Radiography of Bone Tumors and Lesions.
Bone cancer is often fatal, particularly if not detected early. Unfortunately, clinical signs and symptoms often are indistinct and initially may be dismissed as "growing pains." Radiology plays a critical role in detecting and assessing bone tumors and differentiating them from noncancerous lesions. With access to modern radiological imaging and treatment options, 7 in 10 American bone cancer patients will survive 5 years or more after diagnosis.
Skeletal Anatomy and Function
Bone is a matrix of inorganic salts, water, collagen and living bone cells. The skeleton serves as scaffolding around which the rest of the body's tissues are organized and on which they are mechanically supported. In addition, it provides a conduit for the application and redistribution of muscular forces that allow movement. Bones also shield vulnerable soft tissues from injury, and they are important centers of metabolic and physiological activity. The skull and vertebral column together are referred to as the axial skeleton; the bones of paired appendages, the pelvis and remaining nonaxial bones constitute the appendicular skeleton. Appendicular long bones include the humerus, ulna, radius, femur, tibia and fibula. Where movable bones meet, specialized tendons, articulating ends and accessory bones are found. For example, where femur and tibia meet, the patella acts as a hinge-stop, protecting connective soft tissues such as tendons from overextension.
Because primary bone cancers commonly are associated with bone growth, it is important for radiologic technologists to familiarize themselves with the maturational anatomy of bones commonly affected by tumors.
Bone growth is accomplished by osteoblast bone cells, which lay down new bone matrix on the outer layer of the bone surface, like new tree rings. Osteoclasts, on the other hand, break down existing bone matrix on the inner, medullary wall of bone cortex. Osteoblast behavior often underlies observable aspects of bone tumor growth.
In growing long bones, the distal end, or epiphysis, is attached to the flaring end of the long body of the bone, called the metaphysis. The long body or midsection of the bone is the diaphysis. The metaphyseal end of the diaphysis is connected to the epiphysis by a thin growth plate, called the physis. Once bone matures, the only evidence of the growth plate is a lateral scar. Technically, the epiphysis and metaphysis no longer exist in mature bones, though these terms often are used to describe tumor location in adult bones. More correct, some authors have argued, would be the use of "scarred growth plate" for the region of adult bones corresponding to the physis, "articular head" for what was the epiphysis and "shaft" for the diaphysis.
The articulating ends of long bones are made of spongy bone -- a lattice of bone threads called trabeculae. Spongy bone is surrounded by cartilage and muscle tissues, to which primary bone tumors may spread. Most bone is not this spongy material but denser "compact" bone, also known as cortical bone. The shafts of long bones are made up of cortical bone. The medulla is the inner, marrow-containing portion of the bone within the outer cortex. A thin layer of periosteal tissue covers the bone surface. This tissue forms bone or cartilage when traumatized by fracture, infection or tumor growth.
Tumor Biology and Classification
As with any living tissue, bone and joints can develop tumors. The causes of bone tumorigenesis and subsequent tumor progression have not been identified definitively, though several genes have been implicated as risk factors that increase the probability of an individual developing various bone-tumor diseases, including the ras, p53, c-fos, and Rb genes.
Tumors are neoplastic masses. A neoplasm is an area of locally autonomous, growth-dysregulated cellular division that has the potential to compromise the physiological and mechanical function of affected tissue. Nontumor lesions, on the other hand, are not neoplastic but represent either localized developmental anomalies or inflammatory disorders. These are, however, easily and often mistaken for tumors on radiographic examination, and vice versa. In this article, "lesions" refers inclusively to both tumors and tumorlike lesions.
Tumors and tumor-like lesions can be broadly categorized as either benign or malignant. Benign masses usually are slow growing and pose no threat of spreading to other tissues. Unlike benign tumors, malignant tumors have the potential to spread to adjacent or distant tissues, resulting in new and potentially life-threatening tumors. Malignant tumors are further classified as one of the following:
* Primary. Primary tumors are malignant from tumorigenesis onward.
* Secondary. Secondary tumors result from the transformation of originally benign tumors into malignant forms.
* Metastatic. Metastasis refers to the export of tumor cells to previously unaffected tissues, giving rise to multiple, potentially lethal malignancies.
Clinical and Radiological Assessment
It often is difficult to distinguish benign from malignant bone lesions by radiologic examination alone. Neoplasms therefore are evaluated using radiographic data along with clinical and histological data. In addition to symptoms such as localized pain or recurring fracture, patient age helps
clinicians evaluate radiologic evidence when detecting and assessing a tumor. This is because certain bone tumors are likely to occur within specific developmental or age "windows." For example, patients between 12 and 25 years old with a lone tumor within the metaphysis very likely have osteosarcoma.
The imaging examinations selected vary depending on suspected lesion type and location, and based on clinical or previous imaging evidence. Whatever examination strategies are chosen, all diagnostic imaging of bone lesions involves 3 stages of interpretation:2
* Lesion detection. An appropriate imaging technique is essential for detection. Using the wrong technique -- for example, radiography to assess bone marrow lesions, or CT instead of MR to assess involvement of joint spaces -- can yield false-negative results due to insufficient sensitivity.
* Diagnosis. In most cases, diagnoses based on imaging examinations are confirmed histologically.
* Characterization. In the case of tumors, it is critical that imaging examinations yield images from which tumor size and limits (edges) can be clearly identified for treatment planning.
Radiographic examinations for bone tumors always include specification of the affected region of skeleton, lesion location in the specified bone and the borders of the lesion (sometimes called the "zone of transition"). The location of a lesion is determined by where its center sits. Imaginary lines drawn through the center of the tumor at right angles allow radiologists to determine whether the lesion is in the epiphysis, metaphysis or diaphysis. When the lesion center is between the epiphysis and metaphysis, it is called "metapiphyseal." Lesions located between metaphyses and diaphyses are called "metadiaphyseal" lesions.
"Site of origin" refers to where the lesion arose -- within the medulla (an "intramedullary" lesion) or from surface tissues such as the cortex or periosteum. Tumors contained completely within cortical tissue (90% or more of the mass is in the cortex) are defined as "intracortical." This differentiation can be critically important for planning treatment. For example, intramedullary sarcomas are markedly more aggressive tumors as a group than are periosteal sarcomas.
Different tumors have different regional "affinities"; that is, they occur more often in certain characteristic locations. Location alone can be strongly diagnostic.
Other aspects of lesion morphology used for diagnostic assessment are:
* Matrix type. Lesion matrix refers to the composition of the tumor tissue.
* Bone destruction. Patterns of bone destruction can indicate benign vs malignant neoplastic processes. Destruction is described as "geographic" (uniform, with sharply defined borders), "moth-eaten" (separate areas of destruction with irregular or ragged borders) or "permeative" or "permeated" (spreading, speckled areas of bone marrow destruction with poorly defined borders). Geographic destruction may indicate benign lesions; moth-eaten or permeative bone is a sign of malignancy, with permeative destruction indicating a faster-growing, more aggressive tumor.
* Bone reaction. Intramedullary bones may form a rind or rim of peripheral sclerosis around a tumor. Such tumors are called "sclerotic." This important sign nearly always indicates that a tumor is benign. (See Fig. 1.) Benign sclerotic rinds are thought to contain or "wall off" tumors. If a tumor is growing rapidly, however, this antitumor defense usually is overwhelmed, and the rind will not appear on radiologic examination. If the rind is incomplete, this is a sign that the defensive containing wall has been breached, as happens when benign lesions become malignant, or that the benign tumor is quite old and host bone is being rebuilt over it.
* Periosteal reaction. The periosteum is a highly reactive tissue that can respond to tumor growth with new bone deposition. Periosteal response to the lesion is categorized most broadly as either "interrupted" or "continuous." (See Fig. 2.) Interrupted periosteal responses suggest malignant tumors. Slow-growing tumors appear on the surface of the cortex and usually are accompanied by a buttress sign at their borders, beneath the periosteum. Faster-growing tumors penetrate the cortex, and the periosteal reaction to that growth yields multiple thin layers of new bone. If these layers are parallel to the cortex, the sign is described as "onionskin" or lamellated; if perpendicular to the cortex, these layers are said to be "spiculated."
* Soft-tissue involvement. Extension of lesions into adjacent soft tissues almost always indicates that the lesion is an aggressive, often malignant tumor. Benign tumors and tumor-like bone lesions rarely invade adjacent soft tissues; when they do, fatty tissue layers usually are obliterated and other soft-tissue involvement is poorly defined.
* Single or multiple lesions. Multifocal malignant lesions often are due to metastasis.
Staging Bone Tumors
The American Joint Commission on Cancer and International Union Against Cancer recognize the tumor staging scheme known as TNM: tumor, node, metastasis. This staging system can be used to describe practically any intramedullary tumor in terms of tumor progression, lymph node involvement and distant metastasis (spread to other organs).
For cortical or surface tumors, however, many authors prefer the Enneking system, which can be easily applied to both bone and soft tissue tumors. The Enneking system employs 2 parameters:
* Aggressiveness. Biological or clinical aggressiveness is determined by histologic grading. Grade GO represents a benign neoplasm, whereas G1 represents locally aggressive tumors that are unlikely to metastasize. G2 tumors are aggressive and are very likely to metastasize.
* Extent. One bone and its medullary cavity constitute a single "compartment." Tumors affecting only one bone compartment are designated TI, whereas tumors with any extracompartmental extension beyond that bone's cortex are designated T2.
* Using aggressiveness and extent parameters, tumors are staged as follows:
* Stage I, low-grade lesions: G1 and T1.
* Stage IIa, high-grade intracompartmental lesions: G2 and T1.
* Stage IIb, high-grade extracompartmental lesions: G2 and T2.
* Stage III metastasis.
In clinical practice, tumors often are simply referred to as low grade, high grade or metastatic.
Tumors Primary to Bone
There are several forms of primary bone cancer, and some "types" are actually diverse sets of cancers that share some aspect of morphology or demography and treatment, and are therefore lumped together in diagnostic practice. This section describes the more common forms of primary bone tumors.
In osteosarcoma, the bone-building osteoblasts produce a pathological, malignant bone matrix that is weaker than healthy bone. Osteosarcomas tend to develop along long bone metaphyses, particularly around the knees. Eighty percent of pediatric osteosarcomas occur at the distal femur or proximal tibia. Other sites include the mandible, shoulder and pelvis. (See Table 1.)
Table 1 Comparison of Some Different Types of Osteosarcomas Conventional Telangiectatic Parosteal Intramedullary Osteosarcoma Osteosarcoma Osteosarcoma Incidence Two peaks: Affects more men Develops after teenagers, age than women; skeletal matu- 50+ common in teens ration (usually and early 20s age 20 to 40) Common Sites Knee area, Knee area Distal femur, proximal humerus proximal tibia Radiologic Sclerotic tumor Highly vascular- Densely miner- Appearance with moth-eaten ized tumors with alized tumors or permeative permeative bone with a lobular bone destruction destruction outline Periosteal High-grade Osteosarcoma Surface Osteosarcoma Incidence Children (twice Very rare; more as common in common in men girls as boys) than women; teens or 20s Common Sites Long bones of Long bone the legs surfaces Radiologic Radiolucent Contains cloud- Appearance lesions with like opacities; Codman poorly visualized triangles boundaries
Pain lasting several weeks or even months that slowly becomes severe and is accompanied by localized swelling is the most widely shared symptom of osteosarcoma. When the osteosarcoma has traveled through the blood and metastasized in distant organs, particularly the lungs, pain and swelling will be accompanied by marked weight loss. Lab serum analysis of osteosarcoma patients usually reveals elevated alkaline phosphatase levels.
Osteosarcoma most often emerges in adolescence, during the teenage growth spurt. Osteosarcoma patients are usually tall for their age, suggesting that rapid, early bone growth increases the risk of uncontrolled cellular proliferation of bone. Probably because skeletal growth continues for a longer time in boys, more boys and young men are diagnosed with this disease. High levels of radiation exposure, usually related to therapy for other forms of cancer, are known to underlie some cases, particularly with early childhood exposure. Low levels of radiation exposure, such as those related to radiographic examinations, do not contribute to osteosarcoma.
Children with a family history of the disease and children diagnosed with kidney cancer or eye cancer should be screened for osteosarcoma. Clinical signs and symptoms, particularly pain that is worse at night and, later, swelling in the painful region, should be noted in these "at-risk" children. Unfortunately, these are also common complaints among healthy children and adolescents. Only radiologic examination and subsequent histological examination can confirm suspected cases of osteosarcoma.
For unknown reasons, children born without thumbs (thumb hypoplasticity or congenital thumb absence) may be at greater risk of developing osteosarcoma, according to a recent report. Lifestyle risk factors for adults include smoking, sedentary lifestyle, alcohol consumption and high-fat, low-fiber diet, but these factors do not explain cases of childhood osteosarcoma. For most patients, the causes of tumorigenesis are never identified.
Poorly defined surgical margins are a risk factor for local recurrence after surgery in advanced cases of osteosarcoma. This illustrates the critical role of proper preoperative radiologic assessment and staging in patient cure and recovery.
The most common type of malignant bone tumor, osteosarcoma actually represents a diverse array of tumor morphologies and a wide range of progression patterns. All osteosarcomas share the ability to produce immature bone (osteoid), though not all actually do so.
Osteosarcomas can be broadly categorized by growth pattern as intramedullary (ie, those arising in and growing primarily within the bone) or surface osteosarcomas (those growing on the bone surface). Most cases are intramedullary and of a higher grade than surface forms. Intramedullary forms of osteosarcoma include the conventional and telangiectatic subtypes, as well as other, less common subtypes. Surface osteosarcomas include parosteal ("juxtacortical"), periosteal and high-grade surface subtypes. Intracortical or "intraosseous" osteosarcomas are exceedingly rare, with about a dozen cases reported in the medical literature, and some authors believe it to be an early variant of the conventional osteosarcoma subtype. This subtype will not be detailed here; interested readers are referred to other publications.[l0]
* Conventional intramedullary osteosarcoma. Conventional osteosarcoma, the most common osteosarcomic subtype, has a bimodal or 2-peaked age distribution. The first peak of incidence occurs in the teen years, with an apparent second peak after age 50.
It most often occurs near the knee, in the distal femur and proximal tibia, and also is common in the proximal humerus. Less often, the pelvis or proximal femur are tumor foci. Pathologic fractures of the tumor-weakened bone often are evident. Spread to the lungs is another common complication, and metastasis to the brain is seen in some cases.
Multidrug chemotherapy is employed before limb-salvaging surgery is attempted. Wide swaths of bone shaft around the tumor are removed and replaced with prostheses. In children, expandable prostheses can be used, allowing adjustment to match the growth of the opposite limb. If limb sparing cannot be risked, amputation is performed, followed by postsurgical chemotherapy. More than half of patients survive after salvage or amputation surgery and chemotherapy. External beam radiation therapy is ineffective against osteosarcoma, a radio-resistant tumor.
* Telangiectatic osteosarcoma. Also referred to as hemorrhagic osteosarcoma because of the presence of large necrotic and blood-filled spaces in the tumor, this extremely aggressive form of osteosarcoma occurs more often among men than women. It is relatively more common in the teens and 20s and represents 4% to 11% of diagnosed osteosarcomas. More than half of diagnosed cases occur in the knee area. The distal femoral metaphysis is the most commonly affected site, followed by the proximal tibia and humerus. Telangiectatic osteosarcoma is a bone-forming (ie, osteoid-producing) tumor. Tumor tissues are very porous, with blood-filled spaces separated by walls of osteosarcomic tissue. Geographic patterns of bone destruction with wide zones of transition to healthy bone are common. Periosteal reaction and soft tissue involvement are often severe.
Localized pain continuing for many weeks to months and accompanied swelling are early clinical symptoms of telangiectatic osteosarcoma. Lab analysis typically reveals that serum alkaline phosphatase levels are not elevated, as they are in conventional osteosarcoma.
* Multicentric osteosarcoma. Multifocal osteosarcoma involves multiple bones simultaneously. This is rare and probably represents cases of early metastasis from a "founder" tumor to other bone sites.
* Parosteal osteosarcoma. A low-grade, slow-growing and bone-forming tumor found on the surface of long bones, parosteal osteosarcoma accounts for 3% of osteosarcoma diagnoses. It rarely provokes a periosteal reaction and usually develops after skeletal maturation is complete. More than 80% of parosteal tumors are found in the distal femoral shaft, usually on the posterior aspect. Tumor-deposited bone is typically trabecular in appearance. In several cases, this tumor has been connected to high levels of radiation exposure.
Clinical symptoms include limited joint movement and in some, but not most, cases localized pain. Usually, these tumors present as fixed masses unaccompanied by pain.
Unless the tumor is completely resected, parosteal osteosarcoma will recur and metastasize. With proper treatment, survival rates reach 90% at 5 years after diagnosis.[l] Recurrences following incomplete excision tend to be more aggressive and more likely to invade the medullary cavity. High-grade cases are treated with radical surgery (amputation) and chemotherapy.
* Periosteal osteosarcoma. This typically low-grade, bone-forming tumor is found on lower-extremity long bone surfaces among children. Unlike parosteal tumors, periosteal osteosarcoma occurs beneath the periosteum and provokes strong periosteal reactions. Less than 2% of osteosarcomas are periosteal in nature. The sex ratio for this sarcoma is reversed from the subtypes described above, as it is nearly twice as common in girls as boys. Diaphyseal tibial and femoral involvement is most common, although metaphyseal tumors also occur. Very rarely, upper-extremity and even facial (mandible) involvement has been reported.
Amputation or radical surgical resection with wide margins yields the best survival rates, though 25% of patients still die within 3 years because of metastasis. Periosteal osteosarcoma metastasis is resistant to chemotherapy.[11,12]
* High-grade surface osteosarcoma. By definition, this tumor is always high grade and develops along the surface of long bones. Intramedullary involvement is never present. The rarest of surface osteosarcomas (unless intracortical osteosarcomas are counted), high-grade surface sarcomas account for fewer than 1% of osteosarcoma diagnoses. It is more common among men than women and occurs in the teens and 20s. This tumor usually is detected on metaphyseal surfaces of long bones, especially the proximal humerus and distal femur.
Pain and swelling lasting for several months or even years are the most common clinical symptoms. High-grade surface osteosarcomas frequently metastasize to the lungs and other distant tissues. Treatment is identical to that for conventional intramedullary osteosarcoma: radical surgery or amputation and chemotherapy.
This is the second most common primary bone cancer after osteosarcomas; 27% of all primary bone sarcomas are chondrosarcomas. Like osteosarcoma, this "type" of bone cancer is actually a collection of tumors, ranging from low-grade subtypes to extremely aggressively metastasizing forms. (See Table 2.) Chondrosarcomas lack bone-forming capabilities, however, and all are cartilaginous in nature, despite their occurrence in bone.
Table 2 Comparison of Some Different Types of Chondrosarcomas Conventional Clear Cell Chondrosarcoma Chondrosarcoma Incidence Age 50+ (rare in Ages 20 to 50; younger people) twice as common among men than women Radiologic Appearance Radiolucent lesion Thin sclerotic bor- with ring-like opaci- der with a central ties; lobular outline zone of bone destruction; calcifi- cations possible Mesenchymal Dedifferentiated Chondrosarcoma Chondrosarcoma Incidence Very rare; occurs in Older patients (age late adolescence or 70+) 20s Radiologic Appearance Cartilaginous tumor May be mistaken for with calcifications; conventional chon- permeative bone drosarcoma; histologi- destruction cal analysis required
The vast majority of diagnosed chondrosarcomas, more than 90%, belong to the conventional or "central" subtype. The other subtypes -- clear cell, mesenchymal, myxoid and dedifferentiated -- occur rarely.
Conventional chondrosarcoma tumors are low- to intermediate-grade tumors that generally do not metastasize. Histological analysis is often insufficient to differentiate between conventional chondrosarcoma and other subtypes, necessitating a greater diagnostic reliance on radiographic signs and features than with other lesions.
* Conventional chondrosarcoma. Most patients are older than 50 years, and cases among those younger than 45 are rare. Bones of the trunk are often involved, with a quarter of all cases affecting the pelvis, and a fifth affecting ribs. In the hands and feet, where benign cartilage lesions are common, chondrosarcomas are easily misdiagnosed. Occasionally, the cartilaginous components of the larynx are affected. Conventional chondrosarcoma is an intramedullary tumor.
A dull, aching pain that can become severe at night, sometimes accompanied by palpable localized swelling, is the most common complaint. Often, this pain has continued for years before treatment is sought. Restricted motion is common with tumors at or near joints.
Whenever possible, chondrosarcoma is treated surgically, with complete excision and removal of wide margins of healthy bone surrounding the tumor. In more advanced cases or cases in which tumor location precludes excision with wide margins, chemotherapy and radiation therapy may be used. Appendicular chondrosarcomas have better prognoses than axial tumors. Survival rates for low-grade tumors approach 90% but fall to less than 30% for advanced cases.
Advanced cases can metastasize to the lymph nodes, liver, kidneys and brain. Conventional chondrosarcomas do not typically spread to other tissues in early (low-grade) stages, however.
* Clear cell chondrosarcoma. Fewer than 4% of all chondrosarcomas are of the clear cell subtype. It is twice as common among men as women and typically strikes during patients' 20s to 40s. Clear cell chondrosarcomas are low-grade malignancies managed by monitoring, resection with wide margins or, in some cases, amputation. Resection with wide margins is the treatment of choice, despite this tumor type's low grading, because of a propensity toward recurrence if surgical margins are inadequate.
* Mesenchymal chondrosarcoma. These are very rare; less than 1% of malignant bone tumors are mesenchymal chondrosarcomas. They occur in late adolescence or in the patient's 20s.
* Dedifferentiated chondrosarcoma. The most dangerously aggressive of the chondrosarcomas, this malignancy kills most patients within 2 years of diagnosis. It presents with a long history of pain and rapid-onset, localized swelling of the affected limb. This malignancy occurs mainly in older patients (eg, in their 70s).
Up to 8% of all primary malignant bone tumors are Ewing sarcomas, making them the third most common primary bone tumor malignancy overall and the second most common pediatric primary bone cancer. Ewing sarcoma is extremely aggressive, both in terms of its propensity for spreading to distant tissues and its local recurrence after treatment. It is intramedullary, originating in the bone marrow. Its age distribution is bimodal, usually occurring from 5 to 9 years of age or in the 20s. Eighty percent of patients are younger than 20 years of age, and it is rarely found in patients more than 30 years old. Ewing's sarcoma can occur anywhere in the skeleton, but it is most commonly diagnosed in the pelvis, femur or tibia. The diaphyses of major long bones usually are affected.
Caused by chromosomal abnormalities (genetic translocations of sections of chromosomes 11 and 22), Ewing sarcoma is one of the few bone cancers for which genetic underpinnings are fairly well understood. This genetic abnormality is found in 90% of cases diagnosed from clinical and radiopathological examination. Ewing sarcoma seems to be limited to individuals of European ancestry and is practically absent among African Americans. Slightly more boys than girls develop this sarcoma.
Treatment now involves aggressive combined chemotherapy, radiation therapy and surgery, a regimen that yields 5-year survival rates of 70% for patients with a localized tumor. However, for patients whose sarcoma already has metastasized (as many as 28% of those diagnosed with the disease) the 5-year survival rate is 30%.
The site of the primary tumor has prognostic significance, as patients with disease in the pelvis or other bones of the trunk fare more poorly than those with primary tumors in their extremities. For the former group, 3-year survival rates are on the order of 30%, whereas for the latter group 3-year survival rates approach 80%. The difference seems to be due to larger initial tumor masses at diagnosis and the involvement of soft tissues in trunk bone tumors at diagnosis.
Benign Bone Tumors and Tumor-like Disorders
Benign lesions usually are due to localized growth disturbances. It is possible that these involve dysregulation of growth-associated hormone receptors.
* Unicameral bone cysts. Simple, or unicameral, bone cysts are tumor-like in appearance but are not malignancies. They are more common in boys than girls and usually develop in childhood or by late adolescence. (See Table 3.) Most occur at the diaphysis of the femur and humerus. In more than half of diagnosed cases, pathologic fracture occurs when the weakened bone in which the cyst is located can no longer withstand normal forces and pressures and fails.
Table 3 Comparison of Some Different Benign Bone Tumors Unicameral Bone Aneurysmal Cysts Cysts Incidence Children and adoles- Children and adoles- cents; more common cents in boys Common Sites Diaphysis of the femur Long bone metaphyses and humerus or diaphyses, scapula or pelvis Radiologic Appearance No periosteal reaction Eccentric expansion of unless there has been the bone; thin a pathologic fracture periosteal response or buttress Giant Cell Tumors Incidence Ages 20 to 40; twice as many women as men Common Sites Long bone articulating heads, proximal tibia and humerus, distal femur Radiologic Appearance Radiolucent lesions with- out sclerotic margins or periosteal reaction
Simple cysts often are treated by cutting and grafting healthy bone into the cyst in an attempt to induce bone repair (local osteogenesis). In children less than 10 years of age, however, this treatment often fails due to cyst recurrence. Because these cysts occur near the physis, grafting may interfere with growth plate function. Therefore, it is recommended that childhood unicameral cysts be treated by injection of methylprednisolone acetate to promote bone repair.
* Aneurysmal bone cysts. Aneurysmal bone cyst (ABC) involves local venous obstruction or arteriovenous fistula and may arise from reparative processes at sites of local bone trauma. Approximately 6% of all primary bone lesions are ABCs. They are sometimes secondarily associated with other lesions, both benign (eg, giant cell tumors) and malignant (eg, osteosarcomas and chondrosarcomas).
Ninety percent of ABCs occur among children and adolescents. Long bone metaphyses typically are involved, but ABCs may occur in long bone diaphyses as well, or in the scapula or pelvis. They commonly result in pathologic fracture of affected bone. Treatment involves complete surgical excision of the cyst, but recurrence is nevertheless common.
* Giant cell tumors. Osteoclastomas, or giant cell tumors, are aggressive neoplasms but are usually not malignant. Despite their classification as benign tumors, as many as 10% of giant cell tumors are malignant.
These tumors account for up to 9% of all primary bone tumors and nearly a quarter of benign bone tumors. Most occur in long bones, and nearly all long bone osteoclastomas occur at the articulating head. The proximal tibia and humerus and distal femur and radius are the most common locations for these lesions. They are seen after skeletal maturity is reached and the growth plate has disappeared. Twice as many women suffer osteoclastoma as men. Patients are usually between 20 and 40 years old.
Treatment involves surgical curettage and bone grafting, or resection with wide margins and allograft or prosthesis installation. Exposure to radiation therapy can cause recurring giant cell tumors to transform into malignant osteosarcomas or fibrosarcomas. (Fibrosarcomas are not discussed in this reading.) Previously benign forms of giant cell tumor have been known to metastasize to the lungs.
Radiography is the imaging technique of choice for detecting and diagnosing lesions in the appendicular skeleton, and even if subsequent examinations are undertaken with other techniques, conventional radiographs always should be available for comparison.4 There are limitations to radiography, however, including its relative ineffectiveness for identifying soft-tissue extensions of bone tumors. This limits radiography's usefulness for tumor staging and surgical planning, which depend on accurate assessment of soft-tissue involvement. Furthermore, early bone destruction due to tumor growth is not detectable radiographically because lesions are visible using this technique only after as much as 40% of bone has been destroyed. Therefore, early bone tumors cannot be excluded using radiographic exams.
Because of its ability to yield superior contrast resolution and images in anatomical cross-section, computed tomography (CT) is generally the preferred technique for axial skeletal lesion imaging. It is also superior for imaging soft-tissue extension of bone tumor mass. Initial radiographic examination to locate the tumor can be followed by CT imaging for more precise localization and delineation of borders. If soft tissue or bone marrow tumors are suspected, however, magnetic resonance (MR) imaging follow-up is required. If there is no evidence of soft-tissue tumor extension, CT is superior because it allows assessment of cortical destruction and subtle periosteal reactions. For assessing marrow,.joint spaces and soft tissue involvement of bone tumors, MR proves consistently superior to other techniques.
Radionuclide imaging (scintigraphy) permits whole-skeleton screening for bone lesions. This is particularly valuable when multiple tumors are suspected. Tumor specificity for scintigraphy is poor, however, because the radionuclides employed typically concentrate in areas of bone repair activity, including not only tumors but sites of trauma, infection and inflammation. Nevertheless, scintigraphic examinations can be used to assess the efficacy of chemotherapy because a positive response to therapy results in decreasing radionuclide uptake.
Ultrasonography is very rarely used for bone tumor imaging.
The following sections review diagnostic imaging for several of the forms of bone cancer described earlier.
Radiographic exams can yield sufficient information in most cases for the diagnosis of osteosarcoma. (See Table 1.) However, biopsy and histological examination are necessary to confirm diagnoses. Mineralization or calcification of the tumor matrix produces variously sized radio-opacities that appear cloudy on radiographs. (See Fig. 3.) The pattern of bone destruction shows a gradual change across ambiguous transition zones from obliterated osteolytic regions or sclerotic areas to normal bone,
Once the tumor has breached the cortex, erupting outward from the medulla compartment, it typically invades adjacent soft tissue. This causes a mineralized "shadow" around the site of penetration of the cortex and the extracompartmental extent of the tumor. (See Fig. 4.) The mass of osteosarcoma extending beyond the cortical surface typically matches the mass of the intramedullary portion of the tumor. Therefore, when extracortical soft tissues are poorly visualized, a good rule of thumb is that the larger the intramedullary tumor, the more likely it is that adjacent extracortical soft tissues are significantly involved.
Periosteal reactions to underlying osteosarcoma vary in morphology, and can appear hazy or can present as perpendicular, radiating lines called the "sunburst" sign. (See Fig. 5.) Particularly when osteosarcomas occur in diaphyseal rather than metaphyseal regions, they may exhibit layered, onionskin periosteal reactions. It is important to note that rapidly expanding osteosarcoma tumors, which are typified by permeative bone destruction, may provoke no visible periosteal reactions. If a suspected osteosarcoma is not accompanied by radiographic signs of periosteal reaction, however, a bone-destroying infection (osteomyelitis) may be present and must be ruled out.
MR is particularly useful for identifying small additional extracompartmental tumors and intramedullary tumors. CT scans and MR allow precise evaluation of tumor extent, an invaluable aid for optimal biopsy targeting by the surgeon. CT and MR also are useful for evaluating intramedullary extent and extension into soft tissues, including the proximity or involvement of the tumor with neurovasculature. This is an absolutely critical asset in surgical planning for limb-salvaging treatment. Chest CT is used regularly to screen for osteosarcoma metastasis to the lungs.
If distant skeletal metastasis or multifocality is suspected, radionuclide bone scans can be employed using technetium 99. The technetium radioisotope is delivered intravenously and concentrates in areas of osseous deposition, both in the skeleton and in pulmonary sites of osteosarcoma metastasis. Thallium 201 chloride is another radioisotope used in osteosarcoma scintigraphy to differentiate living tumor tissue from focal infection.
* Conventional osteosarcoma. Medullary and cortical bone destruction is evident on plain-film radiographic examination of conventional osteosarcoma, as is marked periosteal reaction. Patchy densities often are seen, even when clear forms of bone destruction are not. Involved soft tissues may contain tumor bone production, and the degree of radiographic opacity often will reveal relative amounts of tumor bone production in these soft tissues, as well as within the lesion.
Tumors may be sclerotic (contained in a scleroticized rind), usually in combination with moth-eaten or permeative bone destruction. Geographic bone destruction is rare in conventional osteosarcoma.
Periosteal response is most commonly of a distinctive "sunburst" type with a Codman triangle. (See Fig. 2.)
CT was preferred for tumor evaluation until recently, particularly when limb-salvaging surgical procedures were planned. MR now is used as often for this purpose, especially when intraosseous or soft-tissue extensions are suspected. MR also is used to monitor the effectiveness of treatment.
* Telangiectatic osteosarcoma. These rare but aggressive tumors are highly vascularized, and blood pools in cystic spaces within the tumor. It is a purely osteolytic (bone-destroying) lesion that typically grows too rapidly for sclerotic borders to form. Osteoblastic new bone formation is rare, though bone expansion due to displacement of cortex by underlying tumor does occur. Bone destruction is of the permeative pattern type and periosteal reactions typically yield no new bone growth nor the onionskin radiographic sign.
Telangiectatic osteosarcoma is a particularly dangerous subtype because in addition to being a very high-grade tumor, it can in some cases have a sclerotic margin that makes it easily confused with benign bone cysts on radiographs. MR follow-up can differentiate between benign cysts and telangiectatic tumors.
Scintigraphic examination often yields a "donut sign," with peripherally increased uptake and central cold spots of reduced uptake.
* Parosteal osteosarcoma. This tumor grows laterally, along the periosteal surface from a cortical point of origin. This often results in a vaguely mushroom-like appearance, with space between the bulk of the tumor and the cortex to which it is rooted.[1,4] (See Fig. 6.)
Parosteal tumors are densely mineralized with lobular or cloud-like outlines. Because these tumors grow along the surface of the periosteum instead of beneath it, periosteal reactions are muted and new bone formation in onion-like or sunburst patterns is not seen. One distinctive characteristic of parosteal tumors is their ability to completely encircle the bone shaft. This is best detected with CT or MR. These techniques also often reveal soft-tissue satellite nodules near a tumor.
Except in advanced cases, the intramedullary compartment is not penetrated because the cortical surface is not breached. Intramedullary noninvolvement is difficult to confirm with radiographs; CT or MR should be used to make this determination. Intramedullary involvement usually is minor compared with extramedullary tumor mass.
Another important radiographic sign is peripheral lesions with lucent spots. These are large, cartilaginous developments representing transition to a high-grade, metastasis-prone sarcoma.
* Periosteal osteosarcoma. These tumors usually present as radiolucent lesions on the surface of long bones, particularly in the legs. Tumors are fusiform (spindle shaped), with periosteal bone formation appearing as Codman triangles (see Fig. 2) and perpendicular rays. Intramedullary involvement is not present, but this must be confirmed with CT or MR to rule out the possibility that a suspected periosteal osteosarcoma is actually the surface portion of an unrecognized conventional osteosarcoma.
* High-grade surface osteosarcoma. These tumors occur on the cortical surface and may appear somewhat like periosteal osteosarcoma on radiographic examination. The matrix mineralization is irregularly distributed and contains cloud-like opacities. The lesion's boundaries tend to be poorly visualized.[1,4] The cortex may be damaged, but except in a few very advanced cases, intramedullary involvement is absent. Codman triangles are the common periosteal reaction to displacement by underlying cortical tumor.
Conventional chondrosarcomas are intramedullary tumors. They grow slowly, yielding clear radiographic tumor boundaries. While not osteoblastic (bone-building), they can contain calcifications. (See Table 2.) Dorfman and Czerniak describe the presence of discrete, calcified opacities as a radiographic hallmark of chondrosarcomas. The lesion itself presents as a radiolucent area containing ring-like opacities. (See Fig. 7.) The tumor outline is often lobular.
The cortical contour around intramedullary chondrosarcomas often is somewhat expanded outward (displaced) and thinned, with an eroded inner surface. In some cases, however, a low-grade chondrosarcoma provokes cortical thickening. This is due to tumor infiltration of the adjacent cortex and cortical osteoblastic response, a reliable indicator of tumor malignancy.
Because of slow tumor growth, chondrosarcomas tend to grow along the interiors of medullary cavities rather than erupting through the cortex. Subtle outward cortical displacement and localized cortical thinning are signs of chondrosarcoma. Only in advanced cases has thinning led to outright extension of the intramedullary chondrosarcoma through the cortex and into adjacent soft tissues.
Chondrosarcoma tumors are not themselves bone producing, but their outward cortical displacement frequently provokes periosteal reactions. Typically, these are seen radiographically as fuzzy cortical borders or parallel layers of onion-like new bone formation. Sunburst signs are absent. Permeative or moth-eaten patterns of bone destruction are strong radiographic signs of high-grade, advanced chondrosarcoma.
MR and CT are used to evaluate tumor dimensions and soft tissue involvement. CT can demonstrate discrete calcifications that may be missed with plain radiography or MR.
Evaluation and detection of early-stage, intramedullary cartilage tumors can be difficult. Changes in bone metabolism and repair of bone destruction associated with conventional chondrosarcoma can be imaged using bone scintigraphy, making this technique valuable for detection and localization. MR or CT then can be used to delineate the extent and margins of tumors. Nevertheless, most chondrosarcomas continue to be detected with radiography.
* Clear cell chondrosarcoma. A thin sclerotic border around a central zone of bone destruction typically is seen on the radiograph. Calcifications may be seen, particularly when the proximal humerus or femur is involved. Because of a radiographic similarity to chondroblastoma, suspected clear cell chondrosarcomas should be biopsied to confirm radiographic diagnoses.
* Mesenchymal chondrosarcoma. On radiographs, mesenchymal chondrosarcoma shows permeative bone destruction and calcifications within the focal cartilaginous tumor itself. It is often impossible to differentiate mesenchymal from conventional chondrosarcomas radiologically.
* Dedifferentiated chondrosarcoma. This deadly malignancy can be mistaken for conventional chondrosarcoma or even an osteosarcoma when radiographs are examined, but it is histologically distinct. Dedifferentiated chondrosarcoma illustrates why radiologic evidence alone is insufficient for definitive diagnosis of bone tumors and underscores the value of a multidisciplinary approach to bone lesion examination.
The radiographic signs for this tumor are not specific, but when considered alongside chromosomal and clinical signs and symptoms, it is diagnosed easily. Bone destruction is seen on radiographs as permeative or moth-eaten foci within this intramedullary lesion. Soft-tissue involvement is common. Periosteal reaction often is prominently layered or "onionskinned."[1,4] Though not as common as in some osteosarcomas, sunburst-type periosteal reactions also occur in Ewing sarcoma.
It should be remembered that soft tissue and intramedullary involvement of Ewing sarcoma tumors is usually far more extensive than suggested by radiographic examination. Therefore, MR and CT examinations should be used in preoperative planning and tumor measurement.
A sign of Ewing sarcoma that is not present in all cases is "saucerization." Saucerization is a tumor-induced concavity of the cortical surface. Usually this is associated with a permeated cortex with soft-tissue involvement that pushes the cortex inward toward the medullary compartment. (See Fig. 8.)
* Simple bone cysts. Unicameral cysts lack periosteal reactions unless they have resulted in a local pathologic bone fracture. In the absence of evidence of a pathologic fracture, periosteal reactions exclude simple bone cyst as a diagnosis. Radiographic examination is sufficiently sensitive for diagnostic imaging, and CT generally is used only in rare, equivocal cases. In some cases, cortical debris from a pathologic fracture sits in the lesion's interior. This indicates that the lesion is hollow or fluid filled, evidence of a simple cyst. This is called the "fallen fragment" sign.
In the proximal humerus or femur, bone abscesses can be mistaken for simple cysts. Careful examination of the radiograph is sufficient to differentiate between the 2, because abscesses extend beyond the growth plate or show evidence of periosteal reaction.
* Aneurysmal bone cysts. Conventional radiographic examination usually is adequate for diagnosis of this benign lesion. Multicystic eccentric expansion of the bone ("blow out") with a thin periosteal response or buttress is a radiographic hallmark.
CT analysis may be required if the continuity (integrity) of the cortex is unclear on the radiograph, and can help determine whether cysts are indeed fluid filled (aneurysmic). Scintigraphic bone scans after injection of technetium 99m radiolabel will localize ABCs, but specific diagnosis is most easily obtained using MR. On MR, ABCs are well-defined lesions with lobulated outlines and cystic, blood-filled cavities with a complete rim of low-intensity material around the lesion. This rim is a sign of benign lesioning of the bone.
* Giant cell tumors. Giant cell tumors are radiographically recognizable as radiolucent lesions lacking sclerotic margins and periosteal reaction. Scintigraphy often yields scans with hot spots of intense uptake around the lesion periphery (the donut sign). If conventional radiography suggests the presence of a soft-tissue mass, CT or MR should be undertaken to evaluate its extent.
Recurrences after treatment are common and are radiologically apparent as the resorption and disappearance of grafted bone from the lesion site. Unfortunately, malignant giant cell tumors cannot be distinguished from truly benign forms radiographically.
The causes and processes underlying the development of tumors and tumor-like lesions primary to bone remain unclear, but radiologic imaging continues to play an important role in the diagnosis and characterization of bone lesions, both malignant and benign, and in monitoring treatment outcomes. Detection and accurate radiologic characterization of tumors allow early intervention and, ultimately, can save patients' lives. The ambiguous early clinical signs and symptoms of bone cancer make diagnostic radiology a patient's best hope for early detection and intervention in many cases, and radiology will continue to play an important role in the multidisciplinary assessment of bone cancers.
Directed Reading Continuing Education Quiz
Radiography of Bone Tumors and Lesions
DRI0001008 Expiration Date: June 30, 2003(*) Approved for 2.0 Cat. A CE credits
To receive Category A continuing education credit for this Directed Reading, read the preceding article and circle the correct response to each statement. Choose the answer that is most correct based on the text. Transfer your responses to the answer sheet on Page 475 and then follow the directions for submitting the answer sheet to the American Society of Radiologic Technologists. You also may take Directed Reading quizzes online at www.asrt.org.
(*) Your answer sheet for this Directed Reading must be received in the ASRT office on or before this date.
1. Benign bone lesions are usually -- growing and pose -- threat of metastasis. a. fast; serious. b. fast; no. c. slow; serious. d. slow; no. 2. The "zone of transition" refers to tumor a. borders. b. location. c. pattern of bone destruction. d. matrix type. 3. Which of the following forms of bone destruction are more typically seen in malignant lesions? 1. geographic. 2. permeative. 3. moth-eaten. a. 1 and 2. b. 1 and 3. c. 2 and 3. d. 1, 2 and 3. 4. Which tumor grade reflects the greatest risk of metastasis? a. G0. b. G1. c. G2. d. G3. 5. Which stage represents a high-grade intramedullary (intracompartmental) lesion? a. stage I. b. stage IIa. c. stage IIb. d. stage III. 6. Radiographic examination of a 14-year-old patient with persistent, localized pain reveals a metaphyseal tumor. Which possible diagnosis should be checked first, as it is most likely? a. aneurysmal cyst. b. giant cell tumor. c. chondrosarcoma. d. osteosarcoma. 7. Eighty percent of pediatric -- occur in the distal femur or proximal tibia. a. aneurysmal cysts. b. giant cell tumors. c. chondrosarcomas. d. osteosarcomas. 8. Children born without -- may be at greater risk of --, according to a recent report. a. large toes; osteosarcoma. b. thumbs; osteosarcoma. c. large toes; chondrosarcoma. d. thumbs; chondrosarcoma. 9. Intramedullary osteosarcomas include which of the following subtypes? 1. telangiectatic. 2. conventional. 3. parosteal. a. 1 and 2. b. 1 and 3. c. 2 and 3. d. 1, 2 and 3. 10. More than half of diagnosed telangiectatic osteosarcomas occur in the a. mandible. b. elbow. c. knee. d. ankle. 11. High-grade surface osteosarcoma is most likely to be found along the -- surface of -- bones. a. metaphyseal; flat. b. metaphyseal; long. c. diaphyseal; flat. d. diaphyseal; long. 12. For which bone cancer are the genetic underpinnings understood? a. clear cell chondrosarcoma. b. conventional chondrosarcoma. c. dedifferentiated chondrosarcoma. d. Ewing sarcoma. 13. Combined chemotherapy, radiation therapy and aggressive surgery allow --% of Ewing sarcoma patients with localized tumors to survive at least 5 years after treatment, but for patients who already have distant metastases at the time of diagnosis, the survival rate drops to --%. a. 90; 70. b. 70; 30. c. 30; 15. d. 15; 10. 14. What percentage of giant cell tumors are malignant? a. 1. b. 5. c. 10. d. 25. 15. Which imaging technique should be used if there is no evidence of soft tissue tumor extension and cortical destruction or subtle periosteal reactions must be assessed? a. conventional radiography. b. computed tomography. c. magnetic resonance. d. scintigraphy. 16. Osteosarcomic breaching of the cortex and invasion of adjacent, external soft tissues causes the -- radiographic sign near the eruption site. a. shadow. b. fallen fragment. c. donut. d. sunburst. 17. A good rule of thumb when assessing radiographs of osteosarcomas is that the larger the -- tumor, the more likely it is that -- tissues are significantly involved. a. intramedullary; extracortical soft. b. intramedullary; cortical. c. extramedullary; extracortical soft. d. extramedullary; cortical. 18. If a suspected osteosarcoma is not accompanied by radiographic signs of periosteal reaction, -- may be present. a. chondrosarcoma. b. aneurysmal cyst. c. osteomyelitis. d. giant cell tumor. 19. Which technique is used when distant skeletal metastases or multifocal lesions are suspected? a. traditional radiography. b. computed tomography. c. magnetic resonance. d. scintigraphy. 20. Conventional osteosarcoma commonly involves which radiographic periosteal sign? a. shadow. b. fallen fragment. c. onionskin. d. sunburst. 21. For conventional osteosarcomas, which imaging technique is preferred when intraosseous or soft-tissue extensions are suspected? a. conventional radiography. b. computed tomography. c. magnetic resonance. d. scintigraphy. 22. Radiographically, it may be impossible to differentiate mesenchymal chondrosarcoma from --. a. clear cell chondrosarcoma. b. conventional chondrosarcoma. c. dedifferentiated chondrosarcoma. d. Ewing sarcoma. 23. Ewing sarcoma commonly involves which radiographic periosteal sign? a. shadow. b. fallen fragment. c. onionskin. d. spiculated. 24. The fallen fragment radiographic sign is evidence of which of the following? 1. pathologic fracture. 2. cortical debris in lesion interior. 3. aneurysmal cyst. a. 1 and 2. b. 1 and 3. c. 2 and 3. d. 1, 2 and 3. 25. Which of the following radiographic signs indicate that a lesion is an aneurysmal cyst? 1. eccentric cortical expansion. 2. thin periosteal reaction or buttress formation. 3. well-defined cortical continuity (integrity). a. 1 and 2. b. 1 and 3. c. 2 and 3. d. 1, 2 and 3. 26. Malignant giant cell tumors often can be distinguished from benign forms radiologically. a. true. b. false. Reference No. DRI0001008
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Bryant Furlow, B.A., studied biology at the University of New Mexico in Albuquerque, graduating with top honors. He is now a freelance science and medical writer living in California.
Reprint requests may be sent to the American Society of Radiologic Technologists, Communications Department, 15000 Central Ave. SE, Albuquerque, NM 87123-3917.
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