ECP 2023 Abstracts

S352 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 methods. Evaluation of PD-L1 IHC was performed by a pathologist and certified external reviewer using the Tumour Proportion Score (TPS) based on the official recommended scoring guidelines and related cut- off levels at 1% and 50% used to stratify patients for immunotherapy with pembrolizumab (KEYTRUDA®). Results: Using the PD-L1 IHC 22C3 pharmDx as a benchmark, 57.6% of the NSCLC cases (n=60) were classified as TPS-negative (<1%), 24.0% as TPS Low (≥1-49%, n=25) and 18.3% as TPS High (≥50%, n=19). An overall analytical concordance of 92% between the two methods was observed. The PD-L1 IHC Assay developed using clone RM320 on the Tissue-Tek Genie® Advanced Staining System showed a positive predictive accuracy of 81.5% and 100% for TPS 1% and 50%, respectively and a corresponding negative predictive accuracy of 98.3% and 96.6%. Conclusion: Based on this initial study, high accuracy and analyti- cal concordance for PD-L1 expression were found using the presently applied cut-off values and guidelines for TPS in NSCLC. More studies with validated positive PD-L1 expression levels in NSCLC cases are required to further evaluate the potential usability of the PD-L1 IHC assay developed on the Tissue-Tek Genie® Advanced Staining System for stratification of patients for immunotherapy with pembrolizumab (KEYTRUDA®) treatment. E-PS-21-054 Assessment of HER2 immunohistochemistry scoring by patholo- gists with or without specific HER2-low training A. Wróbel*, M. Vandenberghe, M. Scott, F. Jones, T. Matsuo, A. Boothman, J. Whiteley, C. Barker *AstraZeneca R&D, Poland Background & objectives: Proven benefit of trastuzumab deruxte- can in HER2-positive and HER2-low (immunohistochemistry [IHC] 1+, IHC 2+/in situ hybridization–negative) metastatic breast cancer means accurate identification of HER2-low tumours is now clinically important. We compared central versus real-world HER2 IHC scoring, including HER2-low. Methods: Consensus scores for 500 archival FFPE breast cancer sam- ples, stained with the Ventana PATHWAY anti-HER2 (4B5) assay, were generated by three pathologists trained for HER2-low scoring. Inter-pathologist concordance was assessed by Fleiss Kappa across all IHC categories and including HER2-low cut-off (IHC 0 vs ≥ IHC 1+). Real-world HER2 IHC scores from 3 CAP/CLIA clinical labs were compared with consensus. Results: Substantial agreement was observed between three patholo- gists trained in HER2-low across all HER2 scores (κ=0.70 by Fleiss Kappa) and for the HER2-low cut-off (i.e., the boundary between IHC 0 vs IHC 1/2/3+), (κ=0.80). Overall, historical real-world patholo- gist scoring performance evidenced moderate agreement (κ=0.60) to trained pathologist consensus across all scores and substantial agree- ment for the HER2-low cut-off (κ=0.71). Conclusion: This study was performed prior to approval of trastu- zumab deruxtecan for treatment of HER2-low metastatic breast cancer patients. The substantial agreement between pathologists trained in HER2-low gives confidence in the ability to robustly categorise above and below the HER2-low cut-off for samples stained with the Ventana 4B5 assay. Higher agreement between trained pathologists versus his- torical real-world pathologist scoring indicate education and training will improve accuracy of HER2 scoring, including at the IHC 0/IHC 1+ boundary. Funding: This work was funded by AstraZeneca in accordance with Good Publication Practice (GPP) guidelines (http://www.ismpp.org/ gpp-2022). In March 2019, AstraZeneca entered into a global devel- opment and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201). E-PS-22 | E-Posters Soft Tissue and Bone Pathology E-PS-22-001 A rare case: a 15 year-old-female patient presenting with multiple vascular tumours and enchondromas: Maffucci syndrome S. Aker*, F.M. Dogukan, S. Toy, A.K. Ganiyusufoglu *Basaksehir Cam&Sakura City Hospital, Turkey Background & objectives: Maffucci syndrome (MS) is a rare phe- nomenon with less than 200 cases have been reported so far. It is char- acterized by multiple enchondromas and benign vascular cutaneous tumours. About 50% of patients harbour a lifetime risk of malignancy. Methods: A 15-year-old female presented with nodular masses on her trunk and lower extremities since the age of 8 years. Results: Magnetic resonance imaging (MRI) revealed multiple vas- cular tumours consistent with arteriovenous malformations on her lower extremities. In addition, several enchondromatous tumours were detected on her left scapula, right 4th and 9th ribs, left 6th and 7th ribs, left proximal femur and left pubic ramus. On histopathological examination, histomorphologic features of the biopsy material sam- pled from the vascular tumour were compatible with an arteriovenous malformation. On the other hand, biopsy sample from the left scapular tumour displayed a cellular cartilaginous proliferation with occasional binucleations and focal enchondral ossification which was diagnosed as enchondroma. In molecular study performed for a potential IDH mutation, results were invalid for both tumours. Conclusion: In conclusion, MS was proposed as the ultimate diag- nosis considering the age, and multiple vascular and enchondroma- tous tumours of the patient. Maffucci and Ollier syndromes constitute a spectrum of diseases with multiple enchondromatous tumours in both and accompanying vascular malformations in the former. They are characterized by post-zygotic somatic mutations in IDH1/IDH2 genes. MS must be noted since it may cause considerable morbidity and mortality through the formation of multiple benign or occasionally malignant neoplasms. E-PS-22-002 An analysis of giant cell-rich lesions of bone with emphasis on the role of p63 expression as a diagnostic biomarker for giant cell tumour of bone S. Al Shehhi*, H. Al Kindi, M. George *Oman medical specialty board, Oman Background & objectives: Objectives: This study aimed to analyse giant cell-rich lesions of bone and determine whether p63 can be used as a biomarker to discriminate giant cell tumours of bone from other giant cell-rich lesions. Methods: A retrospective cross-sectional diagnostic accuracy study of all patients at any age who were diagnosed with giant cell rich lesions on bone biopsy in Khoula Hospital from 2009 to 2021. The sample size was 128 cases. P63 expression was evaluated using immunohis- tochemistry. Data were analysed using MedCalc software 19.1.6 and IBM SPSS Statistics version 28.0. Results: Among the sample size, 45% male and 55% female with a mean age of 23 years have giant cell-rich lesions. Lesions were frequent in the femur and tibia. Immunohistochemical analysis showed a p63 nuclear expression in 92.3% of giant cell tumours of bone, 42.3% of aneurysmal bone cysts, 100% of chondromyxoid fibromas, 13.6% of non- ossifying fibromas, 66.7% of brown tumour of hyperparathyroidism, 75% of chondroblastoma, 25% of giant cell reparative granuloma, and 0% of metaphyseal fibrous defect. The sensitivity and negative predictive value (NPV) of p63 immunohistochemistry of giant cell tumour of bone were 92.31% and 92.0%, respectively. The specificity and positive predictive value (PPV) were 60.53% and 61.54%, respectively.