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Preoperative metabolic classification of thyroid nodules using mass spectrometry imaging of fine-needle aspiration biopsies.

ABSTRACT: Thyroid neoplasia is common and requires appropriate clinical workup with imaging and fine-needle aspiration (FNA) biopsy to evaluate for cancer. Yet, up to 20% of thyroid nodule FNA biopsies will be indeterminate in diagnosis based on cytological evaluation. Genomic approaches to characterize the malignant potential of nodules showed initial promise but have provided only modest improvement in diagnosis. Here, we describe a method using metabolic analysis by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for direct analysis and diagnosis of follicular cell-derived neoplasia tissues and FNA biopsies. DESI-MS was used to analyze 178 tissue samples to determine the molecular signatures of normal, benign follicular adenoma (FTA), and malignant follicular carcinoma (FTC) and papillary carcinoma (PTC) thyroid tissues. Statistical classifiers, including benign thyroid versus PTC and benign thyroid versus FTC, were built and validated with 114,125 mass spectra, with accuracy assessed in correlation with clinical pathology. Clinical FNA smears were prospectively collected and analyzed using DESI-MS imaging, and the performance of the statistical classifiers was tested with 69 prospectively collected clinical FNA smears. High performance was achieved for both models when predicting on the FNA test set, which included 24 nodules with indeterminate preoperative cytology, with accuracies of 93% and 89%. Our results strongly suggest that DESI-MS imaging is a valuable technology for identification of malignant potential of thyroid nodules.

SUBMITTER: DeHoog RJ

PROVIDER: S-EPMC6815148 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Preoperative metabolic classification of thyroid nodules using mass spectrometry imaging of fine-needle aspiration biopsies.

DeHoog Rachel J RJ Zhang Jialing J Alore Elizabeth E Lin John Q JQ Yu Wendong W Woody Spencer S Almendariz Christopher C Lin Monica M Engelsman Anton F AF Sidhu Stan B SB Tibshirani Robert R Suliburk James J Eberlin Livia S LS

Proceedings of the National Academy of Sciences of the United States of America 20191007 43

Thyroid neoplasia is common and requires appropriate clinical workup with imaging and fine-needle aspiration (FNA) biopsy to evaluate for cancer. Yet, up to 20% of thyroid nodule FNA biopsies will be indeterminate in diagnosis based on cytological evaluation. Genomic approaches to characterize the malignant potential of nodules showed initial promise but have provided only modest improvement in diagnosis. Here, we describe a method using metabolic analysis by desorption electrospray ionization m ...[more]

PMID: 31591199

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Project description:Importance Ultrasound-guided fine-needle aspiration biopsies (UGFNA) play a crucial role in the diagnosis of thyroid nodules. There are two techniques for performing an UGFNA: short-axis technique and long-axis technique. There is sparsity in the literature regarding the differences between these two techniques. Objective To compare the efficiency between long-axis and short-axis thyroid UGFNA techniques in trainees. Our secondary outcomes were to define the comfort level and learning curves of trainees. Design A longitudinal prospective cohort study, completed from December 2018 to November 2019, using the Blue Phantom Thyroid Model© for UGFNA. Face and construct validity of the model were verified. Residents completed UGFNA on an assigned nodule using both long-axis and short-axis techniques, the order of which was sequentially allocated. The rate and time to successful biopsy were obtained for both techniques. Biopsy attempts were repeated to establish learning curves. Setting Single-center study. Participants Fourteen Otolaryngology—Head & Neck Surgery residents at the University of Toronto. Main outcome measure Biopsy success and efficiency for novice learners completing UGFNA on a simulated thyroid model using long-axis and short-axis techniques. Results A trend towards higher odds of successful biopsy using the long-axis technique with no difference in procedure duration was observed (OR = 2.2, p = 0.095, CI = 0.87–5.39). Learning curve graphs appeared heterogenous according to trainee level. Trainees found the long-axis technique easier to perform (10/14, 71%), and the simulator valuable for learning (12/14, 86%). Conclusion Thyroid UGFNA using the long-axis technique may have an increased success rate and is generally favored by trainees for being easier to perform. Thyroid simulators have the potential to increase learner comfort and efficiency with UGFNA. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s40463-022-00587-5.

Project description:BackgroundFine-needle aspiration biopsy (FNAB) is a recognized technique for the basic, preoperative cytological diagnosis of thyroid nodules.Aim of the studyTo analyze the accuracy of FNAB in the diagnosis of thyroid cancer in patients with solitary and multiple thyroid nodules and to compare the demographic, clinical and pathological characteristics of patients with thyroid carcinoma in solitary and multiple tumors.Materials and methodsThe case records of 2,403 patients with solitary and multiple thyroid tumors treated consecutively between 2008 and 2013 were analyzed retrospectively. We selected 1,645 for further analysis. A solitary thyroid nodule was observed in 493 patients, and multiple nodules were detected in 1,152 patients. Further classification of the patients in these two groups was performed on the basis of the FNAB results, type of surgery performed and histopathology. TC was histopathologically confirmed in 166 patients, and benign disease was found in 1,479. The TC patients were assigned to the study group, and those with benign thyroid disease were placed into the control group. The study group was divided into two subgroups according to the presence of cancer in a single thyroid nodule or in multiple nodules. Malignancy in a solitary thyroid nodule was diagnosed in 98 (59.0%) patients, and cancer in multiple nodules was diagnosed in 68 (41.0%). Comparative analyses of the demographic, clinical and histopathological characteristics were performed for both subgroups. The following statistical analyses were performed: comparative characteristic of subgroups, ROC analysis for study group and subgroup of patients, and multivariable logistic regression analysis for study group.ResultsThe rate of prediction of TC by FNAB was three times higher in the patients with a solitary thyroid nodule compared with those with multiple thyroid nodules and it was statistically significant (p<0.001). The rate of total thyroid resection and lack of necessity for reoperation were also significantly higher in the TC patients with a solitary nodule. The histopathological results showed that significantly more patients with a solitary nodule had advanced-stage TC (stage III or IV) and tumor progression (pT3 or pT4) (p = 0.002 for both). ROC analysis demonstrated that the overall accuracy of FNAB as a predictor of thyroid cancer presence was high, especially for the subgroup of patients with a solitary thyroid nodule (AUC = 0.958, p<0.0001). Multivariable logistic regression analysis confirmed that a positive FNAB result was the sole predictor of the performance of total resection in the TC study group (p<0.0001), while a negative FNAB result and the presence of a papillary cancer type were independent predictors of the risk of reoperation (p<0.0001 and p = 0.002, respectively).ConclusionsFNAB often produces false-negative results in patients with multiple malignant thyroid tumors, which results in reoperation in many cases. False-negative FNAB results are rare in patients with a solitary tumor. Because of the low predictive capacity of FNAB for thyroid cancer in patients with multiple thyroid tumors, total thyroid excision should be considered in most cases despite a "negative" (no malignant) FNAB result.

Project description:The aim of this study is to perform a cost-effectiveness comparison between palpation-guided thyroid fine-needle aspiration biopsies (P-FNA) and ultrasound-guided thyroid FNA biopsies (USG-FNA).Each nodule was considered as a case. Diagnostic steps were history and physical examination, TSH measurement, Tc99m thyroid scintigraphy for nodules with a low TSH level, initial P-FNA versus initial USG-FNA, repeat USG-FNA for nodules with initial inadequate P-FNA or USG-FNA, hemithyroidectomy for inadequate repeat USG-FNA. American Thyroid Association thyroid nodule management guidelines were simulated in estimating the cost of P-FNA strategy. American Association of Clinical Endocrinologists guidelines were simulated for USG-FNA strategy. Total costs were estimated by adding the cost of each diagnostic step to reach a diagnosis for 100 nodules. Strategy cost was found by dividing the total cost to 100. Incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference between strategy cost of USG-FNA and P-FNA to the difference between accuracy of USG-FNA and P-FNA. A positive ICER indicates more and a negative ICER indicates less expense to achieve one more additional accurate diagnosis of thyroid cancer for USG-FNA.Seventy-eight P-FNAs and 190 USG-FNAs were performed between April 2003 and May 2008. There were no differences in age, gender, thyroid function, frequency of multinodular goiter, nodule location and diameter (median nodule diameter: 18.4 mm in P-FNA and 17.0 mm in USG-FNA) between groups. Cytology results in P-FNA versus USG-FNA groups were as follows: benign 49% versus 62% (p = 0.04), inadequate 42% versus 29% (p = 0.03), malignant 3% (p = 1.00) and indeterminate 6% (p = 0.78) for both. Eleven nodules from P-FNA and 18 from USG-FNA group underwent surgery. The accuracy of P-FNA was 0.64 and USG-FNA 0.72. Unit cost of P-FNA was 148 Euros and USG-FNA 226 Euros. The cost of P-FNA strategy was 534 Euros and USG-FNA strategy 523 Euros. Strategy cost includes the expense of repeat USG-FNA for initial inadequate FNAs and surgery for repeat inadequate USG-FNAs. ICER was -138 Euros.Universal application of USG-FNA for all thyroid nodules is cost-effective and saves 138 Euros per additional accurate diagnosis of benign versus malignant thyroid nodular disease.ClinicalTrials.gov, NCT00571090.

Dataset Information

Preoperative metabolic classification of thyroid nodules using mass spectrometry imaging of fine-needle aspiration biopsies.

Publications

Preoperative metabolic classification of thyroid nodules using mass spectrometry imaging of fine-needle aspiration biopsies.

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