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  • Author: Anna Crescenzi x
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Ralf Paschke
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Silvia Cantara
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Anna Crescenzi
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Barbara Jarzab
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Thomas J. Musholt
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Manuel Sobrinho Simoes
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Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology. Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics. The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF, NRAS, HRAS, KRAS, PAX8/PPARG, RET/PTC) of targeted next generation sequencing and of a microarray gene expression classifier (GEC) test in the diagnostic assessment of an indeterminate cytology thyroid nodule. Moreover, possible surgical consequences of molecular FNA diagnostic results of thyroid nodules and the evidence that analysis of a molecular FNA diagnostic panel of somatic mutations or a microarray GEC test can alter the follow-up were reviewed. Molecular tests may help clinicians to drive patient care and the surgical decision if the analysis is performed in specialized laboratories. These molecular tests require standardization of performance characteristics and appropriate calibration as well as analytic validation before clinical interpretation.

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Ernesto Maddaloni Endocrinology and Diabetes Unit, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Silvia Irina Briganti Endocrinology and Diabetes Unit, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy

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Anna Crescenzi Pathology Unit, Campus Bio-Medico University of Rome, Rome, Italy

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Giuseppina Beretta Anguissola Endocrinology and Diabetes Unit, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy

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Eleonora Perrella Pathology Unit, Campus Bio-Medico University of Rome, Rome, Italy

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Chiara Taffon Pathology Unit, Campus Bio-Medico University of Rome, Rome, Italy

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Andrea Palermo Endocrinology and Diabetes Unit, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy

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Silvia Manfrini Endocrinology and Diabetes Unit, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy

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Paolo Pozzilli Endocrinology and Diabetes Unit, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy

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Angelo Lauria Pantano Endocrinology and Diabetes Unit, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy

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Introduction: Thyroid ultrasound (US) is crucial for clinical decision in the management of thyroid nodules. In this cross-sectional study, we aimed to test if the evaluation of thyroid nodules’ vascularization could improve the risk stratification ability of the American College of Radiology (ACR) TI-RADS classification system. Methods: A total of 873 thyroid nodules undergoing fine-needle aspiration were classified according to ACR TI-RADS US classification. Three types of vascularization were identified: type 0, no vascular signals; type 1, peripheral vascular signals; type 2, peripheral and intralesional vascular signals. Cytology specimens were evaluated conforming to the Italian Reporting System for Thyroid Cytology, and TIR3b, TIR4, and TIR5 were defined as high risk for malignancy. Odds ratios (ORs) with 95% confidence intervals (CI) and the areas under the receiver operating characteristic curves (ROC-AUC) for high-risk cytology categories were calculated. Results: The 3 vascular patterns were differently distributed within the cytology categories: 52.4% of TIR1c, 15.9% of TIR2, 5.9% of TIR3a, 6.7% of TIR3b, 12.5% of TIR4, and 28.9% of TIR5 nodules had no vascular signals (p < 0.001). Nodule vascularity alone was not associated with a higher risk of malignant cytology (OR [95% CI] 0.75 [0.43–1.32], p = 0.32), without differences between peripheral (OR [95% CI] 0.65 [0.35–1.20]) and intranodular (OR [95% CI] 0.88 [0.48–1.62]) vascularization (p = 0.22). The ROC-AUC (95% CI) for the diagnosis of malignant cytology was similar when considering TI-RADS classification alone (0.736 [0.684–0.786]) and when considering TI-RADS classification plus the presence/absence of vascular signals (0.736 [0.683–0.789], p value for differences between the ROC-AUCs: 0.91). Among TR1, TR2, and TR3 TI-RADS classes, no nodules without vascular signals showed a malignant cytology, allowing the identification of nodules with benign cytology with 100% specificity within these US classes. Conclusions: Color Doppler study of thyroid nodules does not improve the risk stratification ability of the ACR TI-RADS US classification system.

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Andrea Palermo Unit of Endocrinology and Diabetes, Campus Bio-Medico University, Rome, Italy

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Andrea Napolitano Department of Medical Oncology, Campus Bio-Medico University, Rome, Italy

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Daria Maggi Unit of Endocrinology and Diabetes, Campus Bio-Medico University, Rome, Italy

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Anda Mihaela Naciu Unit of Endocrinology and Diabetes, Campus Bio-Medico University, Rome, Italy

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Gaia Tabacco Unit of Endocrinology and Diabetes, Campus Bio-Medico University, Rome, Italy

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Silvia Manfrini Unit of Endocrinology and Diabetes, Campus Bio-Medico University, Rome, Italy

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Anna Crescenzi Department of Anatomic Pathology, Campus Bio-Medico University, Rome, Italy

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Chiara Taffon Department of Anatomic Pathology, Campus Bio-Medico University, Rome, Italy

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Francesco Pantano Department of Medical Oncology, Campus Bio-Medico University, Rome, Italy

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Bruno Vincenzi Department of Medical Oncology, Campus Bio-Medico University, Rome, Italy

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Guiseppe Tonini Department of Medical Oncology, Campus Bio-Medico University, Rome, Italy

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Daniele Santini Department of Medical Oncology, Campus Bio-Medico University, Rome, Italy

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Immune checkpoint inhibitors have been recently approved for cancer treatment. Nivolumab is a monoclonal antibody specific for programmed cell death-1 (PD-1) that modulates T-cell response. It was initially used for the treatment of malignant melanoma and then approved in other cancers, such as non-small cell lung cancer and clear cell renal cell carcinoma (ccRCC). So far, the activity of nivolumab in patients with thyroid malignancies has been reported in a single case of anaplastic thyroid cancer. Here, we report the case of a patient with ccRCC who developed a papillary thyroid carcinoma (PTC) under first-line sunitinib treatment. During nivolumab, the second-line treatment for ccRCC, we unexpectedly observed a complete regression of PTC.

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