ECP 2023 Abstracts

S10 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 When applying the new WHO reporting system (WHO-RS), risk of malignancy(ROM) ranged from 71% in the benign/negative category to 97% in the malignant category. However, as an oncological centre, the ROM of our population can present a sampling bias. Conclusion: With the growing need for multiple testing (histologic, molecular) of lung malignant neoplasms and the decreasing size of histological samples, it is essential to determine diagnostic accuracy of additional tests that can be performed concomitantly. Studies demonstrate a BW sensitivity range from 29-78% in central lesions, thus our results in overall lesions are within expected. Regarding WHO-RS, we observed higher ROM than expected for most categories. However estimated ROMs are based on few retrospective studies, thus further studies are needed. OFP-02-014 Routine next generation sequencing testing on lung adenocarci- noma pap-stained (OH-fixed) cytological samples T. Labiano*, E. Almudevar, D. Guerrero-Setas *Hospital Universitario de Navarra, Spain Background & objectives: Minimally invasive methods are used for diagnosis and staging in patients of suspected lung cancer. In Lung Adenocarcinoma (L-ADC) biomarkers testing is mandatory for a com- prehensive diagnosis. Aim of this study is to describe clinico-patho- logical characteristics and NGS results. Methods: We selected 125 L-ADC cytological cases diagnosed in 2021.Oncomine-Focus Assay,52-genes panel (Thermo-Fisher) was used after ADN/ARN extraction from OH-fixed pap-stained slides. Sample procurement techniques were: EBUS-FNA 45.6% (57/125);US- FNA 24% (30/125); CT-FNA 13.6%; Pleural fluid 7.2% and EUS-FNA 5.6% and other 7.2%.Location of tumour was both primary (16%)and metastatic disease (84%).ROSE and Tumour Fraction(T%) and Cel- lularity were assess in all cases by cytopathologists. Results: We included 125 patients (83 M/42F), mean age 66.7 yo (range 46-89).Valid test rate was 89.6% (112/125).In 15 cases we obtained not valid results:7 studies were invalid for both AND & RNA, in 5 for DNA, one for ARN and in two cases without CNV detection. T% median was 90%(mean 75.4%). Among patients with invalid results 10 were rebi- opsied. Thirty two patients have no genomic aberrations (24.4%).Co- ocurring molecular alterations-rate was 47,5%.Molecular alterations in KRAS and EGFR genes were the most frequent identified in 37(33%) and 22(16%) cases respectively. Included 2 Insertions in exon 20 and two cases with concomitant KRAS+EGFR mutations . We found also 6MET alterations, 5BRAF and 2 fusion (EML4-ALK and KIF5B-RET). Conclusion: Cytological samples obtained by minimally invasive pro- cedures are a good source for routine NGS testing. The routine use of these samples for NGS has the potential to improve detection of biomark- ers, essential for lung cancer patients treatment management and better survival in lung ADC patients. Co-ocurring molecular alterations are frequent. Rapid on-site assessment is a useful tool to ensure adequate material is present and to check tumour fraction. Low T% and/or low cellularity are related factors with invalid results and required rebiopsy. OFP-02-015 Immediate and long-term risk of preneoplastic or neoplastic cervi- cal lesion with a low-grade cytology after a positive mRNA-HPV test. The protective role of a negative HPV test result in the first round of a primary HPV screening programme R. Granados*, J. Duarte, A. Gutierrez-Pecharromán, D. Luján, B. Raposo, I. Solís, L. Molpeceres, P. Bajo *Hospital Universitario de Getafe, Spain Background & objectives: Although screening guidelines calculate CIN2+ risks considering previous test results, data is scarce due to the newness of primary HPV programmes. This study analyses the value of a previous HPV test result for managing women with a low-grade cytology test. Methods: A prospective longitudinal study of 2,112 women, aged 25-65. Cotest was performed with ThinPrep cytology and mRNA Aptima HPV-test (AHPV). CIN2+ risks were measured and compared among the following subsets:1) interventional group (IG,n=1,975) recruited for a second cotest 3-5 years later; 2) positive cotest (n=75) with AHPV+ and low-grade (ASCUS/LSIL) cytology; 3) mixed cotest (n=62) with AHPV negative and ASCUS/LSIL. Results: From the IG group, 19 women had positive AHPV and low- grade cytology in the new cotest and a 1-4 year follow-up (FU). Imme- diate (<12 month) and long-term risks for CIN2+ were 0 and 5,3%, respectively. Cases with low-grade cytology but negative AHPV in second cotest had a 0% 0-6y risk. Women with positive initial cotest had an immediate risk of 24% and a 4,4y risk of 33,3%. The group with mixed cotest (ASCUS/LSIL but negative AHPV) had immediate and 4,6y risks of 0% and 3,2%. Risk differences between AHPV positive and negative cases with ASCUS/LSIL and those of AHPV-positive women with or without a previous negative AHPV, were statistically significant. Conclusion: The risk of developing a preneoplastic or a neoplastic (CIN2+) lesion in women with a low-grade cytology and a positive AHPV test is significantly higher when there is no previous history of HPV testing, warranting a colposcopic study and/or biopsy. However, a previous negative AHPV test confers a protective effect, lowering the risk of CIN2+ below the threshold of colposcopy referral. These findings, verified in a longitudinal study, are relevant and pertinent for patient management in primary HPV screening programmes. OFP-03 | Oral Free Paper Session Digestive Diseases Pathology – Liver/Pancreas OFP-03-001 Spatial heterogeneity of immune drivers coordinates the organisa- tion of antitumor immunity in pancreatic cancer, affecting patient outcome A.S. Wenning*, I. Marinoni, P. Aeschbacher, B. Gloor, A. Perren, E. Karamitopoulou *Department of Visceral Surgery, University Hospital Bern, Switzerland Background & objectives: Pancreatic ductal adenocarcinoma (PDAC) is considered low immunogenic with “cold” tumour microenvironment (TME) and is mostly unresponsive to immune checkpoint blockade therapies. Here we decipher the impact of intratumoral heterogeneity of immune determinants on antitumor response. Methods: Each four regions from tumour centre (TC) and invasive front (IF) from 130 PDACs, including long-term survivors (LTSs, n=29, overall survival≥60 months) and short-term survivors (STSs, n=101, overall survival<60 months), were examined by transcriptomic and proteomic analysis (Nanostring platform). Spatial compartments (tumour, leukocytes, stroma) were defined by fluorescent imaging. Additionally, 20 tumours from each group were immunophenotyped by multiplex immunofluorescence. Results: LTSs displayed mostly homogeneous morphology with extended glandular differentiation and immunogenic TME both at TC and IF, with increasing gradient towards the IF. There was higher presence of immune checkpoint-associated and immunogenic genes and proteins at the IF as compared to the TC, including CD40, CD3, CD8, CD4, GZMB and PD-L1. In contrast, STSs were characterized by morphologic heterogeneity, including areas with reduced glandular differentiation and high tumour budding and a mostly immunosup- pressive TME with negative gradient towards the IF. Moreover, there was decreased presence of several genes and proteins, including CD3, CD8, CXCL10, GZMB, IFNG, HLA-DR and CD40, at the IF as compared to the TC.