Evaluation Of Thyroid Nodules Research Articles

Core needle biopsy for thyroid nodules assessment-a new horizon?

Ultrasound-guided fine-needle aspiration is the standard for evaluating thyroid nodules with a high safety profile and a relatively low number of non-diagnostic cytological findings. Nevertheless, this diagnostic method traditionally has its weak points. Several diagnostic categories such as Bethesda I, III and IV are not reliable for thyroid carcinoma risk assessment. Recent advancements in a core needle biopsy made it possible to use this tool as a new method for thyroid nodules evaluation. The main feature of this method is the use of thin needles (18-21G) and guns with an automatic trigger mechanism. The histological material collected with the use of a core needle biopsy is usually superior to cytological. Therefore, the core needle biopsy can be used as a complementary technique to a standard fine needle aspiration in difficult and dubious cases of thyroid neoplasia with uncertain malignant potential.

The Utility of Contrast-Enhanced Ultrasound (CEUS) in Assessing the Risk of Malignancy in Thyroid Nodules.

Ultrasonography is a primary method used in the evaluation of thyroid nodules, but no single feature of this method predicts malignancy with high accuracy. Therefore, this paper aims to assess the utility of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of thyroid nodules. The study group comprised 188 adult patients (155 women and 33 men) who preoperatively underwent CEUS of a thyroid nodule classified as Bethesda categories II-VI after fine-needle aspiration biopsy. During the CEUS examination, 1.5 mL of SonoVue contrast was injected intravenously, after which 15 qualitative CEUS enhancement patterns were analysed. The histopathologic results comprised 65 benign thyroid nodules and 123 thyroid carcinomas. The dominant malignant CEUS features, such as hypo- and heterogeneous enhancement and slow wash-in phase, were evaluated, whereas high enhancement, ring enhancement, and a slow wash-out phase were assessed as predictors of benign lesions. Two significant combinations of B-mode and CEUS patterns were noted, namely, hypoechogenicity with heterogeneous enhancement and non-smooth margins with hypo- or iso-enhancement. The preliminary results indicate that CEUS is a useful tool in assessing the risk of malignancy of thyroid lesions. The combination of the qualitative enhancement parameters and B-mode sonographic features significantly increases the method's usefulness.

Correlation of Ultrasound Guided (USG) Fine Needle Aspiration Cytology (FNAC) With Postoperative Histopathology in the Diagnosis of Thyroid Swelling

Background: Thyroid swelling is a common problem in Bangladesh. Early and systematic evaluation of a nodular thyroid swelling is necessary as it is a frequent presentation of thyroid neoplasia. USG Guided Fine needle aspiration cytology (FNAC) is one of the diagnostic tools for early evaluation of thyroid nodules. USG Guided FNAC is considered as a cost-effective, simple, minimally invasive and easily repeatable procedure for preoperative screening in the diagnosis for most of the thyroid lesions. The objective of this study is to determine the sensitivity and specificity of USG Guided fine needle aspiration cytology (FNAC) and compare the efficacy with histopathology in diagnosis of thyroid swellings. Objective: To evaluate the sensitivity and specificity of USG Guided fine needle aspiration cytology (FNAC) and histopathology for the diagnosis of thyroid swelling. Method: This Observational Prospective Study was performed in the department of Otolaryngology & Head Neck Surgery, Dhaka Medical College Hospital. Dhaka over 6 month’s duration from January 2019-June 2019. Total 50 patients with thyroid swelling was selected after taking informed written consent and fulfilling the inclusion criteria. Smears was taken by standard procedure and then was stained with papanicolaou stain and haematoxylin and eosine stain. The smears was classified into categories like benign, indeterminate, malignant and unsatisfactory. Sensitivity, specificity, positive and negative predictive value and accuracy of USG Guided FNAC was calculated and compared to already available data. Appropriate statistical analysis was done to make comparison between final histopathological findings with initial USG Guided FNAC findings. Result: During the study period a total 73 were found eligible for USG Guided FNAC. Most of the patients (52%) were from 20-39 years age group. Among them 67.12% were female and rest (32.87%) were male. In this government hospital 75.34% were from low income group. ......

Differential diagnosis of thyroid nodules using heterogeneity quantification software on ultrasound images: correlation with the Bethesda system and surgical pathology

Ultrasonography (US)-guided fine-needle aspiration cytology (FNAC) is the primary modality for evaluating thyroid nodules. However, in cases of atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), supplemental tests are necessary for a definitive diagnosis. Accordingly, we aimed to develop a non-invasive quantification software using the heterogeneity scores of thyroid nodules. This cross-sectional study retrospectively enrolled 188 patients who were categorized into four groups according to their diagnostic classification in the Bethesda system and surgical pathology [II-benign (B) (n = 24); III-B (n = 52); III-malignant (M) (n = 54); V/VI-M (n = 58)]. Heterogeneity scores were derived using an image pixel-based heterogeneity index, utilized as a coefficient of variation (CV) value, and analyzed across all US images. Differences in heterogeneity scores were compared using one-way analysis of variance with Tukey’s test. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristic (AUROC) curve. The results of this study indicated significant differences in mean heterogeneity scores between benign and malignant thyroid nodules, except in the comparison between III-M and V/VI-M nodules. Among malignant nodules, the Bethesda classification was not observed to be associated with mean heterogeneity scores. Moreover, there was a positive correlation between heterogeneity scores and the combined diagnostic category, which was based on the Bethesda system and surgical cytology grades (R = 0.639, p < 0.001). AUROC for heterogeneity scores showed the highest diagnostic performance (0.818; cut-off: 30.22% CV value) for differentiating the benign group (normal/II-B/III-B) from the malignant group (III-M/V&VI-M), with a diagnostic accuracy of 72.5% (161/122). Quantitative heterogeneity measurement of US images is a valuable non-invasive diagnostic tool for predicting the likelihood of malignancy in thyroid nodules, including AUS or FLUS.

Abstract LB276: qPCR in the diagnosis of papillary thyroid cancer: Assessment of BRAF V600E mutation in FNA biopsies of thyroid nodules

Abstract Papillary thyroid carcinoma (PTC) accounts for up to 90% of thyroid cancer cases, and its differentiation from benign conditions presents a challenge in clinical practice. Fine needle aspiration biopsy (FNAB) has become a recommended practice for evaluating thyroid nodules (TN) with imaging features suspicious of malignancy. Although FNAB demonstrates high accuracy in discriminating TN, a significant number are classified as malignant indeterminate (MTI), which can only be fully diagnosed by post-surgical histologic evaluation. Up to 30% of FNAB findings are expected to be MTI, leading to a high rate of unnecessary hemithyroidectomies in about 75% of patients. In PTC, the most common mutation is c.T1799A in the BRAF gene (rs113488022), resulting in V600E in the B-raf protein, leading to an increase expression by altering the MAPK pathway. The aim of this study was to evaluate the efficacy of discriminating patients with malignant and benign TNs by detecting BRAF V600E in tissue from FNAB for molecular diagnosis of PTC. The qPCR technique with allele-specific probes was used to detect the BRAF c.1799T&amp;gt;A mutation in somatic DNA samples extracted by FNAB from TN (n=99) with suspected malignancy by ultrasonography. Cytologic diagnosis of biopsies was performed using the Bethesda System (TBSRTC). Diagnostic accuracy measures for evaluation of BRAF c.1799T&amp;gt;A as a diagnostic tool were performed with MedCalc software. Of the 99 patients, it was determined by cytology that 50 patients (50.51%) had PTC and 49 benign neoplasms (49.49%). The mutation was detected in 28 of the PTC samples (56%) (AA homozygotes [n=12, 24%] and AT heterozygotes [n=16, 32%). No mutation carriers were found among patients with benign neoplasms. Regarding accuracy measures were 56% for sensitivity of 56% and 100% specificity. The positive predictive value was 100% and the negative predictive value was 69.01%, with an accuracy of 77.78%. Finally, the negative likelihood ratio (LR-) value was 0.44 (95% CI: 0.32 to 0.60), while the positive likelihood ratio (LR+) value could not be calculated as there were no patients with the mutation in the group of patients with benign TN. In conclusion, our results suggest that the presence of BRAF c.1799T&amp;gt;A mutation could be indicative of PTC, confirming its usefulness in the differentiation between malignant and benign tumors. BRAF V600E detection may be valuable as an adjunct to conventional cytology, improving diagnostic accuracy and reducing the need for unnecessary surgical procedures. While highlighting the potential utility of this technique as a diagnostic tool, further analysis and consideration of other metrics is recommended for a full evaluation of its clinical relevance. Citation Format: Anette R. Gastelum-Quiroz, Andrea Ross-Orozco, Marco A. Álvarez-Arrazola, Eliakym Arambula-Meraz, Karla L. Morales-Hernández, Hanna M. Tolosa-Lerma, Fred Luque-Ortega, Paola Y. Sánchez-Aboytes, Noemí García-Magallanes. qPCR in the diagnosis of papillary thyroid cancer: Assessment of BRAF V600E mutation in FNA biopsies of thyroid nodules [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB276.

Cost-Effectiveness of the ACR TIRADS Compared to the ATA 2015 Risk Stratification Systems in the Evaluation of Incidental Thyroid Nodules

Rationale and ObjectivesThyroid nodules are a common incidental imaging finding and prone to overdiagnosis. Several risk stratification systems have been developed to reduce unnecessary work-up, with two of the most utilized including the American Thyroid Association 2015 (ATA2015) and the newer American College of Radiology Thyroid Imaging, Reporting and Data System (TIRADS) guidelines. The purpose of this study is to evaluate the cost effectiveness of the ATA2015 versus the TIRADS guidelines in the management of incidental thyroid nodules. MethodsA cost-utility analysis was conducted using decision tree modeling, evaluating adult patients with incidental thyroid nodules <4 cm. Model inputs were populated using published literature, observational data, and expert opinion. Single-payer perspective, Canadian dollar currency, 5-year time horizon, willingness to pay (WTP) threshold of $50,000, and discount rate of 1.5% per annum were utilized. Scenario, deterministic and probabilistic sensitivity analyses were performed. The primary outcome was the incremental cost effectiveness ratio (ICER) expressed as incremental cost per quality-adjusted life year (QALY) gained. ResultsFor the base case scenario, TIRADS dominated the ATA2015 strategy by a slim margin, producing 0.005 more QALYs at $25 less cost. Results were sensitive to the malignancy rate of biopsy and the utilities of a patient with a benign nodule/subclinical malignancy or under surveillance. Probabilistic sensitivity analysis showed that TIRADS was the more cost effective option 79.7% of the time. ConclusionThe TIRADS guidelines may be the more cost-effective strategy by a small margin compared to ATA2015 in most scenarios when used to risk stratify incidental thyroid nodules.

Stepwise analysis of thyroid diagnostic modalities with genomic imprinting detection.

The current preoperative malignancy risk evaluation for thyroid nodules involves stepwise diagnostic modalities including ultrasonography, thyroid function serology and fine-needle aspiration (FNA) cytopathology, respectively. We aimed to substantiate the stepwise contributions of each diagnostic step and additionally investigate the diagnostic significance of quantitative chromogenic imprinted gene in-situ hybridization (QCIGISH)-an adjunctive molecular test based on epigenetic imprinting alterations. A total of 114 cytopathologically-diagnosed and histopathologically-confirmed thyroid nodules with complete ultrasonographic and serological examination records were evaluated using QCIGISH in the study. Logistic regression models for thyroid malignancy prediction were developed with the stepwise addition of each diagnostic modality and the contribution of each step evaluated in terms of discrimination performance and goodness-of-fit. From the baseline model using ultrasonography [area under the receiver operating characteristics curve (AUROC): 0.79; 95% confidence interval (CI): 0.71-0.86], significant improvements in thyroid malignancy discrimination were observed with the stepwise addition of thyroid function serology (AUROC: 0.82; 95% CI: 0.74-0.90; P=0.23) and FNA cytopathology (AUROC: 0.88; 95% CI: 0.81-0.94; P=0.02), respectively. The inclusion of QCIGISH as an adjunctive molecular test further advanced the preceding model's diagnostic performance (AUROC: 0.95; 95% CI: 0.91-1.00, P=0.007). Our study demonstrated the significant stepwise diagnostic contributions of standard clinical assessments in the malignancy risk stratification of thyroid nodules. However, the addition of molecular imprinting detection further enabled a more accurate and definitive preoperative evaluation especially for morphologically indeterminate thyroid nodules and cases with potentially discordant results among standard modalities.

Assessment of Thyroid Gland in Children with Point-of-Care Ultrasound (POCUS): Radiological Performance and Feasibility of Handheld Ultrasound in Clinical Practice.

Point-of-Care Ultrasound (POCUS) refers to the use of portable ultrasound machines to perform quick and focused ultrasound examinations at a patient's bedside or point-of-care. POCUS can be performed by all health workers with specific training to use POCUS. This study aimed to investigate the radiological performance and feasibility of POCUS using a handheld ultrasound (HHUSD) system in children from the perspective of the thyroid gland perspective. A pediatric endocrinologist performed thyroid imaging in children referred to our hospital with suspected thyroid disease using an HHUSD system. The same children underwent US imaging using the same device by the first radiologist, and a second radiologist performed thyroid US using an advanced high-range Ultrasound Device (AHUSD) (defined as the gold-standard method) within two hours. The data obtained by the three researchers were compared with each other. This study included 105 patients (68.6% girls [n=72)]; mean age 12.8±3.6 years]. When the thyroid volume was evaluated, a strong correlation was found between the measurements of the three researchers (AA vs. MG: r=0.963, AA vs. GT: r=0.969, MG vs. GT: r=0.963, p<0.001). According to the Bland-Altman analysis, for total thyroid volume, AA measured 0.43 cc (%95 CI: -0.89-0.03) smaller than MG, and 0.11 cc (%95 CI: -0.30-0.52) larger than GT, whereas MG measured 0.52 cc (%95 CI: 0.09-0.94) larger than GT. When evaluated for the presence of goiter and nodules, a near-perfect agreement was found between the results of the three researchers (AA vs GT; κ=0.863, MG vs GT; κ=0.887, p<0.001, and AA vs GT; κ=1.000, MG vs GT; κ=0.972, p<0.001, respectively). When evaluated in terms of the longest axis of nodules, a high correlation was found between the measurements of the three researchers (AA vs MG; r=0.993, AA vs GT; r=0.996, MG vs GT; r=0.996, p<0.001). When evaluated in terms of the final diagnosis, the evaluations of the three researchers showed excellent agreement with each other (AA vs GT; κ=0.893, MG vs GT; κ=0.863, p<0.001, Accuracy rate AA vs GT: 93.3%; MG vs GT: 91.4%). A pediatric endocrinologist, equipped with sufficient training in thyroid US evaluation, incorporates the HHUSD as a routine tool for clinical examinations in outpatient settings, they can effectively assess normal thyroid tissue in pediatric patients. Moreover, the HHUSD system proves to be useful in detecting thyroid pathologies. However, it is crucial to note that for a more comprehensive evaluation of thyroid nodules, including detailed assessment and Thyroid Imaging Reporting and Data System "TIRADS" classification, patients should be referred to radiology departments equipped with AHUSD systems. These specialized devices, along with the expertise of radiologists, are essential for in-depth evaluations and accurate classification of thyroid nodules.

Evaluation of thyroid nodules by high resolution ultrasonography (HRUSG) and its cytological correlation in a teaching hospital

Thyroid nodules are a frequent occurrence. With the widespread use of sensitive imaging methods, a growing number of thyroid nodules are being discovered by chance. High resolution ultrasonography (HRUSG) has emerged as the most appropriate imaging modality for the assessment of thyroid nodules.To Evaluate thyroid nodules by of high resolution ultrasonography (HRUSG) and its correlation with Fine needle aspiration cytology (FNAC). Prospective study done in the department of radiology at Maheshwara medical college and Hospital, Chitkul, near Isnapur, Patancheru, Sangareddy, Telangana for duration of 3 years. A total of 80 cases were studied.HRUSG was done in all cases and Fine Needle Aspiration cytology was done. Radiological and pathological correlation was done and Sensitivity, specificify PPV, NPV and accuracy were calculated. Females were predominant (62.5%) when compared to males (37.5%). Among 80 thyroid nodules , colloid nodule noted in 42.5% cases, Nodular goitre in 27.5%, Hashimotos thyroiditis and follicular adenoma in 12.5%cases and Malignancy in 5% cases HRUSG is a sensitive and specific imaging technique that has a high level of accuracy in the evaluation of thyroid nodules. Solid composition, hypoechogenicity, taller-than-wider form, ill-defined edges, and the presence of calcification are the most effective sonographic markers for predicting cancer.

Role of ultrasonography (USG) and color Doppler in the evaluation of thyroid nodules and its association with USG-guided FNAC - A cross-sectional study.

Thyroid diseases affect approximately 42 million people in India. The majority (15%-40%) of these cases remain asymptomatic and benign and warrant special investigations such as ultrasonography (USG) and fine-needle aspiration cytology (FNAC) for diagnosis. Early diagnosis and management of thyroid disorders determine the disease course in many patients. To determine the role of USG and color Doppler in the evaluation of thyroid nodules and its association with USG-guided FNAC. We did a cross-sectional analytical study over 2 years, where we recruited 108 patients with thyroid swelling attending the OPD. We used a semi-structured data collection proforma that captured information on sociodemographic details, clinical symptoms, physical examination, and all ne cessary laboratory investigations. All patients underwent USG, color Doppler, and FNAC as a part of the investigation of thyroid nodules. The diagnostic value of ultrasound and Doppler parameters was assessed in terms of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for detection of malignancy in comparison to FNAC. Approximately 155 nodules were identified from the selected 108 cases, and the prevalence of malignancy among the selected thyroid nodule patients was found to be 9.1%. We observed that malignant tumors were likely to be solitary with lobulated margins, >2 cm in size with <50% peripheral halo, with markedly hypoechoic, predominantly solid, with nodal involvement and extrathyroidal extension, microcalcifications, and central vascularity. We also observed that tumors that had USG characteristics of being taller than wide (91%), poorly defined margins (92%), marked hypoechoic (95%), and microcalcifications (96%) had the highest diagnostic accuracy in detecting malignancy when compared to FNAC. Thus, through our study findings, we conclude that USG and color Doppler can serve as vital tools for the evaluation of thyroid nodules with high sensitivity and specificity.

Poorly differentiated papillary thyroid carcinoma in a 5-year-old girl: a case report

BackgroundThe incidence of thyroid cancer has been increasing among the population less than 20 years of age, especially during the second decade of life. Differentiated papillary thyroid cancer is the most common pathology in children. It usually presents with thyroid nodules with or without cervical lymphadenopathy. Thyroid nodules carry a considerable risk of malignancy in children.Case presentationWe herein report a 5-year-old girl with poorly differentiated papillary thyroid cancer which is an extremely rare finding at this age. The patient underwent right thyroid lobectomy followed by left hemi thyroidectomy and right central and lateral neck dissection. Pathologic examination revealed a poorly differentiated papillary thyroid carcinoma with nodal deposits.ConclusionIt is essential to raise awareness of proper evaluation and management of thyroid nodules at such an age.

Does the Adoption of Molecular Testing Cause Decreased Thyroidectomy Rates in a National Cohort? A Quasiexperimental Study of High- Versus Low-Adoption States.

Background: Over the last decade, the utilization of molecular testing (MT) for the evaluation of thyroid nodules has increased. Rates and patterns of adoption of MT and its effect on thyroidectomy rates nationally are unknown. Varying rates of MT adoption at the state level provide an opportunity to study the effects of MT on thyroidectomy rates using a quasiexperimental study design. Methods: We performed a retrospective analysis of American adult patients in the Merative™ MarketScan® Research Databases who underwent thyroid fine-needle aspiration (FNA) from 2011 to 2021. MT included commercially available DNA and RNA platforms and traditional targeted mutational analysis. Interrupted time series analysis was used to evaluate the inflection of MT adoption and thyroidectomy rates after 2015. Difference-in-differences (DID) analysis was used to causally analyze the effect of MT adoption on thyroidectomy rates in high-adoption (at least a 10% increase in MT utilization) versus low-adoption states (no more than 5% increase in MT utilization) from 2015 to 2021. Results: We identified 471,364 patients who underwent thyroid FNA. The utilization of MT increased over the study period from 0.01% [confidence interval, CI: 0.00% to 0.02%] to 10.1% [CI: 9.7% to 10.5%], in 2021, with an immediate (β2 = 1.61, p = 0.002) and deeper (β3 = 0.6, p < 0.001) increase in MT adoption after 2015. Utilization of MT was lower in black patients, the elderly, rural areas, and patients with Medicaid (p < 0.05). Thyroidectomy rates were inversely correlated with MT utilization (r = -0.98, p < 0.0001). From 2015 to 2021, the average MT utilization rate increased from 2.4% to 15.3% in high-adoption states and 1.6% to 5.6% in low-adoption states. In low-adoption states, thyroidectomy rates decreased more but to similar levels (18.5-13.2%) compared with high-adoption states (15.9-13.4%) with an adjusted DID rate of -3.3% [CI -5.6% to -0.8%]. Conclusions: The acceleration in adoption of MT after 2015 likely coincides with the publication of American Thyroid Association guidelines. Black, elderly, and rural patients are less likely to receive MT. Although thyroidectomy rates were inversely correlated with MT utilization, our study suggests that this correlation is not causal. The effect of MT on thyroidectomy rates may be overshadowed by decreasing aggressiveness of thyroid nodule evaluation.

Interobserver variability in thyroid ultrasound.

Ultrasound evaluation of thyroid nodules is the preferred technique, but it is dependent on operator interpretation, leading to inter-observer variability. The current study aimed to determine the inter-physician consensus on nodular characteristics, risk categorization in the classification systems, and the need for fine needle aspiration puncture. Four endocrinologists from the same center blindly evaluated 100 ultrasound images of thyroid nodules from 100 different patients. The following ultrasound features were evaluated: composition, echogenicity, margins, calcifications, and microcalcifications. Nodules were also classified according to ATA, EU-TIRADS, K-TIRADS, and ACR-TIRADS classifications. Krippendorff's alpha test was used to assess interobserver agreement. The interobserver agreement for ultrasound features was: Krippendorff's coefficient 0.80 (0.71-0.89) for composition, 0.59 (0.47-0.72) for echogenicity, 0.73 (0.57-0.88) for margins, 0.55 (0.40-0.69) for calcifications, and 0.50 (0.34-0.67) for microcalcifications. The concordance for the classification systems was 0.7 (0.61-0.80) for ATA, 0.63 (0.54-0.73) for EU-TIRADS, 0.64 (0.55-0.73) for K-TIRADS, and 0.68 (0.60-0.77) for K-TIRADS. The concordance in the indication of fine needle aspiration puncture (FNA) was 0.86 (0.71-1), 0.80 (0.71-0.88), 0.77 0.67-0.87), and 0.73 (0.64-0.83) for systems previously described respectively. Interobserver agreement was acceptable for the identification of nodules requiring cytologic study using various classification systems. However, limited concordance was observed in risk stratification and many ultrasonographic characteristics of the nodules.

Should there be a paradigm shift for the evaluation of isthmic thyroid nodules?

Although the thyroid isthmus seems like a rudimentary structure that connects bilateral lobes, it is an undiscovered area that needs to be explored. Currently, the data is evolving that the increase in the risk of malignancy is higher in the isthmic nodules, and extrathyroidal extensions and lymph node metastases are more common in isthmic-derived malignant thyroid nodules. Therefore, we aimed to compare the malignancy rate of isthmic and lobar nodules, the ultrasonographic features of isthmic and lobar nodules, and presence of lymph node metastases, distant metastases, and extrathyroidal invasions in malignant isthmic nodules. In this retrospective study, we enrolled patients between the ages of 18-80years, who had thyroid nodule/nodules cytology and/or pathology results from January 2009 to November 2022. 9504 nodules were selected for the analysis of US findings, cytopathology results, and malignancy rates. A mean ± SD age of 55.3 ± 13.0years with a female to male ratio of [7618 (80.2%)/1886(19.8%)] were included in the study. 962 of the nodules were at isthmic localization; whereas 8542 nodules were at lobar localization. 1188 nodules were resulted as malignant from histopathological evaluation. Of the 1188 malignant nodules, 986 nodules were (83.0%) PTC, 114 nodules (9.6%) were FTC, 55 nodules were (4.6%) MTC, 16 nodules 1.3% were Hurtle cell carcinoma, 8 nodules (0.7%) were anaplastic thyroid carcinoma, and 9 nodules (0.8%) were thyroid tumors of uncertain malignant potential (TT-UMP). 156 of the malignant nodules (13.1%) were located in the isthmus, whereas the majority of the malignant nodules (n = 1032, 86.9%) were located at the lobar parts (right or left) of the thyroid. When the metastasis patterns of isthmic and lobar thyroid cancers were examined, no significant relationship was found between isthmic and lobar cancers in terms of capsule invasion (p = 0.435), muscle invasion (p = 0.294), and lymph node metastasis (p = 0.633). A significant relation was found between nodule localization (isthmus-upper-middle and lower lobes) and malignancy (p < 0.001). In our logistic regression analysis, isthmic and upper pole nodule localizations, age and TI-RADS were evaluated as independent risk factors for malignancy (p < 0.001 for all factors). We recommend nodule localization has to be considered an additional risk factor when performing a Fine Needle Aspiration Biopsy for the increased malignancy risk in this localization.

CRITERIA FOR ULTRASOUND SUSPICION OF THYROID NODULE

A thyroid nodule is a formation well differentiated from the rest of the thyroid. It represents the most frequent thyroidpathology, and the majority of these nodules are benign. Assessment of patients with thyroid nodules includes history,clinical examination, TSH measurement and thyroid ultrasound.In this article, we will detail the criteria for suspicion, including the place of ultrasound in the evaluation of thyroidnodules, based on the EU-TIRADS criteria

Improved cancer risk stratification of isoechoic thyroid nodules to reduce unnecessary biopsies using quantitative ultrasound.

Gray-scale ultrasound (US) is the standard-of-care for evaluating thyroid nodules (TNs). However, the performance is better for the identification of hypoechoic malignant TNs (such as classic papillary thyroid cancer) than isoechoic malignant TNs. Quantitative ultrasound (QUS) utilizes information from raw ultrasonic radiofrequency (RF) echo signal to assess properties of tissue microarchitecture. The purpose of this study is to determine if QUS can improve the cancer risk stratification of isoechoic TNs. Patients scheduled for TN fine needle biopsy (FNB) were recruited from the Thyroid Health Clinic at Boston Medical Center. B-mode US and RF data (to generate QUS parameters) were collected in 274 TNs (163 isoechoic, 111 hypoechoic). A linear combination of QUS parameters (CQP) was trained and tested for isoechoic [CQP(i)] and hypoechoic [CQP(h)] TNs separately and compared with the performance of conventional B-mode US risk stratification systems. CQP(i) produced an ROC AUC value of 0.937+/- 0.043 compared to a value of 0.717 +/- 0.145 (p >0.05) for the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) and 0.589 +/- 0.173 (p >0.05) for the American Thyroid Association (ATA) risk stratification system. In this study, CQP(i) avoids unnecessary FNBs in 73% of TNs compared to 55.8% and 11.8% when using ACR TI-RADS and ATA classification system. This data supports that a unique QUS-based classifier may be superior to conventional US stratification systems to evaluate isoechoic TNs for cancer and should be explored further in larger studies.

Ultrasound microflow patterns help in distinguishing malignant from benign thyroid nodules

BackgroundVascular features are not commonly used to evaluate thyroid nodules by conventional ultrasound due to the low sensitivity. Superb Microvascular Imaging (SMI) is a new ultrasonic Doppler technology that specializes in depicting microvessels and low-speed flow. The objective of this study was to explore the value of microflow features on SMI in differentiating malignant from benign thyroid nodules.MethodsOne hundred and seventy-seven adult patients with thyroid nodules in our center from October 2021 to June 2022 with available histopathological results were recruited, including 125 malignant nodules and 123 benign nodules. Preoperative ultrasound was performed using greyscale, Color Doppler Flow Imaging (CDFI), monochrome SMI (mSMI) and color SMI (cSMI). Vascular features such as flow richness, microflow distribution and microflow patterns of malignant thyroid nodules were compared with those of benign nodules.ResultsPenetrating vessel ≥ 1 (82.4% in the malignant group vs. 30.9% in the benign group, P < 0.001), the crab claw-like pattern (64.0% vs. 10.6%, P < 0.001) and the root hair-like pattern (8.0% vs. 2.4%, P = 0.049) were common in malignant thyroid nodules, among which the crab claw-like pattern was an independent risk factor for malignant thyroid nodules. The wheel-like pattern (1.6% in the malignant group vs. 33.3% in the benign group, P < 0.001) and the arborescent pattern (0 vs. 19.5%, P < 0.001) were more likely to appear in benign nodules. The diagnostic specificities of the crab claw-like pattern and the root hair-like pattern for malignant thyroid nodules were 0.894, 0.976, and the positive predictive values were 0.860, 0.769. The diagnostic specificities of the wheel-like pattern and the arborescent pattern for benign thyroid nodules were 0.984, 1.000, and the positive predictive values were 0.953, 1.000.ConclusionsThe crab claw-like pattern and the root hair-like pattern were microflow characteristics of malignant thyroid nodules. The wheel-like pattern and the arborescent pattern could help exclude the diagnosis of thyroid cancer.

Integrated Diagnostics of Thyroid Nodules.

Thyroid nodules are common findings, particularly in iodine-deficient regions. Our paper aims to revise different diagnostic tools available in clinical thyroidology and propose their rational integration. We will elaborate on the pros and cons of thyroid ultrasound (US) and its scoring systems, thyroid scintigraphy, fine-needle aspiration cytology (FNAC), molecular imaging, and artificial intelligence (AI). Ultrasonographic scoring systems can help differentiate between benign and malignant nodules. Depending on the constellation or number of suspicious ultrasound features, a FNAC is recommended. However, hyperfunctioning thyroid nodules are presumed to exclude malignancy with a very high negative predictive value (NPV). Particularly in regions where iodine supply is low, most hyperfunctioning thyroid nodules are seen in patients with normal thyroid-stimulating hormone (TSH) levels. Thyroid scintigraphy is essential for the detection of these nodules. Among non-toxic thyroid nodules, a careful application of US risk stratification systems is pivotal to exclude inappropriate FNAC and guide the procedure on suspicious ones. However, almost one-third of cytology examinations are rendered as indeterminate, requiring "diagnostic surgery" to provide a definitive diagnosis. 99mTc-methoxy-isobutyl-isonitrile ([99mTc]Tc-MIBI) and [18F]fluoro-deoxy-glucose ([18F]FDG) molecular imaging can spare those patients from unnecessary surgeries. The clinical value of AI in the evaluation of thyroid nodules needs to be determined.

The Diagnostic Utility of Repeat Fine-needle Aspirations of Benign Thyroid Nodules.

Objective This study aims to analyze the diagnostic utility of multiple repeat FNA on thyroid nodules with initially benign diagnosis. Methods In a 5-year period, 1658 thyroid nodules with initially benign FNAs were retrospectively reviewed and followed for subsequent resection and repeat biopsy. Results Out of 2150 thyroid nodules, 1658 (77.1%) were diagnosed as benign on FNAs. The average age was 57.4 years (range 11-93 years), and most were females (83.8%). Repeat FNA was performed on 183 benign nodules, of which 141 (8.5%) were sampled a second time and 42 (2.5%) had 2 or more repeat samplings. For the benign nodules without repeat FNAs, 124 had benign resection. Of cases with one-time repeat FNA, most (n=101) remained benign on repeat FNAs, 13 of which were benign on resection. Eleven had atypical repeat FNAs, 5 were resected, 4 of which were benign and one was atypical follicular neoplasm with HRAS and TERT promoter mutations. Of cases with multiple repeat FNA, most (n=35) were still benign on repeat FNAs, one had benign resection. Two had atypical repeat biopsies, one was PTC on resection with CCD6::RET fusion. The positive predictive value significantly decreased from 41.1% on single FNA to 8.3% on one-time repeat (p<0.001) and 16.7% on multiple repeat (p=0.002). The total cost for workup of previously benign nodules was $285,454. Conclusions Repeat FNA biopsies did not provide an additional diagnostic value in the evaluation of benign thyroid nodules, and often led to unwarranted follow-up procedures and significantly increased health care cost.

Molecular Genetics Augment Cytopathologic Evaluation and Surgical Planning of Pediatric Thyroid Nodules

PurposeMolecular genetic testing in conjunction with cytopathology may improve prediction of malignancy in thyroid nodules, particularly those with indeterminate cytology (Bethesda III/IV). Though now commonplace in adults, pediatric data are limited. This study examines molecular genetics of pediatric nodules with correlation to cytologic and histologic classification at time of surgery and the distribution of mutations. MethodsRetrospective chart review of 164 patients <22 years who underwent surgical resection of a thyroid nodule between 2002 and 2020 with molecular testing on fine-needle aspiration biopsy (FNA) or final histopathology. Results85 (52 %) of 164 patients undergoing thyroid resection had available molecular genetic testing. BRAF V600E testing was performed on the FNA samples of 73 (86 %) patients and on 15 (18 %) surgical specimens; 31 (37 %) were positive. Of the remaining 54 patients, 21 had additional mutation/fusion testing. In 17 (81 %) cases, an alternate mutation/fusion was identified including 8 gene fusions, 3 DICER1 mutations, 4 NRAS mutations, one BRAF variant, and one unknown variant. BRAF, DICER1 mutations, and gene fusions predicted malignancy. Greater than 95 % of BRAF mutations were in Bethesda V/VI lesions and associated with classic variant PTC whereas fusions and DICER1 mutations clustered in Bethesda IV nodules. Bethesda III nodules harbored BRAF and NRAS mutations. In Bethesda IV nodules, a gene fusion or DICER mutation altered the surgical decision-making (upfront thyroidectomy rather than lobectomy) in 70 % of nodules submitted for genetic testing. ConclusionExpanded molecular genetic testing on FNA of pediatric thyroid nodules, particularly Bethesda III/IV, may improve prediction of malignancy and augment surgical decision-making. Level of EvidenceIII.