MON-404 Fine Needle Aspiration of Thyroid Nodules Using the Bethesda System: An Institutional Experience at a Large Academic Center

Objectives: A 2007 conference held at the National Cancer Institute, Bethesda, Md., USA, proposed a new terminology for classifying the results of thyroid fine-needle aspiration (FNA) – The Bethesda System for Reporting Thyroid Cytology (TBSRTC). The need to standardize thyroid FNA terminology was emphasized during the 35th European Congress of Cytology in 2009. An interobserver review study to assess the new terminology for analyzing the results of thyroid FNA was organized by the scientific committee of the European Federation of Cytology Societies. Study Design: Four experts in thyroid FNA examined and classified 116 FNAs according to the 6 levels of TBSRTC which are: nondiagnostic (ND); benign; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN), with those of Hürthle cell type reported as follicular neoplasm, Hürthle cell type/suspicious for a follicular neoplasm, Hürthle cell type (FNHCT/SFNHCT); suspicious (SUS), and malignant. Results: The total consensus was 62.1%; the cytopathologists disagreed on 44 cases, including 8 cases of AUS/FLUS and 18 of FN/SFN; 59% of the cases had no consensus. They agreed on 73 and 80% of the cases classified as benign and malignant, respectively, and on 58.3% of the SUS cases. The percentage of no consensus for each expert was between 32 and 39%. Conclusions: Disagreement regarding the use of TBSRTC terminology for classifying the results of thyroid FNA mainly occurred in the most-often criticized categories of AUS/FLUS and FN/SFN.

Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in thyroid fine needle aspiration (FNA) is a challenging category. The malignancy risk is different by multiple factors and subsequent management strategy is inconclusive. Therefore, we analyzed the malignancy risk of AUS/FLUS according to radiological and clinical features. A total of 687 nodules that had been initially diagnosed as AUS/FLUS were retrospectively reviewed from 6365 thyroid FNAs between 2011 and 2014. The ultrasonographic (US) features were categorized using the Korean Thyroid Imaging Reporting and Data System. Radiological and clinical features were compared according to the second FNA results or histologically confirmed results from surgery. Repeat FNA was performed on 248 (36%) nodules, and 49 (7%) nodules underwent immediate surgery. Among the 248 nodules subjected to repeated FNA, 49 (20%) nodules were diagnosed again as AUS/FLUS, 123 (50%) were found to be benign, and 47 (19%) were diagnosed as follicular neoplasm, suspicious for malignancy or malignant. Among histologically confirmed nodules, the US features were more unfavorable in malignant nodules, and hypo- or anechogenicity was associated with a higher risk of malignancy after adjusting for age, size, and other US features (P < 0.01). In conclusion, we observed that malignant nodules tended to show unfavorable US features, especially hypo- or anechogenicity. Age, sex, and thyroid function were not significantly associated with malignancy risk. We also found out that malignancy risk was not different between the group which underwent immediate operation following the AUS/FLUS diagnosis and the group which underwent repeated FNA after the initial diagnosis.

Fine Needle Aspiration in the Management of Thyroid Nodules: Experience at King Khalid National Guard Hospital, Jeddah

Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is one of six diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (BSRTC). The goal of our study is to assess the outcome of cases classified as AUS/FLUS at our institution. AUS/FLUS cases were identified by computer searching of the thyroid fine-needle aspiration (FNA) cases performed between 2010 and 2016. Outcomes were categorized as: follow-up surgery, repeat FNA or no follow-up available. Demographics, ultrasound findings and FNA diagnostic criteria were reviewed for AUS/FLUS cases with follow-up surgical pathology diagnosis. Our AUS/FLUS thyroid FNA rate was 6% (117 out of 1984 FNAs). Only 15% of the AUS/FLUS cases had repeat FNA, while 41% underwent surgery. The risk of malignancy (ROM) for cases with follow-up surgery was 17%. When considering all AUS/FLUS cases, the ROM was 7%. Statistically, benign neoplasms were more likely to be single lesions on ultrasound comparing to malignant neoplasms, and to exhibit architectural atypia as opposed to non-neoplastic lesions on FNA. The malignancy rates among patients that directly went to surgical resection (17%) and patients having repeat FNA after the first AUS/FLUS diagnosis followed by surgery (29%) was not significantly different. However, repeat FNA was able to reclassify the majority of cases into more definitive categories. The outcome of the thyroid FNAs diagnosed as AUS/FLUS in our institution meets the benchmark statistics for AUS/FLUS rate and ROM. This study constitutes a valuable quality assurance measure and serves as a baseline for subsequent quality improvement.

Background: Thyroid fine needle aspiration (FNA) is currently the most acceptable method for evaluating thyroid nodules. Non-satisfactory sample is the main limitation of FNA. It has been shown that spinal needles can reduce the number of non-diagnostic samples. Objectives: In this study, we decided to compare the results obtained using spinal (stylet) needle and simple needle in thyroid nodule FNA according to the agreement between them and with the pathology results as the gold standard. Patients and Methods: Sampling of thyroid nodules of 156 patients was performed by a simple non-stylet 23 gauge needle (A) and a spinal 22 gauge needle with stylet (B). The samples were provided to the pathologist for blind examination. All samples were obtained by an expert radiologist and the pathology examination was also performed by a pathologist expert in thyroid gland diseases. Blind analysis was done using SPSS Statistics for Windows, version 16 (SPSS Inc., Chicago, Ill., USA). Results: The results of FNA with needles A and B were reported unsatisfactory in 11.51 (18 subjects) and 3.84 (six subjects), respectively (P = 0.01). The result in 63.46% (99 subjects) of the participants, in whom FNA was obtained by needle B was introduced as a better sample by the pathologist in comparison with 36.44% (57 subjects) (P &lt; 0.001). Cancer was diagnosed in 9.56 and 7.66 of the samples yielded by needles B and A, respectively, which was not statistically significant (P = 0.54). There was also a significant relationship between thyroid imaging reporting and data system (TI-RADS) score and FNA result. Conclusion: A significant relationship between the adequate sampling results, the qualitative examination result, TI-RADS score and the needle type indicates the importance of needle type on the results of thyroid FNA. Using spinal (stylet) needles may reduce the number of non-diagnostic samples in fine needle aspiration of thyroid nodules and therefore, can have a better effect on the results of this method.

Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (NEFVPTC) was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Excluding "carcinoma" from the new terminology shifted NIFTP out of the malignant category and altered Bethesda System for Reporting Thyroid Cytopathology (BSRTC) rates of malignancy (ROMs) on thyroid fine-needle aspiration (FNA). Because of potential effects on management guidelines, we examined our ROM data. In total, 750 thyroid FNAs with surgical resections from January 2013 to June 2016 were reviewed (including 87 NIFTPs). ROM was recorded for each BSRTC category: classifying NEFVPTC/NIFTP as "malignant" and reclassifying NEFVPTC/NIFTP as "nonmalignant." ROM changes were as follows: nondiagnostic (ND), no change; benign, 5.5% to 2.5%; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 42.3% to 22.3%; follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 48.7% to 17.9%; suspicious for malignancy (SFM), 93.6% to 61.7%; and positive for malignancy, 100% to 97%. Decreased ROM was seen in most BSRTC categories, most significantly in AUS/FLUS, FN/SFN, and SFM categories.

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

Fine Needle Aspiration of the Thyroid: Correlation with Final Histopathology in a Surgical Series of 797 Patients

Objective: To evaluate the utility of the BRAF(V600E) mutation detection in different cytoloy categories and to determine if the VE1 antibody can serve as a screening tool for the detection of BRAF(V)600E mutation in thyroid fine needle aspiration (FNA) specimens. Methods: A total of 273 FNA residual specimens were collected. BRAF(V600E) testing was performed on these liquid-based specimens. And also 78 specimens with enough residual cells were stained with VE1 antibody. Comparisons of molecular and immunocytochemistry results with clinicopathological outcomes were performed. SPSS 17.0 software was used to analyze the data. Results: There were 70 indeterminated diagnoses in 273 cases with FNAs. Fifty-eight cases were proven to be papillary thyroid carcinoma (PTC) by histology, including 9 cases of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 3 cases of follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), and 46 cases of suspicious for malignancy (SM). BRAF(V600E) analysis detected PTC in 3 of 9 cases with AUS/FLUS, and in 31 (67.4%) of 46 cases with SM. The sensitivity of immunostaining with VE1 antibody was 62.8%(27/43) and the specificity was 91.4% (32/35). VE1 expression showed moderately concordance with the molecular mutation (κ=0.524, P<0.001). Conclusions: Additional BRAF(V600E) detecting can improve the diagnostic efficacy for PTC in AUS/FLUS and SM. VE1 expression may be an alternative method for BRAF(V600E) detecting when molecular detecting is unavailable.

Background:The overall malignancy rate for the thyroid fine-needle aspiration (FNA) diagnosed as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) ranges from 5% to 30%. In this study, we present our institutional experience with thyroid nodules diagnosed as AUS/FLUS and further stratified into subcategories. In addition, we also assessed the significance of various clinicopathologic factors that may influence AUS/FLUS diagnoses and their outcomes.Design:A search of our laboratory information system was performed to identify all in-house thyroid FNA cases diagnosed as AUS/FLUS from 2008 to 2012. The data were collected and characterized by patient demographic information, cytopathology diagnosis with sub-classifiers and follow-up.Results:The case cohort included 457 cases diagnosed as AUS/FLUS. These were further sub-classified into one of six subcategories depending on the cytomorphologic findings and suspicion for or against a neoplastic process. Of the 457 cases, repeat FNA and/or surgical follow-up was available in 363 cases. There were 182 (39.8%) cases with cytologic follow-up only; 18 (9.9%) remained as AUS/FLUS, while 158 (86.8%) were re-classified with the majority being benign (142 cases). Histologic follow-up was available in 181 (39.6%) cases. There were 60 malignant cases confirmed by surgical excision, with an overall malignancy rate of 33.1%. The malignancy rate was 38.8% for cases with a repeat FNA versus 25.6% for cases that went directly to surgery without a repeat FNA. Papillary thyroid carcinoma accounted for 93.3% (56 cases) of the malignant cases.Conclusion:Based on our study, even though the malignancy rate of AUS/FLUS cases is similar to those reported for cases diagnosed as follicular neoplasm/suspicious for follicular neoplasm, we are of the belief that these comparable malignancy rates are a product of better clinical management and selection of patients diagnosed as AUS/FLUS for surgery after a repeat FNA.

The Bethesda System for Reporting Thyroid Cytopathology category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) includes fine-needle aspiration (FNA) specimens that cannot straightforwardly be classified as benign or malignant. To determine whether morphological subcategorization based on atypia qualifiers and molecular testing could improve malignancy risk stratification of AUS/FLUS patients, this study assessed the correlation between these qualifiers and the molecular alterations commonly harbored by thyroid neoplasms. A total of 162 AUS/FLUS cases were subcategorized by atypia qualifiers (Hürthle cell changes, architectural atypia, and cytologic atypia [CyA]) and were tested for BRAF, N-H-KRAS, RET/PTC, and paired box 8 (PAX8)/peroxisome proliferator activated receptor γ (PPARg) mutations. CyA was observed more frequently in mutation-positive AUS/FLUS (14 of 37 [37.84%]) than mutation-negative AUS/FLUS (20 of 125 [16.00%]; P < .0084), and it specifically harbored the BRAFV600E point mutation. Malignancy was confirmed in the available follow-up. Conversely, although RAS was the most frequent mutation identified in AUS/FLUS FNA specimens (26 of 37 cases [70.27%]; P < .0001), it was distributed across various AUS/FLUS subcategories and was not significantly associated with a specific atypia qualifier or malignant outcome according to the available follow-up. Rearrangements of both RET/PTC (n = 1) and PAX8/PPARg (n = 3) were rarely retrieved in the FNA samples. BRAF and RAS mutations are associated with different AUS/FLUS qualifiers and hence have different risks of malignancy. Consequently, a hybrid molecular and morphological subcategorization system could improve the malignancy risk stratification of thyroid FNA samples diagnosed as AUS/FLUS. Cancer Cytopathol 2018;126:317-25. © 2018 American Cancer Society.

The Bethesda System for reporting thyroid cytopathology (BSRTC) predicts an incidence of malignancy of less than 5% in thyroid nodules with a benign diagnosis on fine-needle aspiration (FNA). However, recent series have suggested that the true rate of malignancy might be significantly higher in this category of patients. We reviewed our experience by performing a retrospective analysis of patients with benign thyroid FNA results who underwent thyroidectomy between 2008 and 2013 at a large academic center. Information including demographics, ultrasound features, FNA diagnosis, and surgical follow-up information were recorded. Slides were reviewed on cytology-histology discrepant cases, and it was determined whether the discrepancy was due to sampling or interpretation error. A total of 802 FNA cases with a benign diagnosis and surgical follow-up were identified. FNA diagnoses included 738 cases of benign goiter and 64 cases of lymphocytic thyroiditis. On subsequent surgical resection, 144 cases were found to be neoplastic, including 117 malignant cases. False negative, defined as interpretation error and inadequate biopsy of the nodule harboring malignancy, was 6%. When cases of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were excluded from the analysis, false-negative rate was 5%. When microPTC cases were excluded, false-negative rate was 3% and was slightly less than 3% when both microPTC and NIFTP cases were excluded from the analysis. Retrospective review of neoplastic cases showed that 57% were due to sampling error and 43% were due to interpretation error. Interpretation error was more likely to occur in follicular patterned neoplasms (75%), while sampling error was more common in non-follicular variants of papillary thyroid carcinoma (non-FVPTC) (61%). With the exclusion of microPTC, interpretation errors were still more likely to occur in follicular neoplasms (79%) but there was no significant difference in sampling error between non-FVPTC (37%) and follicular patterned neoplasms (42%). Tumor size was larger in cases with interpretation error (mean = 2.3cm) compared to cases with sampling error (mean = 1.4cm). This study shows that the false-negative rate of thyroid FNA at our institution is not significantly above the rate suggested by the BSRTC. Interpretation errors were more likely to occur in follicular patterned neoplasms, while non-FVPTC was more frequently found in false negative cases due to inadequate sampling.

Thyroid fine-needle aspiration (FNA) is used to assess appropriate management of nodular thyroid lesions safely, but Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance) and category IV (follicular neoplasm/suspicious for follicular neoplasm) lesions are problematic. This study aimed to evaluate the Afirma Gene Expression Classifier (GEC) results for lesions in those categories. Medical records of patients with thyroid FNA and GEC results were obtained from archived material. Results were compared to thyroidectomy histologic diagnoses. Among 66 patients with FNA results (47 women and 19 men aged 26-89 years [mean, 59.4 years]), surgical reports were available for 38. Afirma GEC results were "nondiagnostic" for 10 of 66 (15.2%), "benign" for 22 (33.3%), and "suspicious" for 34 (51.5%). Surgical diagnosis was available for 38 of 66 patients (57.6%); GEC results for 6 (15.8%) of these were "nondiagnostic," 27 (71.0%) were "suspicious," and 5 (13.2%) were "benign." One of 6 (16.7%) samples with "nondiagnostic" results, 1 of 5 (20%) with "benign" results, and 15 of 27 (55.6%) with "suspicious" results were malignant on histology. Papillary carcinoma was the most common tumor type (15 of 38; 39.5%). Afirma GEC results minimize the number of unnecessary operations. Afirma GEC testing may be reserved for FNAs with a category III diagnosis on follow-up cytologic examination. We recommend a conservative approach for "suspicious" Afirma GEC results if Hürthle cells are seen with FNA.

The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) is used to categorise thyroid fine-needle aspiration (FNA). The aim of this study was to validate the BSRTC in a consecutive cohort and to evaluate the derived management in terms of performing repeat FNA or thyroid surgery. Results of thyroid FNAs assessed at the Department of Pathology, Aarhus University Hospital, in the period 2016-2019 were retrieved from The Danish Pathology Registry. FNA category according to the BSRTC along with the histological diagnosis (if available) were linked to the individual patient. In total, 3,669 biopsies were included from 2,873 thyroid nodules in 2,547 patients. Repeat FNA was performed in 23.6% of nodules. The majority of primary FNAs were Benign (BSRTC II; 52.4%). Non-diagnostic (ND) (BSRTC I) was found in 26.3% and BSRTC III-VI were found in 3.6-7.5%. Compared with the first with the last FNA, the frequency of Benign (BSRTC II) increased (61.3%), whereas the frequency of ND (BSRTC I) decreased (14.8%). Surgery was performed in 38.2% (n = 1,097) of nodules. The malignancy rate of 11.5% correlated positively with the BSRTC category, being 2.8% in Benign (BSRTC II) and 95.7% in Malignant (BSRTC VI). The malignancy rates in the BSRTC categories were in accordance with reports from other countries. Since the BSRTC ensures a standardised and concise communication of cytopathology assessments, application of the BSRTC for thyroid nodule management in a Danish setting is recommended. None. Not relevant.

ObjectivesThe usefulness of core needle biopsy (CNB) for the diagnosis of thyroid nodules remains controversial, and preferences vary across hospitals. The purpose of this study was to assess the actual use of CNB in Korea and to analyze the advantages and disadvantages of CNB through a systematic review and meta-analysis of papers published by Korean authors.MethodsA meta-analysis of full-text publications published in English presenting data from Korea retrieved from the Embase literature database was performed.ResultsCNB led to a significantly lower proportion of non-diagnostic results than fine-needle aspiration (FNA). However, the frequency of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) did not decrease as a result of performing CNB in nodules with initial AUS/FLUS results, while it increased in consecutive cases. A subcategory analysis of AUS/FLUS showed that the increased frequency of AUS/FLUS findings on CNB was due to more frequent diagnoses of architectural atypia and follicular neoplasm, which resulted in a higher frequency of inconclusive findings in consecutive cases compared to FNA. Hospitals favoring CNB had a higher proportion of AUS/FLUS diagnoses. Although the complication rate did not differ significantly between CNB and FNA, serious complications of CNB did occur.ConclusionA reduced frequency of non-diagnostic results may be a definite advantage of CNB over FNA. However, the increased frequency of diagnoses of architectural atypia and follicular neoplasm should be considered when selecting CNB as a diagnostic tool.