Primary retroperitoneal extra-skeletal osteosarcoma with synchronous pulmonary metastases: A case report and literature review

Extraskeletal osteosarcoma (ESOS) is a rare high-grade malignant mesenchymal neoplasm characterized by the production of osteoid, bone, or chondroid matrix by malignant cells without direct attachment to bone or periosteum. 
We report a 54-year-old man who presented with two months of progressive abdominal pain, early satiety, abdominal fullness, and weight loss. Cross-sectional imaging revealed a 12-cm necrotic retroperitoneal mass invading the left psoas muscle and multiple bilateral pulmonary nodules. Core biopsy showed pleomorphic spindle cells with marked atypia, brisk mitotic activity, and malignant osteoid. SATB2 and osteocalcin positivity supported osteoblastic differentiation, while the negative epithelial, neural, and MDM2 immunophenotype helped narrow the differential diagnosis; biopsy of a pulmonary nodule confirmed metastatic ESOS. Sequencing identified a complex karyotype without a therapeutically actionable alteration.  
After multidisciplinary review, the patient received neoadjuvant doxorubicin, cisplatin, and high-dose methotrexate, with a 30% reduction in the primary mass. He subsequently underwent negative-margin en-bloc resection requiring partial nephrectomy and psoas resection, followed by adjuvant therapy. Progressive pulmonary disease, followed by hepatic and osseous metastases, developed despite metastasectomy and second-line treatment; he died 14 months after diagnosis. 
This case illustrates the diagnostic complexity, limited durability of response, and aggressive metastatic biology of retroperitoneal ESOS despite intensive multimodal treatment.