Clear Cell Chondrosarcoma

Staging is according to bone sarcoma protocols (see TNM staging of tumors of bone). See also the information on staging in section Bone tumors: Introduction.

Cytogenetic analyses of small series have revealed clonal abnormalities, with diploid or near-diploid complements predominating and loss or structural aberrations of chromosome 9 and gain of chromosome 20. CDKN2A alterations appear to be infrequent, although all clear cell chondrosarcomas examined lacked expression of p16 (CDKN2A). p53 overexpression is frequently found in the absence of detectable mutations. Neither IDH1 nor IDH2 mutations are present. One of 15 clear cell chondrosarcomas investigated for H3.3 mutations to date has shown an H3-3B (H3F3B) p.Lys36Met mutation, a highly specific driver mutation of chondroblastoma, suggesting a pathogenetic relation in at least a small subset of tumors.

Lesions range from 2 to 13 cm in maximum diameter. They contain soft but gritty material, sometimes with cystic areas. Gross features characteristic of hyaline cartilage can be focal or absent.

The tumors consist of lobules of cells with abundant pale, clear or slightly eosinophilic cytoplasm, which resemble hypertrophic cells of the growth plate. The cells have distinct cytoplasmic membranes and large round nuclei with only minor atypia and central nucleoli. Mitotic figures are rare. Further characteristics frequently observed include regularly distributed woven bone formation with intermingled osteoclast-like giant cells. Areas of conventional low-grade chondrosarcoma with minimally atypical nuclei can be observed in about half of cases. The hyaline cartilage can become calcified and/or ossified, which can be detected radiologically as a cartilage-type pattern of mineralization. Areas of cystic degeneration resembling aneurysmal bone cyst can also occur. Infiltrative growth can be seen.

Not clinically relevant

En bloc resection with clear margins is usually curative. Marginal excision or curettage results in high recurrence rates of up to 86%. Metastases, usually to the lungs and other skeletal sites, develop in 15–20% of cases. The overall mortality rate is 15%. Dedifferentiation to high-grade sarcoma has been reported in 3 cases.

Not clinically relevant

Essential: clear cells with abundant cytoplasm and a centrally placed nucleus; presence of woven bone and osteoclast-like giant cells.

Desirable: epiphyseal location.