Clear cell chondrosarcoma: a review of clinicopathologic characteristics, differential diagnoses, and patient management

Clear cell chondrosarcoma (CCC), an extremely rare primary bone tumor, is currently classified by the World Health Organization as a low-grade malignant cartilaginous neoplasm. Clinically, CCC occurs primarily in males with a peak incidence in the third to fifth decades of life, and occasionally, it presents in skeletally immature patients. Unlike conventional chondrosarcoma, CCC has a predilection for the epiphysis of long bones and often displays radiologic features reminiscent of chondroblastoma. The recommended treatment is wide operative resection. CCC has a local recurrence rate of approximately 30%, and nearly 20% cases metastasize mainly to bone and lung often a decade after surgical intervention. Incomplete excision or curettage is associated with a high rate of recurrence. Histologically, the process is characterized by infiltrative lobules and sheets of round to oval cells with abundant cleared cytoplasm and well-defined cell borders associated with trabecula of osteoid and woven bone, scattered osteoclasts, and foci of conventional low-grade chondrosarcoma in about one-half of cases. Correlation with clinical and radiologic characteristics, such as epiphyseal location and young patient age, assists in establishing a correct diagnosis. Pathologic diagnosis of CCC is complicated by the low diagnostic accuracy of core needle biopsy, overlapping histologic features with other matrix-rich primary bone tumors, and a lack of a specific immunohistochemical and molecular profile. DNA methylation-based profiling classifier (sarcoma classifier) is one recent technologic advancement that may help to confirm the histopathological diagnosis of CCC or indicate the need for thorough reassessment in cases where results contradict previous conventional findings.