ECP 2023 Abstracts

S142 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 P<0.001). PD-L1 was associated with prognosis, and tumours with high PD-L1 expression had a median recurrence-free survival of 11.7 months compared to the median not being reached for low PD-L1 expressing tumours (P<0.001). Conclusion: These data demonstrate considerable intratumoral PD-L1 expression heterogeneity within localized RCC tumours, which can be mitigated by multi-region sampling. Additionally, PD-L1 expres- sion positively correlates with metastatic progression after radical nephrectomy for localized disease. PD-L1 expression was particularly high for patients who rapidly progressed; thus, PD-L1 may be possible biomarker for patients who should be treated with adjuvant immuno- therapy. Currently, no biomarkers are routinely used for localized RCC. Validation using an additional 102 localized RCC patients is currently being performed. PS-26-020 mTOR mutated eosinophilic renal cell carcinoma: a distinct tumour characterized by mTOR mutation, loss of chromosome 1, and cathepsin K expression responsive to target therapy S. Marletta*, A. Caliò, G. Settanni, A. Pesci, S. Fratoni, F. Pierconti, M.R. Raspollini, A. Marchetti, G. Martignoni *Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Department of Pathology, Pederzoli Hospital, Peschiera del Garda, Italy Background & objectives: In the wide spectrum of oncocytic renal tumours, a subset of neoplasms with high-grade-appearing histologic features harboring pathogenic mutations in mammalian target of rapamy- cin (MTOR) and hitherto clinical indolent behaviour has been described. Methods: In the present study, we reported three cases (2F, 1M) of mTOR-mutated eosinophilic renal cell carcinoma with histologically documented metastases (lymph nodes, skull, and liver) and we per- formed a comprehensive immunohistochemical panel. Results: All the tumours were composed of eosinophilic cells with prominent nucleoli (G3 by ISUP/WHO) arranged in solid to nested architecture. Additionally, there were larger cells with perinuclear cytoplasmic shrinkage and sparse basophilic Nissl-like granules, superficially resembling the so-called “spider cells” of cardiac rhab- domyomas. Both renal tumours and metastases (skull and liver) were positive for PAX8, CK8-18, and cathepsin K, but not for vimentin. NGS identified mTOR genetic alterations in the three cases (1 deletion in exon 30 p.Tyr1450_Trp1456, 2 mutations in exon 53 p.Leu2427Arg/ p.Leu2427Gln), including metastases, and loss of chromosome 1 in all cases. One patient has been treated with Everolimus (mTOR inhibitor) gaining clinical response (metastatic tumours shrinkage). Conclusion: We present a distinct renal entity characterized by high- grade eosinophilic cells, cathepsin K immunohistochemical expres- sion, and harbouring mTOR gene mutations, demonstrating a malig- nant potential and showing the responsiveness to mTOR inhibitors. The responsiveness of mTOR inhibitors encourages pathologists to investigate mTOR gene mutations in aggressive high-grade/cathepsin K-positive eosinophilic carcinomas. PS-26-021 Cathepsin-K immunostaining and eosinophilic renal tumours: two clones in comparison F.M. Martelli*, A. Caliò, S. Pasinato, S. Marletta, S. Pedron, N. San- tonicco, G. Martignoni *Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Italy Background & objectives: Cathepsin-K is a lysosomal cysteine pro- tease expressed in translocation renal cell carcinoma, PEComa and in a subgroup of eosinophilic renal neoplasms characterized by TSC/mTOR gene mutations. Recently, staining for Cathepsin-K(EPR19992) has been reported in oncocytoma and chromophobe renal cell carcinoma. Methods: Cathepsin-K immunohistochemical analysis was performed in 50 oncocytomas, 50 chromophobe renal cell carcinomas and 8 low grade oncocytic tumours (LOT) using two different clones (3F9, mouse monoclonal, dilution 1:2000, ABCAM and EPR19992, rabbit monoclonal, dilution 1:500, ABCAM). The first clone recognized the procathepsin-K, band 37kDa, whereas the second one recognized the mature form, band 27kDa. Results: Cathepsin-K expression, using clone EPR19992, has been observed in 100% of oncocytomas, in 93% of chromophobe renal cell carcinoma, and in 100% of LOT whereas no staining was seen using cathepsin-K clone 3F9. Immunolabeling of Cathepsin-K clone EPR19992 is also found in the normal distal tubules. Conclusion: Cathepsin-K has been included in the best practices rec- ommendations on the use of immunohistochemical markers in the dif- ferential diagnosis of renal tumours. Staining for Cathepsin-K clone EPR19992 is observed the normal distal tubules and in all eosinophilic renal tumours tested, supporting their origin from distal nephron. There- fore its expression is not helpful in the differential diagnosis of eosino- philic renal tumours whereas Cathepsin-K clone 3F9 is a useful tool. PS-26-022 PD-L1 expression in clear cell type renal cell carcinoma with immunohistochemical loss of BAP-1 J. Martínez*, D. Fernández-Calvo, I. Ortiz, I. Blázquez, E. Condom, A. Vidal, M. Pujol, M.R. Taco, M. Gomà Gallego, M.Á. López, M. Pané-Foix *Hospital Universitari de Bellvitge, Spain Background & objectives: Loss of BAP-1 in clear cell renal cell car- cinoma (ccRCC) is associated with increased aggressiveness and his- tological features like rhabdoid morphology, pleomorphic nuclei and/ or eosinophilic cytoplasmic globules . We analysed the expression of PD-L1 in cases of BAP-1 deficient ccRCC. Methods: We reviewed clinical charts and histological features of cases of ccRCC with loss of immunohistochemical expression of BAP-1 (Clone BSB-109, Gennova) diagnosed in 2021-2022. PD-L1 staining was performed (clones 22C3 from DAKO and SP142 from Ventana-Roche). Results were evaluated calculating the Combined Positive Score (CPS) for 22C3 and the tumour-infiltrating Immune Cells (IC) for SP142. Results: Fourteen cases with immunohistochemical loss of BAP-1 were identified (13 men and 1 woman; mean age 57,9 years). Most debuted with advanced disease (11/14 stage III-IV; 8/14 metastatic disease within 1 year). PD-L1 positivity (CPS>10) was detected in 13/14 cases with 22C3 and in 5/14 with SP142 (CI>5%). SP142 expression was borderline in 4 cases (CI 1-5%). Conclusion: ccRCC with loss of BAP-1 has characteristic phenotypic fea- tures. It is associated with aggressive clinical behaviour. Identifying these cases may have clinical relevance for possible therapeutic strategies. The high rate of PD-L1 positivity observed in our series points to the possibil- ity of considering combined treatment with immunotherapy. However, the series is limited and studies with larger numbers of cases are needed. PS-26-023 Impact of cribriform pattern 4 and intraductal carcinoma on CAPRA-S post-prostatectomy patient stratification N.J. Nguyen*, K.A. Iczkowski, K. Liu, K. Lajkosz, T.H. van der Kwast, M.R.D. Downes *University of Toronto, Canada Background & objectives: We previously demonstrated the impact of cribriform pattern 4 (CC) and intraductal carcinoma (IDC) in biopsies on pre-treatment prostate cancer (PCa) risk stratification