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.

Changes in the diagnosis of thyroid tumours in the 5th edition of the WHO classification of endocrine neoplasms.

The WHO classification of thyroid tumours enters its second half-century of development with the 5th edition. Compared to the previous 4th edition of the clas- sification, the permanent increase in information is mainly at the molecular biological level. This has changed the view of very traditional entities - the preferred name for polynodous goiter is (given the monoclonal nature of some nodules) follicular nodular thyroid disease. Some terminological relics have also been re- moved - Hürthle cells are definitively referred to as oncocytes. Follicular adenoma has a new subtype with papillary arrangement (and missing nuclear features of papillary carcinoma). In the already used NIFTP unit, subtypes smaller than 10 mm and oncocytic are newly defined. All oncocytic tumours have an arbitrarily set minimum proportion of oncocytes at 75 %. A multidisciplinary approach to the treatment of thyropathies and the stratification of therapeutic procedures according to risk brought about the introduction of grading into several nosological units of papillary, follicular, and medullary carcinomas. Grading using the number of mitoses determines their quantification at 2 mm² instead of the previously used non-uniform HPFs (high power fields of view). Clarification was made on the basis of genetic findings in a number of other, less frequent diagnoses (e.g. classification of squamous cell carcinoma among anaplastic). Among rare tumors a new category of salivary gland - type carcinomas is formulated with two representatives: mucoepidermoid and secretory carcinoma. Cribriform morular carcinoma previously classified as a variant of papillary carcinoma is newly separated on the basis of the immunological and genetic profile into the newly created category of tumors of uncertain histogenesis. This category also includes sclerosing mucoepidermoid carcinoma with eosinophilia. Microcarcino- ma as a separate entity is not included in the 5th edition. A tumor smaller than 10 mm must be characterized by the appropriate features of the corresponding category. Thyroblastoma replaces terminologically malignant teratoma from the previous classification. Part of the newly established diagnostic criteria is also applicable in FNAB diagnosis. The newly introduced grading in some nosological units can exceptionally change the diagnosis (NIFTP/EFVPTC/non-invasive HG FVPTC), but above all it will affect the choice of therapeutic procedures.

Integrated analysis of circulating and tissue proteomes reveals that fibronectin 1 is a potential biomarker in papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most frequent subtype of thyroid cancer, but 20% of cases are indeterminate (i.e., cannot be accurately diagnosed) based on preoperative cytology, which might lead to surgical removal of a normal thyroid gland. To address this concern, we performed an in-depth analysis of the serum proteomes of 26 PTC patients and 23 healthy controls using antibody microarrays and data-independent acquisition mass spectrometry (DIA-MS). We identified a total of 1091 serum proteins spanning 10-12 orders of magnitude. 166 differentially expressed proteins were identified that participate in complement activation, coagulation cascades, and platelet degranulation pathways. Furthermore, the analysis of serum proteomes before and after surgery indicated that the expression of proteins such as lactate dehydrogenase A and olfactory receptor family 52 subfamily B member 4, which participate in fibrin clot formation and extracellular matrix-receptor interaction pathways, were changed. Further analysis of the proteomes of PTC and neighboring tissues revealed integrin-mediated pathways with possible crosstalk between the tissue and circulating compartments. Among these cross-talk proteins, circulating fibronectin 1 (FN1), gelsolin (GSN) and UDP-glucose 4-epimerase (GALE) were indicated as promising biomarkers for PTC identification and validated in an independent cohort. In differentiating between patients with benign nodules or PTC, FN1 produced the best ELISA result (sensitivity = 96.89%, specificity = 91.67%). Overall, our results present proteomic landscapes of PTC before and after surgery as well as the crosstalk between tissue and the circulatory system, which is valuable to understand PTC pathology and improve PTC diagnostics in the future.

Radiation Dose Does Not Affect the Predictive Value of Thyroid Biopsy for Diagnosing Papillary Thyroid Cancer in a Belarusian Cohort Exposed to Chernobyl Fallout.

INTRODUCTION: The Chernobyl nuclear accident exposed residents of contaminated territories to substantial quantities of radioiodines and was followed by an increase in thyroid cancer, primarily papillary thyroid cancer (PTC), among exposed children and adolescents. Although thyroid biopsy is an essential component of screening programs following accidental exposure to radioiodines, it is unknown whether the predictive value of biopsy is affected by different levels of environmental exposure. METHODS: A cohort of 11,732 Belarusians aged ≤18 years at the time of the Chernobyl accident with individual thyroid radiation dose estimates was screened at least once 11-22 years later. Paired cytologic conclusions and histopathologic diagnoses were possible for 258 thyroid nodules from 238 cohort members. Cytologic conclusions were divided into five reporting categories, with all follicular lesion aspirates combined into a single indeterminate category. Standard performance indicators, risk of malignancy (ROM), and odds ratios for a correct cytologic conclusion were calculated, both overall and according to quintile of thyroid radiation dose. RESULTS: The arithmetic mean thyroid dose estimate for the study group was 1.73 Gy (range: 0.00-23.64 Gy). The final histopathologic diagnosis was cancer for 136 of 258 biopsies (52.7%; 135 papillary and 1 follicular). The overall ROM was 96.7% for cytologies definite for PTC, 83.7% for suspicious for PTC, 33.0% for indeterminate, 8.1% for benign, and 31.0% for non-diagnostic. The ROM showed little change according to level of radiation exposure. Overall, there was no association between thyroid radiation dose and the odds ratio for a correct cytologic conclusion (p = 0.24). When analyzed according to dose quintile, the odds ratio for a correct conclusion increased two-fold at 0.10-0.29 Gy compared to a dose of 0.00-0.09 Gy and decreased at doses of 0.3-24 Gy (p value for linear trend = 0.99). CONCLUSIONS: At radiation doses received by a cohort of young Belarusians exposed to radioiodines by the Chernobyl accident, the predictive value of thyroid biopsy for diagnosing PTC was not significantly affected by level of radiation exposure.

Low nondiagnostic rate for fine-needle capillary sampling biopsy of thyroid nodules: a singular experience.

OBJECTIVES: This study examined the hypothesis that sonographically guided fine-needle capillary thyroid biopsies performed by an experienced operator and with constant technique on nodules that meet the Society of Radiologists in Ultrasound criteria warranting biopsy can result in a nondiagnostic rate that is significantly lower than prior published reports. METHODS: We retrospectively reviewed the sonographic and pathologic reports from 228 consecutive sonographically guided fine-needle capillary thyroid biopsies performed during a 3-year interval by a single operator with more than 15 years of experience performing fine-needle capillary thyroid biopsies. There were no exclusion criteria. Sonographic and pathologic reports from all nodules biopsied were included in the analysis. The radiologist's protocol included 6 fine-needle capillary biopsies, each with 20 passes of the needle into the periphery and/or solid components of the nodule. The cytologic specimens were reviewed off-site in adherence with the Bethesda system for reporting thyroid cytopathologic findings and classified as diagnostic or nondiagnostic. The nondiagnostic rate in this study was compared with the nondiagnostic rates in prior published reports. RESULTS: Among the 228 fine-needle capillary thyroid biopsies performed during the study interval, cytologic analysis showed 1 nondiagnostic biopsy, yielding a nondiagnostic rate of 0.4%. This rate was significantly lower than previously published reports (P < .001). CONCLUSIONS: Sonographically guided fine-needle capillary biopsies of the thyroid performed by an experienced radiologist can result in a nondiagnostic rate of less than 1%. This finding warrants further investigation into the reasons for the discrepancy between the results of this study and other previous reports.

Ultrasound-guided fine-needle aspiration biopsy of the thyroid: methods to decrease the rate of unsatisfactory biopsies in the absence of an on-site pathologist.

PURPOSE: The rate of unsatisfactory samples from ultrasound-guided fine-needle aspirations of thyroid nodules varies widely in the literature. We aimed to evaluate our thyroid ultrasound-guided fine-needle aspiration biopsy technique in the absence of on-site microscopic examination by a pathologist; determine factors that affect the adequacy rate, such as the number of needle passes and needle size; compare our results with the literature; and establish an optimal technique. MATERIALS AND METHODS: We performed a retrospective review of cytopathology reports from 252 consecutive thyroid ultrasound-guided fine-needle aspiration biopsies performed by a radiologist between 2005 and 2010 in our hospital's radiology department. Sample adequacy, the number of needle passes, and needle size were determined. There was an on-site cytologist who prepared slides immediately after fine-needle aspiration but no on-site microscopic assessment of sample adequacy to guide the number of needle passes that should be performed. Cytopathology biopsy reports were classified as either unsatisfactory or satisfactory samples for diagnosis; the latter consisted of benign, malignant, and undetermined diagnoses. RESULTS: Seventy-seven biopsies were performed with 1 needle pass, 124 with 2 needle passes, and 51 with 3 needle passes. The rates of unsatisfactory biopsies were 33.8%, 23.4% (odds ratio [OR] 0.599 [95% confidence interval {CI}, 0.319-1.123]; P = .110), and 13.7% (OR 0.312 [95% CI, 0.124-0.788]; P = .014), respectively. CONCLUSION: In a hospital in which there is no on-site pathologist, a 3-pass method increases the specimen satisfactory rate by 20% compared with 1 pass, achieves similar rates to the literature, and provides a basis for further improvement of our practice.

The impact of classical music on anxiety and pain perception during a thyroid fine needle aspiration biopsy.

AIM: To determine the impact of classical music on the anxiety and pain perception of patients who underwent thyroid fine-needle aspiration biopsy (TFNAB) for the first time. METHODS: In a prospective randomized controlled design, TFNAB patients were randomized into the intervention and control groups. The State Anxiety Inventory (SAI) before and after the procedure and the visual analog scale (VAS) after procedure were used for measuring anxiety and pain. RESULTS: A total of 82 patients were included. There was no significant difference between the music intervention group (n = 41) and control group (n = 41) in terms of age, gender, work status, highest education level, SAI score before TFNAB, and duration of the procedure (p > 0.05). It was observed that the anxiety level before TFNAB was higher in women in all patient groups (p = 0.009). While the SAI score decreased significantly in the music intervention group (Z = - 3.62, p < 0.001), there was no significant difference in the control group (Z = - 1.41, p = 0.157) after TFNAB. However, no significant difference was found in terms of VAS between two groups (p = 0.075). The duration of the TFNAB procedure was correlated with the change in the SAI score (r = 0.382, p < 0.001). CONCLUSION: This is the first study to examine the impact of music on patients' anxiety and pain perception during the TFNAB procedure. Despite the fact that classical music intervention did not decrease pain perception, it significantly reduced patient anxiety. Music is an easy-to-implement intervention that can be considered as an effective method for reducing patient anxiety during TFNAB.

Correlation of Thyroid Fine Needle Aspiration Biopsy With Histopathological Results.

Introduction Fine needle aspiration biopsy (FNAB) is an effective method used in the differential diagnosis of thyroid nodules. The Bethesda system has contributed to the determination of clinical approaches by bringing standardization to cytopathology reporting. However, the rate of cytological-histological incompatibility varies between 10% and 30%. Results differ according to clinics in the literature. These results create a need to reevaluate the efficacy and safety of fine needle aspiration biopsy. In this study, we aimed to evaluate the diagnostic accuracy of FNAB of thyroid nodules by correlating the cytopathology results of FNAB with the results of postoperative histopathology. Methods In this retrospective study, thyroid FNAB results and postoperative histopathology results of patients who underwent thyroidectomy operations in our clinic between January 2018 and December 2021 were compared. Accuracy, sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), false positive rate (FPR), and false negative rate (FNR) were calculated. Cases with nondiagnostic FNAB results were excluded from the calculations. FNAB results with a follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) and suspicious for malignancy were included in the malignant group. Results A total of 304 patients were included in the study. The male/female ratio was 1:3.3. As a result of the study, malignancy was detected histopathologically in 47 (15.46%) patients. The commonest malignancy detected was papillary carcinoma. According to the Bethesda system, the results were evaluated in six categories. The incidence of malignancy in the Bethesda categories were 0%, 4%, 40%, 69.2%, 100%, and 100%, respectively. Accordingly, the specificity and sensitivity of FNAB for detecting malignancy were 98.7% and 66.6%, respectively. The accuracy was 93.5%. The false positive rate, false negative rate, positive predictive value, and negative predictive value were 1.20%, 33.3%, 91.4%, and 93.8%, respectively. Conclusion Thyroid FNAB is an effective method used with satisfactory reliability in the differential diagnosis of malignancies of thyroid nodules. Still, it has some limitations. This article demonstrates higher rates of malignancy in Bethesda categories III and IV. Therefore, clinical approaches are gaining importance in these categories.

Effect of an Information Video before Thyroid Biopsy on Patients' Anxiety.

AIM: To investigate the effects of video-based information on the anxiety of patients who underwent ultrasound-guided thyroid fine-needle aspiration biopsy. METHODS: Fifty consecutive patients who underwent thyroid fine needle aspiration biopsy were included in the study prospectively. Patients were divided into two groups before the biopsy. 25 patients in Group 1 received only written information about thyroid biopsy. In Group 2, 25 patients received video-based information along with written information. Baseline anxiety of all the patients was evaluated prior to procedure using STAI-S and STAI-T questionnaires. After the written information was provided to the patients in group 1, the STAI-S questionnaire was repeated. In the same way, group 2 patients were asked to repeat the STAI-S questionnaire after written and video-based information were provided. All patients were asked to evaluate pain during biopsy using visual analog scale (VAS). RESULTS: There was no significant difference between the groups in terms of age and gender. Although the VAS score was lower in group 2, there was no statistically significant difference between the two groups. When the groups were compared in terms of basal anxiety scores, STAI-T was similar in both groups (p = 0.708). Although STAI-S values were similar in pre and post-information patients in Group 1, the STAI-S values in group 2 were statistically significantly decreased. CONCLUSION: The video based information provided prior to thyroid biopsy draws the attention as an effective and easy to apply method to decrease the anxiety of the patients.

The Significance of RAS-Like Mutations and MicroRNA Profiling in Predicting Malignancy in Thyroid Biopsy Specimens.

In cytologically indeterminate thyroid nodules undergoing molecular testing, estimated risk of malignancy is variable. Identification of a non-cancer-specific mutation (RAS-like) confirms a neoplastic process but does not differentiate between benign, malignant, and low-risk neoplasms. This study aims to retrospectively evaluate institutional experience of Interpace (ThyGeNEXT® and ThyraMIR®; Pittsburgh, PA) testing and to determine the rate of malignancy in resected nodules, stratified by mutational analysis and microRNA profile. Of 1917 fine need aspirations, 140 (7.3%) underwent Interpace testing: 47 (33.6%) were molecular-not-benign (harbored mutation, fusion, and/or positive miRNA) and 93 (66.4%) were molecular-benign (no mutations or fusions and negative microRNA). Surgery was spared in 79.6% of molecular-benign and 61.4% of all tested patients. Fifty-four (38.6%) underwent resection. Seventeen (89.5%) of the resected molecular-benign were benign and 2 were malignant. Thirteen (37.1%) of the resected molecular-not-benign were benign, 7 (20%) were noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and 15 (42.9%) were malignant (p < 0.05, negative predictive value (NPV) 89.4-95.6%, positive predictive value (PPV) 22.3-42.8%). Most molecular-not-benign (72.3%) had RAS-like mutation. Twenty-three were resected: 3 were malignant and 7 were NIFTP. Nodules with non-RAS-like mutations (BRAF V600E-like, others) were more likely to be malignant than RAS-like (H/N/KRAS, BRAF K601E) (p < 0.05, NPV 86.9-96.5%, PPV 100%). Most nodules had RAS-like mutations and most were benign or low-risk neoplasms (NIFTP). This study supports the role of histologic examination in the distinction of malignancy in RAS-like thyroid neoplasms and underscores the role of molecular testing in risk stratification, patient counseling, and operative management.

Long-Term Impact of Thyroid Biopsy Specialists on Efficiency and Quality of Thyroid Biopsy.

OBJECTIVE: To assess consistency and long-term progress in thyroid biopsy performed by trained sonographers under supervision of a radiologist. METHODS: Trained sonographers started performing thyroid biopsy at our institute in August 2011. The data for this study were extracted from a prospectively maintained database for ultrasound guided thyroid biopsy and included the number of thyroid fine needle aspiration biopsy procedures performed between August 2011 and 2016 and the final cytopathology report as per the Bethesda Classification. For the analysis, the study was divided into two time periods: initial postimplementation period (August 2011 to 2013) and late postimplementation period (2014-2016). RESULTS: In all, 5,538 thyroid biopsies were performed by trained sonographers in the period, 2,561 in the initial implementation period and 2,977 between 2014 and 2016. The unsatisfactory rates dropped from 21% to 10% in the two periods (P < .001), and the proportion of malignant nodules on cytopathology increased from 6% to 7% in the two periods (P = .010). Wait times for thyroid biopsies remained low during the period. CONCLUSION: Sonographers trained to perform ultrasound guided thyroid biopsies provide persistent improved patient care over a long-term period. This reinforces the role of physician extenders in targeted scopes of practice.

A Preliminary Study of Quantitative Ultrasound for Cancer-Risk Assessment of Thyroid Nodules.

Background: Gray-scale, B-mode ultrasound (US) imaging is part of the standard clinical procedure for evaluating thyroid nodules (TNs). It is limited by its instrument- and operator-dependence and inter-observer variability. In addition, the accepted high-risk B-mode US TN features are more specific for detecting classic papillary thyroid cancer rather than the follicular variant of papillary thyroid cancer or follicular thyroid cancer. Quantitative ultrasound (QUS) is a technique that can non-invasively assess properties of tissue microarchitecture by exploiting information contained in raw ultrasonic radiofrequency (RF) echo signals that is discarded in conventional B-mode imaging. QUS provides quantitative parameter-value estimates that are a function of the properties of US scatterers and microarchitecture of the tissue. The purpose of this preliminary study was to assess the performance of QUS parameters in evaluating benign and malignant thyroid nodules. Methods: Patients from the Thyroid Health Center at the Boston Medical Center were recruited to participate. B-mode and RF data were acquired and analyzed in 225 TNs (24 malignant and 201 benign) from 208 patients. These data were acquired either before (167 nodules) or after (58 nodules) subjects underwent fine-needle biopsy (FNB). The performance of a combination of QUS parameters (CQP) was assessed and compared with the performance of B-mode risk-stratification systems. Results: CQP produced an ROC AUC value of 0.857 ± 0.033 compared to a value of 0.887 ± 0.033 (p=0.327) for the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) and 0.880 ± 0.041 (p=0.367) for the American Thyroid Association (ATA) risk-stratification system. Furthermore, using a CQP threshold of 0.263 would further reduce the number of unnecessary FNBs in 44% of TNs without missing any malignant TNs. When CQP used in combination with ACR TI-RADS, a potential additional reduction of 49 to 66% in unnecessary FNBs was demonstrated. Conclusion: This preliminary study suggests that QUS may provide a method to classify TNs when used by itself or when combined with a conventional gray-scale US risk-stratification system and can potentially reduce the need to biopsy TNs.

A Blinded Randomized Trial Comparing 2 Needle Gauges for Fine-Needle Biopsy of Thyroid Nodules.

OBJECTIVE: To compare diagnostic capability and patient pain between 25-gauge (25G) and 27G needles for ultrasound-guided fine-needle biopsy of thyroid nodules. STUDY DESIGN: Prospective blinded randomized trial. SETTING: Thyroid clinic in otolaryngology practice in a community. METHODS: A prospective randomized blinded trial was conducted on 148 thyroid nodules in 107 patients undergoing ultrasound-guided fine-needle biopsy. Needle gauge was randomized to individual nodule. Patients were blinded to the needle size used. All specimens were assessed via the Bethesda System for Reporting Thyroid Cytopathology and assigned a morphologic quantitative score based on number of thyroid cells and lymphocytes, amount of colloid, and degree of blood/fibrin artifact in each sample. Patient pain experience was scored. A chi-square test was used to compare nondiagnostic rates, and differences in cytologic morphology and pain scores were compared with 2-sample Student t tests. RESULTS: Of the 148 nodules, 77 were biopsied with 25G needles and 71 with 27G needles. Twenty-five percent (19/77) of the samples obtained with 25G needles yielded a nondiagnostic cytology result (Bethesda category 1) as compared with 11% (8/70) in the 27G group (P = .0282; 95% CI, 1.47%-25.97%). On average, samples from 25G needles had a higher blood/fibrin quantitative score (P = .043; 95% CI, -0.64 to -0.010). There were no differences in pain between groups. CONCLUSION: Use of a 27G needle for fine-needle biopsies is not only safe and feasible but desirable and highly recommended, as it yields better diagnostic information.

Nerve Injury During Ultrasound-Guided Thyroid Biopsy-A First Reported Complication of Permanent Vocal Fold Paralysis.

Needle biopsy is a well-established component in the evaluation of thyroid nodules. The biopsy is usually performed with an ultrasound guidance and consists of either fine-needle aspiration or core needle biopsy. Although these terms are often used interchangeably, their difference is important. To our knowledge, we discuss the first reported case of biopsy-proven laryngeal nerve injury and permanent vocal fold paralysis following ultrasound-guided core biopsy of the thyroid. We advocate this complication be discussed as part of the consent process.

The real-world performance of ThyroSeqV.2 to diagnose thyroid "neoplasm requiring surgery".

Fine-needle biopsy (FNB) predicts benign or malignant thyroid nodules. For indeterminate (ITN) FNBs, commercial molecular tests may improve the diagnostic accuracy and reduce the number of operations. These tests have had limited independent implementation studies in routine clinical practice. This is a prospective observational study. At Boston Medical Center, the 1,316 consecutive FNBs were classified to one of the six categories in the Bethesda classification system. Those ITN samples were submitted for ThyroSeqV.2 next generation sequencing panel analysis. The performance of ThyroSeqV.2 to predict "neoplasm requiring surgery" (NRS) was evaluated. ThyroSeqV.2 assay was performed in 398 FNBs on 384 cytologically ITN nodules (308 Bethesda III, 47 Bethesda IV and 29 Bethesda V). The first evaluable ThyroSeq result for each nodule was used for final analysis. Seventy-seven (72.0%) of 107 patients with a high risk molecular test underwent thyroid surgery resulting in 41 NRS (53.2%) and 36 benign nodules (46.8%). Of the 249 patients with a low risk or negative molecular analysis, 51 (20.5%) had surgery revealing 47 benign nodules (92.2%) and 4 NRS (7.8%). Based on surgical outcome of 128 ITN with evaluable ThyroSeq results, this molecular test had a sensitivity of 91% (95% CI: 79%-98%), specificity of 56% (45%-67%), positive predictive value (PPV) of 53% (42%-65%), negative predictive value (NPV) of 92% (81%-98%), and an overall accuracy of 69% (55%-85%) with a prevalence of NRS of 35% (27%-44%). ThyroSeqV.2 in this clinical use study in ITN nodules provided a similar NPV but a lower PPV than expected compared to published studies due to the detection of an array of mutations in benign nodules. The NPV of 92.0% for ITN cytology confirmed its utility as a "rule-out" test to exclude NRS.

Utilities of RAS Mutations in Preoperative Fine Needle Biopsies for Decision Making for Thyroid Nodule Management: Results from a Single-Center Prospective Cohort.

Background: It has been advocated to apply individualized strategies to evaluate thyroid nodules due to the growing awareness that the pathogenesis of thyroid cancer is not uniform. Molecular markers in fine needle biopsies (FNBs) may be helpful for the diagnosis and management decisions. Unlike the detection of BRAF mutations, the clinical utility of rat sarcoma viral oncogene homolog (RAS) mutations has not been fully elucidated. This study aimed at presenting a real-world performance of RAS mutations in identifying thyroid malignancies, at investigating the nature of thyroid tumors carrying RAS mutations, and at providing an additional reference for interpreting how to utilize the presence of RAS mutations in the decision-making process of thyroid nodule management. Methods: Between February 2015 and December 2017, 1400 sequential thyroid biopsies were performed at Boston Medical Center. Of these, 546 FNBs were evaluated for RAS mutations by using a ThyroSeq next-generation sequencing panel. Nodules carrying RAS mutations were prospectively followed, and medical records were collected. Results: ThyroSeq successfully provided molecular information in 504 nodules; 173 with molecular alteration(s); and 80 positive for mutations in the Kirsten-, Neuroblastoma-, or Harvey-RAS genes. RAS gene mutations constituted up to 46.2% of the total molecular alterations found in the study. Fifty-six of the 80 RAS-positive nodules underwent surgery, 33 (58.9%) were confirmed to be benign, 7 (12.5%) were noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), and 16 (28.6%) were thyroid carcinomas. The positive predictive value, negative predictive value, and accuracy of RAS mutations for identifying malignancies among cytologically indeterminate nodules were 25.5%, 89.7%, and 54.0% when NIFTP was not counted as cancer. A combination of RAS and other mutations increased the risk of malignancy. Twelve histopathologically proved RAS-only-positive malignant nodules all showed low-risk features and favorable prognosis. RAS isoforms added little assistance for predicting a malignancy and the response to therapy in our series. Conclusions:RAS mutations represent the most frequently detected genetic alterations in our series. RAS mutations, when occurring alone, are not helpful markers to identify malignancy among Bethesda III/IV cytologies, but may predict favorable behavior, and hence should be considered to guide initial management.

American College of Radiology Thyroid Imaging Reporting and Data System standardises reporting of thyroid ultrasounds.

BACKGROUND: Thyroid nodules are common, the majority benign. The small risk of malignancy leads to excessive workup. Thyroid ultrasound is essential for risk stratification and management guidance. Without an organised reporting guideline, reports do not add significant value to referring clinicians. The American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) was developed to aid ultrasound reporting, lessen excessive biopsies and diagnose thyroid cancers. OBJECTIVES: To standardise reporting of thyroid ultrasounds by utilising an organised reporting guideline based on ACR TI-RADS. METHOD: Thyroid ultrasound reports generated by radiology registrars at an academic hospital were studied in two phases. In Phase 1, the reports were generated as free text, and in Phase 2, using a guideline based on ACR TI-RADS. The percentages of reports that described the maximum size, the five ACR TI-RADS features and a management recommendation were compared. RESULTS: A total of 130 reports were studied. Significant improvement was observed in the description of all five ACR TI-RADS categories (p < 0.0001) from Phase 1 to Phase 2. Of all the reports, 89% included a management recommendation. Reports including an ACR TI-RADS-based recommendation increased from 48% to 75% (p < 0.05). Recommendation for biopsy increased from 35.4% to 53.8% (p < 0.05). CONCLUSION: Introduction of an organised reporting guideline based on ACR TI-RADS, standardised reporting of thyroid ultrasounds by increasing description of thyroid nodule features and ensuring appropriate management recommendations. This, in future, will prevent underdiagnosis of thyroid cancer and unnecessary workup of benign nodules.

Instituting Ultrasound-Guided FNA for Thyroid Nodules into a General Surgery Residency Program: What We Learned.

BACKGROUND: Evaluation of a thyroid nodule is a common referral seen by surgeons and frequently requires ultrasound-guided fine needle aspiration (US-guided FNA). While surgical residents may have sufficient exposure to thyroid surgery, many lack exposure to office-based procedures, such as US-guided FNA. General surgery residents should be provided with knowledge and practical skills in the application of diagnostic and interventional neck ultrasound to manage the common workup of a thyroid nodule. METHODS: This study sought to instruct and measure surgical residents' performance in thyroid US-guided FNA and evaluate their views regarding instituting such a formal curriculum. Twelve (n = 12) senior residents completed a written pretest and questionnaire, then watched an instructional video and practiced a simulated thyroid US-guided FNA on our created model. Then residents were evaluated while performing actual thyroid US-guided FNAs on patients in our clinic. Residents then completed the same written exam and questionnaire for objective measure. RESULTS: Eight of the chief residents (62%) felt "not comfortable" with the procedure on the pre-course survey; this was reduced to 0% on the post-course survey. Moderate comfort level increased from 15% to 50% and extreme comfort increased from 0% to 8%. From the 11 residents who completed the pre- and post-test exam, 82% (n = 9) significantly improved their score through the curriculum (pre-test: 40.9 vs. post-test: 61.8; p = 0.05). CONCLUSION: With focused instruction, residents are able to learn ultrasound-guided thyroid biopsy with improvement in subjective confidence level and objective measures. Resident feedback was positive and emphasized the importance of such training in surgical residency curriculum.

Pathologic basis of the sonographic differences between thyroid cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

Ultrasonography is pivotal in triage thyroid biopsy in the era after the identification of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This pictorial essay illustrates the pathologic basis of the sonographic features that distinguish NIFTP from thyroid cancers. In this study, we present the correlations of ultrasonography to ×1 histopathology to assess shape and margin characteristics. Markedly hypoechoic nodules correlate to microfollicular/solid nodules, while isoechoic/hyperechoic thyroid nodules correlate to normofollicular/macrofollicular nodules. The ultrasound findings of NIFTP and minimally invasive encapsulated thyroid cancers are similar. Both are well-circumscribed, oval-to-round nodules with regular margins. Blurred or microlobulated margins indicate infiltrating tumors, while lobulated margins are characteristic of expansile tumors. Overtly invasive encapsulated tumors are characterized by oval-to-round nodules with irregular or lobulated margins. The ultrasound findings for infiltrative thyroid cancers show at least one of the following malignant features: marked hypoechoicity, taller-than-wide shape, microcalcifications, and blurred or microlobulated margins.

A Fresh Cadaver Model for the Instruction of Ultrasound-Guided Fine-Needle Aspiration of Thyroid Nodules.

Objective The aim of our study is to determine if a fresh cadaver model (FCM) for the instruction of ultrasound (US)-guided fine-needle aspiration (FNA) of thyroid nodules is a practical method for instruction. Study Design Pre- and postinstruction assessment of medical students' ability to perform US-guided FNA of artificially created thyroid nodules placed adjacent to the thyroid gland of a fresh cadaver. Setting University-based fresh cadaver laboratory. Subjects and Methods Study participants included a total of 17 first- and second-year medical students with minimal US training. Technical skills were assessed using a 10-item checklist. In addition, a cognitive assessment regarding the indications, contraindications, and complications of the procedure was completed. A postinstruction assessment was provided for participants 5 weeks after their initial assessment. Differences between pre- and postinstruction assessment scores of technical skills were analyzed using McNemar's test. The mean cognitive knowledge gain was analyzed using a paired 2-sample t test. Results Eight of 10 items on the skills checklist were statistically significant between pre- and postinstruction skills assessment ( P < .05). There was a statistically significant change in cognitive knowledge gain regarding the contraindications of the procedure ( P = .001), but not for indications or complications ( P = .104 and P = .111, respectively). Conclusion US-guided FNA continues to be an important diagnostic procedure in the workup of thyroid nodules, making it an essential skill to integrate into surgical skills lab. Our FCM for the instruction of US-guided FNA is the first of its kind, and this pilot study shows this is a viable method for instruction.