Papillary Carcinoma Research Articles

Development and validation of a prognostic nomogram for predicting liver metastasis in thyroid cancer: a study based on the surveillance, epidemiology, and end results database

This study aimed to create a prognostic nomogram to predict the risk of liver metastasis (LM) in thyroid cancer (TC) patients and assess survival outcomes for those with LM. Data were collected from the SEER database, covering TC patients from 2010 to 2020, totaling 110,039 individuals, including 142 with LM. Logistic regression and stepwise regression based on the Akaike information criterion (AIC) identified significant factors influencing LM occurrence: age, histological type, tumor size, bone metastasis, lung metastasis, and T stage (p < 0.05). A nomogram was constructed using these factors, achieving a Cindex of 0.977, with ROC curve analysis showing an area under the curve (AUC) of 0.977. For patients with TCLM, follicular TC, medullary TC, papillary TC, and examined regional nodes were associated with better prognosis (p < 0.001, HR < 1), while concurrent brain metastasis indicated poorer outcomes (HR = 2.747, p = 0.037). In conclusion, this nomogram effectively predicts LM risk and evaluates prognosis for TCLM patients, aiding clinicians in personalized treatment decisions

Application Progress in the Surgical Treatment of Differentiated Thyroid Cancer

Differentiated thyroid cancer accounts for more than 90% of thyroid cancer, including follicular and papillary carcinoma, and surgery is the main way to treat the disease. With the increasing incidence of thyroid cancer in recent years, the progress of its main treatment methods has attracted people's attention. In order to achieve good treatment results and promote the prognosis of patients, they should accurately evaluate their actual condition before surgery, and then choose the appropriate surgical method. This article mainly reviews the technology and application effect of DTC surgical treatment, in order to provide more basis and reference for the formulation of surgical treatment plans for DTC patients.

Central Neck Dissection in Papillary Thyroid Carcinoma: Benefits and Doubts in the Era of Thyroid Lobectomy.

Surgery is still the main line of treatment for papillary thyroid cancer (PTC) with a current trend for de-intensified treatment based on an excellent prognosis. The role of a routine prophylactic central neck dissection (PCND) is still debated as its impact on oncologic outcomes has never been cleared by a randomized clinical trial. In this study, we aimed to report our long-standing experience in PCND and its potential contemporary role in the treatment of PTC. A retrospective institutional review was performed on all patients who underwent operation for PTC including PCND between 1998 and 2021. The primary outcomes were the rate of central lymph node metastases (CLNMs), cancer recurrence and incidence of complications. Survivals were analyzed using the Kaplan-Meier estimator and Cox proportional hazard models. A total of 657 patients were included in this study with a median follow-up of 78 months (48-114 months). Two hundred and one patients presented occult CLNMs (30.6%). The presence of a pathological node represented the unique reason for a completion thyroidectomy and I131 therapy in 12.5% of the population. Age lower than 55 years, microscopic or macroscopic extra-thyroid extension (ETE) and multifocality were independent factors predicting CLNMs. The rate of recurrence in the whole population was 2.7% (18 patients). Five-year and ten-year disease-free survival (DFS) was 96.5% (94.7-97.7) and 93.3% (90.3-95.5), respectively. Two patients relapsed in the central neck compartment (0.3%). Age (>55 years), pathological staging (pT) and extranodal extension (ENE) were independent factors associated with a worse DFS. The rate of temporary and permanent vocal fold palsy was 12.8% and 1.8%, respectively, and did not depend on the type of surgical procedure performed. Hypoparathyroidism was temporary in 42.2% and permanent in 11.9% of the patients. A sub-analysis upon cT1b-T2 patients treated primarily with thyroid lobectomy and ipsilateral PCND demonstrated a 2.6% rate of permanent hypoparathyroidism. PCND allows for a high disease-free survival and a proper selection of patients needing adjuvant treatment, in particular, those treated with a unilateral procedure. On the other hand, bilateral approach is burdened by a not-neglectable rate of permanent hypoparathyroidism.

Changing Clinical Presentation of Pediatric Differentiated Thyroid Cancer in Poland: A Retrospective Cohort Study Spanning 45 Years.

Background: Differentiated thyroid carcinoma (DTC) in children is uncommon; clinical presentation over recent decades is incompletely characterized. Methods: This retrospective cohort study analyzed demographic and disease characteristics of consecutive juveniles with DTC treated from 1970 to 2015 at Poland's largest pediatric DTC referral center, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, who had available records. Sex, age, histopathological characteristics, and DTC stage were documented. We aimed to identify changes in these variables over time and independent risk factors for lymph node or distant metastases. Trends in these variables were assessed using the Cochran-Armitage test and Spearman correlation. Multivariable logistic regression was performed to identify risk factors associated with lymph node or distant metastases. Results: 475 of 479 patients (99.2%) were included in the analysis; roughly half were age ≥15 years, 10%, <10 years. Papillary thyroid carcinoma (PTC) represented 88% of cases and follicular thyroid carcinoma (FTC) 11%. Tumors ≤2 cm constituted 56% of cases with relevant data; those >4 cm accounted for 12%. Multifocality was observed in 37% and extrathyroidal invasion in 22%. Lymph node metastases were noted in 59% and distant metastases in 16%. Over the observation period, significant trends among new cases included: increased proportion of adolescents >15 years; increased frequency of tumors ≤2 cm, decreased multifocality rates, and increased proportion of PTC versus FTC. Extrathyroidal invasion rates remained appreciable throughout, ranging from 17 to 28% during the 5-year study subperiods after 1990. Lymph node metastases significantly increased in frequency in the central neck, remaining consistently common in lateral sites; presence of distant metastases significantly decreased. In multivariable analysis, multifocality, extrathyroidal invasion, and tumor size were independently associated with lateral lymph node metastases and multifocality, larger tumor size, and N1b metastases with distant spread. Conclusions: Our observations of a rising proportion of diagnoses in adolescence, reductions in primary tumor size, and decreased frequency of multifocality and distant metastases may reflect increased detection of patients with less aggressive DTC at earlier disease stages. Nonetheless, we found persistently substantial rates of locoregionally advanced disease features (multifocality, extrathyroidal invasion, and lymph node metastases), which multivariable analyses suggested have significant associations with lateral lymph node and/or distant metastases.

Concerns Regarding Thermal Ablation for Papillary Thyroid Cancer

This Viewpoint discusses drawbacks to thermal ablation for papillary thyroid cancer.

Is Conservative Management of Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP) Possible in Children?

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a newly recognized entity with benign clinical characteristics. We aim to compare NIFTP with invasive encapsulated follicular variant papillary carcinoma (fvPTC) and to discuss the management. Records of patients with fvPTC and NIFTP between 2016 and 2022 were reviewed retrospectively. Two groups were compared according to demographics, surgical management, postoperative management, and long-term follow-up. Twenty patients were included in the study, with 10 in NIFTP group and 10 in fvPTC group. The mean age at operation was 14.10 ± 2.61 years. Demographics and preoperative nodule sizes (P = .912) were statistically similar between the 2 groups. Although lobectomy was more common in the NIFTP group, this difference was not statistically significant compared to the fvPTC group in terms of surgical treatment. Postoperatively, while no patient received radioactive iodine treatment(RAI) in NIFTP group, 6 patients in fvPTC group did (P = .011). Five patients in NIFTP group and 3 in the fvPTC group were followed up with lobectomy only, without any adverse events or recurrence, for 47.50 ± 19.25 and 30.10 ± 19.25 months, respectively. In conclusion, NIFTP appears to be an indolent disease in children. Therefore, observation with lobectomy is sufficient, and RAI is not necessary.

Prognostic Implications of Maintaining the Target Thyroid-Stimulating Hormone Status Based on the 2015 American Thyroid Association Guidelines in Patients with Low-Risk Papillary Thyroid Carcinoma after Lobectomy: A 5-Year Landmark Analysis

Background: The 2015 American Thyroid Association guidelines recommend the maintenance of serum thyroid stimulating hormone (TSH) levels ≤2 mIU/L in patients with low-risk papillary thyroid carcinoma (PTC) who underwent lobectomy; however, the evidence is insufficient. We investigated the association between maintaining the TSH status at ≤2 mIU/L and tumor recurrence in patients with low-risk PTC who underwent lobectomy through a 5-year landmark analysis. Methods: Between 2010 and 2016, 662 patients with low-risk PTC were included. The postoperative TSH status was determined using the ‘TSH &gt; 2 ratio’, which was calculated using the TSH test results during the 5-year follow-up. The optimal cutoff value of ‘TSH &gt; 2 ratio’ for tumor recurrence was determined using a receiver operating characteristic curve analysis. Recurrence-free survival (RFS) was compared between the groups using Kaplan–Meier and Cox proportional hazard regression analyses. Results: Patients with ‘TSH &gt; 2 ratio’ &gt; 0.1833 (n = 498) had a worse RFS outcome compared to patients with ‘TSH &gt; 2 ratio’ ≤ 0.1833 (n = 164; p &lt; 0.001). ‘TSH &gt; 2 ratio’ &gt; 0.1833 was a significant risk factor for tumor recurrence after the 5-year landmark (hazard ratio: 4.795, 95% confidence interval: 2.102–10.937, p &lt; 0.001). Conclusions: Maintaining TSH levels ≤ 2 mIU/L below a certain percentage among the total TSH tests during the 5-year follow-up period has a negative impact on tumor recurrence.

Active surveillance of papillary thyroid carcinoma in Latin America: a scoping review.

Thyroid nodules are a very common finding and have a malignancy rate of 7%-15%. Some malignant nodules have an indolent behavior and may not affect mortality if left untreated. Active surveillance (AS) is a strategy to prevent overtreatment in patients with papillary thyroid microcarcinomas (PTMCs). This review was conducted to evaluate the status of AS for low-risk PTMC in Latin America, including cultural and logistical challenges, disease progression data, and financial viability. We searched PubMed (MEDLINE), SciELO, LILACS, and Web of Science for articles published after 2014 and enrolling adult Latin American patients. Articles cited in the selected studies were also retrieved. We analyzed the AS protocols, technical or logistical challenges, patient adherence, reasons for AS interruption, surgical conversion rates, duration of AS, and disease progression during AS in our region. Three articles were included in the analysis, all of which considered AS a viable option and reported tumor progression and outcomes similar to those reported in other countries. Neck ultrasound and serum levels of thyroglobulin, thyroid-stimulating hormone (TSH), thyroxine (T4), and antithyroglobulin antibodies were included in the follow-up. No cases of new distant metastases were reported, and the outcomes were favorable when surgery was required. Anxiety was the main reason for AS interruption. We conclude that AS can be an acceptable approach and is safe and effective in Latin America, although more prospective studies are needed to consolidate this strategy in our region. Adequate infrastructure, follow-up, and patient education, as well as multidisciplinary healthcare teams trained in conducting AS must be ensured for successful results.

Spontaneous hepatic hemorrhage as presentation of metastasized papillary thyroid carcinoma: a case report

BackgroundSpontaneous hepatic hemorrhage is a rare condition, most commonly diagnosed in patients with hepatocellular carcinoma or hepatic adenomas, and is seldom caused by metastatic disease. In this case report, we present a patient with spontaneous hepatic hemorrhage due to hepatic metastasis of papillary thyroid carcinoma, an exceptionally rare occurrence.Case presentationThe patient was a 77-year-old white male with a history of atrial fibrillation treated with apixaban. He presented at a local hospital with abdominal pain and nausea. A CT scan revealed a hepatic lesion in segment 3 with an adjacent hematoma. He was referred to our tertiary center and treated conservatively. Further evaluation revealed an intrathoracic goiter containing a tumorous process diagnosed as a papillary thyroid carcinoma (PTC), and the patient subsequently underwent thyroidectomy. A biopsy of the hepatic lesion confirmed it as a PTC metastasis. Due to worsening abdominal pain and anorexia, the patient underwent subacute hepatic segmental resection. Postoperatively, he developed iodine-refractory disease with disseminated metastasis and passed away 22 months after the initial admission.ConclusionsTo our knowledge, this is the first recorded case of metastasized papillary thyroid carcinoma presenting with spontaneous hepatic hemorrhage—adding to the list of rare causes for this condition.

Lipoma: An Unusual Iodine-131 Uptake on Whole-Body Scanning: A Case Report

Whole-body radioiodine scintigraphy plays a major role in detecting metastases or recurrence of differentiated thyroid cancers. However, radioactive iodine uptake is not specific to thyroid tissue, and many physiological and pathological variants can bind radioactive iodine, resulting in false positives that can compromise the correct interpretation of results. We report the case of a 73-year-old patient with papillary thyroid carcinoma who underwent surgery 2 years ago, and whose whole-body scan, performed in the face of rising thyroglobulin levels, revealed abnormal fixation on the thigh, and further investigations suggested a lipoma. Our aim in reporting this case is to contribute to the knowledge of new false positives linked to iodine-131 fixation, in order to avoid unusual diagnostic errors that can lead to the unnecessary administration of therapeutic doses of iodine-131 or to aberrant surgical interventions.

Thyroid Cancer Recurrence: Risk Factors and Preventive Strategies

&amp;lt;i&amp;gt;Introduction&amp;lt;/i&amp;gt;: Several risk factors influence the recurrence of thyroid cancer, including age, tumor size, lymph node involvement, and other prognostic indicators. The purpose of this study is to evaluate the impact of these risk factors on the recurrence rates of thyroid cancer, with the aim of improving diagnostic and treatment strategies for better patient outcomes. &amp;lt;i&amp;gt;Aim of the study&amp;lt;/i&amp;gt;: The aim of the study was to evaluate risk factors for thyroid cancer recurrence and preventive strategies. &amp;lt;i&amp;gt;Methods&amp;lt;/i&amp;gt;: This retrospective cohort study conducted at the Department of Otolaryngology-Head &amp; Neck Surgery at Bangabandhu Sheikh Mujib Medical University (BSMMU) included 108 thyroid cancer patients treated between April 2023 and March 2024. Patients were categorized into low-risk and high-risk groups based on prognostic factors. Follow-up for three years assessed recurrence and survival through outpatient visits and telephone interviews. Statistical analyses using SPSS version 22.0 included descriptive statistics, chi-square tests for recurrence rates, and Kaplan-Meier survival analysis. Result: The study identified Differentiated Thyroid Carcinoma (DTC) as the most common type, with Papillary Thyroid Carcinoma being the predominant subtype. Recurrence rates were notably higher in patients aged ≥45 and in males. Significant predictors of recurrence included age, gender, tumor diameter, and lymph node metastasis. High-risk patients mostly received Total Thyroidectomy, Radioiodine ablation, and Thyroxin. Follow-up showed recurrence rates of 8.33% in low-risk and 7.55% in high-risk patients over three years. &amp;lt;i&amp;gt;Conclusion&amp;lt;/i&amp;gt;: The study highlights the critical role of age, gender, tumor diameter, and lymph node metastasis in predicting thyroid cancer recurrence, emphasizing the need for personalized treatment and monitoring based on risk levels.

Efficacy of postoperative radioactive iodine therapy for patients with low and intermediate risk papillary thyroid carcinoma.

This study aimed to evaluate the efficacy of postoperative radioactive iodine (RAI) and its impact on recurrence rates and survival benefits in low- to intermediate-risk papillary thyroid carcinoma (PTC). This retrospective study involved the examination of 1286 patients diagnosed with low- to intermediate-risk PTC who underwent total thyroidectomy with or without neck dissection, supplemented with postoperative RAI therapy or not between the years 2000 and 2021. From the patient pool, 589 (45%) were classified as low-risk and 697 (55%) as intermediate-risk according to the 2015 American Thyroid Association guidelines. Among the low-risk group, 375 (63.7%) underwent postoperative RAI, while in the intermediate-risk group, 566 (82.2%) underwent the procedure. The overall survival and disease-free survival rates were not statistically different between the groups that received RAI and those that did not, in both the low- and intermediate-risk categories. In a subgroup analysis, within the intermediate-risk category, postoperative RAI was significantly correlated with decreased recurrence in two subgroups: patients over 55 years with pN1b disease (hazard ratio 0.043, 95% confidence interval 0.004-0.500, p = 0.012) and patients over 55 years with five or more metastatic lymph nodes (hazard ratio 0.060, 95% confidence interval 0.005-0.675, p = 0.023). Our findings suggest that, while post-total thyroidectomy RAI does not substantially influence recurrence or survival rates in most low-risk and intermediate-risk PTC patients, it may be beneficial in specific subgroups, particularly patients over 55 with pN1b disease or those presenting with five or more metastatic lymph nodes.

MiRNAs in Extracellular Vesicles as Biomarkers in Plasma of Papillary Thyroid Cancer Patients: A Proof-of-Concept Study.

The incidence of various types of cancer, for example, papillary thyroid carcinoma (PTC), is on the rise. Since therapeutic success depends greatly on early diagnosis, reliable diagnostic biomarkers must be identified, and easy-to-apply tools for detecting them must urgently be standardized. Here, we contribute to solving this medical challenge by assessing miRNAs suspected of promoting carcinogenesis in extracellular vesicles (EVs) that can be routinely obtained via liquid biopsy. We profit from current progress in cancerology that provides innovations in liquid biopsy and EVs analysis, along with the identification of miRNAs and chaperone system (CS) components implicated in carcinogenesis. We measured in EVs obtained from circulating blood plasma from PTC patients the levels of three miRNAs implicated in thyroid cancer, hsa-miR-1-3p, hsa-miR-206, and hsa-miR-221-3p, and most likely involved in the regulation of two members of the CS, Hsp60 and CCT. EVs were isolated from the plasma of patients with PTC and controls with benign goiter (BG) and from the culture medium of a PTC cell line (MDAT32) and were appropriately characterized. The levels of miRNAs determined by RT-qPCR were consistently higher in PTC patients and decreased down to control levels after thyroidectomy. Bioinformatics showed that the miRNAs target genes are associated with the molecular pathogenesis of PTC. Our exploratory study reaffirms the potential in clinics of the selected miRNAs in EVs as useful biomarkers of PTC easily accessible via liquid biopsy, which is minimally invasive and amenable to periodic repetition, an improvement compared to the established fine-needle aspirate biopsy.

Development of machine learning models to predict papillary carcinoma in thyroid nodules: The role of immunological, radiologic, cytologic and radiomic features

ObjectiveApproximately 30 % of thyroid nodules yield an indeterminate diagnosis through conventional diagnostic strategies. The aim of this study was to develop machine learning (ML) models capable of identifying papillary thyroid carcinomas using preoperative variables. MethodsPatients with thyroid nodules undergoing thyroid surgery were enrolled in a retrospective monocentric study. Six 2-class supervised ML models were developed to predict papillary thyroid carcinoma, by sequentially incorporating clinical-immunological, ultrasonographic, cytological, and radiomic variables. ResultsOut of 186 patients, 92 nodules (49.5 %) were papillary thyroid carcinomas in the histological report. The Area Under the Curve (AUC) ranged from 0.41 to 0.61 using only clinical-immunological variables. All ML models exhibited an increased performance when ultrasound variables were included (AUC: 0.95–0.97). The addition of cytological (AUC: 0.86–0.97) and radiomic (AUC: 0.88–0.97) variables did not further improve ML models’ performance. ConclusionML algorithms demonstrated low accuracy when trained with clinical-immunological data. However, the inclusion of radiological data significantly improved the models' performance, while cytopathological and radiomics data did not further improve the accuracy. Level of evidenceLevel 4.

The splicing factor QKI inhibits metastasis by modulating alternative splicing of E-Syt2 in papillary thyroid carcinoma

Alternative splicing (AS) plays a crucial role in the hallmarks of cancer and can open new avenues for targeted therapies. However, the aberrant AS events and the metastatic cascade in papillary thyroid carcinoma (PTC) remain largely unclear. Here, we identify the splicing factor, quaking protein (QKI), which was significantly downregulated in PTC and correlated with poor survival outcomes in patients with PTC. Functional studies indicated that low expression of QKI promoted the PTC cell growth and metastasis in vitro and in vivo. Mechanistically, low QKI induced exon 14 retention of extended synaptotagmin 2 (E-Syt2) and produced a long isoform transcript (termed E-Syt2L) that acted as an important oncogenic factor of PTC metastasis. Notably, overexpression of long non-coding RNA eosinophil granule ontogeny transcript (EGOT) physically binds to QKI and suppressed its activity by inhibiting ubiquitin specific peptidase 25 (USP25) mediated deubiquitination and subsequent degradation of QKI. Collectively, these data demonstrate the novel mechanistic links between the splicing factor QKI and splicing event in PTC metastasis and support the potential utility of targeting splicing events as a therapeutic strategy for PTC.

A comprehensive prediction model for central lymph node metastasis in papillary thyroid carcinoma with Hashimoto's thyroiditis: BRAF may not be a valuable predictor.

Papillary thyroid carcinoma (PTC) frequently coexists with Hashimoto's thyroiditis (HT), which poses challenges in detecting central lymph node metastasis (CLNM) and determining optimal surgical management. Our study aimed to identify the independent predictors for CLNM in PTC patients with HT and develop a comprehensive prediction model for individualized clinical decision-making. In this retrospective study, a total of 242 consecutive PTC patients who underwent thyroid surgery and central lymph node dissection between February 2019 and December 2021 were included. 129 patients with HT were enrolled as the case group and 113 patients without HT as control. The results of patients' general information, laboratory examination, ultrasound features, pathological evaluation, and BRAF mutation were collected. Multivariate logistic regression analysis was used to identify independent predictors, and the prediction model and nomogram were developed for PTC patients with HT. The performance of the model was assessed using the receiver operating characteristic curve, calibration curve, decision curve analysis, and clinical impact curve. In addition, the impact of the factor BRAF mutation was further evaluated. Multivariate analysis revealed that gender (OR = 8.341, P = 0.013, 95% CI: 1.572, 44.266), maximum diameter (OR = 0.316, P = 0.029, 95% CI: 0.113, 0.888), multifocality (OR = 3.238, P = 0.010, 95% CI: 1.319, 7.948), margin (OR = 2.750, P = 0.046, 95% CI: 1.020, 7.416), and thyrotropin receptor antibody (TR-Ab) (OR= 0.054, P = 0.003, 95% CI: 0.008, 0.374) were identified as independent predictors for CLNM in PTC patients with HT. The area under the curve of the model was 0.82, with accuracy, sensitivity, and specificity of 77.5%, 80.3% and 75.0%, respectively. Meanwhile, the model showed satisfactory performance in the internal validation. Moreover, the results revealed that BRAF mutation cannot further improve the efficacy of the prediction model. Male, maximum diameter > 10mm, multifocal tumors, irregular margin, and lower TR-Ab level have significant predictive value for CLNM in PTC patients with HT. Meanwhile, BRAF mutation may not have a valuable predictive role for CLNM in these cases. The nomogram constructed offers a convenient and valuable tool for clinicians to determine surgical decision and prognostication for patients.

MAOA uVNTR Polymorphism in a Sample of Patients Diagnosed with Papillary Thyroid Cancer

Thyroid gland carcinoma (TGC), though only 1% of all carcinomas, is the most common endocrine neoplasm with an increasing incidence since the 1990s. Of the TGC types, papillary thyroid carcinoma (PTC) is the most common and has the best overall prognosis. Although primarily studied in various neural spectrum disorders, monoamine oxidase A (MAOA) may also contribute to cancer occurrence. This case control study assessed the prevalence of MAOA uVNTR polymorphism in PTC patients, compared its frequency with a healthy control, and assessed the variant’s impact on clinical features. The research participants consisted of 30 PTC patients (20 female, 10 male) over 18 years old who underwent thyroidectomy and radioiodine therapy at a Federal District private clinic and 30 paired and unrelated healthy volunteers (18 female, 12 male). The most frequent MAOA uVNTR alleles were 3R and 4R. Although no significant difference was detected in the genotypic distribution nor the PTC patients’ thyroglobulin, thyroid-stimulating hormone, and antithyroglobulin levels; body mass indexes; administered radiopharmaceutical (131I) doses; or biological sex, the presence of at least one 3R allele was associated with a larger tumor size (T3 + T4 staging). Thus, the 3R allele seems to be associated with PTC pathogenesis severity.

Serum microRNA-146a-5p and microRNA-221-3p as potential clinical biomarkers for papillary thyroid carcinoma

Abstract Purpose Papillary thyroid carcinoma (PTC) is the most common malignant thyroid neoplasm, accounting for approximately 85% of all follicular cell-derived thyroid nodules. This study aimed to assess the diagnostic potential of circulating microRNA-146a-5p and microRNA-221-3p as biomarkers for PTC and their usefulness in monitoring disease progression during patient follow-up. Methods An observational study was conducted on two cohorts of PTC patients and healthy controls (HCs) using digital PCR. We collected patients’ clinical, biochemical, and imaging data during the post-surgery surveillance. We analyzed the levels of circulating miRNAs in serum samples of patients before surgery and during the follow-up, including those with indeterminate/biochemical incomplete response (IndR/BIR) and residual thyroid tissues (Thy Residue). Results Both miR-146a-5p and miR-221-3p were confirmed as effective biomarkers for PTC diagnosis. They enabled differentiation between pre-surgery PTC patients and HCs with an area under the curve (AUC) of 92% and 87.3%, respectively, using a threshold level of 768,545 copies/uL for miR-146a-5p and 389,331 copies/uL for miR-221-3p. It was found that miRNA fold change levels, rather than absolute levels, can be useful during patient follow-up. In particular, we found that a fold change of 2 for miR-146a-5p and 2.2 for miR-221-3p can identify a progressive disease, regardless of the presence of TgAbs or remnant thyroid. Conclusion MiRNA-146a-5p and miRNA-221-3p, particularly the former, could be valuable diagnostic biomarkers for PTCs. They also seem to be effective in monitoring disease progression during patient follow-up by evaluating their fold change, even when thyroglobulin is uninformative.

Risk stratification of ThyroSeq results in indeterminate thyroid lesions: A single‐institution experience of clinicopathologic correlation with cytologic findings

AbstractBackgroundThyroSeq offers the opportunity to stratify the risk of malignancy (ROM) in the characterization of indeterminate thyroid nodules, especially those categorized as atypia of undetermined significance (AUS). However, whether ThyroSeq interpretations correlate with cytologic features, management, and surgical outcome remains unclear.MethodsThyroid fine‐needle aspiration specimens categorized as AUS and follicular neoplasm (FN) from 2017 to 2021 were identified from a cytology database search. Patient clinical information and ThyroSeq results were collected and correlated with resection diagnosis if available.ResultsA total of 520 cases were classified as AUS and 111 cases were classified as FN. Within the AUS lesions, 190 cases (36.5%) were subcategorized as cytologic atypia (III‐C), 109 cases (21.0%) as architectural atypia (III‐A), 138 cases (26.5%) as both cytologic and architectural atypia (III‐CA), and 69 cases (13.0%) as oncocytic cell aspirate (III‐O). Category III‐C showed the highest malignancy rate (16.7%; p = .29), and a higher ThyroSeq‐defined probability of cancer or noninvasive follicular thyroid neoplasms with papillary‐like nuclear features. Notably, within III‐C, intermediate‐risk mutations led to a significantly higher malignancy rate (46.7%; p = .0012). Conversely, III‐A had the lowest malignancy rate (9.7%) but this was significantly increased by concurrent high‐risk mutations (62.5%). BRAFV600E‐like mutations were frequently associated with III‐C and classical papillary thyroid carcinoma in histology. RAS‐like mutations were the most common alterations across all subcategories, and were frequently associated with follicular‐patterned lesions.ConclusionsAtypia subcategories have differential ThyroSeq‐defined ROMs and histologic outcomes. Combining atypia subcategory interpretation, ThyroSeq‐defined ROMs and molecular results aids in optimal clinical management for indeterminate thyroid lesions.

Synchronous Papillary Thyroid Carcinoma and Right Colon Cancer

Synchronous Papillary Thyroid Carcinoma and Right Colon Cancer