Papillary Carcinoma Research Articles

Clinical and Sonographic Differences between RET Fusion-Positive and BRAFV600E in Papillary Thyroid Carcinoma

Abstract Purpose This study aimed to describe the ultrasound characteristics of papillary thyroid carcinoma (PTC) harboring RET gene fusion and explore its clinical significance. Methods A retrospective study was conducted on 209 patients with PTC diagnosed between Aug 2021 and Jan 2024. All patients underwent ultrasound examination and were confirmed to be positive for RET fusion or BRAFV600E by pathological results. The differences in clinical characteristics and ultrasonography features between the two groups were analyzed. Results Among all PTCs (n=209), we detected 30 RET fusions, and 179 BRAFV600E. RET-fusion PTCs showed younger age (38.5(16.0-69.0) vs. 42.9(20.0-74.0) years, p<.05), larger tumor size (1.09(0.5-4.0) vs. 0.77(0.1-4.0) cm, p<.005), and more advanced N stage (p<.001) than BRAFV600E PTCs. RET-fusion PTCs were mainly classical and diffuse sclerosing subtypes. In terms of ultrasound performance, RET-fusion PTCs were mainly manifested as heterogeneous echogenicity (43.3%), ill-defined tumor margin (90.0%), irregular shape (83.3%) and intranodular microcalcification (83.3%), characterized by scattered microcalcification around the tumor/within thyroid gland (40.0%). In comparison, BRAFV600E PTCs were mainly characterized by hypoechogenicity (95.5%), round/oval shape (80.4%), and intranodular non-calcification (54.2%). Multivariate logistic regression analysis revealed that scattered microcalcification around the tumor/within the normal gland was an independent risk factor for lateral lymph node metastasis (LLNM) in RET-fusion PTCs (OR 9.79, 95% CI, 1.31, 72.93, P=.026). Conclusions Patients diagnosed with PTC harboring RET fusion presented with distinctive clinical characteristics and sonographic patterns, underscoring the unique diagnostic value of ultrasound examination. It can provide a preoperative non-invasive primary screening method for RET-fusion diagnosis, thus facilitating targeted patients with purposeful molecular sequencing to improve treatment outcomes.

Impact of nodal status evaluation on therapeutic strategy for clinically unifocal T1b/small T2 node negative papillary thyroid carcinoma

Impact of nodal status evaluation on therapeutic strategy for clinically unifocal T1b/small T2 node negative papillary thyroid carcinoma

Corrigendum: Predictive factor of large‐volume central lymph node metastasis in clinical N0 papillary thyroid carcinoma patients underwent total thyroidectomy

Corrigendum: Predictive factor of large‐volume central lymph node metastasis in clinical N0 papillary thyroid carcinoma patients underwent total thyroidectomy

Expression of TSPAN1 and its link to thyroid nodules: one step forward on the path to thyroid tumorigenesis biomarkers.

Thyroid cancer is ranked as the most common malignancy within the endocrine system and the seventh most prevalent cancer in women globally. Thyroid malignancies require evaluating biomarkers capable of distinguishing between them for accurate diagnosis. We examined both mRNA and protein levels of TSPAN1 in plasma and tissue samples from individuals with thyroid nodules to aid this endeavour. In this case-control study, TSPAN1 was assessed at both protein and mRNA levels in 90 subjects, including papillary thyroid cancer (PTC; N = 60), benign (N = 30), and healthy subjects (N = 26) using enzyme-linked immunosorbent assay (ELISA) and SYBR-Green Real-Time PCR, respectively. TSPAN1 plasma levels were decreased in PTC and benign compared to healthy subjects (P = 0.002). TSPAN1 mRNA levels were also decremented in the tumoral compared to the paired normal tissues (P = 0.012); this drop was also observed in PTC patients compared to benign patients (P = 0.001). Further, TSPAN1 had an appropriate diagnostic value for detecting PTC patients from healthy plasma samples with a sensitivity of 76.7% and specificity of 65.4% at the cutoff value < 2.7 (ng/ml). TSPAN1 levels are significantly reduced in patients with benign and PTC, demonstrating its potential value as a diagnostic biomarker. Additionally, the significant reduction in TSPAN1 mRNA expression within PTC tumor tissues may suggest its involvement in tumor progression and development. Further studies, including larger-scale validation studies and mechanistic investigations, are imperative to clarify the molecular mechanisms behind TSPAN1 and, ultimately, its clinical utility for treating thyroid disorders.

Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, characterized by a range of subtypes that differ in their cytologic features, clinical behavior, and prognosis. Accurate cytologic evaluation of PTC using fine-needle aspiration is essential but can be challenging due to the morphologic diversity among subtypes. This review focuses on the distinct cytologic characteristics of various PTC subtypes, including the classic type, follicular variant, tall cell, columnar cell, hobnail, diffuse sclerosing, Warthin-like, solid/trabecular, and oncocytic PTCs. Each subtype demonstrates unique nuclear features, architectural patterns, and background elements essential for diagnosis and differentiation from other thyroid lesions. Recognizing these distinct cytologic patterns is essential for identifying aggressive subtypes like tall cell, hobnail, and columnar cell PTCs, which have a higher risk of recurrence, metastasis, and poorer clinical outcomes. Additionally, rare subtypes such as diffuse sclerosing and Warthin-like PTCs present unique cytologic profiles that must be carefully interpreted to avoid diagnostic errors. The review also highlights the cytologic indicators of lymph node metastasis and high-grade features, such as differentiated high-grade thyroid carcinoma. The integration of molecular testing can further refine subtype diagnosis by identifying specific genetic mutations. A thorough understanding of these subtype-specific cytologic features and molecular profiles is vital for accurate diagnosis, risk stratification, and personalized management of PTC patients. Future improvements in diagnostic techniques and standardization are needed to enhance cytologic evaluation and clinical decision-making in thyroid cancer.

Association of the Preoperative Controlling Nutritional Status (CONUT) Score with Clinicopathological Characteristics in Patients with Papillary Thyroid Carcinoma.

The Controlling Nutritional Status (CONUT) score is an immunonutritional test tool based on serum albumin, total cholesterol, and lymphocyte counts. It has been studied as a simple prognostic predictor for various carcinomas. This study aimed to investigate the association between preoperative CONUT scores and the clinicopathological characteristics in papillary thyroid carcinoma (PTC) patients. This study included 2,403 PTC patients who underwent total thyroidectomy between 2012 and 2016 at a single tertiary medical center. The CONUT scores were calculated based on preoperative blood tests. The clinicopathological characteristics were retrospectively reviewed. The patients were categorized by the CONUT score (relatively low, 0-2; relatively high, 3-5). Among the 2,997 PTC patients who underwent total thyroidectomy at Pusan National University Hospital between 2012 and 2016, those without preoperative blood test were excluded (n=149). Finally 2,403 patients were analyzed after excluding 439 patients taking lipid-lowering drugs and six patients without available T stage data after surgery. Based on the CONUT score, the relatively high score group had a lower body mass index (23.7±3.3 kg/m2 vs. 21.9±2.9 kg/m2, P<0.001), more advanced T stage (T stage 3/4, 5.9% vs. 11.4%, P=0.045), and higher extrathyroidal extension (2.1% vs. 7.6%, P=0.005). Patients included in this large, single-center study all had a preoperative CONUT score of 0-5, but this study demonstrated that higher preoperative CONUT scores were significantly associated with advanced T stage and extrathyroidal extension. The CONUT score, which can be easily used in clinical practice, is thought to be helpful in predicting the aggressiveness of PTC.

Prediction of lateral lymph node metastasis with short diameter less than 8mm in papillary thyroid carcinoma based on radiomics.

The aim of this study was to establish an ensemble learning model based on clinicopathological parameter and ultrasound radomics for assessing the risk of lateral cervical lymph node with short diameter less than 8mm (small lymph nodes were used instead) metastasis in patients with papillary thyroid cancer (PTC), thereby guiding the selection of surgical methods. This retrospective analysis was conducted on 454 patients diagnosed with papillary thyroid carcinoma who underwent total thyroidectomy and lateral neck lymph node dissection or lymph node intraoperative frozen section biopsy at the First Hospital of China Medical University between January 2015 and April 2022. In a ratio of 8:2, 362(80%) patients were assigned to the training set and 92(20%) patients were assigned to the test set. Clinical pathological features and radomics features related to ultrasound imaging were extracted, followed by feature selection using recursive feature elimination (RFE). Based on distinct feature sets, we constructed ensemble learning models comprising random forest (RF), extreme gradient boosting (XGBoost), categorical boosting (CatBoost), gradient boosting decision tree (GBDT), and light gradient boosting machine (Lightgbm) to develop clinical models, radiomics models, and clinical-radiomic models. Through the comparison of performance metrics such as area under curve (AUC), accuracy (ACC), specificity (SPE), precision (PRE), recall rate, F1 score, mean squared error (MSE) etc., we identified the optimal model and visualized its results using shapley additive exPlanations (SHAP). In this study, a total of 454 patients were included, among whom 342 PTC patients had small lymph node metastasis in the lateral neck region, while 112 did not have any metastasis. A total of 1035 features were initially considered for inclusion in this study, which were then narrowed down to 10 clinical features, 8 radiomics features, and 17 combined clinical-omics features. Based on these three feature sets, a total of fifteen ensemble learning models were established. In the test set, RF model in the clinical model is outperforms other models (AUC = 0.72, F1 = 0.75, Jaccard = 0.60 and Recall = 0.84), while CatBoost model in the radiomics model is superior to other models (AUC = 0.91, BA = 0.83 and SPE = 0.76). Among the clinical-radiomic models, Catboost exhibits optimal performance (AUC = 0.93, ACC = 0.88, BA = 0.87, F1 = 0.91, SPE = 0.83, PRE = 0.88, Jaccard = 0.83 and Recall = 0.92). Using the SHAP algorithm to visualize the operation process of the clinical-omics CatBoost model, we found that clinical omics features such as central lymph node metastasis (CLNM), Origin_Shape_Sphericity (o_shap_sphericity), LoG-sigma3_first order_ Skewness (log-3_fo_skewness), wavelet-HH_first order_Skewness (w-HH_fo_skewness) and wavelet-HH_first order_Skewness (sqr_gldm_DNUN) had the greatest impact on predicting the presence of lateral cervical small lymph node metastasis in PTC patients. (1) In this study, among the ensemble learning models established based on clinicopathological features and radiomics features for predicting PTC lateral small lymph node metastasis, the clinical-radiomic CatBoost model has the best performance. (2) SHAP can visualize how the clinical and radiomics features affect the results and realize the interpretation of the model. (3) The combined CatBoost model can improve the diagnostic accuracy of suspicious lymph nodes with short diameter < 8mm that are difficult to obtain accurate puncture results. The combined application of radiomics features is more accurate and reasonable than the prediction of clinical data alone, which helps to accurately evaluate the surgical scope and provide support for individual clinical decision making.

Safety and Effectiveness of Percutaneous Ethanol Injection as a Treatment for Locally Recurrent Papillary Thyroid Carcinoma

Background: Reoperation for recurrent papillary thyroid cancer (PTC) is associated with a high risk of complications and limited success in achieving sustained remission. Percutaneous ethanol injection (PEI) presents a potential non-surgical alternative for managing locally recurrent PTC. Objectives: This study aimed to evaluate the safety and effectiveness of PEI in treating recurrent PTC. Methods: From October 2017 to September 2021, PEI was administered to 39 recurrent lesions (23 lateral and 16 central) in 17 patients with PTC. The median follow-up duration was 21.4 months (range, 4.1 - 37.9), with ethanol injections delivered every 3 months under ultrasound (US) guidance as needed. Results: Most patients tolerated the treatment well, experiencing only mild local pain, though one patient reported Horner syndrome following the procedure. In terms of treatment frequency, 31 lesions required 3 or fewer injections, while the remaining lesions required more. The mean initial volume of the lesions decreased from 0.12 mm³ (range: 0.06 - 0.34 mm³) to 0.03 mm³ (range: 0.0 - 0.14 mm³), representing an average reduction of 72.6% (range: 20.0 - 100.0%). Of the 39 lymph nodes treated in 17 patients, 21 lymph nodes (54%) were completely resolved. Seven lymph nodes remain under ongoing ethanol treatment, while 11 lymph nodes in 4 patients were addressed with alternative treatments, including surgery. Conclusions: Percutaneous ethanol injection appears to be a safe and effective treatment option for managing locally recurrent thyroid carcinomas in select patients. However, further comparative, prospective, long-term studies are needed to evaluate PEI’s impact on patient survival and recurrence rates.

Detection of genetic mutations in 855 cases of papillary thyroid carcinoma by next generation sequencing and its clinicopathological features.

To investigate the genetic mutations in patients with papillary thyroid carcinoma (PTC) and their clinicopathological features by next generation sequencing (NGS). NGS technology was used to detect genetic mutations in PTC patients, and clinicopathological features were collected. ①Among 855 PTC patients, 810 patients had genetic mutations, and 45 patients had no genetic mutation. ②BRAF mutation was associated with tumor diameter (P < 0.001) and histological subtypes (P = 0.002). The abundance of V600E mutation was associated with gender (P = 0.004), tumor diameter (P < 0.001), bilateral presentation (P = 0.001), extrathyroidal extension (P < 0.001), lymphatic metastasis (P < 0.001), histological subtypes (P = 0.002) and TNM staging (P = 0.000); The different mutation abundance of V600E was associated with tumor diameter (P < 0.001), multifocal presentation (P = 0.047), bilateral presentation (P = 0.001), extrathyroidal extension (P = 0.001), lymphatic metastasis (P < 0.001), histological subtypes (P = 0.022) and TNM staging (P = 0.000). ③RET fusion was associated with tumor diameter (P < 0.001) and lymphatic metastasis (P = 0.005). ④TERT mutation was associated with gender (P = 0.043), tumor diameter (P < 0.001), extrathyroidal extension (P = 0.028) and TNM staging (P = 0.017). ⑤RAS mutation was associated with histological subtypes (P < 0.001). ⑥NTRK and PIK3CA mutations were not associated with clinicopathological features. NGS technology can comprehensively analyze the genetic mutations in PTC patients, which provides important prompts for the occurrence, development, diagnosis and treatment of PTC. In addition, BRAF V600E mutation, RET fusion and TERT mutation are associated with a number of high-risk clinicopathological features. Detection of genetic mutations in PTC patients by NGS is of great significance.

Sternal resection and reconstruction with a titanium plate and polypropylene mesh for sternal metastasis of papillary thyroid carcinoma: A case report

Sternal resection and reconstruction with a titanium plate and polypropylene mesh for sternal metastasis of papillary thyroid carcinoma: A case report

Spatial and Single-Cell Transcriptomics Unraveled Spatial Evolution of Papillary Thyroid Cancer.

Recurrence and metastasis are the major issues for papillary thyroid cancer (PTC). Current morphological and molecular classification systems are not satisfied for PTC diagnosis due to lacking variant-specific morphological criteria and high signal-to-noise in mutation-based diagnosis, respectively. Importantly, intratumor heterogeneity is largely lost in current molecular classification system, which can be resolved by single cell RNA sequencing (scRNA-seq). However, scRNA-seq loses spatial information and morphological features. Herein, scRNA-seq is integrated and spatially-resolved transcriptomics (SRT) to elaborate the mechanisms underlying the spatial heterogeneity, malignancy and metastasis of PTCs by associating transcriptome and local morphology. This results demonstrated that PTC cells evolved with multiple routes, driven by the enhanced aerobic metabolism and the suppressed mRNA translation and protein synthesis and the involvement of cell-cell interaction. Two curated malignant and metastatic footprints can discriminate PTC cells from normal thyrocytes. Ferroptosis resistance contributed to PTC evolution. This results will advance the knowledge of intratumor spatial heterogeneity and evolution of PTCs at spatial and single-cell levels, and propose better diagnostic strategy.

Association of BRAF V600E allele frequency with clinicopathologic outcomes in papillary thyroid cancer.

BRAF V600E mutation is the most common genetic driver of papillary thyroid cancer (PTC), where it is found with various allele frequency (AF), reflecting the proportion of cells carrying the mutant and wild-type gene alleles. To determine whether BRAF V600E AF can improve prognostication and inform initial surgical management of PTC. Retrospective cohort study (2016-2019). UCLA health. Consecutive patients with Bethesda V/VI nodules and isolated BRAF V600E mutation who underwent surgery with histopathology showing PTC. Blinded ThyroSeq v3 molecular analysis after completion of initial management and follow-up. Aggressive histopathology and cancer persistence/recurrence. Of 73 patients, the median BRAF V600E AF was 25.5% (IQR, 16.7-34.3%). Higher median AF was seen in patients classified as American Thyroid Association (ATA) high-risk (37%) vs. intermediate-risk (25.3%, p<0.01) and low-risk (24.7%, p<0.01), largely attributed to higher AF in patients with gross extrathyroidal extension (ETE) (40.1% vs. 25.2% without gross ETE, p=0.02). No differences in AF were observed on the basis of lymph node positivity or presence of aggressive variants of PTC. A higher BRAF V600E AF was also found in patients with tumors ≥2cm vs. <2cm (median 32.0% vs. 24.4%, p<0.01). Over 4.1 years of follow-up, disease persistence/recurrence was found in 7 patients (9.4%) and was associated with higher median AF than those without recurrence (35.3% vs. 25.2%, p=0.02). Higher AF was associated with poorer recurrence-free survival (AF≥35%, HR 7.40, CI 1.4-38.1). Higher AF was associated with gross ETE and increased recurrence risk. This may inform initial management in patients with PTC harboring an isolated BRAF V600E mutation.

Sonography Could Predict Complete/Near-Complete Necrosis of Thyroid Tumors After Fine-Needle Biopsy: Necrotic Ring Sign.

Necrosis, a rare histologic alteration caused by the fine-needle aspiration biopsy (FNA) of thyroid tumors, could be problematic in the clinical management of such cases due to the difficulty in making a definitive histopathologic diagnosis. The aim of this study was to define US features that may help to predict FNA-induced necrosis which is more common in oncocytic tumors. This cross-sectional study consists of all patients who underwent thyroid surgery in our center between January 2011 and December 2023. All nodules, which complete/near-complete necrosis reported on final histopathology, were included into study when full video record of preoperative US exam also available for re-evaluation. US findings of necrotic tumors compared with control group consisting of similar histopathology without necrosis. A total of 11 patients have met the inclusion criteria during study period. Of these cases, seven were papillary thyroid carcinomas and four were follicular adenomas. Among the evaluated distinctive US features, necrotic ring offers the best accuracy (88%) and area under the curve (0.91) values in detecting necrosis after FNA and most valuable when combined with lack of intranodular vascularity. In the preoperative evaluation of surgical candidates, necrotic ring, refractive edge shadowing, posterior acoustic enhancement, and lack of vascular signal may predict complete/near-complete necrosis with great accuracy.

Abstract B006: Rescuing expression of a tumor suppressor gene – restoring FH in Hereditary leiomyomatosis and renal cell carcinoma

Abstract Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a disorder characterized by the loss of fumarate hydratase (FH) activity, leading to the development of cutaneous leiomyomas, uterine leiomyomas, and aggressive early-onset type 2 papillary renal cell carcinoma. In HLRCC, the disease is driven by the somatic loss of the remaining functional FH allele in individuals carrying a germline pathogenic variant in one copy of the FH gene. The complete loss of FH activity disrupts the tricarboxylic acid (TCA) cycle, resulting in the accumulation of fumarate, which disrupts signaling pathways and contributes to the oncogenic phenotype. We recently identified a single nucleotide polymorphism (SNP) in an intronic region of the fumarate hydratase (FH) gene that leads to the loss of FH activity (Crooks et al., 2023). This SNP introduces a novel splice-acceptor site, resulting in the inclusion of an aberrant exon between wild-type exons 9 and 10. This ‘poison-like’ exon encodes a premature STOP codon, producing a nonfunctional truncated FH protein. Previous studies have shown that restoring FH activity can abrogate pathogenic behavior in patient-derived cells, highlighting the potential for therapeutic interventions targeting FH activity restoration. Our goal is to restore FH enzymatic activity by preventing the inclusion of this cryptic exon in carriers of this variant. To achieve this, we are exploring strategies to restore functional FH production by interfering with the inclusion of the pathogenic intron during splicing by removing the splice acceptor using CRISPR-Cas9 or base editing technologies. We tested these approaches by generating a reporter cell line that recapitulates the splicing pattern observed in patients, where expression of GFP depends on correct splicing between exon 9 and 10. We successfully identified antisense oligonucleotide (ASO) and single-guide RNA (sgRNA) sequences that restore GFP expression in our reporter cell lines. We are now evaluating the efficacy of these reagents in patient-derived cells. An alternative approach involves using synthetic RNA to restore FH expression. The expression of proteins from synthetic RNAs is a promising strategy for treating cancer and infectious diseases. We are currently investigating the efficiency of restoring FH activity through in-vitro transcribed (IVT) mRNA. This approach has the advantage of enabling FH function restoration in cells with mutations that are not amenable to antisense oligonucleotide (ASO) or gene editing techniques. This work serves as an avenue to investigate the application of nucleic acid therapies to restoring activity tumor suppressor genes in kidney cancer. Citation Format: Siddhardha S. Maligireddy, Mariana D. Mandler, Jodie C. Lunger, Christina M. Fitzsimmons, Daniel R. Crooks, Geetha M. Cawthon, Christopher J. Ricketts, Cathy D. Vocke, W. Marson Linehan, Pedro J. Batista. Rescuing expression of a tumor suppressor gene – restoring FH in Hereditary leiomyomatosis and renal cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B006.

Squamous Cells in Thyroid Cytology and Their Clinical Significance: A Multi-Institutional Study.

Squamous cells are uncommon in thyroid fine needle aspirations (FNAs) presenting diagnostic challenges. We report our multi-institutional experience. The electronic data were searched for thyroid FNAs containing squamous cells at the Johns Hopkins Medicine, New York University Langone Hospital, United States, and Fimlab Laboratories, Finland (2001-2023). The patients' demographics, clinical history, and pathologic diagnosis were recorded. One hundred and seven cases (103 patients) were identified 35 males and 68 females (median age 58 years). Forty-eight cases (44.9%) were malignant, primary carcinomas with squamous features, such as anaplastic thyroid carcinoma (ATC), and metastatic or directly invasive squamous cell carcinomas (SqCC) including oral, oropharyngeal (HPV-related), esophageal, and laryngeal SqCC. Twenty-seven cases (25.2%) contained benign squamous cells with cystic background, suggestive of developmental cysts. Nineteen cases (17.8%) contained metaplastic benign squamous cells within an adenomatoid nodule. Seven cases (6.5%) contained atypical squamous cells. Four cases (3.7%) showed squamous cells with bacterial or fungal organisms, suggestive of esophageal fistula/diverticulum, and two cases (1.9%) contained benign squamous cells with unknown source. Thirty-six cases had surgical follow-up, 33 (91.7%) were concordant (23 metastatic or directly invasive SqCC, 8 undifferentiated/ATC, and 10 papillary thyroid carcinoma). Ancillary studies were used confirming HPV-related SqCC, or therapeutic targets (BRAF V600E), with highly variable staining in ATC. Squamous cells in thyroid FNAs carry a broad differential diagnosis with variable prognoses. It is crucial to interpret squamous cells in the context of clinical and radiographic findings for optimal patient care.

ASO Author Reflections: Addressing Radioactive Iodine Recommendations in Low-to-Intermediate Risk Papillary Thyroid Cancer.

ASO Author Reflections: Addressing Radioactive Iodine Recommendations in Low-to-Intermediate Risk Papillary Thyroid Cancer.

LncRNA CASC9 facilitates papillary thyroid cancer development and doxorubicin resistance via miR-28-3p/BCL-2 axis and PI3K/AKT signaling pathway.

Papillary thyroid cancer (PTC) is a malignant tumor that poses a serious threat to human health. LncRNA CASC9 serves as an oncogene in numerous tumors. The purpose of this study was to explore the mechanism of lncRNA CASC9 regulating doxorubicin (Dox) resistance in PTC. The expression of CASC9, miR-28-3p and BCL-2 in PTC tissues or dox-resistant cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot (WB). CCK-8, colony formation assay, flow cytometry and transwell assay were used to measure the semi-inhibitory concentration (IC50) of dox, cell proliferation, apoptosis and migration, respectively. Dual luciferase reporter gene assays were performed to verify the targeting relationship between miR-28-3p and CASC9 or BCL-2. Rescue experiments were applied to verify the mechanism of CASC9. Finally, the role of CASC9 was verified by xenograft modeling in vivo. We discovered that CASC9 was enhanced in PTC tissues, cells and Dox-resistant cells (BCPAP/Dox and K1/Dox). Furthermore, CASC9 inhibition markedly restrained the proliferation, migration and facilitated apoptosis of Dox cells. In vivo experiments also showed that silencing of CASC9 inhibited tumor growth. Meanwhile, knockdown of CASC9 sensitized PTC cells to Dox. CASC9 enhanced tumor progression by activating the PI3K/AKT signaling pathway. Furthermore, bioinformatics analysis identified miR-28-3p as a downstream target of CASC9. MiR-28-3p inhibitor reversed the impact of CASC9 knockdown in BCPAP/Dox and K1/Dox. Further studies showed that CASC9 positively regulated BCL-2 expression through miR-28-3p. miR-28-3p weakened Dox resistance, proliferation, migration and accelerated apoptosis of PTC cells via BCL-2. CASC9, as an oncogenic lncRNA, has a promotional effect on Dox resistance and PTC progression via miR-28-3p/BCL-2 axis and PI3K/AKT signaling pathway.

An AI-driven preoperative radiomic subtype for predicting the prognosis and treatment response of patients with papillary thyroid carcinoma.

8-28% of Papillary thyroid carcinoma (PTC) experience recurrence, complicating risk stratification and treatment. We previously identified an inflammatory molecular subtype of PTC associated with poor prognosis. Based on this subtype, we aimed to develop and validate a noninvasive radiomic signature to predict prognosis and treatment response in PTC patients. We collected preoperative ultrasound images from two large independent centers (n=2506) to develop and validate a Deep Learning Radiomics signature of Inflammation (DLRI) for predicting the inflammatory subtype of PTC, including its correlation with prognosis and anti-inflammatory traditional Chinese medicine (TCM) treatment. Training set 1 (n=64) and internal validation set 2 (n=1108) were from Tianjin Medical University Cancer Institute and Hospital. External validation set 1 (n=76) and 2 (n=1258) were from Fudan University Shanghai Cancer Center. We developed DLRI to accurately predict PTC's inflammatory subtype (AUC=0.97 in the training set 1 and AUC=0.82 in the external validation set 1). High-risk DLRI was significantly associated with poor disease-free survival in the first cohort (HR=16.49, 95% CI: 7.92-34.35, P<0.001) and second cohort (HR=5.42, 95%: 3.67-8.02, P<0.001). DLRI independently predicted disease-free survival, irrespective of clinicopathological variables (P<0.001 for all). Furthermore, patients with high-risk DLRI were likely to benefit from anti-inflammatory TCM treatment (HR=0.19, 95% CI: 0.06-0.55, P=0.002), whereas those in low-risk DLRI did not. DLRI is a reliable noninvasive tool for evaluating prognosis and guiding anti-inflammatory TCM treatment in PTC patients. Prospective studies are needed to confirm these findings.

Heterotopic Ossification with Intrathyroidal Extramedullary Hematopoiesis in Multifocal Papillary Thyroid Carcinoma: Histopathological Findings and Literature Review.

In recent decades, there has been an increase in the identification of thyroid nodules, both benign and malignant, due to the rise in imaging studies and complementary tests. Among thyroid gland tumors, papillary thyroid carcinoma (PTC) stands out as the most prevalent. Degenerative changes, mainly in the form of nodular goiter, have been recorded, occasionally including areas of calcification and, more rarely, ossification; although the latter seldom progresses to calcinosis. Ectopic bone formation, known as osseous metaplasia, is a rare phenomenon in the thyroid gland, even more so when associated with extramedullary hematopoiesis (EMH), characterized by the presence of hematopoietic elements outside the bone marrow. We present the first documented instance in our country of a patient diagnosed with malignant thyroid nodule, specifically PTC, exhibiting areas of heterotopic ossification with EMH on histopathological examination of the surgical specimen. A possible relationship between heterotopic ossification, EMH, and PTC is suggested. Various growth factors such as bone morphogenetic proteins (BMPs), specific BMP subtypes, and associated receptors could play a crucial role in initiating and developing ectopic bone formation in the context of PTC. However, further research is needed to fully elucidate its clinical significance and impact on the therapeutic management of these patients.

Lymph node yield independently predicts local recurrence in papillary thyroid cancer.

Lymph node yield (LNY) is a validated quality control parameter in colorectal cancer surgery, with >12 nodes reflecting an adequate oncological resection. No formal guidelines exist in the context of central and lateral compartment lymph node dissection for papillary thyroid cancer (PTC). This study aimed to investigate the association between LNY and regional recurrence in PTC patients, and to define a threshold LNY that indicates adequate compartmental lymphadenectomy. A retrospective analysis of patient data (1992-2022) was conducted using "The University of Sydney Endocrine Surgery Unit" database. Patients undergoing either prophylactic or therapeutic dissection of the central compartment or therapeutic dissection of the lateral compartment for PTC were included. Multivariate logistic regression analysis was performed to examine the relationship between nodal yield and local recurrence. On multivariate analysis, a central LNY ≤3 was an independent adverse prognostic factor for central recurrence (odds ratios [OR] 2.19, 95% confidence intervals [CI] 1.15-4.17, and p=0.018) and a lateral LNY ≤20 was independently predictive of lateral recurrence (OR 2.45, 95% CI 1.24-5.31, and p=0.007). This study highlights the association between LNY and local recurrence in PTC. Our findings suggest that minimum LNY thresholds (>3 for central and >20 for lateral) may serve as indicators of adequate dissection. Further research should validate these findings across healthcare centers.