The Bethesda System For Reporting Thyroid Cytopathology Research Articles

The Usefulness of Immunocytochemistry of CD56 in Determining Malignancy from Indeterminate Thyroid Fine-Needle Aspiration Cytology.

BackgroundFine-needle aspiration cytology serves as a safe, economical tool in evaluating thyroid nodules. However, about 30% of the samples are categorized as indeterminate. Hence, many immunocytochemistry markers have been studied, but there has not been a single outstanding marker. We studied the efficacy of CD56 with human bone marrow endothelial cell marker-1 (HBME-1) in diagnosis in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III.MethodsWe reviewed ThinPrep liquid-based cytology (LBC) samples with Papanicolaou stain from July 1 to December 31, 2016 (2,195 cases) and selected TBSRTC category III cases (n = 363). Twenty-six cases were histologically confirmed as benign (six cases, 23%) or malignant (20 cases, 77%); we stained 26 LBC slides with HBME-1 and CD56 through the cell transfer method. For evaluation of reactivity of immunocytochemistry, we chose atypical follicular cell clusters.ResultsCD56 was not reactive in 18 of 20 cases (90%) of malignant nodules and showed cytoplasmic positivity in five of six cases (83%) of benign nodules. CD56 showed high sensitivity (90.0%) and relatively low specificity (83.3%) in detecting malignancy (p = .004). HBME-1 was reactive in 17 of 20 cases (85%) of malignant nodules and was not reactive in five of six cases (83%) of benign nodules. HBME-1 showed slightly lower sensitivity (85.0%) than CD56. The specificity in detecting malignancy by HBME-1 was similar to that of CD56 (83.3%, p = .008). CD56 and HBME-1 tests combined showed lower sensitivity (75.0% vs 90%) and higher specificity (93.8% vs 83.3%) in detecting malignancy compared to using CD56 alone.ConclusionsUsing CD56 alone showed relatively low specificity despite high sensitivity for detecting malignancy. Combining CD56 with HBME-1 could increase the specificity. Thus, we suggest that CD56 could be a useful preoperative marker for differential diagnosis of TBSRTC category III samples.

Malignancy rate of atypia of undetermined significance/follicular lesion of undetermined significance in thyroid nodules undergoing FNA in a suburban endocrinology practice: A retrospective cohort analysis

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was created to establish a standard terminology regarding thyroid nodules that can be shared between endocrinologists, pathologists, radiologists, and surgeons. Since its inception and use in 2009, multiple large hospitals and academic institutions have performed retrospective studies to compare their classification rates, specifically those of atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS), with the recommended rates created by the National Cancer Institute. The current study compared AUS/FLUS rates at a private suburban endocrine practice with those of previous publications from large institutions and the rates established by the National Cancer Institute. Charts from 893 patients with fine-needle aspiration (FNA) performed in 2015 were reviewed. Data specific to thyroid aspirates classified as AUS/FLUS were organized into whether patients underwent surgery, underwent subsequent repeat FNA, or required continued observation. These results then were calculated to reveal the rate of malignancy in the AUS/FLUS category with surgical pathology in the study institution. A total of 893 patients underwent FNA, with 43 patients (4.82%) shown to have AUS/FLUS. A total of 21 patients proceeded to undergo thyroidectomy or lobectomy, with 7 patients (33.3%) found to have papillary or follicular thyroid carcinoma. The rate of use of the AUS/FLUS category for thyroid nodules examined at the study institution was found to be within the recommended range set forth by TBSRTC. However, the malignancy rates on histopathology in the study institution were found to be higher than the new proposed malignancy rates from TBSRTC published in 2017. This finding is comparable to those of multiple other community and academic institutions performed prior to and after institution of the new guidelines.

The impact of rapid on-site evaluation on thyroid fine-needle aspiration biopsy: A 2-year cancer center institutional experience.

The impact of rapid on-site evaluation (ROSE) on thyroid aspirates has been a matter of extensive debate. In the current study, the authors reviewed all thyroid fine-needle aspiration biopsies (FNABs) performed in their service in recent years to evaluate the impact of ROSE on final adequacy and diagnostic rates. All ultrasound-guided FNABs of the thyroid performed between July 2015 and July 2017 were included retrospectively. ROSE was performed by experienced cytopathologists, with production of Romanowsky-stained slides for immediate evaluation. When ROSE was not performed, a total of 3 needle passes were performed as the default. Final specimen adequacy and the risk of malignancy (ROM) of each The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category were calculated in the 2 groups (ROSE and non-ROSE) and compared using the chi-square test. An initial search obtained 4649 cytology specimens, 3469 of which (74.6%) underwent ROSE and 1180 of which (25.4%) did not. Patients were predominantly female (85.4%), with a mean age of 53 years. Specimen adequacy was found to be significantly higher in the ROSE group (93.4% vs 69.4%; P<.0001), with a mean number of needle passes necessary for an adequate diagnosis of 1.48±0.71 (median, 1.0 needle passes; range, 1-5 needle passes). No statistical difference was observed with regard to the ROM for each TBSRTC category when the 2 groups (ROSE and non-ROSE) were compared. The current study data support ROSE as a valuable technique in thyroid FNAB. It was proven to significantly improve specimen adequacy with a decreased mean number of needle passes necessary to achieve an adequate cytological diagnosis and no impact on the ROM for any TBSRTC category.

Updates in the Bethesda System for Reporting Thyroid Cytopathology, Version 2

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was firstly proposed in 2007. Its first edition was published in 2009. It has been widely adopted as the standardized reporting system. Based on tremendous advancements in the field of thyroidology after the introduction, the second edition of TBSRTC was officially published in October of 2017. Herein, we list and interpret its major changes in the new edition. (Chin J Endocrinol Metab, 2018, 34: 426-429) Key words: Thyroid; Cytopathology; Bethesda System for Reporting; Update

The surgery and repeat aspiration outcomes of the atypia of undetermined significance/follicular lesion of undetermined significance category in The Bethesda System for Reporting Thyroid Cytopathology

The atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category is one of six diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). In this study, we report the diagnostic distribution of thyroid fine needle aspiration (FNA) cytology and analyze the outcome of AUS/FLUS cases. A total of 29,937 thyroid FNA results, reported between April 2012 and December 2016, were retrieved from the database of a medical center. We reviewed the electronic medical records and analyzed the management of these patients. Overall frequency of AUS/FLUS is 3.1% in our laboratory, which is at the lower limit of the recommended range. Of these, 891 reports of AUS/FLUS from 770 patients were identified. Out of the 770 patients, 367 had surgical intervention. In these 367 patients, final surgical pathology yielded 204 (55.6%) malignancies, 12 indeterminateness (3.3%), and 151 (41.1%) benignity. Among these surgical patients, 113 (30.8%) had received a repeat FNA of the thyroid before thyroid resection. The difference between the malignancy rates among patients who directly received surgery after the first AUS/FLUS diagnosis (132 of 254, 52.0%) and patients having a repeat FNA before surgery (72 of 113, 63.7%) was not statistically significant. Our results are in agreement with AUS/FLUS diagnoses in less than 7% of specimens, and confirm that it is appropriate to perform either a repeat thyroid FNA or thyroid lobectomy, with the clinical decision being subject to the standardized management protocols of the second edition of TBSRTC in the AUS/FLUS category.

Cytologic Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features and Its Impact on the Risk of Malignancy in the Bethesda System for Reporting Thyroid Cytopathology: An Institutional Experience.

BackgroundThis study was performed to analyze cytologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and its impact on the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). MethodsFive thousand five hundred and forty-nine cases of thyroid fine-needle aspiration cytology (FNAC) diagnosed between 2012 and 2014 were included in this study. Diagnostic categories based on TBSRTC were compared with final surgical diagnoses, and the ROM in each category was calculated both when NIFTP was included in malignant lesions and when excluded from malignant lesions. ResultsOf the 5,549 thyroid FNAC cases, 1,891 cases underwent surgical resection. In final diagnosis, 1,700 cases were revealed as papillary thyroid carcinoma (PTC), and 25 cases were reclassified as NIFTP. The cytologic diagnoses of NIFTP were non-diagnostic in one, benign in five, atypia of undetermined significance (AUS) in 14, follicular neoplasm in two, and suspicious for malignancy in three cases. Collectively, NIFTP/encapsulated follicular variant of PTC (EFVPTC) were more frequently classified as benign, AUS, or follicular neoplasm and less frequently categorized as malignant compared to conventional PTCs. Exclusion of NIFTP from malignant diagnoses resulted in a slight decrease in malignancy rates in non-diagnostic, benign, AUS, follicular neoplasm, and suspicious for malignancy categories without any statistical significance. ConclusionsThe decrease in the ROM was not significant when NIFTP was excluded from malignant lesions. In thyroid FNACs, NIFTP/EFVPTCs were mostly classified into indeterminate categories. Therefore, it might be feasible to separate NIFTP/EFVPTC from conventional PTC on FNAC to guide clinicians to conservative management for patients with NIFTP/EFVPTC.

Improvement of diagnostic performance of pathologists by reducing the number of pathologists responsible for thyroid fine needle aspiration cytology: An institutional experience.

Various efforts have been made to improve the diagnostic accuracy of thyroid fine needle aspiration (FNA) cytology. We changed the diagnostic system by reducing the number of pathologists responsible for the thyroid FNA cytology in the routine work, and analyzed the effect on the pathologist's diagnostic performance. Since March 1, 2015, 3 pathologists have been responsible for diagnostic thyroid FNA, previously undertaken by 9 equally. We compared the prechange period (three months, 319 nodules) and the postchange period (12 months, 1194 nodules). The turnaround time was shortened from 1.4 ± 0.7 days to 0.9 ± 0.5 days (P < .001). The utilization rate of the Bethesda system for Reporting Thyroid Cytopathology (TBSRTC) increased from 92.5% to 99.8%. Diagnostic rates of categories that are confirmative [II (benign) and VI (malignant)] increased, while the inadequate (I) or indeterminate (III) categories decreased. With category IV (follicular neoplasm), a challenging category in our country, an elevated malignancy rate was found at follow-up. Overall, the diagnostic performance was improved in terms of sensitivity (from 98.5% to 99.2%) and specificity (from 94.4% to 98.4%), with reduced false-negative rates (from 1.5% to 0.8%) and false-positive rates (from 2.9% to 1.1%). The area under the receiver operating characteristic curve increased from 0.861 to 0.958. Reducing the number of pathologists responsible for diagnostic thyroid FNA cytology resulted in a higher utilization rate of TBSRTC, and more rapid and accurate diagnosis.

Use of the ultrasound-based total malignancy score in the management of thyroid nodules.

PurposeThe purpose of this study was to validate the role of the total malignancy score (TMS) in identifying thyroid nodules suspicious for malignancy through the sum of their ultrasound features.MethodsThe local ethical committee approved this prospective observational study. We examined 231 nodules in 231 consecutive patients (164 females and 67 males; age range, 20 to 87 years; median age, 59 years; interquartile range, 48 to 70 years) who underwent ultrasound followed by fine-needle aspiration cytology (FNAC). The nodules were further classified using the TMS, which considers ultrasound features (number, echogenicity, structure, halo, margins, Doppler signal, calcifications, and growth), and the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), which considers cytological features. Patients with non-negative nodules (TBSRTC categories III to VI) underwent histological analysis, repeated FNAC, or 2 years of regular ultrasound follow-up. The associations between the final diagnosis, each of the ultrasound features, and the TMS were estimated using the chi-square test, the Mann-Whitney U test, and multivariate logistic regression. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of the TMS.ResultsOn ultrasound, 47% of the nodules (108 of 231) had a TMS <3, 18% (42 of 231) had a TMS of 3, and 35% (81 of 231) had a TMS >3. The FNAC results of 85% of the nodules (196 of 231) were benign, while 15% (35 of 231) had non-negative results. Hypoechogenicity, solid structure, the presence of microcalcifications, and the number of nodules were independent predictors of the final diagnosis, and the diagnostic accuracy of the TMS was good (area under the ROC curve, 0.82).ConclusionThe TMS system is simple to use, reliable, easily reproducible, and closely reflects malignancy risk. Based on our results, FNAC could be limited to nodules with a TMS ≥3 without missing any cases of carcinoma.

Investigation of correlation between cytological and histological findings in suspected carcinoma of thyroid

ABSTRACT Introduction: The thyroid cytopathologic classification based on The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) standardized results derived from fine-needle aspiration (FNA). It has facilitated communication among clinicians, seems to reduce the number of unnecessary thyroidectomies and also improves the quality of malignancy detection. Objective: To evaluate the correlation between cytopathological samples classified according to TBSRTC and their histological finding after specimen examination following surgical procedure. Methods: Cytopathological samples classified according to TBSRTC were correlated with the respective anatomopathological finding after thyroidectomy. There were retrospectively included all cases of thyroidectomy with previous FNA in the same lateral position of the organ that occurred within two years. Results: The 200 cases of thyroid FNA analyzed were distributed in 25 nondiagnostic or unsatisfactory cases (I; 12.5%), 45 benign cases (II; 22.5%), 48 atypia or follicular lesions of undetermined significance [(AUS/FLUS), III; 24%], 23 suspected cases for follicular neoplasia or follicular neoplasias [(SFN/FN), IV; 11.5%], 40 cases suspected for malignancy (V; 20%), and 19 malignant cases (VI; 9.5%). The malignancy rates observed for categories I to VI were 12%, 13.3%, 29.2%, 43.5%, 85%, and 100%, respectively. Conclusion: The prevalence of Bethesda II category was lower than predicted by TBSRTC (60%-70%), as well as Bethesda III was higher than recommended (7%). Nevertheless, the corresponding malignancy rates were within the expected ranges.

Implementing noninvasive follicular thyroid neoplasm with papillary‐like nuclear features may potentially impact the risk of malignancy for thyroid nodules categorized as AUS/FLUS and FN/SFN

Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC) has recently been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Implementation of the new terminology may alter the implied risk of malignancy (ROM) across the six categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The study cohort consisted of thyroid fine needle aspiration (FNA) cases which were assessed between January 2011 and June 2016 and led to surgical resections. For each case, patient demographics as well as cytologic and corresponding histologic diagnoses were recorded. The surgical specimens diagnosed as follicular variant of PTC (FVPTC) were re-reviewed to identify cases that met the diagnostic criteria for NIFTP. The ROM with and without exclusion of NIFTP from malignant categorization, as well as the relative change in ROM were calculated for individual categories of TBSRTC. A total of 908 FNA cases with surgical follow-up were retrieved and PTC was identified in 252 (27.8%) surgical specimens. Twenty-nine of 252 (11.5%) were initially classified as FVPTC, of which 17 (6.7%) were reclassified as NIFTP. The cytologic interpretations for the majority of NIFTP cases were atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS, n = 8) or follicular neoplasm/suspicious for neoplasm/(FN/SFN, n = 4). Excluding NIFTP from malignant categorization resulted in a relative decrease in ROM in AUS/FLUS (25.8%) and FN/SFN (22.3%) categories. Our institutional data demonstrates that eliminating NIFTP from malignant categorization may result in a reduction of the implied ROM for AUS/FLUS and FN/SFN categories.

Current Status of Thyroid Fine-Needle Aspiration Practice in Thailand.

Thyroid carcinoma is one of the leading malignancies in Thailand increasingly prevalent in the female population. Fine-needle aspiration (FNA) cytology is a widely used diagnostic tool for evaluation of thyroid nodules and thyroid cancer. Thyroid FNA is a routine procedure universally performed in Thai hospitals by a variety of clinical specialists. Manual guidance is the first-line choice complemented by ultrasound assistance in selected cases. Despite national guidelines recommendations, the diagnostic criteria and terminology of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was slowly adopted in the local settings. Currently, the Bethesda system is actively promoted by the local professional societies as a uniform reporting system. Experience with thyroid FNA has been rarely reported to date—only a handful of publications are available in local journals. Our review, in addition to presenting various aspects of thyroid FNA in Thailand, established for the first time national references for a certain statistical outputs of TBSRTC based on the original multi-institutional cohort. The risk of malignancy in 2,017 operated thyroid nodules collected from three tertiary thyroid cancer centers was 21.7%, 14.7%, 35.9%, 44.4%, 76.7%, and 92.6% for categories I to VI, respectively. The malignancy risk in several diagnostic categories (II to IV) was higher than the risk estimated by TBSRTC and recent meta-analysis studies. We endorse the use of uniform terminology of the Bethesda system in Thailand, which will help facilitate communication among diverse medical professionals involved in the management of patients with thyroid nodules, to share local experience with the international audience.

Thyroid Cytology in India: Contemporary Review and Meta-analysis.

Fine-needle aspiration cytology (FNAC) is a screening test for triaging thyroid nodules, aiding in subsequent clinical management. However, the advantages have been overshadowed by the multiplicity of reporting systems and a wide range of nomenclature used. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was formulated in 2007, to give the world a uniform thyroid cytology reporting system, facilitating easy interpretation by the clinicians. Here, we review the status of thyroid FNAC in India in terms of various reporting systems used including a meta-analysis of the previously published data. An extensive literature search was performed using internet search engines. The reports with detailed classification system used in thyroid cytology were included. The meta-analysis of published data was compared with the implied risk of malignancy by TBSRTC. More than 50 studies were retrieved and evaluated. TBSRTC is currently the most widely used reporting system with different studies showing good efficacy and interobserver concordance. Ancillary techniques have, as of now, limited applicability and acceptability in thyroid cytology in India. Twenty-eight published articles met the criteria for inclusion in the meta-analysis. When compared with TBSRTC recommendations, the meta-analysis showed a higher risk of malignancy for categories I and III. Thyroid FNAC is practiced all over India. TBSRTC has found widespread acceptance, with most institutions using this system for routine thyroid cytology reporting. However, reasons for a high malignancy risk for categories I and III need to be looked into. Various possible contributing factors are discussed in the review.

The 2017 Bethesda System for Reporting Thyroid Cytopathology

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 1 of 6 diagnostic categories, the names of which remain unchanged since they were first introduced: (1) Nondiagnostic or Unsatisfactory; (2) Benign; (3) Atypia of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS); (4) Follicular Neoplasm or Suspicious for a Follicular Neoplasm; (5) Suspicious for Malignancy; and (6) 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 (eg, AUS and FLUS) should not be used to denote 2 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 non-invasive 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.

Thyroid FNAC Reporting Post-Bethesda - Problems and Challenges Faced in Our Center - A Preliminary Study

Aims and Objectives: The Bethesda system for reporting thyroid cytopathology (TBSRTC) was proposed to standardize the reporting of thyroid cytopathology for more effective clinical communication and patient management. This study was undertaken to see the challenges, if any, faced in our center post the implementation of the new system. Materials and Methods: Retrospective analysis of 250 thyroid aspirates was done wherein all slides were reviewed and reclassified as per TBSRTC. Results: The mean age of patients was 40.2 years and females comprised 86.4% of the study group. Histological follow-up was available in 19.6% of cases. On reclassification, 6% of cases were put in the category of atypia of unknown significance/follicular lesion of unknown significance (AUS/FLUS). The benign category comprised 80.6% down from 87.6% reported earlier. The non-diagnostic group also increased marginally from 8% to 8.8%. No changes were observed in the following categories: Follicular/Hurthle cell neoplasm, suspicious for malignancy and malignant. Conclusion: TBSRTC was useful in achieving the goal of improving thyroid cytopathology reporting by adopting a standardized format. However, due to the heterogeneity of the AUS/FLUS category, more cases than warranted were put in this category, which did not correlate with a higher risk of malignancy. More stringent criteria for inclusion of patients in the AUS/FLUS group and further stratification of these patients into high-risk and low-risk categories are suggested.

The largest CAP-certified Chinese reference laboratory experience with the Bethesda system for reporting thyroid cytopathology: correlation with histologic and BRAF data

Thyroid fine needle aspiration biopsy (FNAB) has not been widely used in most areas of China. We investigated a large cohort of thyroid FNAB using the Bethesda system for reporting thyroid cytopathology (TBSRTC) from the largest College of American Pathology (CAP)-certified reference laboratory in China. Patients with thyroid FNAB between 2014 and 2016 from Guangzhou Kingmed Diagnostics were retrospectively retrieved and the histologic follow-up results and BRAF results were collected and analyzed. A total of 7355 thyroid FNAB cases were identified. The average age of these patients was 48.03 years (range: 5-90 years). A total of 875 cases (11.9%) were reported as nondiagnostic, 4041 (54.9%) cases were benign, 736 cases (10.0%) were atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 53 cases (0.7%) were suspicious for follicular neoplasm, 615 cases (8.4%) were suspicious for malignancy, and 1035 cases (14.1%) were positive for malignancy. Histologic follow-up was available on 552 patients. Among 13 cases of AUS/FLUS, 8 (61.5%) had malignancy on histology; 195 (92.0%) of the suspicious for malignancy cases had malignancies on histology, and 320 (98.5%) of the positive for malignancy cases had malignancies on histology. BRAF analysis was performed on 578 cases. Sixty cases with BRAF data had histologic follow-up, all 4 benign cases had negative BRAF, one follicular adenoma had negative BRAF, and 37 of the 55 PTC cases (67.3%) had positive BRAF. BRAF mutation has a 100% positive predictive value of malignancy for the indeterminate thyroid FNABs. This is the largest cohort of thyroid FNA reported using TBSRTC in China and the data are helpful for better understanding the status of thyroid FNA in China.

Predicting thyroid nodule malignancy at several prevalence values with a combined Bethesda-molecular test

Investigation of thyroid nodules using fine-needle aspiration cytology (FNAC) gives indeterminate results in up to 30% of samples using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We present a combined Bethesda-molecular predictor of nodule malignancy to improve the accuracy of the preoperative diagnosis of thyroid nodules. To detect a molecular signature of thyroid nodule malignancy, a molecular test was performed on FNACs from 128 thyroid nodules from prospectively included patients, collected in a tertiary center. The test relied on a transcriptomic array of 20 genes selected from a previous study. An optimal set of seven genes was identified using a logistic regression model. Comparison between the combined predictor (TBSRTC + molecular) and TBSRTC alone used the area under the ROC curve (AUC). Performance of the combined predictor was calculated according to various malignancy prevalence values and benefit-to-harm ratios (B/Hr) (favoring sensitivity or specificity). In our population (36% malignancy prevalence) and with a B/Hr of 1, the combined predictor achieved 95% specificity and 76% sensitivity. The AUC was 93.5%; higher than that of TBSRTC (P = 0.004). Among indeterminate nodules (30% malignancy prevalence), sensitivity and specificity were 52.2% and 96.2%, respectively, with a B/Hr of 1, or 95.7% and 64.2% with a B/Hr of 4 (favoring sensitivity), allowing avoidance of 64% of unnecessary surgeries at the cost of only one false-positive result. In conclusion, this predictor could improve the detection of thyroid nodule malignancy, taking into account malignancy prevalence and B/Hr, and reduce the number of unnecessary thyroidectomies.

Validation of American Thyroid Association Ultrasound Risk Assessment of Thyroid Nodules Selected for Ultrasound Fine-Needle Aspiration.

The aim of this study was to validate the American Thyroid Association (ATA) sonographic risk assessment of thyroid nodules. The ATA sonographic risk assessment was prospectively applied to 206 thyroid nodules selected for ultrasound-guided fine-needle aspiration (US-FNA), and analyzed with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), as well as surgical pathology for the subset undergoing surgical excision. The analysis included 206 thyroid nodules averaging 2.4 cm (range 1-7 cm; standard error of the mean 0.07). Using the ATA US pattern risk assessment, nodules were classified as high (4%), intermediate (31%), low (38%), and very low (26%) risk of malignancy. Nodule size was inversely correlated with sonographic risk assessment, as lower risk nodules were larger on average (p < 0.0001). Malignancy rates determined by cytology/surgical pathology were high 100%, intermediate 11%, low 8%, and very low 2%, which were closely aligned with ATA malignancy risk estimates (high 70-90%, intermediate 10-20%, low 5-10%, and very low 3%). ATA US pattern risk assessment also appropriately predicted the proportion of nodules classified as malignant or suspicious for malignancy through TBSRTC classification-high (77%), intermediate (6%), low (1%), and very low 0%-as well as benign TBSRTC classification-high (0%), intermediate (47%), low (61%), and very low (70%) (p < 0.0001). Malignancy rates of surgically excised, cytologically indeterminate nodules followed ATA sonographic risk stratification (high 100%, intermediate 21%, low 17%, and very low 12%; p = 0.003). This prospective study supports the new ATA sonographic pattern risk assessment for selection of thyroid nodules for US-FNA based upon TBSRTC and surgical pathology results. In the setting of indeterminate cytopathology, nodules categorized as atypia of undetermined significance/follicular lesion of undetermined significance with ATA high-risk sonographic patterns have a high likelihood of being malignant.

Differences in Clinical Features Between Subcategories of "Atypia/Follicular Lesion of Undetermined Significance".

Within the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), category III (atypia or follicular lesion of undetermined significance (AUS/FLUS)) comprises specimens with heterogeneous features and the need for subcategorization has been reported. We compared the clinical features of two subgroups from within the category of AUS/FLUS to determine precise guidelines for clinicians who explain the results of fine-needle aspiration (FNA) to patients. Retrospective review was performed including data from all patients who underwent FNA with results reported as AUS/FLUS at a single tertiary hospital from January 2010 to August 2014. The results of repeated FNA, core needle biopsy, and diagnostic surgery were analyzed. Of the 903 patients with results categorized as AUS/FLUS, 500 were subcategorized as cellular atypia and 160 as architectural atypia. On repeated biopsy, diagnostic results were obtained for 78.9% patients of the cellular atypia group, compared to only 54.3% of the architectural atypia group (p<0.0001). The rate of neoplasm or malignancy was also significantly higher in the cellular atypia group compared to the architectural atypia group (51.8 vs. 25.2%, p<0.0001, 48.2 vs. 14.2%, p<0.0001). Therefore, clinicians can inform patients with architectural atypia that the risk of malignancy is low. However, the high rate of non-diagnostic results on repeated biopsy makes clinical decisions difficult. The data of the present study revealed the necessity of subcategorization of category III of TBSRTC in the future.

Impact of the Reclassification of the Non-Invasive Follicular Variant of Papillary Carcinoma as Benign on the Malignancy Risk of the Bethesda System for Reporting Thyroid Cytopathology: A Meta-Analysis Study

Objectives: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) established diagnostic categories for cytologic specimens of the thyroid. Each category was associated with an estimated risk of malignancy. Recently, the non-invasive follicular variant of papillary thyroid carcinoma has been reclassified as benign. This reclassification may alter the malignancy risk of TBSRTC diagnostic categories. Study Design: A literature search was made for all studies investigating the effect of reclassification of some non-invasive follicular variant papillary thyroid carcinomas as benign on the malignancy risk associated with TBSRTC categories. The authors calculated the malignancy risk for TBSRTC categories in a series of 315 thyroid aspirates when the non-invasive follicular variant of papillary thyroid carcinoma was considered benign. A meta-analysis of malignancy risk data for the 3 published studies and the current study was performed. Results: The meta-analysis showed that the malignancy risk was reduced for all TBSRTC categories except the “non-diagnostic” category. The reduction in malignancy risk was greatest in the categories “suspicious for malignancy” and “atypia/follicular lesion of undetermined significance.” Conclusion: A meta-analysis of all pertinent studies demonstrated that re-categorization of the non-invasive follicular variant of papillary thyroid carcinoma as benign reduces the malignancy risk in the majority of TBSRTC categories.

Risk of Malignancy and Risk of Neoplasia in the Bethesda Indeterminate Categories: Study on 4,532 Thyroid Fine-Needle Aspirations from a Single Institution in India

Objectives: To determine the frequency of category 3 (atypia of undetermined significance [AUS]/follicular lesion of undetermined significance [FLUS]), category 4 (follicular neoplasm), and category 5 (suspicious for malignancy) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), the risk of malignancy (ROM) and the risk of neoplasia (RON) in these categories. Study Design: A retrospective 6-year audit of 4,532 thyroid fine-needle aspirations (FNA) reported as per the TBSRTC from a single institution with cytohistological correlation in 335 cases. Results: The frequency of categories 3, 4, and 5 was 2.5, 3.9, and 0.5%, respectively; the upper and lower bound estimates of ROM being 58.3, 23.6, 75% and 5.1, 5, and 12.5%, respectively. AUS/FLUS (n = 116) cases were subcategorized as AUS, AUS-HC (Hürthle cell), AUS-PTC (AUS-papillary thyroid carcinoma not excluded), FLUS, FLUS-FH (favor hyperplasia), FLUS-HC, and FLUS-PTC. The AUS/FLUS malignancy ratio was 1:3.8. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of FNA thyroid was 80.5, 85.9, 80.7, 85.7, and 82.4%, respectively. Conclusion: Implementation of TBSRTC aided in achieving internal quality control in reporting thyroid FNA cytology. The AUS/FLUS frequency was 2.5%, which is at the lower range of the recommended rate and was associated with a higher than recommended upper bound estimate, but a comparable lower bound estimate of ROM.