The bethesda terminology for reporting thyroid cytopathology: from theory to practice in europe

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.     

BRAF Mutation Testing of Thyroid Fine-Needle Aspiration Specimens Enhances the Predictability of Malignancy in Thyroid Follicular Lesions of Undetermined Significance

Background/Objective: The Bethesda 2007 Thyroid Cytology Classification defines atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) as a heterogeneous category of cases that are neither convincingly benign nor sufficiently atypical for a diagnosis of follicular neoplasm or suspicious for malignancy. At our institution, we refer to these cases as 'indeterminate' and they are further subclassified into two categories. BRAF mutation occurs in 40-60% of papillary thyroid carcinoma (PTC). In this study, we examined cases in the AUS/FLUS category in correlation with BRAF mutation analysis and surgical pathology outcome. Study Design: Thyroid fine-needle aspiration (FNA) cytology specimens interpreted as 'indeterminate' were selected from our files, and available remnants of thin-layer processed specimens were used for BRAF mutation analysis. Surgical pathology reports were reviewed for the final outcomes in these patients. Results: Of the 84 indeterminate cases with BRAF mutation analysis, only 49 had follow-up with surgical intervention. Sixteen cases had BRAF mutation. All of the BRAF-positive cases had a final diagnosis of PTC. Conclusions: The sensitivity and specificity of BRAF mutation in detecting PTC in FNA specimens with indeterminate diagnosis was 59.3 and 100%, respectively, while the positive and negative predictive values were 100 and 65.6%, respectively. The limited data supports the use of BRAF mutation analysis to predict the risk of malignancy in patients with indeterminate thyroid FNAs.     

Risk of Malignancy in Thyroid Cytology: The Impact of The Reclassification of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP)

Objective: Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We aimed to compare the risk of malignancy (ROM) of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) on fine-needle aspiration cytology (FNAC), before and after the reclassification, in a large cohort of patients.Methods: We analyzed 5,625 consecutive FNAC samples performed in 2012–2014 and selected category III (atypia of undetermined significance [AUS]/follicular lesion of undetermined significance [FLUS]), IV (follicular neoplasm [FN]/suspicious for a follicular neoplasm [SFN]), V (suspicious for malignancy [SFM]), and VI (malignant) of the BSRTC. We reviewed the histology of operated patients and compared ROM before and after the introduction of the NIFTP category.Results: A total of 772 patients were identified and 45% underwent surgery (n = 348). There were 180 cases of AUS/FLUS (10 NIFTP), 114 cases of FN/SFN (2 NIFTP), 29 cases of SFM (3 NIFTP), and 25 cases of BSRTC VI (no NIFTP). Exclusion of NIFTP from malignant lesions resulted in a relative and absolute decrease in the ROM in AUS/FLUS (15.2% and 5.5%, respectively), FN/SFN (7.6% and 1.8%, respectively) and SFM (14.2% and 10.3%, respectively) categories. Among the NIFTP patients, 93% underwent total thyroidectomy and 20% received radioiodine.Conclusion: Reclassification of noninvasive EFVPTC as NIFTP resulted in a decrease in overall ROM, and the BSRTC categories most affected were III and V.Abbreviations: AUS = atypia of undetermined significance; BSRTC = Bethesda System for Reporting Thyroid Cytopathology; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FLUS = follicular lesion of undetermined significance; FN = follicular neoplasm; FNAC = fine-needle aspiration cytology; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma; ROM = risk of malignancy; SFM = suspicious for malignancy; SFN = suspicious for a follicular neoplasm     

Cytopathology of non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features: A comparative study with similar patterned papillary thyroid carcinoma variants

Objective

Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) is a recently described, indolent thyroid tumor, with well‐defined histopathological diagnostic criteria. Cytology features are not well documented. We reviewed cytology of histologically proven cases of NIFTP and some of its common differentials to look for salient diagnostic features.

Methods

Cases reported on histopathology as follicular variant of papillary thyroid carcinoma (FVPTC), or NIFTP between July 2015 and April 2017 having available cytology smears were retrieved and reclassified as NIFTP, FVPTC, and classical papillary thyroid carcinoma with predominant follicular pattern (PTC‐FP). Cytological features were assessed, classified as per The Bethesda System for Reporting Cytopathology and compared.

Results

There were 23 NIFTP cases, 18 FVPTC and 8 PTC‐FP. A microfollicle‐predominant pattern was seen in all. Nuclear score was 2 in most NIFTP cases (61%). Pseudoinclusions were absent. NIFTP showed features of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (III) in 61%, follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) (IV) in 35% and suspicious for malignancy (SFM) (V) in 4%. Most of the FVPTCs were also called FN/SFN (IV) (56%) or AUS/FLUS (III) (22%). Nuclear features did not statistically differ from NIFTP. PTC‐FP showed high‐grade cytology in 75%, and higher nuclear score (3 in 75%) in contrast to NIFTP (P = .003).

Conclusion

NIFTP and FVPTC show a similar distribution among the Bethesda categories hence precluding conclusive distinction on cytology. PTC‐FP, in contrast, was found to have a statistically significant higher nuclear score and more commonly showed malignant cytology.

     

Follow‐up of atypia and follicular lesions of undetermined significance in thyroid fine needle aspiration cytology

N. Dincer, S. Balci, A. Yazgan, G. Guney, R. Ersoy, B. Cakir and G. Guler
Follow‐up of atypia and follicular lesions of undetermined significance in thyroid fine needle aspiration cytology Objective: To report our experience of atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) rate and outcome. Methods: Among 7658 patients with 19 569 nodules, 524 (2.7%) nodules were diagnosed as AUS/FLUS on fine needle aspiration (FNA). After exclusion of patients with simultaneous nodules that were suspicious for follicular neoplasm or malignancy or that were malignant, 368 (4.8%) patients were diagnosed as AUS/FLUS. The outcome of 146 patients who had undergone surgery or repeated fine needle aspirate at the time of preparation of this study was evaluated. The original FNAs were matched to repeated FNAs and thyroidectomy or diagnostic lobectomy specimens. Results: Seventy‐two (19.6%) of the 368 patients had directly undergone surgery, either a lobectomy or a thyroidectomy: of these, 27 (37.5%) had neoplastic nodules (21 were malignant). Seventy‐four (20.1%) of the 368 patients had repeat FNA. On second FNA, 47 of 74 (63.5%) were benign, three were suspicious for follicular neoplasm, one was malignant and 23 (31.1%) were non‐diagnostic. Four patients had a third FNA: two were AUS/FLUS, one was malignant and one non‐diagnostic. One patient had a fourth FNA, which was diagnosed as AUS/FLUS. Sixteen (21.6%) of 74 patients with repeat FNA had surgery: three of these had neoplastic nodules (two were malignant). Overall, 88 of the 368 (23.9%) patients had a thyroidectomy of which 30 (34.1%) were neoplastic and 23 (26.1%) malignant. The neoplastic rate for patients who were once diagnosed with AUS/FLUS was 8.2% and the malignancy rate 6.3%. The malignancy rate for patients on follow‐up at the time we prepared the study was 15.7% (23/146); 222 remained on follow‐up without surgery or repeat FNA or were managed elsewhere. Conclusions: Although in this category repeat FNA is expected rather than excision, we suggest evaluation of all AUS/FLUS patients in multidisciplinary meetings to decide management and recommend follow‐up of all patients with this diagnosis.     

A Retrospective Study of Clinicopathologic Outcomes of Nodules With Hürthle Cell Cytology and the Thyroid Nodule App (TNAPP) Ultrasound Recommendations

ObjectivesHürthle cells are a common finding on thyroid fine-needle aspiration, but when they are the predominant cytology, they represent a difficult diagnostic challenge. The Thyroid Nodule App (TNAPP) is a new, publicly available web application utilizing ultrasound (US) features based on the updated 2016 American Association of Clinical Endocrinologists clinical practice guidelines for thyroid nodule management. This pilot study was performed to assess the TNAPP recommendations and surgical pathology outcomes of Hürthle cell-predominant thyroid nodules.MethodsA retrospective review of nodules with Bethesda III (atypia of undetermined significance with Hürthle cells) or Bethesda IV (suspicious for Hürthle cell neoplasm) cytology, for which surgery was performed between 2017 and 2021, was conducted. TNAPP US categories 1, 2, and 3 (low, intermediate, and high risk, respectively) were assigned based on nodule characteristics, and clinical management recommendations were recorded. Results were compared with histology-proven diagnoses.ResultsFifty-nine nodules in 57 patients where surgical pathology was available were analyzed with the TNAPP algorithm. Of the 59 nodules, 4 were US category 1 (low risk/suspicion), 40 were US category 2 (intermediate risk/suspicion), and 15 were US category 3 (high risk/suspicion). All US category 1 nodules were benign, while 30% of the US category 2 and 40% of the US category 3 nodules were malignant. Of the patients who had molecular marker testing with ThyroSeq, 22 out of 29 (76%) were positive, indicating either an intermediate or high risk of malignancy, 7 of which were malignant.ConclusionThis preliminary study suggests that TNAPP is a useful clinical tool for sonographic assessment of thyroid nodules with Hürthle cell cytology.     

Variability in the atypia of undetermined significance/follicular lesion of undetermined significance diagnosis in the bethesda system for reporting thyroid cytopathology: sources and recommendations

Objective: Of the 6 categories in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category has received the most attention. The objectives of this study were to review the use of the AUS/FLUS category in recent studies, to search for likely sources of the variability in its use, and to address possible methods for improvement. Study Design: A PubMed search was performed to retrieve peer-reviewed articles that have comprehensively detailed the incidence and outcome of AUS/FLUS and other BSRTC categories. Related thyroid cytology articles on the BSRTC were also included. Results: Recent series that reported experiences with the BSRTC categories showed that the AUS/FLUS category exhibited a marked variability in incidence (0.7-18%) and malignant outcome (6-48%) in resection specimens. Review of the literature revealed institutional differences in technical aspects, interpretation and application of criteria, analysis of outcome data, and clinicopathologic interactions. Conclusions: A heightened awareness of technical issues, diagnostic borders of AUS/FLUS, and clinical management may aid in diagnostic refinement and help avoid overuse of this category.     

Clinical Impact of Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features on the Risk of Malignancy in the Bethesda System for Reporting Thyroid Cytopathology: A Meta-Analysis of 14,153 Resected Thyroid Nodules

Objective: It is still controversial as to how the reclassification of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) affects the risk of malignancy (ROM) in The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). This meta-analysis was aimed to investigate the impact of NIFTP on the ROM in each TBSRTC category.Methods: We accessed three electronic databases including PubMed, Web of Science, and Scopus to search for relevant data from January, 2016 to July, 2018. Relative risk and meta-analysis of proportions using the DerSimonian-Laird method, and each corresponding 95% confidence interval (CI) was pooled using a random-effect model.Results: A total of 14 studies consisting of 14,153 resected nodules were included for meta-analyses. Overall, there was a significant reduction in ROM in all TBSRTC categories following the NIFTP reclassification, except TBSRTC category I. The largest absolute and relative decrease in ROM was observed in TBSRTC category V (16%; 95% CI = 8 to 24) and category III (32%; 95% CI = 24 to 39), respectively. There was a positive correlation between the rate of NIFTP and resection rate (r = 0.83; P = .02). The decreases in ROM were more prominent in Western than in Asian cohorts.Conclusion: We confirmed the decrease in ROM due to the NIFTP reclassification for most of TBSRTC categories, which was more significant in Western than in Asian practice. The incidence of NIFTP was higher in institutions where surgical resection rates were high in patients with indeterminate cytology nodules.Abbreviations: AUS/FLUS = atypia of undetermined significance/follicular lesion of undetermined significance; CI = confidence interval; FNA = fine-needle aspiration; FN/SFN = follicular neoplasm/suspicious for follicular neoplasm; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; NI-FVPTC = noninvasive follicular variant of papillary thyroid carcinoma; ROM = risk of malignancy; RR = relative risk; SM = suspicious for malignancy; TBSRTC = The Bethesda System for Reporting Thyroid Cytopathology     

Spectrum of risk of malignancy in subcategories of 'atypia of undetermined significance'

Objective: To determine if focal 'nuclear atypia' or 'microfollicular architecture' portends a higher risk of malignancy than other subcategories of atypia of undetermined significance (AUS) in thyroid fine-needle aspirations (FNAs). Study Design: The frequencies of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) categories were calculated from 3,956 thyroid FNAs interpreted over a 26-month period at The Johns Hopkins Hospital after adoption of TBSRTC. TBSRTC criteria were applied strictly. The risk of malignancy, specifically for AUS subcategories, was analyzed by cyto-histo correlation. Results: Of the 133 cases diagnosed as AUS, 32% were found to have stageable carcinoma (not incidental microcarcinoma) on resection. When the subset of AUS with 'nuclear atypia' (AUS-N) was separated from other AUS cases, 48% (30/62) of them had stageable carcinoma on resection; of the AUS subset with 'microfollicular architecture' (AUS-F), 27% (8/30) were malignant on resection. The 'suspicious for papillary thyroid carcinoma' (SPTC) group maintained a higher risk of malignancy versus AUS-N (relative risk, RR 1.57; 95% CI 1.23-1.81). Conclusion: The subcategory of 'nuclear atypia' within AUS indicates a higher risk of malignancy than other subcategories of AUS but has a lower risk of malignancy than SPTC does. Thus, it is an important distinction with potential clinical implications.     

Thyroid fine needle aspiration cytology processed by ThinPrep: an additional slide decreased the number of inadequate results

E. D. Rossi, F. Morassi, G. Santeusanio, G. F. Zannoni and G. Fadda
Thyroid fine needle aspiration cytology processed by ThinPrep: an additional slide decreased the number of inadequate results Background: Fine needle aspiration cytology is the most accurate tool for diagnosing thyroid nodules. Its accuracy is related to the rate of inadequate samples, which can be minimized with the adoption of on‐site assessment of the adequacy of the material. The introduction of liquid‐based cytology (LBC) in the thyroid does not allow checking on the adequacy of the cellularity. The possibility of making a second LBC slide for decreasing the number of non‐diagnostic cases is studied. Methods: Out of 553 cases diagnosed in a single institution from January to March 2005, 166 consecutive cases with an LBC slide reviewed by the same pathologist were evaluated. The cases were classified in a five‐tiered category system (Thy1 to 5 according to the British Thyroid Association guidelines) and all but two (with cystic degeneration) were processed by LBC and stained with Papanicolaou stain. The above‐mentioned categories are defined as follows: Thy1 inadequate or haemorrhagic, Thy2 non‐neoplastic lesion; Thy3 follicular lesion/suspected follicular neoplasm; Thy4 suspicious for malignancy; Thy5 diagnostic of malignancy. For each case the cytological diagnosis was made on the LBC slide and the adequacy of the cellularity for a conclusive diagnosis was assessed. Results: Of the 166 cases, 39 were non‐diagnostic (Thy1—inadequate), ten presented features of cystic degeneration (Thy1—haemorrhagic), 90 were benign (Thy2), 22 were diagnosed as a follicular lesion (Thy3), one as suspicious of malignancy (Thy4) and four as papillary carcinoma (Thy5). Thirty‐nine cases had a second LBC for achieving a definitive diagnosis with eventual re‐classification. Of these cases, 23 (61.5%) led to a conclusive diagnosis (18 Thy2, five Thy3) with a 18.5% decrease of the inadequacy rate. Conclusions: The making of an additional LBC slide helps in achieving a diagnosis in cases classified as non‐diagnostic on the first standard slide (52.1% recovery rate). This procedure is particularly helpful for meeting the adequacy criteria in benign and indeterminate lesions and could also be used for refining the diagnosis of suspicious for a malignant thyroid neoplasm.     

Cell block alone as an ideal preparatory method for hemorrhagic thyroid nodule aspirates procured without onsite cytologists

OBJECTIVE: To study diagnostic efficacy of direct smears (DS) vs. cell block (CB) alone in hemorrhagic thyroid fine needle aspirations (FNAs) performed without a cytotechnologist or cytopathologist. STUDY DESIGN: Ultrasound-guided thyroid FNAs from an offsite location were retrospectively searched during a 53-month period. Aspirates in the initial 13 months were submitted as air-dried DSs. Subsequent specimens were submitted as CBs. Each case was classified into 1 of 4 categories: (1) nondiagnostic, (2) nonneoplastic, (3) follicular lesions and (4) papillary thyroid carcinoma (PTC). RESULTS: There were 77 aspirates: DS = 20 (26%) and CB = 57 (74%). Two cases had both DSs and CBs. Diagnoses of DS: nondiagnostic = 12 (60%); nonneoplastic = 7 (35%); follicular lesion = 1 (5%). Diagnoses of CB cases: nondiagnostic = 4 (7.0%); nonneoplastic = 43 (75.4%); follicular lesion, including 1 Hürthle cell neoplasm = 7 (12.3%), PTC = 3 (5.3%). Repeat FNAs on 4 nondiagnostic cases (3 DSs, 1 CB) utilizing the CB-only technique were diagnostic and included nodular goiter, follicular neoplasm, PTC, and reactive lymph node. CONCLUSION: Without onsite assessment, CB alone is superior to DSs for hemorrhagic thyroid FNAs. It shows increased diagnostic efficacy and slide reduction and obviates repeat FNAs.     

Fine needle aspiration biopsy of Hashimoto's thyroiditis. Sources of diagnostic error.

OBJECTIVE: To determine the accuracy of cytologic interpretation in the diagnosis of Hashimoto's thyroiditis (HT). STUDY DESIGN: At Ottawa Hospital from 1987 to 1994, 1,638 fine needle aspiration biopsies (FNABs) from thyroid were performed. HT was suggested in 184 FNAB samples taken from 157 patients. Of the 184 aspirates diagnosed with HT, 39 had corresponding surgical specimens taken from 31 patients. A retrospective review of these FNABs and surgical pathology slides formed the basis of this study. RESULTS: In 27 (69%) aspirates, HT was diagnosed on both the FNAB and surgical specimens. In 10 of 27 FNABs an associated lesion was not sampled by FNAB. In four of these 10 aspirates some of the cellular features of HT were misinterpreted, and the possibility of an associated neoplasm could not be ruled out. This resulted in four false positive diagnoses. In 12 (31%) FNABs from nine patients, the cytologic diagnosis of HT was not confirmed histologically. These cases included five Hürthle cell adenomas and one case each of follicular adenoma, nodular goiter, macrofollicular adenoma and malignant lymphoma. This resulted in five false negative diagnoses. CONCLUSION: These results support the value of FNAB in the diagnosis of HT. The presence of hyperplastic follicular cells on FNAB samples from HT may mimic a follicular neoplasm and result in a false positive interpretation. Adequate sampling of the thyroid is important, particularly when there is an associated lesion. The diagnosis of lymphocytic thyroiditis should not be made when only a few lymphocytes are present. Finally, pleomorphic Hürthle cells may be present in aspirates from Hürthle cell neoplasms and underdiagnosed as HT, especially when they are associated with a few lymphocytes.     

Using the Ata and Acr Ti-Rads Sonographic Classifications as Adjunctive Predictors of Malignancy for Indeterminate Thyroid Nodules

Objective: Thyroid nodules with indeterminate cytology pose management challenges in clinical practice. The aim of this study was to determine the efficacy of ultrasound features in navigating clinical decision making in thyroid nodules with indeterminate cytology.Methods: We retrospectively reviewed ultrasound imaging from 186 adult patients with thyroid nodules and indeterminate cytology who underwent thyroidectomy at a quaternary hospital from 2010–2017. All nodules were classified based on the American Thyroid Association (ATA) and 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). Nodules were included if good quality pre-operative ultrasound imaging and surgical pathology were available.Results: A total of 202 thyroid nodules were included. The median age was 57 years; 82.8% were female. Risk of malignancy (ROM) in resected nodules with Bethesda 3 and 4 cytology was 19.4% and 30.3%, respectively. ATA high-suspicious and TI-RADS 5 nodules had high ROM, 100% in both systems for Bethesda 3 nodules; 66.7% and 50.0%, respectively, for Bethesda 4 nodules. For ATA very-low suspicious/TI-RADS 1 and 2, ROM was 0%. ROM in ATA low-suspicious/TI-RADS 3 nodules with Bethesda 3 cytology was lower (15.2% and 16.0%, respectively) than Bethesda 4 cytology (33.8% and 34.3%, respectively). ATA intermediate-suspicious/TI-RADS 4 nodules with Bethesda 4 cytology had a lower ROM (11.1% and 18.2%, respectively) than Bethesda 3 cytology (28.6 % and 31.6%, respectively).Conclusion: Using either the ATA or the TI-RADS system to risk-stratify nodules with indeterminate cytology may help clinicians plan better for additional diagnostic testing and treatment.Abbreviations: ACR = American College of Radiology; ATA = American Thyroid Association; AUS = atypia of undetermined significance; FLUS = follicular lesion of undetermined significance; FN = follicular neoplasm; PPV = positive predictive value; ROM = risk of malignancy; SFN = suspicious for follicular neoplasm; TI-RADS = Thyroid Imaging Reporting and Data System     

Differentiation of Hashimoto's thyroiditis from thyroid neoplasms in fine needle aspirates

In order to refine the cytodiagnostic criteria for distinguishing Hashimoto's thyroiditis from thyroid neoplasms, aspirates from six cases of Hashimoto's thyroiditis, five Hürthle cell neoplasms and one papillary carcinoma associated with Hashimoto's thyroiditis were reevaluated. Distinguishing characteristics were cell arrangements, nuclear chromatin pattern and nucleolar appearance. Hashimoto's thyroiditis was characterized by flat sheets and clusters of epithelial cells with oncocytic changes or occasionally by cohesive tissue fragments with cells well oriented one to the other. Thyroid neoplasms were characterized by loosely cohesive, syncytial-type tissue fragments with crowded overlapping cells poorly oriented one to the other and/or numerous isolated single cells. The nuclear chromatin of Askanazy cells in Hashimoto's thyroiditis was bland and even while that of neoplastic cells was finely granular, coarsely granular or irregularly clumped. Macronucleoli were present in Hürthle cell tumors but not in the Askanazy cells of Hashimoto's thyroiditis. Epithelial cellularity, lymphoid cellularity, cellular polymorphism and nuclear pleomorphism were not useful criteria for making the differential diagnosis between the two conditions. An admixture of epithelial cells and lymphoid cells indicated Hashimoto's thyroiditis but was not helpful in ruling out an associated neoplasm.     

Can the American Thyroid Association,K-Tirads,and Acr-Tirads Ultrasound Classification Systems Be Used to Predict Malignancy in Bethesda Category IV Nodules?

Objective: Management of thyroid nodules with Bethesda category III and IV cytology on fine needle aspiration (FNA) is challenging as they cannot be adequately classified as benign or malignant. Ultrasound (US) patterns have demonstrated the utility in evaluating the risk of malignancy (ROM) of Bethesda category III nodules. This study aims to evaluate the value of 3 well-established US grading systems (American Thyroid Association [ATA], Korean Thyroid Imaging Reporting and Data System [Korean-TIRADS], and The American College of Radiology Thyroid Imaging Reporting and Data System [ACR-TIRADS]) in determining ROM in Bethesda category IV nodules.Methods: Ninety-two patients with 92 surgically resected thyroid nodules who had Bethesda category IV cytology on FNA were identified. Nodule images were retrospectively graded using the 3 systems in a blinded manner. Associations between US risk category and malignant pathology for each system were analyzed.Results: Of the 92 nodules, 56 (61%) were benign and 36 (39%) were malignant. Forty-seven per cent of ATA high risk nodules, 53% of K-TIRADS category 5 nodules, and 50% of ACR-TIRADS category 5 nodules were malignant. The ATA high-risk category had 25% sensitivity, 82% specificity, 47% positive predictive value (PPV) for malignancy. K-TIRADS category 5 had 25% sensitivity, 85% specificity, 53% PPV for malignancy. ACR-TIRADS category 5 had 25% sensitivity, 84% specificity, 50% PPV for malignancy. None of the 3 grading systems yielded a statistically significant correlation between US risk category and the ROM (P = .30, .72, .28).Conclusion: The ATA, Korean-TIRADS, and ACR-TIRADS classification systems are not helpful in stratifying ROM in patients with Bethesda category IV nodules. Clinicians should be cautious of using ultra-sound alone when deciding between therapeutic options for patients with Bethesda category IV thyroid nodules.     

Atypical follicular cells with equivocal features of papillary thyroid carcinoma is not a low-risk cytologic diagnosis

Objective: To determine whether or not significant differences in the risk of malignancy exist between subgroups of atypical follicular cells in The Bethesda System for Reporting Thyroid Cytology (TBSRTC) in patients who underwent surgical resection. Study Design: Between 2004 and 2009, consecutive thyroid fine-needle aspirates at our institutions with a cytologic diagnosis of 'atypical follicular cells' were retrieved and subclassified using the diagnosis and diagnostic comment as: (1) atypical follicular cells with equivocal features of papillary carcinoma [cannot exclude papillary thyroid carcinoma (PTC)] and (2) atypical follicular cells, other patterns. The risks of malignancy for excised nodules were calculated and comparisons were made between these subgroups. Categorical analysis was performed using a 2-tailed Fisher's exact test, and p < 0.05 was considered statistically significant. Results: A total of 7,072 thyroid fine-needle aspiration cases were retrieved, with 1,542 (21.8%) having a histologic follow-up. There were 222 (3.1%) cases of 'atypical follicular cells', with 127 (57.2%) having a histologic correlation and 33 having confirmed malignancies. Atypical follicular cells, cannot exclude PTC, have a significantly higher risk of malignancy than atypical follicular cells, other patterns (45.8 vs. 13.9%, p < 0.01). Conclusions: Atypical follicular cells with equivocal features of papillary carcinoma is not a low-risk cytologic diagnosis.     

Repeat Diagnoses of Bethesda Category III Thyroid Nodules: What To Do Next?

Objectives

To assess the malignancy rates of thyroid nodules repeatedly classified as Bethesda category III on fine needle aspiration (FNA), and to suggest management guidelines for these lesions.

Methods

This is a retrospective study that included 395 thyroid nodules categorized as Bethesda III undergone either surgery or ultrasound (US) follow-up. There were 67 nodules classified a second time as Bethesda category III on repeat FNA. We compared malignancy rates, clinicopathologic and ultrasonographic characteristics between direct surgery and repeat FNA groups and between the initial and repeat Bethesda category III groups, each. And in the repeat Bethesda III group, clinicopathologic and US variables were compared between benign and malignant nodules.

Results

Incidence of concurrent cancer, underlying thyroiditis and positive BRAF mutation were significantly higher in 142 nodules with direct surgery than 243 nodules with repeat FNA (p < 0.05). Of the 395 nodules with Bethesda category III cytology on initial FNA, the malignancy rate was 59.5%. In 67 nodules with repeat Bethesda III classification, however, the malignancy rate was 73.1% (p < 0.05). However, none of the variables were significantly different between the initial Bethesda category III group and the repeat Bethesda category III group (p > 0.05). In the repeat Bethesda category III group, solid consistency, irregular/microlobulated margins, nonparallel shape, and number of suspicious findings or “suspicious malignant” US assessments were associated with a high malignancy rate (p < 0.05). On multivariate logistic regression analysis, the factor associated with malignancy in the repeat Bethesda category III group was irregular/microlobulated margin (odds ratio = 15.576; 95% CI, 2.097–115.6804, p = 0.007) with a sensitivity, specificity, positive and negative predictive values, and accuracy of 81.6%, 83.3%, 93.0%, 62.5% and 82.1%, respectively.

Conclusion

Thyroid nodules with repeated Bethesda category III classification and irregular/microlobulated margins on US are at increased risk of malignancy, and operative management should be considered as opposed to repeat FNA.     

Thyroseq®V2.0 Molecular Testing: A Cost-Effective Approach for the Evaluation of Indeterminate Thyroid Nodules

Objective: Approximately 15 to 30% of thyroid nodules have indeterminate cytology. Many of these nodules are treated surgically, but only 5 to 30% are malignant. Molecular testing can further narrow the risk of malignancy of these nodules. Our objective was to assess the cost effectiveness of ThyroSeq®V2.0 compared to diagnostic thyroidectomy for the evaluation of indeterminate nodules.Methods: Cytology and histopathology slides of Bethesda category III and IV (suspicious for follicular neoplasia [SFN]) nodules obtained between January 1, 2014 and November 30, 2016 were re-reviewed by 2 endocrine cytopathologists. Costs for a diagnostic approach using ThyroSeq® were calculated and compared to those of diagnostic thyroidectomy.Results: We included 8 Bethesda category III nodules that underwent ThyroSeq® and 8 that underwent diagnostic surgery. Of those submitted for ThyroSeq®, 4 were positive for mutations and underwent thyroid surgery. The average cost per nodule evaluated was $14,669 using ThyroSeq®, compared to $23,338 for diagnostic thyroid surgery. The cost per thyroid cancer case detected was $58,674 using ThyroSeq® compared to $62,233 for diagnostic thyroid surgery. We included 13 nodules Bethesda category IV that underwent ThyroSeq® and 11 that underwent diagnostic surgery. Of those submitted for ThyroSeq®, 6 were positive for mutation and underwent thyroid surgery. The average costs per nodule evaluated were $14,641 using ThyroSeq® and $24,345 using diagnostic thyroidectomy. The cost per thyroid cancer case detected was $31,721 when using ThyroSeq® compared to $53,560 for diagnostic thyroidectomy.Conclusion: The use of ThyroSeq® in our institution is cost effective compared to diagnostic thyroid surgery for the evaluation of Bethesda categories III and IV (SFN) nodules.Abbreviations: FNA = fine-needle aspiration; GEC = gene expression classifier; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid cancer; SFN = suspicious for follicular neoplasia     

Inter- and intraobserver reproducibility of thyroid fine needle aspiration cytology: an analysis of discrepant cases

OBJECTIVE: To determine the inter- and intraobserver reproducibility and analyse the discrepant cases of fine needle aspiration cytology (FNAC) of the thyroid. METHODS: Cases of thyroid FNAC with a corresponding histological diagnosis were reviewed regarding the original cytological diagnoses by two observers. The final cytological diagnoses (FCD) included both concordant and consensus diagnoses. The inter- and intraobserver reproducibility and efficacy of thyroid FNAC were calculated based on the FCD. RESULTS: A total of 97 FNAC cases with corresponding histopathological specimens were analysed. Although inter- and intraobserver disagreement in the cytological diagnoses occurred in about one-quarter of the cases analysed (24.7% and 23.7%, respectively), a substantial level of diagnostic interobserver (kappa = 0.71) and intraobserver (kappa = 0.66) reproducibility was observed. The efficacy of the method was 94.4%. Disagreement in the diagnosis was detected in 24 cases (24.7%), most of them (41.7%) for follicular lesions. Discordant cytological diagnoses between the two observers were represented by six (16.2%) of the 37 cases with an FCD of colloid nodule, five (41.7%) of the 12 cases of cellular follicular lesion, all three cases of follicular neoplasm, in two (6.3%) of the 32 cases of PTC, one (16.7%) of six cases of follicular neoplasm with a predominance of Hürthle cells and in one case of poorly differentiated neoplasia. Similarly, major disagreement in intraobserver cytological diagnoses was observed for the diagnosis of follicular lesions: 18 (78.3%) of a total of 23 discordant cases. CONCLUSION: As discrepancies in the cytopathological diagnosis can have repercussions in the management of patients, all cases with a cytological diagnosis of follicular lesions/neoplams should be reviewed in multidisciplinary meetings thus minimizing interobserver variability.     

Posters. P17 Accuracy of fine needle aspiration cytology in diagnosis of thyroid swellings

Introduction Fine needle aspiration cytology is regarded as the gold standard investigation in diagnosis of thyroid swellings. Published data suggest an overall accuracy rate of 75% 1 in the detection of thyroid malignancy. The aim of this study was to determine the accuracy of FNA cytology in detection of thyroid malignancy in our surgical unit. Methods Between 1989–2002, 144 patients who underwent thyroid resection by single consultant surgeon and who had pre‐operative FNA were enrolled in this retrospective study. The pre‐operative FNA results were compared with definitive histological diagnosis following thyroid resection. Fine needle aspiration cytology was performed using aspirate and non‐aspirate techniques on each thyroid swelling. The cytological sample was assessed by a single cytopathologist and was classified as inadequate, non‐neoplastic, neoplastic, suspicious or indeterminate. The histology was classified as non‐neoplastic (benign) and neoplastic (malignant). Results Fine needle aspiration cytology analysis revealed 94 (13.88%) non‐neoplastic, six (65.27%) neoplastic and 20 (4.16%) suspicious aspirates. Twenty (13.88%) samples were inadequate and four (2.77%) samples were indeterminate. Histological analysis showed 118 (81.94%) benign, 26 (18.05%) malignant specimens. Fine needle aspiration cytology had a sensitivity, specificity and accuracy rate of 52.6%, 86.6% and 79.1%, respectively for diagnosing thyroid malignancy. Conclusion The results are comparable with the current published data and demonstrate that FNA cytology in our hands is accurate investigation for pre‐operative diagnosis for the detection of thyroid malignancy.