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Background Immune checkpoint inhibitors (ICI) improve survival but cause immune-related adverse events (irAE). We sought to determine if CTCAE classification, IBD biomarkers/endoscopic/histological scores correlate with irAE colitis outcomes. Methods A dual-centre retrospective study was performed on patients receiving ICI for melanoma, NSCLC or urothelial cancer from 2012 to 2018. Demographics, clinical data, endoscopies (reanalysed using Mayo/Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores), histology (scored with Nancy Index) and treatment outcomes were analysed. Results In all, 1074 patients were analysed. Twelve percent (134) developed irAE colitis. Median patient age was 66, 59% were male. CTCAE diarrhoea grade does not correlate with steroid/ infliximab use. G3/4 colitis patients are more likely to need infliximab ( p  < 0.0001) but colitis grade does not correlate with steroid duration. CRP, albumin and haemoglobin do not correlate with severity. The UCEIS ( p  = 0.008) and Mayo ( p  = 0.016) scores correlate with severity/infliximab requirement. Patients with higher Nancy indices (3/4) are more likely to require infliximab ( p  = 0.03). Conclusions CTCAE assessment does not accurately reflect colitis severity and our data do not support its use in isolation, as this may negatively impact timely management. Our data support utilising endoscopic scoring for patients with >grade 1 CTCAE disease, and demonstrate the potential prognostic utility of objective histologic scoring.

Medical liver biopsy reporting is challenging, and maintaining competency with small case numbers is potentially difficult. This study evaluates the discrepancies identified in cases referred to a specialist centre between the specialist reports and those of the referring general departments. Fifty consecutive recently referred cases were selected, and original and final reports were compared. Discrepancies were classified as per the Royal College of Pathologists guidelines and scored for potential clinical impact. The overall rate of discrepancy was 38% with most of these due to differences in interpretation of morphology. Seventy per cent of these discrepancies were judged to have major clinical impact (26% of all referred cases). This study highlights the need for robust systems of quality control of liver biopsies in a general setting.

The presence of “clear” or lipid-rich cells within pancreatic neuroendocrine tumors is thought to be pathognomonic of von Hippel–Lindau (VHL) disease, especially in the context of multiple tumors. However, we encountered the presence of lipid-rich cells in six of 16 patients (eight microadenomas/adenomas) who had multiple endocrine neoplasia type I (MEN I). Three of the lesions (two microadenomas and one adenoma) were composed entirely of lipid-rich cells while the remaining five lesions had a component of lipid-rich cells. All lesions containing lipid-rich cells were negative for α-inhibin, but positive for chromogranin and synaptophysin. In addition, four of the eight lesions were glucagon positive. None of the patients had clinical symptoms related to hormone production. We suggest that lipid-rich cells are not reflexly indicative of VHL, and that they may be encountered in a proportion of cases of MEN I either focally or constituting the entire neuroendocrine lesion.

Digital pathology (DP) offers potential for time efficiency gains over an analog workflow however, to date, evidence supporting this claim is relatively lacking. Studies available concentrate on specific workflow points such as diagnostic reporting time, rather than overall efficiencies in slide logistics that might be expected. This is in part a result of the complexity and variation in analog working, and the challenge therefore in capturing this. We have utilized RFID technology to conduct a novel study capturing the movement of diagnostic cases within the analog pathway in a large teaching hospital setting, thus providing benchmark data for potential efficiency gains with DP. This technology overcomes the need to manually record data items and has facilitated the capture of both the physical journey of a case and the time associated with relevant components of the analog pathway predicted to be redundant in the digital setting. RFID tracking of 1,173 surgical pathology cases and over 30 staff in an analog cellular pathology workflow illustrates the complexity of the physical movement of slides within the department, which impacts on case traceability within the system. Detailed analysis of over 400 case journeys highlights redundant periods created by batching of slides at workflow points, including potentially 2–3 h for a case to become available for reporting after release from the lab, and variable lag-times prior to collection for reporting, and provides an illustration of patterns of lab and pathologist working within the analog setting. This study supports the challenge in evidencing efficiency gains to be anticipated with DP in the context of the variation and complexity of the analog pathway, but also evidences the efficiency gains that may be expected through a greater understanding of patterns of working and movement of cases. Such data may benefit other departments building a business case for DP.

ObjectiveCoeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of immunoglobulin A tissue transglutaminase (IgA tTG) and haemoglobin (Hb) data improves the interobserver agreement of diagnosis.DesignWe undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase 1, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase 2, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data.ResultsWe found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen’s kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen’s kappa coefficient of 0.67 (±0.09).ConclusionWe showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited interobserver agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the importance of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using artificial intelligence.

The COVID-19 pandemic has challenged our diagnostic services at a time when many histopathology departments already faced a diminishing workforce and increasing workload. Digital pathology (DP) has been hailed as a potential solution to at least some of the challenges faced. We present a survey of pathologists within a UK National Health Service cellular pathology department with access to DP, in which we ascertain the role of DP in clinical services during this current pandemic and explore challenges encountered. This survey indicates an increase in uptake of diagnostic DP during this period, with increased remote access. Half of respondents agreed that DP had facilitated maintenance of diagnostic practice. While challenges have been encountered, these are remediable, and none have impacted on the uptake of DP during this period. We conclude that in our institution, DP has demonstrated current and future potential to increase resilience in diagnostic practice and have highlighted some of the challenges that need to be considered.

AimsWith increasing utility of digital pathology (DP), it is important to consider the experiences of histopathologists in training, particularly in view of the varied access to DP across a training region and the consequent need to remain competent in reporting on glass slides (GS), which is also relevant for the Fellowship of the Royal College of Pathologists part 2 examination. Understanding the impact of DP on training is limited but could aid development of guidance to support the transition. We sought to investigate the perceptions of histopathologists in training around the introduction of DP for clinical diagnosis within a training region, and the potential training benefits and challenges.MethodsAn anonymous online survey was circulated to 24 histopathologists in training within a UK training region, including a hospital which has been fully digitised since summer 2020.Results19 of 24 histopathologists in training responded (79%). The results indicate that DP offers many benefits to training, including ease of access to cases to enhance individual learning and teaching in general. Utilisation of DP for diagnosis appears variable; almost half of the (10 of 19) respondents with DP experience using it only for ancillary purposes such as measurements, reporting varying levels of confidence in using DP clinically. For those yet to undergo the transition, there was a perceived anxiety regarding digital reporting despite experience with DP in other contexts.ConclusionsThe survey evidences the need for provision of training and support for histopathologists in training during the transition to DP, and for consideration of their need to maintain competence and confidence with GS reporting.

Abstract Objectives: The aim of the study was to investigate the interobserver agreement for categorical and quantitative scores of liver fibrosis. Methods: Sixty-five consecutive biopsy specimens from patients with mixed liver disease etiologies were assessed by three pathologists using the Ishak and nonalcoholic steatohepatitis Clinical Research Network (NASH CRN) scoring systems, and the fibrosis area (collagen proportionate area [CPA]) was estimated by visual inspection (visual-CPA). A subset of 20 biopsy specimens was analyzed using digital imaging analysis (DIA) for the measurement of CPA (DIA-CPA). Results: The bivariate weighted κ between any two pathologists ranged from 0.57 to 0.67 for Ishak staging and from 0.47 to 0.57 for the NASH CRN staging. Bland-Altman analysis showed poor agreement between all possible pathologist pairings for visual-CPA but good agreement between all pathologist pairings for DIA-CPA. There was good agreement between the two pathologists who assessed biopsy specimens by visual-CPA and DIA-CPA. The intraclass correlation coefficient, which is equivalent to the κ statistic for continuous variables, was 0.78 for visual-CPA and 0.97 for DIA-CPA. Conclusions: These results suggest that DIA-CPA is the most robust method for assessing liver fibrosis followed by visual-CPA. Categorical scores perform less well than both the quantitative CPA scores assessed here.

Needle core biopsy is a key tool in diagnosis and assessment of many medical liver diseases, but there is evidence that the combination of small size of the specimen obtained and the patchy nature of many of these diseases can result in misdiagnosis or incorrect staging. The Royal College of Pathologists has therefore published guidelines for assessment of adequacy. To assess whether these guidelines were being observed, we reviewed cases reported in our department over a 15-year period. Results showed that only 19.8% of cores would be considered adequate, 56.4% were suboptimal and 23.8% were inadequate. We discuss the issues around recommendations on the minimum size of liver biopsies, potential factors limiting biopsy size and whether further refinement of the guidelines for adequacy is required.