Evaluating low back pain in adolescents.

Journal and index pages often block iframe embedding. This reader keeps the evidence details in Orthonotes and leaves the source page one click away.

Abstract

[Indexed for MEDLINE] 4. Genes Chromosomes Cancer. 2024 Nov;63(11):e70015. doi: 10.1002/gcc.70015. Malignant Bone-Forming Neoplasm With NIPBL::BEND2 Fusion. Dashti NK(1)(2), Matcuk G(3), Agaimy A(4), Saoud C(5), Antonescu CR(5). Author information: (1)Department of Pathology and Laboratory Medicine, Dartmouth Health Medical Center, Lebanon, New Hampshire, USA. (2)Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA. (3)Department of Musculoskeletal Radiology, Cedars-Sinai Medical Center, Los Angeles, California, USA. (4)Institute of Pathology, University Hospital of Erlangen, Erlangen, Germany. (5)Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Conventional high-grade 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-like features, which may require molecular confirmation of their complex genetic alterations. We have encountered such a case in a 17-year-old man, who presented with a third metatarsal sclerotic bone lesion, found incidentally in the work-up 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-lesionally with curettings and cryoablation; however, the microscopic findings were non-specific, 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-specific. The 2nd recurrence showed a large mass, with bone destruction and soft tissue extension and an open biopsy revealed features of osteosarcoma with lace-like osteoid deposition, albeit with uniform cytomorphology. The subsequent below knee amputation showed features compatible with high-grade osteosarcoma, including solid growth of uniform epithelioid cells, with vesicular nuclei and scant cytoplasm, set in a lace-like meshwork of osteoid matrix. There was significant mitotic activity and tumor necrosis. Tumor cells were positive for SATB2. Further molecular work-up was performed showing an unexpected NIPBL::BEND2 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-grade osteosarcomas and not with the PMT group. The patient received chemotherapy post-amputation and is alive without evidence of disease, with 10-month follow-up. We report an aggressive, overtly malignant acral bone-forming tumor, harboring a NIPBL::BEND2 fusion. Further studies are needed to evaluate the recurrent potential of this fusion in osteosarcomas and its relationship with PMT. © 2024 Wiley Periodicals LLC. DOI: 10.1002/gcc.70015 PMCID: PMC11977784