4 Tumors and Tumorlike Lesions of Bone, Joints, and the Soft Tissues Primary bone tumors are very rare (1% of all neoplasms) unlike metastases or hematologic malignancies. Plasmacytomas and malignant lymphomas belong to this latter group (see Chapter 5.5). Tumorlike lesions are invariably covered with primary bone tumors, as in this book, but differ fundamentally from primary bone tumors. They are a heterogeneous group of benign lesions with the possibility of spontaneous cessation of growth or even regression. In addition, these lesions do not have the potential to metastasize. Even inflammatory (e.g., osteomyelitis, enthesopathies) or degenerative conditions (e.g., intraosseous ganglia) are capable of mimicking tumors. Important criteria for the evaluation and differential diagnosis of bone tumors are location in the skeleton (e.g., appendicular versus axial skeleton) and in the bone (epiphyseal, metaphyseal, diaphyseal; central, eccentric; intracortical or juxtacortical) as well as the patient’s age (peak age in childhood and adolescence and in late adulthood). There is rarely a significant gender prevalence. Most entities can also arise as rare variants located at intracortical, periosteal, parosteal, or extraosseous sites ( Fig. 4.1). A distinction is made between bone tumors and soft tissue tumors (see Chapter 4.5). • Bone island/osteoma. • Nonossifying fibroma (fibrous metaphyseal cortical defect). • Periosteal desmoid. • Simple (“juvenile/unicameral”) bone cyst. • Aneurysmal bone cyst (primary aneurysmal bone cysts are nowadays considered to be benign bone tumors). • Eosinophilic granuloma (solitary form of Langerhans cell histiocytosis). • Fibrous and osteofibrous dysplasia. • Heterotopic ossification (see Chapter 11.5.2). • Intraosseous ganglion. • Epidermoid. • Giant-cell reparative granuloma. • Brown tumor (of hyperparathyroidism). Note Tumorlike lesions, unlike primary bone tumors, are relatively common. The majority are incidental findings of the 1st to 3rd decades of life. Often tumorlike lesions do not require treatment (“leave-me-alone” or “do-not-touch” lesions) and should be confidently diagnosed radiographically. Here the radiologist has a decisive contribution to make toward avoiding unnecessary biopsy/surgery. The overview presented in Table 4.1 is based on the WHO Classification and deliberately omits rare conditions (for which the reader is referred to the specialized literature). The basic principle of the classification of primary bone tumors is based on the type of matrix production. However, this principle is not applicable to a large number of tumors, so the tumor origin should also be included. The matrix is the intercellular substance produced by mesenchymal cells and includes osteoid (osteogenic), chondroid (chondrogenic), and myxoid ground substance, and (fibrous) collagen fibers. 1. Once a lesion has been recognized as being pathological and has been distinguished from a normal variant, an attempt should be made to interpret and correctly diagnose it. A reasonable differential diagnosis should be proposed comprising, where possible, a maximum of three diagnoses. In some cases it will only be realistic to make a distinction between “probably benign” and “probably malignant.” Providing a synopsis of the results of all the imaging techniques (scintigraphy, PET, MRI, etc.) lies in the hands (and eyes!) of the radiologist. 2. The site for a biopsy should be indicated that ensures the most representative tissue is obtained. The radiologist must be familiar with the principles of staging primary bone tumors to be able to recommend the appropriate imaging modalities. In particular, it should be ensured that a biopsy is not taken until all the imaging studies have been performed. The trauma from a needle or open biopsy will alter signal intensity on MRI, which can distort the apparent size of the lesion. 3. The radiologist must know which imaging modalities should be appropriately utilized for monitoring treatment and subsequent follow-up. Matrix components should be taken into consideration (e.g., calcium or bone: radiography and CT; cysts or fluid levels: MRI). 4. With close cooperation, only the trio of surgeon/pathologist/radiologist is capable of establishing the correct diagnosis and drawing up a rational therapeutic strategy for primary bone tumors. Regular multidisciplinary team (MDT) conferences are an absolute prerequisite. In many cases it will already be possible to deduce the (differential) diagnosis, speed of growth of a lesion (growth rate) and benign or malignant nature of the tumor, as well as the nature of a disorder (systemic disease, circumscribed lesion) from the radiographs. The basic steps of radiological assessment of a bony abnormality are encompassed by the “five Ds”: • Detect. • Describe. • Discuss. • Differential diagnosis. • Diagnosis. Based on the “five Ds,” basic questions should be addressed after taking the radiographic, CT, MRI, scintigraphic, etc. findings into consideration.
Overview of tumorlike lesions
The “Five Ds”
Primary bone tumors are very rare (1% of all neoplasms) unlike metastases or hematologic malignancies. Plasmacytomas and malignant lymphomas belong to this latter group (see Chapter 5.5). Tumorlike lesions are invariably covered with primary bone tumors, as in this book, but differ fundamentally from primary bone tumors. They are a heterogeneous group of benign lesions with the possibility of spontaneous cessation of growth or even regression. In addition, these lesions do not have the potential to metastasize. Even inflammatory (e.g., osteomyelitis, enthesopathies) or degenerative conditions (e.g., intraosseous ganglia) are capable of mimicking tumors. Important criteria for the evaluation and differential diagnosis of bone tumors are location in the skeleton (e.g., appendicular versus axial skeleton) and in the bone (epiphyseal, metaphyseal, diaphyseal; central, eccentric; intracortical or juxtacortical) as well as the patient’s age (peak age in childhood and adolescence and in late adulthood). There is rarely a significant gender prevalence. Most entities can also arise as rare variants located at intracortical, periosteal, parosteal, or extraosseous sites ( Fig. 4.1). A distinction is made between bone tumors and soft tissue tumors (see Chapter 4.5).
• Bone island/osteoma.
• Nonossifying fibroma (fibrous metaphyseal cortical defect).
• Periosteal desmoid.
• Simple (“juvenile/unicameral”) bone cyst.
• Aneurysmal bone cyst (primary aneurysmal bone cysts are nowadays considered to be benign bone tumors).
• Eosinophilic granuloma (solitary form of Langerhans cell histiocytosis).
• Fibrous and osteofibrous dysplasia.
• Heterotopic ossification (see Chapter 11.5.2).
• Intraosseous ganglion.
• Giant-cell reparative granuloma.
• Brown tumor (of hyperparathyroidism).
Tumorlike lesions, unlike primary bone tumors, are relatively common. The majority are incidental findings of the 1st to 3rd decades of life. Often tumorlike lesions do not require treatment (“leave-me-alone” or “do-not-touch” lesions) and should be confidently diagnosed radiographically. Here the radiologist has a decisive contribution to make toward avoiding unnecessary biopsy/surgery.
The overview presented in Table 4.1 is based on the WHO Classification and deliberately omits rare conditions (for which the reader is referred to the specialized literature). The basic principle of the classification of primary bone tumors is based on the type of matrix production. However, this principle is not applicable to a large number of tumors, so the tumor origin should also be included. The matrix is the intercellular substance produced by mesenchymal cells and includes osteoid (osteogenic), chondroid (chondrogenic), and myxoid ground substance, and (fibrous) collagen fibers.
1. Once a lesion has been recognized as being pathological and has been distinguished from a normal variant, an attempt should be made to interpret and correctly diagnose it. A reasonable differential diagnosis should be proposed comprising, where possible, a maximum of three diagnoses. In some cases it will only be realistic to make a distinction between “probably benign” and “probably malignant.” Providing a synopsis of the results of all the imaging techniques (scintigraphy, PET, MRI, etc.) lies in the hands (and eyes!) of the radiologist.
2. The site for a biopsy should be indicated that ensures the most representative tissue is obtained. The radiologist must be familiar with the principles of staging primary bone tumors to be able to recommend the appropriate imaging modalities. In particular, it should be ensured that a biopsy is not taken until all the imaging studies have been performed. The trauma from a needle or open biopsy will alter signal intensity on MRI, which can distort the apparent size of the lesion.
3. The radiologist must know which imaging modalities should be appropriately utilized for monitoring treatment and subsequent follow-up. Matrix components should be taken into consideration (e.g., calcium or bone: radiography and CT; cysts or fluid levels: MRI).
4. With close cooperation, only the trio of surgeon/pathologist/radiologist is capable of establishing the correct diagnosis and drawing up a rational therapeutic strategy for primary bone tumors. Regular multidisciplinary team (MDT) conferences are an absolute prerequisite.
In many cases it will already be possible to deduce the (differential) diagnosis, speed of growth of a lesion (growth rate) and benign or malignant nature of the tumor, as well as the nature of a disorder (systemic disease, circumscribed lesion) from the radiographs.
The basic steps of radiological assessment of a bony abnormality are encompassed by the “five Ds”:
• Differential diagnosis.
Based on the “five Ds,” basic questions should be addressed after taking the radiographic, CT, MRI, scintigraphic, etc. findings into consideration.
• Chondromyxoid fibroma
• Chondrosarcoma (note subclassifications)
• Osteoid osteoma
• Osteosarcoma (note subclassification)
Fibrogenic and fibrohistiocytic tumors
• Desmoplastic fibroma
• Benign fibrous histiocytoma
• Malignant fibrous histiocytoma
Ewing’s sarcoma/primitive neuroectodermal tumor
• Ewing’s sarcoma/primitive neuroectodermal tumor
Giant cell tumor
• Giant cell tumor
Detect. Is this a pathologic bony abnormality? In many cases this may be obvious; however, the initial detection of the lesion is often a difficult task. Detecting pathologic structures is ultimately a matter of experience as, over time, the spectrum of what is normal versus abnormal will develop in the radiologist’s mind. At present, this conscious and subconscious ability is still based on conventional radiomorphology in two planes. These always (!) form a mandatory part of primary imaging work-up. Bone lesions involving the cortex are more readily recognized on radiographs than lesions confined to cancellous bone. Loss of bone substance (e.g., osteoporosis) will make detection of subtle osteolytic lesions difficult.
Describe. Any description involves first determining whether the lesion arises in bone, soft tissues, or joints. Where is the finding located with respect to the skeletal system? In a tubular bone? If yes, where exactly (epiphyseal, metaphyseal, diaphyseal; central or eccentric)? Is it a solitary lesion or are there multiple lesions? Focal bone lesions pose their own specific questions: What type of bone lesion is it (lytic, sclerotic, or a mixed lesion)? Are there cortical changes or periosteal new bone formation? Can matrix production be deduced from the radiograph, the CT, or the MRI? Is the surrounding soft tissue involved? A correct answer to these questions is a prerequisite for the other three “D’s.”
Discuss. This step involves the initial evaluation of the questions addressed above. The speed of growth of a lesion (growth rate) may be inferred from the apparent reaction of the host bone to the pathologic lesion as seen on the radiograph. This is an important factor in differentiating between a benign and a malignant lesion.
Differential diagnosis. In order to develop a differential diagnosis, the radiological findings have to be taken into account together with the clinical findings and laboratory results.
The differential diagnosis of a focal bone lesion is based on the overall assessment of the following parameters:
• Tumor matrix (cf. Chapter 4.1.3).
• Growth rate (cf. Chapter 4.1.4).
• Exact location of the lesion ( Fig. 4.1).
• Patient’s age.
• History and clinical findings (above all pain and its duration).
• Laboratory parameters (ESR, CRP, alkaline phosphatase).
Diagnosis. A diagnosis should only be made if either the radiograph is unequivocal or the combination of radiograph, case history, and clinical findings gives grounds for a clear diagnosis (e.g., the diagnosis of a metastasis based on osteolysis in the presence of the simultaneous identification of multiple lesions and a known primary tumor).
The correlation between the histological biopsy result and the radiograph (validity check), in the broadest sense, is part of establishing and signing off the diagnosis before a treatment plan is implemented. If there is a discrepancy between the proposed radiological differential diagnosis and the histological diagnosis, then the case must be reviewed with regard to all the imaging, the histology and the biopsy site. Radiologists and pathologists should not be reluctant to request a second opinion. The histological differentiation of primary bone tumors is often challenging and belongs in the hands of experts and their multidisciplinary colleagues.
Type of Bone Lesion
The radiomorphological description of bone lesions continues to rely primarily on conventional radiographs in two projections. The following patterns are common:
• Solitary radiolucency ( Fig. 4.2a).
• Solitary radiodensity ( Fig. 4.2b).
• Solitary, mixed lesion ( Fig. 4.2c).
• Irregular multiple radiolucencies (moth-eaten pattern; Fig. 4.3a).
• Homogeneous, multiple radiolucencies (“permeative” pattern; Fig. 4.3b).
Border of a Bone Lesion
The border or margin of a lesion within the host bone reflects the relation between destruction and repair in the bone and is an important indicator of growth rate:
• The border of the lesion is sharp or well-defined if the transition between normal and pathologic bone follows a clearly recognizable line (i.e., can be traced with a pencil without hesitation; Fig. 4.4a). A sharply marginated lesion can be partially or completely surrounded by a sclerotic margin.
• The border of the lesion is ill-defined if the zone of transition between normal and pathologic bone is wide and the margin of the lesion is barely recognizable ( Fig. 4.4b). An irregular (jagged, wavy, ridged) border does not indicate that one is dealing with an ill-defined border.
• A bone lesion may, on occasion, show a mixed pattern margin with both well- and ill-defined sections.
Fig. 4.2 Solitary bone lesions. (a) Solitary radiolucency. (b) Solitary radiodensity. (c) Mixed lesion.
Fig. 4.3 Multiple radiolucencies. (a) Multiple irregular radiolucencies (moth-eaten pattern). (b) Multiple homogeneous radiolucencies (“permeative” pattern).
The cortex of a tubular bone is widest in the diaphysis and gradually narrows toward the metaphysis and epiphysis. There is no cortex at the cartilage-covered joint surfaces but only an extremely thin layer of subchondral bone.
• Endosteal cortical thinning: the thinning from “within” may be linear or half-moon shaped. Lobular thinning is often found in the diaphysis (known as scalloping; Fig. 4.5 a).
• Cortical bone destruction (continuity disrupted or not disrupted): the comparison with a wall is suitable for explaining the alterations. “Continuity disrupted” means that there is a greater or lesser “hole” in the cortex ( Fig. 4.5b). “Not disrupted” means that the wall is still “standing” but it is already starting to crumble. This latter form of bone destruction often results in the impression of being “moth-eaten” (known as permeative osteolysis, Fig. 4.5 c).
• Neocortex: The original cortex has been replaced by an outer bony shell. The bone appears “ballooned” ( Fig. 4.5 d).
Stimulation of new bone production by the periosteum is primarily an adaptive process designed to preserve stability of the bone. This becomes particularly clear when periosteal reaction is induced by underlying osteolysis. However, hyperemia, disturbances of circulation of the surrounding soft tissues, or iatrogenic factors (e.g., prostaglandin administration in neonatales) can also stimulate a periosteal reaction.
Periosteal reaction is an extremely important indicator of the biological activity of a lesion. Aggressiveness and duration of the initiating process can be estimated by analyzing the periosteal reaction.
Periosteal reaction is possible in the presence of an intact as well as a disrupted cortex. On the other hand, the periosteal reaction itself can be interrupted. This latter process is an important sign of an aggressive growth pattern.
Ten days is the minimum time before a periosteal reaction becomes radiographically visible: it must first mineralize. The older the patient the longer this takes. Periosteal reaction is absent in the following situations:
• The lesion grows so slowly that it fails to stimulate the periosteum.
• The lesion grows so rapidly that it is unable to develop a periosteal reaction.
• The lesion is very small.
Absence of periosteal reaction must not be misinterpreted as a sign of slow growth of a focal bone lesion.
Solid periosteal reaction. In this case, multiple layers of bone form a strong layer of new bone on a radiologically intact cortex or replace the original cortex (known as neocortex). Solid periosteal reactions may also take on an undulating, nodular, or trabeculated appearance. These are typically a sign of low biological activity ( Fig. 4.6a).
A single lamellar periosteal reaction. A single lamella consists of a discrete sheet of bone and can vary in thickness—the thicker it is, the slower the growth and accordingly the less aggressive the underlying lesion. The transition to solid periosteal reaction is smooth not discrete; a width of 2 mm and more indicates a solid periosteal reaction. The cortical bone may also be destroyed ( Fig. 4.6b). The term “lamella,” however, does not mean that it is always a sharp line. A Codman angle refers to the interrupted pattern involving a single lamella or several lamellae ( Fig. 4.6b). It typically arises at the periphery of the lesion and the cortex is usually destroyed. A Codman angle must be clearly distinguished from a spur or projection of an uninterrupted solid periosteal reaction buttressing the periphery of a benign lesion.
A lamellated periosteal reaction (“onion skin”). This comprises multiple concentric lamellae of bone. It should be recognized that individual parallel lamellae may differ in thickness and—depending on the quality of the radiograph—may be difficult to separate ( Fig. 4.6c). For this reason, differentiation from a solid periosteal reaction is not always easy, but it can be of diagnostic importance. The identification of a lamellated periosteal reaction means that the growth rate of the lesion is ranked between that of a solid periosteal reaction and that of a single lamellar periosteal reaction. Benign entities (e.g., eosinophilic granuloma) should not be fundamentally ruled out.
Spicules. These are linear, parallel new bone formations, perpendicular to the cortex. The cortex is often morphologically intact (yet histologically already infiltrated [ Fig. 4.6d]).
Complex periosteal reactions. This term includes variants of spiculated periosteal reaction with or without a peripheral lamellar component. These may be termed the sunburst or hair-on-end phenomenon. The longitudinal bone densities of varying thickness and length are divergent, i.e., irregular in appearance. Reactive bony alterations can be difficult to distinguish from tumorous bone formation. Randomly organized or extensive periosteal reactions are classified as complex reactions ( Fig. 4.6e).
Fig. 4.5 Cortical changes. (a) Endosteal thinning, scalloping (arrow). (b) Partially interrupted, fine neocortex (arrow). (c) Uninterrupted, permeative cortical destruction. (d) Neocortex, “ballooning” of the bone.
Fig. 4.6 Periosteal reactions. (a) Solid. (b) Laminated plus Codman angles (arrows). (c) Multilamellated (“onion skin”). (d) Spiculated. (e) Complex (also known as sunburst phenomenon).
Assessment of the matrix on the radiograph can be difficult. It is often impossible to decide whether there is any matrix production at all or whether the calcified areas within a lesion represent the remains of the original bone or periosteal new bone seen en face. A CT can help here. A bony tumor matrix develops in one of two ways:
1. Bony tumor matrix is formed by the autonomous production of tumor osteoid by neoplastic cells—a classic process only seen with osteosarcoma, osteoid osteoma, and osteoblastoma.
2. Tumor-induced osteoblasts produce bone matrix that is typical of certain types of bone metastases. Only after mineralization of the tumor osteoid does it become radiographically visible. Because the tumor-stimulated bone production is extremely rapid (e.g., sclerotic metastasis from prostate cancer), the new bone lacks structure and appears amorphous and is less dense than, for example, osteomas.
A bony matrix may only be diagnosed radiographically if extensive areas of consolidation are present ( Fig. 4.7a). These may appear dense and ivorylike or even less dense and cloudy or latticed.
The radiological appearance of bone that has developed from metaplastic new bone formation (bone formation by pluripotential cells) differs from that of “normal” bone. The term ground glass phenomenon is used to describe its opaque appearance on the radiograph ( Fig. 4.7b). Unlike all forms of bony matrix, chondroid matrix displays primarily a focal, stippled, flocculent calcification pattern, resembling dots and “rings and arcs” ( Fig. 4.7c).
Dystrophic calcification, formed by the precipitation of calcium phosphates and carbonates in necrotic or degenerated tissue, has a heterogeneous pattern that can mimic chondroid matrix and metaplastic new bone formation ( Fig. 4.7d).
Assessment of the aggressiveness of a bone lesion, its rate of growth, and its expansion within the bone is a critical contribution of imaging. This is based on a precise description of the bone lesion (see Chapter 4.1.3). Determining growth rate will often form the basis for differentiating between benign and malignant lesions, providing additional support for differential diagnostic criteria. This applies primarily to bone tumors and tumorlike lesions, but also to inflammatory conditions. Determination of the growth rate from the radiograph also aids the histological assessment of the bony process.
This is based on the classification system proposed by Lodwick that describes the bone destruction pattern visible on radiographs ( Fig. 4.8).
This classification system has two disadvantages, however: on the one hand, it is restricted to osteolytic lesions; on the other, grading into five groups is somewhat laborious for everyday clinical practice.
The following simplified classification may be of assistance for those less experienced in arranging the radiographic patterns into different categories and preparing the way for further diagnostic steps:
• Stage I: Osteolytic lesion with a circumscribed, sharply defined margin; nonaggressive, slow-growing, or even stationary growth (“latent”; Fig. 4.9a).
• Stage II: Osteolytic lesion still demarcated in every direction but with an ill-defined margin; intermediate growth or intermediate rate of expansion (“active”; Fig. 4.9b).
• Stage III: Moth-eaten or permeative pattern of bone destruction; aggressive growth, rapidly expanding lesion (“aggressive”; Fig. 4.9c).
An aggressive growth pattern, Stage III, is a typical feature of malignancy but can also be seen in acute osteomyelitis. Similarly, it is also possible for a metastasis to be surrounded by a sclerotic margin and thereby be classified as Stage I.
One insight gained from advances in diagnostic and molecular imaging techniques is the fact that reality, as seen on radiographs, is relative. One must always bear in mind that it is primarily a question of developing an overview of the pathophysiological processes that are taking place. As the American pathologist, James Ewing, postulated, it is necessary to grasp the “concept” of the disease.
Fig. 4.7 Matrix production. (a) Bony matrix. (b) Ground glass phenomenon of metaplastic bone matrix. (c) Chondroid matrix with typical calcifications. (d) Dystrophic calcification.
Fig. 4.9 Radiological morphology of osteolytic lesions: simple 3-stage assessment of growth rate. (a) Latent. (b) Active. (c) Aggressive.
• Solitary density.
• Well-defined border and marginal sclerosis.
• Only endosteal alteration of the cortical bone.
• Solid periosteal reaction.
Signs of an aggressive growth pattern on the radiograph or CT
• Moth-eaten pattern or permeative pattern.
• Ill-defined border.
• Cortical destruction.
• Spicules, lamellated, or complex periosteal reaction.
• Soft tissue infiltration.
Contemporary staging systems for primary bone tumors, in particular the malignant forms, are based on the UICC (Union for International Cancer Control) TNM Staging System in conjunction with histological grading ( Tables W4.1–W4.3). Apart from detecting metastases on bone scintigraphy and chest CT, it is particularly important for the radiologist to determine the extent of the primary tumor with MRI. The TNM classification of primary bone tumors defines T1 as a tumor of 8 cm or less in the greatest dimension, with T2 defined as a tumor of more than 8 cm in the greatest dimension. T3 is defined as a discontinuous tumor in the primary bone site (“skip metastasis”). The classification according to Enneking has established itself in the clinical surgical disciplines, taking into account above all the anatomical site, metastases, and histological grading (see specialized literature).
4.1.6 Imaging Modalities for Tissue Diagnosis, Assessment of Biological Activity and Staging of Bone Tumors
Radiography. Radiography remains the primary imaging modality for diagnosing suspicious lesions. Given appropriate image quality, matrix calcification and ossification are usually easy to assess. The image is capable of displaying sometimes subtle changes such as bony destruction and periosteal reactions. An incidental finding on imaging, thought to be benign, will also require a radiograph as a baseline study for comparison with follow-up reviews (an enchondroma does not necessarily need to be followed up by MRI!).
NUC MED. Technetium Tc 99 m diphosphonate bone scintigraphy is used for detecting multifocal involvement, for demonstrating metastases in malignant bone tumors, and for follow-up reviews of (chemo) therapy. Only in exceptional cases, such as Paget’s disease and osteoid osteoma, does the bone scan display a diagnostic pattern of radionuclide uptake.
Fluorine–18 fluorodeoxyglucose PET (18F–FDG–PET; also used as hybrid imaging together with CT and MRI) is gradually gaining favor over bone scintigraphy as a sensitive modality for the evaluation of primary bone tumors. T-, N-, and M-stages can be assessed in a single study However, CT is still indispensable for detecting lung metastases (e.g., secondary to osteosarcoma). One benefit of PET is in the detection of local tumor recurrence, particularly if metal implants adversely affect assessment by other modalities (such as CT und MRI). Individual reports are available in the literature showing that PET may be utilized for monitoring tumor response to chemotherapy. Initial hopes that the differentiation between malignant and benign bone tumors could be improved with the aid of PET imaging have been disappointed.
CT. After the initial uncritical enthusiasm for MRI, CT has to an extent regained importance for staging purposes, in particular for those malignant tumors arising in complex anatomical areas such as the spine, pelvis, and shoulder. It also remains a good modality for assessing unclear radiographic and scintigraphic findings in terms of detection of lesions and differential diagnosis. Its greatest value lies in a subtle assessment of calcifications and ossifications. It demonstrates the presence and nature of any tumor matrix better than radiographs and certainly better than MRI. More recent CT-based developments, such as CAD (computerassisted diagnostics), provide valuable additional information for detecting pulmonary nodules, 3D reconstructions of tumors, and computer-aided surgery.
US. This modality is ideally suited at the bedside as a supplement to clinical examination of suspected soft tissue masses. It can improve the diagnostic yield of image-guided percutaneous biopsy and, utilizing the color-coded duplex function, it is suitable for simple differential diagnoses, such as “tumor versus hematoma.”
MRI. MRI is currently regarded as the gold standard for staging malignant tumors. This applies to the entire skeleton, but particularly the extremities. MRI also aids differential diagnosis by assessment of the different signal and contrast enhancement patterns as well as morphological features such as fluid–fluid levels.
Technique. As with all other clinical issues, differential diagnostic criteria are based on the signal pattern of T1W and water-sensitive sequences. The latter comprises “intermediate” (long TR and TE of 35–45 ms) T2W (TE > 70 ms) sequences, typically combined with fat saturation. Intravenous contrast administration together with T1W sequence (fat-suppressed) can be helpful in the work-up of bone tumors.
MRI confirmation of peritumoral edema within the bone or adjacent soft tissues is a nonspecific sign:
• Peritumoral edema can be seen with both malignant and benign tumors. Florid edema is typical of benign tumors such as osteoid osteoma and chondroblastoma.
• Edema is also found in with infection and trauma, and, to a lesser extent, around acute medullary infarction.
• It should be stressed that the peritumoral edema around malignant tumors may contain microscopic nests of tumor cells and so this zone should be included in any measurements of tumor extent when determining resection margins.
Monitoring. MRI is useful for assessing tumor response to chemotherapy. Simple measurement of size reduction is helpful in Ewing’s sarcoma but not in osteosarcoma. Signal reduction of the lesion on water-sensitive sequences is an indicator for increasing ossification and/or increased proportion of fibrous tissue. If there is no increase in signal intensity within the lesion after IV contrast administration, then tumor necrosis may be inferred. Dynamic contrast medium examinations (observation of the increased signal intensity of a volume or a layer over predefined time intervals) have been successfully employed for distinguishing viable tumor tissue from the surrounding reactive tissue. More recent modalities, such as DWI and MR spectroscopy, may be useful additions, but are still the object of research and clinical studies (see specialized literature).
MRI must always be assessed together with the radiograph and, if available, CT if a bone tumor is suspected! Matrix calcifications and matrix ossifications are difficult to differentiate by MRI. Instead, lipogenic, chondrogenic, and cystic structures are often indicative. Changes of signal intensity from pathologic fractures and biopsies as well as technical imaging artifacts should always be considered.
The common feature of all osteogenic tumors is their production of bone matrix. Radiologically, the picture is commonly characterized by bone destruction and osteolysis.
An osteoid osteoma is a benign, bone-forming tumor. It is characterized by its small size (less than 1.5 cm) and slow growth. Perifocal sclerosis and edema are reactive and not part of the tumor itself.
Pathology. The tumor comprises a small focus (the nidus) of highly vascularized fibrous tissue within an area of new bone formation surrounded by osteoblasts ( Fig. 4.10).
Clinical presentation. Patients report slowly increasing severe pain (especially at night). Acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs are effective for symptomatic relief. Systemic signs of inflammation, unlike acute osteomyelitis, are not present.
Age: First to third decades of life; males are more frequently affected than females. Location: Femur (30% of cases) and tibia (25%) are the most commonly affected. The location of the lesion is metadiaphyseal, eccentric, and commonly intracortical (80–90% of cases). Treatment: Therapy of choice is percutaneous radiofrequency or laser ablation.
Clinically, juxta-articular, intracapsular osteoid osteomas present symptoms mimicking arthritis with joint effusion and reactive synovitis. In the spine, osteoid osteomas can present with a painful scoliosis, unlike adolescent idiopathic scoliosis which is typically painless.
Radiography. The tumor produces focal osteolysis (nidus), surrounded by a varying degree of sclerosis. Once the osteoid formed by the tumor has mineralized, a punctate area of increased density develops within the nidus. This ossification and the surrounding sclerosis may obscure the focal lucency on the radiographs.
Site of the nidus
• Intracortical location of the nidus results in a strong, solid periosteal reaction ( Fig. 4.11) with an area of eccentric or fusiform sclerosis. Multiple or longitudinal nidi have been described but are rare.
• With a medullary location of the nidus (e.g., within the skeleton of the hand or foot), there is usually less marked sclerosis or even a local radiolucency ( Fig. 4.12). The nidus itself is commonly demarcated as a sclerotic lesion.
• An osteoid osteoma of the spine is most commonly located posteriorly in the neural arch or in the pars interarticularis ( Fig. 4.13).
• With an intra-articular location of the nidus, there is usually a relatively discrete, subarticular, round to ovoid radiolucency with only a minor sclerotic response. This is due to the absence of overlying periosteum at these sites.
NUC MED. The double-density sign with higher activity in the center and lower activity toward the periphery is typical.
CT. CT is the modality of choice when trying to identify this tumor ( Fig. 4.14; also Fig. 4.11) by its ability to detect the nidus, even with a nidus size of less than 3 mm. It is also the technique of choice when treating these cases with image-guided radiofrequency ablation.
MRI. The nidus is hypointense on T1W, but of varying signal intensity on T2W sequences (regardless of the extent of the osteosclerosis). Strong central contrast enhancement is evident.
An osteoid osteoma can appear very “aggressive” on MRI due to the strong perifocal edema in bone and soft tissues. Unlike with malignant bone marrow infiltration, fatty marrow is still preserved in the immediate vicinity of the osteoid osteoma.
DD. Brodie abscess. This displays a variable enhancement pattern.
Stress fracture. A spinal stress fracture is a differential diagnosis. Commonly only a CT allows a definite differentiation between nidus and fracture line.
Glomus tumor. A possible differential diagnosis is glomus tumor of the nail tuft.
Fig. 4.10 Osteoid osteoma. Micro-CT with a resolution of ~ 20 µm clearly shows the radially arranged, mineralized structure of the nidus, surrounded by rarefaction of structure (osteolysis) and the typical sclerosis.
Fig. 4.11 Osteoid osteoma of the distal femur. (a) Solid periosteal reaction; the nidus is recognizable as a focal lucency. (b) Characteristic image: nidus with surrounding sclerosis.
Fig. 4.14 Osteoid osteoma. (a) A calcified nidus (arrow) is evident on CT. (b) The nidus (arrow) is barely visible on MRI.
Fig. 4.13 Osteoid osteoma of the spine. (a) The nidus is hyperintense on the T2W image; typical periarticular location. (b) On the radiograph only a nonspecific density is recognizable at the facet joint.
An osteoblastoma is a rare, benign, bone-forming tumor, histologically similar to osteoid osteoma (known as the big brother of osteoid osteoma, accordingly larger than 1.5 cm).
Location: More than 40% of cases are found in the spine, particularly thoracic and mostly posteriorly located. All other bones may potentially be affected.
Age: 1st to 5th decades of life.
Radiography. Osteoblastomas lead to osteolysis ( Fig. 4.15), but do not always have a sclerotic margin. Expansion of the bone occurs with preservation of a fine external bone lamella. Intralesional ossifications are recognizable in just over one-half of cases ( Figs. 4.16 and 4.17).
CT/MRI. Unlike osteoid osteoma, there is no discrete nidus. Signal intensity on T2W images depends strongly on the degree of matrix structure and is usually hypointense on T1W sequences. Perifocal bone marrow edema of varying degrees is evident in the surrounding bone and soft tissue.
DD. Aneurysmal bone cysts. Problem: Osteoblastomas may be associated with cystic components and secondary aneurysmal bone cyst formation that can make differentiation difficult.
Osteoblastic, slowly growing osteosarcomas. CT is essential for demonstrating integrity of the cortex or the external bony shell and assessing the proximity of the lesion to important structures such as the spinal cord and nerve roots in the spine.
Fig. 4.15 Periosteal osteoblastoma. (a) Saucer-shaped cortical lysis. (b) The MRI shows the periosteal location.
Fig. 4.16 Osteoblastoma. (a) Focal increased activity on the bone scan (late phase). (b) Sharply defined osteolytic lesion with matrix ossification.
Fig. 4.17 Osteoblastoma. (a) Focal lytic lesion in the talar neck with marginal sclerosis. (b) Perifocal bone marrow edema and reactive joint effusion on MRI. (c) Focal lysis with clear marginal sclerosis and central matrix ossifications, similar to a nidus on CT.
Osteosarcoma is the most common primary malignant bone tumor, accounting for 40% of cases. The tumor has an intramedullary growth pattern and produces osteoid, albeit sometimes in only small amounts. There are numerous histological subtypes that vary from low grade to high grade.
Pathology. Osteosarcomas are anaplastic, pleomorphic tumors with a complex variety of tumor cells (spindle cells, clear cells, epithelioid cells, round cells, etc.). The identification of malignant osteoid is the unifying feature. The tumor cells may also produce cartilage and fibrous matrix. This leads to further histological subtyping, such as osteoblastic, chondroblastic, or fibroblastic osteosarcoma and other variants.
Clinical presentation. Patients present clinically with pain increasing over weeks and months associated with local swelling. An unrelated minor injury is not uncommonly the reason for initial diagnostic investigations.
Age: About 60% of patients are under the age of 25 years. Location: This tumor can affect any bone. More than 80% of osteosarcomas develop in the metaphyses of the long tubular bones (femur, tibia). A diaphyseal location is always regarded as unusual. Prognosis and treatment: The most important prognostic factor is the degree of response to preoperative chemotherapy. Wide excision or amputation follows pre-operative (neoadjuvant) chemotherapy. The surgical procedure depends on local tumor staging (MRI!) and the detection of metastases (bone scan or whole-body MRI and chest CT).
Radiography. The radiological morphology is variable, depending on the subtype and degree of osseous matrix formation. There is often a mixed lytic/sclerotic pattern:
• The tumor margin is ill-defined (Lodwick Grade II–III).
• Periosteal bone formation is almost always seen, with evidence of spicules being an important criterion for malignancy (see Fig. 4.18). Codman angles (elevation of the sclerotic periosteum with undermining cortical destruction) are found (see Fig. 4.21). Lamellated (onion skin), commonly interrupted, periosteal new bone formations are regularly to be seen (see Fig. 4.25).
Osteosclerotic osteosarcoma (ca. 10% of cases). Osteosclerotic osteosarcoma is characterized by ivory or “cloudlike” dense, sclerotic tumor matrix ( Fig. 4.22). Occasionally this variant remains confined within the borders of the affected bone for a relatively long time.
NUC MED. Bone scintigraphy is important for detecting bone metastases. PET-CT can be used to assess prognosis after chemotherapy.
CT. CT can differentiate better than radiography between periosteal reaction and the osteogenic tumor matrix. It should be noted when staging that metastases can display calcifications that—in this clinical context—are not signs of benign disease (chest CT; Fig. 4.23).
MRI. The signal alterations depend on the degree of matrix mineralization. The tumor enhances strongly after administration of gadolinium. MRI is the modality of choice for staging lesions in tubular bones (intramedullary extension, skip metastases, soft tissue infiltration, joint involvement; Figs. 4.24 and 4.25). The surgeon will be particularly interested in any possible association with neurovascular bundles.
DD. Ewing’ s sarcoma (see Chapter 4.2.4). Ewing’s sarcoma usually has a diaphyseal to metaphyseal location and does not demonstrate bone matrix or chondrogenic matrix.
CRMO (Chronic recurrent multifocal osteomyelitis). A chronic reactive form of osteomyelitis, in children and adolescents (see Chapter 10.7.1).
Chondrosarcoma. MRI characteristics of cartilage are to be found here (see Chapter 4.2.2).
High-grade pleomorphic sarcoma. See Chapter 4.2.3 for high-grade pleomorphic sarcoma.
A primary malignant bone tumor in a patient over 30 years old is practically never a central osteosarcoma.
Telangiectatic osteosarcoma (1–10% of osteosarcomas). This is a highly malignant tumor filled with hemorrhagic spaces (beware similarity with an aneurysmal bone cyst!). A moth-eaten pattern of osteolysis without osteogenic matrix is a predominant feature on the radiograph ( Fig. 4.26).
Small cell osteosarcoma. This osteosarcoma has an unfavorable prognosis. The predominant radiological features are bone destruction and sclerosis.
Low-grade central osteosarcoma (1–2% of osteosarcomas). This is a more slowly growing and prognostically more favorable variant occurring in the 2nd and 3rd decades of life. The lesion can simulate many other tumorlike lesions particularly fibrous dysplasia ( Figs. 4.27 and 4.28).
Fig. 4.25 Central, predominantly osteolytic osteosarcoma. (a) Large osteolytic lesion with soft tissue swelling. (b) Circular extraosseous component of the tumor.
Fig. 4.28 Low-grade central osteosarcoma. The differential diagnosis from fibrous dysplasia is difficult.
Parosteal osteosarcoma. Parosteal osteosarcoma is the commonest form of surface osteosarcoma. It is a low-grade malignancy that develops slowly on the surface of the bone and only invades the medullary cavity secondarily. Age: 3rd and 4th decades of life. Location: Over 50% arise on the posterior distal femoral metaphysis. The main radiological feature is the eccentrically located density with solid internal structure ( Figs. 4.29–4.31). Cleft formations between cortical surface and tumor formation are identifiable by CT. DD: Cortical/periosteal desmoid (cortical irregularity), osteochondroma, heterotopic ossification.
Periosteal osteosarcoma. This is an osteoblastic or chondroblastic type that also arises from the surface of the bone, similarly to parosteal osteosarcoma. It has broad-based contact with the bone surface and may show marginal scalloping mimicking a periosteal chondroma or a spiculated periosteal reaction similar to central osteosarcoma ( Fig. 4.32). Location: Commonly diaphyseal. Secondary invasion of the medullary cavity is identifiable by MRI.
Between 5 and 7% of osteosarcomas develop from a preexisting bony disorder:
Paget’s disease. About 1% of patients with Paget’s disease may undergo malignant transformation (95% of cases occur in the polyostotic form of Paget’s). Age: 6th to 7th decades of life. Any change in the clinical symptoms of a patient with Paget’s disease or a pathologic fracture raises the specter of a secondary osteosarcoma. Increasing levels of bone-specific alkaline phosphatase evident in the laboratory results may be an indicator. Increasing lysis and cortical destruction on the radiograph are important diagnostic signs ( Fig. 4.33). MRI confirms a soft tissue component. The prognosis is universally poor.
Radiation-induced osteosarcoma. The risk of developing an osteosarcoma after radiation therapy is reported to be 0.03 to 0.8% of cases with doses over 30 Gy required. The latent period before manifestation of the tumor is typically about 10 years and not less than 3 years ( Fig. W4.1).
Associations between osteosarcomas and medullary infarction or fibrous dysplasia, while recognized, are extremely rare.
Fig. 4.29 Parosteal osteosarcoma. Compare Fig. 4.34. (a) Densely sclerotic parosteal mass. (b) Evidence of tumor infiltration of the medullary cavity.
Fig. 4.30 Parosteal osteosarcoma. (a) Focal sclerotic zone in the distal tibia. (b) CT confirms the secondary invasion of the medullary cavity.
Fig. 4.31 Parosteal osteosarcoma. (a) Extraosseous density. (b) Broad-based, partly homogeneous, lobulated tumor. (c) Chondroid components (arrows) in the distal pole are hardly visible on CT.
Fig. 4.33 Secondary osteosarcoma associated with Paget’s disease. (a) Widening of the medullary cavity with ill-defined cortical margin. (b) Bone destruction and spiculation. (c) Contrast-enhancing tumor. The bilateral signal-intense, subcortical areas (arrows) and the bowing of both femurs are due to the underlying condition (Paget’s disease).
Common to all cartilage tumors is their production of chondroid matrix, which sometimes may be only sparse and nestlike. Benign tumors are frequently asymptomatic and, as an incidental finding, represent the largest group among bone tumors.
Osteochondroma (synonym: cartilaginous exostosis) is the most common bone tumor. They are cartilage-covered bony outgrowths arising from the surface of the bone and containing bone marrow that has trabecular continuity with the central medullary cavity. Cytogenetic studies indicate that both sporadic as well as inherited osteochondromas are genuine benign tumors and not simply developmental abnormalities. Their growth ceases with completion of skeletal growth.
Pathology. An osteochondroma displays a growth platelike differentiation at the junction with a narrow cartilage cap. Calcifications are regularly found. Fatty marrow is found at the base.
If the cartilage cap on imaging is thicker than 2 cm, malignant transformation to a secondary chondrosarcoma should be considered. It can occur in < 1% of solitary osteochondromas and < 5% of cases of the multiple form (hereditary multiple exostoses/diaphyseal aclasis); see Fig. 4.36). Increasing size or pain in an adult is suspicious for malignant transformation. Malignant transformation does not occur in children!
Clinical presentation. It is frequently an incidental finding. Rarely do pain or problems secondary to mechanical compression occur.
Age: Predominantly the 1st to 3rd decade of life. Location: The metaphyseal region of the long tubular bones oriented away from the adjacent joint (~ 70% of cases; Fig. 4.34). The axial skeleton is also affected. Treatment: Leave alone or simple excision at the base of the osteochondroma.
Radiography. The exostosis either arises as a relatively narrow-based bony projection from the underlying cortex (pedunculated) (see Fig. 4.34) or is connected to the bone by a broad base (sessile) in such a manner that the native cortex is hardly recognizable (widening of the bone; Figs. 4.35, 4.36c, and W4.2). Large osteochondromas can cause modeling deformity of the underlying bone and pressure erosion of adjacent bones. Calcifications are commonly found on the surface. The border with the surrounding soft tissue is sharp, but commonly of irregular configuration. The noncalcified cartilage cap is not visible on the radiograph.
US. If the osteochondroma is superficial, then the cartilage cap is well visualized (hypoechoic). Ultrasound is particularly applicable in this respect in children.
CT. The origin of the lesion is readily visualized, with depiction of the pathognomonic remodeling of the cortical bone, especially in the axial skeleton. The noncalcified cartilage cap is identifiable as a hypodense layer compared with surrounding muscle (see Fig. 4.35).
MRI. As on CT, the direct continuity between the host bone marrow and the fatty marrow of a mature osteochondroma is diagnostic. MRI is the best modality for measuring precisely the thickness of the cartilage cap (see Fig. 4.34).
DD. Parosteal osteosarcoma. Whereas osteochondromas have continuity with the normal medullary cavity, parosteal osteosarcomas show an intact cortex or direct tumor invasion with dense osteogenic matrix.
Chondrosarcoma. See “Chondrosarcoma,” page 280.
Nora lesion. This is a bizarre parosteal osteochondromatous proliferation (BPOP) affecting the tubular bones of the hand and foot (see Chapter 4.3.8). Again, there is no continuity between the lesion and the medullary cavity.
Periosteal chondroma. See Fig. 4.42.
Chondromas are the second most common benign bone tumor entities (incidence 2.5%). Enchondromas are usually solitary tumors of the medullary cavity. The less common periosteal (juxtacortical) chondromas develop on the surface of the bone, beneath the periosteum. Enchondromatosis is a disturbance of normal endochondral ossification.
• Enchondromatosis = Ollier’s disease (increased risk of malignant transformation; Fig. W4.3).
• Enchondromatosis and multiple soft tissue hemangiomas = Maffucci’s syndrome.
Pathology. Chondromas are hypocellular tumors with only septal and peripheral vascularization and abundant hyaline cartilaginous matrix production. They usually grow in a clustered, lobulated fashion, with a bunch-of-grapes appearance displacing the original cancellous bone.
Clinical presentation. In tubular bones, chondromas are typically painless; in the fingers they may present as swellings.
Age: 2nd to 5th decades of life. It is not uncommon for pathologic fractures to be the presenting complaint. Location: About 60% of all enchondromas are located in the small tubular bones of the hands and feet. Long tubular bones and the ribs are also affected. Chondromas are rare in flat bones, as well as the spine. Treatment: There is currently no unified approach. A watchful waiting approach may be adopted for asymptomatic chondromas of the tubular bones up to a length of ~ 10 cm with yearly follow-up radiographs. Alternatively, careful curettage is performed. The general rule for small tubular bones is that chondroid tumors are practically always benign. Only slowly progressive pain and enlargement of the tumor as demonstrated by imaging should give cause for a generous biopsy.
Fig. 4.34 Osteochondroma. (a) Pediclelike primary finding. (b) Growth 6 years later. (c) Preserved continuity with the bone marrow is evident on MRI. (d) Hyperintensity of the cartilage on the fluid-sensitive sequence.
Fig. 4.36 Hereditary multiple exostoses. Multiple bony spur formations. (a) Pediclelike exostosis of the humerus. (b) Compression and deformation of adjacent bones of the lower leg. (c) Broad-based exostosis of the fibula.
Progressive enlargement and pain during adulthood are suspicious for chondrosarcoma. A more proximal or more central location of a cartilaginous tumor in the body implies a greater likelihood that it is malignant. Lesion length over 5 cm and unequivocal endosteal scalloping (= resorption of the inner cortex; see Fig. 4.41) are possible signs of malignancy.
Radiography. The classic finding is a focus of osteolysis in which popcornlike, punctate, ringlike or arclike calcifications are interspersed ( Figs. 4.37–4.41). The transition to normal bone is sharp and commonly displays a fine sclerotic margin. In long tubular bones the tumor almost always has a central location. If scalloping and neocortex are present, then the lesion should be assessed for disruption of the cortical bone using CT or MRI. In the small bones of the hand, osteolysis is expansile and the cortex very frequently attenuated and sometimes no longer visible. In the hand, however, this is no proof of malignancy, because the bones are small and the tumor rapidly extends to the cortex.
CT. Typical popcornlike calcifications are more readily recognizable ( Fig. 4.42). Unequivocal cortical destruction is indicative of malignant transformation into a chondrosarcoma.
MRI. There is a hypointense signal pattern on T1W sequences; the signal on T2W sequences depends on the degree of calcification. A noncalcified enchondroma can appear so hyperintense that it is difficult to differentiate it from a cyst on T2W images. Intravenous administration of contrast agent is then helpful. There is a typical lobulated appearance with septation ( Figs. 4.37, 4.39, and Fig. W4.3). A chondrosarcoma should be considered where there is cortical destruction or extraosseous tumor components.
NUC MED. Absent to mild increased activity is evident on the bone scan. Markedly increased uptake would suggest growing tumor and would be suspicious for malignancy. Increased uptake is regularly seen on PET, sometimes quite clearly depending on the proliferation rate. Differentiation from a low-grade chondrosarcoma is not possible. A threshold to higher-grade chondrosarcoma has been reported.
DD. Bone infarction. Calcifications and infarctions are arranged more peripherally at the interface with healthy bone. On MRI, fat and/or cystic degeneration is found in a central location within the infarction area.
Chondrosarcoma G1 (well differentiated). This is a very difficult differentiation histologically and on imaging (see commentary of Fig. 4.41).
Fig. 4.37 Enchondroma. (a) Radiolucency with granular calcifications in the proximal humeral shaft evident on the radiograph. (b) Very hyperintense cartilage signal on the PDW image with grapelike configuration. (c) Septal contrast enhancement.
Fig. 4.38 Sharply defined osteolytic lesion with thinning of the cortex and (pathologic) fracture. Nevertheless, there are no concerns about diagnosing a “benign enchondroma” of the hand.
Fig. 4.39 Enchondroma of the distal forearm. (a) Osteolysis with popcornlike calcification. (b) Sharp margination; the cortex is preserved.
Fig. 4.41 Enchondroma of the distal tibia. The crucial clinical question—“Is this a slowly growing, but benign, tumor or has a growth spurt occurred?”—cannot be answered with this image alone. Is pain of increasing severity a feature? If so, generous biopsy and analysis at a bone tumor referral center are called for. A progressive increase in size as documented on imaging should also prompt a biopsy.
Fig. 4.42 Periosteal chondroma. (a) Egg-shaped periosteal tumor with a partly saucer-shaped border. (b) Typical saucer shape of the cortex.
Pathology. A chondroblastoma is a rare, benign, cartilage-producing tumor.
Clinical presentation. Age: 1st to 3rd decades of life; males are twice as frequently affected as females. Location: Typically it arises in the epiphysis of long tubular bones, occasionally extending into the metaphysis. Chondroblastoma may arise in an apophysis and rarely at other sites such as the talus, calcaneus, patella (where it is the most common tumor!) and spine. Treatment: Curettage or, if small, radiofrequency ablation.
MRI. The typical hyperintense cartilage signal on T2W sequences is absent because this is immature cartilage. A concomitant joint effusion is present in 30% of cases (see Fig. 4.43) with florid perilesional edema.
The typical location in the epiphyses of tubular bones is the diagnostic key for a chondroblastoma, especially if intralesional calcifications are absent. The latter should be preferentially looked for using CT. MRI may well diagnose a tumor, but it is very nonspecific.
DD. Giant cell tumor. A giant cell tumor does not show clear marginal sclerosis and occurs post skeletal fusion.
Low-grade osteosarcoma. Here, the matrix calcifications are decisive. If they are absent, then the differential diagnosis from a slowly growing osteosarcoma may be difficult.
Other differential diagnoses. Subchondral ganglion, chondromyxoid fibroma, clear cell chondrosarcoma, aneurysmal bone cyst (as a secondary finding commonly associated with a chondroblastoma), and epiphyseal abscess.
Pathology. This is a very rare (less than 1% of cases) benign tumor that is characterized by abundant myxoid or chondroid intercellular substance.
Clinical presentation. Age: 2nd to 3rd decade of life. Location: Frequently found in a metaphyseal, rarely diaphyseal, site around the knee joint (50% of cases). A chondromyxoid fibroma is practically only found in tubular bones.
Radiography. Sharply delineated, solitary radiolucency, which demonstrates an elongated oval form along the longitudinal axis of the bone ( Figs. 4.45 and 4.46), are important diagnostic signs. The border of the tumor is not always sharp. Intratumoral calcifications are rare.
CT/MRI. CT and MRI do not make any relevant contribution toward establishing a diagnosis other than determining the extent of the tumor.
DD. Possible differential diagnoses are chondrosarcoma, chondroblastoma, and chondroblastic osteosarcoma. Histological confirmation before planning definitive therapy is essential.
Fig. 4.43 Chondroblastoma. (a) Sharply delineated, epimetaphyseal rounded lucency in the femoral head. (b) Note the intralesional calcifications on the radiograph. (c) MRI: The subchondral plate and the cartilage have been destroyed.
Fig. 4.46 Chondromyxoid fibroma. (a) Eccentric elongated oval areas of osteolysis in the metaphyseal region of the medial tibial plateau. (b) The tumor has two “parts” and extends in a cranial direction along the medial meniscus. (c) A signal-intense tumor matrix on the T2W image. (d) Contrast-enhancing vascularized tumor tissue on the internal aspect. The myxoid part does not enhance with contrast.
Chondrosarcomas are the second most common form of primary malignant bone tumors. They comprise a heterogeneous group of malignant cartilaginous tumors which differ both histomorphologically and clinically:
Secondary chondrosarcoma. This develops as a result of malignant transformation of a primary benign chondroma to a central chondrosarcoma, or of a primary osteochondroma to a peripheral chondrosarcoma ( Fig. 4.50, Figs. W4.4 and W4.5).
Periosteal chondrosarcoma. This develops on the surface bone ( Fig. 4.51).
Dedifferentiated chondrosarcoma. This is a rare type of chondrosarcoma with a poor prognosis. It is characterized by two components: a well-differentiated cartilaginous tumor (enchondroma or low-grade chondrosarcoma, usually with typical matrix mineralizations) and a high-grade, noncartilaginous sarcoma, for example, osteosarcoma. The various radiologically differentiable parts of the tumor should be taken into consideration when determining the site for biopsy. Age: Over the age of 50 years.
Mesenchymal chondrosarcoma. This is a rare variant with undifferentiated small round cells and islands of well-differentiated cartilage ( Figs. 4.52 and 4.53). About 30% are extraskeletal. Age: From the second decade of life. DD: (Extraskeletal) Ewing’s sarcoma.
Clear cell chondrosarcoma. This is a rare, low-grade variant with typically a subarticular location in long tubular bones of 20- to 40-year-olds. DD: Chondroblastoma; this occurs in 20- to 30-year-olds.
Pathology. Myxoid and cystic changes are seen with primary chondrosarcoma, in addition to a dominant cartilaginous matrix production. Histological grading from 1 to 3—based on nuclear size, nuclear staining, and cellularity—has proven its worth with regard to prognostic value. The distinction between enchondroma and low-grade chondrosarcoma (G1) must be assessed using an adequate amount of biopsy material by judging the growth pattern with respect to the cortex and cancellous bone. This is difficult even for an experienced pathologist!
Clinical presentation. Local swelling and pain that may last for weeks or months before the patient seeks medical attention.
Age: Over 50% of cases are over 50 years of age. All adult age groups, however, can be involved. Location: Pelvic bones, proximal femur, proximal humerus and ribs are primary locations. Chondrosarcomas are found in a metaphyseal (less commonly diaphyseal) location.
Radiography. Primary central chondrosarcoma:
• A circumscribed radiolucency presents, sometimes with a permeative pattern. The cortical bone is destroyed ( Fig. 4.47) or remodeled.
• Only rarely is a sclerotic margin present.
• Periosteal reaction and widening of the bone occur ( Fig. 4.49).
• The tumors demonstrate calcifications in about 50% of cases. The calcifications of moderate and high-grade malignant tumors are usually more irregular and patchier than those of enchondromas or low-grade chondrosarcomas.
Enchondromas and low-grade malignant chondrosarcomas are difficult to differentiate using radiographs alone.