Features Of Papillary Thyroid Carcinoma Research Articles

Feasibility of active surveillance in patients with clinically T1b papillary thyroid carcinoma ≤1.5 cm in preoperative ultrasonography: MASTER study.

Active surveillance (AS) is generally accepted as an alternative to immediate surgery for papillary thyroid carcinoma (PTC) measuring ≤1.0 cm (cT1a) without risk factors. This study investigated the clinicopathologic characteristics of PTCs measuring ≤2.0 cm without cervical lymph node metastasis (cT1N0) by tumor size group to assess the feasibility of AS for PTCs between 1.0 cm and 1.5 cm (cT1b≤1.5). This study enrolled clinically T1N0 patients with preoperative ultrasonography information (n= 935) from a cohort of 1259 patients who underwent lobectomy and were finally diagnosed with PTC from June 2020 to March 2022. The cT1b≤1.5 group (n = 171; 18.3 %) exhibited more lymphatic invasion and occult central lymph node (LN) metastasis with a higher metastatic LN ratio than the cT1a group (n = 719; 76.9 %). However, among patients aged 55 years or older, there were no significant differences in occult central LN metastasis and metastatic LN ratio between the cT1a, cT1b≤1.5, and cT1b>1.5 groups. Multivariate regression analyses revealed that occult central LN metastasis was associated with age, sex, tumor size, extrathyroidal extension, and lymphatic invasion in patients under 55, while in those aged 55 or older, it was associated only with age and lymphatic invasion. For PTC patients aged 55 years or older with cT1b≤1.5, AS could be a viable option due to the absence of a significant relationship between tumor size and occult central LN.

Young and resilient: Unraveling papillary thyroid cancer outcomes in males under 40.

While males present with more adverse clinicopathologic features in papillary thyroid carcinoma (PTC), younger age has previously been shown to be a favorable prognostic factor. We examined the combined effect of male sex and young age on PTC outcomes. We conducted a retrospective analysis of a prospectively maintained database of thyroid cancer surgery patients (2000-2020) at a single quaternary care institution. We included papillary thyroid carcinoma cases and excluded those with prior cancer-related thyroid surgery. We examined demographics, cancer stage, surgical outcomes, and complications by age and sex, analyzing groups below and above the age of 40years. A total of 680 patients with PTC were included. Females constituted 68% (age ≥40years: 44% and <40years: 24%) and males 32% (≥40years: 24% and <40years: 8%). A significant difference (p<0.001) of N1 disease distribution was found between the groups. N1a metastasis was greater in patients younger than 40 regardless of sex ((M<40 (15%), F<40 (15%), M≥40 (12%), and F≥40 (9%)). While, M<40 had greater N1b metastasis (36%) than all other groups (M≥40 (28%), F<40 (22%), and F≥40 (10%)). There was no significant difference in the distribution ofT stages between groups. Groups showed no differences in 30-day outcomes, recurrence at 1year, reoperation, mortality, nerve injury, or hypocalcemia. Young males with PTC face increased occurrence of nodal metastasis yet experience similar recurrence rates as their female and older counterparts. Subgroup analysis underscores the predictive role of sex and age in advanced PTC cases.

Cyto-Histological Profile of MicroRNAs as Diagnostic Biomarkers in Differentiated Thyroid Carcinomas.

The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTCs), papillary thyroid carcinoma (PTC) is the most frequent. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis in order to obtain a personalized and more effective treatment for patients. This study aims to evaluate (1) the miRNAs in a series of DTCs, and their association with the presence of selected genetic mutations in order to improve diagnosis and predict the biologic behavior of DTC/PTC. (2) The reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis. This series includes 176 samples (98 cytology and 78 histology samples) obtained from 106 patients submitted to surgery, including 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a through quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The results were analyzed by the 2-ΔΔCT method, using miR16 as an endogenous control. Regarding PTC diagnosis, the discriminative ability of miRNAs expression was assessed by the area under the Receiver Operating Characteristic Curve (AUC). In PTCs, the association of miRNAs expression, clinicopathological features, and genetic mutations (BRAF, RAS, and TERTp) was evaluated. All the analyzed miRNAs presented a tendency to be overexpressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant tumors than in benign tumors. In histology, the discriminative abilities regarding PTC diagnosis were as follows: miR-146b (AUC 0.94, 95% CI 0.87-1), miR-221 (AUC 0.79, 95% CI 0.68-0.9), miR-222 (AUC 0.76, 95% CI 0.63-0.89), and miR-15a (AUC 0.85, 95% CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); miR-221 se = 68.4, sp = 90; miR-222 se = 73, sp = 70; and mi-R15a se = 72, sp = 80. MicroRNAs were associated with worst-prognosis clinicopathological characteristics in PTCs (p < 0.05), particularly for miR-222. Our data reveal a significant association between higher expression levels of miR-146b, miR-221, and miR-222 in the presence of the BRAF mutation (p < 0.001) and miR-146b (p = 0.016) and miR-221 (p = 0.010) with the RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Despite this study having a relatively small sample size, overexpression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs presented a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations can be advantageous for an accurate diagnosis of DTCs/PTCs in FNAC.

Clinical features combined with ultrasound characteristics to predict TERT promoter mutations in papillary thyroid carcinoma: a single-center study over the past 5 years.

Telomerase reverse transcriptase (TERT) has been reported in papillary thyroid carcinoma (PTC). This study aimed to investigate the correlation of TERT promoter mutations with clinical and ultrasound (US) features in PTC and to develop a model to predict TERT promoter mutations. Preoperative US images, postoperative pathological features, and TERT promoter mutation information were evaluated in 365 PTC patients confirmed by surgery. Univariate and multivariate factor analyses were performed to identify risk factors for TERT promoter mutations. A predictive model was established to assess the clinical predictive value. Of the 365 patients with PTC (498 nodules), the number of those with TERT promoter mutations was 67 cases (75 nodules), and the number of those without mutations was 298 cases (423 nodules). The median age was 40 years in the wild-type group and 60 years in the mutant group. Male patients made up 35.82% of the mutant group and 22.82% of the wild-type group. Multivariate analysis revealed that the independent risk factors associated with the occurrence of TERT promoter mutation in PTC were as follows: older age (odds ratio (OR) = 1.07; p = 0.002), maximum diameter of ≥ 10 mm (OR = 3.94; p < 0.0001), unilateral (OR = 4.15; p < 0.0001), multifocal (OR = 7.69; p < 0.0001), adjacent to the thyroid capsule (OR = 1.94; p = 0.044), and accompanied by other benign nodules (OR = 1.94, p = 0.039). A predictive model was established, and the area under the curve (AUC) of the receiver operating characteristic was 0.839. TERT promoter mutations were associated with high-risk US and clinical features compared with the wild-type group. TERT promoter mutations were associated with older ages. They were also found to be multifocal, with a maximum diameter of ≥ 10 mm, unilateral, adjacent to the thyroid capsule, and accompanied by other benign nodules. The predictive model was of high diagnostic value.

Correlation between genetic alterations and clinicopathological features of papillary thyroid carcinomas.

To investigate the correlations between multigene alterations and clinicopathological features in papillary thyroid carcinoma (PTC) samples. In this retrospective study, 111 cytological specimens of thyroid nodules, including 74 PTC samples and 37 benign samples, were analyzed using a 22-gene mutation assay employing next-generation sequencing. Clinicopathological information was retrospectively collected and analyzed. Gene alterations were associated with a higher rate of lymph node metastasis (LNM) and thyroid capsular invasion, a lower rate of coexisting Hashimoto's thyroiditis, the classical PTC subtype, and younger age (<45 years). Among the 22 genes tested, the BRAF mutation rates showed a significant difference between the PTC and benign groups. In the subgroup analysis, younger age (odds ratio = 12.512, 95% confidence interval: 3.126-50.087) was an independent risk factor for LNM. In further analyses, BRAF mutation was significantly associated with LNM in the older subgroup (age ≥ 45 years), suggesting that the BRAF mutation test has greater value for determining PTC prognosis in the older age group. Our findings will provide a more comprehensive understanding of the relationship between gene mutations and PTC and may contribute to improved PTC management.

Correlations between the average Young's modulus and histopathological characteristics of papillary thyroid carcinoma

Objective: To explore the histopathological factors affecting the stiffness of papillary thyroid carcinoma (PTC). Methods: Ninety-six patients with PTC confirmed by surgery and pathology in Shanxi Bethune Hospital from January 2019 to December 2020 were selected, including 101 nodules. Two-dimensional ultrasound and shear-wave elastography (SWE) were performed before surgery and the average Young's modulus (Emean) of PTC nodules were measured. Histopathological examinations on the nodules were conducted after surgery to decide the lesion size, number of lesions, calcification type, presence or absence of capsular and extracapsular invasion, degree of fibrosis, microvessel density, and number of tumor cells. The correlations between the lesion size, degree of fibrosis, microvessel density, and number of tumor cells and the Emean were analyzed. The Emeans of nodules with different numbers of lesions, presence or absence of capsular and extracapsular invasion, and different pathological calcification types were compared. The multiple linear regression analysis was used to evaluate the histopathological factors influencing the Emean. Results: The ranges of the lesion sizes, degrees of fibrosis, microvascular density, numbers of tumor cells, and the Emeans of the 101 investigated PTC nodules were (1.29±0.95) cm, (30.64±18.37)%, (101.64±30.7) vessels per high power field, (373.52±149.87) cells per high power field, and (36.47±19.62) kPa, respectively. Correlation analysis showed that the lesion size of PTC and the degree of fibrosis were positively correlated with the Emean (r=0.660, P＜0.001; r=0.789, P＜0.001), while the microvessel density was negatively correlated with the Emean (r=-0.198, P=0.047). The Emean of the group with capsular and extracapsular invasion was higher than that of the group without (P=0.014). There were statistical differences in the Emeans among different types of pathological calcification (P＜0.001). The multiple linear regression analysis showed that the lesion size (β=0.325, P＜0.001), degree of fibrosis (β=0.563, P＜0.001), psammoma bodies (β=0.177, P=0.001), stromal calcification (β=0.164, P=0.003), and mixed calcification of both psammoma bodies and stroma (β=0.163, P=0.003) were independent influencing factors for the Emean. The degree of fibrosis had the greatest impact on the Emean. Conclusions: The Emean of PTC lesions was correlated with the histopathological characteristics of PTC. The lesion size, degree of fibrosis, and calcification had significant impact on the Emean, among which the degree of fibrosis had the greatest impact.

Retrospective study of BRAFV600E mutation and CT features of papillary thyroid carcinoma.

This study aimed to examine the correlation between BRAFV600E status and computed tomography (CT) imaging characteristics in papillary thyroid carcinoma (PTC) and determine if suspicious CT imaging features could predict BRAFV600E status. This retrospective study included patients with pathologically confirmed PTC at the Department of Thyroid Surgery of Zhongshan Hospital, Xiamen University, between July 2020 and June 2022. We compared the clinicopathologic factors and CT findings of nodules with and without the mutation, and the multiple logistical regression test was used to determine independent parameters of the BRAFV600E mutation. This study included 381 patients with PTC, among them, BRAFV600E mutation was detected in 314 patients (82.4%). Multivariate logistic regression analysis showed that gender (OR = 0.542, 95% CI [0.296-0.993], P = 0.047) and shape (OR = 0.510, 95% CI [0.275-0.944], P = 0.032) were associated with BRAFV600E mutation. Compared to BRAFV600E mutation-negative, BRAFV600E-positive PTC lesions were more likely to be found in female patients and were characterized by irregular shape. However, the CT imaging finding is not enough to predict BRAFV600E status, but an indication.

Characteristics and immune checkpoint status of radioiodine-refractory recurrent papillary thyroid carcinomas from Ukrainian Chornobyl Tissue Bank donors.

The radioiodine-refractory (RAI-R) recurrent papillary thyroid carcinomas (PTCs) are more frequent in elderly patients and have an unfavorable prognosis. Data on the prevalence and characteristics of RAI-R recurrent PTCs in patients of young and middle age with or without a history of radiation exposure in childhood are poorly described. The aim of the current study was: i) to determine the frequency of RAI-R recurrent PTCs among donors of the Chornobyl Tissue Bank (CTB) and analyze the clinicopathological features of primary tumors (PTs), primary metastases (PMTSs), recurrent metastases (RMTSs) and risk factors for RMTS, and ii) to determine the immune checkpoint status (ICS) of the RAI-R recurrent PTCs and to assess the factors associated with ICS positivity. Sixty RAI-R recurrent PTCs (46 exposed to radiation and 14 non-exposed, 2.5% of all cases registered with the CTB) from the Ukrainian patients aged up to 48 years were identified. The clinicopathological characteristics of the PTs moderately to weakly resembled those of the PMTS and RMTS from the same patients while the metastatic tissues were highly similar. The multivariate model of RMTS included the dominant solid-trabecular growth pattern of the PT, cystic changes, N1b metastases, and the probability of a causation (POC) of PTC by radiation as risk factors. Among these factors, the lateral PMTS (N1b) had the strongest effect. The longer period of latency (a POC component) was the second statistically significant characteristic. ICS percent agreement between the PT and RAI-R RMTS was 91.5%; 23.7% of PTs and 28.8% of RMTSs had positive ICS (positive PD-L1 tumor epithelial cells (TECs) and positive PD-L1/PD1 tumor-associated immune cells). ICS positivity of PTs was associated with pronounced oncocytic changes and high density of the p16INK4A-positive TECs in the invasive areas of PTs. In RMTSs, ICS positivity was associated with pronounced oncocytic changes and Ki-67 labeling index ≥ 4.5% of PTs, and the dominant solid-trabecular growth pattern, Ki-67 labeling index ≥ 7.6% and p16INK4A-positivity of RMTS. The findings are of clinical relevance and may be useful for developing individual treatment approaches for patients with RAI-R recurrent PTCs possibly involving immunotherapy.

Oncocytic Follicular Cell–Derived Thyroid Tumors With Papillary Growth Pattern: A Clinicopathologic Study of 32 Cases

Context.— Oncocytic thyroid tumors displaying a papillary growth pattern are rare and may cause diagnostic problems. Objective.— To examine the clinicopathologic features of a series of 32 follicular cell–derived tumors composed of cells with oncocytic cytoplasm and displaying papillary architecture. Design.— Thirty-two cases were collected and studied to assess clinicopathologic features, including immunohistochemical and molecular testing for BRAF V600E. Results.— The patients were 26 women and 6 men, aged 17 to 77 years. The nodules ranged from 0.3 to 6.0 cm. Eighteen cases showed features of oncocytic hyperplastic nodules and were identified against a background of thyroid follicular nodular disease; 4 cases showed features of oncocytic follicular adenoma; and 10 cases corresponded to carcinomas with oncocytic and papillary features. Nuclear features of papillary thyroid carcinoma were absent or exceedingly rare. All cases were negative for HBME-1 and cytokeratin 19 (CK19) and wild type for BRAF V600E. Follow-up in 25 patients showed that all patients with hyperplastic nodules and oncocytic follicular adenomas were alive and well and free of disease from 7 to 20 years. One patient with oncocytic follicular carcinoma showed metastases and died of tumor at 16 months; 2 patients with carcinoma had metastases and recurrence at 6 and 7 years; and 5 patients with invasive tumors were free of disease from 5 to 10 years. Conclusions.— Oncocytic thyroid tumors with papillary features can span a spectrum from benign hyperplastic, to encapsulated neoplastic, to invasive malignant lesions. Owing to their papillary features, it is important not to confuse them for other types of thyroid tumors, such as oncocytic papillary thyroid carcinoma.

The potential association of peripheral inflammatory biomarkers in patients with papillary thyroid cancer before radioiodine therapy to clinical outcomes.

Neutrophil-lymphocyte ratio (NLR), markers-lymphocyte-to-monocyte ratio (LMR), and platelet to-lymphocyte ratio (PLR) have potential roles as prognostic biomarkers in various cancers. The study was evaluated to investigate the predictive value of the peripheral inflammatory biomarkers in patients with papillary thyroid carcinoma (PTC) before radioiodine therapy to the response of clinical outcomes. We retrospectively analyzed the patients diagnosed with PTC at the Second Hospital of Shandong University between September 2018 and January 2020. Patients were divided into low and high inflammatory biomarker groups based on median values. The area under the receiver operating characteristic curves (ROC) and logistic regression were used to explore the potential risk factors. A total of 692 patients were enrolled, which included 197 (28.4%) males and 495 (71.6%) females. The median values of NLR, LMR and PLR of these patients were 1.7 (range 0.3-5.7), 7.1 (range 1.1-23.4) and 137.6 (range 27.6-497.5), respectively, and the mean values were 1.95 ± 0.82, 7.4 ± 2.5 and 148.7 ± 54.8, respectively. Compared to the lower PLR group, the higher group was significantly associated with gender, tumor size, N stage and thyroglobulin level (P<0.05). At the end of follow-up, 75.5% (523/692), 13.3% (91/692), 4.5% (31/692), and 6.7% (47/692) of patients were evaluated as excellent response (ER), indeterminate response (IDR), structural incomplete response (SIR), and biochemical incomplete response (BIR) respectively. In term of clinical outcomes, the NLR, LMR and PLR showed relatively low discriminative power (P≥0.05). We found that higher PLR values was associated with poor clinicopathological features in PTC. However, the peripheral inflammatory indicators (NLR, LMR and PLR) may be insufficient to predict short-term clinical outcomes of patients with radioiodine therapy.

Bilateral papillary thyroid cancer: pitfalls of ACR TI-RADS and evaluation of modified parameters.

To explore modified parameters of the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) for evaluating contralateral nodules based on preoperative ultrasound features of papillary thyroid carcinoma (PTC) in the suspected lobe, thus guiding the management of bilateral PTC. We retrospectively analyzed 389 consecutive patients with PTC (272 in training set, 117 in validation set) who underwent total thyroidectomy from March 2020 to March 2022. According to their postoperative pathological data, the patients were divided into unilateral and bilateral PTC groups. The clinicopathological features and sonographic characteristics of suspected nodules were compared between the groups, and further ultrasonic characteristics of TI-RADS grade (TR grade)-underestimated nodules were analyzed. Patients with a body mass index of ≥25 kg/m2 (P < 0.001), multifocality in the suspected lobe (P < 0.001), and TR > 3 isthmus nodules (P = 0.003) tended to have bilateral PTC. After modifying the TI-RADS classification for contralateral nodules using these three parameters, the area under the curve for diagnosing contralateral lesions increased from 0.79 (95% confidence interval, 0.74-0.84) to 0.83 (0.78-0.87) in the training set. The missed diagnosis rate of contralateral PTC decreased in both the training set [21.1% (28/133) to 4.5% (6/133)] and validation set [11.4% (8/70) to 2.9% (2/70)]. Preoperative ultrasound tended to underestimate the contralateral nodules with the presence of cystic components [100% (6/6)] and halo sign [73.3% (11/15)]. The modified TI-RADS classification based on the suspected lobe may facilitate effective preoperative malignant risk stratification of contralateral nodules in bilateral PTC.

Prediction model of cervical lymph node metastasis based on clinicopathological characteristics of papillary thyroid carcinoma: a dual-center retrospective study.

The overall prevalence of papillary thyroid carcinoma (PTC) patients is expanding along with an ongoing increase in thyroid cancer incidence. Patients with PTC who have lymph node metastases have a poor prognosis and a high death rate. There is an urgent need for indicators that can predict lymph node metastasis (LNM) before surgery as current imaging techniques, such as ultrasonography, do not have sufficient sensitivity to detect LNM. To predict independent risk factors for Central lymph node metastasis (CLNM) or Lateral lymph node metastasis (LLNM), we therefore developed two nomograms based on CLNM and LLNM, separately. In two centers, the Second Affiliated Hospital of Nanchang University and Yichun People's Hospital, we retrospectively analyzed clinicopathological characteristics of PTC patients. We utilized multivariate analysis to screen for variables that might be suspiciously related to CLNM or LLNM. Furthermore, we developed nomograms to graphically depict the independent risk valuables connected to lymph node metastasis in PTC patients. Ultimately, 6068 PTC patients in all were included in the research. Six factors, including age<45, male, mETE, TSH>1.418, tumor size>4cm, and location (multicentric and lobe), were observed to be related to CLNM. Age<45, male, mETE (minimal extrathyroidal extension), multifocality, TSH≥2.910, CLNM positive, and tumor size>4cm were regarded as related risk factors for LLNM. The two nomograms developed subsequently proved to have good predictive power with 0.706 and 0.818 and demonstrated good clinical guidance functionality with clinical decision curves and impact curves. Based on the successful establishment of this dual-institution-based visual nomogram model, we found that some clinical features are highly correlated with cervical lymph node metastasis, including CLNM and LLNM, which will better help clinicians make individualized clinical decisions for more effectively rationalizing managing PTC patients.

The value of total tumor diameter in unilateral multifocal papillary thyroid carcinoma: a propensity score matching analysis.

Tumor multifocality is frequently observed in papillary thyroid carcinoma (PTC). However, the maximum tumor diameter (MTD), currently utilized in various staging schemes, might not accurately indicate the level of aggressiveness exhibited by multifocal tumors. We aimed to investigate the relationship between total tumor diameter (TTD) and clinicopathological features of papillary thyroid carcinoma. Retrospective data analysis was done on 1936 individuals who underwent complete thyroidectomy for PTC. Patients were classified into subgroups according to unilateral multifocality, central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). The relationships of clinicopathological features among these groups were analyzed. Unilateral multifocality was observed in 117 patients. The clinicopathological features of the unilateral multifocal PTC were similar to the unifocal PTC with approximate TTD. The unilateral multifocality played no independent role in CLNM and LLNM. Moreover, the efficiency of TTD in predicting CLNM and LLNM was significantly higher than that of MTD. In the case of unilateral multifocal PTC, TTD is a more accurate indicator of the biological characteristics of the tumor than MTD.

Auxiliary Diagnosis of Papillary Thyroid Carcinoma Based on Spectral Phenotype.

Thyroid cancer, a common endocrine malignancy, is one of the leading death causes among endocrine tumors. The diagnosis of pathological section analysis suffers from diagnostic delay and cumbersome operating procedures. Therefore, we intend to construct the models based on spectral data that can be potentially used for rapid intraoperative papillary thyroid carcinoma (PTC) diagnosis and characterize PTC characteristics. To alleviate any concerns pathologists may have about using the model, we conducted an analysis of the used bands that can be interpreted pathologically. A spectra acquisition system was first built to acquire spectra of pathological section images from 91 patients. The obtained spectral dataset contains 217 spectra of normal thyroid tissue and 217 spectra of PTC tissue. Clinical data of the corresponding patients were collected for subsequent model interpretability analysis. The experiment has been approved by the Ethics Review Committee of the Wuhu Hospital of East China Normal University. The spectral preprocessing method was used to process the spectra, and the preprocessed signal respectively optimized by the first and secondary informative wavelengths selection was used to develop the PTC detection models. The PTC detection model using mean centering (MC) and multiple scattering correction (MSC) has optimal performance, and the reasons for the good performance were analyzed in combination with the spectral acquisition process and composition of the test slide. For model interpretable analysis, the near-ultraviolet band selected for modeling corresponds to the location of amino acid absorption peak, and this is consistent with the clinical phenomenon of significantly lower amino acid concentrations in PTC patients. Moreover, the absorption peak of hemoglobin selected for modeling is consistent with the low hemoglobin index in PTC patients. In addition, the correlation analysis was performed between the selected wavelengths and the clinical data, and the results show: the reflection intensity of selected wavelengths in normal cells has a moderate correlation with cell arrangement structure, nucleus size and free thyroxine (FT4), and has a strong correlation with triiodothyronine (T3); the reflection intensity of selected bands in PTC cells has a moderate correlation with free triiodothyronine (FT3).

Ultrasonographic, clinical, and pathological features of papillary thyroid carcinoma in children and adolescents with or without Hashimoto's thyroiditis.

To compare the ultrasonographic, clinical, and pathological features of children and adolescents with papillary thyroid carcinoma (PTC) with and without Hashimoto's thyroiditis (HT). A total of 52 children and adolescent patients surgically diagnosed with PTC between 2017 and 2022 were included; 14 children and adolescent patients with PTC were diagnosed with HT via pathological examination. The preoperative ultrasonographic, postoperative histological, and molecular and clinical characteristics were retrospectively analyzed. The prevalence rate of PTC in patients with HT was 27%. Papillary thyroid microcarcinomas were found in 11 of 38 patients without HT, but none in patients with HT (p = 0.023). Extrathyroidal extension, capsular invasion, and lymph node metastases were more frequent in patients with PTC and HT than in patients with PTC alone (p < 0.05 for both). The ultrasonographic features of nodule composition, echogenicity, shape, margin, Thyroid Imaging Reporting and Data System categories, and total points were similar. The patterns of echogenic foci were more prominent in the nodules of patients with HT than in those of patients without HT (p = 0.016). The frequency of papillary thyroid microcarcinomas in patients with PTC and HT was less, whereas that of extrathyroidal extension, capsular invasion, and lymph node metastasis was significantly higher in patients with PTC and HT than in those with PTC alone. The patterns of echogenic foci on ultrasonography may represent a risk for PTC.

Multimodal predictive factors of metastasis in lymph nodes posterior to the right recurrent laryngeal nerve in papillary thyroid carcinoma.

The lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) is a crucial component of the central lymph nodes (LNs). We aimed to evaluate multimodal predictive factors of LN-prRLN metastasis in patients with papillary thyroid carcinomas (PTCs), including the clinical data, pathologic data, and preoperative sonographic characteristics of PTCs. A total of 403 diagnosed PTC patients who underwent unilateral, sub-total, or total thyroidectomy with central neck dissection were enrolled in this retrospective study. The clinical data, pathologic data, conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) characteristics of PTCs were collected and evaluated for predicting LN-prRLN metastasis. In this study, 96 PTC patients with LN-prRLN metastasis and 307 PTC patients without LN-prRLN metastasis were included. Univariate analysis demonstrated that PTC patients with LN-prRLN metastasis more often had younger age, larger size, multifocal cancers, A/T < 1, well-margins, microcalcification, petal-like calcification, internal vascularity, centripetal perfusion pattern and surrounding ring enhancement. Multivariate logistic regression analysis revealed that the CEUS centripetal perfusion pattern, central LN detected by ultrasound and LN-arRLN metastasis were independent characteristics for predicting LN-prRLN metastasis in PTC patients. According to our research, it is essential for clinicians to thoroughly dissect central LNs, particularly LN-prRLNs.

The association of hypoxia-inducible factor-1α and hypoxia-inducible factor-2α protein expression with clinicopathological characteristics in papillary thyroid carcinoma: A meta-analysis.

To investigate the correlation of hypoxia-inducible factor-1α (HIF-1α) and hypoxia-inducible factor-2α (HIF-2α) protein expression with clinicopathologic characteristics in patients with papillary thyroid carcinoma (PTC) through a meta-analysis. PubMed, Embase, Web of Science, Cochrane, CNKI, Wanfang, and VIP databases were searched from the establishment of the database to February 2023. The New castle-Ottawa Scale was used to evaluate the quality of the literature. Rev Man 5.3 and Stata14.0 were used to conduct a meta-analysis of the included studies. Twenty-eight articles with 2346 samples were included in the Meta-analysis. Compared with normal thyroid tissues, HIF-1α and HIF-2α proteins were highly expressed in PTC tumor tissues. High expression of HIF-1α protein was associated with tumor size (odds ratio [OR] = 4.50, 95% confidence interval [CI]: 2.88-7.04, P < .00001), lymph node metastasis (OR = 4.76, 95% CI: 3.78-5.99, P < .00001), TNM stage (OR = 3.67, 95% CI: 2.68-5.03, P < .00001), capsular invasion (OR = 2.30, 95% CI: 1.43-3.71, P = .0006 < .05), and extrathyroidal extension (OR = 10.96, 95% CI: 4.80-25.02, P < .00001). High expression of HIF-2α protein was associated with lymph node metastasis (OR = 4.18, 95% CI: 2.63-6.65, P < .00001), TNM stage (OR = 2.56, 95% CI: 1.36-4.82, P = .004 < .05), and capsular invasion (OR = 3.84, 95% CI: 1.66-8.88, P = .002 < .05). In addition, we concluded for the first time that there was a statistically significant difference in the expression of HIF-1α and HIF-2α in PTC patients (OR = 2.36, 95% CI: 1.26-4.42, P = .007 < .05). The high expression of HIF-1α and HIF-2α proteins is closely related to some clinicopathological parameters of PTC, and can provide potential biological indicators for the diagnosis and prognosis of PTC.

The impact of multifocality on lateral lymph node metastasis in papillary thyroid carcinoma

PurposeMultifocality is a common feature of papillary thyroid carcinoma (PTC) and is strongly associated with unfavorable outcome, but its association with lateral lymph node metastasis (lateral LNM) remains unclear. MethodsThe association between tumor foci numbers and lateral LNM was assessed with unadjusted and adjusted logistic regression. Propensity score matching analysis was used to investigate the impact of tumor foci numbers on lateral LNM. ResultsIncreasing tumor foci numbers was strongly associated with a higher risk of lateral LNM (P < 0.05). After adjusting for several confounding factors, ≥4 tumor foci can be regarded as an independent predictor of lateral LNM (multivariable adjusted OR = 1.848, P = 0.011). Similarly, compared with solitary foci, multifocality was associated with a significantly higher risk of lateral LNM after matching propensity scores (11.9% vs. 14.4%, P = 0.018), especially for patients with ≥4 tumor foci (11.2% vs. 23.4%; P = 0.001). Furthermore, age-stratified analyses revealed multifocality was significantly positively correlated with lateral LNM in younger patients (P = 0.013) compared with older patient cohorts (P = 0.669). ConclusionsOverall, tumor foci numbers significantly increased the risk of lateral LNM in PTCs, especially for patients with four or more tumor foci, and patient's age should be considered when interpreting the multifocality and risk of lateral LNM.

Clinical Impact of Androgen Receptor-Suppressing miR-146b Expression in Papillary Thyroid Cancer Aggressiveness.

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Dysregulated expression of miR-146b and androgen receptor (AR) has been shown to play critical roles in tumorigenesis in PTC. However, the mechanistic and clinical association between AR and miR-146b is not fully understood. The purpose was to investigate miR-146b as the potential AR target miRNA and its involvement in advanced tumor characteristics of PTC. Expression of AR and miR-146b were assessed in frozen and formalin-fixed paraffin-embedded tissue samples from PTC and adjacent normal thyroid specimens by quantitative real-time polymerase chain reaction, and their correlation was examined. Human thyroid cancer cell lines BCPAP and TPC-1 were used to evaluate the effect of AR on miR-146b signaling. Chromatin immunoprecipitation (ChIP) assays were performed to determine whether AR binds to the miR-146b promoter region. Pearson correlation analysis confirmed significant inverse correlation between miR-146b and AR expression. Overexpressing AR BCPAP and TPC-1 cells showed relatively lower miR-146b expression. ChIP assay revealed that AR might bind to the androgen receptor element located on the promoter region of miRNA-146b gene, and overexpression of AR suppresses miR-146b-mediated tumor aggressiveness. The low AR/high miR-146b PTC patient group was associated with advanced tumor characteristics, including higher tumor stage, lymph node metastasis, and worse treatment response. To sum up, miR-146b is a molecular target of AR transcriptional repression; therefore, AR suppresses miR-146b expression to reduce PTC tumor aggressiveness.

Clinicopathological features of papillary thyroid carcinoma in HIV-infected patients.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, with an increasing incidence over the last decades. Human immunodeficiency virus (HIV)-induced immune deficiency was one of risk factors for cancer tumorigenesis and development. The aim of this study was to describe the clinicopathological features of PTC in HIV-infected patients and discuss possible connections between PTC and HIV infection. A total of 17670 patients from September 2009 to April 2022 who underwent PTC surgery for the first time were analyzed retrospectively. At last, 10 patients of PTC with HIV infection (HIV-positive group) and 40 patients without HIV infection (HIV-negative group) were included. The differences in general data and clinicopathological characteristics between the HIV-positive group and the HIV-negative group were analyzed. There were statistically significant differences in age and gender between the HIV-positive group and the HIV-negative group (P<0.05), and males and <55 years old accounted for a higher proportion in the HIV-positive group. The differences in tumor diameter and capsular invasion between the HIV-positive group and HIV-negative group were statistically significant (P<0.05). Meanwhile, in terms of extrathyroid extension (ETE), lymph node metastasis and distant metastasis, the HIV-positive group were significantly higher than the HIV-negative group (P<0.001). HIV infection was a risk factor for larger tumors, more severe ETE, more lymph node metastasis, and more distant metastasis. HIV infection could promote PTC proliferation and make PTC more aggressive. Many factors such as tumor immune escape, secondary infection, etc. may are responsible for these effects. More attention and more thorough treatment should be paid to these patients.