A Novel Risk Stratification System for Thyroid Nodules With Indeterminate Cytology—A Pilot Cohort Study
Background: Thyroid ultrasound (US), fine needle aspiration biopsy (FNAB), and molecular testing have been widely used to stratify the risk of malignancy in thyroid nodules. The goal of this study was to investigate a novel diagnostic approach for cytologically indeterminate thyroid nodules (ITN) ba...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2020.00053/full |
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| author | Cristiane J. Gomes-Lima Cristiane J. Gomes-Lima Sungyoung Auh Shilpa Thakur Marina Zemskova Craig Cochran Roxanne Merkel Armando C. Filie Mark Raffeld Snehal B. Patel Liqiang Xi Leonard Wartofsky Kenneth D. Burman Joanna Klubo-Gwiezdzinska |
| author_facet | Cristiane J. Gomes-Lima Cristiane J. Gomes-Lima Sungyoung Auh Shilpa Thakur Marina Zemskova Craig Cochran Roxanne Merkel Armando C. Filie Mark Raffeld Snehal B. Patel Liqiang Xi Leonard Wartofsky Kenneth D. Burman Joanna Klubo-Gwiezdzinska |
| author_sort | Cristiane J. Gomes-Lima |
| collection | DOAJ |
| description | Background: Thyroid ultrasound (US), fine needle aspiration biopsy (FNAB), and molecular testing have been widely used to stratify the risk of malignancy in thyroid nodules. The goal of this study was to investigate a novel diagnostic approach for cytologically indeterminate thyroid nodules (ITN) based upon a combination of US features and genetic alterations.Methods: We performed a pilot cohort study of patients with ITN (Bethesda III/IV), who underwent surgical treatment. Based on standardized sonographic patterns established by the American Thyroid Association (ATA), each ITN received an US score (XUS), ranging between 0 and 0.9 according to its risk of thyroid cancer (TC). DNA and RNA were extracted from pathologic material, available for all patients, and subjected to Oncomine™ Comprehensive Assay v2 (OCAv2) next-generation sequencing. Each genetic alteration was annotated based on its strength of association with TC and its sum served as the genomic classifier score (XGC). The total risk score (TRS) was the sum of XUS and XGC. ROC curves were generated to assess the diagnostic accuracy of XUS, XGC, and TRS.Results: The study cohort consisted of 50 patients (39 females and 11 males), aged 47.5 ± 14.8 years. Three patients were excluded due to molecular testing failure. Among the remaining 47 patients, 28 (59.6%) were diagnosed with TC. BRAFV600E was the most common mutation in papillary TC, PAX8-PPARG fusion was present in NIFTP, pathogenic variants of SLX4, ATM, and NRAS were found in Hürthle cell TC and RET mutations in medullary TC. The diagnostic accuracy of XGC and TRS was significantly higher compared with XUS (88 vs. 62.5%, p < 0.001; 85.2 vs. 62.5%, p < 0.001, respectively). However, this increased accuracy was due to significantly better sensitivity (80.7 vs. 34.6%, p < 0.001; 84.6 vs. 34.6%, p < 0.001, respectively) without improved specificity (94.7 vs. 90%, p = 0.55; 85.7 vs. 90%, p = 0.63, respectively).Conclusion: Molecular testing might not be necessary in ITN with high-risk US pattern (XUS = 0.9), as specificity of TC diagnosis based on Xus alone is sufficient and not improved with molecular testing. OCAv2 is useful in guiding the management of ITN with low-to-intermediate risk US features (XUS < 0.9), as it increases the accuracy of TC diagnosis. |
| first_indexed | 2024-12-19T20:30:30Z |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-19T20:30:30Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-feeaec14157a41b7ac321e789207b2e82022-12-21T20:06:42ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922020-02-011110.3389/fendo.2020.00053507008A Novel Risk Stratification System for Thyroid Nodules With Indeterminate Cytology—A Pilot Cohort StudyCristiane J. Gomes-Lima0Cristiane J. Gomes-Lima1Sungyoung Auh2Shilpa Thakur3Marina Zemskova4Craig Cochran5Roxanne Merkel6Armando C. Filie7Mark Raffeld8Snehal B. Patel9Liqiang Xi10Leonard Wartofsky11Kenneth D. Burman12Joanna Klubo-Gwiezdzinska13National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK), Bethesda, MD, United StatesMedStar Clinical Research Center, MedStar Health Research Institute (MHRI), Washington, DC, United StatesNational Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK), Bethesda, MD, United StatesNational Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK), Bethesda, MD, United StatesNational Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK), Bethesda, MD, United StatesNational Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK), Bethesda, MD, United StatesNational Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK), Bethesda, MD, United StatesNational Institutes of Health/National Cancer Institute (NIH/NCI), Bethesda, MD, United StatesNational Institutes of Health/National Cancer Institute (NIH/NCI), Bethesda, MD, United StatesNational Institutes of Health/National Cancer Institute (NIH/NCI), Bethesda, MD, United StatesNational Institutes of Health/National Cancer Institute (NIH/NCI), Bethesda, MD, United StatesDivision of Endocrinology, Department of Medicine Georgetown University, Washington, DC, United StatesDivision of Endocrinology, Department of Medicine Georgetown University, Washington, DC, United StatesNational Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK), Bethesda, MD, United StatesBackground: Thyroid ultrasound (US), fine needle aspiration biopsy (FNAB), and molecular testing have been widely used to stratify the risk of malignancy in thyroid nodules. The goal of this study was to investigate a novel diagnostic approach for cytologically indeterminate thyroid nodules (ITN) based upon a combination of US features and genetic alterations.Methods: We performed a pilot cohort study of patients with ITN (Bethesda III/IV), who underwent surgical treatment. Based on standardized sonographic patterns established by the American Thyroid Association (ATA), each ITN received an US score (XUS), ranging between 0 and 0.9 according to its risk of thyroid cancer (TC). DNA and RNA were extracted from pathologic material, available for all patients, and subjected to Oncomine™ Comprehensive Assay v2 (OCAv2) next-generation sequencing. Each genetic alteration was annotated based on its strength of association with TC and its sum served as the genomic classifier score (XGC). The total risk score (TRS) was the sum of XUS and XGC. ROC curves were generated to assess the diagnostic accuracy of XUS, XGC, and TRS.Results: The study cohort consisted of 50 patients (39 females and 11 males), aged 47.5 ± 14.8 years. Three patients were excluded due to molecular testing failure. Among the remaining 47 patients, 28 (59.6%) were diagnosed with TC. BRAFV600E was the most common mutation in papillary TC, PAX8-PPARG fusion was present in NIFTP, pathogenic variants of SLX4, ATM, and NRAS were found in Hürthle cell TC and RET mutations in medullary TC. The diagnostic accuracy of XGC and TRS was significantly higher compared with XUS (88 vs. 62.5%, p < 0.001; 85.2 vs. 62.5%, p < 0.001, respectively). However, this increased accuracy was due to significantly better sensitivity (80.7 vs. 34.6%, p < 0.001; 84.6 vs. 34.6%, p < 0.001, respectively) without improved specificity (94.7 vs. 90%, p = 0.55; 85.7 vs. 90%, p = 0.63, respectively).Conclusion: Molecular testing might not be necessary in ITN with high-risk US pattern (XUS = 0.9), as specificity of TC diagnosis based on Xus alone is sufficient and not improved with molecular testing. OCAv2 is useful in guiding the management of ITN with low-to-intermediate risk US features (XUS < 0.9), as it increases the accuracy of TC diagnosis.https://www.frontiersin.org/article/10.3389/fendo.2020.00053/fullthyroid nodulethyroid ultrasoundfine needle aspiration biopsyindeterminate cytologymolecular testing |
| spellingShingle | Cristiane J. Gomes-Lima Cristiane J. Gomes-Lima Sungyoung Auh Shilpa Thakur Marina Zemskova Craig Cochran Roxanne Merkel Armando C. Filie Mark Raffeld Snehal B. Patel Liqiang Xi Leonard Wartofsky Kenneth D. Burman Joanna Klubo-Gwiezdzinska A Novel Risk Stratification System for Thyroid Nodules With Indeterminate Cytology—A Pilot Cohort Study Frontiers in Endocrinology thyroid nodule thyroid ultrasound fine needle aspiration biopsy indeterminate cytology molecular testing |
| title | A Novel Risk Stratification System for Thyroid Nodules With Indeterminate Cytology—A Pilot Cohort Study |
| title_full | A Novel Risk Stratification System for Thyroid Nodules With Indeterminate Cytology—A Pilot Cohort Study |
| title_fullStr | A Novel Risk Stratification System for Thyroid Nodules With Indeterminate Cytology—A Pilot Cohort Study |
| title_full_unstemmed | A Novel Risk Stratification System for Thyroid Nodules With Indeterminate Cytology—A Pilot Cohort Study |
| title_short | A Novel Risk Stratification System for Thyroid Nodules With Indeterminate Cytology—A Pilot Cohort Study |
| title_sort | novel risk stratification system for thyroid nodules with indeterminate cytology a pilot cohort study |
| topic | thyroid nodule thyroid ultrasound fine needle aspiration biopsy indeterminate cytology molecular testing |
| url | https://www.frontiersin.org/article/10.3389/fendo.2020.00053/full |
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