搜索结果：Archives of pathology & laboratory medicine

Pathology laboratories are currently facing remarkable issues in the management of their archives due to the ongoing increase in the production of formalin-fixed paraffin-embedded (FFPE) blocks, which is often coupled with inadequate spatial and environmental storing conditions. The manual process of storage and retrieving further increases the likelihood of human-based mistakes, wastes professionals' working time, and, ultimately, widens reports signing turn-around times. In the present work, we outline the strategies underlying the development of an automated archive at the pathology services of the University of Modena. The proposed project relies on the controlled interaction of a mechanic robotic arm with racks and shelves in a fully traced manner, driven by the integration with the local laboratory information system (LIS). This automated archive aims to significantly improve the time-saving of laboratory professionals and standardize the storage of FFPE samples both before and after the pathology diagnosis is rendered. The system's modularity suits the needs and spaces of the different institutions, opening novel strategies in archiving thanks to its connection with the LIS and integration with artificial intelligence algorithms.

-Prior to 1900, laboratory tests were simple enough to be performed by clinicians on the wards and most pathologists were academicians with little involvement in patient care issues. In the next 2 decades, laboratory test menus expanded rapidly and the increasing complexity of the tests created a potential niche for clinical pathologists (ie, pathologists providing patient-oriented anatomic and clinical pathology services). In the late 1910s and early 1920s, most of these services were provided by mail-order commercial laboratories or state public health laboratories rather than by hospital-based pathologists. -To describe the political events in the 1920s that would drastically alter the practice of pathology and laboratory medicine and that would have been important to the discipline at the time the Archives of Pathology and Laboratory Medicine was being conceived and first published. -Available primary and secondary historical sources were reviewed. -In the 1920s, clinical pathologists organized, forming the American Society of Clinical Pathologists, and took on the powerful American Medical Association for permitting advertisements by private laboratories in the pages of the Journal of the American Medical Association that listed test prices as if these were commodities. They found a strong partner in the American College of Surgeons, which was attempting to elevate surgical practice by creating minimum standards for hospitals. Through this symbiotic relationship, hospital-based practice was firmly established and the commercial laboratory model faltered. -The Roaring Twenties was the time when the practice of pathology and laboratory medicine evolved into what we recognize today.

Pathology education is a core component of medical training, and its literature is critical for refining educational modalities. We performed a cross-sectional bibliometric analysis to explore publications on pathology education, focusing on new medical education technologies. The analysis identified 64 pathology journals and 53 keywords. Relevant articles were collected using a web application, PaperScraper, developed to accelerate literature search. Citation data were collected from multiple sources. Descriptive statistics, with time period analysis, were performed using Microsoft Excel and visualised with Flourish Studio. Two article groups were further investigated with a bibliometric software, VOSViewer, to establish co-authorship and keyword relationships. 8946 citations were retrieved from 905 selected articles. Most articles were published in the last decade (447, 49.4%). The top journals were Archives of Pathology & Laboratory Medicine (184), Human Pathology (122) and the American Journal of Clinical Pathology (117). The highest number of citations was found for Human Pathology (2120), followed by Archives of Pathology & Laboratory Medicine (2098) and American Journal of Clinical Pathology (1142). Authors with different backgrounds had the greatest number of articles and citations. 12 co-authorship, 3 keyword and 8 co-citation clusters were found for the social media/online resources group, 8 co-authorship, 4 keyword and 7 co-citation clusters for the digital pathology/virtual microscopy/mobile technologies group. The analysis revealed a significant increase in publications over time. The emergence of digital teaching and learning resources played a major role in this growth. Overall, these findings underscore the transformative potential of technology in pathology education.

Atypical intraductal proliferation (AIP) of the prostate is characterized by morphologic features exceeding that of high-grade prostatic intraepithelial neoplasia but not meeting strict diagnostic criteria for intraductal carcinoma. We examined the clinical significance of AIP in biopsy specimens. Patients with AIP diagnosed on biopsy were identified from surgical pathology archives. Initial biopsies, any repeat biopsies, and any radical prostatectomy (RP) slides were rereviewed. We also identified a control group of 50 consecutive patients with available prostate biopsies showing invasive prostatic adenocarcinoma but no AIP and having paired RP &#xfeff;for comparison. Medical records were searched for nonsurgical treatment and clinical outcome status. Patients with initial biopsies showing invasive adenocarcinoma with either grade group (GG) &#x2265;3 and/or unfavorable histology (as recently defined) were excluded from both the study and control groups. Correlation with subsequent adverse pathology at rebiopsy or RP, as defined by separate criteria: unfavorable histology, large cribriform/intraductal carcinoma, GG &#x2265;3, pN1, and/or pM1, was assessed for both groups. Phosphate and tensin (PTEN) homolog and ETS-related gene (ERG) immunohistochemistry were performed on biopsies with available paired RP, using standard protocols. One hundred forty-two patients with AIP met inclusion criteria. At initial biopsy, 16 patients (11.3%) had AIP without concomitant invasive carcinoma, whereas 126 (88.7%) also had invasive adenocarcinoma. Of the 126 invasive tumors with AIP meeting study criteria, 19 (15.1%) were GG 1 and 107 (84.9%) GG 2. One hundred thirty-nine of 142 patients with AIP (97.9%) had available clinical follow-up (mean: 36.9 mo). Fifty-two (36.3%) patients with AIP underwent RP, 36 (25.4%) had brachytherapy, 28 (19.7%) had radiotherapy, 17 (12%) remained on active surveillance, 2 (1.4%) had cryoablation, 2 (1.4%) received androgen deprivation therapy, and 1 (0.7%) had high-intensity focused ultrasound. Forty-seven of 52 patients undergoing prostatectomy (90.3%) had glass slides available for review: 30 (63.8%) were GG2, 13 (27.7%) GG3, 1 (2.1%) GG4, and 3 (6.4%) GG5. Seventeen (36.2%) patients were staged as pT2, 25 (53.2%) pT3a, and 5 (10.6%) pT3b. Forty-two of 47 (89.4%) patients had associated unfavorable histology on prostatectomy, including 41 (87.2%) with large cribriform/intraductal carcinoma, 17 (36.2%) GG&#x2265;3, and 5 (10.6%) with metastatic disease. In the 36 AIP lesions examined for PTEN and ERG immunoreactivity, 14 (38.9%) had concomitant PTEN loss and ERG over-expression, 6 (16.7%) showed PTEN loss only, and 6 (16.7%) had ERG overexpression only. AIP morphology was more predictive of risk for unfavorable histology at RP than PTEN/ERG immunophenotype. Seventeen patients not undergoing RP had rebiopsy, of which 5 (29.4%) had at least one adverse feature identified on repeat biopsy. Nineteen of 50 patients (38%) in the non-AIP control group had adverse pathology at RP (by any definition), compared with 89.4% in the AIP study group ( P < 0.0001). In conclusion, AIP in prostate needle core biopsy is strongly associated with unsampled adverse pathology, defined by unfavorable histology and other traditional definitions of aggressive disease. For optimal patient risk stratification and active surveillance management, AIP should gain better recognition as a standard reporting element given its association with an increased likelihood of unsampled high-risk disease.

Lower respiratory infections (LRIs) remain the world's leading infectious cause of death. This analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides global, regional, and national estimates of LRI incidence, mortality, and disability-adjusted life-years (DALYs), with attribution to 26 pathogens, including 11 newly modelled pathogens, across 204 countries and territories from 1990 to 2023. With new data and revised modelling techniques, these estimates serve as an update and expansion to GBD 2021. Through these estimates, we also aimed to assess progress towards the 2025 Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) target for pneumonia mortality in children younger than 5 years. Mortality from LRIs, defined as physician-diagnosed pneumonia or bronchiolitis, was estimated using the Cause of Death Ensemble model with data from vital registration, verbal autopsy, surveillance, and minimally invasive tissue sampling. The Bayesian meta-regression tool DisMod-MR 2.1 was used to model overall morbidity due to LRIs. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for all locations, years, age groups, and sexes. We modelled pathogen-specific case-fatality ratios (CFRs) for each age group and location using splined binomial regression to create internally consistent estimates of incidence and mortality proportions attributable to viral, fungal, parasitic, and bacterial pathogens. Progress was assessed towards the GAPPD target of less than three deaths from pneumonia per 1000 livebirths, which is roughly equivalent to a mortality rate of less than 60 deaths per 100 000 children younger than 5 years. In 2023, LRIs were responsible for 2&#xb7;50 million (95% uncertainty interval [UI] 2&#xb7;24-2&#xb7;81) deaths and 98&#xb7;7 million (87&#xb7;7-112) DALYs, with children younger than 5 years and adults aged 70 years and older carrying the highest burden. LRI mortality in children younger than 5 years fell by 33&#xb7;4% (10&#xb7;4-47&#xb7;4) since 2010, with a global mortality rate of 94&#xb7;8 (75&#xb7;6-116&#xb7;4) per 100&#x2009;000 person-years in 2023. Among adults aged 70 years and older, the burden remained substantial with only marginal declines since 2010. A mortality rate of less than 60 deaths per 100&#x2009;000 for children younger than 5 years was met by 129 of the 204 modelled countries in 2023. At a super-regional level, sub-Saharan Africa had an aggregate mortality rate in children younger than 5 years (hereafter referred to as under-5 mortality rate) furthest from the GAPPD target. Streptococcus pneumoniae continued to account for the largest number of LRI deaths globally (634&#x2009;000 [95% UI 565&#x2009;000-721&#x2009;000] deaths or 25&#xb7;3% [24&#xb7;5-26&#xb7;1] of all LRI deaths), followed by Staphylococcus aureus (271&#x2009;000 [243&#x2009;000-298&#x2009;000] deaths or 10&#xb7;9% [10&#xb7;3-11&#xb7;3]), and Klebsiella pneumoniae (228&#x2009;000 [204&#x2009;000-261&#x2009;000] deaths or 9&#xb7;1% [8&#xb7;8-9&#xb7;5]). Among pathogens newly modelled in this study, non-tuberculous mycobacteria (responsible for 177&#x2009;000 [95% UI 155&#x2009;000-201&#x2009;000] deaths) and Aspergillus spp (responsible for 67&#x2009;800 [59&#x2009;900-75&#x2009;900] deaths) emerged as important contributors. Altogether, the 11 newly modelled pathogens accounted for approximately 22% of LRI deaths. This comprehensive analysis underscores both the gains achieved through vaccination and the challenges that remain in controlling the LRI burden globally. Furthermore, it demonstrates persistent disparities in disease burden, with the highest mortality rates concentrated in countries in sub-Saharan Africa. Globally, as well as in these high-burden locations, the under-5 LRI mortality rate remains well above the GAPPD target. Progress towards this target requires equitable access to vaccines and preventive therapies-including newer interventions such as respiratory syncytial virus monoclonal antibodies-and health systems capable of early diagnosis and treatment. Expanding surveillance of emerging pathogens, strengthening adult immunisation programmes, and combating vaccine hesitancy are also crucial. As the global population ages, the dual challenge of sustaining gains in child survival while addressing the rising vulnerability in older adults will shape future pneumonia control strategies. Gates Foundation.

Recent advances in artificial intelligence (AI) and computer vision empower deep-learning models to infer molecular features from histopathological images to classify CNS tumours. The aim of this study was to test the classification accuracy of a molecular inference-based AI assistant for CNS tumour diagnosis. In this multi-institutional, retrospective study, we used data from whole slide images of samples from patients aged 0-95 years, diagnosed with primary or recurrent CNS tumours. Reference diagnostic labels were determined by DNA methylation-based tumour classification to match one of 52 tumour types selected to encompass most types of gliomas, embryonal tumours, and meningeal and mesenchymal tumours encountered in clinical practice. The Neuropath-AI model was trained on 5835 samples from the National Cancer Institute (NCI; USA), the Children's Brain Tumor Network (USA), and the Digital Brain Tumour Atlas (Austria) to infer molecular features from whole slide images and to use these to predict tumour types with associated confidence scores. The test cohort comprised 5516 samples identified in laboratory archives between May 17, 2024, and May 13, 2025, from the NCI, Northwestern Medicine (USA), University of Pittsburgh Medical Center (USA), and University College London (UK). There were 2753 (50%) female and 2763 (50%) male patients, median age 43 years (IQR 25-59). The primary objective was to measure the classification accuracy of the model family-level and terminal classification predictions in test samples, with coprimary endpoints of sample coverage and prediction and balanced accuracy. Sample coverage was defined as samples receiving a model prediction with a confidence score above a specified threshold. Prediction accuracy and balanced accuracy were analysed in the covered samples (ie, those meeting the confidence criterion) and evaluated by comparing the top-1 or top-2 predictions with reference labels. Family-level classifications were reached in 5299 (96%) of 5516 samples. Predictions to one of the terminal classifications with at least moderate confidence were reached for 4772 (87%) samples. The single highest-scoring classification matched the reference label in 3817 (95% CI 3770-3865; 80% [95% CI 79-81]) of 4772 samples (balanced accuracy 66% [95% CI 63-70]). The two highest-scoring classifications contained the reference label in 4103 (95% CI 4056-4152; 86% [95% CI 85-87]) of 4772 samples (balanced accuracy 75% [95% CI 71-78]). Our model provides the basis for a clinically applicable deep-learning assistant to improve human efficiency and accuracy of CNS tumour diagnosis. The model will be made publicly available and could be implemented to assist human pathologists in future prospective studies. The Intramural Research Program of the National Institutes of Health.

Background As a result of medical and surgical advancements in the management of congenital heart disease (CHD), survival rates have improved substantially, which has allowed the focus of CHD management to shift toward neurodevelopmental outcomes. Previous studies of the neuropathology occurring in CHD focused on cases preceding 1995 and reported high rates of white matter injury and intracranial hemorrhage, but do not reflect improvements in management of CHD in the past 2 decades. The purpose of this study is therefore to characterize the neuropathological lesions identified in subjects dying from CHD in a more-recent cohort from 2 institutions. Methods and Results We searched the autopsy archives at 2 major children's hospitals for patients with cyanotic congenital cardiac malformations who underwent autopsy. We identified 50 cases ranging in age from 20 gestational weeks to 46&#xa0;years. Acquired neuropathological lesions were identified in 60% (30 of 50) of subjects upon postmortem examination. The most common lesions were intracranial hemorrhage, most commonly subarachnoid (12 of 50; 24%) or germinal matrix (10 of 50; 20%), hippocampal injuries (10 of 50; 20%), and diffuse white matter gliosis (8 of 50; 16%). Periventricular leukomalacia was rare (3 of 50). Twenty-six subjects underwent repair or palliation of their lesions. Of the 50 subjects, 60% (30 of 50) had isolated CHD, whereas 24% (12 of 50) were diagnosed with chromosomal abnormalities (trisomy 13, 18, chromosomal deletions, and duplications) and 16% (8/50) had multiple congenital anomalies. Conclusions In the modern era of pediatric cardiology and cardiac surgery, intracranial hemorrhage and microscopic gray matter hypoxic-ischemic lesions are the dominant neuropathological lesions identified in patients coming to autopsy. Rates of more severe focal lesions, particularly periventricular leukomalacia, have decreased compared with historical controls.

The study aimed to assess the opinion of pathologists and thoracic surgeons of the International Association for the Study of Lung Cancer regarding the application and interpretation of the residual tumor (R) classification for lung cancer. On the basis of their membership profiles, a total of 623 pathologists and thoracic surgeons were identified and contacted by email with a cover letter and a link to an online survey. The questionnaire consisted of 12 questions about various aspects of the application and interpretation of the R classification for lung cancer. The response rate (to at least one question) was 72% (144 pathologists and 303 surgeons). The frequency of use of the R classification varies by geographic region. Although R status is regularly reported in Europe and Asia, 70% of pathologists in the United States and Canada never include R status in reports. Similar variations exist about who assigns the R category for the resection-in Europe and the United Kingdom, it is mainly the pathologist, whereas in China, Japan and the United States, it is the surgeon. There are some good agreements about margins examined and how to manage staple lines. The category "uncertain resection" has not been practically implemented in most of the world, except at some centers in Japan and the United Kingdom. This survey shows that surgical resection margins are part of routine reporting in most institutions; but the assignment of an R category is not always part of the pathology report, with considerable variation between countries. Despite the International Association for the Study of Lung Cancer proposals, the application of the uncertain resection category has not been taken up by most institutions, and further evidence is needed.

Chagas disease is a neglected tropical disease caused by the protozoan Trypanosoma cruzi, primarily transmitted by infected bugs, but also through contaminated food, transfusions, congenital transmission, and organ transplantation. Chagas disease has acute and chronic phases; the chronic phase can occur decades after infection, leading to complications such as heart failure, arrhythmias, and megaviscera. Accurate mortality and morbidity estimates are hindered by under-reporting and misclassification. Comprehensive and updated estimates are needed to improve global assessments of Chagas disease burden. We aim to provide a comprehensive description&#x2008;of global and regional burden of Chagas disease and its trends from 1990 to 2023. In this systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we produced estimates of Chagas disease deaths, years of life lost (YLLs), prevalence, incidence, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 204 countries and territories from 1990 to 2023 by age and sex. The GBD 2023 estimates supersede previous estimates for all years. For mortality estimates, we fit a cause of death ensemble model to vital registration data. For non-fatal estimates in endemic locations, we did a systematic review of seroprevalence data, defining a confirmed case as a confirmed diagnosis of T cruzi infection by two different positive tests (or a single ELISA or immunochromatographic test). After adjustment for the population at risk, we used a Bayesian compartmental model (DisMod-MR) to produce estimates. For non-endemic locations, we estimated prevalence on the basis of migration patterns and estimated prevalence from endemic countries. Prevalence of acute and chronic sequelae and corresponding disability weights were used to calculate YLDs. We estimated 10&#xb7;5 million (95% uncertainty interval 9&#xb7;4-11&#xb7;7) Chagas disease prevalent cases in 2023 globally, a 16&#xb7;1% (12&#xb7;6-19&#xb7;2) decrease compared with 1990. The global age-standardised Chagas disease prevalence rate declined by 55&#xb7;0% (53&#xb7;8-56&#xb7;1) from 1990 to 2023, with rates decreasing across all endemic regions. The highest age-standardised Chagas disease prevalence rates in 2023 were in southern Latin America (2485&#xb7;9 [2249&#xb7;6-2707&#xb7;7] per 100&#x2008;000) and Andean Latin America (2313&#xb7;8 [2093&#xb7;7-2570&#xb7;1] per 100&#x2008;000). Non-endemic regions experienced notable increases in prevalence due to migration from endemic countries. The age distribution of cases shifted over time, peaking at older ages in 2023 (between age 45 years and 65 years) compared with 1990 (30-45 years). In 2023, there were 352&#x2008;000 (308&#x2008;000-398&#x2008;000) new cases of Chagas disease globally, with the age-standardised rate decreasing by 55&#xb7;1% (53&#xb7;4-56&#xb7;6) since 1990. There were 8420 (7480-9360) deaths globally in 2023. Age-standardised mortality decreased by 72&#xb7;5% (68&#xb7;9-75&#xb7;4) globally from 1990 to 2023. In 2023, the highest age-standardised mortality rates were in tropical Latin America (2&#xb7;2 [1&#xb7;9-2&#xb7;4] per 100&#x2008;000) and Andean Latin America (0&#xb7;92 [0&#xb7;70-1&#xb7;2] per 100&#x2008;000). The GBD 2023 Chagas disease estimates are notably higher than previous GBD estimates, reflecting additional data and methodological improvements, and those published by the Pan American Health Organization. Nevertheless, these updated estimates show decreasing prevalence and incidence in endemic countries, highlighting the importance of socioeconomic development, housing conditions, and vector-control policies. Conversely, the increase in prevalence in non-endemic countries, mainly due to migration, requires new strategies for screening, early recognition, and access to care. Although the marked decrease in mortality and YLLs might be due to better access to care at different levels, the shift in age distribution highlights the importance of preparing and funding health systems for caring for older populations with advanced sequelae. Finally, the continuous refinement of data-source quality, including adequate coding and classification, is crucial for the accuracy of global estimates, which can ultimately drive health and social policies. The Gates Foundation, the World Heart Federation, and Novartis Pharma.

Accurate measurement of serum creatinine is essential for estimating glomerular filtration rate (GFR), which is central to chronic kidney disease (CKD) detection, staging, and management. However, historical biases in creatinine measurement among several instrument/assay manufacturers compromised estimated GFR (eGFR) reliability, hindering CKD detection and management. Initiatives led by the National Kidney Disease Education Program (NKDEP) Laboratory Working Group and other stakeholders have standardized calibration of creatinine measurement and reporting of eGFR. To summarize the journey toward global standardization of serum creatinine measurement procedures, detailing the coordinated efforts that led to calibration traceability to the NIST (National Institute of Standards and Technology) SRM (standard reference material) 967 reference material, examining the role of proficiency testing in monitoring progress, and contrasting the current state of creatinine assay standardization with that of other key kidney function biomarkers, such as cystatin C and urine albumin. A comprehensive review of peer-reviewed literature from 2005-2025 was conducted, including landmark studies from the Archives of Pathology & Laboratory Medicine, Clinical Chemistry, and clinical practice guidelines from several professional organizations. College of American Pathologists proficiency testing and LN24 survey data were included. The global creatinine standardization initiative, driven by the NKDEP Laboratory Working Group, has dramatically reduced intermethod bias in serum creatinine measurement procedures, vastly improving the reliability of eGFR. While the metrologic traceability of calibration for creatinine measurement is now harmonized, challenges with analytical specificity, particularly for Jaffe-based methods, remain. The success of creatinine standardization serves as an important model for ongoing efforts to harmonize cystatin C and urine albumin measurements, ultimately leading to more accurate, equitable, and standardized care for patients with or at risk for CKD.

Oral carcinoma cuniculatum (CC) is a rare variant of oral squamous cell carcinoma (OSCC), characterized by a well-differentiated, burrowing invasive pattern and minimal cellular atypia. Its diagnosis is challenging owing to its bland morphology, which makes differentiation from non-neoplastic lesions difficult on biopsy. Despite this, CC often requires distinction from conventional OSCC, even in surgical specimens. Histological overlap with conventional OSCC suggests a continuous spectrum of diseases. To clarify the genetic identity of pure CC, we analyzed 23 cases of OSCC with burrowing invasive patterns and classified them into three groups: CC, conventional OSCC (SCC), and uncertain CC (UCC). We retrospectively reviewed 2002 OSCC cases from multicenter archives. From this cohort, 23 cases exhibiting a burrowing invasive pattern characteristic of CC were selected. The cases were classified into the three study groups based on the WHO diagnostic criteria, and clinicopathological features were reviewed. Targeted next-generation sequencing was performed to identify clinically significant genetic alterations, and immunohistochemical staining was also conducted. The 23 cases were histologically classified into CC (n&#x2009;=&#x2009;8), UCC (n&#x2009;=&#x2009;7), and SCC (n&#x2009;=&#x2009;8) groups. Clinically, the CC group predominantly affected the gingiva with no recurrence or metastasis. Conversely, the SCC group primarily involved the tongue and showed recurrence and metastasis. Genetic alterations were detected in 87.5% (7/8) of CC cases, with low frequencies of TP53 (12.5%) and CDKN2A (25.0%) alterations and higher frequencies of FAT1 (50.0%), NOTCH1 (37.5%), PIK3CA (37.5%), and CASP8 (50.0%) alterations. In contrast, the SCC group showed frequent TP53 (75.0%) and CDKN2A (75.0%) alterations, whereas FAT1 and NOTCH1 alterations were absent. Consistent with these findings, p53 staining revealed wild-type patterns in the CC group along with a lower Ki-67 labeling index. The UCC group exhibited intermediate clinicopathological and genetic characteristics. This study provides the first genetic characterization of oral CC, distinct from that of conventional OSCC. This genetic signature may contribute to the biological behavior of CC and offer a potential tool for its differential diagnosis. Further studies with larger cohorts are required to confirm the relationship between CC and conventional OSCC, and to fully elucidate the genetic landscape of CC.

Ewing sarcoma (ES) is an uncommon mesenchymal neoplasm that typically develops as a bone mass, although up to 30% arise in extraskeletal sites. ES of the gastrointestinal (GI) and hepatobiliary tract is rare and may be misdiagnosed as other, more common neoplasms that occur in these sites. However, the correct classification of extraskeletal ES is important for timely clinical management and prognostication. We reviewed our experience of ES in the GI and hepatobiliary tract in order to further highlight the clinicopathologic features of these neoplasms and document the potential for misdiagnosis in this setting. The archives and consultation files of 6 academic institutions were retrospectively queried for cases of ES occurring in the GI and hepatobiliary tract. The histologic slides and ancillary studies were reviewed and clinical data were retrieved for each case through the electronic medical records, when available. Twenty-three patients with ES in the GI and/or hepatobiliary tract were identified from 2000 to 2022. Of these, 11 were women and 12 were men with a median age of 38 years (range, 2 to 64). Tumor locations included the pancreas (n=5), liver (n=2), stomach (n=3), colorectum (n=3), and small intestine (n=5), as well as tumors involving multiple organs, pelvis and retroperitoneum (n=5). Tumor size varied between 2&#xa0;cm and 18&#xa0;cm. Twenty were primary and 3 were metastases. Of the 23 cases, only 17% were initially diagnosed as ES. The most common misdiagnoses involved various forms of neuroendocrine neoplasia due to expression of synaptophysin and other neuroendocrine markers (22%). A wide variety of diagnoses including GI stromal tumor was considered due to aberrant CD117 expression (4%). The diagnosis of ES was ultimately confirmed by detection of the EWSR1 rearrangement in 22 cases. The remaining case was diagnosed using traditional immunohistochemistry. Follow-up information was available in 20 cases, with follow-up time varying between 2 and 256 months. Six patients with follow-up died of disease between 6 and 60 months following initial presentation. Our data indicate ES in the GI and hepatobiliary tract is commonly misdiagnosed leading to a delay in therapy. In light of the attendant therapeutic and prognostic implications, ES should be considered in the differential diagnosis of any GI or hepatobiliary tumor with epithelioid and/or small round cell morphology.

Squamous cell carcinoma (SCC) is one of the most common malignancies involving the parotid gland, but it has been recognized that the vast majority of parotid SCC represents metastases, especially from the ipsilateral facial skin. Bona fide primary SCC of the parotid is so rare that it is unclear whether it truly exists at all. We sought to molecularly characterize cases diagnosed as primary parotid gland SCC to see if they possess a unique genetic makeup.We identified cases in our archives which had been diagnosed as primary SCC of the parotid gland. In all cases, metastatic disease was excluded by a thorough history and physical examination. Cases with histologic evidence of a precursor neoplasm (e.g., carcinoma ex-pleomorphic adenoma) were also excluded. Targeted next-generation sequencing (NGS) was attempted on all cases.Six cases diagnosed as primary parotid SCC were identified, arising in 4 males and 2 females ranging from 8 to 73 years (mean, 51.8 years). All cases exhibited keratinization and unequivocal invasion. Four of 6 appeared to be arising from cystically dilated ducts. Five of 6 exhibited well-developed cellular atypia; the remaining case, while cytologically bland, demonstrated perineural invasion. Targeted NGS was successful in 5 of 6 cases. Two SCC harbored several mutations in a mutational profile reminiscent of SCCs seen in other organs. One case harbored YAP1::MAML2, a fusion previously reported in porocarcinoma and other neoplasms. One case harbored IRF2BP2::RUNX2, and presumably represents keratocystoma or SCC ex-keratocystoma. Finally, one case an increase of C&#x2009;>&#x2009;T mutations consistent with ultraviolet damage, suggesting that this case represented a cryptic metastasis from cutaneous SCC.Our analysis did not confirm a unifying genetic signature for purported primary parotid SCC. Indeed, our findings suggest that true primary parotid gland SCC is even rarer than already believed. In our 5 cases with results, NGS findings demonstrated that one was likely a keratocystoma, one a cryptic metastasis from a cutaneous SCC, and one a porocarcinoma, either metastatic or primary. The two remaining cases had complex genotypes reminiscent of SCCs from other sites. This may be the signature of genuine parotid primary SCC, but metastasis from an SCC from another organ cannot be excluded. Accordingly, a diagnosis of primary parotid gland SCC should be viewed with skepticism.

People with glomerular disease (GD) and comorbid diabetes have similar baseline characteristics irrespective of superimposed diabetic lesions. Immunosuppression for GD with comorbid diabetes is the same regardless of superimposed diabetic glomerular lesions. ESKD or death is more rapid in GD and comorbid diabetes only in the presence of moderate-severe diabetic glomerular lesions. We aimed to evaluate whether concomitant diabetic glomerulosclerosis (DGS) and its severity affect the treatment and outcomes of primary glomerular diseases (GDs) with comorbid diabetes. We conducted a retrospective review of people with diabetes and GD. We searched the GD Collaborative Network for biopsies from 2008 to 2015 among persons with diabetes and any of the following diagnoses: FSGS, IgA nephropathy, minimal change disease, membranous nephropathy, or antineutrophil cytoplasmic autoantibody GN. Data were abstracted from health records and histologic diabetic glomerular class scored. The primary composite end point was ESKD or death. Multivariable Cox regression models tested whether any or the severity of diabetes histopathology affected the primary end point. Data from 134 cases were available for analysis (78 DGS+GD and 56 GD alone). Diabetes duration and glycemic control were similar between the two groups (P = 0.2; P = 0.09, respectively). Use of immunosuppression did not differ between the two groups (P = 0.3). The composite end point was significantly higher in DGS+GD (22.5 cases per 100 person-years [95% confidence interval (CI), 16.6 to 30.5]) versus GD alone (10.2 cases per 100 person-years [95% CI, 6.4 to 16.2]). Regression analyses demonstrated that compared with the GD-alone group, the risk for the composite end point was similar in the group with mild DGS+GD (DGS class 1, 2a) (hazard ratio, 1.15 [95% CI, 0.54 to 2.43]) while the group with severe DGS+GD (DGS class 2b, 3, 4) had a greater risk (hazard ratio, 3.60 [1.79 to 7.22]). Among people with diabetes and GD, mild diabetic glomerular lesions on biopsy do not affect outcomes, but moderate-severe lesions increase the risk for ESKD and death. Whether use of immunosuppression, particularly glucocorticoids, is less successful in inducing GD remission in people with moderate-severe diabetic lesions will be a focus of future study in a larger population.

Digital pathology is an opportunity to revise the routine and old artisanal workflow, moving to standard operating procedures, quality control and reproducibility. Here the results of a survey promoted by the Coordinamento della Medicina di Laboratorio (CRC Med Lab) of the Lombardy region in Italy are reported to shed light on the current situation of digital adoption in the country. The survey composed of 58 questions was sent to 60 pathology laboratories. The results were collected and most significant answers were reported and discussed. Answers were received from 57 (95%) laboratories, a minority organized in spoke-hub networks (16%) with a centralized processing phase (11%). Hybrid manual/computer-assisted traceability was prevalent (36%), with QR/barcode labeling starting within the pathology lab (23%). Different laboratory information systems (LIS) were employed, mostly with alert functions and/or multimedial file attachments (56% and 46%, respectively). The majority opted for a semi-automated tracking management (44, 77%) and 18 centers (32%) were partly digitizing the routine (&#xbe; scanning < 25% of slides). Whole slide images were retained for 3.7 years in average; in-house blocks/slides archiving was still preferred (30, 53%), with 1838 (&#xb1;1551) and 1798 (&#xb1;1950) days (5 years) internal permanence for blocks and slides that are stored in out-source (mean turnaround time for return on-demand 3.7&#xb1;2.1, range 1-10 days). The advantages of digital pathology must be balanced against the challenges faced in the structural revision of the pathology workflow. This regional scouting can represent the foundation to build an efficient and connected digital pathology system in the territory.