The association between BRAF V600E mutation and clinicopathological features of papillary thyroid carcinoma (PTC) remains controversial. This study aimed to explore its prognostic value via meta-analysis. Databases including PubMed, Cochrane Library, Embase, and Web of Science were systematically searched for studies published before June 1, 2025. Pooled odds ratio (OR) with 95% confidence interval (CI) was used as the effect size, analyzed by R 4.4.2. A total of 26 studies (2010-2024) involving 13,999 patients were included. BRAF V600E mutation was significantly positively associated with capsular invasion (OR=1.80, 95% CI:1.16-2.78) and extrathyroidal extension (OR=1.62, 95% CI:1.36-1.94), and negatively associated with concomitant Hashimoto's thyroiditis (OR=0.55, 95% CI:0.32-0.94). A marginal association trend was observed with gender, with male patients showing a higher likelihood of harboring the BRAF V600E mutation (OR=1.26, 95% CI:1.10-1.44, P=0.0525), while no significant associations were found with age, tumor size, multifocality, central or lateral lymph node metastasis. BRAF V600E mutation correlates with specific clinicopathological features of PTC and serves as a potential prognostic predictor.

Abstract Background Thyroid lobectomy (TL) is the gold standard approach for small (<2cm) low-risk papillary thyroid carcinomas (PTC), yet it leads to postoperative hypothyroidism in approximately 60% of cases. Active surveillance or parenchyma-sparing thyroidectomy (PST) (isthmectomy or tumour enucleation) may represent conservative but safe options. This study evaluated the efficacy and safety of PST compared with TL in patients with low-risk PTC who declined active surveillance. Methods A prospective study started in December 2023. Eligible patients had PTC ≤15mm without extrathyroidal extension or lymph node metastasis, with a tumour–capsule distance of ≥2 and <10mm. All patients received comprehensive counselling and freely choose between PST and TL. The primary endpoint was structural recurrence, defined by postoperative ultrasound. Secondary endpoints included complication rate, operative time, and the need for and dosage of levothyroxine therapy. Results Sixty-three patients were enrolled: 27 (42.9%) underwent PST and 36 (57.1%) TL. Baseline and histological features did not differ between groups. No positive surgical margins or disease recurrence at 6 months were observed in both groups. Complication rate was similar between groups (3.7% vs. 5.6%; p=0.732). TL was associated with a longer operative time (40 vs. 30 minutes; p<0.001), a higher rate of levothyroxine requirement at 6 months (52.8% vs. 18.5%; p=0.005), and a higher levothyroxine dosage (72.7 vs. 65.5 μg/day; p=0.028). Conclusion PST appears safe and effective for selected patients with small, low-risk PTC and offers improved preservation of thyroid function. These preliminary findings support its potential role as a conservative surgical option.

Background We aimed to evaluate diagnostic performance of preoperative hydrodissection and grey-scale imaging (US) in predicting extra-thyroidal extension (ETE) of subcapsular thyroid lesions. Methods The retrospective study evaluated hydrodissection between September 2023 and March 2025 for subcapsular thyroid nodules. Biopsy specimen with atypia of undetermined significance and thyroid tumors without surgery were excluded. For US, ETE was determined based on following features: capsule disruption, bulging contour, and perithyroidal infiltrations. For hydrodissection, ETE was determined positive if resistance was encountered. Diagnostic performance comparing US and hydrodissection in predicting ETE was performed for K-TIRADS 5 nodules and thyroid tumors. Results A total of 40 nodules per 33 patients (age: 50.2 ± 12.7; female: 28/33, 84.9%) were included. Out of 40 nodules, 18 nodules were tumors, of which 15 nodules (83.3%) were malignant. Four malignant nodules demonstrated ETE. For K-TIRADS 5 nodules (n = 28), hydrodissection demonstrated better diagnostic performance in terms of specificity (0.96 vs. 0.63, p = 0.008), accuracy (0.93 vs. 0.61, p = 0.004), and AUC (0.854 vs. 0.563, p = 0.013). For thyroid tumors (n = 18), hydrodissection demonstrated higher accuracy (0.89 vs. 0.56, p = 0.031) and higher AUC (0.839 vs. 0.536, p = 0.016). Conclusion Hydrodissection demonstrated better specificity, better accuracy, and higher AUC in predicting ETE than US.

We aimed to develop and validate a radiopathomics model for predicting extrathyroidal extension (ETE) in papillary thyroid carcinoma (PTC). This retrospective study included 388 PTC patients with preoperative ultrasound and 400× cytology images from five medical centers between June 2017 and April 2024. We analyzed ultrasound and cytology images using Python and CellProfiler to extract features. Feature selection was performed using univariate analysis, Spearman correlation, and LASSO regression. The XGBoost algorithm was then used to build radiomics, pathomics, and combined radiopathomics models. The diagnostic performance of the radiopathomics model was compared with that of radiologists in an external validation cohort. Model and radiologist performance was evaluated using the area under the receiver operating characteristic curve (AUC). The radiopathomics model was visualized and interpreted through SHAP analysis. The radiopathomics model selected 21 features for construction. The AUC of the radiopathomics model was 0.887, 0.857, and 0.873 in the training, internal validation, and external validation cohorts, respectively, exceeding those of the single radiomics model (0.824, 0.787, and 0.804) and the pathomics model (0.809, 0.811, and 0.794). Compared with radiologists, the radiopathomics model improved the mean accuracy from 0.661 to 0.821. SHAP analysis showed that radiomics features played a major role in diagnosing ETE, while pathomics features provided additional support. The radiopathomics model serves as a promising auxiliary tool for preoperative ETE risk stratification and can help improve radiologists' diagnostic performance. Not Applicable.

Differentiated thyroid carcinomas (DTC), including papillary thyroid carcinoma (PTC) and follicular carcinoma (FC), account for most thyroid malignancies and are generally associated with excellent prognosis. However, a subset of DTC demonstrate aggressive clinical behavior characterized by increased recurrence, distant metastasis (DM), radioactive iodine (RAI) resistance, and reduced survival. Identification of these tumors is critical for appropriate risk stratification and management. A number of pathologic features have been shown to predict aggressive behavior, including vascular invasion (VI), capsular invasion (CI), and extrathyroidal extension (ETE), as well as high-grade histologic features such as increased mitotic activity and tumor necrosis. In the 2022 World Health Organization (WHO) Classification for Endocrine and Neuroendocrine Tumours, high-grade features are acknowledged as prognostically significant, and DTC meeting these criteria are classified as high grade differentiated thyroid carcinoma (HGDTC), a category with a prognosis similar to PDTC. In addition, certain histologic subtypes of PTC, including the tall cell, hobnail, and columnar cell subtypes, have traditionally been associated with more aggressive clinical outcomes. However, the prognostic significance of histologic subtype alone remains debated, as tumor behavior is often influenced by the presence of invasive features and high-grade morphology. Recent advances in molecular profiling have further refined risk stratification. While the independent prognostic significance of the BRAFV600E mutation remains controversial, TERT promoter mutations have consistently been associated with aggressive tumor biology, including DM, RAI resistance, and decreased survival. Importantly, the coexistence of BRAFV600E and TERT promoter mutations identifies a subset of thyroid carcinomas with particularly poor outcomes. This review summarizes the key pathologic and molecular features associated with aggressive behavior in DTC, highlighting their diagnostic criteria, prognostic significance, and implications for clinical management. Comprehensive pathologic evaluation integrating morphologic and molecular findings remains essential for accurate risk stratification and multidisciplinary care of patients with thyroid carcinoma.

While papillary thyroid carcinoma (PTC) with gene rearrangements is associated with specific pathological features, further validation is needed to determine whether screening based on these specific pathological findings is useful. RNA sequencing was performed on 103 patients with PTC having wild-type BRAF. Group 1 (n = 57) included cases selected by an endocrine pathologist based on distinct pathological features such as multinodular invasive growth, prominent intratumoral stromal fibrosis, mixed growth patterns with varying degrees of nuclear atypia, pale eosinophilic to clear cytoplasm, and/or multiple lymph node (LN) metastases. These cases underwent pan-TRK, ALK and RET IHC and RNA sequencing. Group 2 (n = 46) consisted of randomly selected cases that underwent RNA sequencing. Gene rearrangements were identified in 66 patients (64.1%), with a significantly higher proportion in Group 1 (78.9%) than in Group 2 (45.7%). NTRK was the most frequent gene rearrangement (30.1%), followed by RET (19.4%), ALK (9.7%), and BRAF (2.9%). Patients with gene rearrangements were significantly younger and had smaller primary tumors, although they demonstrated greater extrathyroidal extension and LN metastasis than those without rearrangements. Pan-TRK IHC showed a sensitivity of 52% and a specificity of 94%, whereas RET and ALK IHC demonstrated higher sensitivities (78% and 88%) and specificities (81% and 100%), respectively. This study suggests that pathologic prescreening can enrich for targetable gene rearrangements in BRAF wild-type PTC and serve as a resource-sparing strategy before RNA sequencing. In prescreened cases, ALK IHC performed well, while pan-TRK and RET IHC had limitations.

Multimodal Ultrasound for Evaluating Gross Extrathyroidal Extension in Papillary Thyroid Cancer: A Comparative Study.

A BSTRACT Introduction: Pediatric differentiated thyroid carcinoma (DTC) has a higher incidence of locally advanced disease than adults. The efficacy of external beam radiation therapy (EBRT) prior to radioactive iodine ablation (RAIA) for inadequate resection and gross residual is established in adults, but not supported in children. Aim: The aim of this study was to evaluate the efficacy and toxicity in pediatric DTC patients who received EBRT prior to RAIA. Methodology: Data from November 2005 to November 2025 were retrospectively analyzed. Those who received EBRT to the neck prior to RAIA were included. The toxicity profile and response to RAIA were recorded. Results: A total of 112 children had DTC, of which 8 (3 females, 5 males, age range: 8–17 years, and mean: 12 years) were included. Six received conventional RT [40 Gy in 20 fractions followed by electron boost (16–20 Gy)]. Two received intensity-modulated radiation therapy (60–66 Gy). Total whole body scintigraphy scan (TWBS) showed residual disease in postoperative bed in 1, residual with lung metastases in 4, residual with nodal metastases in 2 and negative scan in 1 patient. Range of first stimulated serum thyroglobulin was 61-2400 ng/ml. Cumulative dose of RAIA ranged from 75 to 395 mCi. All showed significant biochemical and scintigraphic decrease. Response according to the American Thyroid Association (2025) was excellent in four, structurally incomplete in two and biochemically incomplete in two at the end of follow-up (median follow-up: 11.5 years and range: 1–23 years). Except for hypertrophic scar, none had significant patient-reported side effects. Conclusion: EBRT is a feasible adjuvant treatment option for selected pediatric DTC patients with locally aggressive disease – gross extrathyroidal extension or unresectable disease.

BackgroundHigh-grade differentiated thyroid carcinoma (HGDTC) is a recently recognized entity in the 2022 World Health Organization classification, representing a more aggressive subtype of differentiated thyroid carcinoma. Previously, high-grade features such as increased mitotic activity and tumor necrosis were often overlooked, despite being important independent prognostic factors. Although rare, HGDTC carries significant diagnostic, prognostic, and therapeutic implications. Data remain limited in Indonesia.MethodsThis retrospective descriptive study reviewed 565 thyroid carcinoma cases diagnosed at Cipto Mangunkusumo Hospital from 2019 to 2024. Eleven cases (1.9%) met HGDTC criteria. Clinicopathological characteristics, histologic subtypes, Ki-67 proliferation index, molecular alterations, treatment modalities, and clinical outcomes were analyzed.ResultsPatients had a mean age of 54.6 years, with a female-to-male ratio of 2.7:1. Papillary thyroid carcinoma was the main type (90.9%), with the tall cell subtype predominating. Mean tumor size was 6.4 cm. Lymphatic invasion, vascular invasion, and extrathyroidal extension were present in 54.5%, 18.2%, and 45.5% of cases, respectively. All tumors showed necrosis. Mean mitotic count was 3 per 2 mm². The Ki-67 index ranged from 5% to 45% (median, 14%). BRAFV600E and TERT promoter mutations were detected in 18.2% and 36.4% of cases, respectively, with co-mutations in 18.2%. Six cases (54.5%) had metastases at time of diagnosis. During a mean follow-up of 20.5 months, one patient (9.1%) developed new vertebral metastases and all patients (100%) remained alive.ConclusionsHGDTC presents with more aggressive characteristics and a worse prognosis. Accurate diagnosis, molecular profiling, and long-term monitoring are essential for optimal management.

Differentiated thyroid carcinoma (DTC) is rare in children, comprising 2-4% of pediatric cancers. Due to low case volumes at individual institutions, comprehensive data on patient and tumor characteristics and treatment outcomes are limited. The Child and Adolescent Thyroid Consortium (CATC) was established in 2019 to address this gap and to assess impact of changes in practice on outcomes. This inaugural CATC study analyzes the landscape of pediatric DTC and predictors of invasive disease. International, multicenter retrospective analysis of children (< age 19) with DTC diagnosed from 2010-2019. Five high-volume pediatric centers. The cohort included 715 children (78.3% female) diagnosed with DTC at median age 15.2 years (range: 3.2-18.9). There were 673 (94%) patients with papillary thyroid carcinoma (PTC) and 42 (6%) had follicular thyroid carcinoma (FTC). Among PTC patients, Stage 1(M0) disease was present in 562 individuals (83.5%; 222 N0, 161 N1a, and 179 N1b). Stage 2 (M1) disease was present in 111 (16.5%) children with PTC and 1/42 (2.4%) with FTC. Males and children <10 years exhibited more advanced T-, N-, and M-stages. Any extrathyroidal extension (ETE) correlated with increased nodal and pulmonary metastases. Oncogenic fusions, compared with BRAFV600E, were associated with more advanced N- and M-stages. Deintensification of therapy since 2015 was not associated with changes in disease outcomes. Invasive DTC is associated with age <10 years, male sex, tumors driven by oncogenic fusions and ETE. Despite less aggressive therapies in recent years, disease outcomes have not worsened. Recognition of these associations may guide care and prognostication.

Postoperative risk stratification using calcitonin doubling rate in medullary thyroid carcinoma with biochemical persistent disease.

Papillary thyroid carcinoma, columnar cell subtype (PTC-CC) is a PTC characterized by nuclear pseudostratification and elongation. High-grade differentiated thyroid carcinoma is a novel classification of the WHO classification, defined by mitotic count ≥5/2mm2 and/or tumor necrosis, which may exhibit CC morphology and can be termed as high-grade PTC-CC (HGPTC-CC). In this multicenter retrospective study, we conducted a detailed clinicopathologic review in a retrospective cohort of 71 PTC-CC and HGPTC-CC. HGPTC-CC was common among tumors showing columnar cell morphology, accounting for 46% (33/71) of the entire cohort. Compared with PTC-CC, HGPTC-CC was significantly associated with male sex, infiltrative tumors, angioinvasion, microscopic extrathyroidal extension (ETE), positive resection margin, and advanced pT stage. Furthermore, HGPTC-CC had significantly shortened disease-specific survival (DSS), distant metastasis-free survival (DMFS), and regional recurrence-free survival (RRFS). The 10-year DSS was 95% and 57%, the 10-year DMFS was 87% and 26%, and the 10-year RRFS was 85% and 55% for PTC-CC and HGPTC-CC, respectively. Among tumors with known BRAFV600E and RASQ61R status, BRAFV600E mutation was detected in 40% (19/47), whereas RASQ61R was identified in 15% (6/39). HGPTC-CC was associated with a significantly higher percentage of RASQ61R (PTC-CC 4%, HGPTC-CC 36%). In conclusion, a significant percentage (46%) of PTC-CCs are high-grade. HGPTC-CC is associated with adverse clinicopathologic features and poor outcomes. The impression of PTC-CC as an aggressive PTC subtype may be attributed to the high prevalence of high-grade histology in these tumors. Careful examination for mitoses and necrosis is required for accurate diagnosis and prognostication in PTC-CC.

BackgroundExtrathyroidal extension (ETE) critically impacts the treatment and prognosis of thyroid cancer, necessitating accurate preoperative prediction models. This study aimed to develop and validate such a model combining clinicopathological and ultrasonographic features.MethodsThis retrospective study enrolled 435 thyroid cancer patients from The First Affiliated Hospital of Nanchang University, categorized as non-ETE and ETE groups based on postoperative pathology. Patients were randomly divided into training (70%) and validation (30%) cohorts, with an external test cohort (n=70) from Huashan Hospital, Fudan University. Clinicopathological and ultrasonographic features were analyzed. Significant variables (P<0.05) identified via univariate logistic regression were incorporated into multivariate models: a clinicopathological model, an ultrasonographic model, and a combined clinicopathological-ultrasonographic model. Performance was evaluated using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA).ResultsThe combined model demonstrated robust calibration and discrimination across cohorts, with AUCs of 0.872 (training cohort), 0.835 (validation cohort), and 0.858 (external test cohort). Subgroup analyses revealed slightly lower AUC for microcarcinomas vs. non-microcarcinomas (0.772 vs. 0.893, P<0.05) and superior discrimination of gross ETE vs. minimal ETE (AUC: 0.963 vs. 0.824, P<0.05). No significant differences were observed between Hashimoto’s/non-Hashimoto’s (AUC: 0.875 vs. 0.843) or euthyroid/dysfunction subgroups (AUC: 0.852 vs. 0.845) (P>0.05).ConclusionsThe clinicopathological-ultrasonographic model provides reliable preoperative ETE prediction, facilitating personalized surgical planning and improved patient outcomes.

IJV invasion is a rare but significant occurrence in PTC. Although the current staging system categorizes T stages based on organ invasion, the classification for IJV invasion remains unclear. We evaluated the prognostic impact of internal jugular vein (IJV) involvement by extrathyroidal extension (ETE) and extranodal extension (ENE) in papillary thyroid carcinoma (PTC) and investigated the appropriate T-stage classification for ETE to the IJV. This retrospective study included PTC patients who underwent surgery between 2005 and 2011 at our hospital. We analyzed patients with IJV resection due to ETE or ENE, dividing them into ETE and ENE groups. We also compared the ETE group's prognoses with those of patients with stage III or IV PTC to evaluate the T4a vs. T4b classification. Among 5482 PTC cases, 17 were in the ETE group and 47 in the ENE group. We compared the ETE group's prognoses with those of the patients with stage III or IV PTC to evaluate the T4a vs. T4b classification. Compared to the ENE patients, the ETE patients had significantly lower 10-year overall survival (40.6% vs. 81.9%; HR 2.77, 95% CI: 0.99-7.67) and disease-specific survival (44.3% vs. 92.6%; HR 6.81, 95% CI: 1.68-27.51). Survival for ETE to the IJV was significantly worse than for stage III PTC but comparable to stage IV. ETE to the IJV showed a poor prognosis, comparable to stage IV, whereas ENE to the IJV had a favorable prognosis even though we did not exclude the presence of high-risk factors. ETE to the IJV represents an aggressive disease course in PTC, warranting careful consideration in staging and treatment planning.

Differentiated thyroid cancer (DTC) generally has a favorable prognosis; however, intermediate- and high-risk DTC may not progress positively. The optimal timing for radioactive iodine (RAI) after total thyroidectomy in intermediate-risk patients remains uncertain. we evaluated whether delaying RAI by > 6 months affected early treatment responses in 132 consecutive intermediate-risk patients with DTC treated between 2018 and 2022. Patients were grouped by surgery-to-RAI interval: ≤6 months (Group 1, n = 69) and > 6 months (Group 2, n = 63). Administered activities were 3,700 MBq or 5,550 MBq. The primary outcome was excellent response (ER) at 6‑month post‑treatment, per ATA‑2015 criteria. Multivariable logistic regression and 1:1 propensity score matching (age, sex, histology, multifocality, nodal status, and extrathyroidal extension) were used to address confounding factors. Sensitivity analyses included dose-stratified models. At 6 months, ER was more frequent in Group 1 than in Group 2 (35.6% vs. 21.2%; p = 0.049), while incomplete biochemical responses were higher in Group 2 (15% vs. 9.8%). After multivariable adjustment and in the propensity‑matched cohort (63 pairs), an RAI delay > 6 months remained associated with lower odds of ER (adjusted odds ratio 1.98; 95% confidence interval 1.05-3.74; p = 0.035). Aggressive histology and nodal metastasis independently reduced the likelihood of ER. The adverse effect of the delay appeared stronger among patients receiving 3,700 MBq, although the dose-time interaction was not statistically significant. The median follow‑up was 18 ± 6 months. In this cohort, RAI administration beyond 6 months was associated with a lower probability of excellent early response in intermediate-risk DTC, particularly in patients with nodal disease or aggressive histology.

To synthesize evidence on the demographic and prognostic profile of surgically treated intrathyroidal thymic carcinoma (ITC). A PRISMA-compliant systematic review and meta-analysis was conducted. Due to the rarity of the disease, all patients with surgically treated ITC were combined from individual case reports to create a cohort of patients which was subsequently pooled with other eligible case series. Single-arm meta-analysis was used to synthesize a demographic profile and Kaplan-Meier statistics were used for survival analyses. Analysis of 55 articles (154 patients) showed that patients with ITC are likely to be symptomatic (95.2%, 95% CI 91.1-99.2) with neck mass (72.2%, 62.2-82.1) as the most common symptom with no laterality preferences (left:right, 46.4%:53.6%). Overall survival (OS) at 15years was 96.0% (mean OS time:19.7years; median OS time 18years). Recurrence-free survival (RFS) at 15years was 77.9% (mean RFS time:13.4years; median RFS time: 17years). RFS was not affected by symptomatic status (HR: 0.0001, p=0.96), tumor size (HR; 1.044, p=0.113), lymph node metastasis (HR: 1.909, p=0.307), extrathyroidal extension (HR: 0.769, tumorp=0.688), surgery plus radiotherapy (HR: 0.434, p=0.207), surgery plus chemoradiotherapy (HR: 0.0001, p=0.959), subtotal thyroidectomy (HR: 0.821, p=0.854), lobectomy (HR: 0.366, p=0.140), lymph node dissection (HR: 1.088, p=0.888). Surgically treated ITC may have excellent long-term prognosis which seems to be not affected by the extent of resection or use of adjuvant therapy; however, this could be type 2 error; hence more robust evidence is required for definitive conclusions.

The aim of this study is to evaluate the impact of extrathyroidal extension (ETE), multifocality, and lateral neck lymph node metastasis on survival outcomes for pediatric patients with differentiated papillary thyroid carcinoma (PTC). This study was conducted in conformity with the PRISMA statement. The pooled hazard ratios (HRs) and the 95% confidence interval (CI) were calculated to define the impact of different pathological factors on disease-free survival (DFS). A total of 13 studies, enrolling 2641 patients (males: 29.5%, n = 780) with a median age of 16 years (95% CI: 15.4-19.0) years (n = 1370/2641), were included. The incidence of multifocality and ETE was 30.7% (n = 806/2625), and 45.4% (n = 1148/2528), respectively. The incidence of lateral neck lymph node metastasis (LNM) was 51.6% (n = 1224/2372). Overall, 61.5% of patients underwent postoperative radioactive iodine therapy (RAI) (n = 1381/2247). The median follow-up time was 85 months (95% CI: 57.0-176.4) (n = 2534/2641). The estimated pooled HRs for DFS were 1.86 (95% CI: 1.33-2.59; p = 0.002) for multifocality, 1.78 (95% CI: 1.20-2.63; p = 0.010) for ETE and 1.77 (95% CI: 0.76-4.11; p = 0.161) for lateral neck LNM. Multifocality and ETE are significant predictors of recurrence in pediatric PTC, while lateral neck LNM does not seem to be a reliable prognostic factor. These results may warrant consideration in pediatric-specific risk stratification and help guide treatment and follow-up.

Telomerase reverse transcriptase promoter (TERTp) mutations are associated with aggressive thyroid cancer and are most frequently found in anaplastic and poorly differentiated thyroid cancer. Pre-operative thyroid nodule molecular testing can detect TERTp, denoting a high risk of malignancy and possible aggressive clinical features such as extrathyroidal extension, regional lymph node metastases, and distant metastases. There are two described hot spot point mutations: the more common C228T and a C250T variant. Canonically, these mutations are mutually exclusive and drive monoallelic TERT expression. In this case series, we describe thyroid cancers where both the C228T and C250T variants were detected in preoperative thyroid nodule fine needle aspiration samples sent for Afirma molecular testing. All had co-mutations along with BRAFp.V600E or PIK3CAp.H1047R. Each sample was sent for kinship (relatedness between individuals) analysis to confirm the DNA and RNA samples were from the same patient and not due to sample cross contamination. All cases had confirmed thyroid carcinoma on histopathology after surgical resection. To our knowledge, this is the first report of dual TERTp mutations detected in the preoperative setting in thyroid carcinoma. Clinical correlation with future cases will be of interest, particularly if cases with monoallelic dual TERTp mutations are discovered.

PurposeThe management of indeterminate thyroid nodules (ITNs; Bethesda III–V) poses significant clinical challenges. This study sought to identify preoperative ultrasound and clinicopathologic predictors of invasive papillary thyroid carcinoma (PTC) among ITNs and to develop a corresponding risk prediction model.Patients and MethodsIn this retrospective study, 494 patients with FNA-confirmed ITNs and postoperative PTC diagnosis were included. Based on pathology confirming extrathyroidal extension and/or lymph node metastasis, patients were classified as invasive PTC (n=141) or non-invasive PTC (n=353). Univariate and multivariate logistic regression analyses identified independent risk factors, and a predictive nomogram was developed and validated.ResultsMale (odds ratio [OR]=2.91, 95% confidence interval [CI]:1.78–4.76), age ≤45 years (OR=1.93, 95% CI:1.23–3.03), abundant nodule vascularity (OR=4.60, 95% CI:2.42–8.75), and capsule proximity ≤2 mm (OR=3.63, 95% CI:2.15–6.14) were independent risk factors for invasive PTC, while abnormal thyroglobulin antibody (TgAb) levels reduced risk (OR=0.38, 95% CI:0.18–0.77). The prediction model achieved an AUC of 0.776 (95% CI:0.728–0.825) in the training set and 0.759 (95% CI:0.643–0.874) in validation, with decision curve analysis confirming clinical utility.ConclusionAn integrated model incorporating sex, age, vascularity, capsule distance, and TgAb status effectively predicts invasive PTC risk in ITNs. The nomogram provides preoperative risk stratification to guide personalized treatment, potentially reducing unnecessary aggressive surgery in low-risk cases while ensuring optimal management of high-risk patients. An interactive online version is available for clinical implementation.

Selecting patients with cT1N0M0 papillary thyroid carcinoma (PTC) for prophylactic central neck dissection (pCND) remains a challenge. This study aimed to identify predictive factors for occult central lymph node metastasis (oCLNM) in patients undergoing transoral endoscopic thyroidectomy vestibular approach (TOETVA). This cross-sectional, propensity score-matched study included 80 patients with cT1N0M0 PTC who underwent TOETVA with pCND at Hanoi Medical University Hospital between March 2023 and March 2024. Patients were divided into two matched groups (n = 40 each) based on the presence or absence of oCLNM on final pathology. Baseline characteristics were comparable (p > 0.05). The metastatic group had a significantly higher median number of harvested lymph nodes than the non-metastatic group (5.5 vs. 4.0; p = 0.018). No significant associations were found for tumor size, multifocality, or microscopic extrathyroidal extension (mETE). All five cases of bilobar tumors were observed in the metastatic group. Surgical outcomes, including operative time, blood loss, and hospital stay, were similar between groups. The number of harvested lymph nodes is associated with the detection of oCLNM, while the presence of a bilobar tumor may also be a predictive factor. However, reliably predicting oCLNM preoperatively remains difficult. Larger studies are needed to develop more accurate predictive models for selecting patients for pCND.