Synonyms

• Osteosarcoma
• chondroblastic variant

Category

Bone

Behaviour

Malignant

Grade

High

Gender

Male

Tissue of Origin

Bone

Epidemiology

• Second most common subtype of conventional osteosarcoma (25%)
• Peak incidence 2nd decade
• Male predominance
• Same demographics as conventional osteosarcoma

Clinical Features

• Pain and swelling at affected site
• Pathological fracture in 10%
• Decreased range of motion of adjacent joint
• Mass effect on surrounding structures

Location

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

Imaging

• Mixed lytic-sclerotic lesion with aggressive periosteal reaction
• Predominantly chondroid matrix (rings and arcs, popcorn mineralisation)
• Cortical destruction and soft tissue mass
• MRI: heterogeneous signal with cartilaginous lobules

Pathology

• High-grade sarcomatous stroma with abundant Malignant Cartilage
• Osteoid production by tumour cells (required for diagnosis)
• Nuclear pleomorphism and High mitotic activity
• Areas of necrosis common after chemotherapy

Genetics

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

Treatment

• Neoadjuvant chemotherapy (MAP: methotrexate, doxorubicin, cisplatin)
• Wide surgical resection - limb salvage preferred
• Adjuvant chemotherapy based on histological response
• Poor response to chemotherapy more common in chondroblastic variant

Prognosis

• 5-year survival 60–70% for localised disease
• Chondroblastic variant may have slightly worse chemotherapy response
• Pulmonary metastases in 30–40%
• Good histological response (>90% necrosis) associated with better outcome

Key Points

• Chondroblastic variant may resemble chondrosarcoma - osteoid must be identified
• Often shows poorer chemotherapy response than other OS subtypes
• Distinguishing from dedifferentiated chondrosarcoma is critical (different treatment and prognosis)
• IDH1/2 mutation testing helps exclude chondrosarcoma

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 - pre-operative

Workup - Local Imaging

• Plain radiograph
• MRI primary site with gadolinium - local staging, medullary extent, skip lesions

Workup - Biopsy

• Core needle biopsy at sarcoma centre - planned to alLow en bloc excision of tract
• Histology: High-grade stroma with cartilaginous differentiation + osteoid production
• IDH1/2 mutation testing - negative (excludes chondrosarcoma)
• MDM2/CDK4 FISH - negative (excludes parosteal OS or DDLPS)

Workup - Staging

• CT chest - pulmonary metastases
• Bone scan or PET-CT - Bone metastases and skip lesions

Workup - Other

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

Follow-up Summary

• Years 1–2: 3–4 monthly clinical review + CXR; MRI primary site at 3 months post-op then 6-monthly
• CT chest every 3 months for 2 years (main metastatic site = lungs)
• Years 3–5: 6-monthly clinical review + CXR; CT chest 6-monthly
• Years 6–10: Annual clinical review + CXR; CT chest annually
• Histological response to MAP chemotherapy is reviewed at surgery - guides adjuvant strategy
• Limb function assessed using MSTS/TESS scores at each visit