ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 cell clusters (<100um). About 3.3% of negative slides were falsely detected as positive, mainly due to tissue folds and active germinal centres. In the external validation cohort (1033 slides), the method correctly classified 100% of all slides. Conclusion: The deep learning method developed in this study showed excellent performance, making it suitable as an assist- ing tool for CRC-LNM screening. Future studies should include other histological subtypes (mucinous adenocarcinomas, signet ring cell carcinomas), investigate the application for other solid tumour types next to breast and CRC, as well as improve sensitiv- ity for more challenging cases (isolated tumour cell clusters). The specificity could be improved by detecting and excluding tissue folds and germinal centres before applying the metastasis detec- tion model. Funding: Rising Tide Foundation for Clinical Research (CCR-18-295800) and Swiss Cancer Research Foundation (KFS-4427-02-2018) PS-03-034 The creation of a virtual pathology department: a novel solu- tion to a modern crisis R. Chetty*, J. Fitzgerald, M. Colleluori, D. O’Shea *DECIPHEX, Ireland Background & objectives: There are several well-known global challenges confronting Pathology that translate into poor TATs, lack of expertise/access and ultimately poor patient care. Our aim was to alleviate these pressure points to improve patient management. Methods: A multitude of challenges are currently faced in Pathol- ogy resourcing. To this end, we developed an AI-empowered digi- tal pathology system using a proprietary, customizable, scanner agnostic, cloud-based, LIS integratable, state-of-the-art pathology PACS. We then recruited and validated a team of recognized sub- specialists to constitute the world’s first CQC/CLIA accredited virtual pathology department. Results: Across our pathologist network we currently have 56 pathologists in funnel across 12 subspecialities. The team is geographically distributed across Europe, UK, Canada and the US. We have fully validated our pathologists according to RCPath/CAP guidelines and have shown over 97% concordance for glass versus digital cases. Only minor discordances occurred, and a discordance remediation process was put in place whereby blind review of the discordant case was performed again and diagnostic accuracy recorded. We are currently producing successful turnaround times of <2 days in pilot trials. Pathologist efficiency has improved with the use of measuring and mitoses counting tools, including Ki-67 quantification. Conclusion: Overall Client hospital satisfaction is highly evident with TAT decreased, no mailing of slides required, MDT ready reports not being re-typed, and going into LIS directly, saving both time and overheads. Pathologist satisfaction, quality control and efficiency are evaluated for this disruptive workflow, with net pro- moter score systems and tools employed to ensure optimal patholo- gist experience and high-quality reporting achieved. PS-04 | Poster Session Nephropathology PS-04-001 Morphometric analysis of lysosomes in the renal tubule in mon- oclonal gammopathy using transmission electron microscopy: ‘mottled appearance’ and beyond M. Jung*, H. Lee, K.C. Moon *Department of Pathology, Yonsei University College of Medicine, Republic of Korea Background & objectives: Lysosomal ‘mottled appearance’, or uneven electron-dense contents related to monoclonal gammopathy (MG), has been described in light chain proximal tubulopathy (LCPT). We aimed to determine the ultrastructural characteristics of lysosomal mottled appearance in kidney biopsies and its association with LCPT. Methods: Seventy-seven biopsies were grouped into LCPT (n = 5), MG conditions other than LCPT (n = 43), and non-MG conditions (n = 29). The mottled lysosomes in the renal tubules were evalu- ated using transmission electron microscopy and morphometric analysis. Results: Mottled lysosomes were more prevalent (% of present cases) and frequent (no. of mottled lysosomes/20,000x ultrami- croscopic field) in the LCPT group (100% and 8.20 ± 4.15/field) than in the MG (41.9% and 1.13 ± 2.05/field) and non-MG (37.9% and 0.80 ± 1.44/field) groups. In morphometric analysis of all mot- tled lysosomes (n = 520) detected from the 34 biopsies (5 LCPT, 18 MG, and 11 non-MG), we found that mottled lysosomes were larger, more irregular, and more electron-dense for the LCPT group than for the MG and non-MG groups. Conclusion: Mottled lysosomes can be present in disorders other than LCPT or even without MG. The morphological characteristics of mottled lysosomes could provide objective guidance for the diagnosis of LCPT. PS-04-002 Gene expression characteristics of T-cell-mediated alloimmune response in HIV-infected kidney transplant recipients D. Dobi*, A. Zarinsefat, Y. Kelly, P. Stock, Z. Laszik *Semmelweis University, Hungary Background & objectives: The graft survival of HIV-infected renal transplant recipients are comparable to that of non-HIV infected referents. However, the frequency of first-year T-cell- mediated rejection (TCMR) in the former group is higher. We assessed the molecular characteristics of TCMR in HIV-infected individuals. Methods: We studied formalin-fixed paraffin-embedded (FFPE) renal biopsy samples from 68 transplant recipients (34 HIV+, 34 HIV-). The diagnostic groups were normal, borderline changes, and TCMR. We applied gene expression analysis on the FFPE material by using a panel of 760 targets that included immune- response-related and HIV genes. We performed differential gene expression (DE) analysis and pathway analysis (PA) (reactome database). Results: DE analysis revealed multiple genes with significantly increased expression in the diagnostic groups of HIV+ borderline changes and HIV+ TCMR relative to their HIV- counterparts. PA of these genes showed gene enrichment in the following path- ways: toll-like receptor cascades, MYD88:MAL cascade, cyto- solic sensors of pathogen-associated DNA, and NLR-signalling among others. HIV genes were not found to be present in the biopsy material of HIV-infected patients. Conclusion: Upregulation of the innate immune pathways in the biopsies of HIV+ patients with borderline changes and TCMR may indicate the enhanced involvement of natural immunity dur- ing T-cell-mediated alloimmune response in this patient group. This can potentially stem from immune dysregulation caused by HIV infection. S84

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