Abstract

Molecular testing has acquired a relevant role for diagnostic and prognostic stratification of indeterminate thyroid nodules. Besides the available commercial solutions marketed in the United States, various local testing strategies have been developed in the last decade. In this setting, the modern interventional cytopathologist, the physician who performs the both aspirate and the morphologic interpretation plays a key role in the correct handling of fine-needle aspiration (FNA) samples not only for microscopy but also for molecular techniques. This review summarizes experiences with local approaches to the molecular testing of thyroid FNA, highlighting the role of the modern interventional cytopathologist.

Highlights

  • The updated Bethesda classification system for thyroid cytopathology (TBSRTC) includes molecular testing to refine fine-needle aspiration (FNA) indeterminate diagnoses [1].the American and European Thyroid Associations highlighted the importance of thyroid FNA molecular tests, no consensus has yet been reached regarding the best molecular strategy [2,3,4]

  • The American and European Thyroid Associations highlighted the importance of thyroid FNA molecular tests, no consensus has yet been reached regarding the best molecular strategy [2,3,4]

  • This review summarizes experiences with local approaches to the molecular testing of thyroid FNAs, highlighting the role of the modern cytopathologist

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Summary

Introduction

The updated Bethesda classification system for thyroid cytopathology (TBSRTC) includes molecular testing to refine fine-needle aspiration (FNA) indeterminate diagnoses [1]. The two most widely adopted commercially available thyroid FNA testing approaches are based on modern and comprehensive technologies either on classifiers, such as the RNA expression signatures to discriminate between benign and malignant nodules, or on the massive parallel sequencing for the detection of a very large number of genomic alterations, such as point mutations, gene fusions and copy number variations The former includes tests with high NPV and moderate PPV (rule-out tests), whereas the latter may show high PPV (rule-in tests) or both high NPV and PPV [5]. The relevance of proper nodule sampling under ultrasound (US) guidance, the correct handling of the aspirated material, the rapid on-site evaluation (ROSE), the careful cyto-preparations, the correct microscopic interpretation and standardized and meaningful reporting cannot be overemphasized In this context, cytopathologists need to acquire increasingly complex skills beyond the traditional ones to ensure the full comprehension of the cytological material for the microscopic assessment and for the advanced molecular technologies. This review summarizes experiences with local approaches to the molecular testing of thyroid FNAs, highlighting the role of the modern cytopathologist

The 7-Gene Test
From Single Gene Testing to Parallel and Massive Sequencing Analysis
Beyond Mutational Panels
Findings
Interventional Molecular Cytopathology
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