Osteosarcoma — Workup & Management

Osteosarcoma is the most common primary malignant bone tumour, excluding multiple myeloma and lymphoma. It is a high-grade spindle cell sarcoma that produces osteoid or immature bone directly from tumour cells. Despite its relative rarity, osteosarcoma disproportionately affects children and young adults and is associated with significant morbidity and mortality. Modern multimodal treatment — combining chemotherapy and limb-salvage surgery — has transformed survival from less than 20% to approximately 70% for localised disease.

• Incidence: approximately 3 per million per year; bimodal age distribution — first peak in adolescence (10–20 years, 75% of cases); second smaller peak in elderly (>65 years, often secondary to Paget disease or radiation)
• Male:female ratio: 1.5:1 in primary osteosarcoma
• Most common locations: distal femur (40%), proximal tibia (20%), proximal humerus (10%) — all metaphyseal regions of fastest growth (growth plate equivalent)
• The tumour arises in the metaphysis in 90% of cases — the zone of most active bone remodelling
• Risk factors: rapid bone growth (adolescent growth spurt), prior radiation, Paget disease, hereditary retinoblastoma (Rb gene mutation), Li-Fraumeni syndrome (p53 mutation), Rothmund-Thomson syndrome
• Most important prognostic factor: presence of metastases at diagnosis — 15–20% of patients have detectable metastases at presentation; lungs are the most common site (85–90%); skip lesions in same bone in 1–3%

• Symptoms: progressive, worsening bone pain — initially activity-related, becomes constant including at night; swelling over the affected area; limited joint movement; pathological fracture in approximately 5–10% at presentation
• Night pain and rest pain in an adolescent with a metaphyseal bone lesion = osteosarcoma until proven otherwise
• Examination: firm, tender, warm swelling over metaphysis; overlying skin may have dilated veins; joint effusion if tumour approaches articular surface; assess neurovascular status of the limb
• Pulmonary symptoms: cough, haemoptysis in advanced pulmonary metastases — rare at presentation but important to screen
• Alkaline phosphatase: elevated in 40–60% — reflects osteoblastic activity; useful monitoring marker
• LDH: elevated in high-grade disease — independent poor prognostic marker

A systematic staged radiological workup is essential. The principle is: local staging first, then systemic staging.

• Plain radiographs (AP and lateral of affected bone): first-line; classic features — mixed lytic-sclerotic metaphyseal lesion, Codman triangle (periosteal elevation at tumour margin), sunburst periosteal reaction, soft tissue mass; Codman triangle is NOT pathognomonic of osteosarcoma — seen in any rapidly growing periosteal lesion; sunburst pattern more specific
• MRI of the entire affected bone: mandatory for local staging — defines intramedullary extent (determines osteotomy level), soft tissue involvement, neurovascular relationship, skip lesions, and articular involvement; T1 with gadolinium and STIR sequences
• CT chest: mandatory for pulmonary metastasis assessment — CT superior to plain film for small pulmonary nodules; baseline before chemotherapy
• Bone scan (Technetium-99m): whole body — detects skip lesions and distant bone metastases; complements CT chest and MRI
• PET-CT: increasingly used for staging and chemotherapy response assessment — more sensitive than bone scan for metabolically active deposits; guides biopsy of most active site
• MRI planned BEFORE biopsy — biopsy contaminates tissue planes and can compromise limb salvage if placed incorrectly; MRI defines the safe biopsy corridor

• Biopsy of a suspected bone sarcoma should be performed at or referred to the treating sarcoma centre — incorrect biopsy placement is the most common avoidable cause of unnecessary amputation
• Core needle biopsy (Tru-Cut/Jamshidi): preferred — adequate tissue for diagnosis and molecular studies; less contamination than open biopsy; performed under image guidance (CT or USS)
• Open (incisional) biopsy: reserved for failed needle biopsy; must follow oncological principles — longitudinal incision in line with planned resection; strict haemostasis; drain exiting through wound; no transverse incisions
• Biopsy tract must be excised en bloc with the tumour at definitive surgery — contaminated tract is part of the surgical specimen
• Avoid contaminating neurovascular bundles, adjacent compartments, or joints — dramatically complicates or precludes limb salvage
• Send tissue for histology AND microbiology — infection can mimic tumour on imaging

The Enneking staging system (MSTS) and the AJCC TNM system are both used. Enneking staging is most common for bone sarcomas in the musculoskeletal oncology community.

• Most conventional osteosarcomas present as Stage IIB — high-grade, extracompartmental (soft tissue extension)
• Enneking Stage III (metastatic): 5-year survival approximately 20–30% with aggressive treatment including metastasectomy

• Standard protocol: neoadjuvant chemotherapy → surgery → adjuvant chemotherapy (MAP protocol — Methotrexate, Adriamycin/doxorubicin, Cisplatin)
• Neoadjuvant (pre-operative) chemotherapy: 8–12 weeks before surgery — reduces tumour size, facilitates limb salvage, treats micrometastases, allows assessment of chemotherapy response
• Histological response to neoadjuvant chemotherapy (Huvos grading): most important prognostic factor after staging

• Good histological response (>90% necrosis, Huvos III/IV) = best prognostic indicator after surgery; predicts long-term survival
• Poor responders (<90% necrosis): second-line chemotherapy regimens; prognosis significantly worse; current clinical trials exploring alternatives

• Wide surgical margins: the oncological goal — en bloc resection with a cuff of normal tissue around the tumour; margin status is a critical determinant of local recurrence
• Limb-salvage surgery (LSS): now performed in approximately 85–90% of cases — oncologically equivalent to amputation when wide margins achieved; requires careful patient selection and preoperative planning
• Reconstruction options after resection:

• Osteotomy level: minimum 3 cm beyond abnormal MRI signal (marrow extent) or 5 cm from radiographic tumour margin — whichever is more distal from the tumour
• Expandable prostheses (MUTARS, STANMORE): used in skeletally immature patients — lengthened non-invasively or minimally invasively to match contralateral limb growth; avoids multiple open surgeries

• Pathological fracture through osteosarcoma: historically considered an indication for amputation due to contamination of tissue planes; modern evidence suggests limb salvage remains possible in selected cases after neoadjuvant chemotherapy with wide resection — decision made at specialist sarcoma MDT
• Joint involvement on MRI: articular extension or skip lesion in the epiphysis changes the surgery — may require resection of the entire joint and reconstruction with custom implant or allograft-prosthesis composite; do not compromise margins to preserve the joint
• Poor responders to chemotherapy: histological response <90% necrosis — current evidence does not support a survival benefit from changing to second-line chemotherapy agents; enrolment in clinical trials is strongly encouraged; newer agents (mifamurtide, sorafenib) show some promise
• Pulmonary metastasectomy: surgical resection of isolated lung metastases improves survival in selected patients — complete resection of all visible deposits is associated with 20–30% long-term survival; thoracic surgeon should be part of the MDT
• Surveillance after treatment: CT chest every 3 months for 2 years, then every 6 months to 5 years; MRI of operative site every 6 months for 2 years; bone scan annually; late recurrences can occur up to 10 years after treatment

• Most common primary malignant bone tumour (excluding myeloma/lymphoma); distal femur most common site (40%)
• Night pain + metaphyseal lesion in adolescent = osteosarcoma until proven otherwise
• Codman triangle = periosteal elevation; sunburst = more specific for osteosarcoma; neither pathognomonic
• MRI before biopsy — defines safe biopsy corridor; wrong biopsy = unnecessary amputation
• Biopsy tract must be excised en bloc with the tumour — contaminated tract is part of the specimen
• Huvos IV (>90–100% necrosis) = good chemotherapy responder = best prognosis; 5-year survival >80%
• MAP protocol: Methotrexate, Adriamycin, Cisplatin — neoadjuvant + adjuvant
• Parosteal osteosarcoma: low-grade, posterior distal femur, excellent prognosis — surgery without chemotherapy
• Rotationplasty: ankle acts as knee after 180° tibial rotation — excellent function in young children
• Osteotomy level: 3 cm beyond MRI signal or 5 cm from radiographic margin