ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 Background & objectives: A combination of different immune- checkpoint-inhibitors (ICIs) have shown remarkable success in sev- eral tumour entities. However, the likelihood of positive response to ICIs is poor in most tumour entities. Little is known about the spatial orchestration between immune checkpoint+ cells. Methods: To study the spatial interplay between TIM3, PD-L1, PD-1, and CTLA-4 expression on lymphocyte-, macrophage subsets, dendritic cells, in relation to panCK+ malignant cells, and other structural tumour compartments, a 18 marker BLEACH&STAIN multiplex fluorescence immunohistochemistry approach was used to analyse >5000 carcinoma samples from 40 different carcinoma entities. A deep learning-based framework for image analysis was used. Results: TIM3, PD-1, PD-L1, and CTLA-4 expression was successfully quantified on tumour cells (panCK+), cytotoxic T-cells (CD3+CD8+), T-helper cells (CD3+CD4+), regulatory T-cells (CD3+CD4+FOXP3+), M1 and M2 macrophages (CD68+CD163+/ CD68+ CD163-) and dendritic cells (CD11c+). TIM3 as well as CTLA-4 expression on CD3+CD8+ cytotoxic T-cells and CD3+CD4+FOXP3+ regulatory T-cells showed a spatially more diverse expression pattern – particularly in bladder cancer – compared to PD-1 expression on all analysed T-cells subsets that was consistently accompanied by PD-L1 expression on immune and tumour cells (p<0.001). A high density of immune checkpoint positive T-cells, macrophages and dendritic cells was linked to low pT stage (p≤0.014 each). Conclusion: BLEACH&STAIN facilitates deep profiling of 18 bio- markers in more than 40 different carcinoma entities and revealed complex changes in the spatial orchestration of a wide range of immune cell subsets that were driven by the expression profile and composition of TIM3, PD-L1, PD-1 and CTLA-4. OFP-05-006 Successful deployment of an AI solution for prostate biopsies diagnosis in clinical practice O. Sukmanov*, A. Yosepovich, S. Ish – Shalom, S. Ikher, N. Ziv- Sokolovski, N. Temper, R. Ziv, I. Krasnitsky, I. Yazbin, G. Mallel, M. Grinwald, C. Linhart, M. Vecsler *Kaplan Medical Center, Israel Background & objectives: This study aimed to prospectively evaluate the performance and clinical utility of the AI-based Galen Second Read Prostate workflow solution on detection of prostate adenocarcinoma in real world clinical routine use. Methods: A prospective, single-centre observational diagnostic study including digitized histopathology slides of all consecutive prostate core needle biopsies (CNBs), TRUS and MRI-targeted, was performed. Slides were blindly processed by the AI solu- tion, while, in parallel, pathologists reviewed the cases. Alerts were triggered in case of discrepancies between the AI results and initial pathologist’s diagnosis, prompting a second review by the pathologist. Results: Five senior pathologists participated in the study and reported on 109 prostate CNBs comprising 2,684 H&E slides, 60% of which were MRI-targeted biopsies that had up to 66 H&E slides/case. Analysis was performed at block level, 109 cases comprised 986 blocks, 190 (19.3%) were reported as adenocarcinoma, 2 (0.2%) as ASAP and 794 (80.5%) were benign. The AI solution demonstrated extremely high perfor- mance for detection of cancer with AUC = 0.994 (95% CI: 0.991-0.997), sensitivity of 96.9%, specificity of 94.96% and NPV of 99.21%. Moreover, following the second review by the pathologists, five alerted cases were revised from benign to cancer, leading to 4.6% decrease in diagnostic error rate. Conclusion: This prospective study reports the successful deployment of the Galen Prostate diagnostic support solution, in routine clinical practice. The AI solution enabled 100% Quality Control on prostate biopsies and increased diagnostic accuracy and patient safety, decreasing diagnostic errors by 4.6% and pre- venting missed cancers. Thus, AI solutions could be used as sig- nificant aiding tools for pathologists in clinical decision-making in routine pathology practice. OFP-05-007 The new entities LOT and EVT among oncocytic tumours of the kidney: a retrospective mono-institutional experience with re-analysis of 16 cases A. Bressan*, P. Colombo, M. Valeri, M. Cieri, G. Elefante, S. Pan- cetti, V. Belsito, L. Terracciano, R. Hurle, M. Lazzeri, P. Casale *Department of Pathology, IRCCS Humanitas Clinical and Research Hospital, Rozzano, Italy Background & objectives: Low-grade oncocytic and eosinophilic vacuolated tumours (LOT and EVT) have been proposed as dis- tinct entities with low malignant potential in the spectrum of renal oncocytic neoplasms. We report 16 further cases of these rare and controversial categories with clinico-pathological description. Methods: Oncocytomas (RO), Hybrid Tumours (HT), and Chromo- phobe carcinomas (ChRCC) diagnosed in our Institution from 2015 to 2021 were retrospectively reviewed. On all selected cases, we performed immunohistochemical analysis for CD117 and CK7 to identify LOTs and EVTs. Histological features, phenotype, molecu- lar profile, and clinical data were recorded. Results: From 431 tumours, 7 LOTs and 9 EVTs were identified. Male/female ratio was 1:1,3 and 2:1, with median age of 67 and 58 yrs, and median size of 2,7 and 4,2 cm, respectively. LOTs over- lapped RO/ChRCC with eosinophilic cytoplasm and perinuclear halos; EVTs showed intracytoplasmic vacuoles and atypical nuclei. LOTs were positive for CK7, CKpan, CD63, AMACR, CD15 (but CD117 negative overlapping ChRCC). EVT were positive for CD117, AMACR, CKpan, and CD10 (but CK7 negative/focally+, opposed to LOT/ChRCC). Interestingly, EVTs CKpan immunoreac- tivity often reflected a biphasic cellularity (6/9 cases). Rearranged genes in mTOR pathway were occasionally found in both tumours. Both LOTs and EVTs behaved indolently (follow-up 9-72 months). Conclusion: Here, we described a further group of LOTs and EVTs from a retrospective cohort analysis. Our data confirm LOT and EVT as emerging entities with peculiar histological features, a specific immune-profile, and indolent behaviour, which should be identified among “pink” tumours of the kidney. In the future, these tumours deserve further clinico-pathological studies for pro- moting the awareness and improving classification of these new categories that will be described in the 2022 Genitourinary WHO classification. OFP-05-008 A novel pT1 substaging system for high-grade urothelial blad- der carcinoma: a prospective mono-institutional confirmatory progression risk analysis M. Valeri*, R. Contieri, V. Fasulo, M. Cieri, G. Elefante, C. De Carlo, A. Bressan, C. Saitta, A. Gobbo, P.P. Avolio, R. Hurle, M. Lazzeri, G. Taverna, L. Terracciano, P. Colombo *Department of Pathology, IRCCS Humanitas Clinical and Research Hospital, Rozzano, Italy Background & objectives: The Rete Oncologica Lombarda (ROL) system for substaging pT1 high-grade (HG) urothelial car- cinoma (UC) showed high predictive value for progression after S20