2018-19 Section 7-Neoplastic and Inflammatory Diseases of the Head and Neck eBook

Review Article

CONFLICT OF INTEREST DISCLOSURES Mary Y. Roth reports grants from Rosetta Genomics outside the submitted work. David L. Steward reports clinical trial support through the University of Pittsburgh Cancer Institute, from Rosetta Genomics, Veracyte Inc, and AstraZeneca during the conduct of the study. Robert L. Witt made no disclosures. AUTHOR CONTRIBUTIONS David L. Steward : Conception and design of work; acquisition, analysis, and interpretation of data; writing–initial draft; writing– review and revisions; final approval of the version to be published; and agreement to be accountable for all aspects of the work. Mara Y. Roth : Acquisition, analysis, and interpretation of data; writing– review and revisions; final approval of the version to be published; and agreement to be accountable for all aspects of the work. Robert L. Witt : Acquisition, analysis, and interpretation of data; writing– review and revisions; final approval of the version to be published; and agreement to be accountable for all aspects of the work. REFERENCES 1. Guth S, Theune U, Aberle J, Galach A, Bamberger CM. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest . 2009;39:699-706. 2. Cibas ES, Ali SZ. The Bethesda System for reporting thyroid cyto- pathology. Thyroid . 2009;19:1159-1165. 3. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines task force on thyroid nodules and differenti- ated thyroid cancer. Thyroid . 2016;26:1-133. 4. Cooper DS, Doherty GM, Haugen BR, et al. Management guide- lines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid . 2006;16:109-142. 5. Baloch ZW, LiVolsi VA, Asa SL, et al. Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a syn- opsis of the National Cancer Institute Thyroid Fine-Needle Aspira- tion State of the Science Conference. Diagn Cytopathol . 2008;36: 425-437. 6. Crippa S, Mazzucchelli L, Cibas ES, Ali AZ. The Bethesda System for reporting thyroid fine-needle aspiration specimens [author reply]. Am J Clin Pathol . 2010;134:345. 7. Cibas ES, Baloch ZW, Fellegara G, et al. A prospective assessment defining the limitations of thyroid nodule pathologic evaluation. Ann Intern Med . 2013;159:325-332. 8. Sacks WL, Bose S, Zumsteg ZS, et al. Impact of Afirma gene expres- sion classifier on cytopathology diagnosis and rate of thyroidectomy. Cancer Cytopathol . 2016;124:722-728. 9. Nikiforov YE, Seethala RR, Tallini G, et al. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol . 2016;2:1023-1029. 10. Armstrong MJ, Yang H, Yip L, et al. PAX8/PPAR g rearrangement in thyroid nodules predicts follicular-pattern carcinomas, in particu- lar the encapsulated follicular variant of papillary carcinoma. Thy- roid . 2014;24:1369-1374. 11. Bartolazzi A, Orlandi F, Saggiorato E, et al. Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multi- centre study. Lancet Oncol . 2008;9:543-549. 12. Nikiforov YE, Steward DL, Robinson-Smith TM, et al. Molecular testing for mutations in improving the fine-needle aspiration diagno- sis of thyroid nodules. J Clin Endocrinol Metab . 2009;94:2092-2098. 13. Walsh PS, Wilde JI, Tom EY, et al. Analytical performance verifica- tion of a molecular diagnostic for cytology-indeterminate thyroid nodules. J Clin Endocrinol Metab . 2012;97:E2297-E2306.

cases. Indications favoring “rule-out” testing include a low institutional prevalence of cancer for indeterminate thyroid nodules and patients with no high-risk history, physical features, or ultrasound features. The NPV of benign cytology is 96%. 3 Prospective studies suggest that this ideal has been met with several molecular tests, but careful surveillance is recommended given the lack of long-term outcomes. In addition, many of the molecular platforms described herein have limited testing against a true gold standard; because benign nodules, as determined by molecular tests, rarely undergo definitive histologic evaluation. Similarly, the true specificity of molecular tests also must be evaluated in benign nodules to further char- acterize the accuracy of molecular testing results. 3 Although there is hope that cytomolecular testing can potentially inform treatment decisions regarding the clinically low-risk PTCs that may be indolent; currently, molecular tests fail to improve the predictive ability beyond the TNM classification system. 51 The develop- ment of the American Thyroid Association risk- stratification system remains the best way to predict future disease recurrence after initial therapy. 3 However, the future of molecular testing in thyroid pathology holds great promise and may inform not only nodule manage- ment but also the role for radioactive iodine therapy and potentially systemic therapy as well. Further understand- ing of the molecular mutations causing thyroid cancer may allow for new drug development for high-risk disease, help identify and change treatment approaches for patients with specific mutations, and allow more directed risk-stratification and prognosis discussions. Early data have already begun to identify specific molecular markers in thyroid cancer associated with negative outcomes and decreased survival. 63 Further research into the implica- tions of molecular testing on treatment decisions and dis- ease prognosis is warranted. Whereas each test described has its own strengths and limitations, no data compare the performance charac- teristics of each commercially available test among a given collection of samples. Ideally, future research would include head-to-head comparisons of molecular tests, long-term prospective data, and cost-effectiveness studies; however, currently, clinicians and patients who use the tests must understand and weigh the advantages and limitations.

FUNDING SUPPORT No specific funding was disclosed.

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