New Strategies in Diagnosing Cancer in Thyroid Nodules: Impact of Molecular Markers

Abstract

Thyroid cancer is the most common type of endocrine malignancy, with approximately 55,000 new cases diagnosed in the United States in 2012. However, thyroid nodules are much more prevalent, particularly with increased age, and only a small fraction of those are malignant. Therefore, the major clinical challenge is to reliably differentiate those nodules that are malignant and need to be treated surgically from the majority of nodules that are benign and do not require surgery. The traditional diagnostic approach to this clinical situation is ultrasound-guided fine-needle aspiration (FNA) of the thyroid nodule followed by cytologic examination, which together reliably establish the diagnosis in 70% to 80% of cases. However, in the rest of nodules the presence of cancer cannot be ruled out by FNA cytology, hampering appropriate surgical management and frequently resulting in unnecessary surgical interventions. New approaches to diagnosis of cancer in thyroid nodules are based on mutational and other molecular markers, which can be reliably detected in cells aspirated during the FNA procedure. These markers offer significant improvement in the diagnostic accuracy of FNA cytology and are poised to make a profound effect on the management of patients with thyroid nodules. In addition to the molecular markers that have recently become available for clinical use, rapid development of new sequencing techniques is expected to further improve the accuracy of cancer diagnosis in thyroid nodules and allow for a fully individualized approach to the management of patients with thyroid nodules.

The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer

“…Similarly, molecular mutation analyses in cystic neoplasia of the pancreas and of thyroid lesions of indeterminate cytology can be used to help differentiate benign from malignant lesions [16][17][18][19][20][21][22][23][24][25] . In suspected Stratification of cancer has now become a part of the primary diagnosis.…”

“…Now, mutation status has become a part of the disease name of an increasing number of cancers because they predict recurrence or have implications for targeted therapy, sometimes for multiple mutations (e.g., BRAF, MEK, RAS-mutant melanoma [28][29][30] ). MPS can interrogate multiple gene regions that have been characterized as mutational hot spots, providing an efficient method for identifying a number of somatic mutations known to be important cancer drivers 17,[31][32][33] . Just as important as diagnostic efficiency is the limitation presented by specimen type, which can impact the number of tumor cells and/or quantity of DNA available for analysis.…”

BRAFV600E Mutation, RET/PTC1 and PAX8-PPAR Gamma Rearrangements in Follicular Epithelium Derived Thyroid Lesions - Institutional Experience and Literature Review

“…Nikiforov et al (58) mentioned in their manuscript that, specifically, BRAF, RET/PTC or PAX8-PPARγ mutations correlate with the malignant outcome in nearly 100% of cases, assuming that the analysis is performed in a clinical laboratory, following appropriate validation of the detection techniques. Further progress is required in diagnostic accuracy and it will probably be achieved in the near future upon to the availability of novel technologies such as next generation sequencing (NGS), which offers simultaneous sequencing of thousands of millions of short nucleic acid sequences in a massively parallel way and also includes whole genome sequencing (58).…”

“…Further progress is required in diagnostic accuracy and it will probably be achieved in the near future upon to the availability of novel technologies such as next generation sequencing (NGS), which offers simultaneous sequencing of thousands of millions of short nucleic acid sequences in a massively parallel way and also includes whole genome sequencing (58).…”

Annual Financial Impact of Thyroidectomies for Nodular Thyroid Disease in China

“…This is true especially when thyroid FNA results turn out to be indeterminate. When a nodule is indeterminate by FNA, the optimal way is to repeat FNA or undergo molecular tests (Alexander, 2008;Nikiforov et al, 2009;Nikiforov et al, 2011;Alexander et al, 2012;Kim and Alexander, 2012;Zhou et al, 2012;Nikiforov et al, 2013;Ranjbari et al, 2013;Alexander et al, 2014). Surgery, however, should be regarded as the last resort if all the other options still fail to produce satisfactory results.…”