A Novel Risk Stratification System for Thyroid Nodules With Indeterminate Cytology—A Pilot Cohort Study

Autor: 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
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Thyroid nodules
Male
medicine.medical_specialty
Endocrinology
Diabetes and Metabolism
Cytodiagnosis
030209 endocrinology & metabolism
indeterminate cytology
Pilot Projects
Gastroenterology
lcsh:Diseases of the endocrine glands. Clinical endocrinology
Risk Assessment
03 medical and health sciences
0302 clinical medicine
Endocrinology
Internal medicine
Biopsy
fine needle aspiration biopsy
Medicine
Humans
Thyroid Neoplasms
Thyroid cancer
Original Research
Retrospective Studies
Ultrasonography
thyroid ultrasound
lcsh:RC648-665
molecular testing
medicine.diagnostic_test
Receiver operating characteristic
business.industry
Thyroid
Middle Aged
medicine.disease
Prognosis
Carcinoma
Neuroendocrine
030104 developmental biology
Fine-needle aspiration
medicine.anatomical_structure
Molecular Diagnostic Techniques
Thyroid Cancer
Papillary
Cohort
thyroid nodule
Female
business
Biomarkers
Cohort study
Follow-Up Studies
Zdroj: Frontiers in Endocrinology
Frontiers in Endocrinology, Vol 11 (2020)
ISSN: 1664-2392
Popis: 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.
Databáze: OpenAIRE
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