MINI-SYMPOSIUM: ORTHOPAEDIC ONCOLOGY
(ii) Investigation of
musculoskeletal malignancy
Robert U Ashford
K Julia Fairbairn
Abstract
Diagnosis and assessment of the extent of tumour burden are key to
managing musculoskeletal malignancy to avoid the risk of inappropriate
treatment when palliation would be appropriate. This review sets out the
principles of investigating suspected musculoskeletal malignancies for
the non-specialist with a focus also on the musculoskeletal imaging rather
than oncological staging. It is not intended to be a comprehensive review
of all musculoskeletal malignancies.
Keywords biopsy; investigation; metastases; MRI; sarcoma
Introduction
Musculoskeletal malignancy falls into three broad types:
 Primary malignant bone tumours - bone sarcomas
 Primary soft tissue sarcomas
 Metastatic malignancy
While separate entities there is considerable overlap in their
investigation, and to preclude errors, investigation strategies
must be systematic.
History & examination
A thorough history and examination is mandatory. As well as
a systemic review, the history must include any previous history
of malignancy and its treatment, especially radiotherapy, and
any family history of malignancy. A full examination should
include examination of the breasts in female patients and the
prostate in males. Regarding the tumour itself, the red flag
symptoms and signs for soft tissue masses are:
 pain
 size greater than 5 cm
 deep to deep fascia
 increasing size.
Blood investigations
Full haematological and biochemical work-up forms part of the
initial assessment and includes FBC, U&Es, LFTs, ESR or PV,
CRP, tumour markers & serum electrophoresis.
Robert U Ashford FRCS(Tr & Orth) Consultant Orthopaedic and Musculo-
skeletal Tumour Surgeon for the East Midlands Sarcoma Service at
Leicester Royal Infirmary, Infirmary Square, Leicester, LE1 5WW and
Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK.
K Julia Fairbairn FRCR Consultant Musculoskeletal Radiologist for the
East Midlands Sarcoma Service at Nottingham City Hospital, Hucknall
Road, Nottingham, NG5 1PB, UK.
ORTHOPAEDICS AND TRAUMA 23:4
In confirmed cases of Ewing’s sarcoma (both the primary
bone type and the rarer primary soft tissue form) as well as the
related rarer small round blue cell tumours such as PNET
(Primitive Neuro-Ectodermal Tumour) a bone marrow aspirate is
necessary to complete staging.
Imaging
Primary malignant bone tumours
Radiography
The majority of primary malignant bone tumours are clearly
visible on plain radiographs (two views at right angles) and this
is usually how the diagnosis is made. Computerised tomography
(CT) is often used for complex sites such as the shoulder girdle,
pelvis and the spine as CT shows additional bony detail without
overlap of structures, allowing assessment of calcified matrix,
especially if the mineralization is subtle.
Radiographically the lesion may be described as lytic (less
dense than adjacent bone), sclerotic (more dense than adjacent
bone) or mixed. However within an area of lytic destruction
there may be areas of mineralization which may be characteristic
of the type of tumour; two classic types are of ‘cotton wool’ or
‘cumulo-nimbus cloud’ matrix seen in osteosarcoma and the
‘curvi-linear’ or ‘popcorn’ like matrix in chondrosarcoma. The
amount of mineralised matrix is variable but generally an
obvious, well defined matrix is seen in the less aggressive
tumours such as a low grade chondrosarcoma and less matrix is
seen in the more aggressive forms such as a telangiectatic
osteosarcoma (Figure 1).
Some benign lesions can display a characteristic mineraliza-
tion pattern such as the ‘ground glass’ pattern seen in fibrous
dysplasia; typically a long lesion in long bones or ribs with
associated expansion and possible areas of chondroid-like
matrix. An unusual variant includes associated adjacent soft
tissue myxomata (Mazzabraud’s syndrome). Another example is
an osteoid osteoma which has a lytic nidus or centre that may
have stippled calcification within that can be mistaken for
a chondroid matrix. The usually associated cortical thickening
with sclerosis or, in the rare intra-capsular form, an accompa-
nying effusion, should avoid confusion.
The relationship to the medullary cavity (including primary
trabeculae) and the cortex especially the periosteum of the parent
bone is also important. The margin of the lesion often suggests
how aggressive it is. The most aggressive part should be used to
characterise the lesion not the more benign part e.g. a chon-
drosarcoma of the tri-radiate cartilage of the acetabulum may
have a variable thickness of sclerosis extending from the roof of
the acetabulum as a ‘‘mechanical’’ response to the tumour
related to weight bearing but an intermediate margin at the non-
weight bearing inferior aspect extending into the ischium. The
most benign bone margin is a thin rim of sclerotic bone, almost
like a thin cortex, surrounding the lesion For example a bone cyst
which may also have a characteristic ‘‘falling fragment’’ sign
within following recent trauma. Aneurysmal bone cysts may
have a similar but more ‘bubbly’ shape at the margin and
accompanying expansion. Moving towards the aggressive end of
the spectrum is a margin with a surgical cut off, then an inter-
mediate type followed by an aggressive margin that is often
referred to as ‘‘moth eaten’’ or permeative. The latter margin
231 Ó 2009 Elsevier Ltd. All rights reserved.
 MINI-SYMPOSIUM: ORTHOPAEDIC ONCOLOGY
Figure 1 Plain AP radiograph of the knee demonstrating a destructive
lesion of the proximal tibia with osteolysis, periosteal reaction and faint
mineralization. Biopsy confirmed the lesion to be an osteosarcoma.
may be over 1e2 cm or more whilst the surgical cut off is very
sharp or localised with the intermediate margin somewhere in
between. The margins of sclerotic lesions can also be assessed in
a similar fashion e.g. sclerotic metastases have ill-defined or
blurred margins compared to a bone island/enostosis which is
irregular but blends with the adjacent trabeculae.
The cortex may act as a partial barrier to the tumour, but once
this is breached, the periosteum offers little barrier to the spread
of tumour. Various periosteal reactions can help characterize
different bone tumours; the ‘‘onion skin’’ pattern of a Ewing’s
sarcoma with layers of mineralization parallel to the diaphysis of
a long bone. A ‘‘sunburst’’ pattern may be seen in osteosarcomas
with mineralization at right angles to the cortex centred on the
tumour. At the tumour margin there may be mineralization of an
angled elevation of the periosteum known as a Codman’s
triangle. This is seen in aggressive tumours such as an osteo-
sarcoma but also may be seen with sub-periosteal collections
such as haematomas and infection. Sequestra (bone fragments)
and cloacae (cortical openings containing a dead fragment of
bone) are usually thought of as features of infection but they may
also be seen in some tumours e.g. lymphoma of bone.
Some of these are seen in Paget’s disease which has a char-
acteristic pattern of thickened, sclerotic primary trabeculae in
a woven pattern and similar thickening and mild expansion of
the cortex. The pelvis is a common site as well as the long bones
which lesions typically start at the epiphysis, although there is
also the rare diaphyseal form. The early stage is lytic and often
described as a lytic ‘‘flame’’ as it progresses away from the end of
a long bone. As rarely Paget’s can undergo malignant change to
secondary sarcoma (usually osteosarcoma), areas of lysis or
ORTHOPAEDICS AND TRAUMA 23:4
other localised changes to the classic Paget’s disease are suspi-
cious for malignant change including involvement by metastatic
disease which is actually probably more common than the rare
secondary sarcomas.
Magnetic Resonance Imaging (MRI)
MRI complements the radiographic and CT findings prior to
biopsy. It is not as good at assessing any mineralised matrix but
may show a characteristic ‘‘bubbly’’ pattern like the ‘‘cut surface
of a pomegranate’’ in a chondrosarcoma (also in the rarer soft
tissue form). In the unusual but aggressive telangiectatic osteo-
sarcoma, there may be little or no mineralised matrix but there
may be other features such as fluid-fluid levels that are seen in
some more aggressive tumours which may help to suggest the
diagnosis (Figure 2).
MRI is crucial for local staging and evaluation of primary
malignant bone tumours. It will delineate the intra-osseous and
extra-osseous extent of the tumour including joint involvement,
the presence or absence of skip lesions within the involved bone
and the relationship of nerves and vessels to the tumour which
can be either involved in the tumour precluding limb salvage,
abutting the tumour or displaced by the tumour but not involved,
or free from the tumour. This is critical in planning surgical
resectionethe first group requiring amputation, the middle group
usually being appropriate for limb salvage (unless the disease
progresses during chemotherapy) and the latter group usually
being appropriate for limb salvage.
Most tumours will have low signal similar to muscle on T1
scans and high signal similar to fluid on T2 and Fat Suppressed
scans (Short Tau Inversion Recovery ¼ STIR or spectral fat
suppression techniques which are often faster but more suscep-
tible to artefacts). Apart from low signal from a matrix, there are
other unusual signal patterns that help suggest a diagnosis e.g. in
giant cell tumours there is a relative lack of high signal on T2 and
STIR scans from increased collagen or haemosiderin. This is
especially helpful for Giant Cell Tumours (GCTs) that are not in
the typical long bone meta-epiphyseal location e.g. the odontoid
peg, in epiphyseal equivalents (carpus and tarsus) and in the
rarer soft tissue form. This may also be helpful in assessing for
recurrence. GCTs have another unusual trait that cross-sectional
imaging may detect. They can cross joints such as the sacro-iliac
joints without overt destruction of the joint on imaging, a trait
they also share with bone lymphomas and also angiosarcomas
although the latter may cause more joint destruction.
Spinal tumours. A solitary metastasis, plasmacytoma or
lymphoma are all more common than primary bone tumours. A
solitary spinal lesion should be carefully assessed on imaging
prior to biopsy. Apart from the signal pattern and odontoid or
sacral prevalence of GCTs, a chordoma has similar high or low
spinal predominance and may have some mineralization within
on CT. Ten per cent of osteosarcomas are spinal; again CT may
help confirm their typical matrix pattern. Typically osteoid
osteomas or the larger osteoblastomas may cause a short angled
scoliosis and occur in the posterior elements with a surrounding
halo of oedema. CT is again recommended as an adjunct to
assess the nidus and a three phase bone scan will be active on all
three phases.
Vascular tumours are common in the spine especially verte-
bral haemangiomas with a fatty stroma which are of no clinical
232 Ó 2009 Elsevier Ltd. All rights reserved.
 MINI-SYMPOSIUM: ORTHOPAEDIC ONCOLOGY
a Coronal T2 MRI of the same tibial osteosarcoma showing the
medullary and soft tissue extent of the tumourethe matrix is
difficult to characterise. b Axial T2 MRI showing the popliteal
vessels being encased/involved in the tumour. The fluid-fluid
levels suggest an aggressive lesion. Vessel involvement precludes
limb salvage.
Figure 2
significance. Haemangiomas with a vascularised stroma may
cause confusion if the typical ‘‘polka dot’’ pattern on axial
images or ‘‘corduroy cloth’’ pattern on sagittal or coronal scans is
not recognised. The intermediate grade haemangio-endothelioma
and haemangio-pericytoma may share some of these features.
Angiosarcomas usually have a more aggressive appearance, may
be multiple at presentation and also cross joints. Haemangioma,
haemangio-endothelioma, (also haemangio-pericytoma in
ORTHOPAEDICS AND TRAUMA 23:4
Figure 3 Isotope bone scan of the same patientethe proximal tibia shows
marked increased uptake. There is no evidence of skeletal metastases.
author’s experience) or angiosarcomas may have an association
with consumptive coagulopathy, thrombocytopenia and purpura
known as the Kasabach-Merritt Syndrome1,2 with subsequent
risk to biopsy/surgery.
It is always worth remembering that an unusual appearance
for a metastasis is more common than an unusual primary.
Systemic staging: isotope bone scan & CT chest
Systemic staging of bone sarcomas requires a chest radiograph
and CT for pulmonary metastases and an Isotope Bone Scan for
skip lesions and osseous metastases (Figure 3).
The Bone Scan is a map of osteoblastic activity and is often
increased at a primary bone tumour site and metastases but can
appear unremarkable or reduced in aggressive tumours where
the osteoclastic activity is the dominant finding. This would be
classically seen in patients with plasmacytomas or perhaps renal
cell metastases where the lesions are often sizable before they
are detected as areas of reduced activity. A very aggressive bone
primary such as a telangiectatic osteosarcoma could have
a similar appearance. Care needs to be taken when reviewing
scans as osteoblastic activity is common when there is sclerosis
at degenerative sites. Also, not all areas of increased activity at
other sites are malignant tumours e.g. fibrous dysplasia, bone
islands/enostosis especially larger ones and Paget’s disease.
Soft tissue sarcomas
Plain radiographs
The majority of probable soft tissue sarcomas should undergo
plain radiography for the following reasons:
 To exclude a bone lesion with soft tissue extension or vice versa
 To assess any invasion of bone by an extra-osseous tumour
 To assess the presence or absence of phleboliths (remember -
rim calcification like soft centred chocolates as seen in the pelvis
on IVU’s for renal colic) which are often present in arterio-venous
malformations and other vascular tumours
 To assess matrix calcification or ossification such as dystrophic
calcification that has no form seen in synovial cell sarcomas, more
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 MINI-SYMPOSIUM: ORTHOPAEDIC ONCOLOGY
a Axial T1 b Axial T2 c Coronal STIR images demonstrating a large soft tissue mass in the adductor compartment of the thigh with fluid-fluid levels,
consistent with a high grade sarcoma of the thigh.
Figure 4
structured calcification or ossification in liposarcomas, rare curvi-
linear matrix in mesenchymal chondrosarcomas and the even rarer
‘‘cotton wool’’ or ‘‘cumulo-nimbus cloud’’ like matrix in soft tissue
osteosarcomas
 To assess any associated underlying skeletal deformityetypically
vascular tumours or hamartomatous lesions can have under- or over-
development of the limb and some mesenchymal syndromes have
bony and soft tissue tumours e.g. Maffucci’s which has multiple
enchondromas with malignant potential to form chondrosarcomas
and associated overlying haemangiomas.
Computerised tomography
CT is occasionally useful for the assessment of soft tissue
tumours. It is superior to plain films for assessing calcification,
ossification and air and also identifies adipose tissue well and can
thus be complementary to MRI. CT is especially useful in
assessing large lipomatous tumours in patients unsuitable for
MRI due to claustrophobia or for other absolute reasons i.e.
metallic foreign body in the eye, previous brain surgery with use
of vascular clips and a cardiac pacemaker as there is reduced
artefact from implants using modern multi-slice scanners.
Magnetic Resonance Imaging
It has been said that ‘‘Soft tissue tumours should be diagnosed
and staged before biopsy’’.3 While the gold standard must be
histology, MRI is the investigation of choice to assess soft tissue
malignancy. It is used to detect and characterise a tumour, to
ORTHOPAEDICS AND TRAUMA 23:4
determine its local extent and to determine the need and best site
for biopsy. The ultimate goal of imaging is to predict malignancy
and an approximately 25% correct histological diagnosis can be
made from imaging.4
The signal pattern of a lot of soft tissue tumours is non-
specific; (Figure 4) on T1 scans, masses are often low signal
similar to muscle but without the normal fatty marbling. They
are often high signal similar to fluid on T2 and Fat Suppressed
scans (Short Tau Inversion Recovery e STIR - or spectral fat
suppression techniques).
Intravenous contrast in the form of chelated gadolinium (Gd)
shows enhancement depending on the vascularity of the lesion
but this can also be seen with oedema and at the margins of
abscesses and other fluid collections if there is a vascularised
capsule. The use of gadolinium is variable across the UK; we use it
sparingly especially since the recognition of nephrogenic systemic
fibrosis (NSF) which can occur in patients with grade 3 or higher
renal failure. Our main use would be in lesions that have uniform
signal and thus the potential to be just fluid or a predominantly
myxoid tumour that could be benign or malignant. The contrast
will confirm any nodular, cellular areas that should then be tar-
geted at biopsy e.g. myxoid liposarcomas, fibrosarcomas or
chondrosarcomas. Dynamic uptake curves have been used in
Europe, but rarely in the UK, to try and differentiate benign from
malignant lesions but with only limited success.
There are some tumours that show signal variations of the
common pattern of low on T1 and high on T2. The signal may be
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 MINI-SYMPOSIUM: ORTHOPAEDIC ONCOLOGY

increased or high signal on T1 where there is adipose tissue, centre. The fact that scanning detail decreases further from the
methaemaglobin and slow flowing blood; the signal may be probe means that deep large lesions are not scanned well.
decreased or low signal on T2 where there is fibrous tissue, However small superficial lesions are more amenable to ultra-
calcification/ossification, haemosiderin (and hyper-acute blood sound assessment. Additionally ultrasound can assist in charac-
more in the neuro-axis than peripheral) and high flowing blood or terising lesions - especially aneurysms - that mimic tumours and
flow voids. Examples of the high T1 pattern are adipose tumours for targeting of biopsy. It also has a role in assessing regional
such as an Atypical Lipomatous Tumour (ALT) or smaller quan- spread (nodal), can be used to assess vascularity and can
tities may be seen in liposarcomas. Examples of the low T2 pattern differentiate a mass from a cyst and from oedema.
would include aggressive fibromatosis (a variant of a desmoid
tumour with variable local infiltration) which often involves the Systemic staging: CT chest and isotope bone scan
trunk, mineralization in a mesenchymal chondrosarcoma and As with bone sarcomas, systemic staging of soft tissue sarcomas
haemosiderin in pigmented villo-nodular synovitis (PVNS). comprises a chest radiograph with CT for pulmonary metastases
Patterns are also helpful in suggesting specific diagnoses such (Figure 5). If the primary is retroperitoneal, abdominal, pelvic or
as the shape (bubbly in cartilaginous tumours, serpiginous in spinal, CT assessment of the abdomen and pelvis are included. Unlike
vascular tumours), location and signal (close to joints with low bone sarcoma work up, an isotope bone scan is only occasionally of
signal from dystrophic calcification in synovial cell sarcomas) help to assess for any periosteal involvement but it is again a standard
fluid-fluid levels (from organising haematomas to highly malig- requirement in staging soft tissue Ewing’s and other small round blue
nant sarcomas such as synovial cell sarcomas), signal voids (high cell tumours such as a PNET and for rhabdomyosarcomas. A brain CT
flow, mineralization, implants and susceptibility artefact) and is included if there are relevant clinical symptoms or signs.
lastly multiplicity (fibrous tumours such as desmoids to fibrosar-
comas, neural tumours both benign and malignant, vascular New & novel techniques
tumours both benign and malignant, myxomata and of course Positron Emission Tomography (PET eCT)
metastases especially mucinous tumours from ovary or GI tract). PET-CT scanning is a functional imaging modality. 18F-fluo-
Assessment of malignancy can be relatively straightforward if rodeoxyglucose (FDG) is a labeled glucose substrate that is
there is a large, deep mass of mixed signal with a high growth administered to the patient. The patient is then PET scanned
rate. There may also be further clues such as an aggressive, followed by a low dose CT scan (Figure 6). The images are
infiltrating tumour margin, adjacent soft tissue and/or bone viewed independently as well as fused. It is an evolving tech-
involvement, neurovascular invasion and extension beyond nique that has a well defined role in the management of lung and
a compartment. These are the easy cases that obviously require oesophageal cancers as well as lymphoma. The role in sarcoma is
a biopsy to confirm and then staging to formulate al treatment less well defined but potential roles are for staging at primary
plan. There are however some major pitfalls. Some malignant diagnosis and detecting metastases (apart from in the lung where
tumours may have a very indolent appearance; some may even the CT resolution precludes accurate diagnosis and for brain
fool the unwary into thinking that they are simple cysts for metastases as diagnosis is masked by the avid glucose uptake of
example a myxoid sarcoma such as a myxoid liposarcoma. brain activity).
Hence the need for referral to a specialist tumour service for
thorough clinical assessment, imaging review and, if necessary,
repeat MRI with contrast and a targeted biopsy at a nodular,
cellular part of the tumour to confirm the diagnosis. All lesions
that are not small, superficial, mobile and distinct in character
should have an MRI performed. A normal MRI virtually excludes
an underlying malignancy.
There are a number of difficulties imaging soft tissue
sarcomas, many non-specific e.g. the experience and ability of
the interpreter will vary. Then, while MRI is highly specific it is of
low sensitivity, there are a range of appearances within histo-
logical groups and there are evolutionary changes and therapy
changes. Despite these, as already stated, 25% correct histolog-
ical diagnoses can be made from imaging alone.
MRI also assesses structures at risk with marginal and wide
resections, facilitates pre-operative surgical planning and has
a further role in surveillance and follow-up, but this is contro-
versial; some units use regular MRI to form a baseline post-
surgery scan to monitor for local recurrence. In particular
impalpable deep tumours are amenable to such surveillance.

Ultrasound
Ultrasound has a limited role in the management of sarcomas. It
is operator and reader dependant whereas an MRI scan can be Figure 5 Chest radiograph demonstrating multiple metastases from the
reported locally, and still be available for review by a specialist previous soft tissue sarcoma.

ORTHOPAEDICS AND TRAUMA 23:4 235 Ó 2009 Elsevier Ltd. All rights reserved.
 MINI-SYMPOSIUM: ORTHOPAEDIC ONCOLOGY

a PET and b fused PET-CT images showing areas of avid glucose uptake in the proximal femora, right thigh muscles, left lung and axilla, consistent
with a primary lung cancer with skeletal and soft tissue metastases (Reproduced from Current Orthopaedics 2006, Volume 20(4); 299e315).

Figure 6

One area of sarcoma management where PET-CT appears to
have a clear role is in neurofibromatosis type 1 where a lesion is
suspected of having undergone change into a MPNST (Malignant
Peripheral Nerve Sheath Tumour). FDG PET-CT has been shown
to be both sensitive and specific in detecting these tumours.5
Malignancy is not the only condition that will result in an area
of increased uptakeeother causes are inflammation, brown fat
and exercise. It remains to be seen whether there are further clear
definable roles for PET-CT in the management of sarcomas.
Whole Body MRI
Whole Body MRI (WBMRI) is also an evolving technique for
the assessment of bone marrow involvement, tumour staging
and screening which has been developed in recent years using
different methods, either a moving table in combination with
the body coil or a specially designed rolling table platform
with multiple phase array coils. A series of images are
obtained, (typically coronals in our institution) which are
electronically pasted together to produce whole body images
(Figure 7).
There is also recent interest in using diffusion weighted
imaging (DWI) in whole body scans. Diffusion weighted imaging
is a novel technique used in brain imaging to reflect the degree of
restriction to water diffusion in biological tissues. This is
inversely correlated to the cellularity and the integrity of cell
membranes.8 DW imaging is acquired at multiple stations,
reviewed as separate images and then fused producing
a composite DW image of the whole body.

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 MINI-SYMPOSIUM: ORTHOPAEDIC ONCOLOGY
Whole Body MRI: Single Coronal a T1, b STIR and c Summated DWI images of a patient who presented with metastatic sarcoma. WBMRI
demonstrated the primary tumourea large mixed signal tumour in the right thigh on T1 and STIR and also a right external iliac lymph node
adjacent to the bladder.
Figure 7
WBMRI protocols usually include T1 weighted and STIR (short
tau inversion recovery) imaging which have proven highly effi-
cient for the assessment of bone and soft tissue structures6,7 and
therefore may have an evolving role in the assessment of bone and
soft tissue sarcomas. It may especially be helpful for locating the
primary when a patient presents with an unusual lung secondary
or secondaries and there is no obvious primary site after a thor-
ough clinical assessment. Similarly in a patient presenting with
lymphadenopathy in one of the small round blue cell tumours (e.g.
rhabdomyosarcoma) and the primary is not clinically evident.
MR imaging is limited in its ability to detect small lung
metastases. WBMR imaging shares this difficulty especially as
there may be reduced image resolution compared to conven-
tional MR images and this is currently compounded in the DWI
technique. Unlike PET-CT, however, brain metastases may be
assessed. The role of WBMRI in sarcoma remains to be fully
established but promises to be of value.
Metastatic musculoskeletal malignancy
Radiography
Radiographs should be in two planes including the joint above
and below to enable all lesions within the bone to be identified
(Figure 8). Plain radiographs offer good integration of the overall
bone structure and alignment. Radiographic features of skeletal
metastases are variable.
Tumours can be:
 Lytic (osteoclastic), sclerotic (osteoblastic) or mixed
 Solitary or multiple with a differential diagnosis of metastasis,
myeloma or lymphoma for a patient with multiple lesions
ORTHOPAEDICS AND TRAUMA 23:4
 Well or poorly defined
 Permeative and/or destructive
 Varied in their soft tissue involvement.
Cross sectional imaging
Dependent on the site of the lesion, CT or MRI scan may be
appropriate. CT scans are best for looking at bone quality, bone
destruction, calcified tumour matrix and cortical erosions
whereas MRI is highly sensitive but relatively non-specific and is
superior at demonstrating marrow replacement, skip lesions,
quantifying oedema and assessing neurovascular involvement.
Isotope bone scanning
Bone scintigraphy may show multiple hot lesions, but beware the
cold lesions (myeloma, renal cell carcinoma). It is also useful for
demonstrating multiple lesions, and for identifying asymptomatic
lesions. Positron Emission Tomography (PET) scanning is
increasing in frequency and can be useful to determine the extent of
tumour burden. The uptake of F18-FDG (fluorine-18 fluorodeox-
yglucose), a glucose analogue, into tumour cells enables the most
active and viable part of the tumour to be identified and targeted for
biopsy. These modalities will help to identify other sites (metastases)
both skeletal and visceral that may potentially require treatment.
Summary of imaging
As an aide memoire, Gilbert Jr. and Thompson Jr. summarised
the major imaging modalities and their relative (Table 1)
strengths in musculoskeletal malignancy:
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 MINI-SYMPOSIUM: ORTHOPAEDIC ONCOLOGY

The incidence of complications of biopsy is up to five times more

common in referring hospitals than in specialist centres.18e20 Thus
all likely primary bone and soft sarcomas should be biopsied in the
specialist centre that will be managing the patient. However, to
avoid over-burdening the specialist centres, lesions felt highly
likely to be bone secondaries of systemic malignancies (particu-
larly where the lesion is multiple) can usually be safely or
adequately assessed at a non-specialist centre and secondarily
referred for a further opinion and/or repeat biopsy if an un-
expected primary bone sarcoma is biopsied. Nonetheless, such
biopsies should however be done along sarcoma principles.
There are a number of situations in the management of
metastatic disease where biopsy is desirable. Salai grouped
these into five types of patient11 for whom biopsy is
necessary:
 A patient with a known primary malignancy but no known
metastases who develops a new (first) bony lesion.
 A patient with a history of long stable malignancy (breast,
prostate cancer) who was considered cured, who develops a new
bony lesion.
 A patient with a known malignancy who presents with
a pathological fracture.
 A patient, previously healthy, who presents with new multiple
bony lesion suspicious of disseminated metastatic disease, as yet of
unknown origin.
 A healthy patient who presents with a pathological fracture
Figure 8 AP radiograph of right proximal femur with a large lytic lesion in suspected of being metastatic in origin.
the greater trochanter with permeative margins and cortical breakthrough The commonest types of biopsy are:
consistent with a breast cancer metastasis (Reproduced from Current  core needle biopsy (CNB)
Orthopaedics 2006, Volume 20(4); 299e315).  fine needle biopsy (FNB)
 excisional and incisional biopsies
Biopsy Most primary bone malignancies are amenable to core needle
For primary tumours, tissue biopsy is critical to guide appro- biopsy. The advantages of CNB are decreased morbidity, less
priate initial patient management. It is essential that it is carefully haematoma formation, avoidance of open biopsy and they can be
planned. This usually requires assessment with appropriate performed on an outpatient basis.
radiological imaging9,10 to assess the anatomical extent of the Excision biopsy is only applicable to small superficial lesions
tumour prior to biopsy. Soft tissue lesions that are indeterminate smaller than 2 cm diameter or where a diagnosis has been made
on MRI need a tissue sample to be obtained for diagnosis. from imaging. It is not suitable for large lesions or lesions
Poorly performed biopsies have a number of potential conse- without a diagnosis.17 Care should be made when undertaking
quences, including pathological misdiagnosis due non-represen- these lest the tumour bed requires further resection.
tative sampling), functional impairment, amputation and death. Incision biopsies can be used for bone or soft tissue lesions.
They should be performed following consultation with the
surgeon who will be performing any definitive surgical proce-
dure. There are a number of principles:
Strengths of Imaging Modalities in assessment of
 The surgeon performing the biopsy should be aware of the
musculoskeletal malignancy (from (4))
definitive resection approach so that the biopsy site and approach
can be removed en bloc with the tumour.
Bone lesions Soft tissue Metastases Strengths
 Transverse incisions should be avoided (especially on limbs).
lesions
 A tourniquet (if used) should be deflated prior to closure and
Radiograph U U U Bone lesions & haemostasis should be meticulous. If used a drain should be
invasion brought out through or at the tip of the incision. Haematoma
Ultrasound U Cystic lesions & must be avoided as it contaminates uninvolved tissue.
aneurysms  Uninvolved compartments should not be breached, tissue
Bone Scan U U layers should not be developed and neurovascular structures must
CT U not be exposed and contaminated.
MRI U U U Delineates  Tissue should be sent for both microbiology and
tumour extent histopathology.
 A frozen section should be utilised for diagnostic representa-
Table 1 tive tissue12

ORTHOPAEDICS AND TRAUMA 23:4 238 Ó 2009 Elsevier Ltd. All rights reserved.
 MINI-SYMPOSIUM: ORTHOPAEDIC ONCOLOGY
 Biopsy of bone should be taken away from any site of path-
ological fractureereaction of the bone to the fracture can be
difficult to interpret.
The majority of sarcoma services use mainly core needle
biopsy. In specialist centres accuracy exceeds 80%.12e14 These
can be image guided where necessary.15,16
Conclusion
The aim of investigation of musculoskeletal malignancy is to
establish the diagnosis and the extent of the disease burden and
to enable treatment planning. Investigation should be meticu-
lous, thorough and ordered. A 17 Papp DF, Khanna AJ, McCarthy EF, Carrino JA, Farber AJ, Frassica FJ.
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18 Mankin HJ, Lange TA, Spanier SS. The hazards of biopsy in patients
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FURTHER READING
Kransdorf MJ, Murphey MD. Imaging of soft tissue tumors. Lippincott
Williams & Wilkins; 2005.
Levesque J, Marx R, Bell RS, et al. A clinical guide to primary bone tumors.
Lippincott Williams & Wilkins; 1998.
Pollock RE. Soft tissue sarcomas: a volume in the American Cancer Society
Atlas of Clinical Oncology Series. Decker; 2002.
Practice points
C For primary musculoskeletal tumours biopsy is the FINAL
diagnostic step
C Biopsy should be performed by or at the very least after
consultation with a regional sarcoma service
C All imaging modalities can provide useful information but
plain radiographs and MRI remain the gold standard for local
staging of sarcomas (bone and soft tissue)
C Systemic staging is usually a chest radiograph followed by CT
chest and an isotope bone scan for all bone sarcomas and for
a limited number of (specific) soft tissue sarcomas
C PET-CT and Whole Body MRI are evolving techniques for
systemic staging
239 Ó 2009 Elsevier Ltd. All rights reserved.