ECP 2023 Abstracts

S375 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Methods: At each site, operators isolated RNA from 50 FFPE samples, performed RT-qPCR, and determined the CCP Score using the Prolaris Biopsy Report Generator. Each sample was analysed once at each site. After an outlier analysis, overall reproducibility was estimated using a ran- dom intercepts mixed model using restricted maximum likelihood and was then decomposed using variance component estimates from previous work. Results: In total, 43 samples were used for statistical analysis. Using CCP Scores for each sample from all three sites, outlier analysis did not identify any scores that fell outside of 4 MAD (mean absolute deviation). Variance decomposition using these samples, along with previously calculated variance component estimates, demonstrated a site-to-site variability of 0.115 CCP Score units (CCPsu). As accept- ance criterion, a standard deviation of at most 0.31 CCPsu was defined as it leads to a clinically relevant absolute shift of disease-specific mortality risk at the active surveillance threshold of less than 1%. The overall standard deviation for the Prolaris test was 0.184 CCPsu, which fulfilled the defined acceptance criterion. Conclusion: The variance in CCP Scores across the three external sites was within the acceptable range, indicating that Prolaris kit results are reliable and reproducible when performed locally by trained labora- tory staff. E-PS-24-034 Malignant Leydig cell tumour with MDM2 amplification - a case series O. Kuczkiewicz-Siemion*, M. Wągrodzki, A. Chrzan, J.K. Wolski, B. Puton, K. Olszewska, M. Grabowska-Kierył, M. Prochorec-Sobieszek *Department of Pathology, Maria Sklodowska-Curie National Research Institute of Oncology Warsaw, Poland Background & objectives: Malignant cases constitute 5-10% Leydig cell tumours (LCTs) and so far the only objective features of aggres- siveness are metastases. Colecchia et al. indicated the role of MDM2 amplification as a marker of metastatic potential, describing three LCTs with this alteration. Methods: Cases of metastatic LCTs diagnosed in a single Cancer Center in Poland between January 2015 and March 2023 were included. Three cases fulfilled the inclusion criteria. Those cases were tested for MDM2 amplification by both immunohistochemistry (IHC) and fluo- rescence in-situ hybridisation (FISH) as well as assigned the Leydig cell tumour Scaled Score (LeSS). Results: We present a case series of three male patients aged from 44 to 68 years diagnosed with metastatic LCTs. Patients presented metas- tases to lymph nodes or distant sites such as lungs or liver with different time intervals from initial diagnosis. All analysed cases demonstrated MDM2 amplification confirmed by IHC and FISH analyses. In one case the calculated LeSS indicated a low-risk class of metastatic behaviour. The follow-up duration ranged from 9 months to 6 years. Conclusion: LCTs occurring with delayed metastasis could potentially benefit from early retroperitoneal lymphadenectomy. As effective treat- ment options are lacking, retroperitoneal lymphadenectomy at short notice may be beneficial for patients with high-risk tumours. While microscopic evaluation of LCTs is not sufficient to predict metastatic behaviour, therefore the status of MDM2 amplifications seems to be a promising new prognostic marker. E-PS-24-035 Renal Cell Carcinoma with Tubulocystic Morphology, A Great mimicker of Tubulocystic Renal Cell Carcinoma A. Lazim*, A. Arriola, M. Mollaee *Temple University Hospital, USA Background & objectives: Tubulocystic renal cell carcinoma is a rare variant of renal cell carcinoma (RCC), new entity in the WHO clas- sification of renal tumours. Morphologically, characterized by a pure tubulocystic morphology, a pattern that may be also seen in other renal neoplasms. Methods: However, recent studies have identified distinct genomic features of this tumour that can aid in distinguishing it from other RCC. We present a case of a 64-year-old male who presented with abdominal pain and found to have an incidental 7.4 cm left upper pole renal cystic mass on imaging studies. Subsequently, he underwent a partial nephrectomy. Results: Microscopically, the well circumscribed unencapsulated tumour was composed of tubules and cysts, lined by cuboidal, colum- nar, flat, hobnail cells with eosinophilic cytoplasm, occasional large nuclei and prominent nucleoli. The tumour cells were positive for CD10, vimentin, PAX8, AE1/AE3, CAM5.2, AMACR, FH (retained), SDHB (retained), CK7 (focal), negative for CAIX, and TFE3. The preliminary diagnosis was reported as renal cell carcinoma, unclassi- fied. Molecular testing was requested for cytogenetic microarray analy- sis (CMA) and RNA fusion for definite classification of the tumour. Results revealed alterations of chromosome 1, which was not consist- ent with the reported genomic profile of tubulocystic RCC. Hence, a diagnosis of renal cell carcinoma WHO/ISUP grade 3 was rendered. Conclusion: This case demonstrated that a definitive diagnosis of tubulocystic RCC can be challenging by morphology and stains alone, as the tubulocystic pattern can be seen in a variety of other renal neo- plasms. Definitive diagnosis of tubulocystic RCC can be challenging if based on morphology and stains alone. The presence of a pure tubu- locystic architecture combined with the use of molecular testing to identify distinct genomic features, help distinguish tubulocystic RCC from its mimickers, as seen in other renal neoplasms. E-PS-24-037 Gleason grading on a set of 1,903 tumours with known clinical follow-up data allows objectively measuring the quality of Gleason grading and comparing the impact of different grading attitudes M. Lennartz*, F. Büscheck, D. Hoeflmayer, S. Kind, S. Minner, M.C. Tsourlakis, N. Gorbokon, M. Freytag, C. Wittmer, K. Möller, C. Bern- reuther, N. Blessin, M. Graefen, T. Schlomm, G. Sauter *University Medical Center Hamburg-Eppendorf, Germany Background & objectives: In prostate cancer Gleason grading system is the strongest prognostic parameter with high impact for determining patient treatment. However, Gleason grading is subject to substantial interobserver variability, even between specialized pathologists. Methods: To objectively assess the quality of the Gleason scoring of individual pathologists, images of 1,903 H&E stained prostate cancer samples measuring 0.6 mm in diameter were collected. To evaluate the utility of our “Gleasonaut” approach, 11 different pathologists were invited to assign Gleason scores to each of these images and these data were then compared to clinical follow-up data. Results: A comparison of the Gleason scoring of our 11 pathologist identifies substantial differences. A complete agreement of all patholo- gists was only achieved in 5.4% for Gleason 3+3, in 1.9% for Gleason 3+4, and in 0.1% for Gleason 4+3. An agreement of at least 2/3 of the pathologists was reached in only 25.1% for Gleason 3+3, 23.0% for Gleason 3+4, and 2.9% for Gleason 4+3. The availability of follow-up data enabled head-to-head comparisons of the prognostic impact of individual grading attitudes. For tumours initially graded as 3+3=6, 21 of 110 comparisons resulted in significant differences. For tumours initially graded as 3+4=7, 85 of 110 comparisons resulted in signifi- cant differences. Conclusion: Our “Gleasonaut” is highly useful to objectively measure the quality of Gleason grading and to compare the impact of different grading attitudes. The particularly high rate of clinically relevant inter- observer variability in Gleason 3+4 carcinomas is obviously driven by substantial prognostic differences between Gleason 3+4 tumours with very high or low fraction of Gleason 4. Image databases with