Bone Tumor, Primary Malignant
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- Primary malignant bone tumors are rare (<1% of all tumors). Patients >40 years; rule out more common metastatic disease (breast, lung, prostate, thyroid, kidney).
- Osteogenic sarcomas arise from mesenchymal cells capable of differentiating into bone, cartilage, or fibrous tissue. The three histologic types are:
- Osteosarcoma: characterized by the production of osteoid or immature bone by malignant cells
- Chondrosarcoma: cellular cartilaginous tumor with abundant binucleate cells, myxoid areas, pushing borders; lacks osteoid
- Fibrosarcoma: spindle cells and collagen; no osteoid
- Ewing sarcoma: small, round blue-cell neoplasm of unknown histologic origin
- Malignant fibrous histiocytoma (MFH): pleomorphic sarcoma; 10-year survival 20% for high grade, 90% for low grade
- Giant cell tumor of bone (GCTB) has both benign (90%) and malignant forms; prefers epiphyseal long bone, often recurs; 5–10% of primary bone tumors; very destructive
- Chordoma develops from remnants of primitive notochord at base of skull or sacrum; rare; slowly progressive; recurrent; cure possible
- Rare: Estimated 2,970 primary bone tumors is diagnosed in the United States in 2015; 1,490 deaths
- In adults: most common osteosarcoma (35%), chondrosarcoma (30%), Ewing sarcoma (16%)
- In resource-rich populations: Malignant bone tumors represent 3–5% of cancers diagnosed in children 0 to 14 years of age and 7–8% of cancers in adolescents 15 to 19 years of age (1)[A]; third most common childhood cancer (after leukemia and brain tumor)
- In children: Most common is osteosarcoma (52%), Ewing sarcoma (34%) second, and chondrosarcoma third.
- Predominant age
- Osteosarcoma: bimodal: ages 13 to 16 years and >65 years
- Chondrosarcoma: 3rd to 7th decades
- Fibrosarcoma: 2nd to 6th decades
- Ewing sarcoma: children and teen aged 10 to 15 years (70% of Ewing patients <20 years of age)
- MFH: adults and elderly
- GCTB: skeletally mature young adult in 2nd to 4th decades
- Chordoma: >40 years
- Predominant gender
- For most, male = female
- Osteosarcoma, male > female (1.5:1); Ewing sarcoma, male > female; chondrosarcoma, male > female (2:1); chordoma, males > females
- Ewing sarcoma is more common in Caucasian than in African American children.
- Osteosarcoma is slightly more common in African American than in Caucasian children.
Etiology and Pathophysiology
- Generally unknown but likely multifactorial
- Chondrosarcoma may arise in preexisting enchondroma or exostosis.
- MFH often follows irradiation or arises in old bone infarct.
- GCTB RANKL-RANK-OPG signal pathway involved
- Genetic risk factors include:
- Paget disease: osteosarcoma
- Multiple hereditary exostosis: chondrosarcoma
- Multiple enchondromatosis (Ollier disease): chondrosarcoma
- Enchondromatosis and hemangiomatosis (Maffucci syndrome): chondrosarcoma
- Germline retinoblastoma, especially after radiation: osteosarcoma
- Li-Fraumeni syndrome (germline p53 or CHEK2 mutation): osteosarcoma
- Rothmund-Thomson syndrome (autosomal recessive): osteosarcoma
- RAPADILINO syndrome: osteosarcoma
- Diamond-Blackfan anemia (disorder of bone marrow): osteosarcoma
- Tumor genetics
- Ewing sarcoma has chromosomal translocation t(11;22) (q24;q12) in 90% of tumors and resulting EW5-FLI1 fusion protein. Mutation in the EWSR1 causes Ewing sarcoma (somatic mutation).
- Osteosarcoma shows loss of retinoblastoma 1 gene (RB1) and p53 suppressor genes and amplification of the genes c-myc, mdm-2, SAS, and cyclin-dependent kinase.
Commonly Associated Conditions
- Genetic conditions listed previously
- Patients with enchondromatosis more often die of GI malignancies than of metastatic chondrosarcoma.