Tuesday 6 July 2004
Case 166 (HP:166) : osteoblastic osteosarcoma
Case 157 (HPC:157) : giant cell-rich osteoblastic osteosarcoma
Case 140 (HPC:140) : osteoblastic osteosarcoma
Case 127 (HPC:127) : osteoblastic osteosarcoma
Case 126 : pulmonary metastase of an osteosarcoma
Case 115 : chondroblastic osteosarcoma of the calcaneum
UI:323 - Osteosarcoma 1 (NOS)
UI:856 - Osteosarcoma 2 (NOS)
Definition: Osteosarcoma is a primary malignant tumour of the skeleton characterised by the direct formation of immature bone or osteoid tissue by the tumour cells. Most osteosarcomas are highly aggressive malignancies characterized by a complex pattern of chromosome abnormalities.
Osteosarcoma is the most commonly diagnosed primary malignancy of bone, particularly among children and adolescents.
Osteosarcoma is the most common, nonhaemopoietic, primary malignant tumour of bone; estimated incidence of 4-5 per million population.
The classic osteosarcoma is a rare (0.2% of all malignant tumours) highly malignant tumour, with an estimated incidence of 3 cases/million population/year.
Osteosarcoma arises predominantly in the long bones and rarely in the soft tissues. The age at presentation ranges from 10 to 25 years of age.
There does not appear to be significant association with ethnic group
or race. Conventional osteosarcoma is largely a disease of the young.
It most frequently occurs in the second decade with some 60% of patients under the age of 25 years.
Although 30% of osteosarcomas occur in patients over 40 years of age, the possibility of a predisposing condition should always be considered in older patients (e.g., Paget disease of
bone, post-radiation sarcoma).
WHO classification 2002
- osteosarcoma NOS (not otherwise specified) ICD-O:9180/3
- chondroblastic osteosarcoma ICD-O:9181/3
- fibrobastic osteosarcoma (osteofibrosarcoma) ICD-O:9182/3
- central osteosarcoma (conventional central osteosarcoma, medullary osteosarcoma) ICD-O:9180/3
- intracortical osteosarcoma ICD-O:9195/3
small cell osteosarcoma
low grade central osteosarcoma
high grade surface osteosarcoma
osteoblastic osteosarcoma (osteogenic osteosarcoma)
small cell osteosarcoma
giant cell rich osteosarcoma
parosteal osteosarcoma (juxtacortical osteosarcoma)
Osteosarcoma arising in a background of paget’s disease of bone and post-radiation osteosarcoma are examples of secondary osteosarcoma. The former affects elderly patients, and has a poor prognosis and response to treatment. The later affects a wide age group, and has a prognosis and response to treatment comparable with primary osteosarcoma.
Unlike primary osteosarcoma in young patients, which arises most often in the metaphyses of long bones, such as the distal femur, proximal tibia, and proximal humerus, secondary osteosarcoma tends to occur more commonly in axial locations and in areas that have been previously exposure to radiation therapy, alkylating agents or that have underlying diseases such as Paget disease, Rothmund-Thompson, retinoblastoma, Ewing’s sarcoma and Li-Fraumeni syndrome.
Osteosarcoma (OS) is an aggressive sarcoma of the bone characterized by chromosomal instability (CIN) and high copy-number gene amplification.
CIN in OS is likely to arise by a combination of cell cycle dysregulation and defects in DNA repair pathways. Constitutional DNA repair deficiencies have been shown to lead to an elevated frequency of chromosome translocations, but little work has been done regarding the role of these defects. Several pathways that orchestrate genomic fidelity have been shown to be altered in this tumour.
In the Rothmund-Thompson syndrome, the RECQL4 helicase at the 8q24 OS hotspot is thought to play a specific role in maintenance of genomic stability. The high propensity for individuals with RECQL4 mutations to develop OS raises the possibility that deregulation of RECQL4 could drive the chromosomal instability in OS.
There is a correlation between relative RECQL4 copy number and its mRNA expression level in OS-derived cell lines and tumors. In addition, structural analysis of the 8q24.21-8q24.3 region revealed that RECQL4 copy number is independent of the MYC-C amplicon; and that there are different groups of OS exhibiting specific combinations of genomic heterogeneity/ complexity. This makes RECQL4 a potential molecular marker for CIN or prognosis in OS.
However, a subgroup of low-grade, parosteal osteosarcoma exhibits a relatively simple aberration pattern dominated by ring chromosomes carrying amplified material from chromosome 12.
- target genes: CCND2, ETV6, KRAS2, MDM2
Years ago, all patients with osteosarcoma were treated by amputation but the cure rate was under 10% and almost all patients died within a year from diagnosis.
Today, for localised osteosarcoma at onset (80% of cases) treated in specialized bone tumour centres with pre- and postoperative chemotherapy associated with surgery, the percentage of patients cured varies between 60% and 70%.
Surgery is conservative (limb salvage) in more than 90% of patients. Prognosis is more severe (cure rate about 30%) for tumours located in the axial skeleton and in patients with metastasis at onset.
Picci P. Osteosarcoma (Osteogenic sarcoma). Orphanet J Rare Dis. 2007 Jan 23;2:6. PMID: 17244349
Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. Cancer Genet Cytogenet. 2003 Aug;145(1):1-30. PMID: 12885459