicting malignancy in thyroid nodules classified as Bethesda Category III in an endemic region.

BACKGROUND: This study aims to develop a diagnostic model to help physicians determine whether thyroid nodules categorized as atypia of undetermined significance (AUS) in category III of the Bethesda system are benign or malignant preoperatively. To create a diagnostic model for predicting thyroid nodules' benign or malignant with AUS cytology based on clinical, ultrasonographic, and cytopathological findings. METHODS: This is a retrospective cohort study involving patients (>19) at risk of thyroid cancer who had thyroidectomy after an AUS cytology. The dataset consists of 53 variables 204 nodules from 183 patients. Binary logistic regression and factor analysis methods were used to identify risk factors for malignancy. Finally, four prediction models were developed using different approaches, based on clinical, pathological clinical + pathological, and the factors. RESULTS: A total of 88 (48.1%) of 183 patients diagnosed with AUS were benign and 95 (51.9%) the malignant. After determining risk factors, four prediction models were developed based on different approaches to assist physicians in deciding to detect AUS nodules early. It was seen that bilaterality was found to be a risk factor for malignancy in the clinical model (pbilaterality = .03) and it was also seen that the pathological variables pale chromatin and irregular contours in the oncocyte variables were risk factors for malignancy (ppalechromatin = .02, pirregularcontoursintheoncocyte = .04). The best model obtained sensitivity and specificity values are 73% and 87% based on clinical and pathological variables. CONCLUSION: This comprehensive study may provide a more in-depth understanding of AUS and make a notable contribution to healthcare professionals before surgery.

Molecular Alterations and Comprehensive Clinical Management of Oncocytic Thyroid Carcinoma: A Review and Multidisciplinary 2023 Update.

Importance: Oncocytic (Hürthle cell) thyroid carcinoma is a follicular cell-derived neoplasm that accounts for approximately 5% of all thyroid cancers. Until recently, it was categorized as a follicular thyroid carcinoma, and its management was standardized with that of other differentiated thyroid carcinomas. In 2022, given an improved understanding of the unique molecular profile and clinical behavior of oncocytic thyroid carcinoma, the World Health Organization reclassified oncocytic thyroid carcinoma as distinct from follicular thyroid carcinoma. The International Thyroid Oncology Group and the American Head and Neck Society then collaborated to review the existing evidence on oncocytic thyroid carcinoma, from diagnosis through clinical management and follow-up surveillance. Observations: Given that oncocytic thyroid carcinoma was previously classified as a subtype of follicular thyroid carcinoma, it was clinically studied in that context. However, due to its low prevalence and previous classification schema, there are few studies that have specifically evaluated oncocytic thyroid carcinoma. Recent data indicate that oncocytic thyroid carcinoma is a distinct class of malignant thyroid tumor with a group of distinct genetic alterations and clinicopathologic features. Oncocytic thyroid carcinoma displays higher rates of somatic gene variants and genomic chromosomal loss of heterozygosity than do other thyroid cancers, and it harbors unique mitochondrial DNA variations. Clinically, oncocytic thyroid carcinoma is more likely to have locoregional (lymph node) metastases than is follicular thyroid carcinoma-with which it was formerly classified-and it develops distant metastases more frequently than papillary thyroid carcinoma. In addition, oncocytic thyroid carcinoma rarely absorbs radioiodine. Conclusions and Relevance: The findings of this review suggest that the distinct clinical presentation of oncocytic thyroid carcinoma, including its metastatic behavior and its reduced avidity to radioiodine therapy, warrants a tailored disease management approach. The reclassification of oncocytic thyroid carcinoma by the World Health Organization is an important milestone toward developing a specific and comprehensive clinical management for oncocytic thyroid carcinoma that considers its distinct characteristics.

Expression of RASSF1A, DIRAS3, and AKAP9 Genes in Thyroid Lesions: Implications for Differential Diagnosis and Prognosis of Thyroid Carcinomas.

Thyroid carcinoma is the primary endocrine malignancy worldwide. The preoperative examination of thyroid tissue lesion is often unclear. Approximately 25% of thyroid cancers cannot be diagnosed definitively without post-surgery histopathological examination. The assessment of diagnostic and differential markers of thyroid cancers is needed to improve preoperative diagnosis and reduce unnecessary treatments. Here, we assessed the expression of RASSF1A, DIRAS3, and AKAP9 genes, and the presence of BRAF V600E point mutation in benign and malignant thyroid lesions in a Polish cohort (120 patients). We have also performed a comparative analysis of gene expression using data obtained from the Gene Expression Omnibus (GEO) database (307 samples). The expression of RASSF1A and DIRAS3 was decreased, whereas AKAP9's was increased in pathologically changed thyroid compared with normal thyroid tissue, and significantly correlated with e.g., histopathological type of lesion papillary thyroid cancer (PTC) vs follicular thyroid cancer (FTC), patient's age, tumour stage, or its encapsulation. The receiver operating characteristic (ROC) analysis for the more aggressive FTC subtype differential marker suggests value in estimating RASSF1A and AKAP9 expression, with their area under curve (AUC), specificity, and sensitivity at 0.743 (95% CI: 0.548-0.938), 82.2%, and 66.7%; for RASSF1A, and 0.848 (95% CI: 0.698-0.998), 54.8%, and 100%, for AKAP9. Our research gives new insight into the basis of the aggressiveness and progression of thyroid cancers, and provides information on potential differential markers that may improve preoperative diagnosis.