Unnecessary Diagnostic Surgery Research Articles

Outcomes of cytologically indeterminate thyroid nodules managed with Genomic Sequencing Classifier.

Molecular testing can refine the risk of malignancy in thyroid nodules with indeterminate cytology to decrease unnecessary diagnostic surgery. This study was performed to evaluate the outcomes of cytologically indeterminate thyroid nodules managed with Afirma genomic sequencing classifier (GSC) testing. Adult patients who underwent a biopsy at three major academic centers between July 2017 and June 2021 with Bethesda III or IV cytology were included. All patients had surgery or minimum follow-up of 1 year ultrasound surveillance. The primary outcomes were the sensitivity, specificity, PPV, and NPV of GSC in Bethesda III and IV nodules. The median nodule size of the 834 indeterminate nodules was 2.1 cm and the median follow-up was 23 months. GSC's sensitivity, specificity, PPV, and NPV across all institutions were 95%, 81%, 50%, and 99% for Bethesda III nodules and 94%, 82%, 65%, and 98% for Bethesda IV nodules, respectively. The overall false negative rate was 2%. The NPV of GSC in thyroid nodules with oncocytic predominance was 100% in Bethesda III nodules and 98% in Bethesda IV nodules. However, the PPV of oncocytic nodules was low (17% in Bethesda III nodules and 45% in Bethesda IV nodules). Only 22% of thyroid nodules with benign GSC results grew during surveillance. GSC is a key tool for managing patients with indeterminate cytology, including the higher-risk Bethesda IV category. GSC benign thyroid nodules can be observed similarly to thyroid nodules with benign cytology.

Knot-and-ear sign: a pathognomonic ultrasonographic feature of suture granuloma after thyroid surgery.

This study investigated the clinical and ultrasonographic (US) findings of suture granulomas and recurrent tumors, and aimed to identify specific characteristics of suture granulomas through an experimental study. This retrospective study included 20 pathologically confirmed suture granulomas and 40 recurrent tumors between January 2010 and December 2020. The clinical findings included suture material, surgery, and initial TNM stage. The US findings included shape, size, margin, echogenicity, heterogeneity, vascularity, and internal echogenic foci. The distribution, paired appearance, and "knot-and-ear" appearance of internal echogenic foci were assessed. An experiment using pork meat investigated the US configuration of suture knots. Eighteen patients with 20 suture granulomas (15 women; mean age, 52±13 years) and 37 patients with 40 recurrent tumors (24 women; 54±18 years) were included. Patients with suture granulomas exhibited earlier initial T and N stages than those with recurrent tumors. The knot-and-ear appearance, defined as an echogenic dot accompanied by two adjacent echogenic dots or lines based on experimental findings, was observed in 50% of suture granulomas, but not in recurrent tumors (P<0.001). Central internal echogenic foci (68.8%, P=0.023) and paired appearance (75.0%, P<0.001) were more frequent in suture granulomas. During follow-up, 94.1% of suture granulomas shrunk. The knot-and-ear appearance is a potential pathognomonic finding of suture granuloma, and central internal echogenic foci with paired appearance were typical US features. Clinically, suture granulomas showed early T and N stages and size reduction during follow-up. Understanding these features can prevent unnecessary biopsy or diagnostic surgery.

B-200 Preoperative Classification of Thyroid Nodules by Desorption Electrospray Ionization Mass Spectrometry Imaging of Fine Needle Aspiration Biopsies

Abstract Background Preoperative diagnosis of thyroid lesions by fine-needle aspiration (FNA) biopsy cytology can be challenging, and in up to 20% of cases is unachievable. Patients with an indeterminate preoperative diagnosis are often recommended for diagnostic surgery, with the majority receiving a benign diagnosis, rendering the surgery unnecessary. Consequently, new technologies that can provide accurate preoperative diagnosis of thyroid lesions are needed. Here, we have employed DESI-MS imaging along with statistical modeling to determine molecular signatures of benign and malignant thyroid lesions using banked thyroid tissue samples with known histopathology diagnosis. We then applied this methodology for analysis and classification of preoperatively collected FNA smears. Methods A total of 199 fresh-frozen thyroid tissues including 50 normal, 55 follicular adenoma (FTA), 58 follicular carcinoma (FTC), and 36 papillary carcinoma (PTC) were sectioned at a thickness of 10 µm and stored at −80 °C until analysis. FNA biopsies were prospectively collected at Baylor College of Medicine. DESI-MS imaging was performed in the negative ion mode using a Waters Xevo G2-XS mass spectrometer fitted with a DESI-XS source. Samples were H&amp;E stained and pathologically evaluated after analysis. Molecular profiles from tissue regions of clear histology were used to build classification models. For the FNA smears, mass spectra corresponding to clusters of thyroid cells were extracted for statistical prediction, and the predictive performance of the models on FNA smears was assessed in correlation with pathology. Results DESI-MS analysis of thyroid tissue sections generated 151 317 individual mass spectra, comprised of hundreds of lipid and metabolite features, that were used to build and validate two classification models: PTC vs benign thyroid, comprised of normal thyroid and FTA, and FTC vs benign thyroid. For each of these models, the data was randomly split with two-thirds used as a training set to generate the model and one-third used as an independent validation set to assess the performance of the model. For the PTC vs benign thyroid model, a prediction accuracy of 97.7% was achieved for the training set with an accuracy of 96.6% for the withheld validation dataset. For the FTC vs benign model, an accuracy of 78.4% was achieved for both the training and validation datasets. We are currently refining statistical workflows to improve the performance of the FTC model and to generate a model discriminating benign thyroid from thyroid cancer (FTC and PTC combined). When testing the prediction of the classifiers built from tissue imaging data on an initial sample set of 19 FNAs, overall per-sample prediction accuracies of 79% and 89% were obtained using the PTC vs benign thyroid model and the FTC vs benign thyroid model, respectively. We are currently working to collect, analyze, and validate the performance of the classification models on additional FNA biopsies, with a focus on samples with indeterminate cytology. Conclusions Overall prediction accuracies of 79% and 89% were achieved for the benign vs PTC model and benign vs FTC model, respectively, for thyroid FNA classification. With the addition of DESI-MS, unnecessary diagnostic surgeries could be prevented by providing improved preoperative specificity.

Diagnostic Performance of Afirma and Interpace Diagnostics Genetic Testing in Indeterminate Thyroid Nodules: A Single Center Study

Indeterminate thyroid nodules (ITN) represent 20-30% of biopsied nodules, with a 10-60% risk of malignancy. Molecular testing can stratify the risk of malignancy among ITNs, and subsequently reduce the need for unnecessary diagnostic surgery. We aimed to assess the performance of these molecular tests at a single institution. Patients with Bethesda III, IV, and V nodules with Afirma and Interpace Diagnostics genetic testing data from November 2013 to November 2021 were included. Three cohorts were formed, including GSC + XA, ThyGeNEXT + ThyraMIR, and GSC + GEC. Statistical analysis determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic odds ratio (DOR), and accuracy of each type of testing. The PPV of nodules undergoing genetic testing by ThyGeNEXT + ThyraMIR (45.00%, 95%CI: 28.28-62.93%, p = 0.032) and GSC + XA (57.14%, 95%CI: 29.32-81.08%, p < 0.001) were superior to that of GEC + GSC (30.72%, 95%CI: 26.83-34.90%). The NPV was above 85% in all cohorts, suggesting overall suitable rule-out tests. The Afirma platform (GSC + XA) had the highest NPV at 96.97%. The overall accuracy for nodules undergoing ThyGeNEXT + ThyraMIR was 81.42% (95%CI: 73.01-88.11%, p < 0.001). A total of 230 patients underwent thyroidectomy, including less than 60% of each of the ThyGeNEXT + ThyraMIR and GSC + XA cohorts. Specifically, only 25% of patients in the GSC + XA cohort underwent surgery, considerably decreasing the rate of unnecessary surgical intervention. Sub-group analysis, including only patients with surgical pathology, found that PPV tended to be higher in the GSC + XA cohort, at 66.67% (95%CI: 37.28-87.06%), as compared to the ThyGeNEXT + ThyraMIR cohort, at 52.94% (95%CI: 35.25-69.92%). The Afirma genetic testing platform GSC + XA outperformed the other platforms with regards to both PPV and NPV and decreased the rate of surgery in patients with ITNs by 75%, significantly preventing unnecessary surgical intervention.

Application of machine learning methods to guide patient management by predicting the risk of malignancy of Bethesda III-V thyroid nodules.

Indeterminate thyroid nodules (ITN) are common and often lead to (sometimes unnecessary) diagnostic surgery. We aimed to evaluate the performance of two machine learning methods (ML), based on routinely available features to predict the risk of malignancy (RM) of ITN. Multi-centric diagnostic retrospective cohort study conducted between 2010 and 2020. Adult patients who underwent surgery for at least one Bethesda III-V thyroid nodule (TN) with fully available medical records were included. Of the 7917 records reviewed, eligibility criteria were met in 1288 patients with 1335 TN. Patients were divided into training (940 TN) and validation cohort (395 TN). The diagnostic performance of a multivariate logistic regression model (LR) and its nomogram, and a random forest model (RF) in predicting the nature and RM of a TN were evaluated. All available clinical, biological, ultrasound, and cytological data of the patients were collected and used to construct the two algorithms. There were 253 (19%), 693 (52%), and 389 (29%) TN classified as Bethesda III, IV, and V, respectively, with an overall RM of 35%. Both cohorts were well-balanced for baseline characteristics. Both models were validated on the validation cohort, with performances in terms of specificity, sensitivity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve of 90%, 57.3%, 73.4%, 81.4%, 84% (CI95%: 78.5%-89.5%) for the LR model, and 87.6%, 54.7%, 68.1%, 80%, 82.6% (CI95%: 77.4%-87.9%) for the RF model, respectively. Our ML models performed well in predicting the nature of Bethesda III-V TN. In addition, our freely available online nomogram helped to refine the RM, identifying low-risk TN that may benefit from surveillance in up to a third of ITN, and thus may reduce the number of unnecessary surgeries.

Maximizing Small Biopsy Patient Samples: Unified RNA-Seq Platform Assessment of over 120,000 Patient Biopsies.

Despite its wide-ranging benefits, whole-transcriptome or RNA exome profiling is challenging to implement in a clinical diagnostic setting. The Unified Assay is a comprehensive workflow wherein exome-enriched RNA-sequencing (RNA-Seq) assays are performed on clinical samples and analyzed by a series of advanced machine learning-based classifiers. Gene expression signatures and rare and/or novel genomic events, including fusions, mitochondrial variants, and loss of heterozygosity were assessed using RNA-Seq data generated from 120,313 clinical samples across three clinical indications (thyroid cancer, lung cancer, and interstitial lung disease). Since its implementation, the data derived from the Unified Assay have allowed significantly more patients to avoid unnecessary diagnostic surgery and have played an important role in guiding follow-up decisions regarding treatment. Collectively, data from the Unified Assay show the utility of RNA-Seq and RNA expression signatures in the clinical laboratory, and their importance to the future of precision medicine.

BRAF p.V600E genetic testing based on ultrasound-guided fine-needle biopsy improves the malignancy rate in thyroid surgery: our single-center experience in the past 10 years

PurposeUltrasound-guided fine-needle aspiration biopsy (UG-FNAB) was implemented in Qilu Hospital of Shandong University in 2015 as a preoperative diagnostic method for thyroid surgery. BRAF p.V600E genetic testing was implemented in 2019. This study evaluated the impact of these two tests on the malignancy rate in patients undergoing thyroidectomy.MethodsA total of 19,496 patients were included in the study. We retrospectively collected data from patients undergoing thyroid surgery in the Hospital Information System (HIS) of Qilu Hospital of Shandong University from January 2012 to December 2021. Meanwhile, data of FNAB, UG-FNAB, and BRAF p.V600E genetic testing were collected. Differences in means among groups were analyzed via one-way ANOVA, and differences in frequencies were analyzed via Pearson’s chi-squared test.ResultsIn this study, the 10-year period was divided into three stages, with the implementation of UG-FNAB in 2015 and that of BRAF p.V600E genetic testing in 2019 as dividing lines. The malignancy rate in thyroid surgery increased significantly during these three stages (48.06% vs. 73.47% vs. 88.17%; P < 0.001). In the same period (May 2019 to December 2021), the malignancy rate in thyroid surgery was significantly different between the Non-FNAB, UG-FNAB, and UG-FNAB-BRAF groups (78.87% vs. 95.63% vs. 98.32%; P < 0.001).ConclusionsThe successful implementation of UG-FNAB and BRAF p.V600E genetic testing improved the malignancy rate in thyroid surgery and reduced unnecessary diagnostic surgery for benign and marginal lesions. It can, therefore, provide a clinical reference for other hospitals.

Molecular Testing for Thyroid Nodules: The Experience at McGill University Teaching Hospitals in Canada.

Simple SummaryThe aim of this review is to provide a general overview about the molecular markers (mutations and alterations) of thyroid cancers, present several molecular tests, and discuss the clinical applications of identifying these markers supported by the clinical experience of several high-volume thyroid cancer specialists at the McGill university teaching hospitals in Montreal, Canada.In the past few decades, molecular characterization of thyroid cancer has made significant progress and is able to identify thyroid-cancer-related molecular markers that can then be applied clinically for improved decision making. The aim of this review is to provide a general overview about the molecular markers (mutations and alterations) of thyroid cancers, present several molecular tests, and discuss the clinical applications of identifying these markers supported by the clinical experience of several high-volume thyroid cancer specialists at the McGill university hospitals in Montreal, Canada. Our group experience showed that molecular testing can reclassify more than half of the patients with indeterminate thyroid nodules (Bethesda III and IV) into benign and spare these patients from unnecessary diagnostic surgery. Furthermore, it can help optimize the initial management in thyroid cancers with no evidence of high risk of recurrence of disease preoperatively. While routine molecular testing is not firmly established for thyroid FNA specimens that are suspicious or positive for malignancy (Bethesda V and VI), knowledge of a thyroid nodule’s molecular risk group profile in such cases, together with its clinical and radiologic features, can help select the optimal surgical options (lobectomy versus upfront total thyroidectomy and central neck dissection), as demonstrated by our studies.

Improvement in thyroid ultrasound report quality with radiologists' adherence to 2015 ATA or 2017 TIRADS: a population study.

Objectives There has been slow adoption of thyroid ultrasound guidelines with adherence rates as low as 30% and no population-based studies investigating adherence to guideline-based malignancy risk assessment. We therefore evaluated the impact of adherence to the 2015 ATA guidelines or 2017 ACR-TIRADS guidelines on the quality of thyroid ultrasound reports in our healthcare region.Methods We reviewed 899 thyroid ultrasound reports of patients who received fine-needle aspiration biopsy and were diagnosed with Bethesda III or IV nodules or thyroid cancer. Ultrasounds were reported by radiology group 1, group 2, or other groups, and were divided into pre-2018 (before guideline adherence) or 2018 onwards. Reports were given a utility score (0–6) based on how many relevant nodule characteristics were included.Results Group 1 had a pre-2018 utility score of 3.62 and 39.4% classification reporting rate, improving to 5.77 and 97.0% among 2018-onwards reports. Group 2 had a pre-2018 score of 2.8 and reporting rate of 11.5%, improving to 5.58 and 93.3%. Other radiology groups had a pre-2018 score of 2.49 and reporting rate of 32.2%, improving to 3.28 and 61.8%. Groups 1 and 2 had significantly higher utility scores and reporting rates in their 2018-onward reports when compared to other groups’ 2018-onward reports, pre-2018 group 1 reports, and pre-2018 group 2 reports.Conclusions Dedicated adherence to published thyroid ultrasound reporting guidelines can lead to improvements in report quality. This will reduce diagnostic ambiguity and improve clinician’s decision-making, leading to overall reductions in unnecessary FNA biopsy and diagnostic surgery.

National differences in cost analysis of Afirma Genomic sequencing classifier.

Thyroid nodules of indeterminate cytology can be subjected to molecular testing such as the Afirma Genomic Sequencing Classifier (GSC), thereby minimizing the number of unnecessary diagnostic surgeries. This work aimed to evaluate and compare the cost of routine GSC testing of indeterminate thyroid nodules in different countries. The cost of diagnostic hemithyroidectomy of indeterminate thyroid nodules was calculated by performing a Monte Carlo simulation cost analysis on a Markov decision-analytic model and then compared to that of GSC testing in the UK, Australia, USA, and Israel. Assuming that patients are treated by surgical resection and routine GSC testing is performed for all nodules of indeterminate significance, we found the GSC test to be more cost effective compared with diagnostic hemithyroidectomy when malignancy rates of thyroid nodules are less than 22.6%-37.1%, depending on the country where the test is performed. Given the cost of a thyroidectomy in the UK, Australia and Israel, performing routine GSC tests on all Bethesda IV nodules is more expensive than routine diagnostic hemithyroidectomy and becomes cost effective for Bethesda III when the GSC cost is below 3,031-3,087 USD. In comparison, in the USA, higher cost of thyroidectomy makes the GSC test cost effective for Bethesda III nodules at its current cost, but not for Bethesda IV nodules where it becomes cost effective under the price of 3,031 USD. Different molecular testing and surgical costs in different countries should be considered when performing cost analysis. In addition, since different medical centres have different malignancy rates, personalized in-house assessment of cost-effectiveness is warranted.

Real-world applications of deep convolutional neural networks in diagnostic cancer imaging.

Ultrasound is integral to the management of thyroid nodules. However, the interpretation of thyroid ultrasound studies is time- and training-intensive and has inherent inter-observer inconsistencies, resulting in a decrement in its positive predictive value (1). Compounding these limitations, fine-needle aspiration (FNA) yields 15% to 30% cytologically indeterminate nodules, which often leads to unnecessary diagnostic surgeries (2).

PMD5 VALUE of Electromagnetic Navigation Bronchoscopy and Its IMPACT on LUNG Cancer Diagnosis Costs

Lung cancers are frequently diagnosed in advanced stages due to late patients’ symptomatology or difficulties accessing solitary lung nodules (SLN). Electromagnetic navigation bronchoscopy (ENB) has shown to be a safe, effective and minimally invasive technique for SLN diagnosis at initial stages. Its use could avoid unnecessary diagnostic surgeries (DS) and complications from other diagnostic techniques, as computed tomography-guided transthoracic needle aspiration (CT-TTNA). This study aims to estimate potential avoidable costs on lung cancer diagnosis when introducing ENB from a Spanish hospital perspective. A cost analysis was developed to calculate the cost associated with DS and pneumothoraxes caused by CT-TTNA, as well as the impact of ENB’s introduction in a tertiary hospital. It was based on a yearly hypothetic cohort of 70 and 50 suspected lung cancer patients for DS and CT-TTNA, respectively. Clinical parameters from Sant Pau´s hospital were used in the base case, while an alternative analysis using data from the literature was also performed. Cost data was extracted from Spanish databases and expressed in €. 7 DS that accounted for a total cost of €57,882 (including surgery and hospital stay costs) could have been avoided if a previous biopsy would have been done. The introduction of ENB versus CT-TTNA resulted in a reduction of 9 pneumothoraxes, associated with €22,170. In the alternative analysis, compared to the base case, a higher rate of avoidable DS was considered, leading to higher potential savings (€185,224). The use of ENB resulted in a reduction of 8 pneumothoraxes (€21,306). Current diagnostic methods for lung cancer have an economic impact on hospitals. ENB facilitates the access and biopsy of SLN at initial stages, which improves clinical practice by avoiding aggressive diagnostic techniques, reducing complications and allowing histological diagnostic in lung cancer in order to indicate the right surgical approach.

The effect of implementing pre-surgical ultrasound-guided fine-needle aspiration biopsy on thyroid surgery, a 6-year interrupted time series analysis in Qilu Hospital of Shandong University

Thyroid fine-needle aspiration biopsy (FNAB) is not well developed in most of the large academic hospitals in China, including Qilu Hospital of Shandong University. Ultrasound-guided FNAB (UG-FNAB) was initiated as a pre-surgical diagnostic method in 2015 in Qilu Hospital, and the current study evaluates its impact on the number of thyroid surgeries and the ratio of malignancy (ROM) in surgically resected cases, comparing the post and pre-UG-FNAB periods. Thyroid surgery and UG-FNAB data for the study period (Jan 2013 to Dec 2018) were collected from the hospital information system (HIS). A natural experimental approach using segmented linear regression was performed on the interrupted time-series (ITS) data to estimate the level-change of the number and the trend-change of ROM of surgically resected cases following the implementation of UG-FNAB diagnosis. The number of UG-FNAB cases in Qilu Hospital increased rapidly from 1,367 in 2015 to 3,402 in 2018, with an average annual increase of 678 cases. Comparing the pre-UG-FNAB and post-UG-FNAB periods, the overall ROM of thyroid resections increased from 58.7% to 73.2% (P<0.01). Due to the implementation of UG-FNAB, the regression line of surgical cases showed an inflection point in March 2015, and the slope of the regression line of post-intervention was lower than that of pre-intervention. For each additional month, the ROM in thyroid surgical cases increased by 0.389% (P<0.01). After excluding the influence of time, the ROM in surgically resected thyroid cases increased by 4.781% due to the application of the UG-FNAB examination (P<0.01). This successful implementation of UG-FNAB further improved overall ROMs in surgically resected cases particularly as we acquired further experience with the procedure and reduced unnecessary diagnostic surgeries for patients with benign and borderline lesions.

Cervical Bronchogenic Cysts Mimicking Papillary Thyroid Carcinoma on Ultrasound

Here, we describe two cases of cervical bronchogenic cysts mimicking thyroid cancer on ultrasound (US), introducing some sources of diagnostic error with the aim of improving the understanding of cervical bronchogenic cysts. In these cases, US demonstrated ill-defined nonhomogeneous hypoechoic nodules at the inferior pole of the thyroid gland, exhibiting several echogenic foci that mimicked microcalcification of papillary thyroid carcinoma. Although cervical bronchogenic cysts can be presented as highly suspicious thyroid nodules on US, recognition of this disease entity and comprehensive understanding of its presentation can allow an appropriate diagnostic process without unnecessary diagnostic surgery. Key words: Bronchogenic cyst ㆍ Diagnosis ㆍ Papillary thyroid carcinoma ㆍ Thyroid nodule

Performance of 18F-FDG PET/CT in Selecting Thyroid Nodules with Indeterminate Fine-Needle Aspiration Cytology for Surgery. A Systematic Review and a Meta-Analysis.

Thyroid nodules with indeterminate fine-needle aspiration cytology (FNA) represent a major challenge in clinical practice. We conducted a systematic review and meta-analysis evaluating the ability of hybrid imaging using fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to appropriately select these nodules for surgery. PubMed, CENTRAL, Scopus, and Web of Science were searched until July 2019. Original articles reporting data on the performance of 18F-FDG PET/CT in thyroid nodules with indeterminate FNA were included. Summary operating points including 95% confidence interval values (95% CI) were estimated using a random-effects model. Out of 786 retrieved papers, eight studies evaluating 104 malignant and 327 benign thyroid nodules were included. The pooled positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR) of 18F-FDG PET/CT were 1.7 (95% CI: 1.4–2.0), 0.4 (95% CI: 0.2–0.7), and 3.5 (95% CI: 1.7–7.1), respectively. No heterogeneity was found for LR+ and DOR. In patients with thyroid nodules with indeterminate FNA, 18F-FDG PET/CT has a moderate ability to correctly discriminate malignant from benign lesions and could represent a reliable option to reduce unnecessary diagnostic surgeries. However, further studies using standardized criteria for interpretation are needed to confirm the reproducibility of these findings.

The Role of Core Needle Biopsy for the Evaluation of Thyroid Nodules with Suspicious Ultrasound Features.

ObjectiveRecent studies demonstrated that core needle biopsy (CNB) can effectively reduce the possibility of inconclusive results and prevent unnecessary diagnostic surgery. However, the effectiveness of CNB in patients with suspicious thyroid nodules has not been fully evaluated. This prospective study aimed to determine the potential of CNB to assess thyroid nodules with suspicious ultrasound (US) features.Materials and MethodsPatients undergoing CNB for thyroid nodules with suspicious features on US were enrolled between May and August 2016. Diagnostic performance and the incidence of non-diagnostic results, inconclusive results, conclusive results, malignancy, unnecessary surgery, and complications were analyzed. Subgroup analysis according to nodule size was performed. The risk factors associated with inconclusive results were evaluated using multivariate logistic regression analysis.ResultsA total of 93 patients (102 thyroid nodules) were evaluated. All samples obtained from CNB were adequate for diagnosis. Inconclusive results were seen in 12.7% of cases. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for diagnosis of malignancy were 93.8%, 100%, 100%, 78.9%, and 95%, respectively. None of the patients underwent unnecessary surgery. The diagnostic performance was not significantly different according to nodule size. On multivariate logistic regression analysis, larger nodule size and shorter needle length were independent risk factors associated with inconclusive results.ConclusionSamples obtained by CNB were sufficient for diagnosis in all cases and resulted in high diagnostic values and conclusive results in the evaluation of suspicious thyroid nodules. These findings indicated that CNB is a promising diagnostic tool for suspicious thyroid nodules.

Performance of a Genomic Sequencing Classifier for the Preoperative Diagnosis of Cytologically Indeterminate Thyroid Nodules

Use of next-generation sequencing of RNA and machine learning algorithms can classify the risk of malignancy in cytologically indeterminate thyroid nodules to limit unnecessary diagnostic surgery. To measure the performance of a genomic sequencing classifier for cytologically indeterminate thyroid nodules. A blinded validation study was conducted on a set of cytologically indeterminate thyroid nodules collected by fine-needle aspiration biopsy between June 2009 and December 2010 from 49 academic and community centers in the United States. All patients underwent surgery without genomic information and were assigned a histopathology diagnosis by an expert panel blinded to all genomic information. There were 210 potentially eligible thyroid biopsy samples with Bethesda III or IV indeterminate cytopathology that constituted a cohort previously used to validate the gene expression classifier. Of these, 191 samples (91.0%) had adequate residual RNA for validation of the genomic sequencing classifier. Algorithm development and independent validation occurred between August 2016 and May 2017. Thyroid nodule surgical histopathology diagnosis by an expert panel blinded to all genomic data. The primary end point was measurement of genomic sequencing classifier sensitivity, specificity, and negative and positive predictive values in biopsies from Bethesda III and IV nodules. The secondary end point was measurement of classifier performance in biopsies from Bethesda II, V, and VI nodules. Of the 183 included patients, 142 (77.6%) were women, and the mean (range) age was 51.7 (22.0-85.0) years. The genomic sequencing classifier had a sensitivity of 91% (95% CI, 79-98) and a specificity of 68% (95% CI, 60-76). At 24% cancer prevalence, the negative predictive value was 96% (95% CI, 90-99) and the positive predictive value was 47% (95% CI, 36-58). The genomic sequencing classifier demonstrates high sensitivity and accuracy for identifying benign nodules. Its 36% increase in specificity compared with the gene expression classifier potentially increases the number of patients with benign nodules who can safely avoid unnecessary diagnostic surgery.

Case Report: Acute Calcific Tendonitis at the Pectoralis Major Attachment-A Benign Cause of Red Flag Signs

Introduction: Acute calcific tendonitis at the pectoralis major insertion is rarely reported in the radiology literature, but not in the Orthopaedic literature. We present a case that illustrates the typical findings with discussion from a shoulder surgeon, and a senior radiologist. Case Study: A 60-year-old woman was woken at night with sudden onset left shoulder and arm pain. She was otherwise systemically well. Her shoulder range of motion was globally restricted. Past medical history included previous spinal surgery and a hepatitis A infection within the last year. Plain radiographs of the shoulder and humerus were unremarkable save for a small an anterior proximal humeral protuberance at the junction of proximal third and distal two-thirds of the humeral shaft. Blood tests were unremarkable. CT and MRI imaging showed a calcific tendon with associated cortical defect, and surrounding inflammation. Because of the sinister red flag symptoms (night pain) and suggestion of cortical erosion with periosteal reaction, the differential diagnosis list included sarcoma. For this reason, it was referred to the local sarcoma service. This was reviewed by a senior radiologist. The diagnosis of calcific tendonitis of pectoralis major calcific tendonitis was made. The decision was made by the Sarcoma MDT to not biopsy the lesion but instead review clinically with interval scan and safety netting. On six week clinic follow up the patient’s symptoms had improved. Because of the knowledge regarding this potential diagnosis, unnecessary invasive diagnostic procedures (CT biopsy) or surgeries were avoided. Repeat MRI at three month showed resolution of changes. Conclusion: Both Orthopaedic surgeons within sarcoma services and wider members of the multidisciplinary team should be aware of this diagnosis. This would help to prevent over investigation of benign self-limiting pathologies.

Molecular Profiling of Thyroid Nodules: Current Role for the Afirma Gene Expression Classifier on Clinical Decision Making.

Thyroid fine-needle aspiration biopsy results are cytologically indeterminate in 15-30% of cases. When these nodules undergo diagnostic surgery, approximately three-quarters are histologically benign. These unnecessary surgeries diminish quality of life, generate complications, and increase healthcare costs. The Afirma gene expression classifier (GEC) is validated to pre-operatively identify cytologically indeterminate nodules likely to be truly benign so that surgery can be avoided. Its performance is supported by robust multicenter prospective and blinded clinical validation studies, and supported by extensive independent clinical utility publications which show a marked reduction in surgery among patients with benign Afirma GEC results. To rule-out cancer and avoid unnecessary diagnostic surgery, Afirma’s quality and depth of validation stand alone. The accuracy of a benign result is the negative predictive value (NPV). Afirma achieves an NPV ≥94% among cytologically indeterminate nodules (Bethesda III or IV). Thirteen clinical utility studies describing 1468 GEC benign patients demonstrate that few Afirma GEC benign nodules undergo surgery, including after 3 years of follow-up. With a specificity of 52%, over half of the truly benign nodules with indeterminate cytology receive a benign GEC result. High test sensitivity is critical to safely rule out cancer. The Afirma GEC’s 90% sensitivity means that regardless of the pre-test risk of malignancy, 90% of all malignant nodules are GEC suspicious. The Afirma GEC has transformed patient care. Where the majority of cytologically indeterminate patients were once operated to determine if the nodule was benign or malignant, now nearly half of these surgeries can be avoided.

Malignant-looking thyroid nodules with size reduction: core needle biopsy results.

PurposeThe aim of this study was to evaluate whether malignant-looking thyroid nodules with size reduction were malignant or not.MethodsFrom November 2010 to July 2011, we retrospectively enrolled 16 patients with 16 nodules (11 females and five males; mean age, 55 years) who underwent core needle biopsy (CNB), and whose thyroid nodules had malignant ultrasonographic (US) features, although they showed size reduction (>20% decrease in maximum diameter) during the follow-up period (mean, 37±27 months). The histologic findings of the CNB specimen were reviewed and correlated with the US findings. US studies were analyzed for their internal content, shape, margin, echogenicity, the presence of microcalcification and macrocalcification, inner isoechoic rim, and low-echoic halo.ResultsAll nodules were confirmed as benign by CNB. Pathologic analysis was available for 12 CNB specimens. US imaging showed central hypoechogenicity or marked hypoechogenicity in all cases and a peripheral isoechoic rim in 15 nodules. US-pathologic correlation showed that the central hypoechoic area was primarily composed of fibrosis (12/12) and hemorrhage (8/12) and that the isoechoic rim was composed of follicular cells.ConclusionIn our study, the CNB results of all of the malignant-looking thyroid nodules with size reduction were benign and were primarily composed of internal fibrosis and hemorrhage. Understanding these US and pathologic features could prevent repeated fine-needle aspiration or unnecessary diagnostic surgery.