Synonyms

• Osteosarcoma
• osteoblastic variant; sclerosing osteosarcoma

Category

Bone

Behaviour

Malignant

Grade

High

Gender

Male (1.5:1)

Tissue of Origin

Bone

Epidemiology

• Most common subtype of conventional osteosarcoma (50%)
• Peak incidence in 2nd decade
• Bimodal age distribution: adolescents and elderly (secondary OS)

Clinical Features

• Pain and swelling at affected site
• Decreased range of motion of adjacent joint
• Pathological fracture in 10%
• Palpable firm mass

Location

• Metaphysis of long Bones
• Distal femur (40%), proximal tibia (20%), proximal humerus (10%)
• Axial skeleton in older patients
• Jaws in secondary osteosarcoma

Imaging

• Dense sclerotic 'ivory' lesion with aggressive periosteal reaction
• Sunburst periosteal reaction and Codman triangle
• Cortical destruction and soft tissue mass
• MRI: heterogeneous with prominent Low-signal sclerotic areas

Pathology

• High-grade sarcomatous stroma producing abundant osteoid/Bone
• Densely mineralised tumour matrix
• High nuclear grade and mitotic activity
• Necrosis proportional to chemotherapy response

Genetics

• Complex karyotype
• TP53, RB1 alterations common
• MDM2/CDK4 amplification in secondary osteosarcoma
• ATRX mutations

Treatment

• Neoadjuvant MAP chemotherapy (methotrexate, doxorubicin, cisplatin)
• Wide surgical resection - limb salvage in 85%
• Adjuvant chemotherapy based on histological response (>90% necrosis = good response)
• Amputation for unresectable or neuroVascular involvement

Prognosis

• 5-year survival 60–70% for localised disease
• Good histological response (>90% necrosis) is the most important prognostic factor
• Pulmonary metastases in 30–40%
• Paget-related OS: very poor prognosis (10% 5-year survival)

Key Points

• Most common conventional OS subtype - 'classic' osteosarcoma
• Dense ivory sclerosis on X-ray is Highly characteristic
• Histological response to neoadjuvant chemotherapy is the single most important prognostic factor
• High-dose methotrexate is uniquely active in OS - not used in other sarcomas

Workup - Blood Tests

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

Workup - Local Imaging

• Plain radiograph
• MRI with gadolinium of whole bone

Workup - Biopsy

• Core needle biopsy at sarcoma centre
• Histology: High-grade osteosarcoma with abundant mineralised osteoid
• MDM2/CDK4 FISH - negative (excludes secondary OS associated with amplification)
• IHC: TP53, MDM2, H3K27me3 panel

Workup - Staging

• CT chest - pulmonary metastases
• Wole-body MRI - skip lesions and bone metastases
• PET-CT

Workup - Other

• Echocardiogram and audiometry pre-chemotherapy
• Fertility counselling - pre-treatment
• MDT at Bone sarcoma specialist centre (NICE IOG) mandatory

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