ECP 2023 Abstracts

S117 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 PS-18-007 Comprehensive immunohistochemical profiling with hierarchical clustering and self-organising neural maps allows for consistent subtype identification in glioblastomas J. Soukup*, R. Dolezal, L. Gerykova, P. Kasparova, Z. Pleskacova, J. Petera, V. Skarkova *University Hospital Hradec Kralove, Czech Republic Background & objectives: Glioblastomas (GBMs) show divergent biological features. In past, 3 subtypes (mesenchymal, proneural and classical) were consistently identified with comprehensive genomic studies. The aim was to identify these subsets, using simpler and more affordable approaches. Methods: Tissue microarrays were constructed from 86 GBM samples. Immunohistochemistry was performed for 13 selected subtype-related markers, based on previously published data, and scored for intensity and extent of staining. EGFR ISH (either FISH or SISH) was scored either as normal or amplified. The results were analysed using hierarchical cluster- ing (HC) and self-organising neural maps (SOM) in Matlab 2023 software. Results: Using HC, the three groups configuration was generated with high- est stability. These three groups corresponded to predicted classical subtype (n = 28), mesenchymal subtype (n = 29 ), and proneural subtype (n = 29). Comparing HC and SOM, a considerably high prediction correspond- ence in the threefold GBM classification was found (e.g. specificity = 0.95, accuracy = 0.91, F1 = 0.91). According to SOM weight matrix, EGFR+/ MEOX2+/p53wt phenotype showed strongest association with classical subtype. Mesenchymal subtype was characterised by Vimentin+/D2-40+/ Olig2- profile and Olig2+/p53mt/Vimentin- was characteristic of proneural subtype. The profiles were consistent with previously published data. Conclusion: The mathematical analyses of the IHC data enabled to design a predictive SOM-based model for the GBM classification the results of which were in strong agreement with HC approach. Moreo- ver, the weight matrix of SOM elucidates quantitatively the marker contributions to each of the typical GBM classes and provides support for the phenotype interpretation. Funding: Ministry of Health, Czech Republic, project No. NU20-03-00360 PS-19 | Poster Session Paediatric and Perinatal Pathology PS-19-001 Osteolysis and neurofibromatosis type 1 (NF-1): a rare association scarcely reported in the literature. Synopsis of clinical, radiologi- cal, and histopathological findings in a retrospective case series M. Bronte Anaut*, J. Arredondo Montero, J.J. Pozo Krelinger, J.C. López Guitierrez *Hospital Universitario Araba, Spain Background & objectives: 10-20% of patients with NF-1 present skeletal abnormalities such as scoliosis, pseudarthrosis and more rarely osteolytic events. Several theories have been proposed on the etiopathogenesis of the latter such as the presence of vasculo-lymphatic anomalies in neurofibromas. Methods: A search was made in the institution archives reviewing the records of 7 children with NF-1 who had been evaluated for osseous defects (bone loss) on imaging tests. Among the information collected were socio-demographic variables, clinical-radiological characteris- tics, accompanying lesions/abnormalities and evolution. Histologi- cal sections were analysed for microscopic findings in the resected lesions. The presence of coexisting genetic syndromes was excluded. Results: Five patients were female. Mean age at diagnosis was 5.6±2.1 years. During follow-up patients presented neurofibromas in multi- ple locations, mainly cervico-thoracic and in lower extremities, both subcutaneous and in soft tissue. Six patients presented polyostotic bone loss. All osteolytic events were subjacent to a bone loss related plexiform neurofibroma with/without diffuse component (BLRN). All BLRN showed heterogeneous 18F-FDG metabolism with higher uptake foci. Immunohistochemical study (IHS) showed positivity to CD31 (endothelium), CD34 (endothelium, tumour cellularity), and negativity to D2-40, LYVE-1 and WT1. Male patients selectively showed focal WT1 positivity (neurofibroma cellularity). BLRN main locations were cranial base, occipital bone, cervical vertebrae, orbit, mandible and thoracic cage. Conclusion: BLRN in NF-1 appear to have a female predominance and an early age of onset. The most characteristic presentation was a large cervico-cranial neurofibroma affecting more than one bone with a vasculo-lymphatic IHS pattern. Further studies that deepen in the IHS characterization of these lesions are necessary to define the existing relationship between vascular anomalies and osteolysis in NF-1. PS-19-003 Expression of ACE2 and TMPRSS2 in human placental tissue during SARS-CoV-2 infection E. Demaria*, A. Salerno, A. Degiovanni, A. D’Errico, M. Fiorentino *Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Italy Background & objectives: ACE2 and TMPRSS2 are the primary cel- lular receptors involved in SARS-CoV-2 entry, expressed in the lungs but also in the placenta. This case-control study aims to evaluate ACE2 and TMPRSS2 expression during a SARS-CoV-2 infection in first- trimester placental samples. Methods: We selected a case group of first-trimester miscarriage sam- ples. Sample selection criteria were: SARS-CoV-2 positivity during pregnancy or within 14 days from the miscarriage. Then, a comparable pre-COVID-19 control group was identified. Once collected, all sam- ples were stained with antibodies anti-ACE2 and anti-TMPRSS2 for immunohistochemistry. While, for the case group only, virus detection was performed by In Situ Hybridization. Results: 300 cases of miscarriage examined at our institute between January 2020 and March 2022, 9 were collected in the case group. One of them was excluded due to the lack of immunoreactivity. Overall, ACE2 expression was widely distributed in both cases and controls, mostly in vessels but also in the decidua and villi. Surprisingly, ACE2 positivity in the villous trophoblast was only observed in the brush border, but not in the stroma. In contrast, TMPRSS2 positivity was stronger in the case group compared to the control group. SARS-CoV-2 spike protein was identified in 6 cases and exclusively in the maternal compartment of the placenta. Conclusion: These results suggest that, on the one hand, infected tis- sues overexpress the TMPRSS2 receptor. This may be interpreted as an actual activation of the protein following viral infection. On the other hand, although TMPRSS2 expression increases in the placenta and SARS-CoV-2 entry receptors are exposed in the foetal compartment, there is no sign of vertical transmission. Confirming this, national reg- istry statistics show that the annual abortion rate in the Italian popula- tion did not increase during the pandemic years. PS-19-004 Congenital pulmonary airway malformation: a diagnostic challenge. Usefulness of historical classification C.E. Haro Haro*, M. Garrido Pontnou, A. Chaachou Charradi, J.T. Zuñiga Gaitan, J. Camacho Soriano, F. Rodríguez Díaz, A. Navarro Jiménez *Vall d’Hebron University Hospital, Spain Background & objectives: Congenital pulmonary airway malforma- tion (CPAM) is a rare anomaly of the developing lung. It occurs in <25% of all congenital lung abnormalities in infancy. There will be histologic features that may be useful in classifying them.