ECP 2023 Abstracts

S47 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 similar features including infiltrative growth, variable multinodular/plexi- form architecture, intersecting fascicles of spindle cells, prominent thick- walled vessels, scattered osteoclast-like giant cells, peripheral lymphoid aggregates. All tumours expressed smooth muscle actin and one showed desmin positivity, while beta-catenin, CD34, S100, SOX10 and ALKwere negative. Conclusion: We report a subset of low-grade sarcomas with myofi- broblastic features harbouring recurrent USP6 rearrangement. Our findings support the notion that among soft tissue tumours with fibro- blastic/myofibroblastic phenotype, USP6 rearrangement is not limited to benign tumours, and warrant further investigation of genetic changes in myofibroblastic sarcomas. OFP-12-006 Characterisation of immune cells in dysplastic neurofibromas: identification of PD1 and the TIM-3/Galectine 9 pathway as poten- tial targets for immunotherapy A. Brunet*, L. Lacroix, V. Aftimos, O. Hermeziu, P. Maille, K. Radomska, A. Rapinat, P. Wolkenstein, P. Topilko, N. Ortonne *APHP, France Background & objectives: Neurofibromatosis 1 predispose to the development of malignant peripheral nerve sheath tumours (MPNSTs). Dysplastic neurofibromas (DysNF) precedes the transformation of plexiform neurofibromas (pNFs) into MPNSTs. We characterize the immune infiltrates in DysNFs as compared to MPNSTs and NFs. Methods: The study cohort includes 32 cutaneous neurofibromas (cNFs), 49 pNFs, 31 DysNFs, 20 MPNSTs. We quantify the immune cells of the infiltrates, and characterize them using immunohistochem- istry/immunofluorescence. We perform a transcriptomic study using Nanostring technology (panel IO360 pan-Cancer) on a sub-group of the cohort, to identify immune check points and validate their protein expression using immunohistochemistry and immunofluorescence. Results: We identified higher levels of mononuclear cells infiltration in DysNFs in comparison with cNFs, pNFs and MPNSTs (p<0.0001), and more specifically CD3+ T-lymphocytes and CD163+ macrophages (p<0.0001). Transcriptomic analysis showed a pro-inflammatory and immune signature in DysNFs with an overexpression of various immune checkpoints, in particular HAVCR2-mRNA encoding for Tim-3. Multiplex immunofluorescence showed that PD1 was mostly expressed by CD8+ T lymphocytes, and Tim-3/Gal9 by CD163+ mac- rophages, in all tumour types, while PD-L1 was rarely expressed by tumour cells. We found a higher expression of HLA-ABC by tumour cells in MPNSTs, whereas the expression of cleaved caspase 3 was more important in DysNFs and MPNSTs than in pNFs. Conclusion: Our results suggest the development of an anti-tumour immune response in DysNFs, involving both T-lymphocytes and mac- rophages, which might control malignant transformation of DysNFs into MPNST. Because Gal9 is one of the main ligand of Tim-3, an autocrine/paracrine loop may play a role in regulating macrophage functions downstream of Tim-3 activation. Whether the blocking of the PD-L1/PD1 and Tim-3/Gal9 pathways may represent targets for an effective immunotherapy to prevent malignant transformation of DysNF remains to be confirmed by further studies. OFP-12-007 Clinicopathological features of five ultra-rare cases of CIC::DUX4 positive sarcomas B. Rekhi*, R. Rumde, O. Shetty *Department of Pathology Tata Memorial Hospital, Parel, India Background & objectives: According to the recent World Health Organization (WHO) classification, CIC-rearranged sarcomas, including CIC::DUX4-positive constitute an aggressive subtype of undifferentiated round cell sarcomas. There a single study on these tumours from our subcontinent. We present 5 additional cases of this tumour. Methods: Thirty-nine undifferentiated round cell sarcomas, excluding Ewing sarcomas (ES), were tested for CIC::DUX4 fusion, including Type I (165 base pair size) and II(230 bp) by reverse transcription- polymerase chain reaction. Twenty-seven of those cases were tested for EWSR1 gene rearrangement, 5 for SS18 and 4 for SS18::SSX fusion, and were negative for those tests. Five tumours (12.8%) were positive for CIC::DUX4(Type II) fusion. Results: Five CIC::DUX4-positive sarcomas occurred in 4 males and one female; of 25-43 years of age, in soft tissues, including thigh (n=2), chest wall(n=1), iliac region(n=1) and foot(n=1). Tumour size varied from 2.2-19 cm. Microscopically, the tumours were composed of nodules and sheets of malignant round to epithelioid cells, including “rhabdoid-like” (n=2) and spindle-shaped (n=2) with eosinophilic to vacuolated cyto- plasm (4/5), distinct nucleoli (4/5), brisk mitoses, focal myxoid stroma (4/5) and necrosis (5/5). Immunohistochemically, tumour cells were posi- tive for WT1 (5/5), calretinin (3/4), pan-keratin (1/4), CD99/MIC2 (“dot- like” to cytoplasmic membranous) (4/4), while negative for desmin (0/4), S100P (0/4) and NKX2.2(0/5). INI1/SMARCB1 was retained (3/3). All patients underwent excision with adjuvant radiotherapy and chemotherapy (ES regimen). One patient developed recurrence, while 2 developed pul- monary, including one brain metastasis. Conclusion: CIC::DUX4-positive sarcomas are ultra-rare tumours, that mainly occur in the soft tissues and in young adult patients. His- topathologically, these tumours display a wide spectrum, including round to epithelioid cells, variable amount of cytoplasmic vacuoliza- tion and myxoid stroma with necrosis. Immunohistochemically, these tumours express WT1 and calretinin. Despite adjuvant therapies, these tumours have dismal outcomes, espe- cially in large-sized tumours. CIC::DUX4-positive sarcomas need to be differentiated from their histopathological mimics, in view of sig- nificant treatment-related implications. Funding: This constitutes a part of an intramural-funded study at our Institution, Tata Memorial Hospital, Mumbai. OFP-12-008 Solitary fibrous tumour occurring in unusual sites: a clinico-path- ological series of 40 cases M. Mazzucchelli*, G. Angelico, G.N. Rosano, S. Poidomani, G. Magro *Department of Medical, Surgical Sciences and Advanced Technolo- gies "G.F. Ingrassia", Anatomic Pathology, University of Catania, Italy Background & objectives: Extrapleural Solitary fibrous tumour is a rare fibroblastic tumour arising in superficial and deep soft tissues. Herein, we present a clinico-pathologic study of SFTs arising in unu- sual sites, emphasizing the uncommon morphological, clinical and pathological features that cause diagnostic problems. Methods: A series of 40 SFTs were selected from the pathology files of the University of Catania, Italy. Immunohistochemical studies were performed with the labelled strepta- vidin–biotin peroxidase detection system. The following antibodies were tested: vimentin; alpha-smooth muscle actin; desmin; CD34; and STAT6. Pleural SFT with typical morphology, diffusely positive (nuclear immu- noreactivity) for STAT6, served as external positive control. Results: In the present series of SFTs, the following unusual clin- ico-pathological morphological features were observed: i) unusual sites; ii) tumours with a predominant leiomyomatous-like pattern and only focal tumour areas with the classic-type SFT morphology; iii) tumour with a variable epithelioid cell component; iv) myxoid stromal changes; v) focal to absent vasculature characteristic of SFT; tumours without alternating hypocellular and hypercellular areas; vi) tumours with multinucleated floret-like cells; vii) tumour with sarcomatous overgrowth consisting of atypical spindle to epithelioid