Abstract
Primary osteosarcoma (OS) of the uterus is a distinctly rare and aggressive disease with fewer than 20 cases reported worldwide. We describe a case of primary uterine OS with rapid development of pulmonary and brain metastasis in a 50-year-old woman. Histopathologic examination of the uterine tumor showed atypical spindle cells producing an osteoid matrix with calcification in keeping with OS. Despite initial response to doxorubicin and ifosfamide, the patient succumbed to brain metastases just 8 months from diagnosis. Whole genome sequencing was performed on tumor and blood samples to analyze genetic alterations in this highly aggressive tumor. A pathogenic somatic missense mutation resulting in substitution of glutamate for lysine at position 653 within the protein kinase domain of the platelet-derived growth factor receptor beta (PDGFRB) was found. The PDGF pathway is involved in cell proliferation and angiogenesis, and it has been implicated in malignancy. Crucially, this pathogenic mutation may be amenable to PDGFR tyrosine kinase inhibition, representing a possible treatment approach in this rare sarcoma.