ECP 2023 Abstracts

S45 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 OFP-11-010 ATRX loss suggestive for adverse clinical behaviour in conjunctival melanocytic lesions J. van Ipenburg*, Q. van den Bosch, D. Paridaens, N. Naus, R.M. Verdijk *Radboud University Medical Center, The Netherlands Background & objectives: Conjunctival melanoma (CM) with TERT promoter mutations are associated with metastatic disease. Both ATRX mutations and TERT promoter mutations are associated with faulty telomere maintenance. This study aimed to determine the prognostic value of ATRX loss in conjunctival melanocytic lesions. Methods: Conjunctival melanocytic lesions (nevi (n=16), primary acquired melanosis (PAM) without atypia (n= 6), PAM with atypia without associated melanoma (n=5) and CM with/without associ- ated PAM with atypia (n=58)) from the Rotterdam Ocular Mela- noma Study group were collected. ATRX status was determined using immunohistochemical staining. The TERT promoter status was determined by SNaPshot analysis and/or targeted next-generation sequencing. Results: None of the nevi and PAM without atypia showed ATRX loss, while ATRX loss was found in 40% (2/5) of the PAM with atypia without associated CM and in 14% (8/58) CM. Twenty-six of the 57 (46%) CM with known TERT promoter status harboured a TERT promoter mutation, with none of these cases showing ATRX loss. Eleven CM developed metastases, including 8 CM harbouring a TERT promoter mutation, 2 other CM showing ATRX loss and one case showing neither a TERT promoter mutation nor ATRX loss. For 2 metastasized CM cases with a TERT promoter mutation the ATRX status was unknown. Correction for adverse clinicohis- topathological parameters was not possible. Conclusion: ATRX loss was found in (pre-)malignant and not in benign conjunctival melanocytic lesions, comparable to TERT pro- moter mutations, suggesting that both alterations are associated with adverse clinical behaviour. This is emphasized by the finding that most cases with metastatic disease revealed either ATRX loss or a TERT promoter mutation. Similar to TERT promoter mutations ATRX loss may be used as a diagnostic tool in determining whether a conjunctival melanocytic lesion is prone to have an adverse clinical course. OFP-11-012 Prognostic risk stratification of orbital solitary fibrous tumours using Phosphohistone H3 (PHH3) D. O’Dwyer*, L. Hendrie, F. Roberts *Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, United Kingdom Background & objectives: Orbital solitary fibrous tumour (OSFT) is an uncommon and unpredictable tumour. Risk stratification models employ mitotic count to predict outcome. Recently PHH3 has been validated as a mitotic count biomarker. This study assessed PHH3 as a prognostic marker in OSFT. Methods: A retrospective review was performed to identify all patients diagnosed with OSFT (Mar 2003 – Dec 2021). Clinicopathological details were recorded from clinical records and OSFTs were classified according to the previously published Demicco and Thompson risk stratification models. Following PHH3 immunohistochemistry and interpretation by two independent observers, OSFTs were reclassified and outcomes were analysed using SPSS. Results: Sixteen patients diagnosed with OSFT were identified. The average age at diagnosis was 50 years (range 25 – 84 years) and 8/16 were female. Median follow-up time was 45.4 months (range 5.2 – 212.5 months) and 25% of patients developed a recurrence. One patient died during the study period. Overall outcome was predicted by older age (p=0.01) whilst risk stratification by the Demicco and Thompson models did not significantly predict prognosis. Following reclassification of tumours using PHH3 mitotic counts the Demicco risk stratification model successfully categorised patients according to risk (p=0.008). Additionally, PHH3 mitotic count alone predicted prognosis when using both Demicco (p=0.02) and Thompson (p=0.03) mitotic count categorical values. Conclusion: This is a small study of 16 OSFTs with limited follow-up time. However, OSFT is a rare tumour and our recurrence rate of 25% reflects other studies. In this cohort the currently validated risk stratification models failed to predict OSFT outcomes. Following PHH3 staining we successfully predicted prognosis. These findings are consistent with studies reporting PHH3 as an independent prognostic marker. To our knowledge this is the first study to describe PHH3 as a putative prognostic marker in OSFT. OFP-12 | Joint Oral Free Paper Session Soft Tissue and Bone Pathology / Infectious Diseases Pathology OFP-12-001 Prognostic risk stratification of 150 solitary fibrous tumours – a single centre experience D. O’Dwyer*, L. Hendrie, F. Roberts *Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, United Kingdom Background & objectives: Solitary fibrous tumour (SFT) is an uncom- mon and unpredictable tumour. The prognostic stratification model developed by Demicco et al helps predict risk. Here we describe a single centre experience of SFT risk stratification and identification of factors associated with outcome. Methods: A retrospective review was performed to identify all patients diagnosed with SFT (Jul 1997 – Dec 2021). Clinicopathological details were recorded from clinical records and SFTs were classified accord- ing to the previously published Demicco risk stratification models. The association between individual clinicopathological variables and outcome was analysed using SPSS. Results: One-hundred and fifty patients diagnosed with SFT were identi- fied. Mean age at diagnosis was 55.7 years (range 21 – 85 years) and 54% were female (n=81). The primary anatomical sites were: 68 intra-thoracic (45.3%), 46 soft tissue (30.7%), 16 orbital (10.7%) and 20 miscellane- ous (13.3%). Median follow-up time was 51.7 months (range 0.6 – 293.0 months). Seventeen patients (11.3%) developed recurrence - orbital SFTs had higher recurrence rates compared to other sites (p=0.07). Risk stratifi- cation according to the Demicco model was as follows: 82 low risk (54.7%), 49 moderate risk (32.7%) and 19 high risk (12.7%). Orbital SFTs were predominantly categorised as low risk compared to other sites (p=<0.05). Conclusion: This is a descriptive study of 150 SFTs with long term follow-up. SFTs can have an unpredictable clinical course and our recurrence rate of 11.3% is similar to other studies. Despite orbital SFTs tending to have higher recurrence rates compared to SFTs from other sites they were also likely to be categorised as “low risk” accord- ing to the Demicco risk stratification model. These findings highlight the ongoing necessity to further characterise this uncommon tumour and identify putative clinicopathological prognostic markers. OFP-12-002 Multiregional whole genome sequencing to decipher the evolution of complex structural events in osteosarcoma S. De Noon*, J. Espejo Valle-Inclan, A. Flanagan, I. Cortes-Ciriano *UCL Cancer Institute, Royal National Orthopaedic Hospital NHS Trust, United Kingdom Background & objectives: Osteosarcoma is an uncommon malignant bone forming tumour with complex genomes due to genomic insta- bility. Large-scale studies of their evolution are lacking due to their