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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EMolecular testing of thyroid nodules for genetic mutations is being used to augment fine-needle aspiration cytology to improve the accuracy of diagnosing thyroid cancer in the \u223c?25% of thyroid nodules with indeterminate cytology. In this article, commercially available molecular diagnostic methods, as well as the diagnosis of thyroid nodular disease.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eoncology genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ehead \u0026amp; neck cancers\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ethyroid disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EMolecular testing of thyroid nodules for genetic mutations is being used to augment fine-needle aspiration (FNA) cytology (FNAC) to improve the accuracy of diagnosing thyroid cancer in the \u223c 25% of thyroid nodules with indeterminate cytology [Nikiforov YE et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2011].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EUNDERSTANDING COMMERCIALLY AVAILABLE MOLECULAR DIAGNOSTIC METHODS\u003C\/h2\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EThe attributes of the commercially available molecular tests and open questions regarding their validation were reviewed by Steven P. Hodak, MD, New York University Langone Medical Center, New York, New York, USA.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EThree important caveats must be kept in mind about the available molecular tests. One, the methods for each test differ and this may affect the clinical outcomes; tests with high sensitivity require additional validation. Two, the tests for the same markers are not actually the same; the specific mutations in the gene panel vary between the tests. Three, more investigation is required to determine whether low-frequency mutations in a tumor sample is a true positive.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EDr. Hodak noted that the characteristics of each must be understood, including their limitations. The molecular tests have been shown to be reproducible and to accurately detect mutations in laboratory specimens. However, clinical validation of the molecular tests against the clinical outcomes, including the correlation with histology, has not been done for all of the available tests.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EA 7-gene panel test is available from Quest Diagnostics and Asuragen, and an enhanced multigene panel called ThyroSeq is available from the University of Pittsburgh and CBLPath. Three studies showing that molecular testing improved diagnosis and that molecular markers were highly specific have served as the foundation against which the tests from Quest Diagnostics and Asuragen have been validated [Nikiforov YE et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2011; Cantara S et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2010; Nikiforov YE et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2009]. A comparison of the methods and sensitivities between the published studies and the tests is provided in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E. In this comparison, Sanger sequencing had an analytic threshold of \u223c 20% of mutation-bearing cells, and Pyro sequencing had a threshold of \u223c 5% of mutation-bearing cells.\u003C\/p\u003E\n         \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16438\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16438\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16438\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EComparison of Methods and Sensitivity of Molecular Testing in the Literature and Commercially Available Tests\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EThe ThyroSeq molecular test has shown promise as one with high sensitivity and specificity, with a high negative predictive value and positive predictive value, stated Dr. Hodak. The peer-reviewed data about the diagnostic sensitivity and specificity have not been published.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EThe sensitivity of the molecular tests is important because they define a threshold below which any mutation that may be present cannot be detected. Dr. Hodak stated that the methods used by Asuragen and Quest Diagnostics are markedly more sensitive than the methods used in the validation studies, and they will identify tumors with a lower prevalence of mutations, but that different analytical methods may produce different results in the same specimen. Clinical validation is needed to understand whether this greater discrimination is clinically relevant.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EDIAGNOSIS OF THYROID NODULAR DISEASE\u003C\/h2\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EThe diagnosis of thyroid nodular disease (TND) by FNAC may be improved by measuring calcitonin (CT), which is secreted in medullary thyroid cancer (MTC). Rossella Elisei, MD, University of Pisa, Pisa, Italy, stated that CT measurement allows for early diagnosis and the opportunity to plan appropriate surgical treatment and improve outcomes. However, there are some limitations: CT measurement has a low specificity, especially in patients with low CT levels; a stimulation test must be conducted to distinguish between true and false positive serum CT results; and interpretation of CT test results requires skill.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EAn elevation in serum CT in the low-to-medium range alone is not diagnostic of MTC. Further testing should include FNAC, CT measurement in the wash-out, an ultrasound of the neck lymph nodes, and a stimulation test. If the diagnosis still remains unclear, Prof. Elisei recommends waiting for 6 to 12 months and repeating the basal CT measurement and neck ultrasound, especially if the nodule is \u0026lt; 1 cm.\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EA clinical review has shown that FNAC was accurate in detecting MTC in 151 of 192 patients (79%) prior to surgery [Ahmed SR, Ball DW. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2011]. Problems associated with FNAC to diagnose MTC include: overlooking typical features, such as amyloid content, with routine methods; difficulty in detecting occult MTC with nodules that are too small or located posteriorly in the thyroid lobe that cannot be reached; or inconsistency in the cytology pattern of MTC, which can mimic that of other cancers.\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EA stimulation test can be conducted using calcium gluconate 25 mg\/kg (or 2.5 mg\/kg of calcium element) diluted in a final volume of 50 mL of a sodium chloride solution administered intravenously over 5 to 10 minutes. The 2 essential guidelines used to interpret the result of a stimulation test are, first, the peak CT must be \u0026gt; 100 pg\/mL, and second, the delta for the increase in CT should be \u2265 4 times that of the basal value. Prof. Elisei noted that CT values between 60 pg\/mL and 100 pg\/mL are in a gray zone in regard to how they are interpreted. Two other approaches are the pentagastrin stimulation test and the basal ultrasensitive CT measurement [Pina G et al. \u003Cem\u003EClin Endocrinol (Oxf)\u003C\/em\u003E 2013].\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EA consensus statement recommended the addition of CT measurement to screen patients with TND to improve the early diagnosis of MTC [Pacini F et al. \u003Cem\u003EEur J Endocrinol\u003C\/em\u003E 2006]. Another consensus statement could not recommend for or against routine CT measurement because of the unresolved issues related to sensitivity, specificity, assay performance, and cost-effectiveness [Cooper DS et al. \u003Cem\u003EThyroid\u003C\/em\u003E 2009]. A high level of serum CT is usually diagnostic of MTC, yet a complete work-up of the suspected nodule with FNAC and measurement of CT in the wash-out is indicated. If there are discrepancies in the results of these tests, a stimulation test should be conducted.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/20\/22.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm0k2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzm0k2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}