You are in: eMedicine Specialties > Radiology > MUSCULOSKELETAL Osteosarcoma, ClassicArticle Last Updated: Apr 13, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Geoff Hide, MBBS, MRCP, FRCR, Consultant Musculoskeletal Radiologist, Department of Radiology, Freeman Hospital; Honorary Clinical Lecturer, Faculty of Medical Sciences, University of Newcastle upon Tyne Geoff Hide is a member of the following medical societies: British Medical Association, Royal College of Physicians, and Royal College of Radiologists Editors: David S Levey, MD, PhD, Musculoskeletal Radiologist, Department of Magnetic Resonance Imaging, Radsource, LLC; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Murali Sundaram, MBBS, FRCR, FACR, Consulting Staff, Department of Diagnostic Radiology, The Cleveland Clinic Foundation; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Felix S Chew, MD, EdM, MBA, Professor, Department of Radiology, Section Head of Musculoskeletal Radiology, Vice Chairman for Radiology Informatics, University of Washington Author and Editor Disclosure Synonyms and related keywords: conventional osteosarcoma, chondroblastic osteosarcoma, osteoblastic osteosarcoma, fibroblastic osteosarcoma, high-grade intramedullary osteosarcoma INTRODUCTIONSection 2 of 12
  BackgroundOsteosarcoma is the most common primary malignant tumor of bone, excluding plasma cell myeloma. Classic, or conventional, osteosarcoma represents the most common variant of osteosarcoma, accounting for approximately 75% of all lesions. Osteosarcoma can affect any bone and is treated by a combination of surgical excision and chemotherapy. PathophysiologyOsteosarcoma is a malignant mesenchymal sarcoma characterized by the direct formation of bone or osteoid by tumor cells. Osteosarcoma is subclassified depending on the histologic characteristics of the cells. When the majority of the cells produce osteoid, the tumor is called osteoblastic. Where production of chondroid matrix is predominant, the tumor is classified as a chondroblastic osteosarcoma. When spindle cells are in the majority and little matrix is formed, the term fibroblastic osteosarcoma is used. FrequencyUnited StatesThe incidence in those younger than 20 years is 4.8 cases per million population. The incidence of osteosarcoma peaks in those aged 10-20 years; this observation corresponds to the maximal period of skeletal growth. A second smaller peak in the distribution of osteosarcoma as a whole is seen in late adulthood principally due to the occurrence of secondary osteosarcoma, which is usually related to Paget disease. Mortality/MorbidityThe overall prognosis depends on the stage of the tumor at presentation. The overall 5-year survival rate for patients whose disease was diagnosed between 1974 and 1994 was 63% (59% for males, 70% for females). RaceOsteosarcoma occurs in all racial and ethnic groups, but it is slightly more frequent in African American than in Caucasians. SexConventional osteosarcoma is slightly more common in males, with a male-to-female ratio of 3:2. This difference is thought to be due to the longer period of skeletal growth in males. AgeConventional osteosarcoma has a bimodal distribution. It occurs most frequently in those aged 10-20 years, the period coinciding with the time of maximal skeletal growth. Most cases occur in patients younger than 40 years, but a second small peak is seen in those older than 60 years. Osteosarcoma is rare in young children. AnatomyConventional osteosarcoma occurs most commonly in the metaphyses of long tubular bones, particularly around the knee joint (distal femur, proximal tibia) where skeletal growth rates are high. The proximal humeral metaphysis is another common site. The disease commonly extends from the metaphysis into the adjacent diaphysis or epiphysis. In young patients with unfused physes, the tumor can infiltrate or cross the growth plate, although this does offer some resistance and the lesion often appears to be demarcated by the physis. Intra-articular extension is uncommon. Remote additional foci of tumor within the same bone (ie, skip lesions) can occur, though they are infrequent. Imaging the entire length of the bone with MRI is important in excluding these skip lesions. Clinical DetailsThe presentation typically includes pain and swelling. Patients often present when soft tissue extension has already occurred. Symptoms may have been present for weeks or months. Movement can be restricted, or local changes of inflammation or venous stasis may be present. A small proportion of patients present with a pathologic fracture through the tumor, a feature that unfavorably alters the prognosis. Preferred ExaminationRadiography is almost always the initial imaging modality used in the investigation. Once the diagnosis is suspected, MRI is essential to determine the distribution of the tumor within the bone and the extent of any associated soft-tissue mass. CT is less sensitive than MRI in local evaluation of the tumor, but it is used in the staging of pulmonary metastases. Histologic confirmation of the nature of the tumor is required initially and should be performed only after baseline MRI. Biopsy should always be planned in consultation with the patient's orthopedic surgeon to ensure that compartments to be preserved are not contaminated by the needle track (See Osteosarcoma). Bone tumors that are densely sclerotic may not be amenable to percutaneous biopsy. However, the associated soft tissue component may be accessible to ultrasonography-guided biopsy. DIFFERENTIALSSection 3 of 12
Chondrosarcoma Ewing Sarcoma Giant Cell Tumor Osteosarcoma, Variants Stress Fracture Other Problems to Be ConsideredPrimitive neuroectodermal tumors
RADIOGRAPHSection 4 of 12
FindingsRadiographs are essential in the initial evaluation of bone lesions because the results may suggest the diagnosis and ensure appropriate further investigation. Radiographic appearances are variable. Most lesions show a mixture of lytic and sclerotic areas. Rarely, purely lytic or sclerotic lesions can occur. Lesions appear aggressive, either moth eaten with ill-defined edges or, occasionally, permeative and consisting of multiple small cortical holes. After chemotherapy, surrounding bone may form a better-defined shell around the tumor, when it appears more geographic. Soft tissue extension of osteosarcoma is common and seen on radiographs as a soft-tissue mass. Near joints, this extension can sometimes be difficult to differentiate from an effusion. Cloudlike areas of sclerosis due to malignant osteoid production and calcification may be seen within the mass. Periosteal reactions are commonly seen once the tumor extends through the cortex. A spectrum of changes occur; these include Codman triangles and multilaminated, spiculated, and sunburst reactions, all of which indicate an aggressive process. Degree of ConfidenceAlthough essential in establishing the diagnosis, radiographs often cause underestimation of the extent of the tumor, both within and outside the bone. Other tumors, such as Ewing sarcoma, chondrosarcoma, fibrosarcoma, and other aggressive lesions, such infection or Langerhans cell histiocytosis, are part of the differential diagnosis. CT SCANSection 5 of 12
FindingsCT can be helpful locally when the radiographic appearances are confusing, particularly in areas of complex anatomy. Cross-sectional images provide a clearer indication of bone destruction and the extent of any soft-tissue mass than do radiographs. CT can depict small amounts of mineralized osseous matrix not seen on radiographs. CT can be particularly helpful in flat bones in which periosteal changes can be more difficult to appreciate. Degree of ConfidenceCT rarely alters the differential diagnosis when it is used to image conventional osteosarcoma, except when it allows the detection of small amounts of mineralized osseous matrix that are undetectable on radiographs. CT is infrequently required in local evaluation of tumors in the long tubular bones, but it is the most accurate modality for staging of pulmonary metastases. MRI more accurately shows soft tissue extension and medullary bone involvement. MRISection 6 of 12
FindingsMRI is the modality of choice in evaluating the local extent of disease because of its excellent bone marrow and soft tissue contrast and multiplanar capabilities. MRI is the most important imaging technique for the accurate local staging of osteosarcoma and assists in determining the most appropriate surgical management. For the purposes of staging, assessment of the relationship of a tumor to the anatomic compartment in which it originated and other adjacent compartments is of vital importance. Individual bones, joints, and clearly defined fascially enclosed soft-tissue spaces are all compartments. Disease confined to its original compartment carries a better prognosis than disease that has spread beyond into other compartments. The intraosseous and extraosseous extent of the tumor must be assessed. Important features of intraosseous disease are the longitudinal distance of bone containing tumor, the involvement of adjacent epiphyses, and the present or absence of skip metastases. The most accurate sequence for determining the longitudinal extent of disease is the T1-weighted spin-echo sequence. Short-tau inversion recovery (STIR) can significantly cause overestimation of disease because edema and marrow hyperplasia can show high signal intensity similar to that of tumor. The maximum longitudinal extent of the tumor should be measured, and its maximal distance from the articular surface of the nearest joint should be recorded. The longitudinal extent is usually maximal within medullary bone, but occasionally, intracortical extension is more extensive. Epiphyseal extension of tumor is now known to be considerably more common previously believed, and it is commonly radiographically occult. Epiphyseal involvement can be diagnosed when abnormal signal intensity similar to that of the metaphyseal tumor is seen within the epiphysis in association with focal destruction of the growth plate. Both STIR and T1-weighted sequences are accurate in depicting epiphyseal tumor extension, with STIR sequences slightly more sensitive and T1 sequences slightly more specific. Skip metastases are synchronous foci of tumor that are anatomically separate from the primary lesion and that occur within the same bone. Secondary deposits on the other side of a joint are termed transarticular skip metastases. Patients with skip lesions are more likely to have distant metastases disease and lower disease-free survival intervals. The assessment of extraosseous tumor extent involves a determination of which muscle compartments are involved and of the relationship of the tumor to neurovascular structures and adjacent joints. Radiologists must be aware of the compartmental anatomy of the affected area to clearly communicate with the patient's orthopedic oncologist. This is particularly important in planning routes for biopsy to avoid the contamination of previously uninvolved compartments and causing the patient to undergo more-extensive surgical resection. The relationship of extraosseous tumor to neurovascular structures is well shown on STIR and fat-suppressed T2-weighted or proton density–weighted sequences. The neurovascular bundle may be classified as free from tumor (when an intervening plane of muscle or fat can be clearly seen), abutting tumor (when this tissue plane is abolished), or unequivocally involved where infiltration or encasement by tumor is shown. Joint involvement can be diagnosed when tumor tissue is seen directly extending into the joint through subarticular bone and cartilage. In the knee joint tumor extension along the cruciate ligaments is also diagnostic. The performance of dynamic contrast-enhanced (DCE) MRI has been evaluated in a number of these areas. DCE MRI is performed with a bolus injection of a gadolinium chelate (0.1 mmol/kg), which is ideally delivered by using an automatic pump injector at a rate of 3 mL/s to standardize the results. Ultrafast T1-weighted imaging is performed with either spin-echo or gradient-echo sequences. Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble movingor straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape. An evaluation of the images during the first seconds after injection provides information about the speed with which signal intensity changes in particular areas of tissue. Increases in signal intensity reflect the vascularity of different areas of tissue. The characteristics of the enhancement pattern differ in viable tumor compared with other tissues. The use of DCE MRI adds extra cost and time to the examination, in addition to requiring intravenous access. Although it may have a role in staging osteosarcoma, many center do not currently consider it a standard part of the staging protocol. Degree of ConfidenceMRI is insensitive to small amounts of calcium. Calcium usually returns no signal, and large calcified areas appear hypointense on images obtained with all sequences. Small deposits of calcium surrounded by other tissue within the same small volume (voxel) may not be easily identified because the signal from the entire voxel is the average of contributions from all tissues within the voxel. This is termed the partial-volume effect. The presence of a joint effusion alone has a low positive predictive value for intra-articular tumor. DCE MRI has been shown to demonstrate occult microscopic interosseous disease as far as 3.5 cm beyond the edge of tumor identifiable on images obtained with standard sequences. Its overall accuracy in detecting epiphyseal involvement is less than that of T1-weighted or STIR imaging. DCE MRI can be used to differentiate tumor-infiltrated muscle from edematous muscle on the basis of their different enhancement rates. CT is the most accurate modality for detecting small amounts of calcification, although ultrasonography can be helpful in evaluating soft tissue extension when it is superficial. False Positives/NegativesThe precise accuracy of MRI in detecting skip metastases is not clear, but 1 longitudinal sequence covering the entire bone should be performed to detect such lesions. The author prefers T1-weighted images, but STIR images can also be used, though other abnormalities such as focal marrow hyperplasia may cause false-positive findings. ULTRASOUNDSection 7 of 12
FindingsUltrasonography is not routinely used in the staging of such lesions. Ultrasonography can be useful in guiding percutaneous biopsy. In patients treated with prosthetic implants, sonography may be the only imaging modality that can depict early local recurrence because of the artifact produced by the metal on CT scans or MRIs. NUCLEAR MEDICINESection 8 of 12
FindingsOsteosarcomas typically show increased uptake of radioisotope on bone scans obtained by using technetium-99m methylene diphosphonate (MDP). Bone scans are most useful in excluding multifocal disease. Skip lesions and pulmonary metastases may also take up the radioisotope, but skip lesions are most reliably excluded by MRI. Multiple gated acquisition (MUGA) cardiac scans may be required to monitor the toxic effects of certain chemotherapeutic agents by identifying changes in the left ventricular ejection fraction from a baseline prechemotherapy scan. Degree of ConfidenceBecause osteosarcomas typically show increased uptake, bone scans sensitive but not specific. ANGIOGRAPHYSection 9 of 12
FindingsAngiography is no longer used in the staging of osteosarcoma. INTERVENTIONSection 10 of 12
Treatment is directed around surgery, with limb salvage when possible. Presurgical chemotherapy is used. The response to chemotherapy is assessed in the resected specimen or by means of pre-resection biopsy. The response is considered good when tumor necrosis is more than 90%. This is a predictor of successful outcome. MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
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