ECP 2023 Abstracts

S129 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Background & objectives: Primary liver carcinomas (PLC) com- prise hepatocellular carcinoma (HCC), combined hepatocellular- cholangiocarcinoma (cHCC-CCA) and intrahepatic cholangiocarci- noma (iCCA), displaying continuous histopathological features and distinct molecular profiles across PLC spectrum heterogeneity. We aimed to investigate gene expression profiles in a small series of PLC. Methods: Seven patients (5 cirrhotic), with main risk factors being alco- hol intake and viral hepatitis, undergoing liver transplantation/resection were studied, concerning 7 PLC: 2 HCCs CK19-/CK7- and 2 HCCs CK19+/CK7+, 1 cHCC-CCA and 2 iCCAs, classified according with WHO 2019 histopathological criteria. Gene expression profiling and sequencing of relevant microdissected areas were performed by next- generation sequencing (Genexus, Oncomine Precision Assay Panel). Results: Mutations in EGFR predominated in HCC CK19-/CK7-; CTNNB1 in HCC CK19+/CK7+; TP53/FGFR3 in cHCC-CCA and ALK in iCCA; TP53 mutations: HCC CK19+/CK7+, cHCC-CCA and iCCA; ALK and EGFR mutations: HCC CK19-/CK7-, HCC CK19+/ CK7+ and iCCA. HCC CK19+/CK7+ and iCCA shared RET, ALK, EGFR and TP53 mutations; while PIK3CA mutations were present in HCC CK19-/CK7- and cHCC-CCA. AR and KIT mutations were exclusively seen in cHCC-CCA. HCC CK19+/CK7+ shared more mutations with iCCA than HCC CK19-/CK7- with iCCA; cHCC-CCA and iCCA shared more mutations than HCC and cHCC-CCA. An asso- ciation (p<0.05) was determined between: ERBB3, IDH2, MAPK2 and PDGFRA mutations and HCC CK19+/CK7+; FGFR1/FGFR4 and HCC CK19-/CK7-; AR/KIT mutations and cHCC-CCA. Conclusion: This preliminary study suggests that HCC with cholangio- cytic features and cHCC-CCA share hepatocarcinogenic pathways with iCCA, being genetically closer. Acknowledging a probable continuous mutational landscape might elucidate the interpretation in between his- topathological criteria and cell of origin. HCC CK19+/CK7+ targeted therapy might benefit from a CTNNB1, TP53, ALK, EGFR, MAP2K2, RET, PTEN, and IDH2 panel, standardized for PLC spectrum. This knowledge would allow better understanding the clinical course and PLC heterogeneity, together with improving tumour classification and treatment. Funding: ROCHE-APEF (Portuguese Association for the Study of the Liver) research grant. PS-23-008 An HE-only workflow for liver fibrosis assessment using HE-pre- dicted collagen R. Fick*, G. Balezo, C. Bertram, C. Tilmant, S. Petit, S. Ben Hadj *Tribun Health, France Background & objectives: To highlight fibrotic collagen in liver dis- ease, special stains like Masson’s Trichrome (MT), Sirius Red (SR), or Saffron (HES) are required. This study aims to highlight collagen directly from Hematoxylin and Eosin (HE) stained liver biopsies using deep learning. Methods: We obtained 11 retrospective liver cases with varying degrees of fibrosis. For each case, we collected three consecutive slides, each stained with HE, and separately overstained with either HES, MT, or SR. We predict the collagen on the HE (c-HE) using deep learning. We validate our approach by having two pathologists do METAVIR scoring on the special stains and c-HE. Results: Results reveal a strong pixel-wise correlation between c-HE and each registered special stain (HES: 0.87, MT: 0.78, SR: 0.71) with p-value<1e-5, indicating accurate collagen content inference from HE- stained liver biopsies. Pathologist agreement on METAVIR scores was high, with P1 at 10/11 and P2 at 11/11 cases for both special stains and c-HE. This supports the potential for deep learning to replace spe- cial stains in detecting fibrosis, maintaining high-quality METAVIR evaluations. Conclusion: In conclusion, our study demonstrates that deep learning can accurately infer collagen content from HE-stained liver biopsies, both quantitatively and qualitatively, showing a high correlation with the standard special stains traditionally used to highlight collagen. Moreover, the agreement between pathologists on METAVIR scores remains high when using our digital HE-predicted collagen method, suggesting that this approach can potentially replace the need for spe- cial stains in detecting fibrosis without compromising the quality of METAVIR evaluations. PS-23-009 Hepatic resection for colorectal cancer metastases: the role of the histopathologist as a bridge between science and medicine when assessing background liver pathology following chemotherapy M. Hanks*, L. Khasati, C. Santos, A. Zaitoun *Nottingham University Hospital NHS Trust, United Kingdom Background & objectives: The liver is a common site for colorec- tal metastases; chemotherapy is often administered prior to hepatic resection leading to regimen specific effects on liver parenchyma. We assessed these changes to enable pathologists to produce informative reports to optimise patient care. Methods: We reviewed hepatic resection cases containing colorectal metastases between 2013-2022. Samples were assessed for chemo- therapy associated regression and non-tumour parenchyma for steato- sis, lobular inflammation and hepatocyte balloon degeneration using Brunt Scoring; fibrosis was assessed using Metavir grading. Sinusoi- dal dilatation was assessed using Rubbia-Brandt grading. Presence of focal hepatocyte plate disruption, peliosis, veno-occlusive disease-like changes or parenchymal extinction lesions were recorded. Results: 100 cases were reviewed; 74 male and 26 female. Sinusoidal dilatation was seen in 100% of cases with 33% involving over 2/3s of the lobule. Steatosis was noted in 79% with 52 cases showing mild steatosis. Ballooning degeneration was present in 57% of cases and fibrosis in 31%, the most grade was F1 (13%). Lobular inflammation was evident in 62 cases. Hepatocyte plate disruption was noted in 58% of cases and nodular regenerative hyperplasia in 57%; this was most often subtle. 1 case showed peliosis. 16 samples showed veno-occlusive disease-like changes. Parenchymal extinction lesions were seen in 16% of cases. Conclusion: Our findings highlight the variety of background liver parenchymal changes that occur following chemotherapy in the man- agement of hepatic colorectal metastases. It is important to recog- nise chemotherapy-induced liver injury as these may reduce hepatic functional reserve and increase morbidity and mortality. Our findings emphasise the importance of multidisciplinary team discussions to maximise patient care and highlights the key role of the pathologist as a bridge between Science and Medicine in the management of patients with hepatic metastases from colorectal cancer. PS-23-010 Digital spital profiling reveals possible predictive and prognostic markers in pancreatic cancer S.I. Jeong*, K.R. Lee, S. Lee, J.A. Lee, H.Y. Na, J. Kim *Department of Pathology, Seoul National University Bundang Hos- pital, Seongnam, Gyeonggi, Republic of Korea; Department of Pathol- ogy, Seoul National University College of Medicine, Seoul, Republic of Korea Background & objectives: Despite improvements in surgical and medical treatment, the prognosis of pancreatic cancer remains poor. We intended to uncover novel predictive or prognostic markers in pancreatic cancer by using digital spatial transcriptomic and immunohistochemical (IHC) analysis.