ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 OFP-09-012 Molecular-genetic profile of sinonasal tumours: molecularly heterogeneous but histologically distinctive low-grade and high-grade tumours M. Banecková*, A. Agaimy, M. Hyrcza, N. Ptáková, P. Martínek, J. Laco, N.J. Rupp, M.F. van den Hout, O. Koshyk, M. Michal, A. Skalova *Department of Pathology, Charles University, Faculty of Medicine in Plzen, and Bioptic Laboratory, Ltd, Plzen, Czech Republic Background & objectives: Sinonasal adenocarcinomas (SNAC) are classified as salivary and non-salivary adenocarcinomas. Non-salivary adenocarcinomas encompass a spectrum of high- grade intestinal-type adenocarcinomas (ITAC) and low-grade lesions potentially originating from seromucinous structures non-intestinal type adenocarcinomas (non-ITAC). The molecular genetic background is pleomorphic and inconsistent. Methods: Retrospectively, 12 cases of sinonasal lesions with a detected gene mutation or gene fusion were selected from the registry of tumours. The cohort included seven cases of low- grade lesions or benign tumours and 5 cases of high-grade car- cinomas. These tumours were compared morphologically and immunohistochemically. Results: Low-grade lesions represented classic forms of seromucinous hamartoma / respiratory epithelial adenomatoid hamartoma or non-ITAC. High-grade tumours were basaloid, keratin positive, solid to papillary. The architecture was mostly monotonous. In the low-grade malignant/benign subgroup there were detected 6 gene mutations (2x BRAF 2x RET , 1x KRAS , and 1x PDGFRA – this case showed an MYB::NFIB gene fusion). In a group of high-grade carcinomas, ETV6::NTRK3 and EWSR1::COLCA1/2 were found in 2 cases. One case of epi- thelial-myoepithelial sinonasal carcinoma harboured an HRAS mutation. One case of sinonasal undifferentiated carcinoma developed two gene mutations in IDH2 and ASXL1 genes. One case of high-grade carcinoma showed dual CREBBP and BRIP1 gene mutation. Conclusion: The sinonasal tract encompasses a wide spectrum of high-grade or low-grade lesions with pleomorphic molecular- genetic backgrounds and only a few of them are truly defined by gene fusion/mutation. There is a need to perform a further investigation to state the correlation between morphology and molecular genetics to better understand pathogenesis. Funding: This study was supported by study grant SVV 260539 from the Ministry of Education, the Czech Republic. OFP-09-013 Update to seromucinous hamartomas and respiratory epithe- lial adenomatoid hamartomas with dysplastic features and malignant transformation M. Banecková*, M. Hyrcza, J. Laco, T. Vaněček, P. Martínek, P. Grossmann, S. Ihrler, N.J. Rupp, F. Petersson, O. Koshyk, D.V. Spagnolo, J. Sanjiv, M. Schlageter, A. Skalova, M. Michal *Department of Pathology, Charles University, Faculty of Medicine in Plzen, and Bioptic Laboratory, Ltd, Plzen, Czech Republic Background & objectives: Sinonasal hamartomas (SH) and respiratory epithelial adenomatoid hamartoma (REAH) are rare and underestimated lesions. The term hamartoma is used for an indolent lesion without neoplastic potential, however, SH/REAH does not always behave accordingly. Methods: We have investigated twenty cases of “dysplastic” polypoid lesions diagnosed either as REAH and SH, adenoid cystic carcinoma (AdCC) arising in SH or REAH, and low- grade non-intestinal-type tubulopapillary adenocarcinoma (LG non-ITAC) arising in SH, low-grade adenocarcinoma ex REAH, and solitary fibrous tumour with SH. All cases were evaluated morphologically and immunohistochemically and 17 cases were tested by molecular-genetic methods. Results: Dysplastic features of SH/REAH contained irregular cystic glands with atypical epithelial lining with occasional loss of stratification and often intraluminal snouts. The cells had nuclear membrane irregularities and coarse chromatin. The stroma was densely fibrotic almost of desmoplastic character. Immunohis- tochemical expression of p63 was patchy or negative in SH but preserved in AdCC. Interestingly, expressions of both S100 and SOX10 markers were observed in the seromucinous component but were lost in the AdCC component. We have detected 4 cases with gene fusions ( MYB::NFIB and MYBL1::NFIB ) and 5 cases with developed gene mutation ( BRAF, RET , and PDGFRA ). Conclusion: Our findings not only strongly support that SH/REAH are genuine tumours, but also suggest that may represent a precur- sor lesion for the development of malignancies. SH/REAH may develop dysplastic features with the potential for risky behaviour. To the best of our knowledge, this is the largest molecular-genetic study of REAH/SH with the occurrence of glandular atypia in them and with a subset of cases with a direct transition into AdCC or LG non-ITAC. Funding: This study was supported by study grant SVV 22639 from the Ministry of Education, the Czech Republic. OFP-09-014 Multiparametric, in situ study of the microenvironment (MTE) of head and neck squamous cell carcinomas (HNSCC): impact of human papillomavirus (HPV). Macrophagic Infiltration Study J. Martin*, M. Durand, C. Lepine, Y. Harrar, J. Bastian, C. Badoual *laboratoire Inserm U970, PARCC, Université Paris Cité, France Background & objectives: Our study aims to explore the com- position of HPV-driven Head & Neck Squamous cell carcinoma (HNSCC) tumour microenvironment (TME), in particular the mac- rophagic infiltration. Methods: A multiplex immunofluorescence macrophage signature was applied to 127 patients with HPV-driven HNSCC, using the OPAL® technique developed by AKOYA BioSciences®. This technique allowed us to apply a macrophage labelling of 7 mark- ers in a sequential manner. Macrophage polarization (CD68, CD163), expression of immune checkpoint inhibitors (PD-L1, PD-L2), tumour cells (CK) and negative regulation pathway of phagocytosis (SIRPa, CD47). Results: A mapping of the distribution of macrophages between stroma and tumour could be established: unconventional mac- rophages called "M2" would be more abundant in the stroma, con- ventional macrophages called "M1" appear to be evenly distributed between tissues and stroma. The expression of PD-L1 by M1 and M2 macrophages does not seem to be associated with the level of expression of HPV E6 and E7 mRNA in CISH. However, there is a statistical trend in favour of a correlation between the population of intratumoural M1 mac- rophages expressing SIRPa and the level of E6 and E7 expression. Conclusion: Thus, E6 and E7 oncoproteins appear to influence SIRPa expression on macrophages M1 in HPV-driven OPSCC. There is a need to confirm the prognostic value of SIRPa expres- sion and to further identify interactions with different lymphocyte populations. S38