Thyroid FNA terminology: The case for a single unified international system for thyroid FNA reporting.

The use of reporting terminologies for thyroid FNA cytology enables standardisation and international alignment of the reporting of thyroid cytology results, which is essential. There are currently three major internationally recognised systems: Bethesda (TBS), UK RCPath (Thy), and Italian (TIR). A fourth terminology system used in Japan has identical categories to TBS but with different nomenclature. The aim of this review is to discuss the strengths and weaknesses of the TBS, UK RCPath, and TIR systems, and to make the case for international terminology harmonisation and standardisation.

The dilemma of 18F-FDG PET/CT thyroid incidentaloma: what we should expect from FNA. A systematic review and meta-analysis.

PURPOSE: 18F-FDG thyroid incidentaloma (TI) occurs in ~2% of PET/CT examinations with a cancer prevalence of up to 35-40%. Guidelines recommend fine-needle aspiration cytology (FNA) if a focal 18F-FDG TI corresponds to a sonographic nodule >1 cm. The aim of this systematic review and meta-analysis was to provide evidence-based data on the diagnostic distribution of 18F-FDG TIs in the six Bethesda systems for reporting thyroid cytopathology (BETHESDA) subcategories. METHODS: Original studies reporting 18F-FDG TIs and cytologically classified according to BETHESDA were included. Six separate meta-analyses were performed to obtain the pooled prevalence (95% confidence interval, 95% CI) of 18F-FDG TIs in the six BETHESDA subcategories. RESULTS: Fifteen studies were finally included. Nine studies were from Asian/Eastern and six from Western countries. FNA data according to BETHESDA was available in 2304 cases. The pooled prevalence of 18F-FDG TIs according to BETHESDA was BETHESDA I 10% (6-14), BETHESDA II 45% (37-53), BETHESDA III 8% (3-13), BETHESDA IV 8% (5-12), BETHESDA V 6% (4-9), BETHESDA VI 19% (13-25). A significantly different prevalence was found in the BETHESDA IV between Asian/Eastern (2%) and Western (19%) studies. CONCLUSION: Two-thirds of focal 18F-FDG TIs undergoing FNA have either malignant (BETHESDA VI) or benign (BETHESDA II) cytology while a minority will have indeterminate (BETHESDA III or IV) FNA results. Significant differences between Asian/Eastern and Western studies are also present in the prevalence of indeterminate FNA results.

Data set for reporting carcinoma of the thyroid: recommendations from the International Collaboration on Cancer Reporting.

Thyroid cancer therapy is increasingly tailored to patients' risk of recurrence and death, placing renewed importance on pathologic parameters. The International Collaboration on Cancer Reporting (ICCR), an organization promoting evidence-based, internationally agreed-upon standardized pathology data sets, is the ideal conduit for the development of a pathology reporting protocol aimed at improving the care of patients with thyroid carcinomas. An international expert panel reviewed each element of thyroid pathology reporting. Recommendations were made based on the most recent literature and expert opinion.The data set uses the most recent World Health Organization (WHO) classification for the purpose of a more clinically and prognostically relevant nomenclature. One example is the restriction of the term minimally invasive follicular carcinoma to tumors with capsular invasion only. It reinforces the already established criteria for blood vessel invasion adopted by the most recent WHO classification and Armed Forces Institute of Pathology fascicle. It emphasizes the importance of the extent of blood vessel invasion and extrathyroid extension to better stratify patients for appropriate therapy. It is the first data set that requires pathologists to use the more recently recognized prognostically powerful parameters of mitotic activity and tumor necrosis. It highlights the importance of assessing nodal disease volume in predicting the risk of recurrence.The ICCR thyroid data set provides the tools to generate a report that will guide patient treatment in a more rational manner aiming to prevent the undertreatment of threatening malignancies and spare patients with indolent tumors the morbidity of unnecessary therapy. We recommend its routine use internationally for reporting thyroid carcinoma histology.

Should uncertainty concerning the risk of malignancy be included in diagnostic (nongynecologic) cytopathology reports?

In diagnostic cytology, the known site-specific false positive rates at various anatomical sites for the risk malignancy (ROM) when a confirmed malignant diagnosis is made are comparatively well documented. ROM figures for diagnostic cytology specimens may vary according to the anatomical site of the specimen, the exact nature of the specimen received, the staining method(s) used, and the use of additional laboratory techniques including molecular profiling; furthermore, they often differ to some extent from institution to institution, between differing cytologists within the same institution, and over time. A brief literature review for a selected group of routine diagnostic cytology specimens shows a published ROM for a confirmed malignant diagnosis as follows: bile duct brushings, ~99% (range, 97%-100%); breast fine needle aspiration, 98.5% (range, 92%-100%); serous effusion fluid, 98.9% (range, 90%-100% although lower for squamous cell carcinoma, mesothelioma, and lymphoma), pulmonary endobronchial ultrasound cytology, ~99% (range, 86.6%-100%); thyroid FNA, 98% (range, 97%-99% if NIFTP tumors are excluded), salivary gland FNA, ~90%; (range 57%-100%) and lateral neck cyst FNA, ~99% (range, 95.5%-100%). Because most diagnostic cytology specimens have a small but accepted false-positive rate, this information is vitally important for the clinical management of patients and for shared patient decision making. In our view, the known false-positive rate for a given diagnostic cytology specimen could be included within the cytology report to assist in explaining the limitations of the diagnostic cytology interpretation and help facilitate the clinical decision-making process.

Hürthle Cells on Fine-Needle Aspiration Cytology Are Important for Risk Assessment of Focally PET/CT FDG Avid Thyroid Nodules.

This study assesses the role of [18F] FDG PET/CT, fine needle aspiration (FNA) cytology and ultrasound in the 1-2% of patients with focally positive thyroid nodules on FDG PET/CT. All FDG PET/CT scans with focally increased thyroid FDG PET/CT uptake performed over 37 months in one institution were matched to patients undergoing thyroid FNA. Diffuse FDG PET/CT uptake patients were excluded. A total of 47 patients showed focally increased thyroid uptake. Consistent with previous studies, 18 (38.2%) patients had malignancy-12 primary thyroid carcinoma, 1 parathyroid carcinoma, 3 metastatic carcinoma to the thyroid and 2 lymphoma. A total of 15 (31.9%) lesions categorized as non-malignant contained Hürthle cells/oncocytes. A total of 14 lesions (29.8%) had focally increased FDG PET/CT uptake with no specific cytological or histopathological cause identified. No focally PET avid Hürthle cell/oncocytic lesions were found to be malignant. Exclusion of oncocytic lesions increased the calculated risk of malignancy (ROM) of focally PET avid nodules from 38% to 68%. It may be useful to exclude focally FDG PET/CT avid Hürthle cell/oncocytic lesions, typically reported as follicular neoplasm or suspicious for a follicular neoplasm, Hürthle cell type (Oncocytic) type, RCPath Thy 3F: Bethesda IV or sometimes Thy 3a: Bethesda III FNAs) from ROM calculations. Oncocytic focally PET/CT FDG avid lesions appear of comparatively lower risk of malignancy and require investigation or operation but these lesions should be readily identified by FNA cytology on diagnostic work up of focally PET avid thyroid nodules.

Litigation in thyroid cytology and histopathology in England: a very brief overview.

This brief review discusses legal issues in thyroid cytology and histopathology in England. The principal risks in thyroid cyto/histopathology are either underdiagnosis of a malignant condition as benign, overdiagnosis of a benign condition as malignant, or the failure to recognise or the overdiagnosis as malignant of a benign or inflammatory condition. There are multiple diagnostic pitfalls in both cytology and histopathology and these are reasonably well documented. The interobserver reproducibility as assessed by kappa statistics of some of the major criteria for malignancy, specifically papillary-type nuclei in the diagnosis of papillary thyroid carcinoma, capsular invasion or vascular invasion are comparatively poor hence diagnoses of well differentiated papillary or follicular carcinoma may often be to some extent subjective. This article reviews the current legal situation in England discussing recent legal case precedents with a suggestion for improving communication and the preoperative consent process for patients.

Measures to reduce diagnostic error and improve clinical decision making in thyroid FNA aspiration cytology: A proposed framework.

Thyroid fine-needle aspiration cytology (FNA) and histopathology can be subjective areas of medical diagnosis and subject to different interpretations. On the basis of the authors' personal experience, 12 recommendations with potential to improve clinical decision making, ensure quality, and reduce diagnostic error in thyroid FNAC and histopathology are presented. 1) use a standardized reporting terminology for thyroid FNAC; 2) understand and explain to service users the limitations of cytology and the standardized thyroid FNAC reporting terminology used; 3) the cytopathologist should review all relevant clinical and ultrasound findings, if feasible; 4) include the risk of malignancy in all FNAC reports if feasible; 5) collect data to calculate the local institutional risk of malignancy for FNAC if feasible; 6) accept that nondiagnostic FNAC will include small numbers of carcinomas; 7) use rapid on-site evaluation and/or educational sessions for aspirators if the nondiagnostic aspiration rate is high; 8) know the diagnostic pitfalls of both cytology and histopathology; 9) use special immunohistochemical and molecular techniques that are evidence-based; 10) make use of second opinions, either in-house or interinstitutional; 11) multidisciplinary discussion of cases before surgery or therapy is invaluable; and, finally, 12) manage patient and clinician expectations of thyroid cytology and histopathology. These 12 recommendations may assist in quality-improvement initiatives and may reduce diagnostic errors in thyroid cytology and histopathology. Thyroid multidisciplinary case discussion remains the principal, overarching method for error reduction and for providing high-quality clinical decision making.

Thyroid FNA: Is cytopathologist review of ultrasound features useful?

Cytopathologist review of thyroid ultrasound (US) has been proposed to be useful in diagnosis and patient triage. This review explores the implications for practicing cytopathologists of integrating US review into the thyroid fine-needle aspiration diagnosis. At present, there is no agreed-upon system for combining cytologic and US features and communicating those results as a single report. If cytologists are performing tasks that require expertise in US interpretation, then they should know and be fully conversant with US interpretation. Whether cytologists performing aspirations require expertise in US interpretation is not clear. Regardless, cytologists should avoid using US results to alter their cytologic interpretations unless they clearly communicate that this is what they are doing. An evidence-based integrated reporting system that would allow cytologists to clearly explain to other physicians exactly how they reached their interpretation might provide value beyond current standard practice.

Rates of Thy 1-non-diagnostic thyroid fine needle aspiration using the UK Royal College of Pathologists Thy Terminology. A systematic review of the literature comparing patients who undergo rapid on-site evaluation and those who do not.

INTRODUCTION: The UK Royal College of Pathologists (RCPath) Thy terminology is an internationally recognised system for reporting thyroid fine needle aspiration. The terminology has been used throughout the UK and Ireland, in some parts of Italy and Switzerland, and elsewhere in the world. There is no systematic review of the literature specifically addressing the use of the non-diagnostic for cytological diagnosis-Thy1/Thy 1c category in the UK RCPath terminology. METHODS: A comprehensive literature search of online databases was conducted in October 2019 specifically examining overall reported rates of Thy1 and Thy1c in aspirates classified according to the UK Thy terminology. RESULTS: Twenty-five articles were identified showing a Thy1 rate of 13.4% (2540/18 920). The studies were then stratified according to whether or not the patients underwent rapid on-site evaluation (ROSE): 6.0% (353/5841; range 3.0%-10.9%) of ROSE aspirates were Thy1 whereas 18.5% (2072/11 204; range 7.9%-43.3%) of non-ROSE patients were Thy1; (P < .05). Three studies from 2016 reported Thy1c rates of 5.4%, 6.5% and 10.6%, respectively, implying Thy1 rates excluding Thy1c aspirates of 20.9%, 8.7% and 12.7%, respectively. CONCLUSION: This systematic review of the literature shows relatively high rates of aspirates non-diagnostic for cytological diagnosis-Thy1 in the peer-reviewed published literature using the UK terminology. Utilisation of ROSE appears to produce lower rates of Thy1 aspirates and ROSE should be considered if rates of non-diagnostic for cytological diagnosis-Thy1/Thy 1c are high.

Risk of malignancy in the various categories of the UK Royal College of Pathologists Thy terminology for thyroid FNA cytology: A systematic review and meta-analysis.

BACKGROUND: The UK Royal College of Pathologists Thy terminology for reporting thyroid fine-needle aspiration cytology (FNAC), first published in 2009 is used throughout the United Kingdom and Ireland, in some parts of Italy and Switzerland and elsewhere. There is no review of the literature or meta-analysis of the risk of malignancy (ROM) in the various categories of the UK Thy terminology. The goal of this study was to establish the published ROM for each Thy category and compare the results with other existing terminology systems for which similar meta-analyses are available. METHODS: A comprehensive literature search of online databases was conducted in May 2019 to examine the ROMs for histologically proven nodules with preoperative FNAC classified according to the UK Thy terminology. RESULTS: Twenty-five articles were identified that showed results of both cytology and histology. Twelve of these articles were excluded to prevent a selection bias because they showed data in just 1 Thy category. In the remaining 13 articles, the pooled ROMs were as follows: Thy1, 12% (95% confidence interval [CI], 5%-22%); Thy2, 5% (95% CI, 3%-9%); Thy3, 22% (95% CI, 18%-26%); Thy3a, 25% (95% CI, 20%-31%); Thy3f, 31% (95% CI, 24%-39%); Thy4, 79% (95% CI, 70%-87%); and Thy5, 98% (95% CI, 97%-99%). CONCLUSIONS: This meta-analysis shows results comparable to those of meta-analyses of other internationally recognized reporting terminologies for the pooled ROMs for surgically excised nodules in the various Thy reporting categories. There is comparatively little difference (only 6%) between the pooled ROMs of Thy3a and Thy3f surgically excised nodules.

An International Interobserver Variability Reporting of the Nuclear Scoring Criteria to Diagnose Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: a Validation Study.

The aim of the study was to assess interobserver variation in reporting nuclear features of encapsulated follicular variant of papillary thyroid carcinoma, newly reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), based on a proposed standardized scoring system. An education module was individually reviewed as a pre-evaluation teaching guide of the specific features of classical papillary carcinoma, the specific inclusion and exclusion features for the diagnosis of NIFTP, and a catalog of the standardized scoring system of the nuclear features of papillary carcinoma used to reach this diagnosis. Participants subsequently reviewed 30 cases of thyroid lesions previously scored by members of the Endocrine Pathology Society Working Group for the Re-evaluation of the Encapsulated Follicular Variant of Papillary Thyroid Carcinoma. There was one uninvolved reference image to demonstrate fixation, processing, and cell size and one image from each case for scoring, with results recorded for each participant. The location of training (country and program), years as a practicing pathologist, and approximate number of thyroid gland surgical cases diagnosed per year were recorded. The degree of agreement between participants was assessed by kappa statistics, using the individual criteria and the average composite scores of the Working Group as a point of comparison. Using the Nuclear Standardized Scoring System, the interobserver agreement for final diagnosis score was generally excellent: unweighted and weighted kappa values between individual observers ranging from 0.242 to 0.930 (average 0.626). There was significant agreement between observers in reaching an interpretation of the presence or absence of nuclear features to diagnose NIFTP (score 0-1 versus score of 2-3), with California pathologists, 0.63 (median 0.66, SD 0.15); Japanese pathologists, 0.64 (median 0.66, SD 0.16); and UK pathologists, 0.60 (median 0.57, SD 014) compared to the expert panel, 0.70 (median 0.73, SD 0.19). The use of the nuclear scoring system to evaluate the nuclear features of papillary thyroid carcinoma as applied to reach the diagnosis of NIFTP shows a good to substantial interobserver agreement, suggesting that consensus can be reached in diagnosing the nuclear features required for this newly reclassified neoplasm.

Value of cytopathologist review of ultrasound examinations in non-diagnostic/unsatisfactory thyroid FNA.

BACKGROUND: Correlation of cytologic and ultrasound findings is extremely valuable for the cytopathologist in management of thyroid nodules. METHODS: Ultrasound scans (US) of all thyroid FNA taken over a 13 month period and reported by a single cytologist were reviewed at the time of reporting, focusing on aspirates that were non-diagnostic/unsatisfactory, equivalent to Bethesda Class I, UK Royal College of Pathologists Class Thy1 or Thy1c. RESULTS: FNA cases [68 (40.7%)] were classified as Thy1, equivalent to Bethesda Class I. US of 3 Thy1 cases were not available for review. On cytologist US review 9 cases were classified as pure cystic, 28 as mixed cystic/solid, 12 as predominantly solid/focally cystic and 16 as purely solid. 27 (41.5%) of cases on cytological assessment were Thy1 and showed no evidence of a cyst on US, 17 (26.1%) were Thy1/Thy1c showing features suggestive of a possible cyst and 21 (32.3%) were Thy1c showing definite features of a cyst. Fifteen of 16 (93.7%) of pure solid cases on US were Thy1, equivalent to Bethesda Class I and all 9 (100%) of cases that were pure cystic on US were reported as Thy1c-equivalent to Bethesda Category I-cyst fluid only (P < .001). CONCLUSION: Cytopathologist review of thyroid US is extremely useful and can be helpful in triaging patients for further management in cases of solid, mixed cystic and/or solid, and pure cystic thyroid lesions with non-diagnostic/unsatisfactory thyroid FNA.

The Molecular Landscape of Noninvasive Follicular Thyroid Neoplasm With Papillary-like Nuclear Features (NIFTP): A Literature Review.

The encapsulated and noninvasive follicular variant of papillary thyroid carcinoma has been recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). These tumors demonstrate indolent behavior. This change in nomenclature will have great clinical impact by avoiding overtreatment of patients with NIFTP lesions who in the past were diagnosed with thyroid carcinoma and typically received completion thyroidectomy followed by radioactive iodine ablation. The pathologic diagnosis of NIFTP requires surgical removal of the thyroid lesion or the lobe harboring it, and thorough sampling of the complete interface between the tumor capsule and the thyroid parenchyma, to exclude foci of invasion. From a cytologic point of view, the unequivocal differential diagnosis between NIFTP and infiltrative follicular variant of papillary thyroid carcinoma in fine-needle aspiration is close to impossible based on cellular and architectural features. Therefore, use of adjunct molecular testing on fine-needle aspiration specimens may be essential for the preoperative diagnosis of low-risk tumors such as NIFTP for appropriate patient management. This review discusses and summarizes the existing known literature on molecular characteristics of NIFTP tumors, so far reported, including cases retrospectively classified or prospectively diagnosed as NIFTP. Brief reference is also made to new and promising approaches applicable to the diagnosis of this tumor.

Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors.

IMPORTANCE: Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer. OBJECTIVE: To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC. DESIGN, SETTING, AND PARTICIPANTS: International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature. MAIN OUTCOMES AND MEASURES: Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria. RESULTS: Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP. CONCLUSIONS AND RELEVANCE: Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.

BRAF V600 co-testing in thyroid FNA cytology: short-term experience in a large cancer centre in the UK.

AIMS: To ascertain whether BRAF V600 mutational analysis is useful for diagnosis of thyroid cancer in thyroid fine needle aspirate (FNA). METHODS: Over 8 months thyroid FNAs reported as Thy 3F (neoplasm possible/suggestive of follicular neoplasm), Thy4 (suspicious of malignancy) and Thy 5 (malignant) were tested for BRAF V600 mutation and managed as malignant if mutations were present. RESULTS: Of 207 FNAs from 176 patients, 5 were Thy 5, 19 Thy 4, 36 Thy 3f, 13 Thy 3a, 84 Thy 2 and 50 Thy 1. 11 Thy 3f, 15 Thy 4 and 3 Thy 5 FNAs were tested for BRAF V600 mutation. 0 Thy 3F cases, 6 Thy 4 and 1 Thy 5 (24% of the total tested) showed evidence of mutation. Four patients with BRAF V600 mutation underwent surgery to remove all thyroid tissue, two patients received a lobectomy and one patient is awaiting thyroidectomy. All patients with BRAF V600 mutation were found to have malignancy on final histology, with a diagnostic sensitivity for malignancy excluding coincidental microcarcinoma of 43% and specificity of 100%. CONCLUSIONS: BRAF V600 mutational analysis can enable single-stage total thyroidectomy for carcinoma if gene mutation is present in preoperative FNA. BRAF V600 co-testing may reduce the need for completion thyroidectomy with implied cost savings and lower patient morbidity associated with completion thyroidectomy when the cytology is inconclusive but where BRAF V600 mutation is identified in preoperative thyroid FNA.