Search Results (14)

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

Background/Objectives: The 2023 revision of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) simplified the subcategorization of category III into two groups: “AUS-nuclear” and “AUS-other”. The aim of this study was to investigate the risk of malignancy (ROM) of individual BSRTC categories with a particular emphasis on the “AUS-nuclear” and “AUS-other” subcategories and to check whether the low-risk follicular-cell-derived thyroid neoplasm (LRTN) interpretation or EU-TIRADS class of the nodule modify ROM. Methods: The analysis covered the FNA results of 18,225 nodules in 12,470 patients. The rate of malignancy (the upper limit of ROM) was established on the basis of the assessment of 1660 nodules treated surgically in 978 patients. Results: In the broadest variant, with all LRTNs regarded as malignant, the ROM for subsequent categories was as follows: I: 0.4–3.5%, II: 0.1–1.3%, III: 3.8–17.7%, IV: 23.3–27.8%, V: 79.6–90.1%, and VI: 86.3–100.0%. In AUS-nuclear nodules, the ROM was 10.5–28.9%, while in AUS-other nodules, it was 2.2–12.2%. The exclusion of NIFTP or all LRTNs from cancers mainly affected the ROM of AUS-nuclear nodules: 9.4–25.9% or 8.6–23.7%, respectively. EU-TIRADS 5 class increases the ROM in AUS-nuclear nodules to 78.3%, OR: 15.7 and in AUS-other to 40.7%, OR: 6.6. Conclusions: The 2023 BSRTC is a welcome step towards simplification of the way nodules are classified within category III. The AUS-nuclear subcategory is associated with a two-times-higher incidence of malignancy than the AUS-other regardless of LRTN interpretation and EU-TIRADS class of the nodule. The EU-TIRADS 5 class of the nodule is helpful in the identification of category III nodules with a high risk of malignancy. 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

Introduction: Thyroid nodules are extremely common and require complex management to prevent unnecessary surgical intervention and ensure that no malignant disease is overlooked. Several diagnostic tools and scoring systems are available to evaluate the risk of malignancy (ROM). The goal is to assess variables that can aid and support the clinical recommendations suggested by the updated Bethesda System for Reporting Thyroid Cytopathology (TBSRTC-2023), such as the ultrasonographic features of thyroid nodules, particularly for the indeterminate categories III (atypia of undetermined significance) and IV (follicular neoplasm). Methods: We retrospectively analysed the correlation of the demographic and ultrasonographic characteristics of thyroid nodules with the cytopathological and histopathological diagnoses of TBSRTC categories III (atypia of undetermined significance), IV (follicular neoplasm), V (suspicious for malignancy), and VI (malignant) in patients who underwent surgery in a single Portuguese centre over a 10-year period. Results: In total, 360 nodules were evaluated in 341 patients, and 57% were histopathologically malignant or borderline. The majority were included in the TBSRTC indeterminate categories III and IV, with ROMs of 44% and 43%, respectively. The ultrasonographic characteristics associated with a higher TBSRTC category and a greater ROM value were hypoechogenicity, the presence of microcalcifications, irregular margins, and the presence of cervical adenopathy. When correlating with a malignant histology, only adenopathy and the presence of microcalcifications were observed to be statistically significant. Discussion: The indeterminate categories of the TBSRTC have been the most challenging ones to manage. The new TBSRTC (2023) guidelines, as well as the ultrasonographic characteristics of a patient’s nodule, can be helpful in assessing the ROM and deciding on an appropriate course of treatment. Other resources, such as molecular tests, are also playing a more important role in the clinical decision process and may become crucial in the future. Conclusions: The worrisome ultrasound features that this study found to statistically correlate with a malignant histology were the presence of microcalcifications and adenopathy. The clinical management of thyroid nodules requires a careful analysis of clinical history and an evaluation of demographic details, personal and family history, ultrasonographic features, and the results of cytopathology, thyroid function, and molecular/genetic tests. Full article

Background: Fine-needle aspiration cytology (FNAC) is widely used to diagnose and monitor thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is the standard for interpreting FNAC specimens. The risk of malignancy in Bethesda III nodules, also known as Atypia of Undetermined Significance (AUS), varies significantly throughout several studies published worldwide. This retrospective study examines the risk of cancer in thyroid FNAC categorized as Bethesda III as identified in the final histopathology of thyroidectomy specimens at a single endocrine surgery center. Methods: This retrospective cohort analysis included 1038 consecutive patients who underwent elective thyroid surgery with complete follow-up data between January 2020 and March 2024. Preoperative data on clinical and pathological characteristics have been collected. The final histopathology report from the thyroidectomy specimen was compared to the results of the preoperative FNAC on nodules that were judged to be Bethesda category III. Statistical methods were performed using SPSS version 29. Results: A total of 670 ultrasound-guided FNACs (64.5%) performed during the study period were included in the final analysis. The study population was predominantly female, represented by 79.6% of patients with a mean age of 42.5 (SD 12.1), while 20.4% were male and significantly older with mean age of 45.13 years (p = 0.02). The FNAC inadequacy rate was 5.1%, which was associated with a high risk of malignancy (6 out of 34; 17.6%). Out of the total sample size of 170 patients classified as group III, 57 were found to have malignancies in final surgical histopathology, representing 33.5% of the cases within this category. The secondary gender-related outcome analysis showed that female patients classified under the Bethesda II category had a significantly higher risk of malignancy, with a rate of 21.2%, compared to males who had a malignancy rate of 3.4% in the same Bethesda category (p = 0.001, chi-square test). However, the female patients exhibited prognostically superior non-invasive tumors compared to male individuals (p = 0.02, chi-square test). Conclusion: This study’s results indicate that Bethesda categories II and III are associated with a higher risk of malignancy in comparison to the reports of the first and third editions of the TBSRTC, particularly for female patients classified under category II. Full article

This study aims to explore the feasibility of fine-needle aspiration biopsy (FNAB) under dual modal photoacoustic tomography(PAT)/ultrasound (US) imaging. A total of 25 patients who have thyroid nodules with thyroid imaging reporting and data system (TIRADS) 3 and 4 (malignant risk <85%) were recruited. The specimens obtained from the PAT/US-guided FNAB were collected for cytology analysis. Cytological diagnoses for the 25 patients were classified in perspective of the Bethesda system for reporting thyroid cytopathology diagnostic category (DC) I: 4%(1/25); DC II: 12% (3/25); DC III: 20% (5/25); DC IV: 8% (2/25); DC V: 32% (8/25); and DC VI: 24% (6/25). The DC I nodule exhibited inadequate cytology and had structural characteristic of predominant calcifications in PAT/US mapping. The DC V-VI nodules showed lower photoacoustic (PA) signals compared to the DC I-IV nodules. Regions with a high PA signal demonstrated a significant number of erythrocytes in FNAB cytology. Moreover, nodules with microcalcifications did not show a significant difference compared to their surroundings in the PA signal, while nodules with macrocalcifications gave higher PA signals compared to their surroundings. The conclusions are as follows: combining US with PAT can evaluate the structure and function of thyroid nodules in vivo. This study demonstrates that dual modal PAT/US imaging has the potential to be an effective clinical tool to guide FNAB of thyroid nodules. Full article

Significant advancements have been made over the past decade in our understanding of thyroid cancers, encompassing histomorphology, cytology, and ancillary techniques, particularly molecular tests. As a result, it is now feasible to put forth a comprehensive histo/cytomolecular approach to treating these tumors, thereby offering patients treatments that are precisely tailored to their unique circumstances. Full article

While thyroid nodules are less common in children than in adults, they are more frequently malignant. However, pediatric data are scarce regarding the performance characteristics of imaging and cytopathology classification systems validated to predict the risk of malignancy (ROM) in adults and select those patients who require fine-needle aspiration (FNA) and possibly surgical resection. We retrospectively reviewed the electronic medical records of all patients 18 years of age or younger who underwent thyroid FNA at our institution from 1 July 2015 to 31 May 2022. Based on surgical follow-up from 74 of the 208 FNA cases, we determined the ROM for the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) ultrasound risk stratification system and The Bethesda System for Reporting Thyroid Cytopathology and added our results to those of pediatric cohorts from other institutions already published in the literature. We found the following ROMs for 1458 cases using ACR TI-RADS (TR): TR1. Benign: 2.2%, TR2. Not Suspicious: 9.3%, TR3. Mildly Suspicious: 16.6%, TR4. Moderately Suspicious: 27.0%, and TR5. Highly Suspicious 76.5%; and for 5911 cases using the Bethesda system: Bethesda I. Unsatisfactory: 16.8%, Bethesda II. Benign: 7.2%, Bethesda III: Atypia of Undetermined Significance: 29.6%, Bethesda IV. Follicular Neoplasm: 42.3%, Bethesda V. Suspicious for Malignancy: 90.8%, and Bethesda VI. Malignant: 98.8%. We conclude that ACR TI-RADS levels imply higher ROMs for the pediatric population than the corresponding suggested ROMs for adults, and, in order to avoid missing malignancies, we should consider modifying or altogether abandoning size cutoffs for recommending FNA in children and adolescents whose thyroid glands are smaller than those of adults. The Bethesda categories also imply higher ROMs for pediatric patients compared to adults. Full article

Since Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) was introduced as a new thyroid tumour entity, many studies, and meta-analyses on diagnosing NIFTP have been published. NIFTP-revised histopathological criteria emerged in 2018. NIFTP is defined as a histological entity and its diagnosis requires a careful histological examination. Its molecular profile is similar to follicular-like tumours. Ultrasound features are unable to differentiate NIFTP. NIFTP is not a cytological diagnosis, but it influences the risk of malignancy in several categories of The Bethesda System for Reporting Thyroid Cytopathology terminology. Full article

Thyroid nodules are common and typically detected by palpation and/or ultrasound (US). Guidelines have defined the management of large nodules, but controversy exists regarding nodules ≤ 1 cm. We evaluated a cohort of patients with subcentimeter nodules to determine their rate of malignancy (ROM). A total of 475 thyroid FNAs of lesions ≤ 1 cm with available follow-up were identified from January 2015–December 2019. For comparative analysis, we added a control series of 606 thyroid lesions larger than 1 cm from the same reference period. All aspirates were processed with liquid-based cytology and classified according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Subcentimeter nodules were stratified as 35 category I—non-diagnostic cases (ND; 7.3%), 144 category II—benign lesions (BL; 30.3%), 12 category III—atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS; 2.5%), 12 category IV—follicular neoplasm/suspicious for follicular neoplasm (FN/SFN; 2.5%), 124 category V—suspicious for malignancy (SM; 26.1%), and 148 category VI—positive for malignancy (PM; 31.1%). A total of 307 cases (64.6%) underwent subsequent surgery. Only one ND and three BLs had a malignant outcome. ROM for indeterminate lesions (III + IV) was 3.2%; with 1.6% for category III and 3.2% for category IV. ROM for the malignant categories (V + VI) was 88.2%. The control cohort of lesions demonstrated a higher number of benign histological diagnoses (67.3%). We documented that 57.2% of suspected subcentimeter lesions were malignant, with a minor proportion that belonged in indeterminate categories. There were very few ND samples, suggesting that aspirates of subcentimeter lesions yield satisfactory results. Suspected US features in subcentimeter lesions should be evaluated and followed by an interdisciplinary team for appropriate patient management. Full article

Thyroid nodules are a common finding in the adult population including the fact that more than 50% of individuals, over the age of 60, have thyroid nodules. The majority have been mostly detected with ultrasonography and 10% by palpation. The majority of these nodules are benign, whereas 5–15% of them are malignant. The pre-operative diagnosis of cancer is a critical challenge in order to ensure that each patient can be treated with the best tailored management with a reduction of unnecessary surgery for benign lesions. Fine needle aspiration cytology (FNAC) represents the first and most important diagnostic tool for the evaluation of thyroid lesions. According to the literature, FNAC is able to render a conclusive diagnosis in up to 70–80% of all cases. For the remaining 20–30% of nodules, cytological diagnoses fall into the category of indeterminate lesions mostly due to the lack of specific morphological features. According to the Bethesda system for reporting thyroid cytopathology (TBSRTC), indeterminate lesions can be sub-stratified into three different subcategories including “atypia of undetermined significance/follicular lesion of undetermined significance-AUS/FLUS”; “follicular or Hürthle cell neoplasm/suspicious for follicular or Hürthle cell neoplasm-FN/SFN”; and “suspicious for malignancy-SFM”. Many of these indeterminate lesions undergo repetition or diagnostic lobectomy. Nonetheless, the majority of these cases will have a benign diagnosis due to the fact that the rate of cancer ranges between 6 and 30%. It stands to reason that the application of ancillary technique, mostly molecular testing, emerged as a critical additional tool for those thyroid indeterminate lesions. Since the early 1990s, material collected from cytological samples yields sufficient and adequate cells for the detection of point mutation or gene fusions. Nonetheless, the further availability of new sequencing technologies such as next-generation sequencing (NGS) has led to more comprehensive molecular applications adopted now in clinical use. The current review investigates the multiple advances in the field of molecular testing applied in thyroid cytology. Full article

The aim of the study was to identify a possible relation between various ultrasonographic (US) appearances of Hashimoto′s thyroiditis (HT) and the risk of obtaining an alarming cytology of coexisting nodules. The study included 557 patients with HT, who had been referred for fine needle aspiration biopsy (FNA). We divided US patterns of HT (UP-HT) into eight groups: (a) Hypoechoic (compared to submandibular glands), homogeneous/fine echotexture; (b) hypoechoic, heterogeneous/coarse echotexture; (c) marked hypoechoic (darker than strap muscles), heterogeneous/coarse echotexture; (d) heterogeneous echotexture with hyperechoic, fibrous septa; (e) multiple, discrete marked hypoechoic areas (sized as 1 to 6 mm); (f) normoechoic pseudo-nodular areas; (g) echostructure similar to connective tissue; (h) thyroid parenchyma with no signs of HT. Indications for a surgical treatment resulting from the FNA outcome (categories IV–VI of Bethesda System for Reporting Thyroid Cytopathology) were identified only in patients with variants b, c, and e of UP-HT, but merely the “multiple, discrete marked hypoechoic areas” variant significantly increased the odds of obtaining such cytology (OR:5.7). The presence of the “normoechoic pseudo-nodular areas” variant significantly increased the odds for the benign cytology (OR:1.7). There are significant differences in the frequency of obtaining an alarming cytology in relation to the UP-HT variant. Full article

The aim of this study was to compare the diagnostic effectiveness of EU-TIRADS in two groups of nodules with equivocal cytology (categories III-V of Bethesda system), with and without Hürthle cells (HC and non-HC). The study included 162 HC and 378 non-HC nodules with determined histopathological diagnosis (17.9% and 15.6% cancers). In both groups calculated and expected risk of malignancy (RoM) for high, intermediate and benign risk categories of EU-TIRADS were concordant. RoM for low risk category was higher than expected in both groups, but especially in HC (HC: 13.9%, non-HC: 7.0%, expected: 2–4%). The majority of cancers in HC of that category were follicular thyroid carcinomas (FTC) and Hürthle cell thyroid carcinoma (HTC) (60.0% vs. non-HC: 16.7%). The diagnostic efficacy of EU-TIRADS was lower in HC (the area under the receiver operating characteristics curve (AUC): 0.621, sensitivity (SEN): 44.8%, specificity (SPC): 78.9% for high risk threshold) than in non-HC (AUC: 0.711, SEN: 61.0%, SPC: 77.7%). AUC was the highest for category V (AUC > 0.8, both groups) and the lowest for category IV (inefficient, both group). If intermediate risk category was interpreted as an indication for surgery, 25% of cancers from category III and 21.4% from category IV would not be treated in the HC group (0.0% and 7.4% from non-HC group, respectively). EU-TIRADS does not aid making clinical decisions in patients with cytologically equivocal HC nodules, particularly those classified into category IV of Bethesda System for Reporting Thyroid Cytopathology (BSRTC). Full article

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) introduced a new category: Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS) comprising of heterogenous lesions with a lesser degree of atypia. Its routine use is a bit controversial. The study cohort included AUS/FLUS thyroid cytopathological diagnoses signed out at Fimlab Laboratories from the period of 1 October 2013 to 31 December 2016. We analyzed all the AUS/FLUS cases, their cytology subclassification, and their cyto-histological correlation, when available. In total, there were 331 AUS/FLUS cases from 252 patients. The mean age was 59.8 years and there were 196 females and 56 males. Repeated AUS/FLUS was diagnosed in 75 (29.8%) cases. Out of 252 patients, 118 (46.8%) were operated on. Sixty-eight were operated on after the first AUS/FLUS diagnosis, 46 after 2 AUS/FLUS diagnoses, and 4 after 3 AUS/FLUS diagnoses. In total, there were 37 (14.7%) malignancies and 40 benign tumors. The risk of malignancy for AUS/FLUS (14.7%) is in agreement with the original TBSRTC risk of malignancy. The risk of neoplasia was 30.6% in our series. Full article