Edmund S. Cibas, MD; Zubair W. Baloch, MD, PhD; Giovanni Fellegara, MD; Virginia A. LiVolsi, MD; Stephen S. Raab, MD; Juan Rosai, MD; James Diggans, PhD; Lyssa Friedman, RN, MPA; Giulia C. Kennedy, PhD; Richard T. Kloos, MD; Richard B. Lanman, MD; Susan J. Mandel, MD, MPH; Nicole Sindy, MBS; David L. Steward, MD; Martha A. Zeiger, MD; Bryan R. Haugen, MD; Erik K. Alexander, MD
Acknowledgment: The authors thank Dr. Ricardo Lloyd for serving as the third central histopathologist when consensus was not achieved after discussion between the first 2 central histopathologists.
Grant Support: By research grants from Veracyte to the respective institutions of the coauthors.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-0096.
Reproducible Research Statement: Study protocol, statistical code, and data set: Not available.
Requests for Single Reprints: Erik K. Alexander, MD, Brigham and Women's Hospital, 75 Francis Street, PBB-B4, Boston, MA 02115; e-mail, email@example.com.
Current Author Addresses: Drs. Alexander and Cibas: Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.
Drs. Baloch, LiVolsi, and Mandel: University of Pennsylvania School of Medicine, 6 Founders Pavilion, 3400 Spruce Street, Philadelphia, PA 19104.
Drs. Fellegara and Rosai: Centro Diagnostico Italiano, Centro Consulenze Patologica Oncologica, Via Saint Bon 20, 20147 Milan, Italy.
Dr. Stephen Raab: Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's, Newfoundland A1B 3V6, Canada.
Drs. Diggans, Kennedy, Kloos, and Lanman; Ms. Friedman; and Ms. Sindy: Veracyte, 7000 Shoreline Court, Suite 250, San Francisco, CA 94080.
Dr. Steward: University of Cincinnati College of Medicine, Department of Otolaryngology–Head and Neck Surgery, Medical Sciences Building, Room 6507, ML 0528, 231 Albert Sabin Way, Cincinnati, OH 45267.
Dr. Zeiger: Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 606, Baltimore, MD 21287.
Dr. Haugen: University of Colorado School of Medicine, Mail Stop 8106, Aurora, CO 80045.
Author Contributions: Conception and design: E.S. Cibas, L. Friedman, G.C. Kennedy, R.B. Lanman, S.J. Mandel, M.A. Zeiger, B.R. Haugen, E.K. Alexander.
Analysis and interpretation of the data: E.S. Cibas, Z.W. Baloch, J. Rosai, J. Diggans, L. Friedman, G.C. Kennedy, R.T. Kloos, R.B. Lanman, S.J. Mandel, N. Sindy, M.A. Zeiger, B.R. Haugen, E.K. Alexander.
Drafting of the article: E.S. Cibas, Z.W. Baloch, J. Diggans, L. Friedman, G.C. Kennedy, R.T. Kloos, B.R. Haugen, E.K. Alexander.
Critical revision of the article for important intellectual content: V.A. LiVolsi, S.S. Raab, J. Rosai, L. Friedman, G.C. Kennedy, R.T. Kloos, R.B. Lanman, N. Sindy, D.L. Steward, M.A. Zeiger, B.R. Haugen, E.K. Alexander.
Final approval of the article: E.S. Cibas, Z.W. Baloch, V.A. LiVolsi, S.S. Raab, J. Rosai, L. Friedman, G.C. Kennedy, R.T. Kloos, R.B. Lanman, S.J. Mandel, D.L. Steward, M.A. Zeiger, B.R. Haugen, E.K. Alexander.
Provision of study materials or patients: S.S. Raab, G.C. Kennedy, R.T. Kloos, S.J. Mandel, M.A. Zeiger, B.R. Haugen, E.K. Alexander.
Statistical expertise: J. Diggans, G.C. Kennedy.
Administrative, technical, or logistic support: G. Fellegara, L. Friedman, R.B. Lanman, E.K. Alexander.
Collection and assembly of data: S.S. Raab, L. Friedman, G.C. Kennedy, R.T. Kloos, R.B. Lanman, N. Sindy, D.L. Steward, M.A. Zeiger, E.K. Alexander.
Clinical management of thyroid neoplasms is based on light microscopic diagnosis, but its accuracy and precision are poorly defined.
To assess inter- and intraobserver variability of preoperative cytopathologic and postoperative histopathologic thyroid diagnoses.
Samples were collected in a prospective, multicenter trial validating a gene expression classifier between June 2009 and December 2010.
14 academic and 35 community clinical sites.
653 patients with 776 surgically resected thyroid nodules of 1 cm or greater.
Intraobserver concordance among 2 or more central histopathologists who independently read histopathology slides was calculated. Interobserver concordance between the diagnoses made by the central histopathologists and those made by local pathologists were calculated. Intra- and interobserver concordance for cytopathology was similarly calculated by comparing diagnoses made by local pathologists with those made by a central panel of 3 cytopathologists.
Concordance on the histopathologic distinction between benign and malignant diagnoses was 91% comparing local with central histopathologists and 90% comparing 2 central histopathologists. Using the 6-category Bethesda System, 64.0% of diagnoses made by local and central cytopathologists and 74.7% of intraobserver diagnoses were concordant. Central cytopathologists made fewer indeterminate diagnoses than local pathologists (41.2% vs. 55.0%).
Many local pathologists did not use the Bethesda System, so their reports were translated to allow comparison. The study required histopathology, and the study population and specimens did not encompass all newly evaluated patients with a thyroid nodule.
Substantial inter- and intraobserver variability exists in the cytopathologic and histopathologic evaluation of thyroid nodules, confirming an inherent limitation of visual microscopic diagnosis.
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Cibas ES, Baloch ZW, Fellegara G, LiVolsi VA, Raab SS, Rosai J, et al. A Prospective Assessment Defining the Limitations of Thyroid Nodule Pathologic Evaluation. Ann Intern Med. 2013;159:325–332. doi: 10.7326/0003-4819-159-5-201309030-00006
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Published: Ann Intern Med. 2013;159(5):325-332.
Endocrine and Metabolism, Endocrine Cancer, Hematology/Oncology, Thyroid Disorders.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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