Search Results (64)

Thyroid cancer is the most common endocrine malignancy, and preoperative distinction between benign and malignant nodules remains challenging, especially in cytologically indeterminate cases. Circulating microRNAs (miRNAs) have gained interest as non-invasive biomarkers due to their stability and involvement in tumorigenesis. This study aimed to assess the preoperative diagnostic value of circulating miR-146a and miR-221 in patients undergoing thyroidectomy. A total of 56 patients were included, of whom 24 had malignant and 32 had benign thyroid lesions confirmed by histopathology. Preoperative plasma levels of miR-146a and miR-221 were quantified using qRT-PCR, and relative expression was calculated with the 2^−ΔΔCt method. miR-221 expression was significantly higher in malignant cases, with an area under the ROC curve of 1.00, achieving 100% sensitivity and specificity at the optimal threshold. miR-146a showed no significant discriminatory ability. Weak correlations were observed between miRNA expression and clinical parameters such as age, TIRADS score, or thyroid volume. Logistic regression including miR-221 led to perfect separation, indicating strong predictive capacity but precluding multivariate modeling. These findings suggest that circulating miR-221 may serve as a highly accurate biomarker for thyroid malignancy and warrant further validation in larger, prospective cohorts. Full article

Objectives: Oncocyte-rich indeterminate thyroid nodules (O-ITNs) present diagnostic and management challenges due to overlapping features between benign and malignant lesions and differing cytological classifications. This study aimed primarily to assess the ultrasound (US) characteristics and US-based risk of O-ITNs using the American College of Radiology Thyroid Imaging Reporting And Data Systems (ACR TI-RADS). A secondary objective was to compare the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) and Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) cytological systems regarding classification and clinical management implications for O-ITNs. Methods: A retrospective study was conducted on 177 ITNs (TIR3A and TIR3B) evaluated between June 2023 and December 2024 at CTO-Alesini, Rome (Italy). Nodules were assessed with US, cytology, and histology. Oncocyte predominance was defined as >70% oncocytes on fine-needle aspiration (FNA). US features were analyzed according to ACR TI-RADS. Nodules were reclassified by BSRTC, and potential differences in clinical case management (CCM) were analyzed. Results: O-ITNs comprised 47.5% of the sample. Compared to non-O-ITNs, O-ITNs were larger and more frequently showed low-risk US features, including a higher prevalence of ACR TI-RADS 3 nodules. However, no progressive increase in the risk of malignancy (ROM) was observed across ACR TI-RADS classes within O-ITNs. Histological malignancy was identified in 47.1% of O-ITNs, a lower proportion compared to non-O-ITNs, though the difference was not statistically significant. Classification discordance with potential management impact was lower in O-ITNs (20.2%) than in non-O-ITNs (38.7%). Conclusions: O-ITNs typically exhibit benign-appearing US features and lower classification discordance between BSRTC and ICCRTC, yet US risk stratification fails to differentiate malignancy risk within O-ITNs. A tailored approach integrating cytology and cautious US interpretation is essential for optimal O-ITN management. Full article

Thyroid nodules are accidentally found in up to 68% of people undergoing neck ultrasound (US) examination, and fine needle aspiration (FNA) is the current gold standard to discriminate between malignancy and benign lesions. Unfortunately, one-third of FNAs are classified as indeterminate, requiring surgery for definitive diagnosis. This leads to high costs and health risks of unnecessary procedures, since malignancies are observed in less than half of operative specimens. This narrative review aims to describe the most innovative multi-omics approach techniques, including genomics, proteomics, and metabolomics, aimed at making the preoperative evaluation of indeterminate thyroid nodules more accurate. The advantages and disadvantages of the techniques are described in detail, and a SWOT (strengths, weaknesses, opportunities, and threats) analysis of the multi-omic approach is provided. Full article

Background and Objectives: Indeterminate thyroid nodules (Bethesda III and IV) are a common clinical entity that present a diagnostic challenge due to their intermediate risk of malignancy. This study aimed to evaluate the role of ultrasound in risk stratification and malignancy prediction to support clinical decision-making and reduce unnecessary surgical interventions. Materials and Methods: This retrospective multicenter cohort study included patients aged ≥18 years who underwent thyroid surgery between 2016 and 2022 at four centers in the Eastern Province of Saudi Arabia. Only nodules with indeterminate cytology (Bethesda III or IV) were included. Data collected included demographic characteristics, thyroid function, ultrasound features, cytology results, and histopathological findings. Results: A total of 679 patients with 733 nodules were reviewed. Of these, 206 patients with 223 indeterminate nodules were included (median age: 42 years; 88.3% female). The overall malignancy rate was 46.6%. Independent predictors of malignancy included solid hypoechoic composition (OR = 2.26, p = 0.012), microcalcifications (OR = 3.07, p = 0.002), lymph node involvement (OR = 2.43, p = 0.021), American Thyroid Association (ATA) intermediate to high suspicion category (OR = 1.9, p = 0.018), and Thyroid Imaging Reporting and Data Systems (TI-RADS) categories 4–5 (OR = 2.3, p = 0.003). Solid hypoechoic nodules showed 82.3% specificity and 63.0% positive predictive value (PPV); microcalcifications demonstrated 84.1% specificity and 68.4% PPV; lymph node involvement had 87.6% specificity and 68.9% PPV. The ATA and TI-RADS classifications showed higher sensitivity (63.5% and 68.0%, respectively), but lower specificity (53.1% and 52.8%, respectively). Conclusions: Ultrasound features, particularly solid hypoechoic composition, microcalcifications, and lymph node involvement, as well as ATA and TI-RADS classifications, were independent predictors of malignancy in indeterminate thyroid nodules. Although ATA and TI-RADS offered higher sensitivity, individual features demonstrated greater specificity and PPV. These findings support the use of ultrasound risk stratification to guide surgical decisions in high-risk cases and suggest that additional diagnostic evaluation may be appropriate for low-risk nodules. Full article

Background and Objectives: Many diagnostic methods exist for identifying thyroid malignancy, but most of them resemble an odyssey, as the journey from palpating a nodule to receiving a definitive diagnose is often long and costly. The aim of the present study is to investigate the role of Sestamibi scintigraphy in the characterization of cytological indeterminate thyroid nodules. Materials and Methods: A focused literature review was conducted, emphasizing the comparison between Fine Needle Aspiration Biopsy (FNAB), the main diagnostic method for thyroid cancer, and Sestamibi. Results: It is widely accepted that Sestamibi is the primary alternative for patients with non-diagnostic FNAB. As shown in the literature, Sestamibi has a high negative predictive value in excluding thyroid malignancy. Conclusions: Much like Odysseus’ adventurous 10-year journey returning to Ithaca, the path to diagnosing thyroid cancer is not straightforward. Molecular imaging with 99mTc-Sestamibi may serve as a valuable adjunct in evaluating thyroid nodules with inconclusive cytological findings. Full article

Background/Objectives: Diagnosing biliary obstructions is challenging, especially when histopathology is inconclusive. Non-malignant biliary strictures often require additional tests and a personalized approach. This study investigates the prevalence, characteristics, and natural history of indeterminate biliary strictures. Methods: A retrospective analysis was conducted on 510 treatment-naive patients with hyperbilirubinemia due to biliary strictures or obstruction, who were all candidates for endoscopic retrograde cholangiopancreatography (ERCP). Patients with a known etiology before the procedure were excluded. Diagnosis was made via brush cytology or intraductal biopsy during ERCP, with follow-up for indeterminate cases. Statistical analysis was performed with Statistica software (version 13.3; TIBCO Software Inc. (2017), Palo Alto, CA, USA). Results: Out of 510 patients, 186 (36.5%) had non-malignant biliary strictures. Strictures were located in the liver hilum (29.6%), common bile duct (11.8%), and peripancreatic ducts (58.1%). Follow-up ERCP identified malignancy in 21.5% of cases initially deemed benign. Non-malignant causes were confirmed in 41.4% of initially benign strictures, while 37.1% remained indeterminate. After six months, 25.8% of cases remained unresolved. Conclusions: A quarter of benign biliary strictures remain indeterminate despite follow-up, and 20% are later identified as malignant. Improved diagnostic protocols are needed to better manage and expedite the diagnosis of indeterminate biliary strictures. Full article

Introduction and case report: Angiosarcomas, rare soft tissue malignancies originating from endothelial cells, represent only 1–2% of all soft tissue sarcomas. Primary pleural angiosarcoma (PPA) is exceptionally rare, with only 43 reported cases since 1943. There are many diagnostic and therapeutic challenges due to the rarity of these tumors. We present the case of a 72-year-old man presenting with back pain, dyspnea and anemia. Conventional imaging revealed bilateral pleural effusion and a thickened parietal pleura, while contrast chest MR was able to identify pleural sites of contrast enhancement. Left chest tube placement evidenced a hemothorax, and the cytology result was negative. A thoracoscopic approach was chosen, allowing us to perform different parietal pleural biopsies. Radiological and pathological features led to the diagnosis of epithelioid PPA. Despite pleural drainage and blood transfusions, the patient died only 4 days after diagnosis. Objectives: To present a literature review, evaluating the disease epidemiology and the clinical, diagnostic and therapeutic features of PPA. Methods: We reviewed cases of PPA in the literature (1954–2024) by searching the PubMed database for the terms “pleural angiosarcoma” and “pleura + angiosarcoma”. Results: We found a total of 47 cases that were described between 1987 and 2024 with sufficient data to be included in our review. PPA was found to be a challenging diagnosis, found mostly in older Caucasian males. The cytology is mostly indeterminant, and an endoscopic approach is usually needed. Radical surgery is the most common treatment option, and chemotherapy and radiation therapy are also often used. However, the prognosis is poor. Conclusions: PPA is very rare, and complex cases such as this one showcase the importance of innovative approaches like MRI and emphasize the significance of multidisciplinary collaboration for optimal patient management. Bilateral spontaneous hemothorax, as seen in this case, is uncommon and poses additional challenges in disease management. Further research to advance the diagnostic capabilities and treatment efficacy is needed. Full article

Fine-needle aspiration cytology (FNAC) is the gold standard to diagnose thyroid nodules but fails in discriminating the nature of indeterminate lesions. Molecular testing can improve the diagnosis of these nodules and next-generation sequencing (NGS) can be used to test many genes simultaneously. Assess the performance of an NGS 17-gene panel on thyroid indeterminate FNAC. One hundred five indeterminate FNACs, 30.5% high-risk (TIR3B) and 69.5% low-risk (TIR3A), were analyzed by NGS. For TIR3A, the rate of mutated samples was 10.9%, significantly lower (p = 0.0001) compared to TIR3B (63.6%). Twenty-two mutated and fourteen non-mutated samples were submitted to surgery. At histology, the overall malignancy was 85.7% in the indeterminate group that had a positive molecular test and 13.3% in the mutation-negative (p = 0.01). The 17-gene panel had a sensitivity of 90%, specificity of 87%, positive predictive value (PPV) of 91%, and negative predictive value (NPV) of 87%. We reported the utility of Ultrasound Malignancy Risk Stratification of Thyroid Nodules in Adults (EU-TIRADS) in selecting indeterminate nodules for molecular analysis, showing a significant correlation between US score and mutation (p = 0.004). The performance of a 17-gene panel based on NGS technology is promising, allowing the selection of indeterminate nodules to submit to surgery with a great specificity and PPV. Full article

The aim of this paper is to highlight the combined role of ultrasound elastography and contrast-enhanced ultrasound in terms of diagnosis, staging, and follow-up of the post-treatment response. Contrast-enhanced ultrasound (CEUS) and ultrasound elastography are natural extensions of conventional USs that have created new opportunities, facilitating the implementation of multiparametric ultrasounds in the characterization of thyroid nodules, in risk stratification, and in the selection of nodules that request Fine Needle Aspiration (FNA), management, and follow-up of the nodules with indeterminate cytology, evaluation of pre-operative prognostic features, and treatment efficiency. Full article

Background: Molecular assays serve as a potential risk stratification tool for cytologically indeterminate thyroid nodules (ITNs). BRAF V600E mutations are nearly always associated with thyroid cancer. However, the malignancy risk for ITNs with other less common BRAF alterations is less well understood. In this retrospective cohort study, we examine the risk of malignancy (ROM), histopathologic diagnoses, and clinical outcomes for non-V600E BRAF-altered ITNs. Methods: Genomic profiling data obtained from 1034 pre-operative fine-needle aspiration samples from 955 patients were reviewed. Nodules harboring BRAF V600E were excluded. Clinical, radiographic, and histopathologic data were analyzed retrospectively from BRAF-altered ITNs managed surgically at one comprehensive cancer center (2014–2024). Diagnoses were subdivided based on American Thyroid Association (ATA) risk categories. Results: Thirty-seven patients (3.9%) with non-V600E BRAF-altered ITNs were identified (isolated BRAF mutation: n = 29 [78.4%], BRAF + other mutation: n = 3 [8.1%], BRAF fusion: n = 4 [10.8%], BRAF-like gene expression: n = 1 [2.7%]). All BRAF mutations identified in the cohort were class II (RAS-independent, intermediate to high kinase activity). Nodules had a median pre-operative diameter of 1.8 cm (interquartile range [IQR] 1.4–2.5). Patients presented with nodal metastases in 2.7% (n = 1) of cases, and local invasion was not identified in any patients in the cohort. Approximately half of patients (54.1%) were initially treated with a partial thyroidectomy (lobectomy: n = 17 [45.9%], isthmusectomy: n = 3 [8.1%]), and the remaining patients underwent total thyroidectomy (n = 17 [45.9%]). Median post-operative follow-up was 28 months (IQR 17.8–45.5). ROM for BRAF alterations was 73% (95%CI 59–87%; ATA low risk: 64.9%/ATA int risk: 5.4%/ATA high risk: 2.7%). There were no high-risk cancers identified in patients with isolated BRAF mutation (benign: n = 10 [34.5%], ATA low risk: n = 19 [65.5%]), and the most common isolated mutation was K601E (n = 17, 45.9%) which had a 58.8% ROM (all ATA low risk). Patients with isolated BRAF mutations had a significantly lower rate of ATA intermediate or high risk pathology when compared to all other BRAF alterations (0% vs. 37.5%, p = 0.0072). Only three patients were treated with radioactive iodine post-operatively (8.1%), and no completion thyroidectomy procedures were performed in those who did not initially undergo total thyroidectomy. No patients in the cohort were found to have distant metastatic disease or recurrence, and there were no deaths during the follow-up interval. Conclusions: ITNs harboring non-V600E BRAF alterations were rare (3.9% of patients) and typically malignant (73%). Nearly all nodules were benign or ATA low-risk cancers. Only 8% of such nodules were ATA intermediate or high risk cancers. In ITNs with isolated non-V600E BRAF and no other genetic alterations, one-third were non-malignant, and all cancers were ATA low risk. In the appropriate clinical context, thyroid lobectomy or active surveillance can be considered for initial management of non-V600E BRAF-altered ITNs. Full article

Background: Thyroid cancer is the most common endocrine malignancy, and accurate diagnosis is crucial for effective management. Fine needle aspiration cytology, guided by the Bethesda System for Reporting Thyroid Cytopathology, categorizes thyroid nodules into six categories, with Bethesda III and IV representing indeterminate diagnoses that pose significant challenges for clinical decision-making. Understanding the molecular profiles of these categories may enhance diagnostic accuracy and guide treatment strategies. Methods: This study retrospectively analyzed data from 217 patients with Bethesda III and IV thyroid nodules who underwent ThyroSeq v3 molecular testing followed by thyroid surgery at McGill University teaching hospitals. The analysis focused on the presence of specific molecular mutations, copy number alterations (CNAs), and gene expression profiles (GEPs) within these nodules. The relationship between these molecular findings and the clinico-pathological features of the patients was also examined. Results: This study identified notable differences in the molecular landscape of Bethesda III and IV thyroid nodules. Bethesda IV nodules exhibited a higher prevalence of CNAs and distinct GEPs compared to Bethesda III nodules. Interestingly, the BRAFV600E mutation was found exclusively in Bethesda III nodules, which correlated with more aggressive malignant behavior. These findings underscore the potential of molecular profiling to differentiate between the clinical behaviors of these indeterminate nodule categories. Conclusions: Molecular profiling, including the assessment of CNAs, GEPs, and specific mutations like BRAFV600E, provides valuable insights into the nature of Bethesda III and IV thyroid nodules. The distinct molecular characteristics observed between these categories suggest that such profiling could be instrumental in improving diagnostic accuracy and tailoring treatment approaches, ultimately enhancing patient outcomes in thyroid cancer management. Full article

The advent of advanced molecular diagnostic techniques has revealed plenty of information about signaling pathways and gene regulation in cancer, as well as new inputs for the classification of cancer subtypes, diagnosis, prognosis, and prediction of response to therapy. However, in most cases we do not have single biomarkers yet and, therefore, the final diagnosis is often rendered by the combination of multiple results by means of complex algorithms, eventually leading to an increase in their costs. The problem of the costs of such tests is particularly relevant in the case of thyroid cancer (TC), because of the observed increase in the number of patients affected by thyroid nodules (TN)s, in what is considered a global pandemic. High-income countries can afford the cost of the advanced molecular tests for such a multitude of TNs, since they are covered by private insurances. People living in upper-middle, lower-middle, and especially in low-income countries, where the costs for these advanced molecular tests are supported by general taxation and out-of-pocket payments, are exposed as a personal financial burden. Immunohistochemistry in cancer management represents an extremely cost-effective method in different clinical scenarios. In the preoperative recognition of TC, the use of such method, based on Galectin-3 and others protein markers, such as HMBE1, proved to be effective in diagnosing TC in TNs indeterminate at conventional cytology (Bethesda classification III or IV), with an extremely low cost. Moreover, Galectin-3 fulfills one of the major criteria of an ideal marker, being involved in the thyroid cell transformation. Despite this evidence, Galectin-3 ThyroTest is not considered and not even mentioned in many reviews, focused on the appropriate identification of TC, as well as in studies where the cost-effectiveness of the different approaches is comparatively evaluated. The aim of this review is to emphasize the value of the Galectin-3 based immunohistochemistry as a cheap and “good enough” method in the preoperative diagnosis of TC especially in, but not limited to, low-middle income countries. Full article

Background/Objectives: Endobiliary brushing is usually performed in the diagnosis of indeterminate biliary strictures; however, in this setting, brush cytology is limited by a low diagnostic yield and sensitivity. Here, we compared the catheter flushing method (CFM) with the conventional cytologic method (CCM) in terms of cellularity and diagnostic performance. Methods: Endobiliary brushings were obtained during endoscopic retrograde cholangiopancreatography (ERCP) from patients with biliary strictures enrolled at six tertiary hospitals. Additionally, the CFM was performed after brushing. Using liquid-based cytologic preparations of samples, we assessed the diagnostic performance of the CCM using Pap staining and the CFM using methionyl-transfer RNA synthetase 1 (MARS1) immunofluorescence staining. Results: From a total of 399 patients (malignant, 253; benign, 146), 374 CCM samples and 361 CFM samples contained adequate cells, with no significant difference in diagnostic yield (93.7% vs. 90.5%, respectively; p = 0.088). The sensitivity of the CFM (90.3%) was significantly higher than that of the CCM (75.1%; p < 0.001), with no significant difference in accuracy between methods (81.2% vs. 82.6%, respectively; p = 0.608). Conclusions: The diagnostic yield of the CFM was comparable to that of the CCM. Additionally, the diagnostic performance of the CFM was comparable to that of the CCM. These findings indicate that the CFM could be an additional brush cytology method for sample collection in patients with indeterminate biliary strictures. Incorporating both the CCM and CFM might be expected to improve the diagnostic yield of brush cytology in the biliary strictures. Further prospective comparative studies between the CCM and CFM using the same staining method are needed to validate these findings. Full article

Background: Molecular testing can reduce the need for diagnostic thyroidectomy in cytologically indeterminate thyroid nodules. However, the health-related quality of life in patients managed with molecular testing is not well studied. Objective: The objective of this scoping review was to identify and analyze the health-related quality of life outcomes in patients with indeterminate thyroid nodules who are expected to undergo or have undergone surgery or molecular testing. Methods: A comprehensive search was conducted on PubMed, Scopus, PsychINFO, and Embase to identify relevant studies. The search terms included “thyroid neoplasms” or “thyroid nodule” and “molecular testing” or “surgery” and “quality of life”. The included articles were analyzed for their main study objective, study design, participant characteristics, and main results. Results: Eight studies were included in this scoping review. Four evaluated the quality-adjusted life years for patients with indeterminate thyroid nodules. Three of these studies found that molecular testing slightly improved quality-adjusted life years compared to surgery, while one study found no difference. Two studies assessed surgical health-related quality of life outcomes and reported that patients with indeterminate thyroid nodules who were expected to undergo surgery favored surgical procedures, while those who underwent surgery experienced impaired health-related quality of life. Two studies evaluated molecular testing in patients with indeterminate thyroid nodules and found that the final molecular test result significantly impacted health-related quality of life outcomes. Patients with suspicious/positive molecular test results had worse symptoms of goiter, anxiety, and depression, while those with benign results had preserved health-related quality of life scores. Patients with benign results from molecular testing experience better health-related quality of life within the first year compared to those with benign surgical outcomes. Conclusions: This scoping review highlights the importance of considering health-related quality of life outcomes in the management of patients with indeterminate thyroid nodules. Benign molecular testing results yield better quality of life than benign surgical outcomes within the first year, suggesting molecular testing as a preferable option. Further research comparing the impact of surgery and molecular testing on health-related quality of life is needed to improve shared decision-making and patient outcomes. Full article

Thyroidectomy, a pivotal treatment for various thyroid disorders, has seen its indications evolve, particularly with the 2014 American Thyroid Association (ATA) Guidelines advocating for conservative surgical approaches like lobectomy. This retrospective study analyzes thyroidectomy practices at a high-volume center from January 2014 to December 2023, focusing on patients potentially eligible for lobectomy per ATA guidelines. The inclusion criteria were tumors < 4 cm, indeterminate thyroid nodules, or differentiated thyroid carcinoma with clinically uninvolved lymph nodes (cN0). This study analyzed the proportion of patients undergoing lobectomy versus total thyroidectomy (TT) and the oncological outcomes. Of 357 patients, 243 underwent TT and 114 underwent lobectomy. The prevalence of lobectomies rose markedly, comprising 73.9% of surgeries in 2023. TT patients were predominantly female (83.5%) and had higher rates of autoimmune thyroiditis (67.5%) and malignancy (89.7%). Lobectomy patients had larger nodules and more indeterminate cytology. Among 301 malignant cases, TT was associated with higher lymph node metastasis, but similar recurrence rates, compared to lobectomy. This study underscores a shift towards lobectomy, reflecting adherence to ATA guidelines and suggesting conservative surgery is feasible without compromising outcomes. Further research on long-term outcomes and refined patient selection criteria is needed to optimize surgical approaches. Full article