ECP 2023 Abstracts

S38 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 limitations when pathognomonic signs are in too small areas and scat- tered in the sample. But even under an EM, undiagnosed cases remain. OFP-10-002 Brazilian pathology teaching forum: teaching-learning tool G. Brasileiro Filho, D. Nunes Oliveira*, L.C. Lima Ferreira, M. Freire Santana, F. Toledo Bueno Pereira, D. Masashi Sugita, S. Correia Leão, G. Pozzan, A.C. Siquara de Sousa, R. Vilar Lima, J. Carneiro Melo *University of Fortaleza, Brazil Background & objectives: Supported by the Brazilian Society of Pathology (SBP), Pathology teachers from all over Brazil came together to stablish a forum (FEP) aimed at improving the academic work of professors and the teaching-learning of medical students. Methods: The forum actions are conducted by 4 working groups: 1-Metacognition (didactic strategies and resources, which deals with the bases of learning and didactic-pedagogical actions, including com- putational tools); 2- Pedagogical bases (educational objectives, courses contents, expected competences and teaching-learning methodology); 3-Learning assessment; 4 - Elaboration of instructional materials (macro and microcopy figures, clinical cases, autopsies and others). Results: Since 2019, the forum has make available: a) videoclasses on several topics: medical education, general pathology and many aspects of COVID-19; b) recomendations about curricular contents and com- petences (general and specific) in Pathology, for broad use by medical schools in the whole country; c) macroscopic and microscopic figures of around a hundred cases (general Pathology, cytopathology, infec- tious diseases and many cancer types). Conclusion: Providing effective Pathology learning, especially in a very large and diverse country (350 medical schools), is really chal- lenging. Sharing basic educational rules and successful experiences to thousands of professors all over the country can make a notori- ous difference. The initial good adherence from dozens of colleagues, from different parts of the country, has make possible steps ahead. The potential achievement for this group is promising, so we are convinced that this work can really improve medical education in Brazil. OFP-10-003 Truncated titin is incorporated into the sarcomere in human car- diac samples of dilated cardiomyopathy D. Kellermayer*, H. Tordai, B. Kiss, G. Török, A.A. Sayour, M. Pólos, I. Hartyánszky, B. Szilveszter, S. Labeit, A. Gángó, G. Bedics, C. Bödör, T. Radovits, B. Merkely, M. Kellermayer *Department of Pathology, University of Pécs, Hungary Background & objectives: Heterozygous (HET) truncating mutations in the TTN gene (TTNtv) encoding the giant titin protein are the most common genetic cause of dilated cardiomyopathy (DCM). However, the molecular mechanisms by which TTNtv mutations induce DCM are controversial. Methods: Here we investigated 127 clinically identified DCM human cardiac samples with next-generation sequencing (NGS), high-reso- lution gel electrophoresis, Western blot analysis and super-resolution microscopy in order to dissect the structural and functional conse- quences of TTNtv mutations. Results: The occurrence of TTNtv was found to be 15% in the DCM cohort. Truncated titin proteins were detected in the majority of the TTNtv samples. The total amount of expressed titin, which includes the truncated fragments, was comparable in the TTNtv+ and TTNtv- samples. Prot- eomic analysis of washed myofibrils and Stimulated Emission Depletion (STED) super-resolution microscopy of myocardial sarcomeres labelled with sequence-specific anti-titin antibodies revealed that truncated titin is structurally integrated in the sarcomere. Sarcomere length-dependent anti-titin epitope position, shape and intensity analysis pointed at structural defects in the I/A junction and the M-band of TTNtv+ sarcomeres. Conclusion: The comparable amount of titin in the TTNtv+ and TTNtv- samples indicates that titin haploinsufficiency may not be the leading cause of the pathogenesis. The sarcomeric integration of TTNtv may contribute, via faulty mechanosensor function, to the development of manifest DCM. Funding: NVKP_16-1-2016-0017, K135076 (B.M.), K135360 (M.K.) OFP-10-004 Cardiac amyloidosis: the role of endomyocardial biopsy to assess the myocardial damage M. De Gaspari*, L. De Michieli, E. Barbieri, S. Rizzo, T. Berno, M. Perazzolo Marra, M. Della Barbera, D. Mele, C. Basso, A. Cipriani *Cardiovascular Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua - Azienda Ospedaliera, Padova, Italy Background & objectives: The two most common forms of cardiac amyloidosis (CA) are immunoglobulin light chains (AL-CA) and tran- sthyretin (ATTR-CA), with diverse clinical course and prognosis. Our aim was to compare clinical and pathological data of CA patients who underwent endomyocardial biopsy (EMB). Methods: An observational retrospective study was performed on patients with a diagnosis of CA who underwent comprehensive clini- cal evaluation in our centre from 2012 to 2022, including histologi- cal confirmation of cardiac involvement by EMB. Clinical parameters including high sensitivity cardiac troponin I (hs-cTnI) values and echo- cardiographic data were compared to histological findings. Results: A total of 40 patients were included (66% males, mean age 67 years). Fourteen patients were affected by ATTR-CA (35%) and 26 by AL-CA (65%). At histology, mean amyloid burden was 25.9% (range 3%–85%). A perivascular pattern of amyloid deposition was demon- strated in 50% of EMB, being more frequent in AL- than ATTR-CA (62% vs 29%, p=0.047). Myocyte vacuolization was present in 60% of EMB, replacement-type fibrosis in 40% whereas myocyte necrosis, edema and inflammation in less than 10%. An increase in myocyte diameter and amyloid burden corresponded to worse morphofunctional parameters. The perivascular deposition pattern was associated with altered longitudinal strain, reduced ejection fraction and higher hs- cTnI values. Conclusion: In CA significant correlations between the clinical param- eters and the histological changes on EMB are found. Cardiomyocyte diameter, amyloid burden and perivascular deposition were associated with relevant laboratory and echocardiographic morphofunctional alterations reflecting myocardial injury caused by amyloid deposition. These data support the role of EMB in clarifying the mechanisms of myocardial injury responsible for worse prognosis in CA patients. OFP-10-005 Morphological cardiac phenotyping with automated quantification of fibrosis, fat and myocardial tissue using QuPath software P.H. Holm*, K.B. Olsen, B.G. Winkel, J. Tfelt-Hansen, J. Banner *Section of Forensic Pathology, Department of Forensic Medicine, University of Copenhagen, Denmark Background & objectives: Cardiac diseases like arrhythmogenic car- diomyopathy are linked to structural abnormalities like fibrosis and fat replacement. Assessments by pathologists are somewhat subjective and using state-of-the-art stereology is time-consuming. We aimed to develop a standardized semi-automated method for cardiac phenotyp- ing using QuPath. Methods: Whole-slide samples of Picro Sirius Red-stained myocar- dial tissue were used to develop a pipeline in QuPath. Five cases (25 regions) were used for training. The process included training a pixel classifier to annotate the tissue sample, semi-automatically dividing the tissue into regions, training a different pixel classifier to differentiate