Chondrosarcoma -

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 behavior
- 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

Grade	Descriptions
1 Low Grade	Resembles normal cartilage cells with mild cellular atypia Least risk of metastasis Frequent calcification
2 Medium Grade	Frequent double nuclei Atypia with plump cells Rare multinucleated giant cells Calcification
3 High Grade	Most 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
- Osteosarcoma
- Fibrosarcoma
- MFH
Most malignant of chondrosarcoma & highest rate of metastasis

(2) Primary & Secondary Types

Primary

Arise de novo (primary) – most

Secondary

1. From pre-existing cartilage lesions
- Osteocartilaginous exostosis
- Enchondroma (Ollier disease , Maffucci syndrome)
- Periosteal chondroma
- Chondroblastoma
- Chondromyxofibroma
- Synovial chondromatosis
- Earlier age of presentation than the primary tumours
2. From other cause
- Pagets
- 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

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

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

Other cartilage tumours
Chondrosarcomatous osteosarcoma

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