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The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) established a standardized, category-based reporting system for thyroid fine-needle aspiration (FNA) specimens. The 2017 revision reaffirms that every thyroid FNA report should begin with one of six diagnostic categories, the names of which remain unchanged since they were first introduced: (i) nondiagnostic or unsatisfactory; (ii) benign; (iii) atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS); (iv) follicular neoplasm or suspicious for a follicular neoplasm; (v) suspicious for malignancy; and (vi) malignant. There is a choice of two different names for some of the categories. A laboratory should choose the one it prefers and use it exclusively for that category. Synonymous terms (e.g., AUS and FLUS) should not be used to denote two distinct interpretations. Each category has an implied cancer risk that ranges from 0% to 3% for the "benign" category to virtually 100% for the "malignant" category, and, in the 2017 revision, the malignancy risks have been updated based on new (post 2010) data. As a function of their risk associations, each category is linked to updated, evidence-based clinical management recommendations. The recent reclassification of some thyroid neoplasms as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has implications for the risk of malignancy, and this is accounted for with regard to diagnostic criteria and optional notes. Such notes can be useful in helping guide surgical management.

Background: There are few published quality metrics relevant to fine-needle aspirations (FNA) of the thyroid and endocrinology. With the development of a Thyroid Nodule Clinic within an academic practice, the Division of Endocrinology, in collaboration with the Department of Medicine Quality Improvement Team, established a system to monitor the results and follow-up of thyroid biopsies to ensure patient safety and to prevent adverse clinical outcomes attributable to delayed or incomplete follow-up., Methods: All FNA performed are identified using billing data from the Thyroid Nodule Clinic. Results were followed using the Beth Israel Deaconess Online Medical Record (OMR) system, and information is collected on documented follow-up plan and actions taken. Missing data are flagged for review. Over the reporting period, the monitoring process and categories were modified to account for adoption of the Bethesda reporting criteria and implementation of gene expression classifier testing. Specific workflow plans were developed for each cytopathologic classification., Results: Between July 2007 and June 2014, 3895 FNAs were performed. The quality improvement tracking process found that 3856/3895 (99%) biopsy cases had documented follow-up since initiation of the project., Conclusion: This monitoring process has ensured quality patient care, with confidence that patients having FNAs are receiving documented necessary follow-up for treatment of their nodular conditions. This system serves as a potential model for others to use in their endocrine practice in managing the results of thyroid nodule biopsies.

Background: Molecular testing for oncogenic gene mutations and chromosomal rearrangements plays a growing role in the optimal management of thyroid nodules, yet lacks standardized testing modalities and systematic validation data. Our objective was to assess the performance of molecular cytology on preoperative thyroid nodule fine-needle aspirates (FNAs) across a broad range of variables, including independent collection sites, clinical practices, and anatomic pathology interpretations., Methods: Single-pass FNAs were prospectively collected from 806 nodules 1 cm or larger by ultrasonography at five independent sites across the United States. Specimens were shipped in a nucleic acid stabilization solution and tested at a centralized clinical laboratory. Seventeen genetic alterations (BRAF, KRAS, HRAS, and NRAS mutations, PAX8-PPARG and RET-PTC rearrangements) were evaluated by multiplex polymerase chain reaction and liquid bead array cytometry in 769 FNAs that met inclusion criteria. Cytology, histology, and clinical care followed local procedures and practices. All results were double-blinded., Results: Thirty-two specimens (4.2%) failed to yield sufficient nucleic acid to generate molecular data. A single genetic alteration was detected in 80% of cytology malignant cases, 21% of indeterminate, 7.8% of nondiagnostic, and 3.5% of benign cases. Among 109 nodules with surgical histology reference standard, oncogenic mutations were present in 50% of malignant nodules missed by cytology. There were 14 cancers not identified by cytology or molecular tests, including 5 carcinomas with histologic sizes less than 1 cm (3 multifocal) and 8 noninvasive follicular variants of papillary carcinoma (4 encapsulated). No mutations were detected in 89% of the nodules benign by histopathology with 6 false-positive molecular results in 5 adenomas (2-5.5 cm) and 1 cystic nodule with an incidental papillary microcarcinoma (0.15 cm). The posttest probability of thyroid cancer was 100% for nodules positive for BRAF or RET-PTC, 70% for RAS or PAX8-PPARG, and 88% for molecular cytology overall., Conclusions: Centralized and standardized molecular testing for genetic alterations associated with a high risk of malignancy efficiently complements the local cytopathologic diagnosis of thyroid nodule aspirates in the clinical setting. Actionable molecular cytology can improve the personalized surgical and medical management of patients with thyroid cancers, facilitating one-stage total thyroidectomy and reducing the number of unnecessary diagnostic surgeries.

Background: The clinical evaluation of enlarged local lymph nodes (LNs) is difficult at the beginning and throughout the follow-up of differentiated thyroid carcinoma (DTC). Although the examination of samples collected from LNs by fine-needle aspiration biopsy cytology (FNAB-C) is extremely specific for the diagnosis of metastases, its sensitivity is low, especially in paucicellular samples., Summary: The measurement of thyroglobulin (Tg) in the fine-needle aspiration biopsy (FNAB) washout fluid (FNAB-Tg) increases the diagnostic performance of cytology to up to 100% sensitivity and specificity. However, the application of FNAB-Tg is currently hindered by the absence of methodological standardization, a lack of definite cutoff points, and the ongoing debate regarding its accuracy in nonthyroidectomized patients, those with elevated serum Tg, and those with circulating anti-Tg antibodies., Conclusion: FNAB-Tg improves the diagnostic performance of FNAB-C in LN metastases, even when the latter is unable to diagnose the metastases. For that reason, FNAB-Tg should be included in the monitoring of DTC.

Objective: To address terminology and other issues related to thyroid fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted The NCI Thyroid FNA State of the Science Conference. The conclusions regarding terminology and morphologic criteria from the NCI meeting led to the Bethesda Thyroid Atlas Project and form the framework for the Bethesda System for Reporting Thyroid Cytopathology., Design: Participants of the Atlas Project were selected from among the committee members of the NCI FNA State of the Science Conference and other participants at the live conference. The terminology framework was based on a literature search of English language publications dating back to 1995 using PubMed as the search engine; online forum discussions ( http://thyroidfna.cancer.gov/forums/default.aspx ); and formal interdisciplinary discussions held on October 22 and 23, 2007, in Bethesda, MD., Main Outcome: For clarity of communication, the Bethesda System for Reporting Thyroid Cytopathology recommends that each report begin with one of the six general diagnostic categories. Each of the categories has an implied cancer risk that links it to an appropriate clinical management guideline., Conclusions: The project participants hope that the adoption of this framework will facilitate communication among cytopathologists, endocrinologists, surgeons, and radiologists; facilitate cytologic-histologic correlation for thyroid diseases; facilitate research into the understanding of thyroid diseases; and allow easy and reliable sharing of data from different laboratories for national and international collaborative studies.

Background: Fine-needle aspiration (FNA) may be the procedure of choice in the preoperative evaluation of thyroid nodules, yet it suffers as a modality both because of its inherent limitations as well as variability in its diagnostic terminology. The National Cancer Institute recently proposed a classification system. The objective of this study was to report our experience in using this new reporting system to review the distribution of diagnosis categories and to evaluate the specificity of the system based on the cytologic-histologic correlation., Patients and Methods: A total of 3207 thyroid nodules underwent FNA, that is, 3207 FNAs from 2468 patients were examined at our institution between January 1, 2008 and December 31, 2008. All FNAs were classified prospectively into unsatisfactory, benign, indeterminate (cells of undetermined significance), follicular neoplasm (FN), suspicious for malignancy, and positive for malignancy., Results: The distribution of these categories from 3207 evaluated nodules was as follows: 11.1% unsatisfactory, 73.8% benign, 3.0% indeterminate, 5.5% FN, 1.3% suspicious, and 5.2% malignant. Of the 2468 sampled patients, 378 (15%) underwent thyroidectomy. The distribution of diagnoses of patients who underwent surgery was as follows: 10% unsatisfactory, 4.6% benign, 30.3% indeterminate, 61.4% FN, 76.9% suspicious, and 77.2% malignant. There was an excellent association between the categories and in predicting benign versus malignant thyroid nodules (p < 0.0001). However, the false-negative rate cannot be calculated because only a small number of patients with benign diagnosis underwent surgery. The false-positive rate was 2.2%; all were diagnosed as suspicious cytologically. Given that only 15% of the patients underwent surgery, at this time the sensitivity of thyroid FNA for diagnosing malignant thyroid nodules cannot be calculated, nor can the sensitivity of thyroid FNA as a screening test for all neoplasms be accurately estimated. The specificity for diagnosing malignant thyroid nodules was 93%, whereas the specificity as a screening test for all neoplasms was 68%. The positive predictive values for an FN, suspicious, and positive cytologic diagnosis were 34%, 87%, and 100%, respectively., Conclusions: These data demonstrate that the recently proposed classification system is excellent for reporting thyroid FNAs. Each diagnostic category conveys specific risks of malignancy, which offers guidance for patient management.

Background: Thyroid nodules are relatively common and are routinely evaluated by fine-needle aspiration cytology, usually performed by clinicians. We noticed qualitative and/or quantitative variability in samples submitted to the cytopathology laboratory from clinicians, for example, the number of glass slides submitted (2-25) and air-dried smears versus alcohol-fixed slides, with variability in specimen adequacy and interpretability. The objective of this study was to standardize the preanalytic variables to determine if there is an improvement in the specimen quality., Methods: We standardized the method of collection (ultrasound-guided, 25-gauge needle, four passes) and preparation of samples (four total smears: two air-dried, two fixed, with liquid-based preparation and/or cell block) and personnel involved., Results: Standardization of thyroid nodule fine-needle aspiration and sample preparation by clinical staff resulted in an overall improvement in the quality of sample (odds ratio = 3.82, 95% confidence interval 2.02-7.24, p < 0.0001) with an increased proportion of satisfactory samples from 67% prestandardization to 89% poststandardization., Conclusions: Standardization resulted in a significant improvement in specimen interpretability.

Background: The low incidence of thyroid cancer despite the high prevalence of thyroid nodules necessitates a screening tool to determine which patients require surgical management. The utility of fine-needle aspiration biopsy (FNAB) for this purpose requires a low false-negative (FN) rate and an acceptable sensitivity and specificity for the detection of malignancy. While reviewing our institution's experience with thyroid FNAB, we found significant discrepancies in how statistics of thyroid FNAB were tabulated and reported in the literature. Here we examine the sources of these discrepancies by evaluating large series of thyroid FNAB with regard to cytopathologic reporting and statistical calculation., Methods: Published series of thyroid FNAB with >200 FNAB and available histological data with sufficient raw data to recalculate statistics were analyzed. Considering indeterminate and malignant results to be positive FNAB results, since, in a four-tier system, both lead to surgical management, specificity, sensitivity, accuracy, positive predictive value, negative predictive value, FN, and false-positive (FP) rates were recalculated. Differences between reported and recalculated statistics were then evaluated for significance., Results: Nineteen studies and 20 series were identified. The following are reported and recalculated means, respectively: for sensitivity, 81% and 86%; for specificity, 81% and 62%; for accuracy, 77% and 71%; for positive predictive value, 65% and 50%; for negative predictive value, 84% and 93%; for FN rates, 13% and 14%; for FP rates, 10% and 38%. FP rates had a mean of 1.4% when recalculated considering only malignant FNAB as positive tests. Specificity and FP rates had statistically significant differences between the means of reported and recalculated values., Conclusions: Thyroid FNAB remains the screening tool of choice in the evaluation of thyroid nodules. However, the variability in the calculation of reported thyroid FNAB statistics highlights the need for uniformity in statistical reporting for accurate understanding of thyroid FNAB's clinical utility.

Many endocrinologists are dissatisfied with the cytopathology reports from thyroidal aspirates and unsure of how to proceed with the management of their patients. Endocrinologists and cytopathologists should have a symbiotic or complementary professional relationship if patients are going to be well served. The endocrinologist has responsibilities to the pathologist and vice versa. If the endocrinologist performs the thyroidal fine needle aspirations (FNAs), he or she must provide the pathologist with adequate specimens (in terms of quantity or number of cells) that are well smeared so that cells are well preserved and accurate cytologic diagnosis may be rendered. Also, pertinent clinical history and reasonable differential diagnoses should be stated. The pathologist has responsibilities to the endocrinologist. He or she should strive constantly to provide a clear and definite diagnosis. Cytologic reports must be in a "clinical language." By this I mean a language the clinician can understand. The pathologist should not merely provide morphologic descriptions without any clinical meaning. Here I provide my views and suggestions on improving cytopathology reports based on over 30 years' experience of performing and reporting thyroidal FNAs.