Chondrosarcoma

• Malignant primary bone tumor composed of chondrocytes with variable degrees of malignancy
  • primary chondrosarcoma
    • which includes
      • low-grade, high-grade, dedifferentiated chondrosarcoma
      • clear cell chondrosarcoma (see below)
      • mesenchymal chondrosarcoma (see below)
  • secondary chondrosarcoma
    • arises from benign cartilage lesions including 
      • osteochondroma (<1% risk of malignant transfomation)
      • multiple hereditary exostosis (1-10% risk of malignant transformation) 
      • enchondromas (1% risk of malignant transformation)
      • Ollier's disease (25-40% risk of malignant transformation)
      • Maffucci's (100% risk of malignant transformation)
• Epidemiology
  • demographics
    • typically, chondrosarcomas are found in older patients (40-75 yrs)
    • there is a slight male predominance
  • location
    • most common locations include the pelvis, proximal femur, distal femur, scapula 
    • tumor location is important for diagnosis as the same histology may be diagnosed as benign in the hand but malignant if located in the long bones
• Prognosis
  • histologic grade correlates with survival  
    • Grade I
      • 90% 5-year survival
      • grade 1 chondrosarcomas are generally slow growing
    • Grade II
      • 60-70% 5-year survival
    • Grade III
      • 30-50% 5-year survival
    • De-differentiated chondrosarcoma
      • <10% 5-year survival
  • poor prognostic variables
    • axial and proximal extremity lesions
      • have a more aggressive course
      • pelvic location 
    • advanced patient age
    • inadequate surgical margins 
  • increased telomerase activity
    • as determined by reverse transcriptase-polymerase chain reaction (RT-PCR), increased telomerase activity has been shown to directly correlate with the rate of recurrence  
  • referral to orthopedic oncologist is necessary for best prognosis 

• Grade
  • 85% of chondrosarcomas are grade 1 or 2
  • 15% of chondrosarcomas are grade 3 or dedifferentiated chondrosarcoma 
    • de-differentiated chondrosarcomas are high grade lesions which develop from low grade chondroid lesions
• Chondrosarcoma sub-types
  
  • Clear cell chondrosarcoma  
    • malignant immature cartilaginous tumor accounting for <2% of all chondrosarcomas
    • most common in 3rd and 4th decades of life
    • commonly presents with insidious onset of pain 
    • presents as an epiphyseal lesion and can be mistaken for low-grade chondroblastoma
    • locally destructive with potential to metastasize 
  • Mesenchymal chondrosarcoma
    • chondrosarcoma variant which presents with a biphasic pattern of neoplastic cartilage with associated neoplastic small round blue cell component
    • occurs in younger patients than typical chondrosarcomas
    • may occur at several discontinuous sites at presentation and can occur in the soft tissues
    • treatment includes neo-adjuvant chemotherapy followed by wide surgical resection

• Symptoms
  • pain is the most common symptom
  • variable rapidity of presentation dependent on tumor grade and location
  • may present with slowly growing mass or symptoms of bowel/bladder obstruction due to mass effect in the pelvis
  • 50% of de-differentiated chondrosarcomas present with a pathologic fracture

• Radiographs
  • views
    • AP and lateral views
  • findings
    • lytic or blastic lesion with reactive thickening of the cortex 
    • 85% of patients have significant cortical changes
      
      • low-grade chondrosarcomas show
        • similar appearance to enchondromas with additional cortical thickening/expansion and endosteal erosion  
      • high-grade chondrosarcomas show
        • cortical destruction and a soft tissue mass
    • intra-lesional "popcorn" mineralization  may be seen 
      • described as rings, arcs, and stipples of mineralization, more prevalent as lesions age
    • de-differentiated chondrosarcomas radiographically show a lower grade chondroid lesion with superimposed highly destructive area consistent with the high grade transformed dedifferentiated chondrosarcoma  
    • mesenchymal chondrosarcomas appear similar to Ewing sarcoma with permeative bone destruction and periosteal reaction  
• MRI
  • indications
    • MRI helpful to determine marrow and soft tissue involvement 
  • findings
    • typically dark on T1 and bright on T2 in non-mineralized portions due to high water content
    • heterogeneous and moderate contrast uptake, can be most in fibrovascular connective tissue separating cartilage lobules
• CT
  • indications
    • CT most useful study for low grade cartilage neoplasms to determine cortical involvement
  • findings
    
    • matrix calcifications more easily identified on CT compared to radiographs
    • deep endosteal scalloping suggests chondrosarcoma instead of enchondroma
    • 90% have cortical breach
• Bone scan
  • indications
    • can help distinguish (not definitively) chondrosarcoma and enchondroma
    • can determine location of metastastic disease 
  • findings
    
    • usually very hot in all grades of chondrosarcoma

• Chondrosarcoma
  • needle biopsy is not indicated for cartilage tumors due to difficulties with diagnosis
    • lesions are often heterogenous and difficult to diagnose on histology alone
      
    • diagnosis requires clinical, pathologic, and radiographic correlation
  • characteristic histology
    • low-grade chondrosarcomas show
      • features similar to enchondroma
      • few mitotic figures with a bland hyaline cartilage appearance
      • hypercellularity and disorganization
      • enlarged chondrocytes with plump multinucleated lacunae  
    • high-grade chondrosarcomas show 
      • hypercellular stroma consisting of characteristic "blue-balls" of a cartilage lesion which permeate the bone trabeculae 
      • benign cartilage appearance and lacunar structure is absent
      • more disorganization, more pleomorphism, and more mitotic figures
  • enchondromas of hand, Ollier's disease, Maffucci's disease, periosteal chondromas, and chondrosarcoma may all have similar histology
• De-differentiated chondrosarcomas
  • most malignant of cartilage tumors, < 10% long-term survival
  • characterized by a bimorphic histology
    • low grade chondroid component
    • high grade spindle cell component (similar histology to osteosarcoma, fibrosarcoma, MFH)  
    • 80% are chondrosarcomas with an extra destructive area
• Mesenchymal chondrosarcoma
  • biphasic appearance with low grade chondrosarcoma adjacent to small, round blue cells 
• Clear cell chondrosarcoma
  • lobular architecture similar to other cartilage neoplasms, but cells are large and vacuolated 
  • typically low to intermediate grade

• Nonoperative
  • chemotherapy & radiation
    • indications
      • chondrosarcomas are generally resistant to chemotherapy and radiation 
• Operative
  
  • intra-lesional curettage 
    • indications
      • Grade 1 lesions in the extremities (minimal rate of metastasis)
      • treatment of grade 1 lesions located in the pelvis or axial skeleton is controversial (higher rate of local recurrence and metastasis)
        • most authors recommend wide excision of all chondrosarcomas (even grade 1) if located in the pelvis
  • wide surgical excision          
    • indications
      • grade 2 or 3 lesions
      • grade 1 lesions in pelvis
  • wide surgical excision combined with multi-agent chemotherapy  
    • indications
      • mesenchymal chondrosarcoma
      • the role of chemotherapy in de-differentiated chondrosarcoma is very controversial

• Local recurrence
  • for high-grade lesions, local recurrence associated with distant metastasis and decreased survival
  • grade 1 chondrosarcoma: 
    • rare after wide resection with negative margins
    • 5-15% after curettage with adjuvant treatment
  • grade 2 chondrosarcoma:
    • varies depending on resection margins
  • grade 3 chondrosarcoma:
    • 25% local recurrence rate and >30% rate of metastasis

	Location	Xray	Xray	CT	B. Scan	MRI	MRI	Histo(1)
Case A	scapula
Case B	femur
Case C	pelvis
Case D	tibia
Case E	prox femur
Case F	prox. humerus
Case H	pelvis (dedifferentiated)
Case I	femur (dedifferentiated)

(1) - histology does not always correspond to case