Synonyms

Dediff CS

Category

Bone

Behaviour

Malignant

Grade

High

Gender

Both equally

Tissue of Origin

Cartilage

Epidemiology

• 10% of chondrosarcomas
• Peak incidence in 6th–8th decades
• Older patients than conventional chondrosarcoma
• No significant sex predilection

Clinical Features

• Rapid onset of pain or swelling in patient with known or suspected chondroid lesion
• Pathological fracture common (25%)
• Often large tumour at presentation
• Rapid clinical deterioration

Location

• Pelvis and proximal femur most common
• Proximal humerus
• Distal femur
• Same distribution as central chondrosarcoma

Imaging

• Bimorphic lesion: cartilaginous component (rings/arcs calcification) and aggressive lytic component
• Abrupt transition between components characteristic
• CT: calcified chondroid lobules + permeative lytic area
• MRI: High T2 chondroid component + aggressive sarcomatous component

Pathology

• Bimorphic histology: Low-grade chondrosarcoma juxtaposed with High-grade non-chondrosarcomatous sarcoma
• Abrupt transition (no gradual dedifferentiation)
• High-grade component: MFH-like, osteosarcoma-like, or fibrosarcoma-like
• IDH1/2 mutation in Low-grade component

Genetics

• IDH1 (R132) or IDH2 (R172) mutation in chondroid component
• Complex genomic alterations in dedifferentiated component
• CDKN2A loss, TP53 mutation in High-grade component

Treatment

• Wide surgical resection - primary treatment
• Adjuvant chemotherapy (doxorubicin/ifosfamide) for High-grade dedifferentiated component
• Chemotherapy response modest
• Radiotherapy for unresectable disease

Prognosis

• Very poor: 5-year survival 10–25%
• Most patients die within 2 years of diagnosis
• Haematogenous metastasis to lungs in >80%
• Worst prognosis of all chondrosarcoma subtypes

Key Points

• Abrupt bimorphic histology is characteristic - unlike secondary High-grade sarcoma
• IDH mutation confirms chondroid origin of Low-grade component
• Treated as High-grade sarcoma despite cartilaginous component
• Prognosis dramatically worse than conventional chondrosarcoma

Workup - Blood Tests

• FBC, U&E, LFTs, Bone profile - pre-operative baseline
• Alkaline phosphatase - often elevated
• LDH - elevated in aggressive disease

Workup - Local Imaging

• Plain radiograph
• MRI primary site - mandatory; defines extent of dedifferentiated (non-chondroid) component and soft tissue involvement

Workup - Biopsy

• Core needle biopsy - must sample both components (chondroid and High-grade)
• Histology: Low-grade cartilaginous component with abrupt transition to High-grade sarcoma
• Immunohistochemistry: High-grade component Variable; S100 negative in dedifferentiated area
• IDH1/2 mutation testing - positive in 50% (supports diagnosis)

Workup - Staging

• CT chest - metastases present in 10–15% at diagnosis
• Bone scan or whole-body MRI for Bone metastasis survey

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 3–4 months for first 2 years (pulmonary metastasis occurs in >80%)
• Years 3–5: 6-monthly clinical review + CXR; CT chest 6-monthly
• Years 6–10: Annual clinical review + CXR; CT chest annually
• Chemotherapy patients: routine toxicity monitoring and blood counts at each visit
• Discharge at 10 years with documented self-monitoring advice