Chondrosarcoma

Chondrosarcomas may be divided into primary and secondary lesions on the basis of their origins. Primary chondrosarcomas arise de novo, whereas secondary chondrosarcomas arise from preexisting lesions of the cartilage.

Except for their origin in preexisting cartilaginous conditions, secondary chondrosarcomas are similar to conventional chondrosarcomas in all respects. In addition, the genes responsible for the lesions depend on the primary benign cartilaginous condition. Secondary chondrosarcomas occur in individuals with Ollier disease, Maffucci syndrome, multiple hereditary exostosis (diaphyseal aclasis), solitary osteochondroma, solitary enchondroma, solitary periosteal enchondroma, Paget disease, or radiation injury.

Genetics

Bovee et al reported that most peripheral chondrosarcomas had a higher proliferation rate on Ki-67 immunohistochemistry and that they were associated with loss of heterozygosity at many loci. ^{[6, 7]} Only a few chondrosarcomas had anomalies, which were restricted to 9p21, 10, 13q14, and 17p13. These anomalies were peridiploid or near-haploid. Structural chromosomal aberrations and genetic instability were seen during cytogenetic analysis of well-differentiated, grade I chondrosarcomas. Nearly all grade III and some grade II chondrosarcomas were aneuploid.

Amplification of the c-myc proto-oncogene ^[8] and fos/jun ^[9] has been implicated in the pathogenesis of chondrosarcoma.

With extraskeletal myxoid chondrosarcomas, ^[10] the t(9;22)(q22;q12) translocation is common, though t(9;17)(q22;q11.2) has also been described. Numerous genetic alterations have been found for dedifferentiated chondrosarcomas, but a shared loss of chromosome 13 suggests that the differentiated and dedifferentiated components originate from a common precursor.

Isocitrate dehydrogenase 1 and 2 (IDH1, 2) mutations have been identified in chondrosarcomas. ^{[11, 12]}

Histologic grading

Chondrosarcomas can be classified into the following three histologic grades, depending on findings of cellularity, atypia, and pleomorphism:

• Grade I (low grade) – This is cytologically similar to enchondroma ^[2] ; cellularity is higher, with occasional plump nuclei with open chromatin structure
• Grade II (intermediate grade) – This is characterized by a definite and increased cellularity; distinct nucleoli are present in most cells, and foci of myxoid change may be seen
• Grade III (high grade) – This is characterized by high cellularity, prominent nuclear atypia, and the presence of mitosis

The higher the grade, the more likely the tumor is to spread and metastasize. Grade I lesions rarely metastasize, whereas 10-15% of grade II lesions and more than 50% grade III lesions metastasize.

Low-grade chondrosarcomas resemble benign cartilaginous tumors, and it is difficult to differentiate the two lesions on the basis of histologic features alone. The essential differences are the limited growth potential of benign cartilaginous tumors and the slow growth capacity of low-grade chondrosarcomas.

Dedifferentiated chondrosarcomas are more aggressive than grade III conventional chondrosarcomas.

Frequency by tumor type

Conventional central chondrosarcomas account for nearly 80-90% of all chondrosarcomas and 20-27% of all primary bone sarcomas ^[13] .They demonstrate a predilection for the axial skeleton. Rates of involvement are as follows:

• Pelvis and ribs, 45%
• Ilium, 20%
• Femur, 15%
• Humerus, 10%
• Others, 10%

The spine and the craniofacial bones are rarely involved.

Dedifferentiated chondrosarcomas are responsible for as many as 10% of all chondrosarcomas. The femur is the site most commonly involved, accounting for one-third of all dedifferentiated chondrosarcomas. The other sites of involvement are the pelvis (20%), the humerus (16%), the ribs (7%), and the scapula (7%).

Clear cell chondrosarcomas account for fewer than 5% of all chondrosarcomas. They have a predilection for the ends of long tubular bones, involving the epiphysis. Like chondroblastomas, these lesions extend to involve the articular cartilage. The proximal aspect of the femur is the site most often affected (45%), followed by the proximal portion of the humerus.

Fewer than 2% of all chondrosarcomas are mesenchymal chondrosarcomas. The maxilla and the mandible are the most common sites of involvement, followed by the vertebrae, the ribs, the pelvis, and the humerus. The appendicular skeleton is rarely involved.

Juxtacortical chondrosarcomas are rare and generally involve the surface of the diaphysis or metaphysis of long tubular bones.

Age-, sex-, and race-related demographics

Incidences do not differ among ethnic groups. Sex and age distributions are listed in Table 1 below.

Table 1. Sex Ratios and Ages of Peak Incidence for Different Types of Chondrosarcoma (Open Table in a new window)

Chondrosarcomas are considerably rarer in children and adolescents than in adults. ^[14]

The prognosis is correlated with the grade and stage of the lesion at the time of diagnosis. ^[15] The location of the lesion is also important because tumors in areas where complete wide resection is possible are associated with better prognoses. In general, chondrosarcomas of the head and neck are associated with better disease-specific survival and overall survival rates than chondrosarcomas located elsewhere. ^[16]

Recurrence and distant metastasis may develop. The metastasis rate for primary chondrosarcoma is higher than that for secondary chondrosarcoma, and the rate of distant metastasis is higher in patients with local recurrence than in those without local recurrence.

In children and adolescents, chondrosarcoma of bone has a very good prognosis and is less aggressive than in older patients. ^[14]

Mortality and morbidity data for the various types of chondrosarcomas are summarized below.

Conventional chondrosarcoma

Evans et al ^[17] showed that the survival rate depends on the histologic grade of the tumor, as follows:

• Grade I tumors - 90% survival at 5 years
• Grade II tumors - 81% survival at 5 years
• Grade III tumors - 29% survival at 5 years

Overall, the 5-year survival rate for conventional chondrosarcomas is 48-60%. ^[13] Intralesional surgery is not advised even in grade I lesions, especially in the pelvis, because the local recurrence rate is 100% in such cases.

Grade I tumors do not metastasize, whereas 66% of grade III tumors do. The most common sites for metastases are the lungs. Recurrences typically appear 5-10 years or longer after surgery.

Dedifferentiated chondrosarcoma

Dedifferentiated chondrosarcoma is highly lethal. It is associated with a 10% survival rate after 1 year. Even with early surgical treatment, disseminated hematogenous metastasis occurs in most patients. ^[13]

Clear cell chondrosarcoma

Although clear cell chondrosarcomas are low-grade tumors, they can lead to distant metastasis. Late recurrences (>10 years) have been described. Overall, the recurrence rate is 16% ^[13] .

Mesenchymal chondrosarcoma

The 5-year survival rate for mesenchymal chondrosarcoma is less than 50%, with an overall 10-year survival rate of 28%. ^[13]

Juxtacortical chondrosarcoma

Juxtacortical chondrosarcomas are low- to intermediate-grade lesions; the prognosis for these tumors is better than that for other tumors. ^[13]