ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 histological grade (p=0.005) and a solid/macrotrabecular architecture (p=0.017). Conclusion: Our retrospective data confirmed the literature on resected HCCs, showing a worse OS in patients exhibiting MPVI vs MVI. The perspective phase of our study is still in progress, but our preliminary data on NGS results suggest a progression from TERT- mutated HCCs, which develop MVI, to TP53 mutation, which can predict MPVI, besides a more aggressive behaviour. OFP-03-004 Acinar cystic transformation of the pancreas: clinical and molecular analysis for unravelling its heterogeneous nature P. Mattiolo*, O. Basturk, A. Mafficini, O. Kerem, R.T. Lawlor, S. Hong, L.A. Brosens, V. Adsay, A. Scarpa, C. Luchini *Department of Diagnostics and Public Health, Section of Pathol- ogy, University of Verona, Verona, Italy Background & objectives: Acinar cystic transformation (ACT) of the pancreas is a poorly understood and rare entity among pancre- atic cystic lesions. This study aims at clarifying their real nature. Methods: The study cohort includes 25 pancreatic ACT, represent- ing the largest series of ACT in the literature. Here we provide their clinicopathological characterization along with molecular profiling by next-generation sequencing (NGS). Results: ACT were more common in female patients, frequently in body-tail region. At follow-up, all patients were alive and free of disease. Histologically, all cysts were lined by typical acinar epithelium, sometimes intermingled with columnar or ductal-like epithelium. Cell atypia, necrosis, mitoses, and invasive carcinoma were absent. Three cases showed a patchy distribution, and two cases were associated to ductuloinsular complexes with centroaci- nar microcysts. Two ACT showed peculiar histologic features: one showed a distinctive microcystic pattern, and another harboured foci of low-grade dysplasia in the areas lined by ductal-like epi- thelium. NGS detected the presence of two pathogenic / likely- pathogenic mutations in two different cases: KRAS, c.34G>C, p.G12R, and SMO, c.1685G>A, p.R562Q. Conclusion: Overall considered, our findings indicate that ACT is as a heterogeneous entity. It seems to encompass lesions with different possible pathogenesis, which includes the evolution from a centroacinar microcyst, and malformative, obstructive, or neo- plastic origins. The potential presence of driver mutations call for a careful management of ACT patients, taking into account also surgical resection and active imaging surveillance / life-long follow-up. OFP-03-005 Spatially resolved transcriptomic and proteomic analysis of pancreatic cancer reveals distinct profiles which correlate with site of recurrence A.S. Wenning*, B. Gloor, P. Aeschbacher, A. Perren, E. Karamitopoulou-Diamantis *Department of Visceral Surgery, University Hospital Bern, Switzerland Background & objectives: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal neoplasm. The majority of patients with localized disease will eventually develop tumour recurrence after complete surgical resection. Here we investigate tumour- and immune cell determinants of PDAC recurrence. Methods: PDACs (n=284) were classified according to recurrence site as liver (n=93/33%), lung (n=49/17%), local (n=31/11%), peritoneal recurrences (n=38/13%) and no-recur- rence (n=73/26%). Four regions of interest per tumour were selected. Spatial compartments were identified with fluorescent imaging followed by transcriptomic (pancytokeratin+tumour cell compartment) and proteomic (CD45+leukocyte compart- ment) analysis for immune pathway associated targets by using a digital spatial profiling platform. Results: Median overall-sur vival for the PDAC-groups was 16months (liver), 27months (lung), 26months (local), 12.5months (peritoneal) and 64months (no-recurrence). The tumour cell-compartment of 60% of the non-recurrent PDACs, as well as 45%, 40% and 31% of the lung, local and peritoneal recurrences respectively, showed significant upregulation of pathways involved in T cell activation, immune cell adhesion/ migration, antigen presentation and cytokine signalling, as compared to only 20% of liver recurrences. CD66b (granu- locyte-marker) and STING (mediator of immunosuppressive microenvironment and feature of the basal-like subtype) were strongly up-regulated in the liver leukocyte-compartment. The non-recurrent leukocyte-compartment revealed significant up-regulation of CD3, CD4, CD8, CD20, GZMB, HLA-DR, checkpoint molecules and beta-2-microglobulin compared to all recurrent tumours. Conclusion: We found distinct spatial and microenvironmen- tal profiles on gene and protein level in each recurrence group, which differed from each other as well as from the no-recurrence group, underlining the heterogeneity of PDAC. Tumours with liver recurrence display poor prognosis associated with unfavour- able immune signalling and features of the basal-like molecular subtype. OFP-03-006 A comparative analysis of CPA1, BCL10 and chymotrypsin for the distinction of pancreatic acinar cell carcinomas R. Uhlig, S. Minner, A. Luebke, S. Weidemann, P. Lebok, N. Gorbokon, G. Sauter, F. Jacobsen, T.S. Clauditz* *University Medical Center Hamburg, Germany Background & objectives: Pancreatic acinar cell carcinoma (PACC) is a rare tumour of the pancreas with an interme- diate prognosis as compared to pancreatic neuroendocrine tumours (PNE) and pancreatic duct al adenocarcinoma (PDAC) from which it may be difficult to distinguish by morphology alone. Methods: To study was the efficiency of immunohistochemical markers, 18 PACCs, 531 PDACs, 64 PNEs, 117 extrapancreatic neuroendocrine neoplasms (EPNN), 826 colorectal carcinomas (CRC) and 252 gastric carcinomas (GC) were analysed with anti- bodies for CPA1 (MSVA-601M), bcl10 (Santa Cruz sc5273), and chymotrypsin (Biorad 2100-0657) in a tissue microarray format. Results: CPA1 was positive in 18 of 18 (100%) of PACCs, 0 of 49 (0%) of PNEs, 0 of 88 (0%) of EPNNs, 10 of 404 (2.5%) of CRCs, and 0 of 178 (0%) of GCs. Chymotrypsin was posi- tive in 16 (87,5%) PACCs, 1 (2%) PNEs, 2 (2.3%) EPNNs, 10 (2.5%) CRCs, and 1 (0.6%) GCs. Bcl10 was positive in 18 (100%) PACCs, 2 (4.1%) PNEs, 5 (1%) EPNNs, 109 (27%) CRCs, and 18 (10%) GCs. These data resulted in a sensitivity and specificity of 100%/99.2% for CPA1, 100%/88.4% for bcl10, and 94.4%/98.6% for chymotrypsin. Conclusion: CPA1 and chymotrypsin are both highly specific and sensitive for ACC while bcl10 is sensitive but has markedly lower specificity. Because all “false positive” cases identified by CPA1 were CRCs that only showed a positive staining in goblet cells and an identical staining pattern was observed in all these cases for chymotrypsin and bcl10, a pancreatic origin of the mucus in these goblet cells is concluded. S12