Radiography

Radiography remains the primary initial imaging study for detection and characterization of bone tumors. When a classically benign-appearing lesion is detected on routine radiographs, additional studies may not be required unless surgical intervention is contemplated and further anatomic information is needed. In this setting, either CT or MRI may be most appropriate for preoperative evaluation.

For soft tissue masses, certain radiographic features may provide valuable insight into the diagnosis or may guide additional examinations that may be required. For example, a well-defined lucency in the soft tissues may indicate a lipoma, which could be evaluated for either CT or MRI. Patients with subtle bone change or soft tissue calcification may be more appropriately studied with CT. Also, lesions projecting from bone as in osteochondroma can present as deep soft tissue masses clinically.

Arthrography is rarely if at all indicated for evaluation of soft tissue masses. Synovial cysts or ganglion cysts can be documented as benign by demonstrating communication with the joint after intra-articular injection of contrast material. However, this technique is rarely necessary. Similarly, with few exceptions such as arteriovenous malformations and hemangiomas, angiography is also not frequently performed for the detection or staging of soft tissue lesions.

Computed Tomography

For bone lesions, CT is very useful for evaluation of margins, matrix mineralization, and cortical breakthrough. If an osteoid osteoma is suspected, thin-cut CT is helpful in finding the lucent nidus. CT is also useful for visualizing soft tissue masses, defining compartmental involvement, and detecting mineralization and bone involvement. However, since the introduction of MRI, CT has largely been replaced as the technique of choice for evaluation of soft tissue masses. CT may still be appropriate for evaluation of some soft tissue lesions, such as lipomas, calcified lesions, and myositis ossificans. In addition, patient size or location of the lesion may dictate that CT would be the preferred technique. Such locations include the abdominal or chest wall, where motion artifact can create suboptimal imaging with MRI. A report by the Radiology Diagnostic Oncology Group on 133 soft tissue tumors suggested that MRI and contrast-enhanced CT are comparable with reference to determining tumor size and involvement of surrounding structures. Nevertheless, the American College of Radiology expert panel lists MRI as the most appropriate initial imaging examination for evaluation of a suspected soft tissue mass.

Ultrasound

Ultrasound is valuable in differentiating cystic from solid soft tissue lesions and has also been used to study vascularity of lesions (Figs. 6-1 and 6-2). For soft tissue prominence at a joint, ultrasound may offer a specific diagnosis (e.g., ganglion cyst and paralabral or parameniscal cyst; Fig. 6-3). However, ultrasound is not as useful for characterizing pathology or defining the extent of true soft tissue masses, except in situations in which lesion echogenicity (e.g., lipoma; Fig. 6-4) or morphology (e.g., nerve sheath tumor, Fig. 6-5) is specific.

Figure 6-1 Hemangioma of the finger.

Figure 6-2 Liposarcoma of the abdominal wall: flow and complexity.

Figure 6-3 Mass inferior to the knee joint. Ultrasound shows a lobulated fluid collection with a neck to the meniscus, consistent with a parameniscal cyst.

Figure 6-4 Lipoma of the arm.

Figure 6-5 Nerve sheath tumor: posterior tibial nerve.

Magnetic Resonance Imaging

When routine radiographic features of a bone lesion are indeterminate or when the lesion is more aggressive and considered to be potentially malignant, MRI is frequently required and is useful for characterization as well as staging. Soft tissue masses always require evaluation with CT or MRI. More commonly MRI is used unless there is calcification that CT could better characterize. Gadolinium contrast is useful for distinguishing cystic, myxoid, or necrotic components from solid regions; it is also useful when scanned in dynamic fashion rapidly after a bolus to characterize tumor vascularity. Although certain features on MRI can often be used to narrow the differential diagnosis for bone and soft tissue, it is unreliable for characterizing tissue type and is not even specific for distinguishing many benign from malignant lesions. Therefore, the radiologist should not become overconfident and should always keep in mind the limitations of each modality as well as the broad range of nontumors and tumor-like lesions that can simulate true neoplasms.

Even when MRI cannot characterize the type of lesion, it remains very useful for percutaneous biopsy and surgical planning. MRI is the technique of choice for evaluating and staging primary bone sarcomas, including neurovascular involvement. It is useful for determining tissue characteristics of a bone lesion, such as fat, hemorrhage, fibrous tissue, and fluid–fluid levels. Of course, patient size and clinical status as well as the presence of certain metallic or electrical implants may preclude the use of MRI.

Nuclear Medicine

Bone scan is predominantly useful for evaluation of multiplicity of lesions. However, if the primary lesion in question (or lesion detected with another modality) shows no increased uptake on bone scan, the scan should be considered of limited value for detecting other deposits. This is often the case with purely lytic metastases and myeloma (Fig. 6-6). On the other end of the spectrum, diffuse involvement (skeletal carcinomatosis), as seen in cases of metastatic prostate or breast carcinoma, can produce such generalized uptake that the bone scan looks relatively normal except for lack of uptake by the kidneys (described as a “superscan”). Bone scan is also very useful for detecting the metastatic lesions of osteosarcoma, which avidly concentrate radiotracer. Osteosarcoma tends to metastasize to lung, and bone scan can be helpful for surveillance of recurrence as well as distant metastases.

Figure 6-6 Bone scan can be insensitive to lytic metastases. In this case of metastatic lung carcinoma, purely lytic metastases are not well seen on bone scan. Regardless, bone scan is an essential part of any metastatic workup, since it provides global information; but it must be seen as a complementary examination, interpreted in conjunction with other modalities.

Another situation in which bone scan can be useful is the differentiation of a benign sclerotic focus, such as a bone island or fibrous dysplasia with little to no increased uptake, from a blastic metastasis, which has a high degree of uptake. For patients with ill-defined symptoms and normal radiographs, a radionuclide bone scan may be used to localize the abnormality. Following a positive bone scan, either MRI or CT may be selected to better define the nature of the lesion. Radionuclide studies are not indicated in most situations for evaluation of soft tissue masses. Techniques such as positron-emission tomography (PET) scanning have been used mainly for evaluation of metastatic disease and follow-up of treated lesions but show promise for identifying active areas of a tumor before biopsy (Fig. 6-7).

Figure 6-7 Selection of site to biopsy using PET (positron-emission tomography) scan. The area of maximal metabolic uptake could potentially provide the highest diagnostic yield. PET, positron-emission tomography.

Summary of Modalities

Radiography remains the optimal initial examination for a clinically suspected musculoskeletal tumor. When lesions are characteristically benign, imaging workup may cease, but additional imaging may still be useful for preoperative planning. Further characterization of an indeterminate lesion usually requires CT and/or MRI. CT is preferred for patients with suspected osteoid osteoma and subtle cortical abnormalities, and for evaluating lesion calcification or tumor matrix. Bone scan is predominantly useful for evaluation of multiplicity of lesions. MRI is the preferred technique for staging of musculoskeletal neoplasms in soft tissue and bone. PET scanning is useful for evaluation of metastases and tumor recurrence.

Appearance of Lesions Recently Biopsied

Biopsy makes a lesion look more aggressive on CT and MRI, resulting in surrounding edema and enhancement that makes it difficult or impossible to define the lesion’s true margins. If a biopsy is near a neurovascular bundle, this can change a planned surgery from a limb salvage to an amputation. It is very important to obtain all imaging before biopsy.

Appearance of Treated Lesions

The appearance of bone and soft tissue can change after treatment. Considering the lesions themselves, lytic, metastatic lesions can become more sclerotic, especially breast metastases. Bone scan may demonstrate a paradoxic increase in activity because of bone healing (flare phenomenon). The pattern of red marrow can change on MRI. For example, rebound following chemotherapy or treatment with colony-stimulating factor can result in an increase in hematopoietic marrow, which is often more cellular and thereby brighter in T2 and STIR signal than typical red marrow. Radiation therapy results in replacement of red marrow with fatty yellow marrow (Fig. 6-8). Treatment can also affect the soft tissues. For example, radiation therapy causes soft tissue edema, especially of the underlying muscles within the port. This edema may last for years and can simulate a number of pathologic conditions from trauma to infection to neurologic disease; no mass effect is seen. In later follow-up, the muscles may exhibit fatty atrophy.

Figure 6-8 Radiation therapy-related bone marrow changes and osteonecrosis.

Staging of Primary Musculoskeletal Tumors

Description of the imaging appearance of a bone or soft tissue tumor should include a description of local aggressiveness and extension into other compartments, such as from bone to adjacent muscles, from one fascial compartment to another, from anywhere into a neurovascular compartment, and distant metastases (Fig. 6-9 and Table 6-1). This information is combined with histologic aggressiveness (Grade 0: G0 = benign; Grade 1: G1 = low-grade malignant; Grade 2: G2 = high-grade malignant) to determine the overall stage (Table 6-2).

Figure 6-9 Definition of tissue compartments. Aggressive bone lesion with extracompartmental spread to anterior compartment.

(Courtesy of W.F. Enneking, MD.)

Table 6-1 Anatomic Compartments

Table 6-2 Surgical Stages of Sarcomas

Stress Fracture

It is not common for stress fractures to be confused with tumor, since the clinical context usually guides the referring doctor to request specifically to “rule out stress fracture.” Yet it continues to occur, as evidenced by fractures referred for biopsy. There are clearly situations in which the radiologist is more likely to confuse stress fracture with tumor. Biopsy of such a lesion can have devastating results, as in an erroneous pathologic diagnosis of osteosarcoma (due to mitoses and osteoid formation), so it is important to be aware of the following situations.

Figure 6-10 Ill-defined edema in the sacral ala should raise suspicion of stress fracture, especially in the elderly or in those who have recently had pelvic radiation therapy. The vertically oriented fracture line can usually be seen on coronal images but is characteristic on the axial plane as well. In chronic fractures, T2-weighted images typically show a well-defined fracture line surrounded by ill-defined marrow edema. However, depending on acuity the imaging features can vary, so the fracture line should be sought on all imaging planes/sequences. On CT, ill-defined sclerosis can simulate tumor, but close inspection reveals linear nature and/or vertical interruption of the sacral foraminal lines. The fracture is often bilateral and passes across a sacral vertebral body (responsible for the H sign on bone scan).

Figure 6-11 Stress fractures in atypical locations may simulate tumor. History is important, but visualization of a low-signal subcortical line is highly specific; biopsy can be misleading, showing osteoid matrix and mitoses similar to osteosarcoma. Therefore, if stress fracture is a possibility, MRI (to look for the subcortical line) or short-term radiographic follow-up (stress fractures evolve quickly—usually over a few weeks, developing smooth, thick periosteal reaction) is preferred.

Figure 6-12 Longitudinal stress fracture. Atypical locations and appearances of stress on various modalities can simulate tumor. In the tibia, stress fractures can be longitudinally oriented. The key is to look for the fracture line and the subcortical rim of edema/enhancement characteristic of stress.

Radiographs and CT may early reveal indeterminate or confusing findings, such as subtle periosteal reaction or an area of bone sclerosis. Given the clinical context, look closely for sclerosis to be primarily subcortical in location, with the fracture oriented perpendicular to the trabecular pattern. Bone scan shows a focus of markedly increased uptake, usually eccentric, but the pattern is nonspecific. MRI can confirm a suspected diagnosis, with a characteristic dark line on T1- and T2-weighted images extending from the cortex into the medullary cavity, surrounded by edema (see Fig. 6-12). Tumors, on the other hand, show a discrete lesion on MRI without the dark line.

Schmorl’s Node and Hemispheric Spondylosclerosis

Schmorl’s nodes are often associated with reactive sclerosis, or hemispheric spondylosclerosis. When extensive, this can simulate a sclerotic metastasis (Fig. 6-13). On radiographs, communication with the adjacent disk and associated degeneration may not be apparent, but this can be confirmed with CT or MRI.

Figure 6-13 Schmorl’s node and hemispherical spondylosclerosis. Modic-type degenerative changes occur around the node, which represents intraosseous extension of disk material. In later stages, Modic type 3 changes can ensue with rounded sclerosis (hemispherical spondylosclerosis). This can simulate a blastic metastasis. Associated endplate invagination can help differentiate these.

Bone Island (Enostosis) Versus Blastic Tumor

Bone islands are essentially benign hamartomas consisting of a focus of cortical bone within medullary bone. They can simulate a solitary metastasis on radiographs. Bone islands are usually seen as solitary or scattered foci but are seen in greater numbers in tuberous sclerosis and sclerosing bone dysplasias. There are a few imaging features suggesting their benign etiology. First, the margins of bone islands classically “blend” with the adjacent trabeculae. Also, bone islands tend to be ovoid in shape; metastases tend not to be round (Fig. 6-14). These characteristics are not as comforting when reviewing an examination of a patient with a history of cancer. In this setting, a bone scan is very useful. Bone islands show minimal to no increased uptake, whereas, if large enough, a blastic metastasis should show intense uptake. In addition, bone scan can detect other lesions. CT may detect the trabecular blending better than bone scan, but it is not usually very useful. MRI can be useful because bone islands are typically monotonous black signal on all sequences, whereas metastatic lesions often contain some T2 hyperintensity and enhancement, even if blastic. PET scan could be useful, again, only if the lesion is large enough to detect. Like bone scan, if the PET scan is negative and the lesion is less than 1 cm, further workup (such as biopsy) may still be necessary.

Figure 6-14 Bone islands may simulate blastic metastases. Bone islands are generally ovoid in shape with fuzzy margins that blend with surrounding trabeculae. Blastic metastases are typically rounded and have sharper margins. However, there is considerable overlap in appearance. If there is concern, a bone scan can differentiate a blastic metastasis (high degree of uptake) from a bone island (no increased uptake or slightly “warm”).

Paget Disease

Paget disease deserves special mention in this chapter, not only because it can simulate tumor, but also because of its association with certain tumors. The disease usually affects people over age 50, but it can be seen in those in their late 30s. It can affect virtually any bone in the body but it favors the pelvis, proximal femur, sacrum, and spine. The disease passes through an early lytic phase and a late reparative phase. The early phase is characterized by well-defined regions of osteolysis. This has been described on radiographs as osteolysis circumscripta in the skull and a “blade of grass” appearance in long bones, the latter referring to a sharp, dagger-shaped lucency. The margin of osteolysis represents the advancing front of the process, which characteristically begins at the end of a bone with the exception of the tibia, where it may start at the tibial tuberosity. Eventually, the margin extends over a large area. If not recognized as such, early pagetoid bone can simulate a lytic tumor. MRI is very useful as a second modality because the involved bone does not show findings typical of tumor. Various MRI appearances have been described in part reflecting the phasic nature of the disease, but often the marrow shows some retained fat signal and/or mild diffuse edema. Bone scan is especially helpful for establishing the diagnosis because involved bone shows intense, geographic uptake of radiotracer along an entire bone or an extensive portion of the bone.

In the healing, or reparative, phase, bone is laid down appositionally (i.e., along the cortex) and within the medullary cavity, causing the bone to appear denser and forming the characteristic hallmarks of Paget disease: cortical thickening, trabecular coarsening, and an appearance of bone expansion. In its softened state, the deformities of Paget disease occur in affected bones owing to stresses from weight-bearing. This includes protrusio acetabuli and bowing of long bones, with a “shepherd’s crook deformity” of the proximal femur. Deformity at joints can cause osteoarthritis, and expansion of bone can result in narrowing of vascular and neural foramina.

Late involvement of Paget disease is characteristic on radiographs, with the hallmarks as above. However, in unclear cases, CT is useful to confirm the presence of cortical thickening and fat density in the marrow. Bone scan is quite specific, with geographic uptake as previously discussed. MRI often shows some fat in the underlying marrow. Secondary tumors can occur, and any focal lytic areas, cortical destruction, or soft tissue mass associated with pagetoid bone should be pursued (Fig. 6-15). Sarcomas, including osteosarcomas, chondrosarcomas, and fibrosarcomas can occur and are very aggressive with a poor prognosis. Giant cell tumors can also occur and appear very similar, but usually without a significant soft tissue mass. Biopsy is needed to document histology of suspicious areas.

Figure 6-15 Lytic area in pagetoid bone—secondary sarcoma (osteosarcoma, fibrosarcoma, or chondrosarcoma) until proven otherwise. Giant cell tumors can also occur and present as a lytic lesion, as in this case.

Sclerosing Bone Dysplasias

Osteopoikilosis, osteopathia striata, and melorheostosis are sclerosing bone dysplasias, which are benign conditions resulting in areas of bone formation. This dysplasia occurs either within the medullary cavity, as with osteopoikilosis and osteopathia striata, or along the cortex and adjacent soft tissues, as with melorheostosis. Osteopoikilosis is the one most often confused with tumor. In this condition, numerous small foci of sclerotic bone representing bone islands are seen in the epiphyses and apophyses. The correct diagnosis is usually suggested by the fact that this distribution is the opposite of typical metastatic disease, which usually spares the growth centers. Osteopathia striata (Voorhaave disease) has a linear pattern of medullary sclerosis and is not usually confused with malignancy. In melorheostosis (Fig. 6-16), the bone formation is along the cortex and/or adjacent soft tissues (dripping wax pattern) in a sclerotomal distribution along the neural supply of the affected bones. Because of this, multiple bones may be involved along the nerve distribution. These dysplasias can also appear together in mixed patterns.

Figure 6-16 Melorheostosis with characteristic “dripping wax” pattern of sclerosis.

Sarcoidosis

Sarcoid is most common in the middle and distal phalanges of the hands and feet but can involve any bone. The classic lacy destruction and lack of periosteal reaction are usually recognized in the phalanges, but in other bones the pattern may mimic an aggressive neoplasm. The bone lesions are usually painful. When seen in young adults, these lacy lesions should prompt correlation with history or chest radiographs. If imaged with MRI alone, the findings may not appear characteristic, and the lesion can be misinterpreted as an aggressive one (Fig. 6-17).

Figure 6-17 Sarcoid can affect any bone and may require biopsy even with the appropriate history or corresponding pulmonary findings. The pathologist should be alerted to the possibility of sarcoid of bone, and an adequate specimen should be obtained to evaluate for noncaseating granulomas that are characteristic of the disease.

Pseudolesion/Red Marrow

Areas of normally sparce trabeculae can simulate a lytic lesion on radiographs and sometimes on CT (Fig. 6-18). Common locations are the greater tuberosity of the proximal humerus, the proximal femur (called Ward triangle), and the body of the calcaneus. If unclear, MRI can confirm the presence of fat or hematopoietic marrow within these regions.

Figure 6-18 Humeral pseudolesion. Relative lack of trabeculation and projection results in focal lucency of the greater tuberosity. This is also common at the proximal femur and the calcaneal body.

On MRI, hematopoietic marrow is usually overlooked except when it is perceived on images from a certain sequence (e.g., STIR), when it is in an atypical location (as in the proximal radius), or when it is seen in older persons with heterogeneous replacement with fatty marrow. The key to recognizing hematopoietic marrow is signal and location.

Figure 6-19 Normal red and yellow marrow distribution in the pelvis and hips of an adult.

Figure 6-20 Breast metastases with diffuse marrow involvement.

Figure 6-21 Principle for use of in-phase and out-of-phase imaging for differentiation of red marrow from tumor.

Figure 6-22 Marrow in sickle cell disease. Severe anemias can result in red marrow hyperplasia with prominent distribution, lower T1 signal due to higher cellularity, and persistence or repopulation of epiphyses and apophyses. Multiple transfusions can also result in hemosiderin deposition in the marrow and lower signal on all sequences.

Figure 6-23 Hematopoietic marrow and appearance in adults.

Figure 6-24 Metastatic neuroblastoma in a child. The ossified portion of the epiphysis should always be composed of fatty marrow, the exception being the humeral head and occasionally the femoral head, both of which can have a strip of red marrow in the subchondral bone even in adulthood.

BOX 6-1 DIFFERENTIAL DIAGNOSIS: PROMINENT HEMATOPOIETIC MARROW

Young age

Obesity

Female

Smoker

Anemia

Sickle cell disease

Thalassemia

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