Validating the Modified McGill Thyroid Nodule Score for Assessment of Preoperative Risk of Pediatric Thyroid Malignancy.

OBJECTIVE: The McGill Thyroid Nodule Score (MTNS) is a preoperative tool used to predict the risk for well-differentiated thyroid cancer in adults. It was developed by a multidisciplinary team using established evidence-based risk factors for thyroid cancer. The modified McGill Thyroid Nodule Score (mMTNS) was developed to predict malignancy risk in children. A pilot study suggested the mMTNS was able to assess malignancy risk in children with indeterminate cytology on fine needle aspiration (FNA). This study seeks to validate these findings. METHODS: Retrospective chart review identified subjects who underwent FNA biopsy and subsequent resection. Each patient was assigned a score to compare to final pathology. Statistical analysis was performed with SPSS. All tests were 2-tailed and statistical significance defined p < 0.05. Logistic regression used to determine predictive values of scores. RESULTS: 46 patients ≤21 years of age underwent resection of a thyroid nodule. Female predominance of 85% (n = 39). 78% (n = 36) of patients had palpable nodule. 65% (n = 30) found to have benign pathology and 35% (n = 16) found to have malignancy. Malignant nodules associated with greater mean mMTNS compared to benign [13.63 vs 7.23]. An mMTNS greater >12 had sensitivity of 86.7%, specificity of 90.3%, positive predictive value of 81.3%, and negative predictive value of 93.3%. CONCLUSION: Our data suggests the mMTNS continues to be a useful adjunct in predicting malignancy risk of pediatric thyroid nodules. An mMTNS >12 has a high risk for malignancy, which can aid in counseling and clinical decision making, particularly when there is indeterminate cytology on FNA. LEVEL OF EVIDENCE: IV.

Prevalence of thyroid diffuse goiter and its association with body mass index and the presence of cysts and nodules in children and adolescents: the Fukushima Health Management Survey.

The main cause of diffuse thyroid goiter is autoimmune chronic thyroiditis, otherwise known as Hashimoto's thyroiditis. Thyroid hormones play pivotal roles in growth and development during childhood. However, the prevalence of diffuse goiter and the relationships between diffuse goiter, thyroid volume, cysts and nodules, and anthropometric measurements in children are not well known. Among 789,459 participants who participated in thyroid ultrasound examinations, 320,206 participants (male: 161,728; female: 158,478) aged 1-23 years were analyzed. Logistic regression analyses were conducted to calculate the odds ratios of the standard deviation score of body mass index (BMI-SDS), the SDS of bilateral width multiplied thickness area (BWTAR-SDS) as a provisional determination of thyroid volume, and the presence of nodules or cysts for positive diffuse goiter compared with negative diffuse goiter after correction for sex and age. The prevalence of diffuse goiter increased in a female-dominant manner with aging. Compared with the absence of diffuse goiter, the age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS (1 SD), BWTAR-SDS (1 SD), cysts, and nodules were 1.24 (1.21-1.27), 3.21 (3.13-3.29), 0.53 (0.50-0.58), and 1.38 (1.17-1.64), respectively. The odds ratios of nodules for positive diffuse goiter were 4.18 (1.08-16.08), 1.76 (1.01-3.07), 1.80 (1.32-2.45), and 1.34 (1.08-1.67) in the age groups 1-7, 8-11, 12-15, and 16-23 years, respectively. The age-dependent increase in the prevalence of diffuse goiter was independently associated with increased BMI and positive prevalence of nodules in young individuals.

Comparison of safety, efficacy, and patient satisfaction with thermal ablation versus endoscopic thyroidectomy for benign thyroid nodules in a propensity-matched cohort.

BACKGROUND: Thyroid nodules (TNs) often require intervention due to symptomatic or cosmetic concerns. Radiofrequency ablation (RFA) has shown promise as a treatment option, offering potential advantages without neck scars. Recently, the scarless treatment alternative of transoral endoscopic thyroidectomy vestibular approach (TOETVA) has emerged. When surgery can be performed in a scarless manner, it remains unclear whether ablation is still the preferred treatment choice. This study aims to compare the safety, efficacy, and patient satisfaction of RFA and TOETVA. STUDY DESIGN: A retrospective data analysis was conducted on patients treated with RFA or TOETVA for unilateral benign TNs between December 2016 and September 2021. Propensity score matching was employed to create comparable groups. Various clinicopathologic parameters, treatment outcomes, and costs were assessed. RESULTS: Of the 2814 nonfunctional thyroid nodules treated during this period, 642 were benign and unilateral. A total of 121 and 100 patients underwent thermal ablation and transoral endoscopic thyroidectomy, respectively. After matching, 84 patients were selected for each group. Both RFA and TOETVA demonstrated low complication rates, with unique complications associated with each procedure. Treatment time (30.8±13.6 vs. 120.7±36.5 min, P <0.0001) was shorter in the RFA group. Patient satisfaction (significant improvement: 89.3% vs. 61.9%, P <0.0001) and cosmetic results (cosmetic score 1-2: 100.0% vs. 54.76%, P <0.0001) favored TOETVA. RFA was found to be less costly for a single treatment, but the cost of retreatment should be considered. The histological diagnoses post-TOETVA revealed malignancies in 9 out of 84 cases, underscoring the significance of follow-up assessments. CONCLUSION: Scarless procedures, RFA and TOETVA, are effective for treating unilateral benign TNs, each with unique advantages and drawbacks. While RFA is cheaper for a single treatment, TOETVA offers superior cosmetic results and patient satisfaction. Further research is needed to evaluate long-term safety and cost-effectiveness. It is crucial to remain vigilant about the possibility of malignancy despite benign cytology pre-treatment.

Assessing the Frequency of Deferrable Thyroid Nodule Biopsies to De-escalate Low-Value Care.

OBJECTIVE: Thyroid nodules are common, yet fewer than 1 in 10 harbors malignancy. When present, thyroid cancer is typically indolent with excellent survival. Therefore, patients who are not candidates for thyroid cancer treatment due to comorbid disease may not require further thyroid nodule evaluation. The goal of this study was to determine the rate of deferrable thyroid nodule biopsies in patients with limited life expectancy. METHODS: We identified patients who underwent thyroid fine needle aspiration (FNA) between 2015 and 2018 at our institution. The primary outcome was the number of deferrable FNAs, defined as FNAs performed in patients who died within 2 years after biopsy. Secondary outcomes included cytologic Bethesda score, procedure costs, and final diagnosis on surgical pathology. Multivariable logistic and Cox proportional hazards regressions were used to evaluate factors associated with FNA in patients with limited life expectancy. RESULTS: A total of 2565 FNAs were performed. Most patients were female (79%), and 37 (1.5%) patients died within 2 years. Nonthyroid specialists were significantly more likely to order deferrable FNAs (odds ratio 4.13, P < .001). Of the patients who died within 2 years, most (78%) had a concomitant diagnosis of nonthyroid cancer, and 4 went on to have thyroid surgery (Bethesda scores: 3, 4, 4, and 6). Spending associated with deferrable FNAs and subsequent surgery totaled over $98 000. CONCLUSIONS: Overall, the rate of deferrable thyroid nodule biopsies was low. However, there is an opportunity to reduce low-value biopsies in patients with a concurrent nonthyroid cancer by partnering with oncology providers.

Value of repeated US-guided fine-needle aspiration (US-FNAB) in the follow-up of benign thyroid nodules: a real-life study based on the MoCyThy (Modena's Cytology of the Thyroid) DATABASE with a revision of the literature.

PURPOSE: The utility of repeating ultrasound-guided fine-needle aspiration (US-FNAB) in the follow-up of benign (THY2) thyroid nodules is still debated. The aim of this study was to retrospectively investigate the diagnostic value of re-biopsy of thyroid nodules following an initially benign result. METHODS: We retrospectively analyzed US-FNABs performed at the Unit of Endocrinology of Modena from 2006 to 2009. The firstly benign cytological result was compared with the cytological results of subsequent US-FNABs (2nd and/or 3rd) executed on the same nodule. RESULTS: Among 10449 US-FNABs, 6270 (60%) received a THY2 cytological categorization. Of them, 278 (4.43%) underwent a subsequent US-FNAB: 86.7% maintained the same cytology, 32 (11.5%) changed to THY3 (indeterminate) and 5 (1.8%) to THY4 (suspicious of malignancy). Among the 24 nodules addressed to surgery, 9 (37%) were histologically malignant, with an overall miss rate of 3.2%. Male patients had higher risk of discordant results at subsequent US-FNAB (p = 0.005, OR:3.59, 95%CI:1.453-7.769) while dimensional increase above 5 mm was predictive of concordant benign cytology (p = 0.036, OR:0.249, 95%CI:0.068-0.915). Age, suspicious US characteristics, and distance between US-FNABs resulted not predictive. CONCLUSIONS: Re-biopsy of benign nodules confirmed the benign nature in most cases. In case of discordant cytology, relocation in indeterminate category was the most common. The histological diagnosis of cancer occurred in one quarter of nodules surgically removed, with a low overall clinically significant miss rate. Thus, a small percentage of false negatives exists; males and subjects with US suspicious nodules should be carefully followed-up, considering case by case re-biopsy possibility.

Percutaneous ethanol injection in thyroid nodular pathology and metastatic cervical adenopathies: A systematic review, meta-analysis and economic evaluation.

BACKGROUND: Percutaneous ethanol injection (PEI) has been shown to be a valuable treatment for thyroid nodular pathology and metastatic cervical adenopathies. OBJECTIVE: To evaluate the effectiveness, safety, and cost-effectiveness of PEI in thyroid nodular pathology and metastatic cervical adenopathies. METHODS: A systematic review (SR) using meta-analysis was conducted on the effectiveness and safety of PEI. A SR on cost-effectiveness was also performed. The SRs were conducted according to the methodology developed by the Cochrane Collaboration with reporting in accordance with the PRISMA statement. A cost-minimization analysis was carried out using a decision tree model. Assuming equal effectiveness between two minimally invasive techniques (PEI and radiofrequency ablation (RFA)), the model compared the costs of the alternatives with a horizon of six months and from the perspective of the Spanish National Health System. RESULTS: The search identified three RCTs (n=157) that evaluated PEI versus RFA in patients diagnosed with benign thyroid nodules: ninety-six patients with predominantly cystic nodules and sixty-one patients with solid nodules. No evidence was found on other techniques or thyroid nodular pathology. No statistically significant differences were observed between PEI and RFA in volume reduction (%), symptom score, cosmetic score, therapeutic success and major complications. No economic evaluations were identified. The cost-minimization analysis estimated the cost per patient of the PEI procedure at €326 compared to €4781 for RFA, which means an incremental difference of -€4455. CONCLUSIONS: There are no differences between PEI and RFA regarding their safety and effectiveness, but the economic evaluation determined that the former option is cheaper.

Learnability of Thyroid Nodule Assessment on Ultrasonography: Using a Big Data Set.

OBJECTIVE: The aims of the work described here were to evaluate the learnability of thyroid nodule assessment on ultrasonography (US) using a big data set of US images and to evaluate the diagnostic utilities of artificial intelligence computer-aided diagnosis (AI-CAD) used by readers with varying experience to differentiate benign and malignant thyroid nodules. METHODS: Six college freshmen independently studied the "learning set" composed of images of 13,560 thyroid nodules, and their diagnostic performance was evaluated after their daily learning sessions using the "test set" composed of images of 282 thyroid nodules. The diagnostic performance of two residents and an experienced radiologist was evaluated using the same "test set." After an initial diagnosis, all readers once again evaluated the "test set" with the assistance of AI-CAD. RESULTS: Diagnostic performance of almost all students increased after the learning program. Although the mean areas under the receiver operating characteristic curves (AUROCs) of residents and the experienced radiologist were significantly higher than those of students, the AUROCs of five of the six students did not differ significantly compared with that of the one resident. With the assistance of AI-CAD, sensitivity significantly increased in three students, specificity in one student, accuracy in four students and AUROC in four students. Diagnostic performance of the two residents and the experienced radiologist was better with the assistance of AI-CAD. CONCLUSION: A self-learning method using a big data set of US images has potential as an ancillary tool alongside traditional training methods. With the assistance of AI-CAD, the diagnostic performance of readers with varying experience in thyroid imaging could be further improved.

Ultrasound-Based Risk Stratification System for the Assessment of Partially Cystic Thyroid Nodules.

OBJECTIVE: To develop and validate a risk stratification system for the prediction of malignancy in partially cystic thyroid nodules (PCTNs). METHODS: We retrospectively reviewed the sonography data of patients with PCTNs from 2 medical centers-Hangzhou Traditional Chinese Medicine Hospital and Hangzhou First People's Hospital-from January 2020 to December 2021. The independent risk factors for malignant PCTNs were evaluated using the univariate and multivariate logistic regression analyses. The nomogram prediction efficiency was assessed using the area under the curve and calibration curves. The decision curve analysis was used to determine the clinical value of the predictive model. RESULTS: A total of 285 patients were enrolled in this retrospective study, and of 301 PCTNs, 242 were benign and 59 were malignant. Younger age, hypoechoic, irregular margin, and microcalcifications were found to be the independent risk factors for malignant PCTNs. The area under the curve, sensitivity, and specificity were 0.860, 77.1%, and 84.7% in the training data set and 0.897, 91.7%, and 87.0% in the external validation data set, respectively. The total point of nomogram was >161, which showed the best to predict malignancy in PCTNs. CONCLUSION: Our findings demonstrated that the risk stratification system for the assessment of PCTNs showed good prediction capacities.

The role of elastography in the assessment of thyroid nodules in acromegaly.

BACKGROUND: Nodular thyroid disease is a frequent finding seen in patients with acromegaly. Ultrasound-elastography (US-E) appears to be a helpful tool for the diagnosis of thyroid cancer. The aims of this study were to evaluate thyroid nodules in acromegaly and to assess the diagnostic accuracy of US-E in detecting thyroid cancer in this population. METHODS: US-E was applied to 166 nodules detected in 102 acromegalic patients and to 105 nodules found in 95 nonacromegalic subjects. The lesions were classified according to the elasticity scores (ES) as soft (ES 1-2) or hard (ES 3-4). RESULTS: : Mean age was 55.1 ± 12.47 years [59 (58%) women]. The prevalence of hard nodules (ES 3 and 4) was significantly higher in the group of acromegalic patients than in control subjects (48% to 20%, p < 0.001). Mean ES was higher in patients with acromegaly (2.45 to 2.22, p: 0.001), however, the mean strain index (SI) was similar between groups (1.53 to 1.65, p: 0.204). DISCUSSION: Thyroid nodules in acromegaly patients have a higher elasto score and the prevalence of hard nodules is higher in active disease. However, increased stiffness of nodules by US-E in patients with acromegaly does not seem to estimate the malignancy of the nodules.

A Comprehensive Assessment of the Harms of Fine-Needle Aspiration Biopsy for Thyroid Nodules: A Systematic Review.

BACKGRUOUND: There have concerns related with the potential harms of fine-needle aspiration biopsy (FNAB). We aimed to summarize the clinical complications and evaluate the safety of FNAB. METHODS: Studies related with the harms of FNAB were searched on MEDLINE, Embase, Cochrane library, and KoreaMed from 2012 to 2022. Also, studies reviewed in the previous systematic reviews were evaluated. Included clinical complications were postprocedural pain, bleeding events, neurological symptoms, tracheal puncture, infections, post-FNAB thyrotoxicosis, and needle tract implantation of thyroid cancers. RESULTS: Twenty-three cohort studies were included in this review. Nine studies which were related with FNAB-related pain showed that most of the subjects had no or mild discomfort. The 0% to 6.4% of the patients had hematoma or hemorrhage after FNAB, according to 15 studies. Vasovagal reaction, vocal cord palsy, and tracheal puncture have rarely described in the included studies. Needle tract implantation of thyroid malignancies was described in three studies reporting 0.02% to 0.19% of the incidence rate. CONCLUSION: FNAB is considered to be a safe diagnostic procedure with rare complications, which are mainly minor events. Thorough assessement of the patients' medical condition when deciding to perform FNABs would be advisable to lower potential complications.

Thyroid Nodule Margin Assessment Using ACR TI-RADS: Adding Points for Macrolobulation Impairs Performance.

OBJECTIVE: We evaluated the performance of ACR TI-RADS when points for lobulated margins are applied only when the margins meet a quantified measure of margin microlobulation and not applied when nodules only demonstrate macrolobulation. METHODS: We retrospectively reviewed ultrasound and pathology records (May 01, 2018 to July 31, 2020) to find all thyroid nodules at one institution characterized as having lobulated margins using the ACR TI-RADS lexicon and subsequently undergoing fine needle aspiration (FNA). Nodule margins were evaluated to note the presence or absence of microlobulation, quantitatively defined as a protrusion with a base <2.5 mm in length. The impact to detection of malignant nodules and avoidance of benign FNA when margin points for lobulation were added only when microlobulated was analyzed. RESULTS: 58 of 516 thyroid nodules undergoing US-guided FNA were classified as lobulated, comprising the study population. 21 (36.2%) had microlobulated margins, with 12 of the 21 (57.1%) being malignant. Comparatively, of the 37 nodules showing only macrolobulated margins without microlobulation, only 2 (5.4%) were malignant (P < .0001). For 53 nodules ≥10 mm, 15 (28.3%) benign nodules would not have met size criteria for FNA had points for margins not been applied when only showing macrolobulation, whereas all 10 malignant nodules would still have been sampled. CONCLUSION: Adding two points to the ACR TI-RADS score for lobulated thyroid nodules should only apply when microlobulations are present.

A prospective comparison of ACR-TIRADS and EU-TIRADS in thyroid nodule assessment for FNA-US.

OBJECTIVE: Prospective data on the accuracy of ultrasound (US) classification systems in thyroid nodules are still scarce. The aim of this study is to compare the accuracy of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS) and European (EU)-TIRADS classification systems. DESIGN AND PATIENTS: Consecutive patients with one or more thyroid nodule(s) who underwent fine-needle aspiration (FNA) under ultrasonographic guidance (FNA-US) were prospectively evaluated. MEASUREMENTS: Clinical evaluation and US data were collected. The reference standard used for this study was FNA-US cytology and histopathological diagnosis. RESULTS: A total of 186 thyroid nodules in 166 patients were evaluated, resulting in 168 nodules from 149 patients with conclusive benign or malignant results. Sensitivity, specificity, negative predictive value (NPV) and false negative (FN) were 100.0%, 28.7%, 100.0% and 0.0%, respectively, for ACR-TIRADS; and 90.0%, 19.1%, 96.8% and 9.1% (n = 1), respectively, for EU-TIRADS. The number of unnecessary FNA-US indicated by ACR-TIRADS was lower than EU-TIRADS (71.3% vs. 80.9%, p = .017), and the number of possibly avoided FNA-US was higher (26.7% vs. 17.8%). Using the same threshold of ACR-TIRADS to indicate FNA-US in EU-TIRADS 3 nodules (2.5 cm), there was an improvement in specificity (30.6%) and avoided FNA-US (28.6%). The best performance of both systems was demonstrated when FNA-US would be indicated only in highly suspicious nodules and/or in the presence of lymphadenopathy, with 85.7% and 89.3% of possibly avoided FNA-US for ACR-TIRADS and EU-TIRADS, respectively, without increasing FN. CONCLUSION: Both systems presented high sensitivity, but low specificity in selecting nodules for FNA-US. The use of nodular size for FNA-US selection is questioned.

Interobserver and Intraobserver Reliability in Sonoelastographic Assessment of Thyroid Nodules.

BACKGROUND: Thyroid ultrasonography is the first and perhaps most fundamental step for the radiological distinction of benign and malignant nodules. In this study, 2 radiologists reviewed the sonoelastographic and Doppler images of thyroid nodules and evaluated for the intraobserver and interobserver reliability. PURPOSE: We aimed to determine confusing nodule identifiers and sonographic features differently defined by observers. METHODS: A total of 157 nodules in 91 patients (male/female, 72:19) with ages ranging from 18 to 72 years old were included in the study. Ultrasonographic images and video clips of the nodules were obtained and presented to 2 reviewers unaware of the cytopathology results. Two observers defined the characteristics of the nodules based on previously determined criteria. Then, intraobserver and interobserver correlation coefficients were calculated for each subcategory. RESULTS: In the grayscale ultrasonographic examination, varying degrees from low to high interobserver correlation coefficients were obtained for different subcategories (between κ = 0.359 and κ = 0.821). In color Doppler examination, we obtained medium correlation coefficients ( κ = 0.493 and κ = 0.553). On the other hand, there was a high correlation coefficient in tissue compression elastography ( κ = 0.617 and κ = 0.638).According to our study results, elastographic pattern, shape of the nodule, presence of echogenic foci, and pathological lymph nodes are better predictors to determine the malignant potential of thyroid nodule with higher interobserver correlation. Therefore, these criteria may be used primarily for the evaluation of thyroid nodules. The intraobserver correlation coefficient was higher in the practitioner with longer experience, suggesting the importance of professional practice period on the decision-making process.

An innovative synthetic support for immunocytochemical assessment of cytologically indeterminate (Bethesda III) thyroid nodules.

Background: Fine needle aspiration (FNA) is the procedure of choice in the evaluation of thyroid nodules. Nodules with indeterminate cytological categories, Bethesda III and IV, pose challenges in clinical practice and are frequently submitted to diagnostic surgery. CytoFoam Core (CFCS) uses an absorbent foam device inserted into the needle hub to collect the cytological sample aspirated during FNA. Specimen is formalin-fixed and paraffin-embedded. Aim of the study: Assessing diagnostic efficacy of CFCS, compared to traditional cytology, in re-evaluating thyroid nodules classified as Bethesda III, using post-surgical histology as reference standard. Method: Retrospective study on 89 patients with a first indeterminate cytological report who were referred to the Department of Endocrinology of Regina Apostolorum Hospital (Albano L. Rome, Italy) for a second FNA. FNA was performed after at least one month under ultrasound guidance with a 23G needle according to the established procedure. During the second procedure, both traditional cytological (TC) smears and a single-pass CFCS specimen were obtained for each patient. On CFCS samples immunocytochemical staining for Galectin-3, HBME-1, and CK-19 was also performed. 51 patients eventually underwent surgery, and their histological diagnoses were compared to the TC and CFCS reports. Four parameters were evaluated: inadequacy rate, rate of persistent indeterminate (Bethesda III and IV) reports, rate of malignancy in persistently indeterminate nodules, and rate of cancer in lesions cytologically classified as malignant. Results: Non-diagnostic samples were 6 (11.8%) in TC vs 3 (5.9%) in CFCS (p=0.4). Persistent indeterminate samples were 31 (60.8%) in TC vs 19 (37.2%) in CFCS (p=0.01). Rate of malignancy in persistently indeterminate nodules was 8/19 (42.1%) in CFCS vs 9/31 (29%) in TC group (p=0.3). Nine/51 (17.6%) samples were classified as benign by TC vs 21/51 (41.2%) samples by CFCS (p<0.01). All nodules resulted benign at post-surgical evaluation. Five/51 (9.8%) samples were classified as suspicious for malignancy/malignant in TC group against 8/51 (15.7%) samples in CFCS (p=0.5). Post-surgical evaluation confirmed malignancy in all these cases. Conclusion: CFCS demonstrated greater diagnostic accuracy than TC in repeat FNA assessment of cytologically indeterminate nodules. CFCS increased the conclusive diagnosis rate and decreased the number of cytologically indeterminate cases.

Interobserver variability in ultrasound assessment of thyroid nodules.

The first diagnostic tool for thyroid disease management is ultrasound. Despite its importance, ultrasound is an extremely subjective procedure that requires a high level of performance skill. Few studies have assessed thyroid ultrasound performance and its effectiveness, particularly the variability between observers in the assessment of ultrasound images. This study evaluated the variability in ultrasound assessments and diagnoses of thyroid nodules between 2 radiologists. In this retrospective study, 75 thyroid nodules in 39 patients were reviewed by 2 experienced radiologists. The nodule composition, margin, shape, calcification, and vasculitis were determined using echogenicity. The study evaluation included these 5 assessments and the final diagnosis. Interobserver variation was determined using Cohen kappa statistics. The interobserver agreements in the interpretation of echogenicity, shape, and margin were fair (κ = 0.21-0.40), whereas there were substantial agreements for vascularity and calcification (κ = 0.62-0.78). The agreements between the observers for individual ultrasound features in this study were the highest for vascularity and the presence/absence of calcification. The interobserver reproducibility for thyroid nodule ultrasound reporting was adequate, but the diagnostic evaluation ability of the observers was inconsistent. The variability in the interpretation of sonographic features could influence the level of suspicion of thyroid malignancy. This study emphasizes the need for consistency in the training of sonographic interpretation of thyroid nodules, particularly for echogenicity, shape, and margin.

Washout DNA copy number analysis by low-coverage whole genome sequencing for assessment of thyroid FNAs.

Background: Papillary thyroid microcarcinoma (PTMC) is defined as a papillary carcinoma measuring ≤ 10 mm. The current management of PTMC has become more conservative; however, there are high-risk tumor features that can be revealed only postoperatively. For thyroid cancer, BRAF mutations and somatic copy number variation (CNV) are the most common genetic events. Molecular testing may contribute to clinical decision-making by molecular risk stratification, for example predicting lymph node (LN) metastasis. Here, we build a risk stratification model based on molecular profiling of thyroid fine needle aspiration (FNA) washout DNA (wDNA) for the differential diagnosis of thyroid nodules. Methods: Fifty-eight patients were recruited, FNA wDNA samples were analyzed using CNV profiling through low-coverage whole genome sequencing (LC-WGS) and BRAF mutation was analyzed using quantitative PCR. FNA pathology was reported as a Bethesda System for Reporting Thyroid Cytopathology (BSRTC) score. Ultrasound examination produced a Thyroid Imaging Reporting and Data System (TIRADS) score. Results: In total, 37 (63.8%) patients with a TIRADS score of 4A, 13 (22.4%) patients with a TIRADS score of 4B, and 8 (13.8%) patients with a TIRADS score of 4C were recruited after ultrasound examination. All patients underwent FNA with wDNA profiling. CNVs were identified in 17 (29.3%) patients. CNVs were frequent in patients with a BSRTC score of V or VI, including eight (47.1%) patients with a score of VI and five (29.4%) with a score of V, but not in patients with a score of III, II, or I (0%). BRAF mutation was not significantly correlated with BSRTC score. LN metastasis was found more frequently in CNV-positive (CNV+) than in CNV-negative (CNV-) patients (85.7% vs. 34.6%, odds ratio = 11.33, p = 0.002). In total, three molecular subtypes of thyroid nodules were identified in this study: 1) CNV+, 2) CNV- and BRAF positive (BRAF+), and 3) CNV- and BRAF negative (BRAF-). For the CNV+ subtype, 10 (83.3%) lesions with LN metastasis were found, including four (100%) small lesions (i.e. ≤ 5 mm). For the CNV- and BRAF+ nodules, LN metastases were detected in only seven (60.0%) larger tumors (i.e. > 5 mm). For CNV- and BRAF- tumors, LN metastasis was also frequently found in larger tumors only. Conclusions: It is feasible to identify high-risk LN metastasis thyroid cancer from FNA washout samples preoperatively using wDNA CNV profiling using LC-WGS.

Battle of the axes: simulation-based assessment of fine needle aspiration biopsies for thyroid nodules.

IMPORTANCE: Ultrasound-guided fine-needle aspiration biopsies (UGFNA) play a crucial role in the diagnosis of thyroid nodules. There are two techniques for performing an UGFNA: short-axis technique and long-axis technique. There is sparsity in the literature regarding the differences between these two techniques. OBJECTIVE: To compare the efficiency between long-axis and short-axis thyroid UGFNA techniques in trainees. Our secondary outcomes were to define the comfort level and learning curves of trainees. DESIGN: A longitudinal prospective cohort study, completed from December 2018 to November 2019, using the Blue Phantom Thyroid Model© for UGFNA. Face and construct validity of the model were verified. Residents completed UGFNA on an assigned nodule using both long-axis and short-axis techniques, the order of which was sequentially allocated. The rate and time to successful biopsy were obtained for both techniques. Biopsy attempts were repeated to establish learning curves. SETTING: Single-center study. PARTICIPANTS: Fourteen Otolaryngology-Head & Neck Surgery residents at the University of Toronto. MAIN OUTCOME MEASURE: Biopsy success and efficiency for novice learners completing UGFNA on a simulated thyroid model using long-axis and short-axis techniques. RESULTS: A trend towards higher odds of successful biopsy using the long-axis technique with no difference in procedure duration was observed (OR = 2.2, p = 0.095, CI = 0.87-5.39). Learning curve graphs appeared heterogenous according to trainee level. Trainees found the long-axis technique easier to perform (10/14, 71%), and the simulator valuable for learning (12/14, 86%). CONCLUSION: Thyroid UGFNA using the long-axis technique may have an increased success rate and is generally favored by trainees for being easier to perform. Thyroid simulators have the potential to increase learner comfort and efficiency with UGFNA.

Differential diagnosis and feature visualization for thyroid nodules using computer-aided ultrasonic diagnosis system: initial clinical assessment.

BACKGROUND: To assess the diagnostic efficacy of the computer-aided ultrasonic diagnosis system (CAD system) in differentiating benign and malignant thyroid nodules. METHODS: The images of 296 thyroid nodules were included in validation sets. The diagnostic efficacy of the CAD system was compared with that of junior physicians and senior physicians, as well as that of the combination diagnosis of the CAD system with junior physicians. The diagnostic efficacy of the CAD system for different sizes of thyroid nodules was compared. RESULTS: The diagnostic sensitivity and accuracy of the CAD system were higher than those of junior physicians (83.4% vs. 72.2%, 73.0% vs. 69.6%), but the diagnostic specificity of the CAD system was lower than that of junior physicians (62.1% vs. 66.9%). The diagnostic accuracy of the CAD system was lower than that of senior physicians (73.0% vs. 83.8%). However, the combination diagnosis of the CAD system with junior physicians had higher accuracy (81.8%) and AUC (0.842) than those of either the CAD system or junior physicians alone, and comparable diagnostic performance with those of senior physicians. The Kappa was 0.635 in the combination diagnosis of the CAD system with junior physicians, showing good consistency with the pathological results. The accuracy (76.4%) of the CAD system was the highest for nodules of 1-2 cm. CONCLUSION: The CAD system can effectively assist physicians to identify malignant and benign thyroid nodules, reduce the overdiagnosis and overtreatment of thyroid nodules, avoid unnecessary invasive fine needle aspiration, and improve the diagnostic accuracy of junior physicians.

Ultrasound for the assessment of thyroid nodules: an overview for non-radiologists.

Upon discovery of a thyroid nodule (or nodules), a patient is usually referred for evaluation by ultrasound, which is typically performed by a trained radiologist or sonographer. More recently, this technology has been used intraoperatively by endocrine surgeons and also by endocrinologists, often in the context of 'one-stop shops' or point of care ultrasound in the outpatient setting. Although thyroid nodules are common and most will be benign, the subsequent work up of these can cause anxiety for patients and place a burden on radiologists. In the UK, sonographic features of benign, suspicious or malignant nodules are classified by the British Thyroid Association U1-U5 criteria, which decide whether to biopsy the nodule (typically U3 and above). This article provides an overview of ultrasound in assessing the thyroid nodule in the context of this classification. This can be used as a guide to interpretation of thyroid ultrasonography for non-radiologists.

Assessment of Papillary Thyroid Carcinoma with Ultrasound Examination.

Ultrasound examination of the thyroid is useful for preoperative assessment of thyroid nodules including papillary thyroid carcinoma. The examination mainly is to determine the malignant potential of thyroid nodule(s). There are different systems to predict malignant potential in the thyroid nodules and cervical lymph nodes by ultrasound. Ultrasound is used in conjunction with fine-needle aspiration to diagnosis papillary thyroid carcinoma. It is used as guidance to locate the sites to obtain the samples for diagnosis and research in papillary thyroid carcinoma.