{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:43:25Z","timestamp":1791510205044,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Conventional high\u2010grade osteosarcomas are characterized by aggressive radiologic features, cytologic pleomorphism, and complex genomics. However, rare examples of osteosarcomas remain challenging due to unusual histology, such as sclerosing or osteoblastoma\u2010like features, which may require molecular confirmation of their complex genetic alterations. We have encountered such a case in a 17\u2010year\u2010old man, who presented with a third metatarsal sclerotic bone lesion, found incidentally in the work\u2010up of a foot trauma. The initial imaging revealed a lesion with sclerotic\/blastic features proximally and lucent\/lytic portion distally, findings interpreted consistent with osteoblastoma. The lesion was managed intra\u2010lesionally with curettings and cryoablation; however, the microscopic findings were non\u2010specific, showing a bland osteoblastic proliferation embedded in a densely sclerotic matrix. Subsequently, the patient developed two rapid recurrences; the first recurrence was treated similarly despite its associated soft tissue extension radiographically, and the histologic findings remained non\u2010specific. The 2nd recurrence showed a large mass, with bone destruction and soft tissue extension and an open biopsy revealed features of osteosarcoma with lace\u2010like osteoid deposition, albeit with uniform cytomorphology. The subsequent below knee amputation showed features compatible with high\u2010grade osteosarcoma, including solid growth of uniform epithelioid cells, with vesicular nuclei and scant cytoplasm, set in a lace\u2010like meshwork of osteoid matrix. There was significant mitotic activity and tumor necrosis. Tumor cells were positive for SATB2. Further molecular work\u2010up was performed showing an unexpected <jats:italic>NIPBL::BEND2<\/jats:italic> fusion, which has been previously reported in two cases of phosphaturic mesenchymal tumor (PMT). FGF23 (ISH) was performed and was negative. By DNA methylation profiling, unsupervised clustering and UMAP dimensionality reduction revealed grouping with high\u2010grade osteosarcomas and not with the PMT group. The patient received chemotherapy post\u2010amputation and is alive without evidence of disease, with 10\u2010month follow\u2010up. We report an aggressive, overtly malignant acral bone\u2010forming tumor, harboring a <jats:italic>NIPBL::BEND2<\/jats:italic> fusion. Further studies are needed to evaluate the recurrent potential of this fusion in osteosarcomas and its relationship with PMT.<\/jats:p>","DOI":"10.1002\/gcc.70015","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T05:30:28Z","timestamp":1732771828000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Malignant Bone\u2010Forming Neoplasm With <scp><i>NIPBL::BEND2<\/i><\/scp> Fusion"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-3458","authenticated-orcid":false,"given":"Nooshin K.","family":"Dashti","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Dartmouth Health Medical Center  Lebanon New Hampshire USA"},{"name":"Geisel School of Medicine at Dartmouth  Lebanon New Hampshire 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