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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 the Italian (TIR). A fourth system, the Japanese terminology, has diagnostic categories identical to TBS but with different nomenclature. The aim of this review is to discuss the strengths and weaknesses of the TBS, UK RCPath and the TIR systems and to make the case for international terminology harmonisation and standardisation.

BACKGROUND: To the authors' knowledge, the impact of the coronavirus disease 2019 (COVID-19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported. METHODS: Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID-19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine-needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta-analytical approach. RESULTS: Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%-98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%-7.35%) in the malignancy rate in nongynecological samples during the COVID-19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%-9.27%). CONCLUSIONS: The COVID-19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted. ispartof: CANCER CYTOPATHOLOGY vol:128 issue:12 pages:885-894 ispartof: location:United States status: published

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.

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.

This review article summarises systems for categorisation of diagnostic errors in pathology and cytology with regard to diagnostic accuracy and the published information on human factors in pathology to date. A 12 point event-based checklist for error in diagnostic accuracy in histopathology and cytopathology is proposed derived from Dupont’s ‘Dirty Dozen’ human factor checklist, as utilised in the aerospace industry for aircraft maintenance. This human factor checklist comprises 12 human factors implicated in defects in aircraft maintenance; (i) failure of communication, (ii) complacency, (iii) lack of knowledge, (iv) distractions, (v) lack of teamwork, (vi) fatigue, (vii) lack of resources, (viii) pressure, (ix) lack of assertiveness, (x) stress, (xi) norms, and (xii) lack of awareness. The accompanying article explains practical examples of how each of these 12 human factors may cause errors in diagnostic accuracy in pathology. This checklist could be used as a template for analysis of accuracy and risks of diagnostic error in pathology either retrospectively ‘after the event’ or prospectively at the time of diagnosis. There is a need for further evaluation and validation of this proposed 12 point human factor checklist and similar systems for categorisation of diagnostic errors and diagnostic accuracy in pathology based on human factor principles.

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

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.

Background The aims of this study were to compare neoplasia detection rates for nontargeted biopsies (Seattle protocol) versus acetic acid-targeted biopsies (Portsmouth protocol) during Barrett’s surveillance and to explore feasibility, patient/clinician experience, acceptance, and barriers/enablers to study participation and implementation of the acetic acid technique. Methods This was a mixed-methods feasibility study including a pilot multicenter, randomized, crossover trial with qualitative interviews. Patients under Barrett’s surveillance with no history of neoplasia were included. Patients underwent two endoscopies, one with each protocol, 8 weeks apart. Outcomes included recruitment and retention rates, neoplasia yield, and number of biopsies. Results 200 patients were recruited from 6 centers, and 174 (87.0 %) underwent both procedures. Neoplasia prevalence was 4.7 % (9/192). High grade dysplasia and cancer were detected with both protocols. Five low grade dysplasias were detected (two with acetic acid, four with nontargeted biopsies; one lesion was detected with both techniques). A total of 2139 biopsies were taken in the nontargeted arm and 226 in the acetic acid arm. Both patients and clinicians found the acetic acid technique acceptable. Based on these data, a noninferiority, tandem, crossover trial would require an estimated 2828 patients. Conclusions We demonstrated the feasibility of performing a crossover endoscopy trial in Barrett’s surveillance. Low neoplasia yield makes this design necessary and qualitative results demonstrated patient and clinician acceptance. The reduced numbers of biopsies suggest that the acetic acid technique could result in cost savings, providing the lack of missed pathology can be proven in a fully powered definitive trial.

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.

This study assesses the role of [18F] FDG PET/CT, fine needle aspiration (FNA) cytology and ultrasound in the 1&ndash, 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&mdash, 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 H&uuml, rthle 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 H&uuml, rthle 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 H&uuml, rthle cell/oncocytic lesions, typically reported as follicular neoplasm or suspicious for a follicular neoplasm, H&uuml, rthle 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.

The role of human factors (HFs) in medical error is now widely acknowledged, although there are few publications that deal with pathology-specific HF issues. A definition of HF that is widely accepted is as follows: ‘ environmental, organisational and job factors in human and individual characteristics which influence behaviour at work in a way which can affect health and safety’ .1 HF analysis has been widely applied in aviation and aerospace industries but has been increasingly seen as important in medicine, particularly in critical care and acute medical settings to explain and reduce rates of clinical error and improve decision-making in areas that are of high clinical risk.2–4 There has been little discussion of the role of HF in diagnostic specialties such as cytology, pathology or radiology. Published HF studies in diagnostic specialties have primarily addressed …

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.

Background and study aims Barrett’s esophagus is a potentially pre-cancerous condition, affecting 375,000 people in the UK. Patients receive a 2-yearly endoscopy to detect cancerous changes, as early detection and treatment results in better outcomes. Current treatment requires random mapping biopsies along the length of Barrett’s, in addition to biopsy of visible abnormalities. As only 13 % of pre-cancerous changes appear as visible nodules or abnormalities, areas of dysplasia are often missed. Acetic acid chromoendoscopy (AAC) has been shown to improve detection of pre-cancerous and cancerous tissue in observational studies, but no randomized controlled trials (RCTs) have been performed to date. Patients and methods A “tandem” endoscopy cross-over design. Participants will be randomized to endoscopy using mapping biopsies or AAC, in which dilute acetic acid is sprayed onto the surface of the esophagus, highlighting tissue through an whitening reaction and enhancing visibility of areas with cellular changes for biopsy. After 4 to 10 weeks, participants will undergo a repeat endoscopy, using the second method. Rates of recruitment and retention will be assessed, in addition to the estimated dysplasia detection rate, effectiveness of the endoscopist training program, and rates of adverse events (AEs). Qualitative interviews will explore participant and endoscopist acceptability of study design and delivery, and the acceptability of switching endoscopic techniques for Barrett's surveillance. Results Endoscopists’ ability to diagnose dysplasia in Barrett’s esophagus can be improved. AAC may offer a simple, universally applicable, easily-acquired technique to improve detection, affording patients earlier diagnosis and treatment, reducing endoscopy time and pathology costs. The ABBA study will determine whether a crossover “tandem” endoscopy design is feasible and acceptable to patients and clinicians and gather outcome data to power a definitive trial.

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 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.

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.

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.

The main goals of the symposium entitled “Thyroid Fine-Needle Aspiration: New Classifications and New Interpretations” are the presentation and discussion of the thyroid fine-needle aspiration terminologies most commonly used, an analysis of their respective advantages and limitations, and a statement of how ancillary techniques could reduce the number of indeterminate cases.

Introduction Barrett’s surveillance traditionally requires mapping biopsies to identify neoplasia. Acetic acid (AA) allows only targeted biopsies, potentially reducing the number of biopsies required. This study aims to compare neoplasia detection with AA targeted biopsies and protocol guided non-targeted biopsies during Barrett’s surveillance. Methods Multicentre randomised crossover feasibility study in UK secondary care. Patients under surveillance for Barrett’s metaplasia (>2 cm) with no history of dysplasia or cancer were recruited. All patients underwent two gastroscopies 8 weeks apart, one with AA guided biopsy of abnormal areas only (Portsmouth Protocol) and one with non-targeted mapping biopsies (Seattle Protocol). Neoplasia yield (low grade dysplasia LGD, high grade dysplasia (HGD) and cancer) from each strategy was evaluated and the number of biopsies recorded. Results 200 patients recruited from 6 centres. Mean age 66 years. 145 were male. Mean length C4M6. 175 patients completing both procedures. The prevalence of LGD, HGD and cancer was 11/192 (5.8%). All HGD and cancer was found with both protocols and confirmed with definitive treatment. One LGD was found with Portsmouth protocol not found with Seattle. 5 LGD were found with Seattle protocol not found with Portsmouth. This difference was not significant (p=0.2188), and on follow up gastroscopy no neoplastic changes were found in any of the LGD cases. 2139 biopsies were taken using Seattle protocol at a cost of £1 25 987 (306 biopsies per neoplasia, £18,023). 226 biopsies with Portsmouth Protocol at a cost of £13 311 (75 biopsies per neoplasia, £6,656) a 4 fold difference. In terms of HGD/cancer, 1070 biopsies/neoplasia found using Seattle protocol and 113 biopsies/neoplasia using Portsmouth Protocol, a 9.5 fold difference. Conclusions This is the first RCT comparing these techniques. No HGD or cancer was missed with either technique. There was a 4 fold reduction in biopsies per neoplasia detected with Portsmouth compared to Seattle protocol and a 9.5 fold difference when restricted to high risk neoplasia. If implemented nationally then this could lead to a massive reduction in histopathology work load and costs. LGD remains controversial and we believe inflammation could have resulted in false positive LGD as subsequent OGD and biopsies did not reveal any LGD. This feasibility data would support a definitive trial of AA targeted biopsies in a surveillance population.

In this paper, we aim to focus on false positive results in the evaluation of thyroid aspirations, covering cystic, inflammatory, follicular and oncocytic lesions, papillary carcinoma, and medullary carcinoma of thyroid. The recently described entity noninvasive follicular thyroid neoplasm with papillary-like nuclear features is also discussed detailing the impact of its introduction on the sensitivity and specificity of thyroid FNA, as well as the use of molecular tests for diagnostics. Medicolegal issues in relation to current practice in English law are also described. This paper review the main causes of false positives in thyroid FNA and give some tips in how to avoid these mistakes.

This review summarises molecular pathological techniques applicable to thyroid FNA. The molecular pathology of thyroid tumours is now fairly well understood. Molecular methods may be used as a rule-in test for diagnosis of malignancy in thyroid nodules, eg BRAF V600E point mutation, use of a seven-gene mutational panel (BRAF V600E, RAS genes, RET/PTC or PAX8/PPARG rearrangement), or as a comprehensive multigene next-generation sequencing panel, eg ThyroSeq v2. Molecular methods can also be applied as rule-out tests for malignancy in thyroid nodules, eg Afirma or ThyroSeq v2 or as markers of prognosis, eg TERT promoter mutation or other gene mutations including BRAF V600E, TP53 and AKT1, and as tests for newly defined tumour entities such as non-invasive follicular thyroid neoplasm with papillary like nuclei, or as a molecular marker(s) for targeted therapies. This review describes practical examples of molecular techniques as applied to thyroid FNA in routine clinical practice and the value of molecular diagnostics in thyroid FNA. It describes the range of molecular abnormalities identified in thyroid nodules and thyroid cancers with some practical applications of molecular methods to diagnosis and prognosis of thyroid nodules and thyroid cancer.

The histopathological features of thyroid cancers can be used to risk stratify patients, allowing prognostication and treatment decisions. A detailed accurate histological assessment by experienced pathologists working within a multidisciplinary context is crucial. Experience is also essential for interpretation of preoperative thyroid cytology specimens, which can be challenging. There is now more international harmonisation of numerical reporting systems for thyroid cytology. Understanding of the molecular basis of thyroid cancer has increased dramatically in recent years. Preoperative molecular pathology testing, when available, can refine cytological diagnosis to rule in or out for surgery, as well as assisting prognostication and enabling targeted treatment for thyroid tumours.

Worldwide the rising incidence of cancer is attributed to ageing populations, environmental and lifestyle factors, and increased cancer surveillance. Cancer surveillance leads to increased early detection of indolent cancers, and in some cases to cancer ‘overdiagnosis’.1 In the thyroid, the increased incidence of thyroid cancer and cancer detection is primarily due to widespread use of thyroid ultrasound.2 This excess of newly diagnosed thyroid cancers occurs almost entirely because of greater detection of papillary thyroid cancers, a tumour which under the microscope shows a characteristic papillary growth pattern together with typical nuclear features. Follicular variant of papillary thyroid carcinoma (FVPTC) is one of two major subtypes of papillary thyroid cancer. The encapsulated type of FVPTC (eFVPTC), a tumour that under the microscope shows no invasion of surrounding thyroid, blood vessels or lymphatics, has increased in incidence 2–3 times over the last 20–30 years. eFVPTC is now estimated …

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.

The overall interobserver reproducibility of thyroid fine-needle aspiration (FNA) has not been comprehensively assessed. A blinded 6-rater interobserver reproducibility study was conducted of 200 thyroid FNA cases using the UK System, which is similar to The Bethesda System for Reporting Thyroid Cytology: Thy1, nondiagnostic; Thy2, nonneoplastic; Thy3a, atypia, probably benign; Thy3f, follicular lesion; Thy4, suspicious of malignancy; and Thy5, malignant. There was good interobserver agreement for the Thy1 (κ = 0.69) and Thy5 (κ = 0.61), moderate agreement for Thy2 (κ = 0.55) and Thy3f (κ = 0.51), and poor agreement for Thy3a (κ = 0.11) and Thy4 (κ = 0.17) categories. Combining categories implying surgical management (Thy3f, Thy4, and Thy5) achieved good agreement (κ = 0.72), as did combining categories implying medical management (Thy1, Thy2, and Thy3a; κ = 0.72). The UK thyroid FNA terminology is a reproducible and clinically relevant system for thyroid FNA reporting. This study demonstrates that international efforts to harmonize and refine thyroid cytology classification systems can improve consistency in the clinical management of thyroid nodules.

BACKGROUND Although fine-needle aspiration (FNA) of the thyroid is the key preoperative investigation of thyroid lesions, there are overlaps in the criteria for diagnosis of certain lesions, particularly important among which are those for follicular neoplasms. A proposal for a 5-category working system for thyroid FNA diagnosis is presented, devised using clearly defined diagnostic guidelines with a prospective 2-year evaluation in 1 center. METHODS The results of FNA of 156 patients with nodular thyroid lesions are presented. All patients were observed over a 2-year period in a multidisciplinary thyroid clinic. In some cases, the aspirates were repeated before excision of the lesion. The results of the FNA are classified by worst category for each patient, according to a 5-category scheme: THY1: inadequate; THY2: benign; THY3: indeterminate; THY4: suspicious lesion; THY5: malignant. RESULTS Seventy-five of the 156 patients (48.1%) proceeded to excision, of these 50 (67%) showed multinodular goiter or adenomatoid nodule within a goiter, 7 (9.3%) showed evidence of Hashimoto thyroiditis or lymphocytic thyroiditis alone, 1 (1.3%) showed evidence of Reidel thyroiditis, and 1 (1.3%) showed evidence of a parathyroid cyst. Eight patients (11%) showed evidence of follicular adenoma, and 5 patients (6.6%) showed papillary carcinoma; 1 (1.3%) showed follicular carcinoma, and 2 (2.7%) showed lymphoproliferative disease. There was a significant difference in the number of benign as compared with neoplastic thyroid lesions excised in the indeterminate (THY3) (2 of 13 [15%]) as compared with the suspicious categories (THY4) (10 of 24 [42%]), (P = 0.05). Although no false-negative FNAs were identified in this series, there was 1 false-positive (THY5) FNA. CONCLUSIONS The use of an indeterminate (THY3) category is helpful because it improves the diagnostic efficacy of thyroid FNA. The indeterminate (THY3) category is clinically useful and may markedly reduce or eliminate false-negative FNA in many patients with thyroid nodules. Cancer (Cancer Cytopathol) 2000;90:239–44. © 2000 American Cancer Society.

A series of 346 patients with primary operable breast cancer and a series of 145 patients with advanced breast cancer were investigated for c-erbB-3 protein expression using the monoclonal antibody RTJ1. Formalin-fixed, paraffin-embedded tumour samples were stained using a standard immunochemical method and staining was assessed on a four-point scale. The study aimed to observe the expression of the c-erbB-3 protein and investigate any relationship between expression and established prognostic indicators and prognosis. In both the primary and advanced series breast tumour tissue was found to stain heterogeneously for c-erbB-3. The staining was observed to be predominantly cytoplasmic and the majority of tumours exhibited moderate positivity. However, 15% and 35% of cases in the primary operable and advanced series respectively displayed strong positive staining. No significant difference was found between the staining in the primary and advanced series. In the primary operable breast cancers, no significant associations were demonstrated with overall survival, disease-free interval, regional recurrence, the presence of distant metastases, age, menopausal status, oestrogen receptor status, histological grade, lymph node stage, vascular invasion and c-erbB-2 protein expression. However, a significant association was seen between the degree of c-erbB-3 immunoreactivity and both tumour size (P < 0.01) and tumour type prognostic group (P = 0.05). No overall association with local recurrence was seen when the four groups of c-erbB-3 expression were analysed (P = 0.12), but when those tumours showing no or weak staining were compared with those showing moderate and strong immunoreactivity it was seen that the latter were significantly more likely to develop local recurrence (P = 0.03). In the series of patients with advanced disease, no significant associations were demonstrated with survival, UICC criteria, age, menopausal status, oestrogen receptor status, histological grade, c-erbB-2 status or the presence of vascular invasion. In conclusion this study found variable expression of c-erbB-3 protein in human breast carcinoma and an association with some recognised prognostic factors in those patients with primary operable breast carcinoma. It seems, however, unlikely that c-erbB-3 protein expression will emerge as a powerful enough prognostic factor to be of value in clinical practice. Images Figure 1 Figure 2

Background & Aims Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett's esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. Methods We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. Results Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. Conclusions We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.

The expression of oestrogen receptor protein (ER) was examined in 151 cases of symptomatic or screening detected pure ductal carcinoma in situ (DCIS) of the breast by immunocytochemical assay (ERICA), in formalin-fixed paraffin-embedded tissue, with the monoclonal antibody H 222 (Abbott). Forty-eight tumours (31.8%) of cases were ER positive. Twenty-seven (17.9%) of cases showed high level ER expression and 21 (13.9%) of cases showed low level ER immunoreactivity. Significant associations of positive tumour ER immunoreactivity and non-comedo architecture chi 2 = 6.76; (d.f. = 1): P < 0.001, small cell size chi 2 = 4.49; (d.f. = 1): P = 0.034, higher S-phase fraction chi 2 = 4.71; (d.f. = 1): P = 0.03 and lack of c-erbB-2 protein overexpression chi 2 = 7.96; (d.f. = 1): P < 0.01 were identified. No significant associations of ER expression and patient age, histological grade of necrosis in DCIS, or DNA ploidy were found. ER expression is detectable in less than one third of symptomatic and screening detected cases of DCIS, implying that endocrine therapy of DCIS may be a more appropriate form of management for morphological subtypes of DCIS which show higher rates of oestrogen receptor expression, particularly those of non-comedo and small cell type. Images Figure 1

We describe the case of a patient with Rett syndrome, a syndrome characterized by progressive infant encephalopathy, developmental delay, dementia, autism, ataxia, microcephaly, spastic paraparesis, and autonomic neuropathy with constipation. At colonoscopy, multiple foci of tiny white, sessile, polypoid lesions were seen throughout the colon and rectum, mimicking the appearances of small hyperplastic or adenomatous polyps, associated with generalized melanosis coli. This is the first case to our knowledge describing melanosis coli in a patient with Rett syndrome. As melanosis pigment deposition is characteristically not seen in lymphoid tissue, the lymphoid tissue was identifiable at endoscopy as multiple white nodules mimicking generalized colonic polyposis throughout the colon. We discuss the likely mechanisms of lymphoid hyperplasia and coexistent melanosis coli in Rett syndrome.

Background & Aims Diagnosis of Barrett's neoplasia requires collection of large numbers of random biopsy samples; the process is time consuming and can miss early-stage cancers. We evaluated the role of acetic acid chromoendoscopy in identifying Barrett's neoplasia. Methods Data were collected from patients with Barrett's esophagus examined at a tertiary referral center, between July 2005 and November 2008 using Fujinon gastroscopes and EPX 4400 processor (n = 190). All procedures were performed by a single experienced endoscopist. Patients were examined with white light gastroscopy and visible abnormalities were identified. Acetic acid (2.5%) dye spray was used to identify potentially neoplastic areas and biopsy samples were collected from these, followed by quadrantic biopsies at 2 cm intervals of the remaining Barrett's mucosa. The chromoendoscopic diagnosis was compared with the ultimate histological diagnosis to evaluate the sensitivity of acetic acid chromoendoscopy. Results Acetic acid chromoendoscopy had a sensitivity of 95.5% and specificity of 80% for the detection of neoplasia. There was a correlation between lesions predicted to be neoplasias by acetic acid and those diagnosed by histological analysis (r = 0.98). There was a significant improvement in the detection of neoplasia using acetic acid compared with white light endoscopy (P = .001). Conclusions Analysis of this large series showed that acetic acid-assisted evaluation of Barrett's esophagus detects neoplasia better than white light endoscopy, with sensitivity and specificity equal to that of histological analysis.

The expression of p53 protein, oestrogen receptor protein, epidermal growth factor receptor (EGFR) and overexpression of the c-erbB-2 oncoprotein was examined in a series of 149 primary symptomatic breast carcinomas. Expression of p53 was present in 62 of 146 cases (42.5%) of the invasive carcinoma and one of three cases (33.3%) of ductal carcinoma in situ (DCIS) examined. Statistical associations of tumour oestrogen receptor positivity and lack of p53 protein expression, chi 2 = 19.78 (d.f. = 1), P less than 0.001, positive tumour p53 status and poor tumour grade; chi 2 = 14.1 (d.f. = 2), P less than 0.001, EGFR expression chi 2 = 7.07, (d.f. = 1), P less than 0.01 and tumour c-erbB-2 protein overexpression; chi 2 = 4.61 (d.f. = 1), P = 0.032 were identified. Expression of p53 is rare in invasive lobular carcinoma of classical type (8.3% of cases examined) in contrast to other common types of mammary carcinoma. Non-significant trends of p53 protein expression and increased regional tumour recurrence; chi 2 = 3.20 (d.f. = 1), P = 0.074 and also poorer patient survival; chi 2 = 3.76 (d.f. = 1), P = 0.053 were identified. p53 protein expression is a common event in human breast cancer and is present in both DCIS and invasive mammary carcinoma. Abnormal expression of p53 protein is a feature of both in situ and invasive breast carcinoma, implying that the abnormal p53 protein expression may be implicated in the early stages of mammary carcinoma progression. Images Figure 1

Aim —To determine the frequency of skip lesions in an unselected series of temporal artery biopsies and compare the results with other series. Methods —The study was a retrospective review of 102 consecutive temporal artery biopsies taken in a five year period (1992–1997) in one large hospital. Results —35 cases (34.3%) showed evidence of active cranial vasculitis with pathological evidence of inflammation of the intima or media, with or without giant cells. Three of these cases (8.5%) showed apparent skip lesions: normal intima, media, and adventitia in one segment while in other segments there was clear evidence of active vasculitis. Immunocytochemical stains for leucocyte common antigen (LCA) and CD15 were helpful in identifying the absence of intimal or medial inflammatory cell infiltrates within skip lesions. Skip lesions have been described in up to 28.3% of cases in some series, while others have not found evidence of skip lesions or have identified them in a much smaller percentage of cases. Conclusions —In this series skip lesions were relatively rare, accounting for 8.5% of cases of active vasculitis. The degree of inflammation in temporal arteritis is discontinuous. Immunostaining for inflammatory cells, for example LCA and CD15, may be helpful in identifying the presence of an inflammatory cell infiltrate in skip lesion segments of the temporal artery.

Objectives: Current models of clonal expansion in human Barrett’s oesophagus are based upon heterogenous, flow-purified biopsy analysis taken at multiple segment levels. Detection of identical mutation fingerprints from these biopsy samples led to the proposal that a mutated clone with a selective advantage can clonally expand to fill an entire Barrett’s segment at the expense of competing clones (selective sweep to fixation model). We aimed to assess clonality at a much higher resolution by microdissecting and genetically analysing individual crypts. The histogenesis of Barrett’s metaplasia and neo-squamous islands has never been demonstrated. We investigated the oesophageal gland squamous ducts as the source of both epithelial sub-types.\ud \ud Methods: Individual crypts across Barrett’s biopsy and oesophagectomy blocks were dissected. Determination of tumour suppressor gene loss of heterozygosity patterns, p16 and p53 point mutations were carried out on a crypt-by-crypt basis. Cases of contiguous neo-squamous islands and columnar metaplasia with oesophageal squamous ducts were identified. Tissues were isolated by laser capture microdissection and genetically analysed.\ud \ud Results: Individual crypt dissection revealed mutation patterns that were masked in whole biopsy analysis. Dissection across oesophagectomy specimens demonstrated marked clonal heterogeneity, with multiple independent clones present. We identified a p16 point mutation arising in the squamous epithelium of the oesophageal gland duct, which was also present in a contiguous metaplastic crypt, whereas neo-squamous islands arising from squamous ducts were wild-type with respect to surrounding Barrett’s dysplasia.\ud \ud Conclusions: By studying clonality at the crypt level we demonstrate that Barrett’s heterogeneity arises from multiple independent clones, in contrast to the selective sweep to fixation model of clonal expansion previously described. We suggest that the squamous gland ducts situated throughout the oesophagus are the source of a progenitor cell that may be susceptible to gene mutation resulting in conversion to Barrett’s metaplastic epithelium. Additionally, these data suggest that wild-type ducts may be the source of neo-squamous islands.

Introduction Endoscopic therapy of Barrett9s Oesophagus (BE) with high grade dysplasia (HGD) and/or intramucosal cancer (IMC) by endoscopic mucosal resection (EMR) or radiofrequency ablation (RFA) is a recognised alternative to surgical resection. The aim of this study is to compare the outcomes of two radically different endotherapy approaches of focal EMR of neoplastic foci followed by RFA versus focal EMR followed by more radical EMR as necessary. Methods Patients referred with Barrett9s HGD and/or IMC where treated with either focal EMR to visibly elevated lesions with subsequent intensive RFA of residual BE (Group A) or by a protocol of focal EMR to eradicate neoplasia (Group B). There were 37 patients (83% males) in Group A with a mean age of 66 years and a mean Barrett9s segment length was 6.9 cms (1–14). In Group B we had 44 patients (90% males) with a mean age of 68 years and mean segment length of 5.0 cms (2–15). All patients were followed up in a rigorous endoscopic programme. The mean duration of follow-up was 23 months in Group A and 32 months in Group B. Results In Group A total of 23 EMR procedures were performed with a mean of 0.6 sessions per patient. Treatment then proceeded with a RFA-intensive protocol such that a total of 79 ablations were administered with a mean of 2 sessions per patient. Thereafter, Nd:YAG laser was applied to residual islands less than 0.5 cm in length. In Group B a total of 72 EMR procedures were performed with a mean of 1.6 sessions per patient. In this group RFA was employed in 6 patients only. No significant post-procedural complications were identified in these patients. Eradication of neoplasia (HGD and IMC) was achieved in 35/37 patients (95%) in Group A and 41/41 (100%) in Group B. Furthermore, during this relatively short follow-up period eradication of Barrett9s oesophagus was achieved in 31/37 of patients (84%) in Group A. Conclusion This is the largest reported series demonstrating similarly excellent outcomes for two radically different endoscopic approaches for the ablation of Barrett9s neoplasia. In addition, the RFA-intensive strategy has proved effective in eradicating residual Barrett9s oesophagus. These observations call for a randomised controlled trial comparing these two strategies in order to identify the most cost-effective option.

Introduction Endoscopic ultrasound (EUS) guided sampling of advanced malignant pancreatic lesions is increasingly being performed in order to confirm malignancy prior to chemotherapy and or treatment. Meta-analysis of 33 studies examining solid lesion EUS FNA tissue acquisition in 4984 patients showed a pooled sensitivity of 85%, increasing to 91% if suspicious atypia was included 1 . Higher sensitivities have been demonstrated in large volume single operator centres where sensitivities of 92–97% 2,3 have been reported. The four Wessex EUS centres all work from a regional HPB MDT, where pancreatic cases are discussed and EUS procedures requested. Each centre has two EUS operators, performing between 148 and 214 cases per annum. Additionally the regional EUS endoscopists, pathologists and biomedical technicians meet three times a year for EUS network meetings to audit outcomes and review practice standards. In 3 of the 4 centres cytopathology staff are present in the endoscopy room to provide rapid on site evaluation and confirm adequate sample cellularity and give a preliminary diagnosis. Methods Each centre prospectively audited the results of EUS guided biopsy of suspected malignant solid pancreatic lesions over a 6 month period from 1.7.13 to 31.12.13. From this data the true positive rate was calculated to determine if such networking produced results comparable to large volume single centres. Results There was a regional sensitivity of 96%. The majority of lesions were adenocarcinoma but other results included: 1 lymphoma, 8 neuroendocrine tumours, 1 renal cell cancer metastasis. Conclusion A regional sensitivity of 96% is comparable with results from a single large volume UK EUS centre. This demonstrates that smaller volume centres working within a regional network can achieve similar standards to high volume centres. References 1 Hewitt et al. GI Endoscopy 2012; 75 (2):319–331 2 Cherian et al. HPB 2010; 12 (6):389–395 3 Manzia et al. Annals of RC Surgeons England 2010; 92 (4):295–301 Disclosure of Interest None Declared.

The expression of the p53 and Rb1 proteins was examined in an unselected consecutive series of 250 primary operable colorectal carcinomas with a mean follow-up of 4.3 years (range 43-77 months). The overall cancer-specific mortality was 34.8%, with 87 cancer deaths and 35 deaths as the result of other causes. Expression of p53 protein was identified in 152 of 250 (60.8%) cases, with expression of Rb1 protein in 207 of 250 (82.8%) cases. There was no association of p53 or Rb protein expression with patient age, sex, tumour site, tumour size, tumour type, tumour grade, peritumoral fibrosis, tumour lymphocytic infiltrate, nature of the tumour margin, extramural vascular invasion, number of lymph nodes or high apical lymph node involved or local peritoneal infiltration by tumour, Dukes' stage or Jass group. There was no difference in overall survival or recurrence-free survival for those cases that showed p53 expression or Rb1 protein expression compared with those cases showing absence of p53 or Rb1 protein expression, although patients with tumours showing aberrant (reduced) Rb1 protein expression demonstrated shorter recurrence-free survival and overall survival. The effect of 'aberrant' Rb1 protein expression and shorter recurrence-free and overall survival did not, however, achieve independent statistical significance. The results from this study would suggest that expression of p53 and Rb1 proteins does not appear be useful in determining the prognosis of operable colorectal cancer. Images Figure 1 Figure 3

Introduction Cost effectiveness of Barrett’s surveillance has recently being questioned due to the low neoplasia detection rate. Acetic acid chromoscopy (AAC) has been shown to improve neoplasia detection in Barrett’s oesophagus but not in surveillance population. The aim of this study is to compare the effectiveness of AAC with Cleveland clinic protocol (2 cm quadrantic) guided biopsies at detecting high risk neoplasia during Barrett’s surveillance. Methods Prospective Cohort study comparing two different Barrett’s surveillance strategies. All patients who underwent Barrett’s surveillance between 2008–12 were recorded on a Barrett’s database. All neoplasias were independently reviewed by two GI Pathologists. Barrett’s surveillance patients were randomly allocated to acetic acid chromoscopy lists (cohort B) or protocol guided biopsy (Cohort A) lists. AAC involved targeted biopsy of area of concern & 3 additional biopsies from lower, middle & top end of Barrett’s. Protocol guided were taken as quadrantic biopsies every 2 cm & any visible abnormality. Fisher’s exact test was used for statistical analysis. Results N = 982 Barrett’s surveillance gastroscopy between 2008–12. Median age was 66 years & Median Barrett’s length was 4.5 cm (range: 1–20). Male: Female = 3.3:1 . Protocol guided Cohort A N = 655/982(66.7%). 7/655 (1%) patients were found to have high grade dysplasia (HGD) & 3/655(0.4%) had T-1 cancers with an overall high risk neoplasia detection rate of 10/655(1.5%). Acetic acid Cohort B N = 327/982(33.2%). 18/327(5.5%) patients were found to have HGD & 14/327(4.2%) had T-1 cancers with an overall high risk neoplasia detection rate of 32/327(9.7%). This shows a statistically significant 6.5 fold (p = 0.0001) increased detection of high risk neoplasia with acetic acid guided biopsies as compared to protocol guided biopsies in Barrett’s surveillance. Conclusion This is the first report from a large exclusively Barrett’s surveillance population. Our data demonstrates that acetic acid chromoscopy significantly (6.5 fold) improves the detection of high risk neoplasia in Barrett’s surveillance as compared to the current standard of 2 cm quadrantic biopsies. AAC also results in significantly less number of biopsies taken so overall it will be very cost-effective. This questions the validity of the current standard of non targeted protocol guided biopsies during Barrett’s surveillance. Disclosure of Interest None Declared

Editor,—We noted in the guidelines for the management of iron deficiency anaemia ( Gut 2000; 46 (suppl IV):iv1–iv5) that it is recommended that small bowel biopsies should be taken in all patients presenting with iron deficiency anaemia. This has been the subject of much discussion between the pathology department and ours recently. Antiendomysial antibodies (EMAs) give at best close to 100% sensitivity and specificity1 2 although other studies suggest around 95% sensitivity with much lower values for specificity depending on the exact criteria for gluten sensitive enteropathy adopted.3 4 This has been discussed at both the recent British Society of Gastroenterology (BSG) meeting (Ciclitira PJ. State of the Art Lecture: Coeliac Disease—pathogenesis and prevention . BSG Annual Meeting, March 2000) and the American Gastroenterology Association (AGA) meeting (Schuppan D. Sprue: new insights into pathogenesis and management . AGA Postgraduate Course, May 2000). A possible reason for these differences in sensitivity and specificity in the literature is that standards vary between different pathology departments in the techniques of anti-EMA assessment.5Most hospital biochemistry departments perform the tests using monkey oesophagus tissue bought from commercial suppliers; on the market at present there are 19 different suppliers of monkey oesophagus and 23 different suppliers of the enzyme immunoassay (EIA) (United Kingdom External …