Introduction
Osteoma | Osteoid osteoma | Osteoblastoma | Conventional osteosarcoma | |
---|---|---|---|---|
Clinical features | • Benign | • Benign | • Locally aggressive | • Malignant |
• Mostly found incidentally | • < 2 cm in size | • > 2 cm in size | • Located at metaphysis of long bones | |
• Located at bone surface | • Located in long bones | • Located in posterior column of spine | ||
Radiology | Homogenous and sharply demarcated tumour | Oval radiolucency (nidus) with surrounding sclerosis | Often lytic lesion , may be alike aneurysmal bone cyst | Lytic, sclerotic or mixed lesion, often expanding into surrounding soft tissue |
Karyotype | Simple karyotype | Simple karyotype | Simple karyotype | Complex karyotype |
Molecular pathology | Can be associated with Gardner’s syndrome: germline APC mutation | FOS and to a lesser extent FOSB translocations | FOS and to a lesser extent FOSB translocations | Chromothripsis and kateagis with most often alterations in TP53 |
Osteoid osteoma and osteoblastoma
Clinical presentation
Histology
Molecular pathology
Osteosarcoma
Clinical presentation
Histology
Subtype | Location | Grade | Histology |
---|---|---|---|
Low-grade central osteosarcoma | Medulla | Low grade | Spindle cells with low-grade nuclear atypia and well-formed neoplastic woven bone trabeculae, often 12q13 amplification |
Parosteal osteosarcoma | Surface | Low grade | Spindle cell proliferation, often with cartilaginous differentiation, and 12q13 amplification |
Periosteal osteosarcoma | Surface (typically underneath the periosteum) | Intermediate grade | Predominantly chondroblastic bone-forming sarcoma |
Conventional osteosarcoma | Medulla | High grade | High-grade sarcoma in which the tumour cells produce bone. Tumour cells can be fibroblastic, chondroblast- or osteoblast-like |
Fibroblastic Chondroblastic Osteoblastic | |||
Small-cell osteosarcoma | Medulla | High grade | Small cells with scant cytoplasm, associated with variable osteoid formation; may resemble Ewing sarcoma |
Telangiectatic osteosarcoma | Medulla | High grade | Osteosarcoma composed of blood-filled or empty cystic spaces closely simulating aneurysmal bone cyst |
High-grade surface osteosarcoma | Surface | High grade | Similar to conventional osteosarcoma |
Germline predisposition to osteosarcoma
Molecular alterations in osteosarcoma
Gene | Type of alteration | Somatic/germline | Function | Frequency in sporadic OS (%) | Literature |
---|---|---|---|---|---|
TP53 | Translocation; deletion; mutation | Germline (Li-Fraumeni syndrome) and somatic | Genome stability; cell cycle control | 47–90 | |
RB1 | Mutation; deletion | Germline (retinoblastoma) and somatic | Genome stability; cell cycle control | 29–47 | |
MYC | Amplification | Somatic | Cell proliferation | 39 | [39] |
CCNE1 | Amplification | Somatic | Cell cycle control | 33 | [39] |
DLG2 | Deletion | Somatic | Cell signalling | 29–52 | |
COPS3 | Amplification | Somatic | Signal transduction | 20–39 | |
AURKB | Amplification | Somatic | Cell cycle | 13 | [39] |
PTEN | Mutation; deletion; copy number alteration | Somatic | Cell cycle control | 12–50 | |
CDKN2A | Deletion | Somatic | Cell cycle control | 15 | [38] |
ATRX | Mutation; deletion | Germline (ATR-X syndrome) and somatic | Genome stability; chromatin remodelling; ALT | 10–29 | |
CDKN2A | Mutation; deletion | Somatic | Cell cycle control | 10 | [36] |
CDK4 | Amplification | Somatic | Regulates RB activity | 9–11 | |
MDM2 | Amplification | Somatic | Regulates P53 activity | 5–12 | |
IGF1R | Mutation; amplification | Somatic | Bone growth and development | 5 | [36] |
AKT | Amplification | Somatic | Cell proliferation; apoptosis | 5 | |
RECQL4 | Mutation | Germline (Rothmund-Thomson syndrome) | DNA repair; genome stability | 0 | [32] |
WRN | Mutation | Germline (Werner syndrome) | DNA repair; genome stability | 0 | [32] |
BLM | Mutation | Germline (Bloom syndrome | DNA repair; genome stability | 0 | [32] |