Pathophysiology
Summary
Malignant bone tumors most commonly arise due to metastasis to bone from other cancers, often originating from ‘PB-KTL’ sites: prostate, breast, kidney, thyroid, lung.
Osteosarcoma is the most common primary malignant bone tumor. A notable genetic factor is the hereditary retinoblastoma, which increases the risk of osteosarcomas due to mutations in the RB1 tumor suppressor gene. Li-Fraumeni syndrome is caused by a mutation in the TP53 tumor suppressor gene—a cell cycle checkpoint protein—increases the risk of osteosarcoma and various other cancers. Radiation therapy, particularly when administered to children, also increases the risk. In patients < 40 yrs old diagnosed with osteosarcoma, the malignancy often arises from a sarcomatous transformation linked to Paget’s disease, a condition marked by disordered bone growth.
Histologically, osteosarcomas are marked by the presence of pink-staining osteoid and a gritty white mass with cystic degeneration & areas of hemorrhage. Osteosarcomas tend to invade the medullary cavity, and most frequently occur near the knee.
Diagnostic imaging plays an important role in evaluating osteosarcomas. On X-ray, these tumors exhibit a distinctive ‘sunburst’ pattern indicative of spiculated osteoid accompanied by zones of cortical destruction. Osteosarcoma and other bone tumors like Ewing sarcoma can manifest the ’Codman triangle’ on X-ray—a feature that arises when the tumor breaches the cortex, which subsequently pushes the periosteum away from the bone, leading to calcification in the corner and the formation of a triangle. Osteosarcomas frequently metastasize to the lungs through hematogenous routes, with some cases already metastasized at the time of diagnosis.
Ewing sarcoma is a malignant bone tumor predominantly people under 20 yrs old, and arises from neuroectodermal tissue. Ewing sarcoma is characterized by a distinct genetic translocation between the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11, resulting in the EWS-FLI fusion protein. Clinically, these tumors manifest as localized pain and swelling.
Ewing sarcoma originates in the medullary cavity and extends to invade the cortex and periosteum—predominantly localized to the diaphysis of long bones in the extremities. Grossly, the tumor appears tan-white and may display regions of necrosis and hemorrhage. Histologically, it is marked by sheets of small, round blue cells, often forming circular groups of cells with central clearing known as Homer-Wright rosettes. Radiographically, Ewing sarcoma presents a ‘moth-eaten’ appearance due to small lucencies in the medullary cavity and an ‘onion peel’ appearance stemming from multiple cycles of periosteal reactions forming concentric bone layers. Ewing sarcoma metastasizes hematogenously, most commonly spreading to the lungs.
Chondrosarcoma is distinctive in that it secretes cartilage, and most commonly affects individuals over 20 yrs of age, with the most diagnosed after the age of 50. Like Ewing sarcoma, chondrosarcoma also originates in the medullary cavity and progresses to invade the cortex and periosteum. Histologically, chondrosarcomas display lobules of cartilage invading the bone marrow. Chondrosarcomas also display a hematogenous pattern of metastasis, frequently targeting the lungs.
Lesson Outline
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FAQs
Osteosarcoma is the most prevalent malignant bone tumor is is associated with several risk factors. Hereditary retinoblastoma, resulting from a mutation in the RB1 tumor suppressor gene, increases the risk of osteosarcoma. Li-Fraumeni syndrome, caused by a mutation in the TP53 tumor suppressor gene. Additionally, radiation therapy, especially when administered to children, can also heighten the risk of osteosarcoma.
Osteosarcoma predominantly occurs near the knee, specifically in the regions of the distal femur and proximal tibia. It has a propensity to invade the medullary cavity. Histologically, osteosarcoma is characterized by a pink-staining osteoid. The tumor itself forms a gritty white mass, often accompanied by cystic degeneration and areas of hemorrhage.
Osteosarcoma is often identified by its characteristic ‘sunburst’ pattern on radiographic imaging. Another notable feature is the "codman triangle", which is seen when the tumor extends beyond the cortex, leading to the detachment of the periosteum from the bone. Ewing sarcoma, on the other hand, displays a ‘moth-eaten’ appearance, marked by small radiolucent areas within the medullary cavity. A distinctive ‘onion peel’ appearance can also be observed in Ewing sarcoma, which arises from repeated periosteal reactions that create layered, concentric rings of thin bone.
Ewing sarcoma predominantly is believed to arise from neuroectodermal tissue. Patients commonly present with localized pain and swelling. The tumor frequently develops in the diaphysis or shaft of long bones, especially in the extremities. Under microscopic examination, Ewing sarcoma is distinguished by its sheets of small, round blue cells. A notable histological feature includes Homer-Wright rosettes, which are circular arrangements of cells with a central clearing.
Chondrosarcoma stands out among malignant bone tumors due to its ability to produce cartilage. Histologically, this is manifested as lobules of cartilage that infiltrate the bone marrow. The tumor typically originates within the medullary cavity and subsequently invades the cortex and periosteum. Like osteosarcoma and Ewing sarcoma, chondrosarcomas often spread to the lungs.
