Two-center validation of assays for the detection of binding and neutralizing anti-factor VIII antibodies.

INTRODUCTION: Patients with hemophilia A treated with coagulation Factor VIII (FVIII) products are at risk for developing anti-FVIII antibodies. The ABIRISK Consortium aimed to provide knowledge on the formation and detection of anti-drug antibodies against biopharmaceutical products, including FVIII. Accordingly, standardized and validated assays for the detection of binding (total) and neutralizing antibodies are needed. AIM: Two-center validation of an ELISA for the detection of total FVIII-binding IgG-antibodies and Nijmegen-Bethesda assays for the quantification of FVIII-neutralizing antibodies according to consensus validation guidelines. METHODS: Validation of assays at both sites was done according to published recommendations and included preanalytics, the determination of key assay parameters, including cut-points, assay sensitivity, precision, and FVIII interference. RESULTS: The validated assays reproducibly detected FVIII-binding and -neutralizing antibodies with comparable performance in both laboratories. Floating screening cut-points were established for both assays. Determined mass-based sensitivity of both assays (all values ≤66 ng/mL) complied with the minimum sensitivity for the detection of anti-drug antibodies as recommended by the FDA (<100 ng/mL). Intra- and inter-assay coefficients of variation did not exceed 25%. Assay validation further revealed that pre-analytical heat treatment led to potentially false-positive ELISA results, while up to 0.15 IU/mL, residual FVIII showed no significant impact. Overall, good agreement of results was found for patient samples analyzed at both study sites. CONCLUSION: Comprehensive validation of different anti-FVIII-antibody assays in two laboratories gave novel insights into the impact of pre-analytical sample treatment as well as the comparability of test results generated by the use of methodically different assays.

Diagnosis and management of factor XI alloinhibitors in patients with congenital factor XI deficiency-A large single-centre experience.

INTRODUCTION: Factor (F) XI deficiency is an inherited bleeding disorder with increased prevalence in Ashkenazi Jews where it is mainly caused by two variants, p.Glu135* (type II, leading to a null allele) and p.Phe301Leu (type III, missense variant). Inhibitor development is rare, and only seen in severe FXI deficiency (<20 IU/dL) upon exposure to plasma-based products. We report our experience of a large cohort of patients with severe FXI deficiency, including seven patients who developed FXI alloinhibitors, their presentation, natural history and subsequent perioperative management. METHODS: A single-centre retrospective database review of patients with FXI deficiency, including those who have subsequently developed inhibitors, and extraction of clinical, laboratory and genotype data, including operative management records. RESULTS: A total of 682 patients were identified with FXI deficiency, of whom 113 had FXI < 20 IU/dL and 42 had FXI ≤ 1 IU/dL. Factor XI inhibitors were seen in seven patients, six of whom were homozygous for the type II variant (prevalence of inhibitor with this genotype of 30%, risk of inhibitor upon plasma exposure 50%). FXI inhibitors were not seen, despite similar exposures, in patients with other genotypes. No alteration in bleeding phenotype occurred after inhibitor development and subsequent surgery was managed on 13 occasions with recombinant factor VIIa (rFVIIa), including low doses (15-30 µg/kg), with good haemostasis. The inhibitor spontaneously disappeared in four of seven patients over 1-22 years. CONCLUSION: FXI inhibitors were only observed in severe FXI deficient patients homozygous for p.Glu135* (null allele) upon plasma or FXI concentrate exposure, with a 30% prevalence. The bleeding phenotype was not altered and inhibitors may disappear with time. Adequate haemostasis in the perioperative setting is achievable with low doses of rFVIIa.

Assessing Adequacy: A Meta-Analysis of Rapid Onsite Evaluation of Thyroid Nodules.

INTRODUCTION: Fine-needle aspiration (FNA) is the standard form of preoperative evaluation of thyroid nodule cytological status. A significant number FNAs are classified as inadequate for interpretation, requiring a repeat FNA which is potentially avoidable, costly, and delays treatment. To address these concerns and maximize first-time FNA adequacy, rapid onsite evaluation (ROSE) of FNA specimens was introduced. Our study aims to determine the impact of ROSE on FNA adequacy. METHODS: PubMed, Embase, and Web of Science were searched for primary articles assessing the adequacy of ROSE in thyroid nodules. RESULTS: A total of 17 studies were included for a total of 24,649 thyroid nodes. Thirteen thousand two hundred fifteen (53.6%) thyroid nodules were assessed utilizing ROSE and 11,434 (46.4%) were not. Pooled adequacy increased significantly from 76% without ROSE to 92% with rose (P = 0.001). Use of ROSE increased the odds of adequate FNA by 22% (risk ratio (RR) = 1.22, 95% confidence interval (CI) = 1.12-1.32). At institutions with less than 85% effective diagnostic adequacy without ROSE, the risk for diagnostic adequacy increased by 28% with ROSE implementation (RR = 1.28, 95% CI = 1.20-1.37). In contrast, in studies reported from institutions with an effective diagnostic rate greater than 85% without the use of ROSE, the diagnostic adequacy only increased by 5% with ROSE implementation (RR = 1.05, 95% CI = 1.03-1.06). CONCLUSIONS: The use of ROSE during first-time FNA of thyroid nodules can significantly improve adequacy, especially at institutions with baseline high inadequacy rates. Implementation of ROSE can reduce repeat FNAs and its associated consequences.

Efficacy and safety of microwave ablation for treatment of follicular thyroid neoplasms: a preliminary study.

OBJECTIVE: To assess the feasibility, efficacy, and safety of microwave ablation in treating follicular thyroid neoplasms and suspicious follicular thyroid neoplasms. METHODS: In this retrospective study, the data of patients treated with microwave ablation for follicular neoplasms from December 2016 to January 2024 were summarized. The changes in nodule size, volume, technical success rate, disease progression, complete tumor resolution, thyroid function, and complications post-ablation were evaluated. RESULTS: Seventy-four patients (15 men, 59 women; mean age 46.3 ± 15.2 years) with follicular neoplasms were included. Over a median follow-up of 13 months, complete ablation was achieved, giving a 100% technical success rate. At the first month post-ablation, the maximum diameter of nodules showed no significant change (p = 0.287). From the third month, both maximum diameter and volume significantly decreased (p < 0.005 for all). Volume reduction rates remained stable at one and three months (p = 0.389 and 0.06, respectively) but increased significantly thereafter (p < 0.005 for all). By 24 months, the median maximum diameter had reduced from 2.3 cm to 0 cm, achieving a median volume reduction rate of 100%. Nodules disappeared completely in 20.3% (15/74). Local recurrence was noted in 2.7% of cases (2/74), with no metastasis or neoplasm-related deaths reported. Thyroid function remained unchanged post-treatment (p > 0.05). The complication and side effect rates were 8.1% and 4.1%, respectively. CONCLUSIONS: Initial findings suggest microwave ablation is an effective and safe treatment for follicular neoplasms, with low incidences of disease progression and complications, while maintaining thyroid function.

Accuracy and diagnostic performance of the Bethesda system for reporting thyroid cytopathology in a tertiary endocrine surgical referral center in Belgium.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology is a commonly used classification for fine needle aspiration (FNA) cytology of suspicious thyroid nodules. The risk of malignancy (ROM) for each category has recently been analyzed in three international databases. This paper compares the diagnostic performance of the Bethesda classification in a high-volume referral center in Belgium. METHODS: All consecutive thyroid procedures were registered in a prospective database from January 2010 till August 2022. Patient and surgical characteristics, preoperative Bethesda categories, and postoperative pathology results were analyzed. RESULTS: Out of 2219 consecutive thyroid procedures, 1226 patients underwent preoperative FNA. Papillary thyroid cancer was the most prevalent malignancy (N = 119, 70.4%), followed by follicular (N = 17, 10.1%) and medullary thyroid cancer (N = 15, 8.9%). Micropapillary thyroid cancer was incidentally found in 46 (3.8%) patients. Bethesda categories I, II, III, IV, V, and VI, respectively, represented 250 (20.4%; ROM 4.4%), 546 (44.5%; ROM 3.8%), 96 (7.8%; ROM 20.8%), 231 (18.8%; ROM 15.2%), 62 (5.1%; ROM 72.6%), and 41 (3.3%; ROM 90.2%) patients. Overall ROM was 13.8%. An negative predictive value (NPV) of 96.2% was found. Overall specificity was 64.2% with a positive predictive value (PPV) of 31.9%. Diagnostic accuracy was 67.8%. Compared to international databases (CESQIP, EUROCRINE, and UKRETS), ROM in this study appeared lower for Bethesda category IV (15.2 vs. 26.7% and p = 0.612). CONCLUSION: Despite being validated in numerous studies, ROM based on preoperative FNA cytology classified according to the Bethesda classification may vary among surgical centers and countries as this study reveals a higher NPV and lower PPV.

Consistency in the Distribution of Bethesda System for Reporting Thyroid Cytology Categories Over 9 Years: A Single Institute, Retrospective Study.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) has evolved since it was first introduced in 2009 to become a worldwide accepted cytologic analysis reference, due to its simplicity and reproducibility. To date, the consistency of BSRTC throughout time has yet to be investigated. METHODS: Retrospective single institution case series with chart review of all patients who underwent fine-needle aspirations for a thyroid nodule in our institution between the years 2010 and 2018 with a documented BSRTC classification. Data collection included demographics, risk factors, sonographic evaluation, nodule size, and final pathology when feasible. The main outcome is the difference in the rates of BSRTC categories benign, atypia of undetermined significance (AUS), follicular neoplasm, suspicious for malignancy, and malignant (BSRTC II-VI, respectively) between the study years. RESULTS: A total of 2830 thyroid nodules were included. BSRTC II-VI distribution was 83.9% (2373), 8.2%, (232), 2.7% (75), 3.3% (93), and 2.0% (57), respectively. There was no significant change in the overall trend of each BSRTC category distribution throughout the study. There was a significant increase in the benign cytology rate (BSRTC II) in 2011 compared to 2015 and 2018 (76.4% compared to 88.7% and 87.6%, respectively. P < .005) alongside a significant decline in the AUS category rate (BSRTC III) between the same years (13.0% compared to 4.8% and 5.5%, respectively. P < .005). CONCLUSION: BSRTC showed consistency throughout the study across all observed categories. An overlap between AUS and benign may exist, possibly due to the heterogenic definition of AUS as reflected in the 2023 BSRTC subclassification for AUS.

Thyroid Nodules: Past, Present, and Future.

BACKGROUND: Over the past millennia, the evaluation and management of thyroid nodules has essentially remained the same with thyroidectomy as the only reliable method to identify malignancy. However, in the last 30 years, technological advances have significantly improved diagnostic management of thyroid nodules. Advances in imaging have allowed development of a reliable risk- based stratification system to identify nodules at increased risk of malignancy. At the same time, sensitive imaging has caused collateral damage to the degree that we are now identifying and treating many small, low risk nodules with little to no clinical relevance. OBJECTIVE: To review the history of thyroid nodule evaluation with emphasis on recent changes and future pathways. METHODS: Literature review and discussion. RESULTS: Thyroid ultrasound remains the best initial method to evaluate the thyroid gland for nodules. Different risk-of-malignancy protocols have been developed and introduced by different societies, reporting methods have been developed and improved each, with goals of improving the ability to recognize nodules requiring further intervention and minimizing excessive monitoring of those who do not. Once identified, cytological evaluation of nodules further enhances malignancy identification with molecular markers assisting in ruling out malignancies in indeterminate nodules preventing unneeded intervention. And all societies have urged avoidance of overdiagnosis and overtreatment of low-risk cancers of little to no clinical relevance. CONCLUSION: In this review, we describe advancements in nodule evaluation and management, while emphasizing caution in overdiagnosing and overtreating low-risk lesions without clinical importance.

Accuracy of ultrasound-guided fine-needle aspiration cytology in evaluation of thyroid nodules using different ultrasonographic and cytological features.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a reliable method for preoperative evaluation of thyroid nodules particularly if ultrasound-guided (USG-FNAC). The main purpose of this study is to evaluate the efficacy of USG-FNAC and its accuracy. METHODS: We retrospectively studied 212 thyroidectomy cases with preoperative ultrasonography and FNAC data during the period 2015-2022 using TI-RADS for final ultrasound diagnosis and Bethesda system for cytological diagnosis. RESULTS: The studied cases were 200 females and 12 males. Thyroid cancer was more prevalent under 20 years old (78.5%). Papillary thyroid carcinoma comprises 84% of all cancer cases. Significant ultrasound features (p-value <0.05) favour malignancy were hypoechogenicity (66%), mixed echogenicity (84%), irregular border (61%), microcalcification (68%) and rim halo (63.6%). Malignancy was found in 21% of TI-RADS-2, 65% of TI-RADS-4 and 100% of TI-RADS-5. There is a significant difference between different categories of Bethesda system. All cases in Cat-VI were malignant (100%). Malignancy was also found in 81% of Cat-V, 20% of Cat-IV, 33% of Cat-III, 16% of Cat-II and 43% of Cat-I. Cytological features consistent with malignancy were as follows: grooving (94%), nuclear irregularities (89%), nuclear pseudoinclusion (89%) and little colloid (82%). In our study, USG-FNAC sensitivity was 83%, specificity 85%, PPV 85%, NPV 83% and accuracy 84%. CONCLUSION: Ultrasound features in favour of malignancy in thyroid nodules are hypoechoic or complex echogenicity, irregular border, punctuate calcification and presence of rim halo. Cytological features in favour of malignancy are grooving, nuclear irregularities, nuclear pseudoinclusion and little or absent colloid.

Are we ready to bridge classification systems? A comprehensive review of different reporting systems in thyroid cytology.

The evaluation of thyroid lesions is common in the daily practice of cytology. While the majority of thyroid nodules are benign, in recent decades, there has been increased detection of small and well-differentiated thyroid cancers. Combining ultrasound evaluation with fine-needle aspiration cytology (FNAC) is extremely useful in the management of thyroid nodules. Furthermore, the adoption of specific terminology, introduced by different thyroid reporting systems, has helped effectively communicate thyroid FNAC diagnoses in a clear and understandable way. In 1996, the Papanicolaou Society thyroid cytological classification was introduced. This was followed in 2005 by the first Japanese and then in 2007 by the Bethesda System for Reporting Thyroid Cytopathology, which subsequently underwent two revisions. Other international thyroid terminology classifications include the British, Italian, Australasian and other Japanese cytology systems. This review covers similarities and differences among these cytology classification systems and highlights key points that unify these varied approaches to reporting thyroid FNAC diagnoses.

The Bethesda System for Reporting Thyroid Cytopathology in the African American population: A tertiary centre experience.

BACKGROUND: The reported risk of malignancies (ROM) remains controversial for fine needle aspiration (FNA) of thyroid nodules in the African American (AA) population. Herein, the ROM along with frequency was assessed for each of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) diagnostic categories. MATERIALS AND METHODS: The electronic pathology archive of a large academic hospital was retrospectively searched for cytopathology reports of thyroid nodules in AA patients (2010-2019) and Non-African American (NAA) control cases. The patients' demographic, thyroid nodule characteristics, FNA results using TBSRTC and surgical diagnoses were recorded, whenever available. RESULTS: Three hundred ninety-one cases were identified, 317 females (81.1%) and 74 males (18.9%) with median age 50.0 (SD = 14.4). The mean size of the nodules was 2.1 cm (SD = 1.4). The Bethesda categories were: 5.4% (I), 35.0% (II), 35.3% (III), 7.7% (IV), 3.3% (V) and 13.3% (VI). The overall ROM of thyroid nodules was 43.8% (89/203) on surgical follow-up (203/391). The ROM in each Bethesda categories were: 33.3% (I), 11.6% (II), 35.2% (III), 15.8% (IV), 83.3% (V) and 100% (VI) on surgical follow-up. The frequency of thyroid nodules was higher in AA females; however, the ROM was higher in AA males (48.3%) compared with AA females (41.2%). CONCLUSION: The ROM in Categories I, II and III was higher than those reported in the TBSRTC while being similar in Categories IV, V and VI. The overall risk of thyroid malignancy in our AA patient population was higher than those in the literature. The overall ROM of thyroid nodules in AA males was higher than of AA females.

[SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: Interest and place of thyroid cytology]. / Consensus SFE-AFCE-SFMN 2022 sur la prise en charge des nodules thyroïdiens : intérêt et place de la cytologie thyroïdienne.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a symptom that is a frequent reason for consultation in endocrinology. Thyroid nodules are very common and mostly benign. Thyroid ultrasound and thyroid fine-needle aspiration biopsy (FNAB) are the reference tests for the analysis of these nodules. The aim of this article is to describe for the cytopathologist the key points of the SFE-AFCE-SFMN 2022 consensus involving thyroid cytology: the indications for thyroid FNAB, the technique and analysis, and the management (treatment, follow-up) following this cytological screening examination, a key element in the management of the thyroid nodule.

Cervical cancer screening practices in HIV positive females - a missing link in health care delivery in Pakistan.

Objectives: To probe cervical cancer screening practices in local women positive for human immunodeficiency virus, and to determine the cervical cytological changes in them. METHODS: The serial cross-sectional study was conducted at the Jinnah Hospital and Services Hospital, Lahore, Pakistan, from April 2019 to October 2020, and comprised female patients aged 18-45 years who were positive for human immunodeficiency virus or acquired immunodeficiency syndrome and were registered with the relevant programme being run by the provincial government in Punjab. Blood samples of all the patients were collected for the determination of human immunodeficiency virus viral load and cluster of differentiation 4+ count. Cervical smears were taken for cytopathological analysis, while the swabs were analysed for culture sensitivity. The same individuals were subjected to the same testing one year later, and the status of the disease and clinical stability or disease progression was explored. Data was analysed using SPSS 25. RESULTS: There were 150 women with mean age 32.08±7.13 years (range: 21-45 years). Age at marriage/sexual activity was 17.33±4.73 years in 15(10%) subjects. Cytological examination showed atypical squamous cells of undetermined significance in 6(4%) of the cases whereas 3(2%) cases showed atypical squamous cells, which cannot rule out high grade squamous intraepithelial lesion on cytology, while the rest were classified as negative for intraepithelial lesion or malignancy. Cervical microbial changes revealed methicillin-resistant staphylococcus aureus infection in 9(6%) cases, extended-spectrum beta-lactamase in 15(10%) cases, whereas fungal infection and trichomonas vaginalis infection were found in 30(20%) smears. There was a significant association between cluster of differentiation 4+ cell count and stability of high-risk patients (p<0.001). After one year, 84(56%) patients remained clinically stable, while 51(34%) developed some chronic illness. There was a significant association between cluster of differentiation 4+ cell count <200/mm3 and the risk of developing a chronic illness (p<0.001). CONCLUSIONS: There was a dire need to educate healthcare workers to offer regular cervical screening to patients with high-risk sexually-transmitted infections to prevent them from the morbidity and mortality related to cervical cancer.

Changes in thyroid cytology reporting in the 3rd edition of the Bethesda system.

Reporting fine-needle aspiration of thyroid nodules in the Bethesda classification is a practice widely used internationally and by us. The revised third edition of the Bethesda System of Reporting Thyroid Cytopathology brings changes in terminology, content, and new chapters. In terms of terminology, an obvious change is the removal of the two-word names of three categories while maintaining the six diagnostic categories of the previous versions - new: BI - non-diag- nostic, BIII - atypia of undetermined significance, BIV - follicular neoplasia. In the detailed description of the findings within the individual categories, the ter- minological changes adopted by the fifth edition of the WHO classification of thyroid neoplasia are respected - in particular, the recommended name follicular thyroid nodular disease for the most frequently represented category BII - benign. In the evaluation itself, the diagnostic specifications accepted by the current WHO classification of histopathological findings are reflected in the individual categories - if they are applicable at the cytological level. Targeted attention will need to be paid to high grade features. The revised version brings new chapters dedicated to molecular testing and evaluation of the paediatric population.

UTILITY OF THE 2023 BETHESDA SYSTEM AUS SUBCATEGORIZATION ON THYROID ASPIRATES.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is widely used for the standardized reporting of thyroid fine-needle aspiration (FNA) cytology. The 2023 revision of TBSRTC introduced specific subcategories for the classification of atypia of undetermined significance (AUS). This study tests the association between AUS subtypes and malignant diagnoses, namely AUS-nuclear atypia and AUS-other, in archived thyroid - FNA specimens with atypia from 2018-2022 at King Abdulaziz University Hospital. A total of 104 thyroid - FNA specimens with AUS were re-evaluated cytologically and correlated with subsequent surgical outcomes, along with a discussion of discrepant cases.

Correlation of ultrasound-based TIRADS and the Bethesda system for reporting of thyroid cytopathology: A study in a tertiary care centre.

BACKGROUND: The age-standardised incidence rate of thyroid cancer in India is 1 in 416 in the general population. This increased incidence has mainly been attributed to improved detection methods for small thyroid lesions. Two such methods are the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS) and the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). AIMS AND OBJECTIVES: To study the correlation between ACR TIRADS and TBSRTC, and between each system and the final histopathological report. MATERIALS AND METHODS: Thyroid cytopathology cases were retrieved for the period January 2019 to July 2022. For each case, the TIRADS score and Bethesda category were noted. Histopathology specimens were also traced. RESULTS: The study comprised 1100 cases, with 955 female and 145 male patients (M:F = 1:6.59), and ages ranging between 7 and 85 years. The TIRADS scoring was available for 1036 cases. Histopathology was available for 231 cases. There was a significant correlation between TIRADS and TBSRTC, with a p-value of 0.000 and a substantial Kappa agreement of 0.688. Both TIRADS and TBSRTC also had significant correlations with the histopathology data, with a p-value of 0.000 for each. The sensitivity values for TBSRTC and TIRADS were 69.4% and 65.8%; specificity, 99.3% and 96.5%; positive predictive value (PPV), 98.3% and 91.8%; and negative predictive value (NPV) 84.7% and 84.4%, respectively. The risk of malignancy (ROM) was also calculated and was found to be high, especially for TBSRTC II, III, IV and V (11.3%, 20%, 61.5%, 97.4% respectively) and TIRADS 2 and 3 (10.3% and 29.6% respectively). CONCLUSION: The TIRADS and TBSRTC systems of categorisation of thyroid lesions are concordant and could help improve the overall survival rate of patients with thyroid malignancies.

A Killian-Jamieson diverticulum potentially mimicking a thyroid nodule: A case report highlighting the cytology of a pharyngoesophageal diverticulum.

The authors highlight the important contribution of rapid on-site evaluation by the cytopathologist of a pharyngoesophageal diverticulum in a mass initially interpreted clinically as thyroidal in origin. They discuss pitfalls in avoiding interpretive diagnostic error and inappropriate thyroid Bethesda reporting.

Diagnosis of patients with Lynch syndrome lacking the Amsterdam II or Bethesda criteria.

BACKGROUND: Lynch Syndrome (LS) is an autosomal dominant inheritance disorder characterized by genetic predisposition to develop cancer, caused by pathogenic variants in the genes of the mismatch repair system. Cases are detected by implementing the Amsterdam II and the revised Bethesda criteria, which are based on family history. MAIN BODY: Patients who meet the criteria undergo posterior tests, such as germline DNA sequencing, to confirm the diagnosis. However, these criteria have poor sensitivity, as more than one-quarter of patients with LS do not meet the criteria. It is very likely that the lack of sensitivity of the criteria is due to the incomplete penetrance of this syndrome. The penetrance and risk of developing a particular type of cancer are highly dependent on the affected gene and probably of the variant. Patients with variants in low-penetrance genes have a lower risk of developing a cancer associated with LS, leading to families with unaffected generations and showing fewer clear patterns. This study focuses on describing genetic aspects of LS cases that underlie the lack of sensitivity of the clinical criteria used for its diagnosis. CONCLUSION: Universal screening could be an option to address the problem of underdiagnosis.

Thyroglobulin is a poor predictor of differentiated thyroid cancer in patients who undergo surgery for thyroid nodular diseases.

OBJECTIVES: Thyroglobulin, produced exclusively by thyroid follicular cells, serves as a specific tumor marker for the follow-up of differentiated thyroid cancer (DTC) patients after thyroidectomy. However, its role as a predictor of malignancy in patients with thyroid nodules is controversial. We assessed the potential role of preoperative serum thyroglobulin concentration to predict DTC in patients without a preoperative diagnosis of malignancy who underwent partial or total thyroidectomy. METHODS: This retrospective study included patients with a preoperative diagnosis of benign multinodular goiter (MNG) or a thyroid nodule with indeterminate cytology (INC) (Bethesda system categories III/IV) who underwent partial or total thyroidectomy between January 2014 and May 2019. We compared the patients' demographic, clinical, imaging, and biochemical data according to their final diagnosis: DTC or benign thyroid nodular disease. Further statistical analysis included odds ratio calculation and receiver operating characteristic (ROC) curve analysis. RESULTS: Of 131 patients who met inclusion and exclusion criteria, the indication for surgery was benign MNG in 69 patients and a thyroid nodule with INC in 62 patients. A final diagnosis of DTC was reported in 18 of the 69 benign MNG patients (26%) and in 30 of the 62 thyroid nodule with INC patients (48%). The preoperative measurements of nodule diameter and serum thyroid-stimulating hormone and thyroglobulin concentrations did not significantly differ between patients with a final diagnosis of DTC and those with benign histology. CONCLUSIONS: Preoperative serum thyroglobulin alone is insufficient to differentiate between malignant and benign thyroid nodular disease.

Interobserver variability in inconclusive diagnostic categories of thyroid fine needle aspiration cytology: An urban-based tertiary hospital experience.

INTRODUCTION: Thyroid nodules are typical lesions, usually non-malignant, and surgery is unnecessary in most patients. However, distinguishing between benign and malignant is challenging. Fine needle aspiration cytology (FNAC) is considered a primary diagnostic and prognostic tool with an effective cost for evaluating thyroid enlargement. Unfortunately, using FNAC to diagnose inconclusive lesions in the category III-Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS) based on TBSRTC classification is a problematic issue. This study aimed to evaluate the interobserver variability of AUS/FLUS interpretation among pathologists. METHODS: A retro-observational study: previous 127 AUS/FLUS cases were enrolled. Seventy-two cases met inclusion criteria and were then reclassified by different anatomical pathologists under blinded-design assignments. The concordance among pathologists and the percent alteration of the risk of malignancy (ROM) were compared to the original reports and histological diagnosis. RESULTS: About 72 % of AUS/FLUS cases were changed after the reclassification. Approximately 46 % were changed to benign while 12.5 % were reclassified as carcinoma. Moreover, 30 % of those original AUS/FLUS were histologically diagnosed as malignant or carcinoma lesions. The concordances among consensus diagnosis and results from each pathologist are acceptable, Kappa(s) were 0.674 to 0.898 (p < 0.001) and Spearman correlations were 0.820 to 0.957 (p < 0.0001). CONCLUSION: There are substantial interobserver differences and changes in cytological diagnosis when re-evaluation is performed by multiple pathologists using TBSRTC. A second or third opinion should be sought routinely to establish a consensus diagnosis as a supplement to the initial diagnosis of AUS/FLUS. The reclassification reduces medical expenses and the rate of unnecessary surgery, especially in patients with cytologically confirmed benign thyroid nodules. Preoperative molecular evaluation is a promising method for assisting in the diagnosis of thyroid nodules, but additional research is necessary.

The Role of "Critical" Ultrasound Reassessment in the Decision-Making of Bethesda III Thyroid Nodules.

Background and Objectives: Bethesda III (BIII) thyroid nodules have an expected malignancy rate of 5-15%. Our purpose was to assess which US criteria are most associated with cancer risk, and the value of critical ultrasound (US) reassessment. Methods: From 2018 to 2022, 298 BIII nodules were enrolled for thyroidectomy (79 malignancies). We evaluated ultrasonographic data: hechogenicity, intralesional vascularization, spiculated margins, micro-calcifications, "taller than wide" shape, extra-thyroidal growth, size increase, as well as their association with histology. We also evaluated if the ultrasound reassessment modified the strategy. Results: Spiculated margins and microcalcification were significantly correlated with malignancy risk. Spiculated margins showed a specificity of 0.95 IC95% (0.93-0.98); sensitivity 0.70 IC95% (0.59-0.80). Microcalcifications showed a sensitivity of 0.87 CI95% (0.80-0.94); specificity 0.75 CI95% (0.72-0.83). The presence of these signs readdressed the strategy in 76/79 cases Then, the indication for surgery was appropriate in 75% of cases. Conclusions: Microcalcifications and spiculated margins should be routinely sought during a final ultrasound reassessment in BIII nodules. These signs allowed for a modification of the strategy in favor of surgery in 96% of the cases that were not otherwise referred to surgery. The importance of integrating ultrasound and cytology in the evaluation of BIII thyroid nodules is confirmed. Reassessment with ultrasound of BIII nodules allowed for a redirection of the surgical choice.