Synonyms

• Osteosarcoma
• fibroblastic variant

Category

Bone

Behaviour

Malignant

Grade

High

Gender

Male

Tissue of Origin

Bone

Epidemiology

• Accounts for 25% of conventional osteosarcoma
• Peak incidence in 2nd decade
• Same demographics as conventional osteosarcoma

Clinical Features

• Pain and swelling at affected site
• Pathological fracture in 10%
• May grow faster than chondroblastic variant
• Decreased range of motion of adjacent joint

Location

• Metaphysis of long Bones
• Distal femur most common
• Proximal tibia, proximal humerus
• Axial skeleton in older patients

Imaging

• Predominantly lytic with minimal matrix mineralisation
• Aggressive periosteal reaction (Codman triangle, sunburst)
• Cortical destruction and soft tissue mass
• MRI: large heterogeneous mass with extensive soft tissue involvement

Pathology

• High-grade spindle cell sarcoma with herringBone/fascicular pattern
• Osteoid production by tumour cells (essential for diagnosis)
• Minimal chondroid matrix
• High nuclear grade and mitotic activity

Genetics

• Complex karyotype
• TP53 and RB1 alterations common
• MDM2/CDK4 amplification in some cases
• ATRX mutations

Treatment

• Neoadjuvant MAP chemotherapy (methotrexate, doxorubicin, cisplatin)
• Wide surgical resection - limb salvage when feasible
• Adjuvant chemotherapy based on histological response
• Good response to chemotherapy - generally better than chondroblastic variant

Prognosis

• 5-year survival 60–70% for localised disease
• Generally better chemotherapy response than chondroblastic variant
• Pulmonary metastases in 30–40%
• Good histological response (>90% necrosis) is the most important prognostic factor

Key Points

• Predominantly lytic lesion - may be confused with fibrosarcoma of Bone or MFH
• Identification of osteoid (even focal) is required for OS diagnosis
• Generally more chemosensitive than chondroblastic OS
• Must be distinguished from High-grade surface osteosarcoma

Workup - Blood Tests

• FBC, U&E, LFTs, Bone profile - baseline and pre-chemotherapy
• Alkaline phosphatase - tumour marker; elevated in 50%
• LDH - prognostic marker
• Coagulation screen

Workup - Local Imaging

• Plain radiograph
• MRI whole bone with gadolinium - local staging, medullary and soft tissue extent

Workup - Biopsy

• Core needle biopsy at sarcoma centre - en bloc excision of tract required
• Histology: High-grade spindle cell sarcoma with osteoid production
• MDM2/CDK4 FISH - negative (excludes parosteal OS)
• IHC panel: TP53, MDM2, H3K27me3

Workup - Staging

• CT chest - pulmonary metastases
• PET-CT - skeletal staging

Workup - Other

• Echocardiogram and audiometry baseline pre-chemotherapy
• MDT at Bone sarcoma specialist centre (NICE IOG)

Follow-up Summary

• Year 1: Post-operative visit within first 6 weeks (if primary surgery); 2-monthly clinical examination, CXR, plain films of primary site; annual blood biochemistry (U&E, LFT, Ca, PO4, Mg, HCO3); end of Year 1 - gonadal function (males: testosterone, LH, FSH; females: oestradiol, LH, FSH)
• Years 2–3: 3-monthly clinical examination, CXR, plain films of primary site; annual blood biochemistry; end of Year 2 - MUGA or ECHO
• Year 4: 6-monthly clinical examination, CXR, plain films of primary site; annual blood biochemistry; end of Year 4 - MUGA or ECHO
• Year 5: 6-monthly clinical examination, CXR, plain films of primary site; annual blood biochemistry
• Years 6–10: Annual clinical examination, CXR, plain films of primary site; annual blood biochemistry; end of Year 6 - MUGA or ECHO
• Discharge at 10 years after surgery