Expanding the differential diagnosis of bone-forming tumors: a new entity characterized by a NIPBL::BEND2 fusion.

We report two bone-forming tumors driven by a newly recognized fusion. The first is a lesion in the distal radius of a 59-year-old female subject, which had been present for 10 years. Imaging showed an intramedullary tumor with an exophytic dorsal component and marked sclerosis, histologically best classified as low-grade osteosarcoma. The second was a destructive lesion in the left ulna of a 13-year-old female with a short history of elbow pain. Imaging showed a lytic lesion with subtle tumor ossification, histologically best classified as an atypical osteoblastoma-like tumor. A NIPBL::BEND2 fusion was found in both cases on whole genome sequencing. This fusion has been previously reported in three bone lesions, two of which were reported as phosphaturic mesenchymal tumors and the other exhibited features of a high-grade osteosarcoma. These newly reported cases were bone-forming, but histologically indolent, with no features of high-grade osteosarcoma, and did not demonstrate the typical features of a phosphaturic mesenchymal tumor nor evidence of tumor-induced osteomalacia. The World Health Organization has not established a specific name for tumors associated with a NIPBL::BEND2 fusion, and their biological potential cannot currently be predicted. These cases add to the expanding clinical and histological knowledge of this entity and illustrate that, in addition to the other rarely reported phenotypes, low-grade bone-forming tumors may also be caused by this exceptionally rare fusion.