{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:32:38Z","timestamp":1782495158097,"version":"3.54.5"},"reference-count":17,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of National Defense Medical Affairs Bureau","award":["MND-MAB-D-112156"],"award-info":[{"award-number":["MND-MAB-D-112156"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Sarcomas, particularly undifferentiated small round cell sarcomas of bone and soft tissue, pose significant diagnostic challenges due to their nonspecific morphology and the necessity for comprehensive molecular analyses. This paper discusses a rare case of round cell sarcoma exhibiting the EWSR1-CREM fusion, offering insights into the complexities of its diagnosis and management. The patient, a 15-year-old female with a history of Type 1 diabetes, presented with persistent right thigh tenderness and swelling. MRI revealed a large necrotic mass in the retroperitoneal region. Histological analysis showed a well-demarcated tumor with diverse cellular morphologies and distinct necrotic areas. Immunohistochemical (IHC) tests identified dot-like staining for Desmin and Vimentin but negative results for several markers, including Cytokeratin and CD45. Strong ALK positivity was noted. Next-generation sequencing with the Illumina TruSight\u2122 Oncology 500 assay revealed the fusion gene EWSR1-CREM, along with benign and uncertain mutations in other genes. The tumor\u2019s morphology and immunoprofile, along with molecular findings, led to a diagnosis of round cell sarcoma with EWSR1-CREM fusion. This case adds to the spectrum of tumors associated with this fusion, often presenting diverse morphologies. The rarity of EWSR1-CREM fusion sarcomas poses a challenge in treatment, highlighted by the development of pulmonary metastases and disease progression after surgical excision in this patient despite the lack of an effective targeted therapy. In conclusion, this case emphasizes the need for a multidisciplinary diagnostic approach in complex sarcomas and highlights the importance of continued research on rare sarcomas, their genetic underpinnings, and potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/medicina60040544","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T14:14:09Z","timestamp":1711548849000},"page":"544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Elucidating the Diagnostic Complexity of Round Cell Sarcoma with EWSR1-CREM Fusion: A Comprehensive Case Study"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8897-4368","authenticated-orcid":false,"given":"Hao","family":"Yen","sequence":"first","affiliation":[{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Liang","family":"Chou","sequence":"additional","affiliation":[{"name":"Instrument Center, Department of Research and Development, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9601-8149","authenticated-orcid":false,"given":"Yao-Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Der-Shiun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s12957-021-02310-6","article-title":"Clinicopathological features of desmoplastic small round cell tumors: Clinical series and literature review","volume":"19","author":"Wang","year":"2021","journal-title":"World J. Surg. Oncol."},{"key":"ref_2","unstructured":"WHO Classification of Tumours Editorial Board (2024, February 02). Soft Tissue and Bone Tumours, Available online: https:\/\/publications.iarc.fr\/588."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.wneu.2020.07.015","article-title":"Primary Intracranial Mesenchymal Tumor with EWSR1-CREM Gene Fusion: A Case Report and Literature Review","volume":"142","author":"Liu","year":"2020","journal-title":"World Neurosurg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1097\/PAS.0000000000001331","article-title":"Expanding the Phenotypic Spectrum of Mesenchymal Tumors Harboring the EWSR1-CREM Fusion","volume":"43","author":"Yoshida","year":"2019","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1097\/PAS.0000000000000788","article-title":"EWSR1 Fusions with CREB Family Transcription Factors Define a Novel Myxoid Mesenchymal Tumor with Predilection for Intracranial Location","volume":"41","author":"Kao","year":"2017","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1038\/s41379-020-0646-5","article-title":"EWSR1\/FUS-CREB fusions define a distinctive malignant epithelioid neoplasm with predilection for mesothelial-lined cavities","volume":"33","author":"Argani","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1111\/pin.13030","article-title":"EWSR1-CREM fusion in pulmonary mesenchymal neoplasm showing distinctive clear cell morphology","volume":"70","author":"Komatsu","year":"2020","journal-title":"Pathol. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"959","DOI":"10.21037\/tcr-21-2331","article-title":"A EWSR1-CREM-rearranged gastric mesenchymal tumor accompanied by gastritis cystica profunda and with probable benign behavior: A case report","volume":"11","author":"Cui","year":"2022","journal-title":"Transl. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1097\/PAS.0000000000001096","article-title":"Ectomesenchymal Chondromyxoid Tumor: A Neoplasm Characterized by Recurrent RREB1-MKL2 Fusions","volume":"42","author":"Dickson","year":"2018","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/gcc.23094","article-title":"Metastatic sporadic paraganglioma with EWSR1::CREM gene fusion: A unique molecular profile that expands the phenotypic diversity of the molecular landscape of the EWSR1::CREM gene fusion positive tumors","volume":"62","author":"Javaid","year":"2023","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/ijgo.14831","article-title":"Ovarian epithelioid malignant peripheral nerve sheath tumor with EWSR1-CREM fusion: A case report and literature review","volume":"163","author":"Li","year":"2023","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1097\/PAS.0000000000001114","article-title":"Molecular Profiling of Hyalinizing Clear Cell Carcinomas Revealed a Subset of Tumors Harboring a Novel EWSR1-CREM Fusion: Report of 3 Cases","volume":"42","author":"Chapman","year":"2018","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1111\/cup.14390","article-title":"Compound clear cell sarcoma with EWSR1::CREM fusion","volume":"50","author":"Li","year":"2023","journal-title":"J. Cutan. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s00428-021-03140-3","article-title":"Intra-abdominal EWSR1\/FUS-CREM-rearranged malignant epithelioid neoplasms: Two cases of an emerging aggressive entity with emphasis on misleading immunophenotype","volume":"480","author":"Agaimy","year":"2022","journal-title":"Virchows Arch."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/PAS.0b013e31814b18fb","article-title":"Clear cell sarcoma of soft tissue: A clinicopathologic, immunohistochemical, and molecular analysis of 33 cases","volume":"32","author":"Hisaoka","year":"2008","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/PAS.0000000000001103","article-title":"ALK Expression in Angiomatoid Fibrous Histiocytoma: A Potential Diagnostic Pitfall","volume":"43","author":"Cheah","year":"2019","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1159\/000449204","article-title":"Activity of c-Met\/ALK Inhibitor Crizotinib and Multi-Kinase VEGF Inhibitor Pazopanib in Metastatic Gastrointestinal Neuroectodermal Tumor Harboring EWSR1-CREB1 Fusion","volume":"91","author":"Subbiah","year":"2016","journal-title":"Oncology"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/4\/544\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:19:34Z","timestamp":1760105974000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/4\/544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,27]]},"references-count":17,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["medicina60040544"],"URL":"https:\/\/doi.org\/10.3390\/medicina60040544","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,27]]}}}