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

Review Article

Figure 2. The Bethesda system has improved the consistency of terminology and communication regarding the potential risk of malignancy of indeterminate cytologic findings. Adapted from: Baloch ZW, LiVolsi VA, Asa SL, et al. Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol . 2008;36:425-437. 6

added to cytologic evaluation (Fig. 3). The most common mutations identified in thyroid cancer improved the spe- cificity of thyroid cytology, but it was still not a sensitive enough detection method to rule out cancer for cases in which no mutation was identified. 12 Approaching the question of benign versus malignant cytopathology from a different perspective, a gene expres- sion classifier (GEC) was developed through an iterative process designed a priori to have a high sensitivity and high NPV, similar to the NPV of thyroid nodules diagnosed as benign on cytology. 13,14 Designed specifically to help rule out malignancy, the Afirma GEC (Veracyte, South San Francisco, Calif) was developed to potentially decrease the rate of diagnostic surgeries in the case of indeterminate nodules. In addition, as molecular testing was beginning to develop for clinical use to improve the diagnostic accuracy of thyroid FNA, The Cancer Genome Atlas (TCGA) pro- ject mapped the mutations attributed to both classical and follicular variants of PTC, significantly reducing the num- ber of unknown specific mutations causing differentiated thyroid cancer. 15 Incorporating the new information obtained through TCGA, an updated gene panel using next-generation sequencing (NGS) was developed for clinical use (ThyroSeq NGS, v2.0 [and now v2.1]; CBLPath, Orlando, Fla). 16-18 This test was developed to improve the overall accuracy of molecular testing to

papillary-like features (NIFTP). However, diagnostic lobectomy is still required for both pathologic diagnosis and clinical treatment of NIFTP. 9,10 Similar to distin- guishing between follicular adenoma and follicular carci- noma, histopathologic evaluation is necessary to exclude capsular or vascular invasion in the diagnosis of NIFTP.

THE DEVELOPMENT OF THYROID MOLECULAR TESTING

The initial development of immunohistochemical evalua- tion with Galectin-3 and other biomarkers demonstrated some potential to improve the diagnostic accuracy of thy- roid cytology, but it lacked sufficient reproducibility and sensitivity to reliably exclude malignancy. 11 Subsequently, new investigations sought to identify specific gene muta- tions and gene rearrangements that were pathogenic in thyroid cancer. The feasibility of cytomolecular testing for known DNA and RNA mutations, which accounted for 70% of thyroid carcinomas (Harvey rat sarcoma viral oncogene homolog [H-Ras], neuroblastoma rat sarcoma viral oncogene homolog [N-Ras], Kirsten rat sarcoma viral oncogene homolog [K-Ras], rearranged during trans- fection/PTC 1 [Ret/PTC1], Ret/PTC2, Ret/PTC3, v-Raf murine sarcoma viral oncogene homolog B1 [BRAF], and paired box gene 8-peroxisome proliferator-activator receptor c [Pax8-PPAR c ]) was demonstrated, which improved the diagnostic accuracy of needle biopsy when

Cancer

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