ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 One patient with history of pleomorphic adenoma in the orbit was diagnosed with carcinoma ex pleomorphic adenoma. In 2 patients FNAB disclosed primary salivary duct carcinoma and recurrence of basal cell carcinoma respectively. The remaining cases included 3 cases of lymphoid hyperplasia, 3 cases of inflammatory pseudotumour and 1 haemangioma. With exception for minor hematomas in some patients, no severe complications were observed. Conclusion: FNAB may be considered a useful technique in the diagnostic approach to orbital masses according to strictly defined indications. This technique allows a confident diagnosis with a low risk of complications and is particularly useful in the evaluation of malignant, unresectable and retrobulbar orbital lesions. OFP-03 | Oral Free Paper Session Digestive Diseases Pathol- ogy - Liver/Pancreas OFP-03-001 Histopathological tumour response scoring in resected pan- creatic cancer following neoadjuvant therapy (ISGPP-1): an international interobserver study B. Janssen*, S. van Roessel, S. van Dieren, O. de Boer, M. Bes- selink, J. Verheij, H. Wang, C. Verbeke, A. Farina, for the Interna- tional Study Group of Pancreatic Pathologists (ISGPP) *Amsterdam UMC, The Netherlands Background & objectives: This study investigated whether gastro- intestinal/pancreatic pathologists can reliably identify neoadjuvant treatment effects in pancreatic tumours based on histomorphol- ogy. Moreover, it aimed to determine the interobserver agreement for current (internationally used) tumour response scoring (TRS) systems. Methods: Overall, 23 gastrointestinal/pancreatic pathologists reviewed whole H&E-slides of neoadjuvantly treated or treatment- naive resection specimens of pancreatic cancer. The accuracy in identifying treatment effect was investigated in 60 patients (30 treatment-naïve, 30 after NAT). Interobserver agreement for the College of American Pathologists (CAP) and MD Anderson Cancer Center (MDACC) TRS systems was assessed in 50 patients using intraclass correlation coefficients (ICC). Results: The sensitivity and specificity for identifying NAT effect were 76.2% and 49.0%, respectively. The histological features: reduced cancer cell density, mucin pools, and cell degeneration were most frequently stated to allow distinction between treated and treatment-naïve cases. In 50 patients after NAT, the ICC val- ues for both TRS systems were ‘moderate’; 0.66 CAP and 0.71 MDACC. The ICC values of <0.50, ≥0.50 and <0.75, ≥0.75 and <0.90, and >0.90 indicate poor, moderate, good, and excellent reliability, respectively. None of the cases scored as a complete response by at least one pathologist had 100% concordance. Conclusion: Identification of the effect of NAT in resected pan- creatic cancer proved unreliable. The interobserver agreement for the current TRS systems was suboptimal. These findings support the recently published ISGPP recommendations to score residual tumour burden rather than tumour regression following NAT, which will require a new TRS system. OFP-03-002 Two step- progression of non-functioning pancreatic neuroen- docrine tumours (PanNET) I. Marinoni*, A. Di Domenico, P. Kirchner, K. Bräutigam, R. Maire, C. Thirlwell, C. Kim-Fuchs, A. Perren *Institute of Pathology, Switzerland Background & objectives: PanNETs with mutations in ATRX, DAXX and MEN1 (ADM) originate from α-cells. Alpha-like Pan- NETs, small and indolent, progress into intermediate (ADM), larger and with high relapse risk. We dissected epigenetic changes and activation of related pathways, occurring during such progression. Methods: We combined DNA methylation profiles of 155 and RNA sequencing of 45 PanNET samples. DNA methylation analy- sis was performed using the ChAMP pipeline. Consensus cluster- ing was performed following the ConsensusClusterPlus (v1.54.0) pipeline. Spearman correlation between expression values and cor- respondent beta or M values of methylation was used to identify genes which changes in both DNA methylation and expression. Results: Combining RNAseq and DNAme data, we delineated three groups of PanNET originating from alpha cells: alpha- like PanNET, intermediate-ADM and intermediate-ADM3. We compared DNA methylation and transcriptome profiles of the three groups. We found that alpha-like PanNETs develop first into intermediate-ADM and then into intermediated-ADM3 following a two steps progression. Notably, alpha-like tumours develop into intermediate-ADM upon DAXX/ATRX mutations and changes in DNA methylation mainly at heterochromatin regions increasing Chromosomal Instability. Interestingly, only genes regulating cell proliferation were found differently expressed between alpha-like and intermediate-ADM tumours. Intermediate-ADM develop into intermediated-ADM3 acquiring changes in DNA methylation at regulatory regions, resulting in an altered expression of genes involved in cell differentiation and metabolism. Conclusion: We described pathways of progression dependent on DAXX and ATRX and subsequent epigenetic changes, characterized by increased cellular dedifferentiation and metabolic adaptation. Addi- tionally, our study confirmed the high relevance of DNA methylation in stratifying and classifying PanNETs with different molecular and clinical characteristics. OFP-03-003 Mutational profile of hepatocellular carcinomas with microvas- cular invasion and microscopic portal vein invasion. Implica- tions for tumour progression and recurrence S. Chillotti*, T. Maloberti, D. de Biase, G. Gerinario, M. Cescon, M. Ravaioli, A. D’Errico, F. Vasuri *Department of Pathology, IRCCS Azienda Ospedaliero-Univer- sitaria di Bologna, Italy Background & objectives: The aims of the present study are to confirm the prognostic role of microscopic portal vein invasion (MPVI) in resected hepatocellular carcinoma (HCC), and to cor- relate MPVI with the mutational status to create risk categories based on NGS data. Methods: Out of 400 retrospective resected HCCs we selected all cases with a diagnosis of microvascular invasion (MVI). Then we reviewed the histopathology, subclassifying each case according to the presence of MVI vs MPVI. Survival data for each patient was then obtained. We then performed NGS analysis with a custom panel on a perspective cohort of recent resected HCCs. Results: Kaplan-Mayer survival analysis was performed on the retro- spective cohort which showed a statistically significant better Overall Survival (OS) for HCCs without MPVI (p=0.007). NGS analysis found that TERT(65%) TP53(26%), and CTNNB1(22%) were the most fre- quently observed mutations. NGS results and MVI were studied using a Chi-Square test and found that TP53-mut and MPVI were positively correlated (p=0.039), while TERT-promoter mutation correlates with the presence of any MVI (p=0.038). Although MPVI and CTNNB1- mut correlation was not significant (p=0.076), none of the 5 CTNNB1- mut cases had MPVI. TP53-mut HCCs were characterized by a higher S11