Imaging 15:298-323 (2003)
© 2003 The British Institute of Radiology
Evaluation of focal bone lesions: basic principles and clinical scenarios
P O'Donnell, MRCP, FRCR
Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, Middlesex HA7 4LP, UK
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Summary
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- The plain film is essential to reveal biological behaviour of the entire lesion.
- The plain film often suggests the tissue of origin.
- Lesion location (in both the longitudinal and transverse planes of the bone) and patient age narrow the differential diagnosis.
- Certain tumours and tumour-like conditions occur in characteristic locations, for example simple bone cysts and chordomas.
- If a diagnosis cannot be made from radiographs, CT may yield further diagnostic information.
- Staging MRI should be performed before any biopsy.
- Referral to a bone tumour unit may be required for diagnostic assistance from imaging, or for biopsy. The latter is more appropriately performed in a specialist centre.
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Evaluation of focal bone lesions part I: basic principles
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Focal bone lesions fall into three broad categories: benign, malignant (primary and secondary), and non-neoplastic. The latter include a number of lesions commonly regarded as benign neoplasms, for example, simple (unicameral) bone cyst (SBC) and primary aneurysmal bone cyst (ABC), both of which contain no neoplastic cells, and fibrous dysplasia. The plain film is the mainstay of diagnosis, and should be evaluated in a logical manner regardless of diagnosis.
The general radiologist plays a central role, ensuring appropriate and timely triage of tumours to a specialist centre. Primary malignant bone tumours are however rare and infrequently encountered in general radiological practice. This low frequency, the varied appearances of tumours and tumour-like lesions, and the fact that a significant number of lesions may not represent tumours, reinforces that a systematic approach is required in the evaluation of these abnormalities.
The radiologist's role can be summarized as follows:
- lesion detection
- lesion characterization
- staging—local/distant
- biopsy guidance
- identification of residual/recurrent disease
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General principles
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Even before the radiographic features are analysed, it is essential to know the patient's age, the location of the lesion, and whether it is a solitary abnormality. Benign, malignant and a large number of non-neoplastic bone lesions occur at typical sites and in certain age groups, and knowledge of these details can usually reduce the list of differential diagnoses considerably. Within long bones, the lesion location in both the longitudinal (epiphysis, metaphysis, diaphysis) and transverse (intramedullary, intracortical, surface) planes must be determined. Surface (juxtacortical) lesions may be parosteal or periosteal. Most primary bone lesions are metaphyseal and intramedullary. The reason for this is not entirely certain, but the metaphysis is certainly the most metabolically active and most vascular area in a growing long bone [1], and this is accentuated at the more rapidly growing end. The vascularity of the metaphysis during growth appears to determine its predilection for involvement in haematogenous infective and metastatic disease.
It has been suggested that a tumour of a given cell type will develop in the area of bone where normal cells of that same type are most active [2]. Bone formation occurs at the cartilaginous physis. Tumours of chondral origin are thought to arise from dysplastic growth plate cartilage incorporated into the epiphysis (chondroblastoma) or metaphysis (enchondroma) of a growing bone. The metaphysis immediately adjacent to the physis shows intense osteoclastic activity, responsible for remodelling the large diameter growth plate to a slender long bone shaft. Giant cell tumours (GCTs) and lytic sarcomas tend to develop in these areas of rich osteoclastic activity, but the former rapidly traverse the fused growth plate to assume their conventional subarticular location. GCTs when small or occurring prior to skeletal fusion may be entirely metaphyseal. There is predominant osteoblastic activity in the diaphyseal half of the metaphysis, allowing further remodelling and cortical reconstitution: osteoblasts are active on both the endosteal and periosteal surfaces, and these are the preferential sites of origin of both parosteal and intramedullary osteosarcomas. The distribution of osteoblasts may also explain the location of other tumours of osseous origin, such as osteoid osteomas which, some authors have proposed, arise in a subperiosteal location, becoming intracortical due to surrounding bone reaction [3].
At or around the time of birth, marrow conversion from the predominant red (haemopoietic, functional) to yellow (fatty, non-functional) type commences, starting in the peripheries of the long bones from distal to proximal. By the age of 25 years, the adult marrow pattern has been achieved, and red marrow only remains in the axial skeleton, flat bones, the proximal ends of femora and humeri, ribs and calvarium. Myeloma and metastases develop in adults in areas of red marrow distribution, and involvement of other sites suggests diffuse red marrow replacement with subsequent yellow–red reconversion, and finally tumour infiltration of red marrow in these peripheral sites [4]. Malignant round cell tumours (Ewing's sarcoma in the child and lymphoma in the adult) also occur in skeletal sites containing red marrow. After age 16 years, the frequency of Ewing's sarcoma in the diaphyses of long bones declines, again reflecting red marrow distribution [4]. Other tumours appear to "take advantage" of the disappearance of cancellous bone from the diaphyses of long bones, and this is the preferential site of origin of fibrosarcoma [1]. Diaphyseal lesions are frequently malignant.
The majority of primary bone tumours develop in childhood, late adolescence or early adulthood, coinciding with the growth spurt and time of maximal metabolic and reconstructive activity of bone. They frequently affect long bones, which undergo greater growth and remodelling. They also tend to occur at the end of the bone where growth is greatest [2]. Malignant tumours do, on occasions, develop from pre-existent benign tumours, and this may also relate to excessive cellular activity. Malignant fibrous histiocytoma (MFH) may develop in a benign fibrous lesion, such as non-ossifying fibroma [5] or fibrous dysplasia [6], or other pre-existing benign tumours [5]. Both fibrosarcoma and MFH occur secondary to bone infarcts [7, 8], radiotherapy [9, 10] and Paget's disease [5, 7]. However, the most common secondary malignancy in Paget's is osteosarcoma [11]. Chondrosarcoma frequently arises in pre-existing enchondroma [12] or osteochondroma (3–5% of lesions in diaphyseal aclasia [13]).
Certain lesions show characteristic distribution within the skeleton, including:
- SBC—proximal humerus, neck of femur (os calcis in adults)
- Osteofibrous dysplasia and adamantinoma—middle third of tibia
- Enchondroma—phalanges of the hand (most common bone tumour in the hand)
- Chordoma—proximal and distal extremes of spine (clivus, sacrum)
- Chronic recurrent multifocal osteomyelitis—medial third of clavicle.
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Lesion detection and characterization
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The radiograph is essential in the evaluation of a focal lesion in bone. A bone tumour cannot be diagnosed accurately without reference to a radiograph. A biopsy only samples a small portion of the lesion; a plain film is mandatory to assess the biology of the tumour as a whole, by assessing the rate of growth. Undoubtedly, malignant bone tumours can show fast rates of growth and aggressive patterns of bone destruction, but rapidly growing benign lesions, such as osteomyelitis and Langerhans cell histiocytosis (LCH), may have similar worrying appearances. Conversely, some malignant lesions are slow-growing and may show less aggressive features. Assessment of growth rate is important not only to reach an accurate plain film differential diagnosis, but to add prognostic information—the radiographic rate of growth correlates with the aggression of the tumour [14] or virulence of infecting organism [15].
As previously mentioned, the radiograph should be evaluated in a systematic manner. The following features should be assessed:
- pattern of bone destruction
- edge of lesion/zone of transition
- cortical response
- matrix mineralization
- periosteal reaction
- extraosseous extension/soft tissue mass
Pattern of bone destruction
Geographic
Bone destruction is confined to one area, within which all the bone is destroyed. This implies a slow rate of growth. It is usually seen in benign and slow-growing malignant tumours, and also infection, particularly granulomatous.
Moth-eaten
Radiographically, the lesion consists of multiple lucencies, each 2–5 mm in diameter. It implies fast growth, often due to malignant conditions, but is also seen in LCH and pyogenic osteomyelitis. The lesion grows rapidly through the medulla of the bone, but leaves small islands of tissue intact. Visualization on plain films suggests cortical involvement, and the lesion is generally more extensive histologically than radiographically.
Permeative
The most aggressive pattern of bone destruction, seen with the fastest-growing tumours and infection. Plain films show multiple tiny lucencies, which are usually less than 1 mm in diameter. By the time the lesion is visible, the cortex has usually been breached and an extraosseous mass may be evident. Again, radiographs underestimate the size of the lesion. A similar appearance can be seen in rapidly progressive osteoporosis, as may be seen in reflex sympathetic dystrophy (RSD) and disuse.
Edge
Well-defined, sclerotic
The host bone responds to a focal lesion by reactive bone formation. If the lesion is growing slowly, there is time for the bony reaction to become radiographically visible. The margin of the lesion on the radiograph corresponds with that seen histologically, and there is a sharply defined interface between normal and abnormal bone—a narrow zone of transition.
Well-defined without sclerosis
Again, the interface between normal and abnormal is sharply defined, but the reactive bone formed in response to the lesion is destroyed before it becomes radiographically visible. This is a common appearance is fast-growing benign tumours, such as GCT, and some malignant lesions.
Ill-defined
The distinction between normal and destroyed bone is not well-demarcated—a wide zone of transition. This implies rapid growth, and is uncommonly seen in benign conditions.
Combining the pattern of bone destruction and lesion edge, an assessment of growth rate can be made [16]. It is evident that the most indolent lesion will show geographic bone destruction and a sclerotic, well-defined margin (Figure 1a
). Progressively more rapid growth is suggested by the following sequence: geographic destruction, well-defined edge, no marginal sclerosis (Figure 1b); geographic destruction, ill-defined margin (Figure 1c); geographic destruction, ill-defined margin, moth-eaten elements (Figure 1d); moth-eaten destruction, ill-defined edge/wide zone of transition (Figure 1e); permeative destruction, ill-defined edge/wide zone of transition (Figure 1f).
Cortical response
An intact cortex suggests slow growth. It may respond in a variety of ways to the presence of a focal lesion. Cortical trabeculation implies a slow-growing, usually benign lesion, and is common in SBC and GCT (Figure 1c
). Endosteal scalloping reflects the lobular growth pattern of the underlying tumour, and commonly suggests a chondral (Figure 2) or fibrous lesion, but cannot differentiate benign from malignant. Cortical expansion is a misnomer, but implies that endosteal bone removal due to tumour is occurring at a similar speed to periosteal bone production, again suggesting slow growth. In more aggressive lesions, the outer cortical layer may be too thin to be seen on plain films, but evident on CT (Figure 3).
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Figure 2. Enchondroma of the middle phalanx. A well-defined lesion showing geographic bone destruction, a narrow zone of transition, and a little marginal sclerosis proximally is suggestive of slow growth. Endosteal scalloping (arrows) and chondral-type matrix mineralization suggest a tumour of cartilage origin.
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Figure 3. Aneurysmal bone cyst (ABC) proximal tibial metaphysis. The marked expansion has thinned the posterior and medial cortex such that it is no longer radiographically visible. The interface with preserved tibia is well-defined with some sclerosis (a, arrow). A multilamellated periosteal response can be seen at the inferior margin of the lesion—a periosteal buttress (b, arrow)—often identified in this condition.
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Destruction of the cortex suggests rapid growth. The most aggressive malignant lesions can occasionally penetrate the cortex before destruction is evident radiographically. Apparent preservation of the cortex does not preclude extension of disease from the medulla. Saucerization, whereby an extraosseous mass of tumour causes pressure erosion on the bone's outer surface, usually occurs with an apparently intact cortex (Figure 4). Although the soft tissue mass may not be visible, the scalloping of the outer cortex implies its presence. These last two entities (penetration of an apparently intact cortex and cortical saucerization) are most frequently seen with malignant round cell tumours, particularly Ewing's sarcoma.
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Figure 4. Ewing's sarcoma in the femoral diaphysis. (a) Anteroposterior radiograph shows subtle lucency in the mid-femur, with periosteal reaction and soft tissue mass. A prominent mass of periosteal new bone on the medial side of the femur shows smooth indentation called saucerization, typically found in Ewing's sarcoma. (b) Coronal short tau inversion recovery MRI shows the cause of saucerization—the periosteal new bone has been pressure-eroded by extraosseous tumour.
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Matrix mineralization
The presence calcification within the matrix of the tumour may suggest its origin.
Chondroid
Calcification within a lesion, if evenly distributed, should result in maximum radiodensity centrally. Typically, calcification in chondral tumours is punctate, and may be C-shaped, comma-shaped, or appear as rings or arcs (Figure 5a). Malignant transformation within a chondral tumour may lead to focal destruction of the chondral calcification.
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Figure 5. (a) Chondrosarcoma of the right ilium. Matrix mineralization of chondral type (punctate, in rings, arcs and commas), both in the ilium and also in the extraosseous mass (arrow). (b) Distal femoral osteosarcoma, matrix ossification. Aggressive, destructive lesion, with ill-defined medullary sclerosis and a large extraosseous mass surrounding the distal metadiaphysis. The mass contains streaks, and some cloud-like, fluffy densities, due to tumour bone formation. A small ossified nodule at the posteroinferior aspect of the mass is likely to represent metastasis to a local lymph node (arrow). A Codman's triangle can be seen at the anterosuperior aspect (curved arrow). (c) Ground glass density due to fibrous dysplasia. A well-defined lesion with a sclerotic rim is projected over the intertrochanteric region of the femur: it contains a uniform hazy increased density, due to fine bone spicules or thin calcified trabeculae.
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Osseous
Mature ossification typically shows greatest density peripherally, where the immature mineralization is forming a cortex. Immature ossification may be difficult to distinguish from calcification, as it resembles an ill-defined, homogeneous, cloud-like increased density ("cumulus cloud") (Figure 5b). CT is more accurate for characterization of the tumour matrix than radiographs. Increased density within a bone lesion may be due to either tumour bone or reactive bone formation.
Fibrous
Fibrous dysplasia is characterized by a "ground-glass" matrix (Figure 5c). This hazy, increased radiodensity is due to numerous fine spicules of woven bone or thin calcified trabeculae within the lesion, and the radiodensity is dependent on the mineralization of the woven bone [17]. Punctate calcification may also be present.
Periosteal reaction
The periosteum consists of two layers; an outer fibrous layer and an inner vascular layer, responsible for reactive bone formation [18]. The periosteal response reflects the duration and aggression of a process, and may indicate the nature of the underlying lesion. There may be local destruction of the bony cortex. Growth of tumour through the periosteal new bone results in an interrupted periosteal reaction, suggesting an aggressive process.
Solid
Radiographically, this is seen as a focal area of cortical thickening (Figure 6a). It represents consolidation of many slowly-applied laminae of periosteal new bone, and suggests slow growth. This pattern is commonly seen with osteoid osteomas, traumatic periostitis, and also chronic osteomyelitis.
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Figure 6. (a) Solid periosteal reaction which has absorbed onto the underlying cortex of the mid-tibia due to stress response. No fracture line is seen in the tibia but localized periosteal reaction at the superior aspect of the fibula indicates a fatigue fracture (arrow). (b) Langerhans cell histiocytosis distal humerus. There is a periosteal reaction indicated by a single lamella of bone, with a moth-eaten pattern of bone destruction. (c) Proximal tibial osteosarcoma. There is a spiculated periosteal reaction with a "hair-on-end" appearance at the posterior aspect of the diaphysis proximally, and diffuse medullary sclerosis with permeative destructive pattern indicates the underlying aggressive tumour.
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Single lamella
A single sheet of periosteal new bone, seen as a dense line 1–2 mm from the outer surface of the cortex (Figure 6b). The space between the reaction and underlying cortex will eventually be filled by reactive new bone, resulting in a solid periosteal reaction. Single lamellae suggest slow-growing, often benign processes, and are usually seen in chronic osteomyelitis and LCH.
Multilamellated
Multiple layers of periosteal new bone may be seen in a number of conditions (Figure 1f). Lamellated reactions are seen in 15–57% of Ewing's sarcoma ("onion skin") [19, 20], but are also seen in osteosarcoma, osteomyelitis, stress fracture and hypertrophic osteoarthropathy [18]. Ewing's sarcoma also commonly shows other patterns of periosteal response. Multilamellated periosteal reactions can also be seen at the margins of benign lesions (Figure 3), typically ABC (periosteal buttress) [21].
Spiculated
The two major patterns are perpendicular ("hair-on-end"), and divergent ("sunburst"). A spiculated reaction usually indicates rapid growth (Figure 6c).
The perpendicular pattern is most commonly seen in Ewing's sarcoma (10–28% of Ewing's) [19, 20], and may co-exist with a lamellated pattern. In the majority of cases, the bone is reactive, and separated by vascular channels formed from enlarged periosteal vessels. The reactive bone may later be replaced by tumour. Hair-on-end patterns are also seen in metastasis and osteosarcoma. Similar appearances may be seen in the calvarium due to haemolytic anaemias.
The divergent pattern usually indicates malignant osteoid production due to extraosseous tumour, rather than a reactive phenomenon: two-thirds of osteosarcomas have a spiculated periosteal reaction [22]. The individual spicules are separated by tumour, which may gradually ossify and replace the sunburst appearance. More aggressive tumours may destroy focal areas of tumour bone. A small proportion of metastases (commonly prostate) and haemangiomas can cause a sunburst appearance. Other, less organized types of reaction, such as "velvet" (sloping) may also be seen.
Codman's triangle
The triangle formed between the elevated periosteum and the adjacent cortex can be seen in both benign and malignant conditions (Figure 5b), and may be caused by any process that lifts periosteum away from bone. It suggests an aggressive process when associated with an interrupted periosteal reaction.
Extraosseous mass
Both tumours and inflammatory conditions can be associated with soft tissue mass or swelling, and if the mass is large or mineralized, it may be visible on radiographs. Extraosseous mass due to tumour is an aggressive feature, and cortical destruction may be subtle. It can occasionally be seen in benign conditions however. Displacement of intermuscular fat planes aids visualization of masses due to tumour, the fat itself remaining well-defined. Inflammatory masses are typically associated with loss of definition of fat planes. Primary soft tissue masses occurring in a parosteal location can stimulate periosteal new bone formation without medullary involvement (Figure 7).
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Figure 7. Parosteal lipoma anterior to left femur. (a) A fatty, lucent mass can be seen associated with mature ossification and cortical thickening at the anteromedial aspect of the bone (arrows). (b) Axial T1 weighted MR image shows fatty marrow within the ossified component (arrow), the homogeneously fatty mass and cortical thickening anteromedially. In this case, the periosteum has reacted to the parosteal location of the mass—there is no cortical breakthrough or involvement of the medulla.
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Lesion staging
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Aggressive bone lesions require local staging before biopsy is performed, and subsequent to the confirmation of malignancy, a search for metastases is required.
Local
MRI has revolutionized the local staging of malignant bone lesions. The evaluation should include extent of intraosseous disease (longitudinal medullary extent, evidence of skip metastases and epiphyseal extension). Skip metastases are defined as further foci of tumour, separated from the main lesion by normal marrow, and are seen in osteosarcoma in up to 25% of cases [23], and rarely in Ewing's. They are often located in the diaphysis of the same bone, although transarticular skip lesions also occur. Assessment of intraosseous extent requires long axis T1 weighted imaging of the whole bone [24]. Epiphyseal extension is also best assessed using this sequence: this may occur via transphyseal or lateral perichondral vascular channels [25, 26]. Inversion recovery (STIR) images can overestimate tumour size as the perilesional oedema or hyperplasia of the adjacent marrow may show similar signal.
Extraosseous extension is also best evaluated by MRI, and this should include an assessment of presence and compartmental distribution of the extraosseous mass, whether an intact periosteum can be seen around the tumour, extension into the nearby joint, and involvement of the neurovascular bundle. Regarding the latter, neurovascular structures may be uninvolved, abutted, or encased, and the encasement may make limb salvage impossible.
As the intraosseous extent of disease on MRI appears to correlate well with histology [27], one further use of this imaging technique is assessment of a suitable transection point for manufacture of a custom-made endoprosthesis.
Distant
An assessment of multifocal skeletal (either metastatic or multiple primary) and pulmonary disease is required in the evaluation of primary malignant bone lesions. Whole body isotope bone scanning and CT of the thorax are the techniques used most frequently.
Isotope bone scanning
The primary lesion is usually demonstrated on isotope bone scanning and aggressive bone destruction often shows an active area of uptake with central photopenia. The local disease extent is inaccurately assessed by scintigraphy. This may be because of reactive osteoblastic activity, hyperaemia and periosteal reaction leading to overestimation of intramedullary extent, and occasionally, to the spurious impression of extension across the adjacent joint [28]. Transarticular skip metastases are usually not identified on the staging MRI, and require scintigraphy for exclusion.
Isotope bone scanning may reveal multiple lesions due to metastatic disease, multiple primary tumours or multifocal benign or non-neoplastic lesions: it is sensitive but not specific. It has reduced sensitivity for the multiple lesions of myeloma, and for this reason, radiographic skeletal survey or MRI marrow screening is used: the sensitivity of plain films ranges from 75% to 91%, compared with 46% to around 60% for scintigraphy [29, 30]. The latter may also be of use in the further assessment of lesions not thought to be malignant—it may be useful to exclude further foci of osteomyelitis, multiple sites and activity of fibrous dysplasia, and may also show characteristic appearances in some benign conditions (such as the "double-density" sign (Figure 8) in osteoid osteomas [31]).
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Figure 8. Double-density sign in mid-tibial osteoid osteoma. (a) Frontal and (b) lateral static images from radioisotope bone scan show central high activity due to the tumour nidus, and a surrounding zone of lesser activity due to reactive bone.
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Chest CT
Chest CT is very sensitive to the presence of parenchymal disease, but occasionally images may also reveal metastases in other sites (bones, lymph nodes). It is necessary in all cases of malignant primary bone tumour, as the lung is the most common site of secondary disease [32].
Positron emission tomography (PET)
PET assesses glycolysis rates in tumours by integration of 18F-labelled 2-fluoro-2-deoxyglucose (18FDG), and enables simultaneous evaluation of the primary tumour and metastases. The rationale for its use assumes greater metabolic activity in malignant tumours, but it has relatively low specificity for assessment of a solitary lesion, as FDG may also accumulate in aggressive benign tumours, inflammatory conditions and miscellaneous disorders such as fibrous dysplasia and Paget's disease [33]. False negative results are possible in well-differentiated, slow-growing tumours. Its use in staging of primary malignant bone lesions remains to be established: it is likely to have a major role in assessment of recurrence.
Whole-body MRI
Improved MRI technology has enabled rapid scanning of the entire body, and allows assessment of both metastases to bone and extraskeletal metastatic disease. Contiguous coronal acquisitions can cover the whole body, but require either a moving tabletop or manual repositioning of the patient. Fast-STIR images are very sensitive to pathology, and constitute the most frequently used sequence: addition of T1 spin-echo images aids evaluation of bone marrow, and may be of use in myeloma and metastases [34, 35]. MRI accurately detects skeletal metastases, is superior to bone scintigraphy in lesions without marked osteoblastic response, and results in better visualization of pelvic structures which may be obscured by a full bladder during scintigraphy [34]. Areas which are less well visualized by MRI include the ribs and calvarium [36]. Although it may be possible to replace bone scintigraphy with MRI, the latter's sensitivity to small lung metastases appears low [37], and CT of the thorax is still required for lung staging. Additional soft tissue staging, including the brain and liver is, however, possible using whole-body MRI—these two areas not routinely assessed by standard staging tests. This may be of greater importance in assessing metastatic burden due to non-skeletal tumours, as these areas are rarely involved in primary bone lesions.
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Biopsy guidance
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A proportion of bone lesions can be diagnosed from imaging appearances, but biopsy is frequently required for the remainder to guide appropriate local and systemic therapy. The biopsy should be performed by a radiologist of sufficient experience, using an approach acceptable to the surgeon who will eventually resect the lesion—this is most appropriately done in a bone tumour centre. The biopsy should take a safe, usually the shortest, route to the tumour, avoiding the neurovascular bundle, and aim not to transgress an uninvolved compartment or joint. The biopsy tract should be resected with the tumour, as sarcoma seedlings are highly implantable in soft tissue. Attention to haemostasis is also important, as post-biopsy haematoma may also contaminate adjacent normal tissue [32].
Guidance to bone lesions typically utilizes CT or fluoroscopy. Ultrasound is also useful and accurate, particularly for accessing the extraosseous component of bone tumours [38]. Diagnostic yield is increased if vascular areas of tumour are targeted, as these are more likely to be viable, and using ultrasound guidance, necrotic areas can be avoided. Yield is likely to be greatest from the edge of a necrotic lesion.
A logical extension to imaging-guided biopsy is imaging-guided therapy, and in particular, percutaneous CT-guided treatment of osteoid osteoma. Traditionally, these lesions have been resected with image-intensifier guidance, but the lesion itself is often difficult to see within the mass of reactive bone. The nidus of the osteoid osteoma is best seen using CT, and can be treated with great accuracy using CT guidance (Figure 9). A number of techniques are available, including percutaneous resection of a plug of bone containing the nidus, injection of alcohol, laser photocoagulation, and radiofrequency (RF) ablation [39]. The latter involves insertion of a RF probe into the centre of the lesion, which heats to a temperature of approximately 90°C, resulting in necrosis of a 1 cm sphere of tissue [40]. As the nidus is usually small, it is normally possible to place the probe accurately enough for effective treatment. Larger lesions require several treatments or a different sized electrode. A biopsy can also be taken prior to RF treatment to confirm the diagnosis.
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Figure 9. (a) Axial CT image showing the nidus of osteoid osteoma, with surrounding reactive sclerosis, in the femoral head. (b) A radiofrequency electrode has been placed percutaneously into the centre of the lesion.
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RF ablation has subsequently been used to treat other benign tumours, such as chondroblastoma [41], and as a palliative procedure for malignant lesions [42]. The latter usually require a generator with greater power output and larger, occasionally expandable, electrodes to increase the radius of necrosis, but the procedure is not curative. Other palliative, imaging-guided procedures which may be of use in patients unfit for surgery include osteoplasty—the injection of bone cement with imaging guidance into painful bone lesions [43]. This is an extension of vertebroplasty, where the pain from vertebral collapses may be successfully relieved by bone cement augmentation. The analgesic mechanism may be due to the cytotoxic effect of bone cement directly to the tumour, or to sensory nerve endings, both of which may be damaged by the exothermic reaction between the cement monomer and the solvent. There are also contributions from the mechanical augmentation of pathological bone by cement and fracture stabilization. Osteoplasty, which may be combined with radiotherapy, may be useful in the treatment of a particularly painful metastasis, where curative surgery is not possible.
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Evaluation of focal bone lesions part II: clinical scenarios
P O'Donnell, MRCP, FRCR
Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, Middlesex HA7 4LP, UK
Rather than give a comprehensive account of the clinical and imaging features of bone lesions, a number of relatively common clinical scenarios and their differential diagnoses are presented.
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Scenario 1: Young adult, tibial pain
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Imaging findings
The radiographs (Figure 1) show focal medullary sclerosis and solid periosteal reaction/cortical thickening. No nidus, fracture or focal bone destruction is seen. MRI shows medullary oedema, cortical thickening and oedema in the surrounding soft tissues. Periosteal and endosteal callus is seen adjacent to an ill-defined fracture line in the posterior femoral cortex on high resolution CT—sagittal reconstruction shows its path longitudinally. In retrospect, the fracture can be identified on axial MRI.
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Figure 1. (a) Eccentric solid periosteal reaction/cortical thickening, and medullary sclerosis in the proximal tibia. No nidus or fracture line is seen, and there is no focal bone destruction. (b) Coronal short tau inversion recovery MR image. There is medullary oedema and low signal (representing callus), with adjacent cortical irregularity. Oedema is seen adjacent to tibia in muscle and subcutaneous tissues. (c) Sagittal T1 MRI. Medullary oedema is seen as reduced signal within fatty marrow, and a cortical lesion is seen posteriorly. (d) Axial proton density and (e) T2 fat-saturated images showing medullary and soft tissue oedema. The cortex is thickened posteriorly, and contains a sagitally-orientated defect, which could be followed on adjacent axial images (arrow). (f) Axial high-resolution CT and (g) sagittal reconstruction. An ill-defined fracture line (arrow) with adjacent periosteal and endosteal callus is seen in the posterior tibia. A longitudinal/sagittal fracture line with surrounding callus is seen on the reconstructed image. Diagnosis: longitudinal tibial fatigue fracture.
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Differential diagnosis: osteoid osteoma, stress fracture, chronic osteomyelitis.
Diagnosis: longitudinal stress (fatigue) fracture.
Stress fractures of fatigue type usually occur in the lower limbs in long distance runners. There may be a history of activity, which may be unaccustomed, endurance training or recent increased exercise intensity, but no acute episode of trauma. Alternatively, abnormal bone can fracture under normal stresses (insufficiency fracture), and a history of activity is absent. The fracture is often transverse, but a longitudinal variant was described in the tibia in 1960 [1], thought to account for approximately 10% of tibial stress fractures. The fracture line is usually occult on the radiograph, which shows non-specific medullary and periosteal callus formation: other possible causes are shown in the differential diagnosis above. High resolution CT can demonstrate the fracture and exclude the nidus of an osteoid osteoma. MRI also demonstrates a cleft in the cortex in most cases, with associated oedema in bone and soft tissue [2]. A recent paper reported on the position of the fracture in relation to the nutrient foramen and distribution of oedema in bone and soft tissue [3]. The fracture commonly originated level with the nutrient foramen or at the site of entry of the nutrient vessel. The eccentric soft tissue oedema and periosteal reaction suggested a longitudinal rather than transverse fracture line. Medullary oedema was variable. Stress lesions without an identifiable fracture can also lead to similar radiographic and MRI findings, and also increased uptake on bone scintigraphy: these are also commonly found in the tibia. Fatigue fractures are found in typical locations, depending on the precipitating activity [4].
The major differential consideration is osteoid osteoma (Figure 2). The typical history of night pain, relieved by salicylates, may help to differentiate, but is not sensitive (present in only about 60% of osteoid osteomas [5]) or specific (it may also be present in other lesions). The radiographic findings may be identical to those of stress fracture: the tumour nidus is often completely obscured by the surrounding reactive new bone. They occur almost anywhere in the body, their possible locations overlapping with those of stress lesions. The nidus may be visible on MRI studies, but these often only show marrow oedema and reactive bone formation. A recent study of 43 cases showed that the tumour was poorly visualized or not seen in 35% of patients [6], resulting in potential misdiagnosis. The imaging technique of choice to demonstrate the tumour is high resolution CT: a lucent cortical focus, which measures less than 1 cm in diameter and which may contain a punctate density or densities centrally, represents the vascularized and innervated tumour nidus, surrounded by reactive bony sclerosis.
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Figure 2. (a) Solid periosteal reaction/cortical thickening in the mid-tibia due to osteoid osteoma. (b) Axial high resolution CT with (c) sagittal reconstruction shows the small lucent tumour nidus within the surrounding reactive bone. MR images showed marked bone and extraosseous oedema.
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If neither a fracture nor a nidus is demonstrated, the possibility of chronic osteomyelitis remains. There may be no associated systemic symptoms or serological evidence of sepsis with low grade infections, and if CT fails to demonstrate a nidus or fracture, biopsy may be required. Other, rarer, conditions which may cause medullary sclerosis include a number of rare sclerosing bone dysplasias, which will have a different clinical presentation and affect multiple bones. A series of nine female patients with chronic leg pain exacerbated by activity, all of whom showed medullary sclerosis, cortical thickening, activity on scintigraphy, and oedema in adjacent soft tissues, predominantly in the tibia, has recently been published [7]. The lesions were mainly diaphyseal, with bilateral lower limb involvement in seven. However, imaging showed no evidence of fracture or nidus, and biopsy confirmed only sclerotic and thickened trabeculae—these cases, termed intramedullary osteosclerosis—also enter the differential.
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Scenario 2: Child, tibial pain and deformity
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Imaging findings
There is a multilocular lesion within the tibial cortex anteriorly, with extension into the medulla (Figure 3). The individual lucencies comprising the abnormality show geographic bone destruction and the cortex is expanded, in keeping with slow growth. The tibia is bowed anteriorly. The fibula is normal.
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Figure 3. (a) Lateral and (b) anteroposterior radiographs of the mid-tibia in a child showing multilocular expansion affecting predominantly the cortex, but medullary sclerosis and lucency are also seen. The tibia is bowed anteriorly. No fibular involvement can be identified. Diagnosis: osteofibrous dysplasia.
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Differential diagnosis: osteofibrous dysplasia, adamantinoma, fibrous dysplasia (FD).
Diagnosis: osteofibrous dysplasia (OFD).
There are two relatively uncommon lesions that show a predilection for the tibia. OFD (ossifying fibroma) is a lesion of childhood, usually occurring in the first decade. It affects the tibia in over 90% [8] of cases, most commonly the anterior cortex of the middle third. Occasionally, the lesion is more extensive, extending into proximal or distal thirds, and spreading to the medulla. Anterior bowing is typical but not invariable. The ipsilateral fibula may also rarely be involved. The radiographic appearances vary from a single, well-defined cortical lucency to multiple locules and extension into proximal or distal cortices. Individual locules show non-aggressive appearances, with cortical thinning superficially and deep marginal sclerosis. Locules may contain faint density, similar to the ground glass mineralization of FD [9]. Lesions may be slowly progressive up to age 15 years, but do not progress after skeletal maturation and may regress spontaneously [9].
Adamantinoma (Figure 4) is a rare, low grade primary malignant bone lesion. It typically occurs in the long bones, with approximately 80% of cases occurring in the tibia [10]. It tends to affect an older age group, with the peak age in men of 30–50 years and in women 10–30 years [10]. Only 3% of patients are less than 10 years old [11]. Plain film appearances are similar to OFD, with a multilocular lucent lesion, most commonly seen in the middle third of the tibia. It arises in the medulla [10], but the overlying cortex is also usually involved at presentation, with rare fibular involvement [12]. Anterior bowing is rare [12]. There may be reactive sclerosis and a periosteal reaction, but no ground glass matrix.
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Figure 4. (a) Lateral and (b) anteroposterior radiographs of the mid-tibia and distal tibia and fibula in an adult. A multilocular lesion occupies the medulla with mild cortical expansion. The surrounding bone is sclerotic, and a further lesion is seen in the distal fibula. Diagnosis: adamantinoma. The imaging appearances can be identical to those of osteofibrous dysplasia.
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Imaging features of OFD and adamantinoma may be identical. Distinction has traditionally been based on the age of the patient, and also on evidence of malignant behaviour in adamantinoma. The older age, more aggressive pattern of bone destruction and periosteal reaction favour adamantinoma [12]. Histologically, adamantinoma is a malignant epithelial neoplasm, and may contain components resembling OFD. The identification single or strands of keratin-positive cells in OFD by immunohistochemistry suggests they share a common histogenetic relationship [11], and they may belong to a spectrum of related disorders with increasing epithelial component: OFD; differentiated adamantinoma (regressing, juvenile, intracortical, OFD-like adamantinoma); and adamantinoma [11].
FD may also resemble these lesions. It can occur in any location, but monostotic disease is most common in the proximal femur and ribs. Confusion with polyostotic disease should not occur: with the exception of rare fibular involvement, neither OFD nor adamantinoma affect more than one bone. Monostotic FD is commonly discovered during the first three decades, often incidentally [13]; polyostotic disease is often symptomatic, and usually presents earlier (under age 10 years). It is relatively rare to discover OFD after age 10 years, and adamantinoma usually presents later still. FD is also predominantly intramedullary, and rarely causes eccentric expansion, cortical involvement or bowing [9].
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Scenario 3: Adult, medullary chondral tumour
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Imaging findings
There is a well-defined area of calcification centrally within the medulla of the distal femur (Figure 5). The calcification is punctate, and evenly dispersed throughout the tumour. The inner margin of the cortex is scalloped. No cortical destruction, periosteal reaction or extraosseous mass is seen.
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Figure 5. (a) Anteroposterior and (b) lateral radiographs of the femur. The features are those of a well-differentiated/low grade cartilaginous tumour, with chondral-type matrix mineralization and endosteal scalloping (arrows). Histology confirmed a chondrosarcoma, but enchondromas in long bones appear identical. (c) Coronal T1 weighted MR image showing the hypointense lobular chondral tumour. (d) Coronal short tau inversion recovery (STIR) MR image shows a high signal lobular tumour, with small foci of contained signal void due to matrix mineralization. Uncalcified hyaline cartilage typically shows marked hyperintensity on T2 and STIR images. Diagnosis: low grade chondrosarcoma.
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Differential diagnosis: enchondroma (EN), low grade chondrosarcoma (CS).
Diagnosis: low grade CS.
The plain film features support the diagnosis of a slow-growing tumour of cartilaginous origin. The matrix is typically chondral, appearing punctate, with ring, arc and comma shapes. Endosteal scalloping suggests slow growth, and is typically seen in chondral tumours, due to their lobular growth pattern, and fibrous tumours. CT, which shows faint matrix calcification with greater clarity, would not be able to distinguish these chondral lesions. MRI demonstrates low signal on all sequences depending on the amount of calcium, and high T2 signal due to unmineralized hyaline cartilage (Figure 5c, d). Mature ENs are frequently heavily mineralized centrally. The differentiation between these tumours is entirely histological, and the plain film can only be reported as showing a low grade/well-differentiated chondral tumour (EN, grade 1 (or even grade 
) CS).
ENs are most commonly found in the hands, particularly in the proximal phalanges, but approximately 25% are found in the metadiaphyses of long bones [14]. Small ENs are often incidental findings, seen for example in the distal femur during MRI of the knee or, may present with bony swelling or pathological fracture, particularly in the hands.
CSs are divided according to location into peripheral (parosteal) and central (medullary). The former usually develop in the cartilage cap of an exostosis, more commonly in syndromes of multiple exostoses. Central CS can be secondary to a pre-existing lesion, such as an EN in Ollier's disease, in Paget's disease or following irradiation, but also arise de novo, commonly in the pelvis and femur. They display a variety of growth rates, from slow (well-defined lesion with a sclerotic edge) to fast (permeative bone destruction due to dedifferentiated tumour). Pain is frequently present with malignant lesions according to some authors [14], but is not a helpful discriminator between EN and central grade 1 CS in another large study [15]. Confirming the pain is due to the tumour is often difficult. With relatively indolent features, as seen in this case, histology is required for diagnosis. Distinction is problematic despite an ample biopsy, as tumour heterogeneity can result in sampling error [16], and the differentiation of benign from low grade malignant disease is dependent on subtle pathological interpretation. The chance of a low grade lesion being CS rather than EN is increased by certain findings: age of patient; axial location; pain; extraosseous mass; lesion size; deep rather than shallow endosteal scalloping, and activity on bone scintigraphy. Patients with CS are usually older than those with EN by on average 10 years [18]. Solitary ENs in the axial skeleton or flat bones are unusual [15], and hand lesions are less likely to be malignant unless cortical destruction and extraosseous extension are present [14]. This is not always the case, however, with CS in the hands and feet occasionally showing non-aggressive features and slow growth [19]. Pain [14] and mass suggest malignancy, but are not usual with the plain film appearances shown in Figure 5. Large lesions (>5 cm) are more likely to be malignant [15]. Deep cortical scalloping (over two-thirds of cortical thickness) reflects greater biological activity [18], and tracer uptake in the lesion greater than the internal standard of the anterior superior iliac spine has been suggested as a sign of CS rather than EN [18]—the specificity of this finding remains to be proven in well-differentiated lesions. MRI appearances of the chondral lesion may be helpful: abnormal peritumoural signal consistent with marrow oedema was present in none of 10 ENs and all of 13 CSs in one study, with 8 of the latter being low grade tumours [16]. The authors also found soft tissue oedema in 8 of 13 CS, but no EN. Finally, there may be differences in the enhancement patterns, with diffuse and earlier [20] enhancement following intravenous gadolinium in CS, compared with peripheral enhancement in EN [21].
In faintly mineralized lesions, CT is useful to display the distribution of the calcification. The typical chondral mineralization may only be visible using CT. Other dense medullary lesions which may need consideration include bone infarcts. Mineralization in infarcts is most dense at the periphery of the lesion close to the endosteum. This marks the interface between ischaemic and vascular bone. CT is again useful to confirm the peripheral distribution of the calcium (Figure 6).
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Figure 6. (a) Anteroposterior radiograph shows a radiodense lesion with predominantly peripheral mineralization, consistent with a large, mature proximal tibial infarct. (b) Axial CT image confirming peripheral distribution of mineralization typical of an infarct, with no matrix mineralization.
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Scenario 4: Child, diaphyseal aggressive bone destruction
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Imaging findings
There is an aggressive lesion in the proximal humerus affecting metaphysis and diaphysis (Figure 7). A permeative pattern of destruction is seen, with an interrupted periosteal response and Codman's triangles. There is a circumferential extraosseous mass.
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Summary
Evaluation of focal bone...
