1. After a lesion has been detected, distinguished from a normal variant, and categorized as pathological, a reasonable differential diagnosis of three most likely possibilities should be offered. In many cases, the lesion can only be classified as ‘probably benign’ or ‘probably malignant.’ If a lesion is judged by the examiner on the basis of his or her experience as unequivocally benign, this should be stated as such to avoid unnecessary biopsy or surgical therapy.
   
2. The location of the lesion should be described to help plan the safest approach for biopsy or surgical excision. Depending on the presumptive nature of the lesion (benign versus malignant), either biopsy or primary excision should be considered in consultation with the surgeon. The radiologist should be conversant with the staging of primary bone tumors and with the imaging modalities most suitable for staging the individual case. A biopsy should be obtained only after a thorough imaging evaluation. It should be remembered that an open biopsy alters the MRI signal. Therefore, definitive diagnosis in patients who have had biopsies becomes more difficult.
   
3. The radiologist should know the imaging modality suitable for monitoring any therapy and be familiar with the practical intervals of follow-up examinations.
   
4. A correct diagnosis and rational therapeutic strategy for primary bone tumors can only be accomplished by the close cooperation of the radiologist, the surgeon, and the pathologist.

All imaging methods play a role in diagnosing and staging primary and secondary bone tumors (metastases).

After radiographic or scintigraphic detection of an osseous lesion that could be a tumor, its radiographic features should be analyzed. These include:

• type of destruction,
  
• margin of the lesion,
  
• cortical changes,
  
• periosteal reaction,
  
• soft-tissue infiltration or mass.

This analysis generally determines the biologic activity (inactive, active, aggressive). This information coupled with the type of matrix production can often provide a definitive diagnosis.

The following lesions should be recognized and distinguished from other conditions:

• Inactive and benign ‘leave-me-alone’ lesions not requiring any therapy. Typical examples are bone infarcts, non ossifying fibromas, and bone islands.
  
• Bone lesions highly likely to be benign, which do not need immediate histologic evaluation and can be observed. Examples are fibrous dysplasia and post-traumatic myositis ossificans. Histologic confirmation is needed in individual cases only if an aggressive clinical course ensues after the lesion is discovered.
  
• Lesions that are probably benign and are unresectable for anatomic reasons regardless of the histologic finding. Examples are enchondromas and osteochondromas.
  
• All lesions of undetermined biologic activity or categorized as aggressive (perhaps malignant). These lesions must be biopsied after further diagnostic imaging and staging. Going straight to surgical resection is justified only if malignancy could be excluded by imaging.

Analysis of unknown skeletal lesions using the following ten determinants should lead to a definitive diagnosis, suggest a presumptive diagnosis or, at least, offer a limited and reasonable differential diagnosis.

1. Age of the patient: Many tumors have a typical age distribution. This applies to Ewing sarcoma (childhood and adolescence), aneurysmal bone cyst (adolescence and young adulthood), osteosarcoma (childhood to young adulthood), and several sarcomas, such as chondrosarcoma and malignant fibrous histiocytoma (after the age of 30 years). Metastases and plasmocytomas usually do not occur before the fourth decade, with the notable exception of breast cancer metastases, which can occur at a younger age.
   
2. Soft-tissue involvement: Cortical destruction with tumor extension into the soft tissue generally indicates a more aggressive growth and suggests a malignant lesion.
   
   

   Caution: Aneurysmal bone cyst and eosinophilic granuloma are notable exceptions. Lesions with pathologic fractures may also present diagnostic problems.

   
   
   

   A primary soft-tissue tumor is best demonstrated by MRI. Except for very aggressively infiltrating tumors, soft-tissue tumors respect the fascias for quite some time (in contrast to soft-tissue infection).

   
   
3. Growth pattern: Analyzing the bone lesion (pattern of bone destruction, cortical involvement, periosteal reaction, etc.) usually allows categorization into three groups of biologic activity:
   
   

   a) slow growth (‘inactive’),

   
   

   b) intermediate growth (‘active’),

   
   

   c) fast growth (‘aggressive’).

   
   
4. Size of the lesion: The size of the lesion coupled with the pattern of bone destruction frequently reveals additional information about the biologic nature of the lesion. Large lesions with cortical destruction and little periosteal reaction should, for all intents and purposes, be assumed to be malignant.
   
5. Location of the lesion: Some tumors commonly involve particular bones; for example the adamantinoma almost exclusively occurs in the tibia. Other lesions occur predominately in a preferred location in a tubular bone; for example chondroblastoma, is always an epiphyseal tumor. Some tumors occur more frequently in the axial than in the appendicular skeleton. Furthermore, the location within the bone (central versus eccentric, epiphyseal versus diaphyseal) can suggest the diagnosis. This will be discussed in more detail in the appropriate sections.
   
6. Zone of transition: The transition from abnormal, pathologic bone to normal bone provides an additional indication of the nature of the lesion. A wide and indistinct zone of transition invariably indicates an aggressive and rapidly growing lesion, while a narrow zone of transition, in particular one with a sclerotic rim, can be assumed to be slow growing.
   
7. Margin of the lesion: Though the margin is included in the preceding rule (6, Zone of transition), it can be seen as a different entity. Despite a very thin and well-demarcated zone of transition, a lesion can still be malignant or aggressive. This is seen in plasmocytomas and giant cell tumors.
   
8. Tumor matrix: A categorization of bone and cartilage-forming tumors is possible by analyzing the visible tumor matrix. Furthermore, MRI can distinguish between myxoid substances and water-containing components (cysts).
   
9. Host response: The response of the host bone to the tumor is reflected by cortical reaction (cortical thickening, formation of a neocortex, destruction, infiltration) and by periosteal reaction.
   
10. Monostotic, oligostotic, or polyostotic lesions: Benign polyostotic lesions may include fibrous dysplasia, Paget disease, eosinophilic granuloma, and enchondromas. Malignant polyostotic lesions include metastases, plasmocytoma, and lymphoma.

The Enneking method is the generally accepted staging systems for primary bone tumors, especially malignant tumors.

This method is based on the histologic grading of the tumor (benign, low-grade malignant, high-grade malignant), its anatomic extent (mostly as determined by imaging), and the presence of metastases (in the skeleton or, above all, in the lung). These three factors are combined to plan the treatment strategy for a particular bone or soft-tissue tumor. The major role of the imager is to determine the local extent of the tumor and to search for skeletal metastases by scintigraphy and pulmonary metastases by chest CT.

A distinction should also be made between the intra- and extracompartmental locations of the tumor.

Intracompartmental lesions are defined as follows:

• All lesions confined to the subcutaneous fat (soft-tissue tumors).
  
• All lesions confined to the parosteal soft tissues. These tumors displace the muscles without infiltrating either muscle or osseous cortex.
  
• All bone tumors that are intracortical, i.e., the cortex or a surrounding neocortex is still visible.
  
• All soft-tissue tumors confined to a muscle compartment. The fascial planes enclosing these compartments are not violated. Examples of recognized muscle compartments are the posterior compartment of the calf, the anterior compartment of the calf, and the dorsal compartment of the forearm.

Extracompartmental lesions are defined as follows:

All tumors that violate any of the above-mentioned compartments or that abut or invade major neurovascular bundles. In addition, tumors are considered primary extracompartmental if located at a site without natural barriers.

These anatomic sites include mid-hand, midfoot, hind foot, popliteal fossa, femoral triangle, and axilla. Any tumor (bone or soft-tissue tumor) with articular extension is also considered extracompartmental.

Radiography remains in the forefront of detecting skeletal lesions. Furthermore, it is the primary imaging modality to suggest the tissue diagnosis and to judge the biologic nature of tumorous lesions. For tumorlike or benign lesions, it can determine their extent.

Tc 99 m diphosphonate scintigraphy of the skeleton is used primarily to establish multifocality such as that seen with osseous metastases, and to monitor osseous lesions following therapy. Only a few entities, such as Paget disease and osteoid osteoma, exhibit a diagnostic pattern of bone uptake. The intensity of uptake within a lesion is not a reliable differentiating imaging finding.

Although the role of CT for staging malignant tumors has decreased with the growth of MRI, it remains the standard method of evaluating uncertain radiographic and scintigraphic findings in the spine and pelvis. Some comparison studies could demonstrate that CT has the same accuracy as MRI for staging lesions as intra- versus extracompartmental in location. Because of its sensitivity in detecting calcifications and ossifications, CT is superior to conventional radiography in determining the tumor matrix and can add to the differential diagnostic assessment.

Sonography is an acceptable bedside method for the detection and further evaluation of an undetermined swelling of the peripheral soft tissues, and supplements palpation and inspection. Ultrasonography is also suitable to guide percutaneous biopsies, especially of lesions in the peripheral soft tissues. Color Doppler duplex sonography can also provide differential diagnostic criteria, distinguishing, for instance, a solid tumor from a hematoma.

Angiography has become obsolete for detecting and staging tumors and for offering differential diagnostic information. Even establishing the relationship between the neurovascular compartments and tumors has been taken over by MRI. Angiography still plays a role if embolization is contemplated (e.g., preoperative embolization of metastases or embolization of soft-tissue hemangiomas).

MRI is considered the gold standard for staging malignant and benign tumors. This applies to the entire skeleton, but above all to the extremities. Furthermore, MRI can provide a variety of differential diagnostic criteria by means of the different signal intensities and contrast enhancement. This application has increased significantly in recent years, showing a definite change from the initial verdict that MRI, like scintigraphy, provided only ‘non-specific’ data.

Technical Considerations: Differential diagnostic criteria are furnished by the signal intensities of the T1-weighted and T2-weighted SE sequences. The STIR sequence is a very good screening sequence. After intravenous administration of contrast medium, the Tl-weighted sequences, preferably with fat suppression, generally add useful clues. Depending on the size of the tumor, large body coils or special surface coils, adapted to the anatomy, are applied. MRI has the advantage of multiplanar imaging, providing a comprehensive assessment of the transitional zone between tumor and healthy tissue.

Caution: If a bone tumor is suspected, the MRI findings must be correlated with those from conventional radiography.

The detection of peritumoral edema, within or outside the bone, is a non-specific finding, but can aid in detecting tumors and arriving at a tissue diagnosis:

The most elemental question in staging is whether the lesion is intracompartmental or extracompartmental, and this is determined by MRI in the majority of cases. The multiplanar capability of MRI also makes it the modality of choice for determining the osseous and soft-tissue extent of the tumor and the relationship of the tumor to fascia and adjacent articular structures. Furthermore, MRI can reliably delineate the relationship of the tumor to the major neurovascular compartments.

The intraosseous extent of a lesion is best determined on the T1-weighted SE images. The imaging plane should be determined by the anatomy (e.g., coronal or sagittal planes for tubular bones). The T2-weighted images, especially the so-called turbo SE sequences, are not suitable for determining the osseous extent of the lesion. The administration of contrast medium is only meaningful if the T1-weighted sequences can be combined with fat suppression.

The soft-tissue extent is best assessed on STIR sequences because these sequences achieve a high contrast between tumor, muscle, and fat. The T1-weighted SE sequences, excellent for anatomic detail, are most helpful when obtained with fat suppression and after administration of contrast medium.

When assessing the relationship between the tumor and the adjacent joints as part of the staging, the following questions must be addressed:

• Is the joint involved?
  
• Do the tumor margins abut the joint, producing a sympathetic effusion? Remember, however, that the effusion may not be induced by the tumor itself. A tumor-induced effusion occurs only after direct tumorous invasion of the capsule.
  
• Is the tumor intracapsular?
  
• Is the tumor growth transarticular?

Tumors can extend directly to the subchondral interface, as is the situation with aneurysmal bone cysts, giant cell tumors, or chondroblastoma. This is relevant for planning the surgical approach since the articular surface might not be preserved in many of these cases, and it might be necessary to modify the surgical technique, possibly resorting to an endoprosthesis.

The different therapeutic strategies, primarily surgical, are determined by the tissue diagnosis and the extent of the lesion. Intralesional excision (curettage) is to be distinguished from marginal excision. An additional surgical strategy is the wide excision (4 cm beyond the tumor margin) or radical resection (resection of the tumor, including the entire surrounding musculature and surrounding bone). Malignant bone and soft-tissue tumors generally undergo preoperative and often also postoperative chemotherapy. This is especially true in tumors such as Ewing sarcoma and osteosarcoma. Radiotherapy of primary bone and soft-tissue tumors is less commonly performed today. However, palliative radiation remains effective for certain bone and soft-tissue metastases.

The tumor consists of highly vascularized stroma with osteoid and immature bone.

Severe pain (especially at night), relieved by aspirin (less than 50% of cases).

Age: First through third decade.

Location: The femur (30%) and tibia (25%) are most frequently involved. The lesion is eccentric, frequently intra-cortical (80–90%).

Therapy: Surgical excision (immediate pain relief indicates successful removal). Percutaneous excision or alcohol ablation can be used in selected cases.

The pain is less severe than that experienced with osteoid osteoma.

Location: About 40% of osteoblastomas are in the spine; the rest are found in the tubular bones, skull, and other bones.

Therapy: Curettage.

Relevant findings:

Fig. 3.2 Osteoid osteoma of the tibia with typical fusiform periosteal reaction.

Fig. 3.3 Osteoid osteoma of the distal tibia surrounded by only a minimal reaction.

Fig. 3.4 MRI of osteoid osteoma, T2-weighted images.

a Lesion of relatively low signal intensity corresponding to delicate calcifications not yet visible radiologically.

b Lesion of high signal intensity in the cortex.

Fig. 3.5 Osteoblastoma of the rib. The margin is not completely discernible (→CT).

Fig. 3.6 Osteoblastoma of the vertebral arch.

Synonym: Osteogenic sarcoma

The tumor cells form osteoid. Histologically, subclassifications are made on the basis of the dominating tissue differentiation (osteoblastic, chondro-blastic, fibroblastic, etc.). Numerous variants exist:

• ‘conventional’ osteosarcoma (about 75%, see below),
  
• periosteal osteosarcoma (see below),
  
• parosteal osteosarcoma (see below),
  
• telangiectatic osteosarcoma (highly malignant, purely lytic osteosarcoma),
  
• ‘low-grade’ osteosarcoma (prognostically favorable, slow-growing osteosarcoma),
  
• osteosarcoma of older patients (above 60 years of age, e.g., associated with Paget disease, post-radiotherapy),
  
• soft-tissue osteosarcoma (beginning after the age of 40 years).

Slowly worsening local pain.

Age: Two incidence peaks: age 10–25 years and age 60–80 years, but can occur at any age.

Location: The tumor can arise in any bone but over 80% occur in the long tubular bones (femur, tibia) and involve the metaphysis in the majority of cases.

Prognosis and therapy: The five-year survival rate depends on the type of tumor and on the time of the diagnosis, ranging between 30 and 80%. Preoperative chemotherapy is followed by amputation or wide resection. The surgical approach depends on the local tumor stage, best shown by MRI, and on the presence of metastases shown by bone scintigraphy and chest CT.

The radiographic findings are variable.

For left:

Fig. 3.8 Predominately osteoblastic osteosarcoma.

Near left:

Fig. 3.9 MRI of an osteosarcoma.

Fig. 3.10

a Parosteal osteosarcoma (frame from an angiographic series).

b Local soft-tissue metastasis after tumor excision and insertion of a prosthesis.

Synonym: Cartilaginous exostosis

The cartilaginous center ossifies with the outer layer, remaining as a non-ossified layer of cartilage of varying thickness forming a cartilaginous cap. Because of its self-limiting growth, it is more appropriately characterized as a tumorlike lesion.

No pain, usually an incidental finding, unless there is mechanical pressure on a neurovascular bundle or formation of a ‘pseudobursa’.

Age: First to third decade of life.

Location: Metaphyseal region of the tubular bones.

Therapy: None, or simple excision, depending on clinical symptoms and location.

Fig. 3.14 Osteochondroma of the cervical spine. The point of origin of the tumor can no longer be determined. Coarsened trabecular pattern, stippled calcifications, and slow expansile growth permit the diagnosis.

Fig. 3.15 Parosteal osteoma. It can be differentiated from an osteochondroma by the underlying cortex. The fatty marrow within the internal tumor space is noteworthy (MRI:T1-weighted image).

Synonym: Chondroma

The tumor consists of mature cartilage. A distinction can be made between the central enchondroma and the eccentrically growing enchondroma with cortical destruction and formation of a ‘subperiosteal enchondroma’.

No pain (a feature distinguishing it from chondrosarcoma).

Age: Usually discovered before age 40 years.

Location: All bones with enchondral ossification can be affected. The tumor has a predilection for the tubular bones of the hands and feet. In the long bones, the enchondroma is characteristically located in the metadiaphyseal region.

Therapy: Lesions of the tubular bones should be left alone. Curettage should pe performed only if the lesion is painful or if it is located in the axial skeleton.

Synonym: Codman tumor

Benign tumor consisting of chondroblasts and numerous giant cells.

Mild, increasing pain. Possible joint effusion.

Age: About 75% of cases occur between 10 and 25 years of age.

Location: All bones with enchondral calcification can be affected (especially the humerus). Characteristically, the lesion is centrally located within the epiphysis and may have metaphyseal extension.

Therapy: Curettage. There is a recurrence rate of 15%.

Fig. 3.18 Periosteal chondroma. This eccentric lobulated tumor has a thick sclerotic rim which is somewhat atypical.

Fig. 3.19 Enchondroma. The differentiation from a cyst on MRI can be difficult. Conventional radiography provides the definitive findings of calcifications and absent marginal sclerosis.

Fig. 3.20 Chondroblastoma. Classic location and thick sclerotic rim.

Fig. 3.21 Chondroblastoma of the posterior vertebral arch with intralesional calcification (axial CT).

This is a very rare benign cartilaginous tumor, characterized by an abundance of myxoid or chondroid intracellular substance. It occurs almost exclusively in the proximal tibia and usually presents radiographically as a sharply demarcated solitary radiolucency that rarely calcifies.