Extraskeletal osteosarcoma- A diagnostic and therapeutic dilemma

Dear Editor,

Extraskeletal osteosarcoma (ESOS), first described in 1941, is a rare malignant mesenchymal tumour arising in soft tissues, accounting for ~1% of soft tissue sarcomas and 4–5% of all osteosarcomas.^[1,2] While histologically similar to conventional osteosarcoma, it is located in soft tissues and organs, which are not extensions of a primary bone osteosarcoma. Although chemotherapy reduces metastatic recurrence in skeletal osteosarcoma, there is no consensus regarding its role in ESOS due to its rarity.

A 51-year-old woman presented with a progressively enlarging swelling over the dorsum of the left foot for 5–6 months. Ultrasound demonstrated a solid-cystic lesion overlying the 2nd and 3rd metatarsals without bony involvement, and cytology suggested a high-grade sarcoma, prompting a core needle biopsy revealing a high-grade malignant neoplasm composed of pleomorphic spindle and polygonal cells with abundant neoplastic osteoid in lace-like and trabecular patterns. Immunohistochemistry was positive for SATB2 and vimentin and negative for keratin, S100, desmin, and melanocytic markers, supporting a diagnosis of ESOS. Positron emission tomography-computed tomography (PET-CT) demonstrated an isolated metabolically active foot lesion and small indeterminate pulmonary nodules.

Wide local excision of the forefoot mass, including the 2nd and 3rd metatarsals, was performed with free fibula flap reconstruction. The resected tumour measured 4×3×1.5 cm and was confirmed as FNCLCC grade 3, pT1, with clear margins. Genomic testing identified somatic KRAS p.(G12A) and POLE p.(E1001*) mutations; germline testing confirmed the POLE truncating variant, though its significance is unclear as it lies outside the exonuclease domain associated with ultra-mutated tumours.

After multidisciplinary discussion, the patient received four cycles of platinum-based chemotherapy (doxorubicin and cisplatin). At 18-month follow-up, she remains disease-free, with stable benign-appearing pulmonary nodules and no local recurrence on MRI.

Given the rarity of ESOS, further multicentre studies are needed to refine diagnostic criteria and guide optimal management.