Molecular Tests for Risk-Stratifying Cytologically Indeterminate Thyroid Nodules: An Overview of Commercially Available Testing Platforms in the United States
Abstract
:1. Background
2. Molecular Profiles of Thyroid Tumors
2.1. DNA Sequence Alterations, Gene Fusions, and Chromosomal Copy-Number Alterations
2.2. Gene and microRNA Expression Profiles
3. Molecular Assays for Cytologically Indeterminate Thyroid Nodules
- (1).
- High-probability results, where the probability of cancer is so high that thyroidectomy is indicated for therapeutic purposes (the decision between lobectomy versus total thyroidectomy may be informed by clinical, sonographic, cytologic, and molecular features of a nodule).
- (2).
- Intermediate-probability results, for which a diagnostic lobectomy is recommended for definitive nodule classification and in many cases may suffice from a therapeutic standpoint.
- (3).
- Low-probability results, where the cancer risk is similar to that of cytologically benign aspirates, for which clinical surveillance would be adequate.
3.1. ThyroSeq v3
3.2. ThyGeNEXT/ThyraMIR
3.3. Afirma GSC and Xpression Atlas
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Haugen, B.R.; Alexander, E.K.; Bible, K.C.; Doherty, G.M.; Mandel, S.J.; Nikiforov, Y.E.; Pacini, F.; Randolph, G.W.; Sawka, A.M.; Schlumberger, M.; 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 Differentiated Thyroid Cancer. Thyroid 2016, 26, 1–133. [Google Scholar] [CrossRef] [Green Version]
- Cooper, D.S.; Doherty, G.M.; Haugen, B.R.; Kloos, R.T.; Lee, S.L.; Mandel, S.J.; Mazzaferri, E.L.; McIver, B.; Pacini, F.; Schlumberger, M.; et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009, 19, 1167–1214. [Google Scholar] [CrossRef] [Green Version]
- Hirokawa, M.; Suzuki, A.; Higuchi, M.; Hayashi, T.; Kuma, S.; Ito, Y.; Miyauchi, A. The Japanese reporting system for thyroid aspiration cytology 2019 (JRSTAC2019). Gland Surg. 2020, 9, 1653–1662. [Google Scholar] [CrossRef]
- Vuong, H.G.; Ngo, H.T.T.; Bychkov, A.; Jung, C.K.; Vu, T.H.; Lu, K.B.; Kakudo, K.; Kondo, T. Differences in surgical resection rate and risk of malignancy in thyroid cytopathology practice between Western and Asian countries: A systematic review and meta-analysis. Cancer Cytopathol. 2020, 128, 238–249. [Google Scholar] [CrossRef]
- Davies, L.; Morris, L.G.; Haymart, M.; Chen, A.Y.; Goldenberg, D.; Morris, J.; Ogilvie, J.B.; Terris, D.J.; Netterville, J.; Wong, R.J.; et al. American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: The Increasing Incidence of Thyroid Cancer. Endocr. Pract. 2015, 21, 686–696. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frates, M.C.; Benson, C.B.; Charboneau, J.W.; Cibas, E.S.; Clark, O.H.; Coleman, B.G.; Cronan, J.J.; Doubilet, P.M.; Evans, D.B.; Goellner, J.R.; et al. Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Ultrasound Q. 2006, 22, 231–238; discussion 239–240. [Google Scholar] [CrossRef] [PubMed]
- Kim, P.H.; Suh, C.H.; Baek, J.H.; Chung, S.R.; Choi, Y.J.; Lee, J.H. Unnecessary thyroid nodule biopsy rates under four ultrasound risk stratification systems: A systematic review and meta-analysis. Eur. Radiol. 2021, 31, 2877–2885. [Google Scholar] [CrossRef] [PubMed]
- Trimboli, P.; Knappe, L.; Treglia, G.; Ruberto, T.; Piccardo, A.; Ceriani, L.; Paone, G.; Giovanella, L. FNA indication according to ACR-TIRADS, EU-TIRADS and K-TIRADS in thyroid incidentalomas at (18)F-FDG PET/CT. J. Endocrinol. Investig. 2020, 43, 1607–1612. [Google Scholar] [CrossRef]
- Mistry, R.; Hillyar, C.; Nibber, A.; Sooriyamoorthy, T.; Kumar, N. Ultrasound Classification of Thyroid Nodules: A Systematic Review. Cureus 2020, 12, e7239. [Google Scholar] [CrossRef] [Green Version]
- Castellana, M.; Castellana, C.; Treglia, G.; Giorgino, F.; Giovanella, L.; Russ, G.; Trimboli, P. Performance of Five Ultrasound Risk Stratification Systems in Selecting Thyroid Nodules for FNA. J. Clin. Endocrinol. Metab. 2020, 105. [Google Scholar] [CrossRef] [PubMed]
- Ali, S.Z.; Cibas, E.S. The Bethesda System for Reporting Thyroid Cytopathology: Definitions, Criteria, and Explanatory Notes; Springer: Cham, Switzerland, 2018. [Google Scholar]
- Trimboli, P.; Crescenzi, A.; Castellana, M.; Giorgino, F.; Giovanella, L.; Bongiovanni, M. Italian consensus for the classification and reporting of thyroid cytology: The risk of malignancy between indeterminate lesions at low or high risk. A systematic review and meta-analysis. Endocrine 2019, 63, 430–438. [Google Scholar] [CrossRef]
- Poller, D.N.; Bongiovanni, M.; Trimboli, P. Risk of malignancy in the various categories of the UK Royal College of Pathologists Thy terminology for thyroid FNA cytology: A systematic review and meta-analysis. Cancer Cytopathol. 2020, 128, 36–42. [Google Scholar] [CrossRef] [PubMed]
- Poller, D.N.; Baloch, Z.W.; Fadda, G.; Johnson, S.J.; Bongiovanni, M.; Pontecorvi, A.; Cochand-Priollet, B. Thyroid FNA: New classifications and new interpretations. Cancer Cytopathol. 2016, 124, 457–466. [Google Scholar] [CrossRef]
- Poller, D.N.; Schmitt, F. Should uncertainty concerning the risk of malignancy be included in diagnostic (nongynecologic) cytopathology reports? Cancer Cytopathol. 2021, 129, 16–21. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, T.P.X.; Truong, V.T.; Kakudo, K.; Vuong, H.G. The diversities in thyroid cytopathology practices among Asian countries using the Bethesda system for reporting thyroid cytopathology. Gland Surg. 2020, 9, 1735–1746. [Google Scholar] [CrossRef]
- Cooper, D.S.; Doherty, G.M.; Haugen, B.R.; Kloos, R.T.; Lee, S.L.; Mandel, S.J.; Mazzaferri, E.L.; McIver, B.; Sherman, S.I.; Tuttle, R.M. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006, 16, 109–142. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nikiforov, Y.E.; Seethala, R.R.; Tallini, G.; Baloch, Z.W.; Basolo, F.; Thompson, L.D.; Barletta, J.A.; Wenig, B.M.; Al Ghuzlan, A.; Kakudo, K.; 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. [Google Scholar] [CrossRef] [Green Version]
- Baloch, Z.W.; Seethala, R.R.; Faquin, W.C.; Papotti, M.G.; Basolo, F.; Fadda, G.; Randolph, G.W.; Hodak, S.P.; Nikiforov, Y.E.; Mandel, S.J. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): A changing paradigm in thyroid surgical pathology and implications for thyroid cytopathology. Cancer Cytopathol. 2016, 124, 616–620. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lloyd, R.V.; Osamura, R.Y.; Kloppel, G.; Rosai, J. (Eds.) WHO Classification of Tumours of Endocrine Organs, 4th ed.; International Agency for Research on Cancer (IARC): Lyon, France, 2017; Volume 10.
- Nikiforov, Y.E.; Baloch, Z.W.; Hodak, S.P.; Giordano, T.J.; Lloyd, R.V.; Seethala, R.R.; Wenig, B.M. Change in Diagnostic Criteria for Noninvasive Follicular Thyroid Neoplasm with Papillarylike Nuclear Features. JAMA Oncol. 2018, 4, 1125–1126. [Google Scholar] [CrossRef] [PubMed]
- Rossi, E.D.; Faquin, W.C.; Baloch, Z.; Fadda, G.; Thompson, L.; Larocca, L.M.; Pantanowitz, L. Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): Update and Diagnostic Considerations—A Review. Endocr. Pathol. 2019, 30, 155–162. [Google Scholar] [CrossRef]
- Zhou, H.; Baloch, Z.W.; Nayar, R.; Bizzarro, T.; Fadda, G.; Adhikari-Guragain, D.; Hatem, J.; Larocca, L.M.; Samolczyk, J.; Slade, J.; et al. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): Implications for the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Cancer Cytopathol. 2018, 126, 20–26. [Google Scholar] [CrossRef] [Green Version]
- Nishino, M.; Nikiforova, M. Update on Molecular Testing for Cytologically Indeterminate Thyroid Nodules. Arch. Pathol. Lab. Med. 2018, 142, 446–457. [Google Scholar] [CrossRef] [Green Version]
- Ngo, H.T.T.; Nguyen, T.P.X.; Vu, T.H.; Jung, C.K.; Hassell, L.; Kakudo, K.; Vuong, H.G. Impact of Molecular Testing on the Management of Indeterminate Thyroid Nodules Among Western and Asian Countries: A Systematic Review and Meta-analysis. Endocr. Pathol. 2020. [Google Scholar] [CrossRef]
- Ohori, N.P.; Landau, M.S.; Manroa, P.; Schoedel, K.E.; Seethala, R.R. Molecular-derived estimation of risk of malignancy for indeterminate thyroid cytology diagnoses. J. Am. Soc. Cytopathol. 2020, 9, 213–220. [Google Scholar] [CrossRef] [PubMed]
- Nylen, C.; Mechera, R.; Marechal-Ross, I.; Tsang, V.; Chou, A.; Gill, A.J.; Clifton-Bligh, R.J.; Robinson, B.G.; Sywak, M.S.; Sidhu, S.B.; et al. Molecular Markers Guiding Thyroid Cancer Management. Cancers 2020, 12, 2164. [Google Scholar] [CrossRef]
- Kumar, N.; Gupta, R.; Gupta, S. Molecular testing in diagnosis of indeterminate thyroid cytology: Trends and drivers. Diagn. Cytopathol. 2020, 48, 1144–1151. [Google Scholar] [CrossRef]
- Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell 2014, 159, 676–690. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yoo, S.K.; Lee, S.; Kim, S.J.; Jee, H.G.; Kim, B.A.; Cho, H.; Song, Y.S.; Cho, S.W.; Won, J.K.; Shin, J.Y.; et al. Comprehensive Analysis of the Transcriptional and Mutational Landscape of Follicular and Papillary Thyroid Cancers. PLoS Genet. 2016, 12, e1006239. [Google Scholar] [CrossRef]
- Ganly, I.; Makarov, V.; Deraje, S.; Dong, Y.; Reznik, E.; Seshan, V.; Nanjangud, G.; Eng, S.; Bose, P.; Kuo, F. Integrated genomic analysis of Hürthle Cell cancer reveals oncogenic drivers, recurrent mitochondrial mutations, and unique chromosomal landscapes. Cancer Cell 2018, 34, 256–270.e255. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gopal, R.K.; Kübler, K.; Calvo, S.E.; Polak, P.; Livitz, D.; Rosebrock, D.; Sadow, P.M.; Campbell, B.; Donovan, S.E.; Amin, S. Widespread chromosomal losses and mitochondrial DNA alterations as genetic drivers in Hürthle cell carcinoma. Cancer Cell 2018, 34, 242–255.e245. [Google Scholar] [CrossRef] [Green Version]
- Giordano, T.J. Genomic hallmarks of thyroid neoplasia. Annu. Rev. Pathol. Mech. Dis. 2018, 13, 141–162. [Google Scholar] [CrossRef]
- Chu, Y.H.; Dias-Santagata, D.; Farahani, A.A.; Boyraz, B.; Faquin, W.C.; Nose, V.; Sadow, P.M. Clinicopathologic and molecular characterization of NTRK-rearranged thyroid carcinoma (NRTC). Mod. Pathol. 2020, 33, 2186–2197. [Google Scholar] [CrossRef]
- Panebianco, F.; Nikitski, A.V.; Nikiforova, M.N.; Kaya, C.; Yip, L.; Condello, V.; Wald, A.I.; Nikiforov, Y.E.; Chiosea, S.I. Characterization of thyroid cancer driven by known and novel ALK fusions. Endocr. Relat. Cancer 2019, 26, 803–814. [Google Scholar] [CrossRef]
- McFadden, D.G.; Dias-Santagata, D.; Sadow, P.M.; Lynch, K.D.; Lubitz, C.; Donovan, S.E.; Zheng, Z.; Le, L.; Iafrate, A.J.; Daniels, G.H. Identification of oncogenic mutations and gene fusions in the follicular variant of papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 2014, 99, E2457–E2462. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, D.S.; Kim, D.W.; Heo, Y.J.; Baek, J.W.; Lee, Y.J.; Choo, H.J.; Park, Y.M.; Park, H.K.; Ha, T.K.; Kim, D.H.; et al. Utility of including BRAF mutation analysis with ultrasonographic and cytological diagnoses in ultrasonography-guided fine-needle aspiration of thyroid nodules. PLoS ONE 2018, 13, e0202687. [Google Scholar] [CrossRef] [Green Version]
- Najafian, A.; Noureldine, S.; Azar, F.; Atallah, C.; Trinh, G.; Schneider, E.B.; Tufano, R.P.; Zeiger, M.A. RAS Mutations, and RET/PTC and PAX8/PPAR-gamma Chromosomal Rearrangements Are Also Prevalent in Benign Thyroid Lesions: Implications Thereof and A Systematic Review. Thyroid 2017, 27, 39–48. [Google Scholar] [CrossRef] [PubMed]
- Sykorova, V.; Dvorakova, S.; Vcelak, J.; Vaclavikova, E.; Halkova, T.; Kodetova, D.; Lastuvka, P.; Betka, J.; Vlcek, P.; Reboun, M.; et al. Search for new genetic biomarkers in poorly differentiated and anaplastic thyroid carcinomas using next generation sequencing. Anticancer Res. 2015, 35, 2029–2036. [Google Scholar]
- Kunstman, J.W.; Juhlin, C.C.; Goh, G.; Brown, T.C.; Stenman, A.; Healy, J.M.; Rubinstein, J.C.; Choi, M.; Kiss, N.; Nelson-Williams, C.; et al. Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum. Mol. Genet. 2015, 24, 2318–2329. [Google Scholar] [CrossRef] [Green Version]
- Xu, B.; Ghossein, R. Genomic Landscape of Poorly Differentiated and Anaplastic Thyroid Carcinoma. Endocr. Pathol. 2016, 27, 205–212. [Google Scholar] [CrossRef] [PubMed]
- Corver, W.E.; Ruano, D.; Weijers, K.; den Hartog, W.C.; van Nieuwenhuizen, M.P.; de Miranda, N.; van Eijk, R.; Middeldorp, A.; Jordanova, E.S.; Oosting, J.; et al. Genome haploidisation with chromosome 7 retention in oncocytic follicular thyroid carcinoma. PLoS ONE 2012, 7, e38287. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kasaian, K.; Chindris, A.M.; Wiseman, S.M.; Mungall, K.L.; Zeng, T.; Tse, K.; Schein, J.E.; Rivera, M.; Necela, B.M.; Kachergus, J.M.; et al. MEN1 mutations in Hurthle cell (oncocytic) thyroid carcinoma. J. Clin. Endocrinol. Metab. 2015, 100, E611–E615. [Google Scholar] [CrossRef] [Green Version]
- Ganly, I.; McFadden, D.G. Short Review: Genomic Alterations in Hurthle Cell Carcinoma. Thyroid 2019, 29, 471–479. [Google Scholar] [CrossRef]
- Lubitz, C.C.; Sadow, P.M.; Daniels, G.H.; Wirth, L.J. Progress in Treating Advanced Thyroid Cancers in the Era of Targeted Therapy. Thyroid 2021. [Google Scholar] [CrossRef]
- Chudova, D.; Wilde, J.I.; Wang, E.T.; Wang, H.; Rabbee, N.; Egidio, C.M.; Reynolds, J.; Tom, E.; Pagan, M.; Rigl, C.T.; et al. Molecular classification of thyroid nodules using high-dimensionality genomic data. J. Clin. Endocrinol. Metab. 2010, 95, 5296–5304. [Google Scholar] [CrossRef] [Green Version]
- Eszlinger, M.; Krohn, K.; Frenzel, R.; Kropf, S.; Tonjes, A.; Paschke, R. Gene expression analysis reveals evidence for inactivation of the TGF-beta signaling cascade in autonomously functioning thyroid nodules. Oncogene 2004, 23, 795–804. [Google Scholar] [CrossRef] [Green Version]
- Eszlinger, M.; Wiench, M.; Jarzab, B.; Krohn, K.; Beck, M.; Lauter, J.; Gubala, E.; Fujarewicz, K.; Swierniak, A.; Paschke, R. Meta- and reanalysis of gene expression profiles of hot and cold thyroid nodules and papillary thyroid carcinoma for gene groups. J. Clin. Endocrinol. Metab. 2006, 91, 1934–1942. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rossi, E.D.; Bizzarro, T.; Martini, M.; Capodimonti, S.; Sarti, D.; Cenci, T.; Bilotta, M.; Fadda, G.; Larocca, L.M. The evaluation of miRNAs on thyroid FNAC: The promising role of miR-375 in follicular neoplasms. Endocrine 2016, 54, 723–732. [Google Scholar] [CrossRef]
- Dettmer, M.; Vogetseder, A.; Durso, M.B.; Moch, H.; Komminoth, P.; Perren, A.; Nikiforov, Y.E.; Nikiforova, M.N. MicroRNA expression array identifies novel diagnostic markers for conventional and oncocytic follicular thyroid carcinomas. J. Clin. Endocrinol. Metab. 2013, 98, E1–E7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nikiforova, M.N.; Tseng, G.C.; Steward, D.; Diorio, D.; Nikiforov, Y.E. MicroRNA expression profiling of thyroid tumors: Biological significance and diagnostic utility. J. Clin. Endocrinol. Metab. 2008, 93, 1600–1608. [Google Scholar] [CrossRef]
- Yip, L.; Kelly, L.; Shuai, Y.; Armstrong, M.J.; Nikiforov, Y.E.; Carty, S.E.; Nikiforova, M.N. MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma. Ann. Surg. Oncol. 2011, 18, 2035–2041. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Labourier, E.; Shifrin, A.; Busseniers, A.E.; Lupo, M.A.; Manganelli, M.L.; Andruss, B.; Wylie, D.; Beaudenon-Huibregtse, S. Molecular Testing for miRNA, mRNA, and DNA on Fine-Needle Aspiration Improves the Preoperative Diagnosis of Thyroid Nodules With Indeterminate Cytology. J. Clin. Endocrinol. Metab. 2015, 100, 2743–2750. [Google Scholar] [CrossRef] [PubMed]
- Eszlinger, M.; Krogdahl, A.; Munz, S.; Rehfeld, C.; Precht Jensen, E.M.; Ferraz, C.; Bosenberg, E.; Drieschner, N.; Scholz, M.; Hegedus, L.; et al. Impact of molecular screening for point mutations and rearrangements in routine air-dried fine-needle aspiration samples of thyroid nodules. Thyroid 2014, 24, 305–313. [Google Scholar] [CrossRef] [PubMed]
- Eszlinger, M.; Piana, S.; Moll, A.; Bosenberg, E.; Bisagni, A.; Ciarrocchi, A.; Ragazzi, M.; Paschke, R. Molecular testing of thyroid fine-needle aspirations improves presurgical diagnosis and supports the histologic identification of minimally invasive follicular thyroid carcinomas. Thyroid 2015, 25, 401–409. [Google Scholar] [CrossRef]
- Nikiforov, Y.E.; Ohori, N.P.; Hodak, S.P.; Carty, S.E.; LeBeau, S.O.; Ferris, R.L.; Yip, L.; Seethala, R.R.; Tublin, M.E.; Stang, M.T.; et al. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: A prospective analysis of 1056 FNA samples. J. Clin. Endocrinol. Metab. 2011, 96, 3390–3397. [Google Scholar] [CrossRef]
- Nikiforova, M.N.; Mercurio, S.; Wald, A.I.; Barbi de Moura, M.; Callenberg, K.; Santana-Santos, L.; Gooding, W.E.; Yip, L.; Ferris, R.L.; Nikiforov, Y.E. Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules. Cancer 2018, 124, 1682–1690. [Google Scholar] [CrossRef] [Green Version]
- Nikiforova, M.N.; Lepe, M.; Tolino, L.A.; Miller, M.E.; Ohori, N.P.; Wald, A.I.; Landau, M.S.; Kaya, C.; Malapelle, U.; Bellevicine, C.; et al. Thyroid cytology smear slides: An untapped resource for ThyroSeq testing. Cancer Cytopathol. 2021, 129, 33–42. [Google Scholar] [CrossRef] [PubMed]
- Steward, D.L.; Carty, S.E.; Sippel, R.S.; Yang, S.P.; Sosa, J.A.; Sipos, J.A.; Figge, J.J.; Mandel, S.; Haugen, B.R.; Burman, K.D.; et al. Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology: A Prospective Blinded Multicenter Study. JAMA Oncol. 2019, 5, 204–212. [Google Scholar] [CrossRef] [Green Version]
- Haugen, B.R.; Sawka, A.M.; Alexander, E.K.; Bible, K.C.; Caturegli, P.; Doherty, G.M.; Mandel, S.J.; Morris, J.C.; Nassar, A.; Pacini, F.; et al. American Thyroid Association Guidelines on the Management of Thyroid Nodules and Differentiated Thyroid Cancer Task Force Review and Recommendation on the Proposed Renaming of Encapsulated Follicular Variant Papillary Thyroid Carcinoma Without Invasion to Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features. Thyroid 2017, 27, 481–483. [Google Scholar] [CrossRef] [PubMed]
- Kumar, G.; Timmaraju, V.A.; Song-Yang, J.W.; Repko, B.; Narick, C.; Mireskandari, A.; Finkelstein, S. Utility of microdissected cytology smears for molecular analysis of thyroid malignancy. Diagn. Cytopathol. 2019, 47, 289–296. [Google Scholar] [CrossRef] [PubMed]
- Ablordeppey, K.K.; Timmaraju, V.A.; Song-Yang, J.W.; Yaqoob, S.; Narick, C.; Mireskandari, A.; Finkelstein, S.D.; Kumar, G. Development and Analytical Validation of an Expanded Mutation Detection Panel for Next-Generation Sequencing of Thyroid Nodule Aspirates. J. Mol. Diagn. 2020, 22, 355–367. [Google Scholar] [CrossRef] [Green Version]
- Ciarletto, A.M.; Narick, C.; Malchoff, C.D.; Massoll, N.A.; Labourier, E.; Haugh, K.; Mireskandari, A.; Finkelstein, S.D.; Kumar, G. Analytical and clinical validation of pairwise microRNA expression analysis to identify medullary thyroid cancer in thyroid fine-needle aspiration samples. Cancer Cytopathol. 2021, 129, 239–249. [Google Scholar] [CrossRef]
- Lupo, M.A.; Walts, A.E.; Sistrunk, J.W.; Giordano, T.J.; Sadow, P.M.; Massoll, N.; Campbell, R.; Jackson, S.A.; Toney, N.; Narick, C.M.; et al. Multiplatform molecular test performance in indeterminate thyroid nodules. Diagn. Cytopathol. 2020, 48, 1254–1264. [Google Scholar] [CrossRef]
- Sistrunk, J.W.; Shifrin, A.; Frager, M.; Bardales, R.H.; Thomas, J.; Fishman, N.; Goldberg, P.; Guttler, R.; Grant, E. Clinical impact of testing for mutations and microRNAs in thyroid nodules. Diagn. Cytopathol. 2019, 47, 758–764. [Google Scholar] [CrossRef] [PubMed]
- Alexander, E.K.; Kennedy, G.C.; Baloch, Z.W.; Cibas, E.S.; Chudova, D.; Diggans, J.; Friedman, L.; Kloos, R.T.; LiVolsi, V.A.; Mandel, S.J.; et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N. Engl. J. Med. 2012, 367, 705–715. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hao, Y.; Duh, Q.Y.; Kloos, R.T.; Babiarz, J.; Harrell, R.M.; Traweek, S.T.; Kim, S.Y.; Fedorowicz, G.; Walsh, P.S.; Sadow, P.M.; et al. Identification of Hurthle cell cancers: Solving a clinical challenge with genomic sequencing and a trio of machine learning algorithms. BMC Syst. Biol. 2019, 13, 27. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Patel, K.N.; Angell, T.E.; Babiarz, J.; Barth, N.M.; Blevins, T.; Duh, Q.Y.; Ghossein, R.A.; Harrell, R.M.; Huang, J.; Kennedy, G.C.; et al. Performance of a Genomic Sequencing Classifier for the Preoperative Diagnosis of Cytologically Indeterminate Thyroid Nodules. JAMA Surg. 2018, 153, 817–824. [Google Scholar] [CrossRef]
- Angell, T.E.; Wirth, L.J.; Cabanillas, M.E.; Shindo, M.L.; Cibas, E.S.; Babiarz, J.E.; Hao, Y.; Kim, S.Y.; Walsh, P.S.; Huang, J.; et al. Analytical and Clinical Validation of Expressed Variants and Fusions from the Whole Transcriptome of Thyroid FNA Samples. Front. Endocrinol. 2019, 10, 612. [Google Scholar] [CrossRef]
- Krane, J.F.; Cibas, E.S.; Endo, M.; Marqusee, E.; Hu, M.I.; Nasr, C.E.; Waguespack, S.G.; Wirth, L.J.; Kloos, R.T. The Afirma Xpression Atlas for thyroid nodules and thyroid cancer metastases: Insights to inform clinical decision-making from a fine-needle aspiration sample. Cancer Cytopathol. 2020, 128, 452–459. [Google Scholar] [CrossRef]
RCPath | Bethesda | Italian | Australian | Japanese |
---|---|---|---|---|
Thy1 Non-diagnostic for cytological diagnosis Thy1c Non-diagnostic for cytological diagnosis–cystic lesion | I. Non-diagnostic or unsatisfactory | TIR 1 Non-diagnostic TIR 1c Non-diagnostic cystic | 1 Non-diagnostic | 1 Inadequate |
Thy2-Non-neoplastic Thy2c-Non-neoplastic–cystic lesion | II. Benign | TIR 2 Non-malignant | 2 Benign | 2 Normal or Benign |
Thy3a Neoplasm possible–atypia / non-diagnostic | III. Atypia of undetermined significance or follicular lesion of undetermined significance | TIR 3A Low risk indeterminate lesion (LRIL) | 3 Indeterminate or follicular lesion of undetermined significance | 3 Indeterminate B others |
Thy3f Neoplasm possible, suggesting follicular neoplasm | IV. Follicular neoplasm or suspicious for a follicular neoplasm | TIR 3B High risk indeterminate lesion (HRIL) | 4 Suggestive of a follicular neoplasm | 3 Indeterminate A-follicular neoplasms A-1 favor benign A-2 borderline A-3 favor malignant |
Thy4 Suspicious of malignancy | V. Suspicious for malignancy | TIR 4 Suspicious of malignancy | 5 Suspicious of malignancy | 4 Malignancy suspected |
Thy5 Malignant | VI. Malignant | TIR 5 Malignant | 6 Malignant | 5 Malignancy |
ThyroSeq v3 | ThyGeNEXT and ThyraMIR | Afirma GSC and Xpression Atlas | |
---|---|---|---|
Test methodology | NGS for DNA and RNA | NGS for DNA and RNA; qRT-PCR for microRNA | NGS for RNA |
SNV, insertions, deletions, and gene fusions | 12,135 variants in 112 genes; 120+ fusions | 42 variants in 10 genes; 38 gene fusions | 905 variants and 235 gene fusions from 593 genes |
Gene expression analysis | 19 genes | 4 genes | 10,196 genes (1115 for the GSC classifier algorithm) |
MicroRNA expression analysis | None | 10 microRNAs | None |
Copy-number alterations | 10 chromosomal regions | None | Loss-of-heterozygosity analysis |
QC for follicular cell content | Yes | Yes | Yes |
Recognition of parathyroid | Yes | Yes | Yes |
Recognition of MTC | Yes | Yes | Yes |
ThyroSeq v3 | ThyGeNEXT & ThyraMIR | Afirma GSC | |
---|---|---|---|
Sample collection | Prospective, multi-institutional | Retrospective, multi-institutional | Archival samples remaining from previous (2012) multi-institutional, prospectively accrued study for GEC |
Number of Bethesda III/IV nodules | 247 | 178 | 190 |
Prevalence of NIFTP and cancer | 28% | 30% | 24% |
Benign-call rate | 61% | 46% | 54% |
Sensitivity | 94% | 93% * | 91% |
Specificity | 82% | 62% * | 68% |
NPV | 97% | 95% * | 96% |
PPV | 66% | 52% * | 47% |
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Nishino, M.; Bellevicine, C.; Baloch, Z. Molecular Tests for Risk-Stratifying Cytologically Indeterminate Thyroid Nodules: An Overview of Commercially Available Testing Platforms in the United States. J. Mol. Pathol. 2021, 2, 135-146. https://doi.org/10.3390/jmp2020014
Nishino M, Bellevicine C, Baloch Z. Molecular Tests for Risk-Stratifying Cytologically Indeterminate Thyroid Nodules: An Overview of Commercially Available Testing Platforms in the United States. Journal of Molecular Pathology. 2021; 2(2):135-146. https://doi.org/10.3390/jmp2020014
Chicago/Turabian StyleNishino, Michiya, Claudio Bellevicine, and Zubair Baloch. 2021. "Molecular Tests for Risk-Stratifying Cytologically Indeterminate Thyroid Nodules: An Overview of Commercially Available Testing Platforms in the United States" Journal of Molecular Pathology 2, no. 2: 135-146. https://doi.org/10.3390/jmp2020014
APA StyleNishino, M., Bellevicine, C., & Baloch, Z. (2021). Molecular Tests for Risk-Stratifying Cytologically Indeterminate Thyroid Nodules: An Overview of Commercially Available Testing Platforms in the United States. Journal of Molecular Pathology, 2(2), 135-146. https://doi.org/10.3390/jmp2020014