ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 recurrences. Further studies focusing on chromatin regulators could elucidate the molecular pathogenesis of chordoma. OFP-04-002 Extraskeletal myxoid chondrosarcoma: a morphological, immunohistochemical and molecular analysis of 31 cases A. Llombart-Bosch*, F. Giner, i. Machado, S. Navarro, A. Ferrandez Izquierdo *Dep Pathology Univ. Valencia, Spain Background & objectives: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant tumour. Their spectrum is wide but a diagnosis based on histology can be difficult. NR4A3 gene rearrangement is the hallmark in these tumours but still lack specific immunohistochemical profile for this neoplasm. Methods: We collected 31 cases diagnosed as EMC between 1999 and 2018 from two institutions. Corresponding clinical data were recorded. We performed a histopathological and molecular study with a wide immunohistochemical panel. Results: The mean age of our patients was 50 years with a range between 22 and 86 years. We found a slight predominance for males. The majority of EMCs showed a typical architectural pat- tern. EMCs expressed (focal or positive) the following markers: FLI-1 (100%), CDK4 (100%), TRK-A (96.8%), STAT-6 (90.3%), CD99 (90.3%), CD117 (83.9%), HNK-1 (80.6%), SATB2 (67.7%) and S-100 (58.1%). Neuroendocrine markers chromogranin, synap- tophysin and INSM1 showed intense and focal expression in 22.6%, 22.6% and 38.7% of cases respectively. The EWSR1-NR4A3 rear- rangement was found in 19 cases and 7 patients presented the TAF- 15-NR4A3 fusion. The TAF15-NRA43 rearrangement correlated with a non-typical histology (more cellular with solid pattern). Conclusion: EMCs express some immunohistochemical markers which are used in diagnosis for other neoplasms that can also be positive for EMC and can cause extra difficulty for differential diagnosis in EMCs with non-typical histology and where molecu- lar rearrangement is not informative. Some immunohistochemical markers such as CD99, CDK4, FLI-1, SATB2 and STAT6 may be considered positive in EMCs suggesting the possibility of incor- porating these markers in the differential diagnosis with other entities. Funding: Supported by the IVO Cancer Fundation.Valencia Spain OFP-04-003 A single-institution experience with 11 cases of extraskeletal myxoid chondrosarcoma: rare fusions, unusual morphology and the utility of INSM1 immunohistochemistry N. Klubickova*, J. Lenz, M. Michal, M. Michal *Bioptical Laboratory Ltd., Czech Republic Background & objectives: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma of uncertain differentiation, most commonly driven by fusion of EWSR1 and NR4A3 genes. A recent report identified INSM1 as a useful immunohistochemical marker, being positive in 90% of EMC cases. Methods: 11 cases of EMC from our institutional files where molecular genetic results were available were included in the study. Immunohistochemistry for INSM1 was performed in 10 cases. Targeted RNA sequencing (RNA-seq) using customized Archer FusionPlex Kits or FISH with EWSR1 and NR4A3 break-apart probes were carried out in 5 and 6 cases, respectively. Results: 8/10 cases were positive for INSM1. However, only 4 cases showed strong expression in more than 50% of tumour cells. Using FISH or targeted RNA-seq, the classic EWSR1::NR4A3 fusion was detected in 7/11 cases. Less common TAF15::NR4A3 and distinctly rare TCF12::NR4A3 fusions were detected in 1 case each. In 1 case, FISH was positive for NR4A3 but negative for EWSR1 rearrangement. 10 cases displayed typical morphology i.e., anastomosing cords of round/oval tumour cells situated in abun- dant myxoid stroma, while the case with the TCF12::NR4A3 fusion showed a highly unusual morphology consisting of a solid cellular proliferation of bland monomorphic ovoid/spindled cells with only small foci of myxoid stroma. Conclusion: Our analysis confirms that most cases of EMC are positive for INSM1. However, the diagnostic utility of this marker is limited by the fact that only 50% of cases show a strong INSM1 expression in most tumour cells. Furthermore, our study highlights that EMC with alternative gene partners may present with unusual morphology. As illustrated by the case with the TCF12::NR4A3 fusion, some of these cases can be confidently diagnosed only with the use of high throughput sequencing methods. Funding: This study was supported by study grant SVV 260539 from the Ministry of Education, Czech Republic (NK). OFP-04-004 Differential Cyclin-E1 expression in CIC-rearranged sarcoma and Ewing sarcoma B. Karabulut*, O. Kandemir, S. Yenidunya, K. Kösemehmetoglu, F. Ardıc Yukruk *Ankara Oncology Training and Research Hospital, Department of Pathology, Turkey Background & objectives: CIC-rearranged sarcomas(CRS) - one of EWSR1-negative undifferentiated round cell sarcoma(URS)- show more aggressive behaviour than Ewing Sarcoma(ES). As CCNE1 expression is associated with tumour growth in CIC::DUX4-rearranged CRS, we aimed to demonstrate the value of CyclinE1 expression in CRS. Methods: CyclinE1 immunohistochemistry (Abcam, 1/50, EDTA) and break-apart FISH for EWSR1 and CIC gene rearrangements (ZytoLight, Zytovision) were performed on 3-mm tissue microar- rays composed of 40 small round cell tumours. CyclinE1 expres- sion was evaluated as low and high similar to the previous study by Wei et al (J Orthop Res. 2020;38(9):1952-1964). Results: By morphology and FISH, 5 cases were CRS, and 22 cases were ES, while 13 cases were regarded as URS. Among all three diagnostic groups, Cyclin E1 expression was higher in CRS (4/5,80%) and URS (8/13,62%) groups compared to ES (1/22,5%; p<0.001). Higher mean age at diagnosis, presence of atypical his- tological findings (such as nuclear aberrations and myxoid stroma), lack of CD99 expression, and presence of metastasis at diagnosis were significantly associated with high CyclinE1 expression. The sensitivity and specificity of the high expression of CyclinE1 in detecting EWSR1(-) cases were 66.7% and 95.5%, respectively. However, the correlation between CyclinE1 expression level and survival was not statistically significant. Conclusion: CyclinE1 expression is significantly lower in ES com- pared to CRS and URS suggesting that it can be used as an adjunct in the diagnostic immune panel of small round cell sarcomas. OFP-04-005 PDL1 expression correlates with the density of tumour-infil- trating lymphocytes (TILs) in high-grade osteosarcoma and is an independent marker irrespective of disease progression and metastasis - an ambispective cross sectional study S. Salman*, A. Barwad, A.R. Mridha, S. Bakhshi, V.K. Iyer *AIIMS, New Delhi, India S15