Discrepant Cases Research Articles

Abstract 4125497: Diagnostic Discrepancies Revealed by Explant Pathology at the Time of Cardiac Transplant in Patients Clinically Diagnosed with Nonischemic Cardiomyopathy: Role of Cardiac Magnetic Resonance Imaging

Background: Differentiating between causes of non-ischemic cardiomyopathy is important for disease-directed treatment. Cardiac MRI (CMR) and the use of late gadolinium enhancement (LGE) have proven useful for enhancing diagnostic accuracy. Definitive assessment of cardiomyopathy etiology by explant pathology facilitates direct evaluation of CMR utility. Hypothesis: We hypothesized direct comparison between pre-transplant (Tx) CMR and explant pathology will improve the characterization of undifferentiated cardiomyopathy through examination of cases where pre- and post-Tx diagnoses were discordant. Aims: To evaluate discrepant cases to describe imaging patterns in relation to post-Tx diagnosis. Methods: Institutional Tx recipients between 2000 and June 2023 were queried for pre-Tx MRI (n=122). Discrepant cases were identified (n=8). Pre-Tx diagnostic modalities, including CMR, were reviewed, and CMR patterns were evaluated in association with ultimate explant diagnosis. Results: Of the eight patients with discrepant diagnoses, five carried clinical diagnosis of dilated cardiomyopathy, one hypertrophic cardiomyopathy, one peripartum cardiomyopathy, and one congenital heart disease having undergone tricuspid valve and ASD repair. Pathologic evaluation most frequently identified biventricular or left ventricular arrhythmogenic cardiomyopathy (ARVC) (n=6), where CMR disclosed a diffuse pattern of subepicardial LGE and pre-Tx diagnosis of DCM was most common. Two of these pathologic descriptions represented a different disease on genetic evaluation: one patient had Danon disease, another had a LMNA pathogenic variant. The presumed peripartum cardiomyopathy was identified as Fabry’s disease on pathology (however, genetic testing consistent with Danon disease). Both Danon disease patients had primarily subendocardial LGE on CMR. One patient with a DCM phenotype had HCM pathologically. Results summarized in Table 1. Conclusions: Cardiac MRI can be a useful modality for the evaluation of underlying cardiomyopathy and should prompt appropriate genetic testing. Diffuse subepicardial LGE frequently accompanied the diagnosis of ARVC whereas a non-subepicardial pattern reflected alternative etiologies identified only through genetic testing.

PATH-46. DETECTION OF CDKN2A/B HOMOZYGOUS DELETION BY DNA METHYLATION AND DNA NEXT GENERATION SEQUENCING: A COMPARISON

Abstract CDKN2A/B homozygous deletion status is critical for grading of several central nervous system (CNS) tumors, including IDH mutant astrocytoma, pleomorphic xanthoastrocytoma, and meningioma. CDKN2A/B status can be assed using variety of methods, but the accuracy varies due to technical and analytical variables. Here we sought to compare sensitivity of CDKN2A/B homozygous deletion detection by NGS and DNA methylation array derived copy number analysis. We retrospectively analyzed 100 CNS tumors diagnosed at NYU Langone Health between 2020 and 2023. All tumors were profiled by whole genome DNA methylation profiling using the Illumina EPIC array. Copy numbers were analyzed using the ‘conumee’ R package and visual inspection. Next-generation sequencing (NGS) analysis was performed by NYU Langone Genome PACT, a 510(k) FDA cleared (K202304) matched tumor-normal 607 gene panel. Variant allele frequency of canonical driver mutations was used to molecularly estimate tumor cell content. Discrepant cases were assed using targeted qPCR. Our cohort of 100 CNS tumors included glioblastoma (N=75), IDH mutant astrocytoma (N=14), oligodendroglioma (N=4), pleomorphic xanthoastrocytoma (N=2), meningioma (N=1), infantile hemispheric glioma (N=1), central neurocytoma (N=1), diffuse midline glioma K27-altered (N=1), and anaplastic pilocytic astrocytoma (N=1). By DNA methylation, CDKN2A/B homozygous deletion was detected in 54 cases, hemizygous deletion was detected in 13 cases, and no deletion was detected in 33 cases. By NGS, CDKN2A/B homozygous deletion was detected in 31 cases, hemizygous deletion was detected in 28, and no deletion was detected in 41 cases. DNA methylation detected a homozygous deletion in 23 cases that were not detected by NGS. All cases of homozygous deletion detected by NGS were also detected by DNA methylation. DNA methylation derived copy number assessment is more sensitive for CDKN2A/B homozygous deletion than next generation sequencing.

Utility of digital cell imaging as an aid to enhance pathologist peripheral blood smear review for routine and on call practice: A verification study

Abstract Introduction/Objective Microscopic examination of peripheral blood smear (PBS) provides important information to support the diagnosis of hematological diseases. However, manual microscopic examination of PBS is labor-intensive and cannot be done remotely. CellaVision is digital cell imaging technology that provides pre-classification and digital imaging of the red blood cells (RBCs), white blood cells (WBCs), and platelets, myeloid, lymphoid and erythroid precursors. Several studies have evaluated the performance of this technology in the hematology laboratory as tool to assist laboratory technologists; our study evaluates its use for pathologist review of peripheral blood smears both during routine and on call practice. Methods/Case Report Our study included 30 PBS and two hematopathologists with greater than 10 years’ experience in performing PBS review. We compared pathologist’s own impression of microscopic PBS review to their own impression using CellaVision software (intraobserver comparison). Additionally, pathologist to pathologist impression was compared for both methods (interobserver comparison). All 30 cases revealed abnormal findings including, but not limited to: pancytopenia, leukocytosis, leukopenia, anemia, thrombocytopenia, and thrombocytosis. Of the 30 cases, 5 “on-call” were cases when the pathologist had to come on–site for pathologist PBS review. Results (if a Case Study enter NA) The pathologists own PBS interpretation (intraobserver) by microscopy and CellaVision had a concordance of 96.7%. The pathologist to pathologist interpretation of both methods had a concordance of 96.7%.The one discrepant case was a smear with platelet clumping and normal platelet count. On chart review of this case, this discrepancy would have minimal impact on patient care. Conclusion Pathologist use of CellaVision in their routine practice may result in speedier PBS review, particularly in cases with leukopenia, and better communication with laboratory technologists. CellaVision is less reliable in identifying platelet clumps and should not be used in isolation in evaluating thrombocytopenia. Used with other relevant data, CellaVision has the potential to preempt in person microscopic review of PBS when on-call in certain situations.

Comparison of Clinical Diagnosis and Autopsy Findings of Early Neonatal Deaths: Diagnostic Challenges and the Value of Autopsy in Identifying Rare Pathologies.

In a non-forensic hospital setting, neonatal death within the first week of life is often related to premature birth and/or lung diseases. Without post-mortem examination, the identification of the cause of death may be challenging. Autopsy can confirm the clinical diagnosis, uncover additional information or change the diagnosis. Our study aimed to assess the correlation between the clinical diagnosis and post-mortem findings in early neonatal deaths. The retrospective study included autopsy cases with neonatal deaths within the first 7 days of life (arbitrary time interval 2006-2021). Discrepancies between clinical and histopathological findings were classified into 3 groups: (i) full agreement, (ii) additional findings discovered by autopsy, or (iii) autopsy changed the diagnosis. A cohort of 27 cases could be identified and lung pathologies were the most common finding (56%). Additional findings could be discovered in 48% of cases. Major discrepancies which changed the clinical diagnosis could be found in 11% (n = 3/27) of cases. Frequently, post-mortem examinations validate the clinical diagnosis while revealing crucial information in a few cases. In these discrepant cases, autopsy findings can provide information for genetic counselling and quality control of clinical management.

Abstract A028: MTAP deficiency is frequent and mostly homogeneous in ductal adenocarcinomas of the pancreas

Abstract Complete expression loss of S-methyl-5′-thioadenosine phosphorylase (MTAP) is caused by homozygous 9p21 deletion and results in a critical vulnerability of cancer cells towards drugs targeting multiple different pathways. MTAP deficiency is common in ductal adenocarcinoma of the pancreas, but data on its intratumoral heterogeneity - a potential obstacle for targeted therapies - are lacking. To learn more on the role and potential heterogeneity of MTAP deficiency in pancreatic adenocarcinoma, 236 primary tumors were analyzed in a tissue microarray (TMA) format by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for MTAP expression and 9p21 deletions. The cohort included 236 cancers from which 6 samples were taken from as many as possible different tumor containing primary tumor blocks and 3 samples were added from as many as possible lymph node metastases to construct a “heterogeneity TMA”. All available tumor containing blocks (average 4) from 6 selected cancers were also analyzed by IHC and FISH on whole sections. Complete absence of MTAP staining was seen in 350 (38.6%) of 907 interpretable TMA samples. 284 (98.6%) of 288 samples with a complete MTAP expression loss and FISH data had a homozygous 9p21 deletion while there were only two tumor spots with homozygous deletions within 557 samples with retained MTAP expression (99.6% concordance). On a patient level, an MTAP deficiency was found in 64 (41.0%) of 156 tumors for which at least 3 different samples were interpretable on the TMAs. 62 (96.9%) of these patients showed an MTAP loss in all interpretable samples (homogeneous MTAP deficiency). The TMA data were confirmed on whole sections in 5 of 6 patients. In the discrepant case a focal MTAP loss was identified in a tumor considered MTAP wild type based on the TMA results. It is concluded that MTAP expression loss is frequent and highly homogeneous in ductal adenocarcinomas of the pancreas. Given the high concordance rate between homozygous deletion and MTAP expression loss homozygous deletion may represent the only mechanism for MTAP deficiency in pancreatic cancer. MTAP IHC is an excellent tool for identification of MTPA deficient cases. MTAP IHC may also have considerable diagnostic value as even low-grade cancer glands can be easily identified in small biopsies from MTAP deficient cases. Considering also their aggressive clinical behavior, pancreatic adenocarcinomas may represent an ideal cancer type for studying new drugs targeting MTAP deficient cancer cells in clinical trials. Citation Format: Natalia Gorbokon, Katharina Teljuk, Frank Jacobsen, Till Krech, Till Clauditz, Stefan Steurer, Ronald Simon, Guido Sauter, Sarah Minner, Lukas Bubendorf, Thilo Hackert, Nina Schraps, Faik G Uzunoglu, Martina Kluth. MTAP deficiency is frequent and mostly homogeneous in ductal adenocarcinomas of the pancreas [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A028.

A rare case of ABO grouping discrepancy due to probable blood group switching which presented as lost antigens detectable only with indigenous reagents in less sensitive platforms compared to highly sensitive automated platforms using non indigenous reagents

Abstract: Blood group switching in the form of loss or diminished expression of RBC antigens has been reported in malignancies and infections. Blood group antigens are present on the red cell surface. ABO blood group system is the most clinically significant system. Some cases can present as grouping discrepancy. Here we present a rare case of ABO grouping discrepancy due to probable blood group switching which presented as lost antigens detectable only with indigenous reagents in less sensitive platforms compared to highly sensitive automated platforms using non indigenous reagents. 66 year old female whose historic blood group was A Rh D positive with history of uneventful transfusion of 2 units of A Rh D positive packed red cell one and half years back now presented with mycoplasma pneumonia and acute pulmonary edema. On routine complete blood count testing her hemoglobin was 3.6 gm%, request send to blood bank for pretransfusion testing. Testing performed via conventional tube technique and ABO blood group discrepancy was noted with forward grouping turned to be A Rh D positive (positive reaction with anti A1 lectin) and on reverse grouping 3+ reactions was observed in both A and B cell giving a picture of O blood group. Blood grouping was performed in different platforms including fully automated, semi automated and manual using commercially available antisera and human plasma as a source of anti A, anti B antibodies for forward grouping. The antisera used in automated platforms are non indigenous and that for manual are indigenous. Discrepancy was noted (Forward A and Reverse O) in CTT with commercially available antisera and human plasma as reagents for forward grouping .The same discrepancy was noted with CAT in neutral card with commercially available antisera for manual grouping. But when grouping performed with Column Agglutination Technology using matrix grouping gel card the discrepancy was resolved reporting the blood group as O. For further confirmation we repeated the blood grouping in another fully automated platform, SPRCA Technology (Immucore NEOIRIS) and in that also no discrepancy noted giving a picture of O group. This patient probably had undergone a blood group switching from A to O by losing some but not all A epitopes and started anti A antibody production. Some A epitopes which were not lost had been picked up by the commercially available antisera intended for manual grouping. These antisera are indigenous in origin. Also when human plasma was used as source of antibodies the A epitopes which were not lost were detected. But when grouping was done with non-indigenous antisera in both manual and automatic platform the A epitopes were not detected. This case points towards the relevance of incorporating indigenous antisera in automated platforms.

Comparison of antigenicity between frozen section vs non-frozen section tissue blocks: An immunohistochemical study of antibodies commonly used in gynecologic pathology.

Frozen section (FS) is a technique widely used intraoperatively to render a preliminary histopathologic diagnosis, allowing for immediate decisions at the time of surgery. We aimed to investigate potential variations in tissue antigenicity induced by rapid freezing in a variety of gynecologic tumor samples. A total of 177 FS and 177 non-frozen section (NFS) tissue slides were tested using a panel of immunostains commonly used in gynecologic pathology, including hormone receptors (estrogen receptor, progesterone receptor), HER2, mismatch repair proteins (MSH6, PMS2), programmed cell death 1 ligand 1 (PD-L1), p53, napsin A, and ɑ-methylacyl coenzyme-A racemase. Immunohistochemistry results were categorized as positive or negative, and positive cases were subsequently scored based on the distribution and intensity of the staining. Certain immunostains, such as HER2, PD-L1, and p53, were scored according to the established guidelines. The overall concordance between FS and NFS blocks was 87%; among the 13% of discrepant cases, most (10.7%) were classified as minor, with only quantitative differences without foreseeable clinical significance. In 2.3% of cases, there were major qualitative changes with potential impact on disease management. We concluded that FS tissue blocks may, in most cases, safely be used for immunohistochemical studies because most discrepant cases showed only minor differences in staining, with no anticipated clinical significance. Nevertheless, for certain markers, including HER2, p53, and PMS2, a NFS block is preferred when that option is available.

Practical Considerations for the Use of the Rapid AcuStar® ADAMTS13 Activity Assay in the Diagnosis of Acute Thrombotic Thrombocytopenic Purpura (TTP).

Introduction: Conventional practice in the management of acute TTP entails empirical treatment of suspected cases whilst awaiting confirmatory ADAMTS13 deficiency testing. Rapid ADAMTS13 assays offer increased accessibility and rapid diagnostics. The new automated HemosIL AcuStar® ADAMTS13 assay has seen increasing use among UK TTP Specialist Centres alongside the traditional ELISA method to confirm severe ADAMTS13 deficiency. Methods: A multi-centre retrospective case-control study was performed to review patients demonstrating discrepant ADAMTS13 activity results measured using rapid (AcuStar®) and ELISA assays in parallel from September 2019 to December 2021. Cases were compared with a cohort of suspected TTP patients exhibiting no difference in assay results and in relation to their presenting characteristics and pre-test probability of a diagnosis of TTP. Results: Where the clinical index of suspicion for TTP was high at presentation, acute TTP was confirmed using the AcuStar® assay < 0.2 IU/dL and subsequently < 10 IU/dL by ELISA with zero incidence of discrepancy. For patients with low clinical suspicion of acute TTP, a discrepancy between the AcuStar® and ELISA assay results was observed in 2% of cases; 5-10 IU/dL in AcuStar®, confirmed as >20 IU/dL by ELISA. A concurrent cancer diagnosis or sepsis was observed in 40% of discrepant cases. Conclusions: Where acute TTP is strongly suspected, there is a good correlation between the rapid AcuStar® ADAMTS13 assay and the conventional ELISA assay. Where the clinical suspicion of acute TTP is low, caution should be exercised in the interpretation of the ADAMTS13 activity using the AcuStar® assay. Accurate interpretation requires robust ADAMTS13 testing algorithms to be incorporated into diagnostic pathways.

Multicenter Study on Tumor Budding in Lung Squamous Cell Carcinoma: Comparison Between Biopsy and Resection With Interobserver Variability Assessment

Grading lung squamous cell carcinoma (LUSC) is controversial and not universally accepted. The histomorphologic feature of tumor budding (TB) is an established independent prognostic factor in colorectal cancer, and its importance is growing in other solid cancers, making it a candidate for inclusion in tumor grading schemes. We aimed to compare TB between preoperative biopsies and resection specimens in pulmonary squamous cell carcinoma and assess interobserver variability. A retrospective cohort of 249 consecutive patients primarily resected with LUSC in Bern (2000-2013, n = 136) and Lausanne (2005-2020, n = 113) with available preoperative biopsies was analyzed for TB and additional histomorphologic parameters, such as spread through airspaces and desmoplasia, by 2 expert pathologists (M.M., C.N.). Results were correlated with clinicopathologic parameters and survival. In resection specimens, peritumoral budding (PTB) score was low (0-4 buds/0.785 mm2) in 47.6%, intermediate (5-9 buds/0.785 mm2) in 27.4%, and high (≥10 buds/0.785 mm2) in 25% of cases (median bud count, 5; IQR, 0-26). Both the absolute number of buds and TB score were similar when comparing tumor edge and intratumoral zone (P = .192) but significantly different from the score obtained in the biopsy (P < .001). Interobserver variability was moderate, regardless of score location (Cohen kappa, 0.59). The discrepant cases were reassessed, and consensus was reached in all cases with identification of causes of discordance. TB score was significantly associated with stage (P = .002), presence of lymph node (P = .033), and distant metastases (P = .020), without significant correlation with overall survival, tumor size, or pleural invasion. Desmoplasia was significantly associated with higher PTB (P < .001). Spread through airspaces was present in 34% and associated with lower PTB (P < .001). To conclude, despite confirming TB as a reproducible factor in LUSC, we disclose areas of scoring ambiguity. Preoperative biopsy evaluation was insufficient in establishing the final TB score of the resected tumor.

Smartwatch a new tool in the assesment of ischaemic heart disease

Abstract Introduction Outpatient ECG tracing is getting more important. Therefore, an everyday tool such as the watch has become "smart" (127.5 M units sold in 2021), and its key application is the heart rate measurement through ECG tracing. Some devices are already approved for atrial fibrillation detection. However, their role in ischemic heart disease (IHD), leading cause of cardiovascular death, has not been appropriately tested. Objetcive The aim of this study was to evaluate the usefulness of smartwatch ECG registry in IHD. Methods We present an observational study of 25 consecutive patients with acute IHD. Conventional ECG and smartwatch tracing were obtained simultaneously at admission. Waves of conventional and smartwatch ECGs were objectively compared. A survey on medical attitude was conducted among 12 physicians (3 cardiologists, 3 intensivists, 3 emergency physicians, and 3 general practitioners) and a score (1–5) of concordance between the records was requested. Figure 1. Results There were no differences in Q-wave, Rwave, ST segment, or T-wave. There was a very strong correlation between ST segments, a strong correlation in Q-waves and R-waves, and a moderate correlation in T-wave measurements. All specialists obtained a high level of agreement (4.45 ± 0.45). Smartwatch tracings would lead to similar management compared to conventional ECG. There were only 6 (2%) discrepant cases due to differences in inferior repolarization, showing an almost perfect agreement (kappa = 0.96). Conclusions In most patients with acute IHD, smartwatch ECG tracing is a reliable tool to make the diagnosis and guide appropriate medical care. However, due to their intrinsic limitations, inferior myocardial infarctions may be missed and require a conventional 12-lead ECG to rule them out.

КОНСТИТУЦИОННЫЕ ОСНОВЫ ПРЕДОТВРАЩЕНИЯ ЧРЕЗВЫЧАЙНЫХ СИТУАЦИЙ

Some norms of the Constitution of the Russian Federation are considered, which together form the basis for the prevention of natural and man-made emergencies, as a legal foundation for the protection of human life and health, and other legally protected values. The mapping of constitutional norms to some provisions of the main federal laws, acts of the President of the Russian Federation and resolutions of the Government of the Russian Federation, their connection with the functional and territorial systems of the unified state system for the prevention and elimination of consequences of emergency situations is carried out. The powers of the highest institutions of state power – the President of the Russian Federation and the Government of the Russian Federation – are considered from the perspective of state discipline. The constitutional principle of harmonization of mutual relations at the federal level and at the level of Russian regions is touched upon. Possession of the constitutional legal apparatus is presented as a condition for preventing cases of discrepancies and conflicts in legislative acts or departmental regulatory legal acts. The directions of development and improvement of regulatory segments that require a new scientific and legal rethinking and revision in the course of further legal work in the field of regulation are presented.

Implications of right aortic arch prenatal diagnosis: the multicentric nationwide ARCADE cohort

ObjectivesThis study aims to describe the various presentations of the prenatally diagnosed isolated right aortic arch (RAA), that is, without associated congenital heart defect and to evaluate the impact of...

An artificial intelligence-powered PD-L1 combined positive score (CPS) analyser in urothelial carcinoma alleviating interobserver and intersite variability.

Immune checkpoint inhibitors targeting programmed death-ligand 1 (PD-L1) have shown promising clinical outcomes in urothelial carcinoma (UC). The combined positive score (CPS) quantifies PD-L1 22C3 expression in UC, but it can vary between pathologists due to the consideration of both immune and tumour cell positivity. An artificial intelligence (AI)-powered PD-L1 CPS analyser was developed using 1,275,907 cells and 6175.42 mm2 of tissue annotated by pathologists, extracted from 400 PD-L1 22C3-stained whole slide images of UC. We validated the AI model on 543 UC PD-L1 22C3 cases collected from three institutions. There were 446 cases (82.1%) where the CPS results (CPS ≥10 or <10) were in complete agreement between three pathologists, and 486 cases (89.5%) where the AI-powered CPS results matched the consensus of two or more pathologists. In the pathologist's assessment of the CPS, statistically significant differences were noted depending on the source hospital (P = 0.003). Three pathologists reevaluated discrepancy cases with AI-powered CPS results. After using the AI as a guide and revising, the complete agreement increased to 93.9%. The AI model contributed to improving the concordance between pathologists across various factors including hospital, specimen type, pathologic T stage, histologic subtypes, and dominant PD-L1-positive cell type. In the revised results, the evaluation discordance among slides from different hospitals was mitigated. This study suggests that AI models can help pathologists to reduce discrepancies between pathologists in quantifying immunohistochemistry including PD-L1 22C3 CPS, especially when evaluating data from different institutions, such as in a telepathology setting.

Evaluating the Generalizability of an Electronic Algorithm to Identify Vancomycin-Associated Acute Kidney Injury

Introduction: Vancomycin-associated acute kidney injury (V-AKI) is a common adverse reaction; however, there is currently no method to systematically monitor its incidence. We previously developed and internally validated an electronic algorithm to identify cases of V-AKI using structured electronic health record data at the Johns Hopkins Hospital, which demonstrated excellent agreement with chart review (percent agreement 92.5%; weighted kappa coefficient 0.95), as well as excellent sensitivity (89.7%) and specificity (98.2%) in detecting at least possible V-AKI events. The objective of this study was to evaluate the generalizability of the V-AKI electronic algorithm. Methods: We identified a retrospective cohort of adult and pediatric patients who received ≥1 dose of intravenous vancomycin while admitted to University of Virginia (UVA) Medical Center from 1/2021-1/2023. An increase in creatinine (Cr) of ≥0.3 mg/dL within 48 hours or ≥50% increase in baseline Cr within 7 days, occurring after the first dose and up to 72 hours after the last dose of IV vancomycin, was considered a potential V-AKI event. The electronic algorithm was executed at UVA with only limited contextualization of hospital specific variables (e.g., procedure names). Patients were categorized as excluded/not meeting criteria, or as having an unlikely, possible or probable V-AKI event using a causality framework. A random subset of the cohort underwent chart review by a blinded reviewer for external validation. Percent agreement and a weighted kappa coefficient were calculated. The sensitivity and specificity in identifying at least possible V-AKI events was determined. Results: The electronic algorithm was validated using 200 cases and demonstrated 60.0% percent agreement with chart review (Figure). The weighted kappa coefficient was 0.75. The algorithm was 83.8% sensitive and 71.4% specific in detecting at least possible V-AKI events. Among the 80 discrepant cases, there was only a 1-category difference in 62.5% of cases. The most common reasons for discrepant assessments, which were partly due to inconsistencies in chart review, included disagreement regarding timing of AKI onset (18.6%) and whether renal function returned to baseline (16.3%). Conclusions: An electronic algorithm to identify V-AKI events was successfully implemented at another institution. Although agreement with chart review was only fair, sensitivity in detecting at least possible V-AKI events remained excellent. The electronic algorithm may be useful for systematically and reproducibly identifying V-AKI events across institutions in a scalable manner to inform stewardship interventions. However, further refinement of the algorithm and improvement in consistency of chart review assessments is needed.Disclosure: Lindsay Donohue: Advisor – Abbvie

Intraoperative frozen section evaluation of ovarian sex cord-stromal tumours and their mimics: a study of 121 cases with emphasis on potential diagnostic pitfalls

Ovarian sex cord-stromal tumours (SCSTs) present diagnostic difficulties during frozen section (FS) consultations due to their diverse morphology. This study aimed to evaluate the accuracy of FS evaluation of SCSTs in our institution, as well as to examine the reasons leading to incorrect FS diagnosis. Cases mimicking SCSTs and diagnosed as such during FS were also highlighted. We analysed 121 ovarian SCST cases and their mimics which underwent FS consultations over a 10-year period, to evaluate FS accuracy, reasons for deferrals and discrepancies. FS diagnoses were concordant, deferred and discrepant compared to the final diagnosis in 50 (41.3%), 39 (32.2%) and 32 (26.5%) cases, respectively. Major discrepancies (9/121, 7.4%) were mostly related to the diagnosis of adult granulosa cell tumour (AGCT). A fibromatous AGCT was misinterpreted as fibroma on FS, while a cystic AGCT was called a benign cyst. Conversely, a mesonephric-like adenocarcinoma, a sertoliform endometrioid carcinoma and a thecoma were misinterpreted as AGCT on FS. Another discrepant case was a Krukenberg tumour with prominent fibromatous stroma in which malignant signet ring cells were overlooked and misinterpreted as fibroma. Minor discrepancies were primarily associated with fibroma (21/23, 91.3%), wherein minor but potentially impactful details such as cellular fibroma and mitotically active cellular fibroma were missed due to sampling issues and misinterpretation as leiomyoma. FS evaluation for ovarian SCSTs demonstrated an overall accuracy of 78.5%, 81.0% and 81.8% for benign, uncertain/low malignant potential and malignant categories, respectively. There was no FS-related adverse clinical impact in all cases with available follow-up information (120/121 cases). Intraoperative FS evaluation of ovarian SCSTs is challenging. A small number of cases were misinterpreted, with AGCTs being the primary group where errors occur. Awareness of common diagnostic pitfalls and difficulties, alongside application of a stepwise approach, including (1) obtaining comprehensive clinical information, (2) thorough macroscopic examination and directed sampling, (3) meticulous microscopic examination with consideration of pitfalls and mimics, (4) effective communication with surgeons in difficult cases, and (5) consultation of subspecialty colleagues in challenging cases, will enhance pathologists' reporting accuracy and management of such cases in the future.

#1130 Biopsy-based transcript diagnostics identify early antibody-mediated rejection phenotypes in biopsies with subclinical donor-specific antibodies

Abstract Background and Aims Biopsy based transcript diagnostics using the molecular microscope diagnostic system (MMDx) have the potential to add diagnostic clarification in the antibody mediated rejection (AMR) continuum. While de novo donor specific antibody (dnDSA) or preformed DSA accompanied by allograft function deterioration are accepted indications for allograft biopsy with therapeutic implications, management strategy for subclinical DSA lacks consensus. MMDx might show clinical utility in this controverse scenario by helping with therapeutic decisions. Method In this single-center cohort of 326 indication kidney transplant biopsies assessed by histology and MMDx at the University Hospital Zurich, we analyzed 58 cases with subclinical DSA as biopsy indication. Cases with (n = 44) and without (n = 14) histopathologic features of AMR according to Banff 2022 were compared for molecular AMR rejection transcripts. Results When biopsied for subclinical DSA, all 14 cases without histopathologic features of AMR showed absence of molecular AMR. In contrast, molecular AMR was detected in 6/19 (32%) cases with histopathologic diagnosis of AMR and 2/25 (8%) with probable AMR (p = 0.059), Fig. 1. Microvascular inflammation below threshold with C4d negativity was significantly associated with absence of molecular AMR (p &amp;lt; 0.0001). Higher number of calculated epitope mismatch load for HLA class II as measured by PIRCHE II Score was significantly associated with molecular AMR (p = 0.01). In cases with molecular AMR, early AMR scores predominated (R4 vs R6, 0.0002 and R4 vs R5 0.051). Conclusion No molecular AMR was observed in absence of histopathologic AMR. Yet, in cases with histopathologic features of AMR, only 8/44 showed molecular AMR. Predominance of early AMR rejection phenotype in cases with molecular AMR transcripts allows hope for MMDx to identify treatment amenable cases with subclinical DSA. Discrepant cases call for re-biopsy to guide therapeutic decisions.

Digital Pathology is a Fast and Effective Platform for Providing Head and Neck Pathology Consultations.

Surgical pathology of the head and neck is one of the more challenging areas in all of diagnostic pathology. Its unparalleled diversity and complexity renders it highly vulnerable to diagnostic error compelling unconstrained access to specialized diagnostic expertise. Digital pathology (DP) is a state-of-the-art tool that could facilitate access to specialized expertise, but it is relatively untested in the context of pathology consultations. In a collaboration between Labcorp Dianon and a large academic hospital with subspecialized surgical pathology, DP was implemented to provide the pathology community access to head and neck pathology expertise. From this collaborative experience, glass slides from consecutive consult cases that had been previously diagnosed using DP were reviewed by an expert consultant in a blinded manner following an extended wash-out period. The intraobserver discrepancy rate was recorded. Major discrepancies were defined as those resulting in significant impact on clinical management and/or prognosis, whereas minor discrepancies were those with no impact on care or prognosis. Slides from 57 cases were available for review. The average wash-out period was 19 months. Five discrepancies were recorded (intraobserver concordance rate of 91%). All discrepancies were minor (major discrepancy rate, 0%; minor discrepancy rate, 9%). On appraisal of the discrepant cases, discordant diagnoses were attributed to subjective differences in interpretation rather than objective differences related to the inferiority of DP. DP decreased the median turnaround time by 97% (from 70h 26min to 2h 25min). DP provides efficient and fast access to expert consultants. The speed of case delivery does not compromise diagnostic precision. Discrepancies are uncommon, minor, and reflect subjective interpretative differences inherent to difficult and ambiguous head and neck cases, and not the inferiority of DP as a diagnostic platform. High concordance can be achieved even for those difficult and complex cases that are concentrated in the consultation practice. This observation carries profound implications regarding universal health care access to specialized diagnostic expertise.

Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists.

Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2-negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti-programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.

Sexist, Racist, and Homophobic Violence against Paramedics in a Single Canadian Site.

Violence against paramedics is widely recognized as a serious, but underreported, problem. While injurious physical attacks on paramedics are generally reported, non-physical violence is less likely to be documented. Verbal abuse can be very distressing, particularly if the harassment targets personal or cultural identities, such as race, ethnicity, gender, or sexual orientation. Leveraging a novel, point-of-event reporting process, our objective was to estimate the prevalence of harassment on identity grounds against paramedics in a single paramedic service in Ontario, Canada, and assess its potentially differential impact on emotional distress. In an analysis of 502 reports filed between 1 February 2021 and 28 February 2022, two paramedic supervisors independently coded the free-text narrative descriptions of violent encounters for themes suggestive of sexism, racism, and homophobia. We achieved high inter-rater agreement across the dimensions (k = 0.73-0.83), and after resolving discrepant cases, we found that one in four violent reports documented abuse on at least one of the identity grounds. In these cases, paramedics were 60% more likely to indicate being emotionally distressed than for other forms of violence. Our findings offer unique insight into the type of vitriol paramedics experience over the course of their work and its potential for psychological harm.

Towards clinical implementation of an AI-algorithm for detection of cervical spine fractures on computed tomography

BackgroundArtificial intelligence (AI) applications can facilitate detection of cervical spine fractures on CT and reduce time to diagnosis by prioritizing suspected cases. PurposeTo assess the effect on time to diagnose cervical spine fractures on CT and diagnostic accuracy of a commercially available AI application. Materials and methodsIn this study (June 2020 - March 2022) with historic controls and prospective evaluation, we evaluated regulatory-cleared AI-software to prioritize cervical spine fractures on CT. All patients underwent non-contrast CT of the cervical spine. The time between CT acquisition and the moment the scan was first opened (DNT) was compared between the retrospective and prospective cohorts. The reference standard for determining diagnostic accuracy was the radiology report created in routine clinical workflow and adjusted by a senior radiologist. Discrepant cases were reviewed and clinical relevance of missed fractures was determined. Results2973 (mean age, 55.4 ± 19.7 [standard deviation]; 1857 men) patients were analyzed by AI, including 2036 retrospective and 938 prospective cases. Overall prevalence of cervical spine fractures was 7.6 %. The DNT was 18 % (5 min) shorter in the prospective cohort. In scans positive for cervical spine fracture according to the reference standard, DNT was 46 % (16 min) shorter in the prospective cohort. Overall sensitivity of the AI application was 89.8 % (95 % CI: 84.2–94.0 %), specificity was 95.3 % (95 % CI: 94.2–96.2 %), and diagnostic accuracy was 94.8 % (95 % CI: 93.8–95.8 %). Negative predictive value was 99.1 % (95 % CI: 98.5–99.4 %) and positive predictive value was 63.0 % (95 % CI: 58.0–67.8 %). 22 fractures were missed by AI of which 5 required stabilizing therapy. ConclusionA time gain of 16 min to diagnosis for fractured cases was observed after introducing AI. Although AI-assisted workflow prioritization of cervical spine fractures on CT shows high diagnostic accuracy, clinically relevant cases were missed.