Clear cell chondrosarcoma

Clear cell chondrosarcomas are low-grade malignant chondrogenic bone neoplasms of the epiphysis. They got their name from the presence of clear cell chondrocytes which contain abundant vacuolated cytoplasm due to the presence of glycogen.

Epidemiology

Clear cell chondrosarcomas make up around 2% of all chondrosarcomas ^1,2 and are usually seen in the 3^rd to 5^th decade even though they have been reported in an age range of 12-84 years ¹. Men are almost three times as often affected as women ¹.

Diagnosis

The diagnosis of clear cell chondrosarcomas is mainly based on typical pathology ¹.

Diagnostic criteria

Diagnostic criteria according to the WHO classification of soft tissue and bone tumors (5^thedition) ¹:

Essential criteria are ¹:

• clear cells with abundant cytoplasm and central nuclei
• woven bone and osteoclastic giant cells

An epiphyseal location of the tumor is a desirable criterion ¹.

Clinical presentation

Clinically, clear cell sarcomas most commonly present with pain. Symptoms persist for an average duration of one year or up to 5 years, suggesting slow growth of the lesion ¹.

Complications

Complications include ^2,3:

• pathological fractures
• tumor recurrence
• metastases to lung and bone (in exceptional cases)

Pathology

Clear cell chondrosarcomas are low-grade malignant cartilaginous bone neoplasms often found in the epiphyses and characterized by the presence of lobules of clear cells that contain an abundant clear or mildly eosinophilic cytoplasm with centrally placed nuclei ^1-3.

Etiology

The etiology of clear cell chondrosarcomas is not known ¹.

Location

The lesion is most often in an epi-metaphyseal location of long tubular bones ^1-4 (in contradistinction to conventional chondrosarcoma, which is usually metaphyseal-diaphyseal). Yet, they have been described in several locations of the skeleton including the skull, spine, ribs, hands and feet ^1-4

• proximal femur: 55-60% (commonest)
• proximal humerus: 10-15%

Macroscopic appearance

Grossly clear cell chondrosarcomas usually contain soft gritty material with features of hyaline cartilage, the latter can be also focal or absent ¹.

Microscopic appearance

Histologically clear cell chondrosarcomas are characterized by the following ^1-4:

• lobules of cells with abundant clear or mildly eosinophilic cytoplasm
• distinct cytoplasmic membranes
• large round nuclei with prominent central nucleoli
• only mild atypia, rare mitoses
• reactive (woven) bone formation
• intermingled osteoclastic giant cells
• calcified or ossified hyaline cartilage
• areas of low-grade chondrosarcoma might be present
• possible aneurysmal bone cyst-like changes

Immunophenotype

On immunohistochemistry, clear cells express S100 ^1,4-6 and show reactivity for collagen type II and X ¹. They can also be positive for cytokeratins ¹. 

Radiographic features

Clear cell chondrosarcomas are usually well-defined osteolytic lesions often found in the epi-metaphysis of the proximal femur or humerus ^1-3. A diaphyseal extension is rare ⁷. They might have matrix mineralization, thin sclerotic borders or cystic changes ^2-4,7.

Lesions in the proximal humerus usually appear more aggressive than in other long bones ^2,7.

Lesions in the axial skeleton are typically more expansive, lack mineralization and tend to show soft tissue extension more often than their counterparts in the long bones ². 

Plain radiograph

On radiographs, clear cell chondrosarcomas are predominantly radiolucent and expansile ^2,3,5-7: 

• endosteal irregularity is not infrequent
• a periosteal reaction is usually absent
• soft tissue extension and cortical break are usually seen only if a pathologic fracture occurs
• a calcified matrix might be present
• a peripheral sclerotic rim is common (simulating a benign lesion)
• variable transition zone

They are usually classified as grade 1A or 1B on the Lodwick classification of lytic bone lesions ⁶.

CT

Clear cell chondrosarcomas may appear as solitary lucent bone lesions on CT ².

Matrix mineralization with a chondroid matrix as well as concerning features such as cortical involvement and soft tissue extension can be more readily depicted ².

MRI

On MRI clear cell chondrosarcomas are mostly characterized as low T1/high T2 bone lesions with signal heterogeneity due to matrix mineralization or intralesional hemorrhage ^2,7.

Surrounding perilesional bone marrow edema is absent or minimal in most cases ^2,7.

Signal characteristics

Typically reported signal characteristics on MR imaging include ^1,2,5-7:

• T1: low signal intensity
• T2: moderate to high signal intensity 
• T1 C+ (Gd): diffuse or heterogeneous enhancement 

Radiology report

The radiological report should include a description of the following ⁸:

• location and size
• tumor margins and transition zone
• relation to the growth plate and articular surface
• cystic and solid tumor components
• fluid-fluid levels suggesting aneurysmal bone cyst-like changes
• additional features
  • cortical involvement
  • soft tissue extension
  • pathologic fracture
  • periosteal reaction
  • surrounding bone marrow edema
  • solid mass-like enhancement

On CT and MRI the lesion can be categorized as Bone-RADS 4 unless histology has been already obtained ⁸.

Treatment and prognosis

Clear cell chondrosarcomas are relatively slow-growing. The treatment of choice is en bloc resection, which is usually curative with clear margins ^1,2,9, whereas marginal excision and curettage are associated with high recurrence rates ^1,2. Bone and lung metastases occur in 15-20% ^1,9, and the overall mortality is about 15% ^1,6, therefore surveillance of 10 years or longer has been advocated ⁹.

History and etymology

Clear cell chondrosarcomas were first described by the American pathologist K.Krishnan Unni in 1976 ^2-5,10. 

Differential diagnosis

The differential includes lesions with a predilection for the epiphysis (see differential for an epiphyseal lesion). Specific lesions that need to be considered include the following ¹:

• chondroblastoma: a particular feature of clear cell chondrosarcomas is a predilection for the epiphysis, in which case they mimic chondroblastomas; distinguishing between the two can be difficult (see chondroblastoma vs. clear cell chondrosarcoma)
• lytic bone metastases (especially from clear cell renal cell carcinoma)
• chondroblastoma
• giant cell tumor of bone
• chondrosarcoma
• osteosarcoma
• multiple myeloma
• benign notochordal cell tumor

See also

• chondrosarcoma
• chondrosarcoma grading