Clinical Considerations and Imaging of Bone Tumors

Chapter 2

Clinical Considerations and Imaging of Bone Tumors

Colleen M. Costelloe MD, John E. Madewell MD


Bone lesions lend themselves to radiographic assessment because of the fact that bone has a built-in contrast agent, the calcium hydroxyapatite crystal. Much information about bone destruction, bone production, matrix calcification and ossification, and the reactive response of the surrounding bone and periosteum is available from plain radiographs. Although other imaging techniques play a role in the diagnostic process, the plain film is still the method of choice and should never be bypassed. Imaging is an important tool for diagnosis, staging, therapeutic response evaluation, and oncologic surveillance of bone tumors and can be used to augment histopathologic findings. Imaging modalities such as radiography, computed tomography (CT), and magnetic resonance imaging (MRI) have major roles in the initial characterization and identification of bone lesions through the assessment of characteristics such as margin, bone expansion, periosteal reaction, soft tissue extension, and matrix mineralization. Additional imaging modalities such as bone scan, single-photon emission computed tomography with fused CT (SPECT/CT), 18F-fluorodeoxyglucose positron emission tomography with fused CT (FDG PET/CT), and whole-body MRI can be used to stage patients for distant metastases. These modalities, in addition to ultrasonography, can also be used for restaging and oncologic surveillance. In this chapter, we discuss the general imaging and diagnostic features of bone tumors, assessment of therapeutic responses, and staging of both primary and metastatic bone tumors. Specific imaging features of individual bone tumors and radiographic-pathologic correlations are discussed in their respective chapters.

In general, at least 95% of bone tumors can be diagnosed with precision when the clinician, radiologist, and pathologist work in concert and share their information. The clinical history, age of the patient, location of the lesion, and radiographic appearance provide a foundation for the analytic approach to the diagnosis of bone tumors. It is important to state that the identification of a bone abnormality per se does not definitively indicate that a biopsy or indeed any surgical intervention is required. Easily recognizable fibrous cortical defects, small osteochondromas, phalangeal enchondromas, and common traumatic and avulsion lesions can be treated by observation alone. Often these are incidental findings observed on radiographs taken for other reasons. Lesions that cannot be confidently assigned to a benign radiologic category or that have aggressive or malignant appearances require biopsy.

Clinical Considerations

The analytic approach begins with an appreciation that tumors of bone have different predilections for certain age groups, anatomic locations, and even specific sites within a bone.42,7281,83,84 Some lesions are painless, and some present with specific pain patterns. Thus a small, painful lesion in the neck of the femur in an adolescent is far more likely to be an osteoid osteoma than a chondroblastoma. A large lytic lesion in the end of a long bone of an adult is likely to be a giant cell tumor and not a nonossifying fibroma. Computerized radiographic techniques, such as CT and MRI, facilitate analysis of bone lesions in greater detail and are indispensable techniques in planning therapy. They also provide reliable clues for the pathologist.71,78,82 The clinical, radiographic, and pathologic recognition patterns of the most common bone tumors and tumorlike lesions are summarized in Table 2-1.


Summary of Clinicopathologic Recognition Patterns of Most Common Bone Tumor and Tumorlike Lesions

Type of Tumor Peak Age Incidence (years) Most Frequent Sites Radiographic Features Microscopic Features
Malignant osteosarcoma 10-20 Metaphyseal parts of long bones (knee, proximal humerus) Destructive lytic or blastic lesion with cloudlike opacities Highly atypical sarcomatoid cells exhibiting tumor bone formation
Chondrosarcoma >50 Pelvis, proximal femur Destructive lesion with punctate calcifications, cortical scalloping, or disruption Exclusively cartilaginous tumor with atypical cartilage cells
Ewing’s sarcoma 10-20 Shafts of long bones Permeative, lytic pattern of bone destruction Small cell tumor
Malignant fibrous histiocytoma >50 Pelvis, long bones, predominantly lower extremity (femur, tibia) Lytic moth-eaten or permeative bone destruction with cortical disruption Highly atypical spindle or pleomorphic cell sarcoma (no tumor bone production)
Adamantinoma of long bone >20 Predominantly tibia with synchronous involvement of fibula Lytic lesion with predominant involvement of anterolateral cortex Nests of epithelioid cells in fibrous stroma
Borderline giant cell tumor 20-40 Ends of long tubular bones (knee regions, distal radius) Eccentric epiphyseal lytic lesion Multiple osteoclast-like giant cells with mononuclear stromal cells
Epithelioid hemangioendothelioma >30 Lower extremity, multifocal Multifocal, sharply demarcated lytic lesions involving bones of one extremity (predominantly lower extremity) Vascular neoplasm with epithelioid endothelial cells
Benign osteoid osteoma 10-30 Long bones of lower extremity (femoral neck) Well-demarcated intracortical lytic lesion with sclerosis of adjacent cortex Interlacing network of bone trabeculae in vascular stroma
Osteoblastoma 5-45 Posterior neural arch of vertebral column and craniofacial bones Similar to osteoid osteoma (radius >1.5 cm), less sclerosis Same as osteoid osteoma
Enchondroma Wide-range Small bones of hands and feet, long tubular bones Radiolucent defect with punctate or stippled calcifications (<2 cm) Mature cartilage (low cellularity)
Chondroblastoma 10-20 Epiphyses of long tubular bones in skeletally immature patients Sharply demarcated epiphyseal defect Tumor composed of chondroblasts with focal immature cartilage formation (chicken wire calcifications)
Chondromyxoid fibroma 10-30 Metaphyses of long tubular bones Eccentric cortical-based lytic defect with scalloped margin Myxoid tissue with septa containing chondroblasts and giant cells
Hemangioma >40 Craniofacial bones and vertebral bodies Lytic defect with prominent striations; honeycomb appearance Vascular lesion with capillary or cavernous vessels
Nonneoplastic fibrous dysplasia 0-20 Craniofacial bones, ribs, femur Central, lytic defect with ground-glass appearance Woven bone trabeculae in fibrous stoma
Nonossifying fibroma 0-20 Metaphyses of long tubular bones (femur, tibia) Eccentric cortex-based lytic defect with sharp scalloped margins Fibrohistiocytic lesion with giant cells
Aneurysmal bone cyst 10-25 Metaphyses of long tubular bones Expansile lytic defect Cystic lesion with hemorrhage; septa containing histiocytic and giant cells
Synovial chondromatosis >40 Major joints of lower extremity Punctate or stippled calcifications in periarticular soft tissue Island of atypical cartilage in synovial membrane
Pigmented villonodular tenosynovitis >40 Periarticular synovial tissue and tendons Ill-defined, multinodular periarticular mass Histiocytic cells, giant cells, hemosiderin deposits
Osteofibrous dysplasia 0-15 Tibia, fibula Multilocular lytic defects of anterolateral tibial cortex associated with sclerosis and tibial bowing; synchronous fibular lesions Fibroosseous lesion with zonal architecture
Giant cell reparative granuloma
Craniofacial bones, acral skeleton Central lytic defect Giant cell lesion with fibrohistiocytic cells and reactive bone
Myositis ossificans >20 Parosteal or periosteal soft tissue Zonal maturation, peripheral shell of bone Histiocytic cells; reactive bone formation maturing toward periphery
Florid reactive periostitis 20-40 Acral skeleton Ill-defined bone surface lesion Metaplastic cartilage; reactive bone and giant cells
Avulsion/stress fracture 20-40 Attachment of major tendons, long bones, and pelvis Ill-defined surface bone lesion; presence of fracture line Reactive process with metaplastic cartilage and reactive bone
Pubic osteolysis Females >50 Pubic bones Lytic lesion with florid periosteal reaction Reparative process with prominent metaplastic cartilage and reactive bone



Most benign tumors and tumorlike lesions, including osteoid osteoma, chondroblastoma, chondromyxoid fibroma, solitary bone cysts, aneurysmal bone cysts, and nonossifying fibromas, occur in adolescents and young adults (second and third decades of life). Giant cell tumor is a lesion that almost exclusively occurs in skeletally mature patients (i.e., those with growth plates fused) between ages 20 and 50 years. Of the malignant bone tumors, osteosarcoma and Ewing’s sarcoma are tumors of children and young adults. On the other hand, chondrosarcoma, malignant fibrous histiocytoma, plasma cell myeloma, metastatic tumors to the skeleton, and secondary malignancies in Paget’s disease of bone, after radiation injury, and adjacent to bone infarcts usually develop during the sixth through the eighth decades of life.

In this text the age distribution of various tumors and tumorlike lesions is discussed under the separate diagnostic headings, and the peak incidence for most is presented graphically. Although exceptional cases of individual bone tumors occur at unusual ages (e.g., chondrosarcomas in children or Ewing’s sarcoma in middle-aged patients), it is best to be circumspect with regard to these statistical guidelines.


The fact that tumors of bone have predilections for certain bones and even for characteristic locations in an individual bone provides an additional clue about the nature of the lesion. Figure 2-1 shows the sites of predilection of the more common benign bone tumors. In some instances, the location alone strongly suggests the diagnosis, as in a heavily ossified tumor on the posterior surface of the distal femur. That will most likely prove to be a parosteal osteosarcoma. Adamantinoma and osteofibrous dysplasia almost exclusively involve the tibia or fibula. Chondroblastoma is most often seen in the epiphyses of long bones in children or in tarsal or carpal (epiphysioid) bones. Periosteal chondroma has a strong predilection for the surface of the proximal humeral metaphysis. Solitary bone cysts in childhood are almost always found in the proximal humeral shaft or upper end of the femur. Nonossifying fibromas in childhood are lesions that favor the metaphyses of long bones of the lower extremities.

Similar generalizations can be made for bone sarcomas. Chondrosarcomas have a predilection for the femur, pelvis, ribs, and sternum and are almost never found in the spine or short tubular bones. Osteosarcomas arise most often in the distal femoral shaft or proximal tibial shaft before closure of the growth plates, and they seldom penetrate the cartilaginous physis to involve the epiphysis. Ewing’s sarcoma tends to have a diaphyseal point of origin, although it may also involve the metaphysis. Ewing’s sarcoma seldom affects the epiphyseal ends of bones. Figure 2-1 shows the growth patterns of the most frequent primary malignant bone tumors, osteosarcoma, chondrosarcoma, and Ewing’s sarcoma.

Initial Staging

Diagnostic Principles

Bone lesions come to clinical attention due to symptoms such as swelling and local pain with or without pathologic fracture, or they can be incidentally discovered on imaging studies performed for other reasons. Bone lesions can be divided into benign and malignant categories. Benign lesions occur more frequently than malignant tumors, and the initial diagnostic maneuvers should include obtaining a complete medical history and performing both physical examination and radiography.1 The radiographic appearance of a tumor often suggests benignity or malignancy. When the radiographic analysis is coupled with clinical information, decisions can be made concerning the need for additional imaging studies and procedures. Radiologic imaging reflects the gross anatomy and pathology of the tumor. Although the final diagnosis of the tumor ultimately resides with the pathologist, the overall process is best performed as a multidisciplinary correlation of clinical, imaging, and pathologic factors.

Benign primary bone tumors are common but not typically troublesome. Because these lesions are often incidentally found on imaging studies performed for other purposes, their true incidence is unknown. Common benign bone tumors include bone islands (enostoses), enchondromas, osteochondromas, fibroxanthomas (nonossifying fibromas), and fibrous dysplasia. The growth of most of these tumors is indolent, allowing bony remodeling that limits the loss of structural integrity of the bone. Although some benign bone lesions can grow rapidly (e.g., aneurysmal bone cyst), they rarely if ever metastasize. One of the most common benign bone tumors that can (rarely) produce distant metastases is giant cell tumor of bone.2,3 These lesions rarely cause death.4 Consequently, it is hypothesized that the metastases occur due to the passive venous embolism of tumor cells.5,6 This is in contradistinction to secondary sarcomas that develop at the site of treated giant cell tumors, actively metastasize, and carry a poor prognosis.79 Benign bone tumors are a rare cause of patient demise, but they can cause morbidity through mass effect (e.g., osteochondromas abrading adjacent tendons, muscles, or neurovascular bundles), by predisposing to pathologic fracture due to cortical thinning, or by mimicking malignancy when they arise in a location that is in close proximity to an undiagnosed source of pain (e.g., distal femoral enchondroma in a patient with a meniscal tear of the knee in Figure 2-2). In the case of an enchondroma, the lack of aggressive imaging features such as osteolysis, periosteal reaction, or cortical breakthrough may aid the pathologist in rendering a benign interpretation of the sample, particularly when advanced imaging demonstrates an alternative source of pain. Pathologists and radiologists must be familiar with the strengths and weaknesses of both specialties for both disciplines to augment each other and increase the likelihood of correct patient diagnosis and treatment.

Malignant primary bone tumors are not common but are of critical importance due to their high likelihood of metastasizing and causing death in the absence of proper treatment. The five most common primary bone sarcomas account for the majority of these lesions and include osteosarcoma, chondrosarcoma, Ewing’s sarcoma, fibrosarcoma, and malignant fibrous histiocytoma. Nevertheless, bone metastasis and multiple myeloma are much more common. The age of the patient and the location of the tumor are two of the most important demographic features in diagnosing bone tumors. The typical age range for Ewing’s sarcoma and osteosarcoma is in childhood or adolescence10,11 with a second peak of osteosarcoma in adults.12 Chondrosarcoma, fibrosarcoma, and malignant fibrous histiocytoma most commonly occur in middle age or older age groups.1315

Bone sarcomas occur in predictable locations within the bone. Primary chondrosarcomas and osteosarcomas typically occur in the metaphysis, whereas Ewing’s sarcoma most commonly arises in the diaphysis of long bones. Fibrosarcoma and malignant fibrous histiocytoma can occur in many sites but are preferentially found in the metaphysis or metaphyseal/diaphyseal junction. The dominant anatomic sites of many of these tumors have been described by Johnson et al.16,17 The locations in which these bone tumors arise tend to be areas of current or previous rapid skeletal growth (Fig. 2-3), and tumor development may be related to the high rate of cell division. The distal femur and proximal tibia are most commonly involved. However, bone sarcomas may arise in other areas and any bone may be involved. Most benign bone tumors also arise in or near the metaphysis of long bones. Some lesions, such as osteochondromas or nonossifying fibromas/fibroxanthomas, may arise in the metaphysis and “migrate” away with skeletal growth. Due to lack of symptoms they may be incidentally discovered in the diaphysis of older patients.

Biopsy is an integral part of the diagnostic process and is indicated in tumors that are suspicious for malignancy. Percutaneous core biopsy is less invasive, less costly, and typically more convenient for patients than open surgical biopsy. Contrast-enhanced MRI is commonly used to guide selection of the biopsy site. Enhancing portions of the tumor are viable and preferable for sampling, as opposed to nonenhancing areas, which are likely cystic or necrotic.18,19 Because the biopsy track must be excised for complete resection of malignancies, the biopsy must be performed in such a way as to minimize contamination of the anatomic compartments, neurovascular structures, or tissues that may be necessary for surgical reconstruction.20 This advanced surgical planning can be greatly facilitated by the excellent soft tissue contrast resolution provided by MRI.21,22 All intervention must be planned in light of the surgical options. Therefore, the diagnosis of bone tumors cannot be separated from treatment. A multidisciplinary approach is critical in evaluation and treatment planning for bone sarcomas.

Imaging Modalities

Radiography is essential for the initial staging of primary bone tumors and is the least expensive and most readily available of the imaging modalities.23 Radiographic images are produced by bombarding anatomic structures with x-rays. The x-rays that pass through the body are responsible for forming the image by exposing/darkening the film or other receiving device.24 Dense anatomic structures such as bone impede the course of the x-rays, leaving the corresponding areas unexposed. Bone is therefore white in appearance on conventional radiographs. Unlike CT, which provides anatomic cross-sections (see the discussion of CT below), radiographs are a “summation” of the density of all points in the plane (frontal, lateral, or oblique). This quality portrays the tumors in a unique fashion that is often essential for properly assessing the appearance of key diagnostic attributes of the tumors such as margins, periosteal reactions, and matrix mineralization. Radiography is recommended for all bone tumors because it provides well-established, reliable information on which to build further analyses, such as the cross-sectional and multiplanar imaging studies discussed below.

CT is a useful adjunct to radiography for staging primary bone tumors. Unlike radiography, in which a single x-ray source strikes a film or detector, most CT scanners utilize multiple x-ray sources that strike multiple detectors positioned opposite their respective sources on a circular frame. This hardware is located in a circular gantry through which the patient table moves during the scan. The majority of CT scanners utilize this design to either rotate source/detector pairs around the patient or to rotate an x-ray source within a ring of stationary detectors embedded in the gantry. These source/detector combinations allow the imaging of “slices” of anatomy per revolution. Most modern scanners are operated in helical mode, allowing rapid scanning while the patient table moves continuously through the gantry.25 CT scanning eliminates the effect of overlapping structures and can provide sharp delineation of the anatomy. CT is the most efficacious imaging modality for evaluating mineralized structures, such as tumor matrix.21,26 For example, CT can be used to detect small areas of mineralized matrix that are not evident on radiography. Nevertheless, the indistinct quality of aggressive bone tumor margins can be underestimated with CT; it is not recommended that CT be substituted for radiography during the initial evaluation of bone tumors.

Skeletal scintigraphy, commonly known as bone scan, is a whole-body method of surveying the entire skeleton in a single imaging session and is often used to detect metastases to bone. Bone scan typically plays a limited role in the initial staging of bone tumors unless the disease is metastatic to bone or multifocal at presentation. Uptake of technetium-based tracers such as technium-99m methylene diphosphonate (MDP) is dependent on a combination of factors such as blood flow and the binding of the diphosphonate molecules to hydroxyapatite found in areas of new bone formation.27,28 Diphosphonate uptake is nonspecific and can be seen with benign and malignant primary bone tumors, as well as with metastases. For example, uptake in benign cartilaginous lesions, such as enchondromas, can be problematic because similar uptake can also found in chondrosarcomas.29 Enchondromas may also be difficult to differentiate from low-grade chondrosarcomas on radiographs, other imaging modalities,30 and even on histopathologic analysis.31 Although radiography, CT, and MRI can each be limited regarding the diagnosis of enchondromas versus low-grade cartilage tumors, the combined information provided by multiple imaging studies can be valuable in management decisions and can often aid the diagnostic process.

Bone scan can be used for initial staging for skip metastases. Skip metastases occur in the same bone as the primary malignancy but in a noncontiguous location or across the adjacent joint32 and are associated most commonly with osteosarcoma33 and Ewing’s sarcoma.34 The ability to survey large anatomic regions makes bone scan a useful imaging modality for this purpose.

MRI is capable of producing greater soft tissue resolution than other imaging modalities and is commonly used to assess the extent of disease prior to the surgical treatment of bone tumors. MRI scanners manipulate free protons. Protons precess, or spin, randomly. When placed in a strong magnetic field, the majority of protons align with the field. Radiofrequency pulses or magnetic gradients are used to reorient proton spins.35 As the spins return to normal, radio waves are released and interact with a receiver coil. An electric current is generated, from which computer-generated images are derived.36

High soft tissue resolution makes MRI the optimal imaging modality for evaluating the extent of tumors inside the medullary cavity of bone as well as the extent of soft tissue masses.21,22 MRI can allow unparalleled presurgical evaluation of the relationship of the tumor to vital structures such as nerves and blood vessels. Most untreated bone tumors demonstrate T1 signal that is similar (isointense) to muscle, as well as heterogeneously high T2 signal, and enhance on administration of a gadolinium-based intravenous contrast medium. The entire length of the bone can be imaged in detail; MRI is also considered the imaging method of choice for evaluating for skip metastases.37 Heavily mineralized structures such as cortex and matrix mineralization do not typically contain a sufficient number of free protons to produce a magnetic resonance signal. Therefore, bone cortex appears as a black signal void on MRI (Fig. 2-4), and fine cortical detail is not well discerned. MRI is therefore best used in combination with radiography or CT with which cortical detail and other mineralized features can be more fully evaluated. The combined strengths of each imaging modality permit excellent evaluation of the many and varied features of bone tumors.

Imaging Characterization of Primary Bone Tumors

The initial diagnosis of bone tumors on imaging studies begins by dividing lesions into “aggressive” or “nonaggressive” categories on the basis of characteristics such as lesion margin, expansion of the bone, periosteal reaction, and soft tissue extension. Aggressive lesions often correspond to malignancy with a small number of notable exceptions, such as giant cell tumors of bone, that are often aggressively destructive but rarely result in patient demise. Conversely, nonaggressive lesions are typically benign with the exception of indolent malignancies such as low-grade chondrosarcomas. Further refinements to the differential diagnosis are made through features such as the presence or absence of mineralized matrix and the appearance of the periosteal reaction.

The most important factor in determining the aggressive or nonaggressive nature of a lesion is the appearance of its margin, which is a product of the osteoclastic activity of the host bone in response to the tumor and of reparative, osteoblastic activity. The radiographic appearance of the margin is an indicator of the growth rate of the lesion.38,39 Three main types of lesion margins have been identified on radiographs. Greater tumor aggression is found with progression up the scale (Fig. 2-5).17 Type I margins are geographic (round or ovoid) and have been divided into three subcategories. Type IA margins are well defined and have a narrow zone of transition, which is defined by the presence of normal cortical bone in close proximity to the lesion. A sclerotic rim is present, indicative of a successful reparative response by the host bone. Type IA margins are commonly seen with tumors such as fibrous dysplasia, chondroblastoma, enchondroma, and fibroxanthoma/nonossifying fibroma (Fig. 2-6). Type IB margins are well defined but have no sclerotic rim and are therefore of indeterminate biologic potential (Fig. 2-7). The tumor may be aggressive and growing only slightly faster than the bone’s ability to produce a reparative response. Alternatively, the tumor may produce factors that inhibit osteoblastic activity, such as in myelomatous lesions.40 Type IB margins are commonly seen with tumors such as aneurysmal bone cyst, giant cell tumor, chondromyxoid fibroma, low-grade chondrosarcoma, myeloma, and early metastasis. Type IC margins are typically seen with aggressive bone tumors. While retaining a geographic round or ovoid shape, the margin is ill-defined and indistinct, demonstrating a wide zone of transition with no sharp margination (Fig. 2-8). Type IC margins are commonly seen with lesions such as chondrosarcoma, osteosarcoma, fibrosarcoma/MFH, metastasis/myeloma, and giant cell tumors (Fig. 2-9).

Type II and III margins are frankly aggressive, represent disorganized areas of osteolysis, and are typical of high-grade sarcomas such as osteosarcoma and Ewing’s sarcoma. Type II is described as moth-eaten; either the periphery or the entire lesion is composed of lucent areas of varying size and shape, representing nonuniform osteolysis. MRI will typically demonstrate complete or near-complete invasion of the marrow cavity (see Figs. 2-10 and 2-11). The type III margin corresponds to the most highly aggressive bone tumors and is described as permeative. This radiographic appearance is primarily caused by tumor-stimulated osteoclastic cutting cones that tunnel rapidly through the bone, producing lesions with wide zones of transition and a more uniform pattern of cortical lysis than does the moth-eaten margin (Fig. 2-12). The margin classification system is most appropriately applied to radiographs because CT can produce a “smoothing” effect that can underestimate the aggressiveness of the margin of geographic lesions, and MRI does not directly image calcified structures.

May 31, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Clinical Considerations and Imaging of Bone Tumors

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