MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES
(ii) The investigation and
radiological features of
primary bone malignancy
Thomas Kuchenbecker
A Mark Davies
Steven LJ James
Abstract
Primary malignant bone tumours are rare. Imaging provides the founda-
tion of surgical and oncological management as it offers a differential
diagnosis for the nature of the lesion, defines its local extent and facili-
tates local-regional and distant staging. The role of radiographs,
computed tomography (CT), magnetic resonance imaging (MRI) and
bone scintigraphy is reviewed. In addition, some newer techniques
such as whole-body MRI and FDG-PET imaging are discussed. Finally,
we describe the epidemiology, subtypes and imaging features of the
most common primary malignant bone tumours including osteosarcoma,
chondrosarcoma, Ewing’s sarcoma and chordoma.
Keywords Bone tumor; computed tomography; imaging; magnetic
resonance imaging; radiographs
Introduction
Primary malignant tumours of the skeleton are rare and account for
only 0.2% of all neoplasms. The annual incidence of new diagnoses
in North America and Europe is 0.8/100 000 population.1 Primary
bone tumours comprise a wide spectrum of diagnoses as described
by the World Health Organization (WHO), whose classification is
based on their histopathological characteristics.2
The clinical and imaging assessment of a potential primary
bone tumour requires a systematic approach in order to ensure
that appropriate management can be instituted. In the first
instance, a clinical assessment is required at the time of presen-
tation to assess symptoms, which typically are fairly non-specific.
Pain may at first be mild and intermittent, but will become more
unremitting over time as the tumour enlarges. A sudden increase
may reflect a complication such as a pathological fracture through
Thomas Kuchenbecker MRCS FRCR Clinical Fellow, Department of Radi-
ology, The Royal Orthopaedic Hospital NHS Foundation Trust, Bristol
Road South, Northfield, Birmingham B31 2AP, United Kingdom.
A Mark Davies FRCR Consultant Radiologist, Department of Radiology,
The Royal Orthopaedic Hospital NHS Foundation Trust, Bristol Road
South, Northfield, Birmingham B31 2AP, United Kingdom.
Steven LJ James FRCR Consultant Radiologist, Department of Radiology,
The Royal Orthopaedic Hospital NHS Foundation Trust, Bristol Road
South, Northfield, Birmingham B31 2AP, United Kingdom.
ORTHOPAEDICS AND TRAUMA 24:4
weakened bone. Proximity of a lesion to a joint or invasion into it
may limit the range of movement. Systemic symptoms such as
fever, lethargy and weight loss are late signs. Whilst these clinical
signs may raise the suspicion of a potentially malignant lesion,
further investigation is required to establish the cause.
Radiographs remain of paramount importance in the assessment
of a primary bone tumour and are mandatory in all patients.3 In some
cases, a characteristic appearance is identified such that furthermore
advanced cross-sectional imaging techniques are not required.
Frequently, however, multiple differential diagnoses will need to be
considered and further investigation will be warranted. The poten-
tial diagnosis may include conditions which both clinically and
radiologically resemble a primary bone neoplasm. It is therefore
important to remember that both traumatic or stress-related injury
and infective lesions may mimic bone tumours.4,5 In order to try to
differentiate between pathological entities a combination of multiple
imaging modalities is often required including computed tomog-
raphy (CT), magnetic resonance imaging (MRI), bone scintigraphy
and positron emission tomography (PET). Despite ongoing devel-
opments in imaging techniques, biopsy remains vital for histological
confirmation in many cases. Once a histological diagnosis has been
achieved, further information regarding potential suitability for
resection is needed in the form of local staging to assess possible
primary excision and detection of distant metastatic disease.
The aim of this article is to equip the reader with an under-
standing of an appropriate method for evaluating a potential
primary bone tumour. The role of imaging studies will be dis-
cussed both in terms of diagnosis as well as local and distant
staging. The typical appearances which need to be recognized in
order to facilitate assessment of the radiographic features of
a bone tumour will be described. We will briefly discuss the role
and optimal methods for obtaining tissue for histological evalu-
ation. Finally, we will review a number of more specific
diagnoses including osteosarcoma, chondrosarcoma, Ewing’s
sarcoma and chordoma. The role of imaging in patient follow-up
will also be addressed. A number of tumours commonly
encountered in daily practice are excluded from this review such
as skeletal metastatic disease, myeloma and lymphoma as their
detailed description is beyond the scope of this article.
Age and location
The incidence of bone sarcomas as a group is bimodal with the
first peak occurring during the second decade of life and a second
peak occurring over the age of 60 years. This is in contrast to the
incidence rate of soft tissue sarcomas, which is seen to increase
gradually with age.2 Metastatic disease and myeloma become
increasingly important differential diagnoses in patients over the
age of 40 years. The age of the patient at presentation will
provide important diagnostic information as most tumours have
a characteristic predilection for certain age groups (Table 1).
Knowledge of the typical age at presentation therefore
provides significant help in narrowing potential diagnosis. It
should, however, be stressed that exceptions to the rule are
relatively frequently encountered at specialist centres and age
should be taken into account with additional diagnostic infor-
mation available from imaging and histology.
Most bone tumours, both benign and malignant, have a propen-
sity to affect certain locations within the long bones (Table 2).
252 Ó 2010 Elsevier Ltd. All rights reserved.
 MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES

Age distribution of malignant lesions Learning point

Type of bone lesion Age range C Age at presentation and lesion site are important parameters
Simple bone cyst 0e20 in guiding the differential diagnosis.
Ewing’s sarcoma 0e20
Chondroblastoma 0e25
Non-ossifying fibroma 15e25
Osteochondroma 15e25 The use of different imaging modalities in diagnosis and staging
Osteoblastoma 15e25
Conventional radiography
Osteosarcoma 15e30
Conventional radiography has been in clinical use for over
Osteoid osteoma 15e35
a hundred years and thus the cumulative experience with this
Aneurysmal bone cyst 15e35
imaging modality is much greater than with any of the more
Chondromyxoid fibroma 15e35
recent methods of cross-sectional and functional imaging.
Giant cell tumour 25e45
Radiographs remain essential in the evaluation of bone tumours
Lymphoma of bone 25e45
and frequently provide the most useful diagnostic information.
Fibrosarcoma 35e45
There are a number of radiographic features which can be
Malignant fibrous histiocytoma 35e45
appreciated that are of value in the assessment of a potential
Osteoma 35e55
primary bone tumour. These include lesion location, zone of
Parosteal osteosarcoma 35e55
transition, periosteal reaction, opacity and matrix mineralization,
Chondroma 15e55
cortical destruction and soft tissue extension.
Haemangioma 35e75
Chondrosarcoma 35e65 Zone of transition and margin
Myeloma 40e75 The zone of transition is the interface between the bone tumour
Chordoma 35e75 and the host medullary bone. Bone lesions may be characterized
as having a narrow zone of transition, i.e. being well-defined
Table 1 (Figure 1a), or having a wide zone of transition, i.e. being ill-
defined (Figure 1b). The zone of transition reflects the rate of
Conventional osteosarcoma, for example, tends to occur in tumour growth. A well-defined margin, particularly if sclerotic,
the metaphysis, which represents an area of rapid bone reflects slow or no growth with osteoblastic containment by the
growth, whereas Ewing’s sarcoma, histologically a round cell host bone. A wide zone of transition implies a more rapid growth
tumour, follows the distribution of red marrow.3 If the tumour of the lesion and therefore a more aggressive process, which can
location in reference to diaphysis, metaphysis and epiphysis is include infections as well as tumour infiltration. Furthermore,
identified and compared with the characteristic age of radiographic terms such as a ‘moth-eaten’ or ‘permeative’
presentation, the differential diagnosis may be further pattern can be used to describe ill-defined areas of lysis at the
narrowed. periphery of the tumour (Figure 1b).

Periosteal reaction
Characteristic locations of bone lesions6 The periosteum may react to the presence of a lesion that may be
located at a number of locations relative to the host bone including
Epiphysis Chondroblastoma the surface, cortex or medulla. Periosteal reaction can be subdivided
Giant cell tumour in end of bone in adult into several subtypes according to the appearance on radiographs.
Metaphysis Osteosarcoma The types of periosteal reaction identified include solid (Figure 2a),
Simple bone cyst lamellated (Figure 2b) and spiculate (Figure 2c) (either hair-on-end or
Osteoblastoma sunburst) and represent in ascending order a spectrum of increasing
Peripheral chondrosarcoma aggressiveness. Whereas a periosteal reaction of solid type may be
Giant cell tumour in child encountered in benign processes such as a healing fracture, osteoid
Diaphysis Ewing’s sarcoma osteoma and osteomyelitis, an increasing degree of interruption of
Central chondrosarcoma the integrity of the periosteum, as seen in a spiculate pattern, points to
Adamantinoma a more aggressive process. A Codman angle is the radiographic
Osteoid osteoma appearance of periosteum lifted off the underlying cortex at the
Chondromyxoid fibroma leading edge of a lesion and is commonly seen with osteosarcoma
Lymphoma of bone and Ewing’s sarcoma, but may also be caused by infection
Myeloma (Figure 3).7
Fibrous dysplasia
Fibrosarcoma Matrix mineralization
Fibrous cortical defect (non-ossifying fibroma) Matrix mineralization refers to the radiographic density of
a lesion and is determined by the composition of tissue within
Table 2 the tumour. The commonly described patterns of matrix

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 MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES

a AP radiograph of the femur demonstrating a well-defined lesion in the proximal femur with a narrow zone of transition and sclerotic margin. This
lesion shows the typical ground glass pattern of fibrous dysplasia. b AP radiograph of the tibia shows a lytic slightly expansile lesion showing
a wide zone of transition with a permeative pattern at the periphery. An interrupted periosteal reaction is evident (arrow) in this telangiectatic
osteosarcoma.

Figure 1

mineralization include osseous, chondroid and fibrous. Osseous
matrix typically appears as confluent areas of amorphous cloud-
like opacification (Figure 3) whereas chondroid lesions show
punctate, arc-like or dot and comma shaped calcifications
(Figure 4). A fibrous matrix is often described as showing
a ‘ground glass’ appearance (Figure 1a).
The degrees of relative lucency and opacity seen on radio-
graphs are usually described as either sclerotic, lytic or a mixed
sclerotic/lytic appearance. This is the result of the balance
between osteoclast and osteoblastic action. There can be
considerable variation amongst individual tumour types and
their relative degrees of lucency/sclerosis. Whilst osteosarcoma
typically demonstrates a sclerotic metaphyseal lesion, both
mixed and lytic variants are not infrequent.
Cortical destruction and soft tissue extension
An expansile medullary lesion may erode the inner surface of the
cortex and thereby cause endosteal scalloping. This may be
identified in cartilage lesions such as enchondroma or low-grade
chondrosarcoma. If the process is slow, it will be balanced by
periosteal deposition of new bone and the cortex remains intact
(Figure 5). If, however, the endosteal erosion outpaces the
periosteum’s capacity for new bone formation, cortical breach
results e the hallmark of an aggressive process. Furthermore,
frank soft tissue extension is often but not invariably a sign of
malignancy. A lesion may also originate in the periosteum or
adjacent soft tissues and cause erosion of the outer surface of the
cortex thereby causing saucerization. This radiographic appear-
ance may be seen in Ewing’s sarcoma of a long bone (Figure 6).
Periosteal reaction adjacent to saucerization of the cortex may
result in a buttressed appearance.3
Computed tomography (CT)
In areas of the skeleton such as the pelvis or other flat bones
where the pattern of bone destruction and the presence of matrix
mineralization may be difficult to appreciate on radiographs, CT
may be helpful in the diagnosis.8 In particular, it can aid in the
identification of subtle areas of chondroid matrix in the spine and
pelvis (Figure 7). Occasionally, CT can be utilised as a method of
local staging if MRI is contraindicated. CT does, however, allow
the degree of extraosseous tumour to be assessed and reporting
examinations on a console with careful windowing further helps
with this. CT angiography can also be utilized if the relationship
to the neurovascular bundle needs to be further clarified.
In view of the propensity of malignant bone tumours to
metastasize to the lungs, CT is widely used in tumour staging to
evaluate the thorax for metastatic disease. With the advent of
multi-detector CT technology, a common problem in clinical
practice is the identification of small pulmonary nodules which
are of indeterminate significance. These may be due to old
calcified granuloma, intrapulmonary lymph nodes or previous
histoplasmosis (the latter being more common in USA). It
is, however, impossible in many cases to exclude small metas-
tases and follow-up imaging in the form of interval chest CT is
required to ensure no progression of the imaging findings is
identified.
In patients over the age of 40 years, where the bone lesion is
apparently solitary on other staging investigations, CT of the

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 MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES

a Lateral radiograph of the forearm illustrates an osteoid osteoma with a smooth solid periosteal reaction in the distal radius. b Lateral radiograph
of the elbow shows a lamellated periosteal reaction in the distal humerus (arrow) secondary to a Ewing’s sarcoma. The AP view shows a mixed
pattern, which can be appreciated in many tumours, with a spiculate component (arrowhead) also being present. c AP radiograph of the ankle
illustrates an aggressive spiculate periosteal reaction (arrow) in this distal tibial osteosarcoma.

Figure 2

chest, abdomen and pelvis may be required. 10% of bone
metastases present as solitary lesions and screening CT may
identify the primary tumour though biopsy will still be required
for histological subtyping.
Magnetic resonance imaging (MRI)
MRI plays an extremely important role in the diagnosis and
management of bone tumours. Firstly, it adds to the information
which should have been gained from radiographs in terms of
diagnosis. A number of specific MRI appearances can aid in
differentiating benign from reactive and neoplastic processes.
Secondly, MRI with its inherent soft tissue contrast is the imaging
modality of choice for local staging and assessment of potential
resectability of a bone tumour especially in the presence of an
extraosseous mass. Finally, it seems increasingly likely that
whole-body MRI will supplant bone scintigraphy as the optimal
method of assessing the presence of skeletal metastatic disease.
A basic MRI protocol would include a combination of T1,
STIR and T2-weighted sequences in the axial, coronal and
sagittal planes. It is essential that the whole affected bone be
imaged either in the coronal or sagittal plane to identify the
presence of skip metastases.9,10 It is the authors’ preference to
perform this using a single T1-weighted sequence (Figure 8).
The extent of tumour involvement in the medullary cavity is
best assessed on T1-weighted sequences as short tau inversion
recovery (STIR) sequences tend to overestimate the tumour
extent by highlighting the degree of peritumoral oedema.
The longitudinal intraosseous extent of the tumour needs to be
established on coronal or sagittal images. Measurement of the
tumour extent from the adjacent articular surface facilitates
planning the margins of the surgical resection and the manu-
facture of the endoprosthetic replacement.9 The relationship to
or involvement of the growth plate should be described where
applicable. The extraosseous extent of tumour and its rela-
tionship to the neurovascular bundle should be assessed
(Figure 9). The presence of a joint effusion per se does not
necessarily imply tumour spread into the joint and is
commonly reactive in nature. It is, however, helpful if no

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 MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES

Figure 5 Lateral radiograph of the femur shows cortical expansion over

a short focal segment (arrow) in this low-grade chondrosarcoma of the
Figure 3 AP radiograph of the knee demonstrates a distal femoral oste- femur.
osarcoma. It shows an osseous matrix with an area of periosteal elevation
being evident on the lateral aspect of the tumour e a Codman triangle
osteosarcoma.9,11 Intravenous contrast can, however, be useful
(arrow).
in distinguishing solid from cystic lesions and this latter finding
may aid in planning biopsy should a necrotic area be present
effusion is present as this increases diagnostic confidence that
within a malignant lesion. Dynamic contrast-enhanced MRI has
the joint is spared.
been used to depict the vascularization and perfusion of lesions
Contrast-enhanced MR images are helpful in characterizing
although an overlap in appearance between highly vascular
bone tumours, assessing response to therapy and detecting
benign lesions and malignant lesions has been reported.12
tumour recurrence. The contrast agent gadolinium decreases the
Contrast enhancementetime curves have been found to differ
T1 relaxation time and thereby increases signal intensity on T1-
for viable extraosseous tumour and infiltrated muscle and merely
weighted images from tissues where the contrast accumulates. In
oedematous peritumoral muscle. Viable tumour enhances more
order to mask the high signal from fat on a T1-weighted image,
quickly than oedematous muscle, causing a significant difference
fat suppression needs to be applied, thereby highlighting areas of
in the slope of the enhancement curve. Dynamic contrast-
contrast enhancement. Static gadolinium enhancement has not
been shown to be of significant benefit in defining the margins of

Figure 4 AP radiograph of the pelvis shows the typical chondroid matrix in Figure 6 AP radiograph of the femur shows classic saucerization of the
this chondrosarcoma arising in the ilium in a patient with diaphyseal aclasis. cortex (arrow) secondary to Ewing’s sarcoma.

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 MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES
Figure 7 Axial CT of the pelvis showing the typical chondroid matrix of
a chondrosarcoma involving the left sacral ala.
Figure 8 Sagittal T1-weighted image demonstrating multiple areas of
intermediate signal intensity within the humerus in keeping with skip
metastases. The patient had a distal humeral Ewing’s sarcoma.
ORTHOPAEDICS AND TRAUMA 24:4
Figure 9 Sagittal T1-weighted sequence demonstrates intra-articular
invasion of a distal femoral osteosarcoma.
enhanced MRI has improved the assessment of post-chemo-
therapy response of high-grade osteosarcoma and Ewing’s
sarcoma to chemotherapy by helping distinguish tumour from
post-therapy inflammatory changes.10
Although conventional radiographs are the mainstay in the diag-
nosis of bone tumours, a number of features can be analyzed on MRI
to aid the further characterization of bone tumours and tumour-like
conditions.13 Oedema may be found in both an intramedullary and
extraosseous location adjacent to both benign and malignant entities.
It is, however, most frequently encountered with benign and reactive
conditions including infection. It may be associated with malignant
tumours such as osteosarcoma, metastasis, chondrosarcoma and
Ewing’s sarcoma, though it will almost invariably be present if
a pathological fracture has occurred.14 The distinction between
tumour and surrounding oedema can be difficult, but is important in
guiding biopsy and surgical planning.13 Tumour-related oedema
(TRO) is of a signal intensity between that of fat and skeletal muscle
on T1-weighted images and of high signal intensity on T2-weighted
fat-suppressed images. It typically shows a poorly defined margin in
bone and a feathery appearance in the adjacent soft tissues.13
Fluid-fluid levels (FFLs) are not specific to either benign or
malignant disease.15 The greater the proportion of FFLs to solid
component, the more likely the lesion is benign. Conversely,
a lesion that is composed of FFLs to less than one third of its overall
size is more likely malignant (Figure 10), commonly conventional
central osteosarcoma.16 Differentiating aneurysmal bone cyst, the
quintessential benign lesion associated with FFLs, from telangi-
ectatic osteosarcoma can be difficult on imaging (Figure 10).13
Flow voids result from rapid blood flow in arteries where blood
leaves the slice between the application of the radiofrequency pulse
and its sampling in order to create an MR image.17 Flow voids
correlate with areas of abnormal blood vessels in hypervascular
lesions such as certain metastases (renal) and benign lesions, but
257 Ó 2010 Elsevier Ltd. All rights reserved.
 MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES

Figure 10 Axial T2 fat-suppressed sequence showing a fluid-fluid level

(arrow) in a telangiectatic osteosarcoma of the proximal fibula. Fluid-fluid
levels make up less than one third of the lesion.

also rare vascular tumours such as haemangioendothelioma, hae-

mangiopericytoma and angiosarcoma.18
Fat signal intensity within a tumour usually denotes a benign
lesion. Liposarcomas of bone are rare and would show, in
addition to the presence of fat, aggressive features such as bone
destruction.19 MRI depicts fat as high signal on T1, high signal on
T2 and low signal on STIR or fat-suppressed imaging. As a note
of caution, high signal on T1-weighted imaging due to fat must
be differentiated from haemorrhage commonly seen in tumours
such as cystic fibrous dysplasia and giant cell tumour and
melanin in melanoma and its metastases.20
Well-differentiated cartilaginous lesions have a characteristic
MRI appearance both morphologically and with regard to signal
intensity. Low-grade chondral tumours are commonly lobulated in
outline, isointense to muscle on T1-weighted images and markedly
hyperintense on T2-weighted and STIR images.13 Internal and
peripheral vascularized septa are hypointense and enhance Figure 11 Sagittal STIR of a low-grade chondrosarcoma in the distal femur
(same patient as Figure 5) demonstrates a small area of cortical breach
following administration of gadolinium. The distinction between
with soft tissue extension (arrow).
enchondroma and low-grade chondrosarcoma can be difficult on
imaging and at histology. Features suggestive of malignancy
would include endosteal scalloping to greater than two thirds of maturity, cartilage cap thickness greater than 2 cm in children and
cortical thickness, cortical destruction, epiphyseal and soft tissue 3 cm in adults and an associated soft tissue mass.22
extension (Figure 11), size greater than 5 cm and areas of Dedifferentiation is the transformation of a benign chondral
heterogeneous low signal on T2-weighted imaging, the latter due tumour or low-grade chondrosarcoma into a high-grade non-chon-
to more fibrovascular components in chondrosarcoma.21 Chon- droid tumour.23 Identification of dedifferentiation on MRI is helpful
drosarcomas show enhancing low signal septa in a ring and arc- in targeting biopsies and providing accurate diagnosis and prognosis.
like arrangement between high signal lobules of cartilage. Whole-body MRI is emerging as an interesting alternative
Osteochondromas are common benign tumours with charac- imaging modality for staging purposes, holding as advantages
teristic continuity with the underlying bone marrow at the level of over CT and FDG-PET/CT the lack of ionizing radiation and
the metaphysis. They are often covered by a cartilage cap, which is improved anatomic resolution.24 Recent technological advances,
low to intermediate signal on T1-weighted imaging and high signal including a rolling MRI scanner platform, parallel imaging and
on T2-weighted and STIR sequences.13 Malignant transformation phased array coils, have helped reduce imaging times and
occurs in 1% of solitary and 3e5% of hereditary multiple exos- thereby made the technique useful in clinical practice.25
toses (diaphyseal aclasis) (Figure 4). Imaging features of malig- The role of whole-body MRI in staging of primary bone
nancy are an increase in size of the cartilage cap after skeletal tumours however remains to be formally defined with limited

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 MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES
studies currently available on the sensitivity and specificity of the
technique.26,27 It is clear from studies assessing metastatic
disease from other primary malignancies, however, that whole-
body MRI is a promising technique (Figure 12). Whole-body MRI
has been reported to be superior to isotope bone scanning with
Tc-99m MDP for skeletal metastatic disease from a whole range
of primary visceral tumours. This is easily explained by the fact
that isotope bone scanning requires an osteoblastic reaction to
have been induced by a metastatic deposit, leading to increased
radiopharmaceutical uptake e a relatively late phenomenon in
medullary metastases.25 A possible exception are paediatric
patients where increased bone marrow cellularity may render
Figure 12 Coronal STIR whole-body MRI showing a metastasis in the
proximal left femur (arrow).
ORTHOPAEDICS AND TRAUMA 24:4
MRI less sensitive for the detection of bone metastases.27,28
Studies that included relatively high proportions of patients
with primary musculoskeletal malignancies demonstrated that
both whole-body MRI and FDG-PET/CT identified more skeletal
metastases than Tc-99m MDP skeletal scintigraphy alone.
Nuclear medicine
Bone scintigraphy is widely employed for evaluating the entire
bony skeleton for the presence of metastatic disease. It may
depict non-specific areas of increased radionuclide uptake, which
represent raised osteoblastic activity. Osteoblastic activity can be
increased in the context of tumour infiltration, degenerative joint
disease, Paget’s disease and infection. These areas of abnormal
uptake may require further confirmation as to their true nature
through the use of other imaging techniques such as CT or MRI
and occasionally biopsy. Osteosarcoma metastases, even if
extraskeletal, may show increased radionuclide uptake on scin-
tigraphy and, when situated in the lungs, can simulate rib
deposits (Figure 13a, b).
Positron emission tomography (PET) utilizes the accumulation
of 18-fluoro-2-deoxyglucose (18-FDG) in metabolically active
tissues and abnormal uptake can be seen in a variety of different
tumours and their metastases. Studies comparing the relative
ability of FDG-PET and Tc-99m MDP bone scintigraphy to detect
skeletal metastases from primary bone tumours showed that the
FDG-PET was more sensitive in demonstrating metastases from
Ewing’s sarcoma (Figure 14), but less sensitive in identifying
metastases from osteosarcoma.29 With regard to depicting small
pulmonary metastases, FDG-PET has been shown to be less sensi-
tive for small nodules less than 7e10 mm in size.30 However, FDG-
PET as a stand alone imaging modality has been increasingly
superseded by FDG-PET/CT, which combines two imaging
modalities. Since the spatial resolution of PET itself is inferior to that
of other cross-sectional imaging techniques, the functional tissue
information of the PET scan is co-registered with the anatomical
information of a simultaneously acquired CT scan. In this way,
fused images of both imaging modalities allow for attribution of
areas of increased tracer uptake to well-defined anatomical areas.
FDG-PET/CT is superior in demonstrating lung metastases due to
providing better contrast resolution between pulmonary nodules
and the surrounding pulmonary parenchyma and excluding motion
artefact with a fast data acquisition.24 It is likely that the role of PET/
CT will continue to expand in forthcoming years. However, at this
stage it is most frequently used as a ‘problem solving tool’ rather
than as a routine part of bone tumour staging.
Biopsy
Biopsy still remains of paramount importance in establishing
a histological diagnosis in most cases. It is extremely important
when performing such procedures that samples are obtained and
sent for both histological and microbiological examination.
Infectious processes including tuberculosis may mimic primary
bone tumours in terms of their radiographic appearances and
should be excluded in all cases.
Image guided biopsy with ultrasound and CT plays an
increasingly important role in obtaining tissue samples. When
this is compared with open biopsy it has been demonstrated that
there is a reduction in net cost, increased diagnostic yield and the
minimal access nature of the procedure reduces associated soft
259 Ó 2010 Elsevier Ltd. All rights reserved.
 MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES
a Technetium 99m bone scan demonstrating areas of abnormal
uptake over the right hemi-thorax in a patient with a large oste-
osarcoma of the pelvis. b CT showed this to relate to radionuclide
uptake within calcified pulmonary metastases.
Figure 13
ORTHOPAEDICS AND TRAUMA 24:4
Figure 14 Fused coronal FDG-PET/CT showing abnormal areas of uptake in
the right pelvis in a patient with a rib Ewing’s sarcoma consistent with
metastatic disease (arrow).
tissue trauma.31 CT guidance is particularly useful in small
lesions or those involving the pelvis and spine.
Once tissue has been obtained, it is vital that the clinical,
radiological and histopathological findings are reviewed in
consensus at a multidisciplinary meeting. This should involve
input from surgeons, radiologists, pathologists and oncologists. It
is not uncommon that the radiological and pathological findings
do not correlate and decisions regarding treatment including the
possibility of repeat biopsy are required in order to reduce
diagnostic error. Given the rarity of primary bone tumours, this is
best performed at dedicated specialist orthopaedic oncology
units. If a suspected bone tumour is identified on imaging, it
should be referred once appropriate staging investigations have
been performed for further evaluation. Biopsy is best undertaken
at the treating institution. It is vital that surgical advice is taken
before proceeding to biopsy so that the tract does not contami-
nate the resection field. Previous studies have demonstrated that
inappropriate biopsy may be undertaken at centres not used to
treating such cases. In the most unfortunate instances this can on
occasion lead to amputation in patients whose primary tumour
would have been suitable for limb salvage surgery.32
260 Ó 2010 Elsevier Ltd. All rights reserved.
 MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES
Learning points: the use of different imaging
modalities in diagnosis and staging
C Conventional radiography is still indispensible in the initial
assessment of bone tumours.
C A systematic approach to the interpretation of radiographs is
required. Features to assess are location, zone of transition,
periosteal reaction, opacity and matrix mineralization, cortical
destruction and soft tissue extension.
C CT allows for imaging of tumour matrix in radiographically
difficult areas of the axial skeleton and flat bones. CT is
superior to other imaging modalities in assessing the thorax
for metastatic disease.
C MRI most accurately assesses the intraosseous and extraoss-
eous tumour extent and is an essential tool in local staging
and preoperative planning.
C Bone scintigraphy is still the preferred technique for assessing
the entire skeleton for bone metastases. However, the role of
whole-body MRI continues to expand.
C PET/CT combines the functional information of FDG imaging
with the anatomical information of CT, but is still inferior to
conventional CT in detecting small lesions below 5 mm in
diameter, particularly in the thorax. At this time, its use is as
a ‘problem solving tool’.
Common primary bone malignancies
Osteosarcoma
Osteosarcoma is the most common non-haematological primary
bone tumour with an estimated incidence of 4e5 per million per
annum.2 There is no particular ethnic or racial predisposition. It
predominates in the younger population with 60% of patients
being under the age of 25 years. The male to female ratio is 3:2
with this male predilection being more pronounced for the
younger age peak.33
The classical tumour type arising within medullary bone is
referred to as conventional osteosarcoma and accounts for approx-
imately 75% of all cases, but the WHO classification describes
a number of rarer variants which are covered later in this section.
In patients over 40 years, a predisposing condition such as
Paget’s disease or prior radiation treatment may be a contribu-
tory factor. Osteosarcoma secondary to prior radiotherapy can
show a median time lag of 11 years prior to presentation. Paget’s-
associated osteosarcoma is usually observed in patients with
widespread Paget’s disease with an estimated incidence of
0.7e0.95% of Paget’s disease. The median age of diagnosis is
64 years and the male to female ratio is 2:1.34
The radiographic appearance of conventional osteosarcoma is
extremely variable and can show a purely lytic, mixed or sclerotic
appearance (Figures 1b, 2c, 3). Areas of mineralized osteoid
production within the tumour mass show cloud-like amorphous
calcification whereas areas of unmineralized fibrous tissue and/or
cartilage give a lytic appearance.35 Aggressive features will be
present such as wide zone of transition, cortical breach with soft
tissue mass and periosteal reaction, classically of the spiculate,
sunburst type. A Codman angle with elevation of the periosteum is
common but not exclusive to osteosarcoma (Figure 3). CT can
ORTHOPAEDICS AND TRAUMA 24:4
demonstrate small areas of matrix mineralization that may not be
evident on radiographs and can aid in differentiating osteosarcoma
from Ewing’s sarcoma. MRI typically shows extensive medullary
infiltration with a tumour mass of intermediate signal intensity on
T1-weighted imaging relative to skeletal muscle and of heteroge-
neous intermediate/high signal intensity on T2-weighted imaging
(Figure 9). Fat-suppressed T1-weighted gadolinium-enhanced
images can help in assessing extension of tumour into a joint
although reactive synovial enhancement may mimic tumour spread.
MRI is best suited for identifying skip metastases when a T1-
weighted sequence of the entire length of the bone is obtained.24
Telangiectatic osteosarcoma accounts for less than 4% of all
cases of osteosarcoma and is most frequent in the second decade of
life with a male predominance of 1.5:1. It usually arises in the
metaphysis around the knee and may extend into the epiphysis. Its
outcome following treatment is similar to that of conventional
osteosarcoma. Telangiectatic osteosarcoma usually causes a moth-
eaten, lytic appearance with a wide zone of transition and with an
aggressive periosteal reaction, but without significant sclerosis
(Figure 1b).2,35 Oblique and parallel striations in early cases within
the shaft of the bone are thought to reflect hypertrophy of intra-
osseous veins, but will be obliterated as the destruction of the bone
architecture progresses. A multilocular or pseudocystic appearance
on MRI with multiple fluidefluid levels due to blood products may
be present and can mimic an aneurysmal bone cyst (Figure 10).
Small cell osteosarcoma accounts for 1.5% of osteosarcomas.
It occurs in patients over a wide age range, but mostly in the
second decade of life. Its prognosis is very poor. Radiographi-
cally, its appearances are identical to those of conventional
central osteosarcoma.35
Low-grade central osteosarcoma constitutes 1e2% of osteo-
sarcomas with a peak incidence in the second and third decades of
life. It has a distinct predilection for the distal femur and proximal
tibia. The tumour grows more slowly and is more indolent than
conventional osteosarcoma and symptoms may have been present
for many months up to several years prior to diagnosis. There is
a high incidence of local recurrence after inadequate resection with
a tendency for the recurrence to be of a higher histological grade or
to become dedifferentiated. This higher grade recurrence can be
associated with increased risk of metastatic disease. Low-grade
central osteosarcoma has been reported as showing one of four
radiographic patterns, lytic with coarse trabeculation, predomi-
nantly lytic, densely sclerotic and mixed lytic and sclerotic.35 The
radiological differential diagnosis includes fibrous dysplasia,
ossifying and non-ossifying fibroma and fibroxanthoma.
Parosteal osteosarcoma is a low-grade osteosarcoma arising
on the surface of bone and accounts for approximately 4% of all
osteosarcomas. Most patients are young adults and females
predominate slightly. The prognosis is excellent with 91%
overall survival at 5 years unless the tumour is incompletely
excised and occurs in a dedifferentiated form. Parosteal osteo-
sarcoma has a tendency to wrap around bone and on radiographs
presents as a large, densely sclerotic and irregularly marginated
mass (Figure 15). The marked mineralization is reflected by low
signal intensity on MRI. CT and MRI are helpful in assessing the
extent of any medullary involvement, if present.
Periosteal osteosarcoma accounts for less than 2% of osteosar-
comas. Its peak incidence is in the second and third decades with
a slight male predominance. Arising from the deep surface of the
261 Ó 2010 Elsevier Ltd. All rights reserved.
 MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES
Figure 15 Lateral radiograph of the distal femur showing a parosteal
osteosarcoma of the distal femur.
periosteum, it has a distinct predilection for the diaphysis of long
bones, particularly the tibia and femur. Periosteal osteosarcoma on
radiographs commonly has the appearance of a broad based soft
tissue mass attached to the diaphyseal cortex, sparing the medul-
lary cavity. Soft tissue mineralization is variable and a chondroid
type of matrix calcification may be demonstrated on CT and MRI.35
High-grade surface osteosarcoma accounts for less than 1% of
osteosarcoma cases. The peak incidence is in the second decade
and there is a slight male predilection. High-grade surface oste-
osarcoma may appear radiologically similar to periosteal osteo-
sarcoma, but often encircles the host bone completely and
invades the medullary cavity.
Learning points: osteosarcoma
C Osteosarcoma is the most common non-haematological
primary malignant bone tumour.
C Cases in the younger age group are mainly de novo, but at the
second, older age peak there may be a predisposing factor
such as prior radiation treatment or Paget’s disease.
C The most common site of origin is the metaphysis of long
bones, particularly around the knee.
C Conventional osteosarcoma displays a combination of
aggressive features on radiographs, including wide zone of
transition, cortical breach with soft tissue mass, aggressive
periosteal reaction and cloud-like calcific density due to
malignant osteoid production.
C Certain radiographic and MRI features can aid in the further
subcategorization of osteosarcomas.
ORTHOPAEDICS AND TRAUMA 24:4
Chondrosarcoma
Chondrosarcoma represents a malignant tumour showing hyaline
cartilage differentiation. However, areas of myxoid change,
calcification or ossification may be present within the tumour
mass. Histologically, the tumour can be assigned to grades 1e3,
corresponding to low, intermediate and high-grade chon-
drosarcoma. The grade is based on nuclear size, staining and
cellularity. A higher grade tumour grade confers a worse prog-
nosis. Chondrosarcomas can be classified as central, if they orig-
inate in the medullary canal, peripheral and, rarely, juxtacortical.
Primary chondrosarcoma represents approximately 20% of
malignant bone neoplasms. The majority of patients are above the
age of 50 years with the peak incidence in the fifth to seventh
decades. There is a slight male preponderance.36 The most
common sites of involvement include the pelvis, particularly the
ilium (Figure 4), in the long bones, such as the proximal or distal
femur and proximal humerus, and in the ribs. The majority of
primary chondrosarcomas are grade 1 or 2. Periosteal chon-
drosarcoma arises from the surface of bone and is very rare. It
affects the metaphyses of long bones, particularly the distal femur.
Secondary chondrosarcoma develops from a benign precursor
condition such as osteochondroma, enchondroma or periosteal
chondroma. Solitary osteochondroma has an estimated 2% risk and
multiplicity of osteochondromas (diaphyseal aclasis) a 5e25% risk
of malignant transformation (Figure 4).36 Malignant transformation
of enchondroma is related to Ollier’s disease and Mafucci’s
syndrome, entities that are characterized by the formation of multiple
enchondromas. An association with previous radiation treatment or
pre-existing Paget’s disease has also been reported.37,38
Dedifferentiated chondrosarcoma is a distinct category that is
associated with a very different and dismal prognosis. Histologically,
the tumour shows an area of cartilage differentiation abruptly inter-
faced with another area of high-grade non-cartilaginous sarcoma.
This subtype accounts for 10% of all chondrosarcoma cases. The
average age at diagnosis is 50e60 years. The tumour most commonly
occurs in the pelvis, femur and humerus.39
The radiographic finding of a ring-and-arc pattern of matrix
mineralization suggests a chondroid lesion (Figures 4, 5, 7). The
slow growth of central chondrosarcoma may result in endosteal
scalloping. Periosteal reaction and soft tissue extension may occur
in higher grade lesions (Figure 11). MRI demonstrates a lobular
mass wherein non-calcified areas of high signal intensity on T2-
weighted imaging and calcified areas of low signal intensity on all
pulse sequences are evident. This causes a very heterogeneous
Learning points: chondrosarcoma
C Chondrosarcoma may arise de novo or on the basis of a pre-
existing precursor lesion such as an osteochondroma.
C Patients with diaphyseal aclasis, Ollier’s and Mafucci’s disease
are at increased risk of malignant transformation.
C The typical radiographic appearance is characterized by a chon-
droid matrix with a ring and arc-like pattern of calcification. The
appearances become more aggressive in higher grade tumours.
C Dedifferentiated chondrosarcomas are bimorphic with a non-
cartilaginous, sarcomatous component and have a distinctly
poor prognosis.
262 Ó 2010 Elsevier Ltd. All rights reserved.
 MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES

signal pattern on T2-weighted images. However, since low signal

on T2-weighted imaging is not specific to calcification, but may
also be seen with fibrous tissue with high collagen content, CT is
superior in characterizing matrix calcification (Figure 7).40

Ewing’s sarcoma and Primitive Neuroectodermal Tumour

(PNET)
Both tumours are round cell tumours and constitute parts of the
same disease spectrum. The histological hallmark is the dense
packing of small round cells some of which are arranged in a
rosette-like pattern (HomereWright rosettes). Ewing’s sarcoma/
PNET accounts for 6e8% of primary malignant bone tumours. It
is the second most common bone sarcoma in children. 80% of
cases occur in patients under the age of 20 years. There is a male
preponderance with a ratio of 1.4 to 1. The tumour is much more
common in people of white ethnic origin than in other races.41
Ewing’s sarcoma commonly arises in the diaphysis or proximal Figure 16 Axial T2 fat-suppressed MRI demonstrating a chordoma of the
meta-diaphyseal region of long bones, the pelvis or ribs. sacrum. It shows a lobular outline and has a hyperintense signal pattern.
The typical feature on radiographs is a pattern of ill-defined,
permeative, moth-eaten bone destruction. Most lesions (75%) tissue mass may invade the rectum and is better demonstrated on
are mixed lytic-sclerotic, some (25%) are purely lytic. A spiculate cross-sectional imaging. The tumour commonly has a lobulated
periosteal reaction is visualized in 50% of tumours (Figure 2b) margin (Figure 16). MRI shows a low to intermediate signal
and Codman angle is evident in 27%.42 Cortical permeation and intensity mass on T1-weighted and a high intensity mass lesion
destruction are seen in a little over one third of cases. A large soft on T2-weighted and STIR images relative to skeletal muscle.44
tissue mass may cause saucerization of the bone cortex
(Figure 6). MRI shows medullary infiltration with tumour that is
of intermediate signal intensity on T1-weighted and of interme-
diate/high signal intensity on T2-weighted and STIR imaging Learning points: chordoma
relative to skeletal muscle. Skip metastases (14%) and distant
metastases (22%) may be present at presentation. C Low to intermediate grade malignant tumour of notochordal
remnants with a predilection for either end of the axial skel-
eton and a tendency for local recurrence.
C MRI is important in defining tumour extent and involvement of
Learning points: Ewing’s sarcoma important adjacent anatomical structures.

C Aggressive round cell tumour, mainly of children and adoles-

cents, in the long bones, pelvis or ribs.
C There is a strong predilection for the white ethnic group.
C Radiographs show an ill-defined, permeative, moth-eaten
pattern of bone destruction. Periosteal reaction, cortical sau-
cerization and soft tissue mass are further recognized
features.
Chordoma
This tumour arises from notochordal remnants and therefore in
the midline of the axial skeleton. It has a predilection for the clivus
and the sacrum. It accounts for 1e4% of all primary malignant
bone tumours. It grows slowly for months to years prior to diag-
nosis and is hence classed as a low to intermediate grade malig-
nant tumour. Nonetheless it has a high potential for involvement
of important local structures including cranial nerves, the pitui-
tary, spinal nerve roots and spinal cord.2 There is a tendency for
local recurrence following surgical resection. The tumour
commonly presents in patients over the age of 30 and most
commonly in the sixth decade. The male to female ratio is 1.8:1.43
Sacral tumours may be difficult to identify on radiographs, but
may show a lytic midline lesion with loss of definition of the
arcuate lines within the sacrum. An associated presacral soft
Follow-up imaging
Osteosarcoma, with the exception of parosteal and low-grade
central osteosarcoma, and Ewing’s sarcoma are treated with
chemotherapy prior to surgery. Radiotherapy may be added to
the treatment regimen for Ewing’s sarcoma. Although regarded
as ineffectual in the treatment of chondrosarcoma as a general
rule, neoadjuvant therapy may be utilized in the treatment of
dedifferentiated chondrosarcoma.
Surgery is aimed at resecting the tumour with clear margins
and reconstructing the affected limb. Through the use of neo-
adjuvant therapy and limb salvage surgery, the quality of life and
survival rates for patients have improved.
Learning points: follow-up imaging
C MRI is the main tool for assessing the response of the primary
tumour to neoadjuvant chemotherapy and for assessing local
disease recurrence.
C Chest radiographs and CT of the thorax are used for moni-
toring for pulmonary metastatic disease.

ORTHOPAEDICS AND TRAUMA 24:4 263 Ó 2010 Elsevier Ltd. All rights reserved.
 MINI-SYMPOSIUM: MALIGNANT BONE TUMOURS: PRINCIPLES
MRI plays an important role in assessing the effect of neo-
adjuvant therapy prior to definitive surgery. To ensure direct
comparability it is important to use the same MRI technique for the
pre- and post-treatment studies. Follow-up MRI is also important
in monitoring for local recurrence and is much more sensitive than
radiography. Chest radiographs at three monthly intervals for the
first two years and six-monthly intervals for the following five
years and then annually are used to monitor for pulmonary
metastases. CT of the thorax is used in cases where abnormality
was suspected on the chest radiograph or where the initial CT scan
had shown definite or suspected metastatic disease to the lungs.A
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