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Malignant or benign? Diagnosis from radiographic features of bone lesions
Author : NATALIE WEBSTER
Categories : Vets
Date : March 3, 2008
NATALIE WEBSTER discusses x-ray diagnosis of non-aggressive and aggressive bone lesions in small animals
DECIDING whether a bony lesion seen on a radiograph is malignant or benign is a challenge frequently faced by veterinarians.
Bone responds to injury or a pathological process with osteolysis, osteoproduction or a combination of the two. In veterinary medicine, very few processes are easily categorised as black or white, and bone lesions are no exception.
Non-aggressive and aggressive lesions
A spectrum of bony changes may be seen, ranging from severely aggressive to intermediate, lowgrade malignancy (non-aggressive and aggressive features) to non-aggressive. Often a lesion will have both aggressive and non-aggressive characteristics representing different stages of the disease process. Aggressive bone lesions are characterised by rapid growth with minimal or absent host response to confine and wall-off the lesion. Aggressive lesions are usually malignant - for example, due to a primary bone neoplasia - but may also be due to an infectious process such as fulminant osteomyelitis.
Non-aggressive lesions are slow-growing and relatively benign. They are characterised by a smooth, non-active host response with clear demarcation of the lesion as seen with a healing
1 / 39 fracture callus. The distinction between aggressive and non-aggressive lesions is important because of the potentially life-threatening consequences of their underlying causes. The prognosis and treatment vary widely depending on whether the lesion is thought to be aggressive or non- aggressive. With aggressive bony changes (as seen with osteosarcoma), timely identification and implementation of a diagnostic plan can be crucial in the treatment of the disease.
However, with a benign condition, performing a full diagnostic work-up - including invasive procedures, such as surgical biopsy - may not be indicated.
Evaluation
The parameters for evaluating whether a bone lesion is radiographically aggressive or nonaggressive include the following.
• Demarcation of lesion
Non-aggressive lesions usually have well-defined margins, whereas aggressive lesions are poorly demarcated. Non-aggressive lesions are slow growing and the bone is able to wall-off the lesion. In contrast, aggressive lesions grow rapidly and the bone is not able to form a response to confine the lesion.
• Zone of transition
Non-aggressive lesions have a short zone of transition and it is easy to tell where the lesion ends and normal bone begins. Aggressive lesions have a long zone of transition of abnormal to normal bone as they permeate into the surrounding bone, and the bone is not able to confine the lesion.
• Pattern of osteolysis
Non-aggressive lesions either do not produce osteolysis or produce a localised form. - Geographic osteolysis, the least aggressive form, is seen with slower-growing lesions. Geographic osteolysis usually consists of a single radiolucent area with a sclerotic rim, with or without cortical thinning and displacement, but no disruption. Such an appearance denotes an expansile lesion.
Non-aggressive lesions are slow growing and the body has time to form a response such as cortical remodelling or new bone formation surrounding the lesion. Geographic osteolysis is typically seen with bone cysts, osteoclastomas and enchondromas.
Aggressive lesions show more diffuse forms of osteolysis:
- Moth-eaten. Characterised by multiple, small, ill-defined areas of osteolysis that may coalesce into larger lesions.
2 / 39 - Permeative. The most aggressive form of osteolysis, which is seen with rapidly growing aggressive lesions, such as osteolytic osteosarcomas and haematogenous osteomyelitis. Permeative osteolysis is characterised by a large number of small to pinpoint areas of osteolysis with poorly defined borders. Permeative osteolysis is often best visualised superimposed over the cortex and displays a long zone of transition.
- Punched-out lesions. Radiolucent, well-defined areas of osteolysis are seen and there is no evidence of a sclerotic margin demarcating the lesion. They may appear well defined and, thus, less aggressive. However, the absence of a host response indicates that the lesions are more aggressive. Punched-out lesions are typically seen with multiple myeloma or metastatic bone disease.
• Cortical involvement
Non-aggressive lesions may cause thickening or displacement and thinning of the cortex, but will rarely cause disruption. Aggressive lesions will usually display cortical destruction, interruption and disruption due to the rapid and aggressive growth of the lesion.
Non-aggressive lesions display continuous solid or smooth periosteal reactions:
- Smooth and solid. Indicative of a slow-growing, benign process. The degree of opacity of the periosteal reaction is an indicator of chronicity; the more radioopaque the periosteal reaction, the more long-standing the process. Causes include fracture callus, panosteitis and chronic low-grade osteomyelitis.
- Lamellar and lamellated. Onion skin-like periosteal reaction as the periosteum is slowly and repeatedly lifted by the disease process and new bone is laid down beneath it. Causes include metaphyseal osteopathy and repeated trauma. Lamellated periosteal reaction may also be seen with a more aggressive lesion that has settled with time and/or treatment - for example, remodelled osteomyelitis.
Aggressive lesions display interrupted, irregular forms of periosteal reactions, when new bone is present:
- Brush border and palisading. As a bone lesion grows and displaces or destroys the cortical bone, the periosteum is lifted rapidly over a large area of the cortex. New bone is formed in a plane perpendicular to the cortex, resembling a brush border or palisade. If the reaction is less aggressive and takes place over a relatively longer time, the spicules are thicker and known as palisading or thick brush border, as seen in hypertrophic osteopathy (Marie’s disease).
3 / 39 More aggressive lesions cause rapid and continual lifting of the periosteum and the resulting brush border is composed of finer, more slender spicules. This is termed a thin brush border and indicates a more aggressive lesion - for example, acute haematogenous osteomyelitis or neoplasia.
- Sunburst. Highly aggressive lesions grow extremely rapidly, expanding outwards from the bone and causing rapid lifting of the periosteum overlying the lesion. A sunburst periosteal reaction consists of spicules of new bone radiating out from the centre of the lesion and an osteosarcoma is the most likely diagnosis.
- Amorphous. The mos t aggressive periosteal reaction and highly suggestive of a primary bone neoplasia. There is unstructured, neoplastic new bone with a complete loss of recognisable structure.
• Presence of Codman’s triangle
Lifting of the periosteum causes production of a solid triangle of new bone at the periphery of the lesion. It is often seen at the edge of a primary malignant bone tumour. However, Codman’s triangle can occur with benign processes.
• Presence of sclerosis
Sclerosis can be used as a radiological term to describe increased bone radiopacity. Sclerosis is either due to increased density of the bone or superimposed periosteal or endosteal new bone, and sclerosis represents the new bone laid down by the body to confine the lesion. Non-aggressive lesions will often have surrounding sclerosis, while aggressive lesions will not have surrounding sclerosis due to their rapid rate of growth.
• Rate of change
Non-aggressive lesions will have a slow rate of change or appear static, whereas a feature of aggressive lesions is that they have a rapid rate of change. Many of the radiological signs of an aggressive lesion are due to the rapid rate of change where there is minimal time for the bone to adapt or remodel.
Follow-up radiographs are a valuable tool in assessing lesions that display intermediate or low- grade aggressive features. Repeating the radiographic examination several weeks later will allow assessment of any radiographic changes and, thus, allow interpretation of the degree of aggression. A non-aggressive lesion will not change significantly in radiographic appearance over this time scale, whereas an aggressive lesion will.
• Location of the lesion
4 / 39 The location of a lesion can help in formation of a differential diagnosis list as certain disease processes have predilection sites where lesions are common.
- Osteosarcoma predilection sites are the metaphysis of the distal radius, proximal humerus, distal femur and proximal tibia (ie, away from the elbow and towards the knee). If an aggressive bone lesion is seen in one of these sites, osteosarcoma or other primary bone neoplasia should be ranked high on the differential list.
- Hypertrophic osteopathy (Marie’s disease) is characterised by a palisading periosteal reaction and soft tissue swelling, initially on the medial surface of the second digit, and the lateral surface of the fifth digit, before progressing proximally.
- Number of lesions. Polyostotic lesions (those that are present in more than one bone) occur with multiple myeloma, neoplasia that has metastasised to bone and, occasionally, with haematogenous infection.
- Presence of joint involvement. A lesion affecting two or more adjacent bones - for example, at a joint - is likely to be a soft tissue neoplasm invading bone or septic arthritis, since primary malignant bone neoplasms will rarely cross joints or affect multiple bones. Such soft tissue neoplasms include synovial sarcoma, histiocytic sarcoma and other soft tissue sarcomas.
Note that some lesions may display both aggressive and nonaggressive features and should be classified according to the most aggressive feature.
Bone neoplasia and bone infections have an aggressive radiographic appearance and, unfortunately, it is often impossible to distinguish between them by radiography alone. Histopathology of a bone biopsy and, in some cases, culture of the site is needed for the definitive diagnosis of an aggressive bone lesion. However, the location of the lesion, number of bones involved and the history and signalment of the patient can be used to form a differential diagnosis list. Most primary bone neoplasia will only affect one bone and will not cross the joint. The extent and severity of osteolysis is usually more severe with malignancy than with infection, and pathological fractures rarely occur with infectious processes. For example, an aggressive lesion with a pathological fracture affecting the proximal humerus in a large-breed dog will have an osteosarcoma as the primary differential.
Differential diagnoses for aggressive lesions in multiple bones (polyostotic) will include multiple myeloma, metastatic neoplasia and infection. Bacterial infections occur secondary to trauma, surgical intervention and haematogenous spread. The presence of a bite wound overlying the lesion will naturally put bacterial osteomyelitis at the top of the differential list.
Bacterial bone infections are usually limited to one limb but may affect more than one bone, especially if the infection is spread haematogenously. Haematogenous bacterial or fungal
5 / 39 osteomyelitis causes multifocal lesions that may occur in multiple bones (polyostotic), and the lesion appearance may range from osteolytic, osteoproductive or mixed with an active periosteal reaction. The presence of a portosystemic shunt predisposes to bacteraemia, which may lead to haematogenous osteomyelitis. Thus, radiographs of dogs with portosystemic shunts should be examined carefully for evidence of osteomyelitis, especially affecting the ventral lumbar vertebrae. Fungal osteomyelitis is endemic in some parts of the US and is generally of haematogenous origin, leading to polyostotic aggressive lesions.
In cases with aggressive bone lesions, thoracic radiographs to check for pulmonary metastasis should be performed prior to invasive procedures. The presence of pulmonary metastases will give information regarding the nature of the lesion and the prognosis of the patient. Right and left lateral radiographs, plus a dorsoventral or ventrodorsal view, should be performed to examine the lung fields thoroughly. Abdominal ultrasonography should be performed to check for the presence of abdominal metastases.
In summary, upon recognition of a bone lesion, following a logical, systematic approach and examining the lesion for criteria that allows classification as aggressive, low-grade aggressive or non-aggressive allows formation of a list of differential diagnoses and diagnostic plan.
Figures 1-8 are paired to demonstrate non-aggressive and aggressive bone lesions of the same anatomical area.
Further reading
Dennis R et al (2001). Small animal radiological differential diagnosis (first edn), W B Saunders. Thrall D (2002). Textbook of veterinary diagnostic radiology (fourth edn), W B Saunders. Thrall D (2002). Textbook of veterinary diagnostic radiology (fourth edn), W B Saunders.
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Figure 10a. Right lateral recumbent chest radiograph of an eight-year-old female boxer. There are numerous very small, discrete opacities scattered over the lung field - predominantly ventrally. They are extremely radiopaque for their small size; therefore, they must be mineralised and represent small areas of mineralisation or ossification in the lung parenchyma and/or pleura. This is an incidental finding.
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Figure 10b. Right lateral recumbent chest radiograph showing cannonball pulmonary metastases typical of osteosarcoma pulmonary metastatic disease.
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Figure 1a. A ventrodorsal intra-oral radiograph of the mandible of an eight-month-old German shepherd dog. There are multiple, discrete mineral/dental opacity structures superimposed over the lateral right mandible at the level of the fourth premolar tooth, which is displaced laterally (PM1 is absent on the right side). There is no evidence of osteolysis, periosteal reaction or cortical destruction; therefore, this is a non-aggressive lesion. The histological diagnosis was odontoma.
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Figure 1b. Intra-oral ventrodorsal radiograph of the mandible of a nine-year-old German shepherd dog with malignant melanoma. There is a soft tissue mass adjacent to the lingual surface of the left mandible. Note the severe underlying osteolysis and periosteal reaction with a long zone of transition to normal bone. There is an irregular, spiculated periosteal reaction and new bone formation on the lingual surface of the mandible between premolar-3 and molar-1. Radiological diagnosis is of a soft tissue mass with underlying aggressive bone lesion - therefore, probably malignant. The histological diagnosis was amelanotic melanoma invading bone.
Figure 2a. Craniocaudal radiograph of the antebrachium and carpus of a four-year-old
13 / 39 Rottweiler. There is a large, expansile, septated lesion in the distal ulna with a short zone of transition to normal bone. There is no evidence of radial or carpal bone involvement. This lesion is typical of a slow-growing expansile lesion - such as a bone cyst or osteoclastoma. The histological diagnosis was bone cyst.
Figure 2b. Radiograph of a nine-year-old Rottweiler with osteosarcoma of the distal radius centred on the metaphysis. There is an aggressive, mixed osteolytic/proliferative lesion of the distal radius with a long transition to normal bone. Note the motheaten and permeative osteolysis and the spiculated, unstructured periosteal new bone and soft tissue swelling. A Codman’s triangle is seen at the proximal edge of the lesion on the medial aspect of the radius.
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Figure 3a. Close up view of the lumbar spine of a 10-year-old Labrador with hindlimb paresis. Note the ill-defined area of reduced opacity 2cm diameter of the neural arch and body of L6; only one transverse process is visible. The poorly defined osteolysis with no evidence of sclerosis suggests an aggressive bone lesion. This case was diagnosed as soft tissue neoplasm causing destruction of part of L6.
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Figure 3b. Right lateral recumbent radiograph of an 11-yearold domestic short-haired cat. There is marked widening of the L5 vertebral canal; the dorsal surface of the vertebral body is concave with a mild, smoothly marginated increase in subchondral bone opacity. The smooth bone remodelling, cortical displacement and lack of osteolysis or periosteal reaction indicate that this is a non-aggressive bone lesion - for example, pressure atrophy of L5 caused by an expansile, soft tissue mass. The histological diagnosis was meningioma causing pressure atrophy of L5.
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Figure 4a. Mediolateral radiograph of the shoulder of a seven-year-old cocker spaniel. There is remodelling of the shoulder joint with subluxation and significant remodelling of the glenoid. There is new bone superimposed on to the cranial humerus, which may represent joint mice or bicipital groove soft tissue mineralisation. These changes are consistent with congenital shoulder dysplasia.
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Figure 4b. Mediolateral radiograph of the proximal humerus of a five-year-old German shepherd dog. There is a highly aggressive mixed, but mainly osteolytic, lesion affecting the proximal humerus. There is permeative osteolysis with overlying cortical thinning and destruction, amorphous new bone formation and a long zone of transition to normal bone. There appears to be a non-displaced pathological fracture. Histological diagnosis was osteosarcoma.
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Figure 5a. Radiograph of the lumbosacral region of a 10-year-old boxer with lumbar and lumbosacral spondylosis. Note the smooth, well-demarcated margins and lack of osteolysis, cortical involvement or reactive periosteal reaction. This is typical of a non- aggressive, non-active lesion.
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Figure 5b. Discospondylitis of the lumbosacral junction in a five-monthold greyhound. The vertebral end plates of L7 and S1 are osteolytic and irregular with extensive sclerosis. There is irregular new bone formation ventral to the LS junction and collapse of the dorsal part of the intervertebral space.
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Figure 6a. Mediolateral radiograph of the stifle of a seven-year-old bull mastiff showing severe stifle arthrosis. There is marked bony remodelling of the stifl e joint with large osteophytes seen. There is compression of the infra-patellar fat pad indicating the presence of a joint effusion. Note that the proliferative new bone is smooth and well demarcated with no evidence of osteolysis or cortical destruction. This is typical of a non-aggressive lesion.
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Figure 6b. Mediolateral radiograph of the stifle of a six-year-old Bernese mountain dog showing permeative osteolysis of the distal femur and proximal tibia. The femoral subchondral bone is thinned and there is displacement of the distal patella from the trochlear groove. There is an irregular soft tissue opacity within the joint, which compresses the infrapatellar fat pad. This is an aggressive lesion affecting both the femur and the tibia and causing an irregular soft tissue opacity within the joint - typical of an aggressive soft tissue neoplasm located near a joint. Histological diagnosis was histiocytic sarcoma.
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Figure 7a. Dorsopalmar radiograph of the right carpus of a six-year-old boxer. There is a solid, lamellated to palisading periosteal reaction present on the lateral aspect of the fifth metacarpal and digit, the medial aspect of the second metacarpal and the distal radius and ulna. There is diffuse soft tissue swelling of the limb. This patient had similar changes in the left distal limb and pulmonary metastases secondary to a renal carcinoma. The location and appearance of the periosteal reaction with the additional finding of pulmonary masses is pathognomonic for primary hypertrophic osteoarthropathy (Marie’s disease).
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Figure 7b. Craniocaudal radiograph of the tibia of a skeletally mature dog imported from the USA. The patient did not exhibit clinical signs of lameness and the lesion was identified on an abdominal radiograph. There is an extensive, exuberant, irregular periosteal reaction with a long zone of transition to normal bone and little evidence of osteolysis. It was diagnosed as osteomyelitis, of uncertain origin, but most likely a fungal aetiology.
Radiograph: COURTESY OF UNIVERSITY COLLEGE DUBLIN.
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Figure 8a. Severe hip osteoarthrosis, secondary to hip dysplasia, in a 10-year-old Maremma. There is subluxation of the hip and chronic, severe remodelling of the femoral head, neck and acetabulum. Note that the changes are smooth and well demarcated with no evidence of osteolysis, cortical destruction or aggressive periosteal reaction.
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Figure 8b. Osteosarcoma in an eightyear-old Dobermann. There is a highly aggressive, destructive lesion of the proximal femur with permeative and moth-eaten osteolysis and amorphous new bone. Multiple myeloma in a nine-year-old Labrador retriever.
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Figure 9a. Multiple myeloma in a nine-year-old Labrador retriever. There is extensive osteolysis of the spinous process of the fourth thoracic vertebra and destruction and displacement of the cortex with no evidence of sclerosis.
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Figure 9b. Multiple myeloma in a nine-year-old Labrador retriever. There is a poorly defined permeative osteolytic lesion in the body of L5 and the vertebral body is slightly shortened, suggesting a subtle pathological fracture. There is osteolysis of the dorsal lamina of L6 and ill-defined osteolysis of the neural arch. The presence of poorly demarcated osteolytic lesions in multiple sites is highly suggestive of multiple myeloma or bone metastases.
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