ECP 2023 Abstracts

S87 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 training set and one from fully external sources. The first set achieved an AUC of 0.981 (0.96 - 0.99) on slide level. The second, fully external test set, containing 78 cases with STIC/STIL lesions and 112 control cases, reached an AUC of 0.949 (0.90-0.99), showing an overall underlining robustness of the algorithm. Subsequent visual inspection confirmed accurate detection of STIC/STIL lesions in relation to the morphology, immunohistochemistry and the reference standard set by the expert panel. Conclusion: Reliably diagnosing STIC is critical for the safety of patients who opt for alternative risk-reducing surgery. Moreover, women with STIC seem to be at an increased risk of developing peri- toneal carcinoma, raising issues about management and follow-up. Accurate detection of STIC is therefore essential but is constrained by limited experience and observer variability. In this study, we dem- onstrate that a deep-learning algorithm has the potential to identify STIC automatically and thus may improve the accuracy of this difficult diagnosis. Funding: Dutch Cancer Society (KWF) PS-10-010 Change in the incidence trend of early miscarriages during the COVID-19 pandemic: Single-centre retrospective cohort study D.P. Burlacu*, A. Burlacu, B. Szabo, T. Mezei *Department of Pathology of Emergency Clinical Hospital of Targu- Mures, Romania, Romania Background & objectives: Pregnant women, especially during the first trimester, are considered more vulnerable to viral infections due to their pro-inflammatory state. This study aims to assess the incidence trend of early miscarriages and the influence of the COVID-19 pandemic on pregnancy outcomes. Methods: A retrospective-cohort study was conducted including all pregnant women admitted to Targu-Mures Clinical Hospital, Romania, between January 2018-December 2022. Early miscarriages percent- age recorded during pre-pandemic was compared with those registered during the COVID-19-pandemic, March 11th 2020 being officially declared the pandemic beginning. Early pregnancy outcomes (viable and ectopic pregnancies, medical and spontaneous abortions) were measured as total number and percentage. Results: The annual incidence of registry-identified early miscar- riages has declined from 5.4% 12– 46-year-old women in 2018 to 3.6% in 2022 (p=0.008). An overall incidence rate of 3.66% [95% C.I. 3.26-4.05] was calculated, with 4.25% [95% C.I. 3.35-4.41] in the pre-pandemic period and 3.24% [95% C.I. 2.82-3.57] during the pandemic. A higher incidence rate was identified among nulliparous (36.9%), followed by multiparous (35.9%) and primiparous women (27.2%) (p<0.0001). It mostly occurred during the 8th gestational week (14.1%, p<0.0001), in women aged > 30 years (23.8%), > 20 years (19.9%), and < 20 years (17.5%), (p<0.0001). 0.9% of early miscarriages and one maternal death were associated to Sars-COV2 infection (p= 0.978). Conclusion: Our study demonstrates that the increase of early miscar- riages incidence rate is attributable to advanced maternal age. To our knowledge, the present study is the first European study that proves the incidence rate of early miscarriages during the COVID-19 pandemic was not significantly increased, suggesting that this viral infection does not alter the risk of miscarriages. These findings should help women to cope with any additional emotional stress caused by pregnancy during periods of pandemics. PS-10-011 panTRK is expressed in a variety of malignant uterine mesenchymal tumours without identifiable NTRK-associated gene fusions C. Connolly*, C. Murray, A. Hodgson *Toronto General Hospital, Canada Background & objectives: Previous work has documented panTRK immunohistochemical positivity in a subset of uterine leiomyosarcomas and high grade endometrial stromal sarcomas. We aimed to assess pan- TRK expression in a wider spectrum of uterine mesenchymal neoplasms. Methods: Malignant uterine mesenchymal neoplasms diagnosed at our institution which had previously undergone targeted next generation sequencing (assessment of fusions +/- mutations) were immunohis- tochemically evaluated with panTRK immunohistochemistry (clone EPR17341). Whole tumour sections from resection specimens were stained and pattern (cytoplasmic, nuclear, membranous), extent (focal, patchy, diffuse) and intensity (weak, moderate, strong) of expression was recorded. Results: 12 uterine mesenchymal tumours were studied: 6 endometrial stromal sarcomas (3 low grade, 3 high grade), 2 inflammatory myofi- broblastic tumours, 2 adenosarcomas, and 2 leiomyosarcomas. All tumours had typical disease-defining fusions or no detectable fusion (i.e., no identifiable fusion involving NTRK genes). panTRK immu- noexpression was identified in 11/12 tumours and the neoplasm that showed no expression was a low grade endometrial stromal sarcoma with a EPC1::EED fusion. Diffuse strong cytoplasmic staining was seen in 3/3 high grade endometrial stromal sarcomas as well as 1/2 adenosarcomas. The remaining positive tumours (n = 7) showed focal to patchy often weak cytoplasmic expression and 2/7 showed focal or patchy strong nuclear staining. Conclusion: This study supports the known conclusion that the diag- nosis of a NTRK-related fusion-driven neoplasm cannot be made based solely on the immunohistochemical expression of panTRK. The signifi- cance of panTRK immunohistochemical expression in multiple differ- ent uterine mesenchymal neoplasms without NTRK-related fusions is, as of yet, not entirely clear but continues to raise questions regarding a) the exact mechanisms causing this, and b) the possible therapeutic utility of selective TRK inhibitors in the treatment of these neoplasms. PS-10-012 Complex genomic and transcriptomic analysis in uterine tumours resembling ovarian sex cord tumour (UTROSCT) M. Flídrová*, N. Hájková, K. Němejcová, J. Hojný, J. Dvořák, R. Jakša, Q.H. Bui, J. Laco, J. Škarda, G. Mccluggage, G. Giordano, E.M. Silini, P. Dundr, M. Kendall Bártů *Department of Pathology, First Faculty of Medicine, Charles Uni- versity and General University Hospital in Prague, Czech Republic Background & objectives: UTROSCT is a rare entity. Most tumours behave in a benign fashion, but clinically aggressive neoplasms have been described. Our aim was to perform a comprehensive genomic and transcriptomic analysis in a series of UTROSCT to reveal clinically relevant alterations. Methods: DNA and RNA isolated from 30 UTROSCT were analysed using capture DNA NGS analysis (KAPA HyperPlus kit and a panel of 788 genes/gene parts; 2044 kbp; Roche) and transcriptome RNA-Seq (KAPA RNA HyperPrep kit; Roche), and pair-end sequenced on Next- Seq 500 or NovaSeq (Illumina). Only likely pathogenic or pathogenic (class 4/5) mutations and gene fusions were evaluated. Results: The analyses of our sample set revealed the presence of several recurrent gene fusions in the majority of the cases, including NCOA2/3. Moreover, whole transcriptome RNA-Seq revealed addi- tional rare gene fusions such as COL6A3::FAM13B. Other alterations detected included rare class 4/5 mutations in CHEK2 and RECQL4. Conclusion: Our complex study of the molecular alterations in UTRO- SCT has revealed potentially significant gene fusions and genetic alter- ations in these tumours, some of which may be clinically actionable. Supported by Ministry of Health of the Czech Republic (project no. NU21-03-00122 and RVO64165, General University Hospital in Prague) and by Charles University (Project UNCE204065).

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