Chondrosarcoma

Chondrosarcoma is a malignant cartilage forming tumour of adults, most often in the pelvis, proximal femur and proximal humerus. It resists chemotherapy and radiotherapy, so wide surgical excision is the main treatment, and histological grade guides prognosis.

Definition

  • Malignant tumour of cartilage-producing cells
    • Proximal femur
    • Pelvic Girdle
    • Knee
    • Spine
  • 20% of primary bone tumours
  • 2nd in frequency to Osteosarcoma
  • It has a wide range of biologic behaviour
    • Low grade (grade 1): <5% risk of metastasis
    • Intermediate grade (grade 2): 20-30% risk of metastasis
    • Dedifferentiated (grades 3 and 4): 70% risk of metastasis
    • Mesenchymal: >50% risk of metastasis
  • 6-8th Decade of Life

Classification

  • Classified according to
    • Histological grade & subtypes
    • Primary & Secondary
    • Central & Peripheral

(1) Histological Grade & Subtypes

  • Based on the histological appearance
    • Conventional chondrosarcoma
      • Hyaline or myxoid cartilage tumour of various grades
    • Special types
      • Clear cell
      • Mesenchymal
      • Soft tissue chondrosarcoma
      • Chondrosarcoma of skull base
      • De-differentiated

Conventional Chondrosarcoma

GradeDescriptions
1 Low GradeResembles normal cartilage cells with mild cellular atypia
Least risk of metastasis
Frequent calcification
2 Medium GradeFrequent double nuclei
Atypia with plump cells
Rare multinucleated giant cells
Calcification
3 High GradeMost abnormal-appearing cartilage with highest risk of metastasis
Marked atypia & mitotic figures
Double nuclei & crowding of lacunae
Frequent multinucleated giant cells
No calcification
Grading of Conventional Chondrosarcoma
  • lesions in axial skeleton & proximal appendicular skeleton more likely to be malignant than distal limb lesions (ie. the digits)
  • Most chondrosarcomas are grade 1 or 2
  • Chondrosarcomas are occasionally grade 3
  • The only tumour that has higher risk of metastasizing than Grade 3 is De-differentiated Chondrosarcoma

Clear Cell Chondrosarcoma

  • Young adults 20-50 years
  • M:F – 2:1
  • Low grade usually
  • Thought to be malignant counterpart of the benign chondrhttp://chondroblastomaoblastoma
    • Hence “epiphyseal chondrosarcoma”
  • Most common in
    • Proximal humerus
    • Proximal femur
  • Involve the epiphyseal centre & metaphysis
  • Histology
    • Larger & more rounded tumour cells with clear or vacuolated cytoplasm (sheets of clear cells)
    • Abundant intracellular glycogen
    • Chondroid & osseous matrix with numerous osteoclast-like giant cells (may resemble renal cell carcinoma)
    • Foci of calcification

Mesenchymal Chondrosarcoma

  • 2nd-3rd decade of life
  • High-grade
  • Less common than clear cell
  • Most common in
    • Rib
    • Spine
    • Pelvis
    • Femur
  • Can appear in soft tissues
  • Histology
    • Nodules of benign cartilage in background of undifferentiated small round cells (biphasic appearance)
    • Small cell component has appearance of Haemangiopericytoma or Ewings
  • 60% 5 year survival

Soft Tissue Chondrosarcoma

  • Rare tumour
  • Little about natural history
  • Treated like other STS

Base of Skull Chondrosarcoma

  • Confused with chondroma of clivus
  • Presents with neurological deficits
  • Treated with curettage & irradiation

De-differentiated Chondrosarcoma

  • High-grade
  • Non-chondroid sarcoma
  • 10% of all chondrosarcomas
  • Usually arises from
    • Benign cartilage lesion
    • Low grade chondrosarcoma
  • Consists of areas of malignant spindle cells that cannot be recognised of cartilage origin adjacent to areas of neoplastic chondrocytes surrounded by hyaline ± bizarre giant cells
  • Cartilage matrix has tissue resembling
  • Most malignant of chondrosarcoma & highest rate of metastasis

(2) Primary & Secondary Types

TypeDescription
PrimaryArise de novo, most
Secondary, from pre-existing cartilage lesionsOsteocartilaginous exostosis
Enchondroma (Ollier disease, Maffucci syndrome)
Periosteal chondroma
Chondroblastoma
Chondromyxofibroma
Synovial chondromatosis
Earlier age of presentation than the primary tumours
Secondary, from other causePagets
Radiation
Later presentation than the primary tumours

(3) Central & Peripheral

Central (Medullary)

  • Arise from
    • medullary canal
      • Meta-diaphyseal
        • Metaphysis extending into diaphysis
      • Femur & Humerus most commonly
  • All primary types are central
  • Secondary types usually arise from Enchondroma

Peripheral (Juxtacortical)

  • Arise from the surface of bone
    • Pelvic & Shoulder girdle
    • Upper Femur & Humerus
    • Ribs
  • Majority secondary to Exostosis

Risk of Malignant Transformation

  • Solitary osteochondroma < 1%
  • Diaphyseal aclasia 1% per year
  • Solitary enchondroma < 1%
  • Multiple enchondroma (Ollier’s*, Marfucci’s) 20-30%
    • Patients with Ollier’s disease have 25% incidence of chondrosarcoma in lifetime
    • Patients with Maffucci syndrome have 100% incidence of chondrosarcoma in lifetime
  • Synovial chondromatosis 5%

Clinical Features

  • Classically patients in 5th-6th decades
  • 4% < 20yo
  • M:F – 1.5:1
  • Long history of pain & mass
  • Most commonly seen in medullary cavity of
    • Femur
    • Humerus
    • Pelvis (incl. acetabulum)
    • Ribs
  • Patients initially complain of mild local pain & swelling
  • Laboratory findings normal

Radiography

Chondrosarcoma, ct and radiograph of a chondrosarcoma of the proximal femur
CT and radiograph of a chondrosarcoma of the proximal femur. Image by Hellerhoff, Wikimedia Commons, CC BY-SA 3.0.

Central

  • Diaphyseal or less often Metaphyseal
  • Lucent expansile lesion
  • Sclerotic margins
  • Endosteal scalloping
  • Intralesional calcification
    • Amorphous
    • Punctate
    • Chicken Wire
    • Popcorn
  • Cortical destruction & soft tissue mass may be present
  • More destructive lesions have
    • Less calcification
    • More scalloping
    • More cortical destruction

Peripheral

  • Soft tissue mass
  • Multiple calcific densities
  • Ill-defined margins
  • Destruction of underlying bone
  • Some are using Thallium & DMSA scans to differentiate low from high grade lesions
    • uptake suggests ↑ metabolic activity (ie. high grade lesion)
  • Approach to CLUMP lesions
    • Bone scan cold
      • expect good histological characteristics
      • no need to biopsy
    • Bone scan hot
      • may have worrying histological features
      • MRI with gadolinium producing a contrast enhancement curve with images taken at a specific site every 7 seconds for 2 minutes
      • if there is a steep curve (rapid take-off) then suggestive of angiogenesis which may indicate aggressive lesion
      • if so then should consider biopsy

Histology

Chondrosarcoma, histology of chondrosarcoma
Histology of chondrosarcoma. Image by No machine-readable author provided. KGH assumed (based on copyright claims)., Wikimedia Commons, CC BY-SA 3.0.

Gross

  • Pearly white
  • Cauliflower-like mass
  • Surrounded by pseudocapsule

Histology

  • Lobules of cartilage
  • Matrix may have
    • Calcification
    • Necrosis
    • Myxoid degeneration
  • Features that suggest malignancy
    • Pleomorphism
    • Hypercellularity
    • Mitotic figures
    • Double nuclei in single lacunae
    • Multinucleated Giant Cells
  • Realise that the pathologist will accept chondromas with atypical features (↑ cellularity, binucleate cells, anaplasia etc) for certain lesions & still call them benign
    • Solitary enchondroma
    • Olliers or Marfucci’s
    • Periosteal chondroma
    • Synovial chondromatosis
  • Some chondromas are indistinguishable from low grade chondrosarcoma
  • 50% of Grade I chondrosarcomas are indistinguishable from cellular enchondroma
    • Distinction is made on the radiological appearance (bone destruction etc), soft tissue extension, location etc
    • Enchondromas & periosteal chondromas should be reviewed every year to see if they progress or change (particularly if multiple or part of a syndrome)

Genetics

  • Numerous chromosomes have been implicated
  • Patients with hereditary multiple exostoses and an EXT1 mutation are at higher risk than are patients with an EXT2 or EXT3 mutation
  • Myxoid chondrosarcoma is associated with a 9-22 chromosomal translocation

Grading

  • Grading based on complete patient
    • Age
    • Location
    • XR
    • Histology (see above)
  • More likely to be worrisome if
    • Central
    • Large
    • Old patient
    • Polyploid

Differential Diagnosis

Treatment

  • The mainstay of treatment is wide surgical resection
  • Highly resistant to chemotherapy & radiotherapy
    • Rate of DNA synthesis slow
    • Slow growing, low grade nature of tumours
  • Surgery should aim to be curative but sometimes margins are close d/t location of neurovascular structures
  • Aggressive excision with wide margin
    • Probably safest regardless of grade
  • Adjunctive treatment rarely used
  • May be indicated in
    • High grade lesions
    • Incomplete margins
      • Phenol to lyse remaining tumour cells then neutralised with alcohol
  • Irradiation most useful where wide resection not possible (eg. spine)
    • High dose irradiation can arrest growth of the tumour for several years but will only delay the local recurrence
  • Chemotherapy has been limited to the young patient with de-differentiated chondrosarcoma
    • Little data to support usage & in metastatic disease will slow growth but cure rare

Prognosis

  • Low-Moderate Grade
    • If treated with wide excision
    • 90% 5-year survival
  • High Grade
    • < 10% 5-year survival
  • Thus patients with low grade tumours can expect a cure but metastasis common in high grade
  • Depends on
    • Histological grade
    • Adequacy of resection

Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 10 October 2026.