ECP 2023 Abstracts

S382 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 E-PS-24-060 Immunohistochemical assessment of PD-L1, Trop2, HER2 as potential targets for renal collecting duct carcinomas therapy, an ancillary study of the BEVABEL GETUG/AFU 024 trial R. Pirlog*, J. Fontugne, M. Nourieh, C. Krucker, S. Oudard, C. Thiba- ult, Y. Allory *Institute Curie, Saint Cloud, France Background&objectives: Renal collecting duct carcinomas (CDC) are an aggressive type of cancer with poor survival. Standard chemotherapy, i.e. platinum agents and gemcitabine, is of limited efficacy. We aimed to investi- gate the immunohistochemical expression of potential new targets in CDC. Methods: We included 20 CDC surgical specimens from patients of the prospective BEVABEL trial (NCT02363751). After pathological review, immunohistochemical staining was performed for the following potential predictive biomarkers: HER2 (clone A0485), Trop2 (clone AF650); PD-L1 (clone 22C3). RNA was extracted from from FFPE tumour sections for 3’RNA sequencing. Results: Immunohistochemical staining was completely negative on tumour cell membranes for both HER2 and Trop2 proteins in all 20 cases, which was consistent with the low mRNA expression of ERBB2 and TACSTD2 genes. PD-L1 protein expression evaluated by tumour positivity score (TPS) and combined positivity score (CPS) was high in 4 cases (TPS ≥10%, CPS > 10), low in 6 cases (TPS <10%, CPS < 10) and negative in 10 cases. There was a positive correlation between CD274 mRNA expression and PD-L1 TPS (r=0.60) and CPS (r=0.62) scores, CD274 and CD8A (r=0.51) and CD4 (r=0.55) mRNA gene expression. Conclusion: HER2 and Trop2 were not expressed on CDC cell mem- branes, not supporting the use of related antibody-drug conjugates. Nectin4, another possible target, is currently under study. High CPS and TPS PD-L1 was seen in 20% of cases, suggesting a possible benefit of immunotherapy for this subgroup of CDC. Despite an improved morphological definition, CDC remains a heterogeneous tumour group, and further studies integrating immune and tumour cell characteristics for identifying possible therapeutic targets are required. E-PS-24-061 E-Cadherin expression in different variants of prostate adenocarcinoma R.M. Plesea*, M. Ș erbănescu, F. Giuroiu, R.N. Ciurea, F. Gherghi- ceanu, I.E. Ple ș ea *Department of Cell and Molecular Biology, University of Medicine and Pharmacy of Craiova, Romania Background & objectives: The study aims to compare the expres- sion of E-Cadherin (ECHAD), one of the main cell adhesion mol- ecules related to epithelial malignancies evolution in the classic form (P_ADK) and the ductal form (D_ADK) of prostate carcinoma (PC) according to Gleason system. Methods: A series of 435 areas of P_ADK and 90 areas of D_ADK with different Gleason’s system patterns were stained with ECHAD. Images were evaluated through a computational algorithm designed by the authors. The location of ECHAD expression was strati- fied as follows: E1=Membrane only, E2=Membrane+Cytoplasm, E3=Cytoplasm only. Results were compared using chi-square test. Results: ECHAD expression site evolved differently in the two vari- ants of prostate adenocarcinoma. In P_ADK, ECHAD had a dominant E1 expression in well-differenti- ated (WD) areas and evolved towards a predominant E3 expression in poorly differentiated (PD) areas, with a chi-square test p value < 0.0001. In D_ADK, in turn, ECHAD had different types of expression in the four main types of Gleason patterns (chi-square test p value = 0.022) but with an oscillating trend of expression, with obviously dominant E1 expression in the most PD areas (Gleason pattern 5), followed by moderately (Gleason pattern 3) and WD areas (Gleason pattern 2) and predominant E3 expression only in Gleason pattern 4 areas. Conclusion: The degree of intercellular adhesion, expressed by the ECHAD presence on cell membrane, has different profiles in the main morphological variants of PC. Thus, whereas in classic forms of PC it correlates with lower degrees of differentiation of epithelial malignant proliferation, in ductal adenocarcinoma this correlation is not present, not being statistically validated. E-PS-24-062 Unusual extragonadal presentation of testicular germ cell tumours E. Poon*, K. Trpkov, T. Cheng, A. Yilmaz *University of Calgary, Canada Background & objectives: Diagnosis of primary testicular germ cell tumour (TGCT) presenting initially with extragonadal metastasis can be challenging. We reviewed our institutional files to identify cases with unusual extragonadal presentations where testis primary was clinically unsuspected. Methods: 9 patients were identified from our testicular cancer database with 1236 cases over a 20-year period. We documented the clinical and pathologic findings to emphasize the impact and challenge of accurate diagnosis in these unusual clinical settings. Results: Initial presentation (8/9) included gastrointestinal discomfort(x4), leg swelling/DVT(x3), neck mass(x1); psychiatric disor- der/seizures(x1). Extragonadal sites included duodenum(x3), pelvis(x2), thoracic spine(x1), neck node(x1) and abdominal mass(x1). Diagnosis of GCT was established by a biopsy of the extragonadal mass in 6/9 patients and was clinically suspected in 3/9. Testicular primary was confirmed in all cases. Median age was 39 years (range 20-79 years); 3/9 patients were >65 years. Mean tumour size in testis was 1.7 cm (range 0.6-3.5 cm). Treatment included chemotherapy (8/9) and orchiectomy (5/9) which showed seminoma with regression in 3/5 cases, burned-out tumour in 2/5. Two patients died of disease, 7/9 were disease-free. Conclusion: Diagnosis of TGCT should be included in the differential of extragonadal neoplasms and in patients with a disseminated metastatic disease of unknown primary. Pathologists play a crucial role in the accu- rate diagnosis and the proper management of a potentially curable disease. Regression related changes at the primary site were a common finding and may have contributed to a clinically unsuspected testicular primary. E-PS-24-063 Urothelial carcinoma with trophoblastic differentiation – a case report M.C. Popelea*, D. Porav, A. Loghin *Pathology Department of Mures County Clinical Hospital, Romania Background & objectives: Urothelial carcinoma (UC) is a very heter- ogenous tumour, with a diversity of morphological appearances. Up to 25% of urothelial carcinoma display squamous or glandular differentia- tion. UC with trophoblastic differentiation is very rare and is associated with a poor prognostic. Methods: A 64-year-old patient presented in August 2022 at the Urol- ogy Department with gross haematuria. A CT-scan revealed a tumour in the bladder, and cystoscopy revealed a multifocal tumour infiltrating the prostatic urethra. TURV was performed and the specimen was sent to our Pathology Department. Results: Microscopically, we observed a tumour consisting of nests, sheets and trabeculae of tumour cells with a urothelial appearance. The cells presented cyto-nuclear atypia, marked pleomorphism and numerous atypical mitoses. We identified several cells with monstrous nuclei and multinucleated cells with eosinophilic cytoplasm, with an appearance of syncytiotrophoblasts. In immunohistochemistry, tumour cells were diffusely positive for GATA3, CK34βE12 and p63 and syncytiotrophoblastic-like cells were focally positive for β-hCG. The tumour was pT2 pathologic stage, with extensive areas of necrosis. The