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R E V I E W A RT I C L E

Osteosarcoma:
Pathology, staging and management
DJ van der Spuy MBChB (Stell)
Orthopaedic Surgery Registrar, University of Stellenbosch
GJ Vlok MBChB, MMed(Orth), FC(Orth) SA
Professor and Head: Dept of Orthopaedic Surgery, Tygerberg Hospital/University of Stellenbosch

Reprint requests:
Dr DJ van der Spuy
Dept of Orthopaedic Surgery
PO Box 19063
Tygerberg
7505
Tel: +27 21 938-9266

Introduction
Osteosarcoma (OS) is a malignant spindle cell sarcoma in which the malignant cells produce osteoid or bone in the
background of a sarcomatous stroma. However, fibrous or cartilaginous tissue may co-exist or even predominate.
The classic or so-called conventional osteosarcoma develops in the medullary cavity of the metaphysis of long
bones. It has a predilection for the knee area with 50% of cases in either the distal femur or proximal tibia, with the
second most common site being the proximal humerus (10%).1 However, osteosarcoma has been described in every
bone.
Osteosarcoma has a bimodal peak incidence. It is the most common bone tumour in children and adolescents with
a peak incidence between ten and 20 years. This correlates with the adolescent growth spurt. It is also the third most
common malignancy in childhood following leukaemia and lymphoma.1 Adults are less affected with a second peak
incidence between 50 and 70 years. This later incidence is usually associated with secondary OS that could arise in
Pagets disease, bone infarcts and fibrous dysplasia.2 Surface osteosarcomas tend to affect younger adults in the third
and fourth decade.3,4
Many variants of the conventional or classic high-grade OS have been described. The two most common of these
variants are the surface or juxtacortical group and the telangiectatic osteosarcomas. The surface osteosarcomas arise
on the surface of long bones, most prominently the posterior aspect of the femur.5

Aetiology There is an increase in the incidence of OS in hereditary

The cause of OS remains uncertain. Many carcinogens retinoblastoma as well as in the autosomal recessive
and oncogenes have been proposed. Simian virus 40, a Rothmund-Thomson syndrome9 (skin pigmentation,
contaminant of the polio virus, was implicated but current hypogonadism and bone abnormalities).
thinking doubts its contribution in the oncogenesis.6,7
Irradiation is long known to cause OS in patients receiv- Clinical presentation
ing this therapy for other malignancies. Early diagnosis of a malignancy remains the biggest chal-
There is reason to believe that there might be a genetic lenge for general practitioners and orthopaedic surgeons
component in the aetiology of OS. Osteosarcoma is a confronted with non-specific pain in a limb. In OS the
component of the familial Li-Fraumeni syndrome,8 which most common presentation is site specific pain. This is
is known to have mutations in the p53 tumour suppressor generally worsened by physical exertion. Approximately
gene. This syndrome is associated with OSs, soft tissue 20% complain of night pain. Nearly half of the patients
sarcomas, breast carcinomas and adrenal cortex tumours. associate the pain with a traumatic event (Table I).10
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Surface osteosarcomas usually have a patched-on

Table I: Clinical signs of osteosarcoma10 appearance often leaving an incomplete line between cortex
and tumour, sometimes referred to as the string-sign.4
Clinical sign Percentage present These tumours do not usually infiltrate the medulla and due
at first consultation to their cartilaginous nature often have radiodense and radi-
olucent areas creating a lobulated effect on X-ray (Figures 5
Local tenderness 92% and 6).
Palpable mass 39%
Painful joint movement 39%
Limp 30%
Limited range of movement 23%
Atrophy of muscle 5%
Fever 3%

Fewer than 5% of those with OS will actually complain of

a palpable mass.
In a recent study by Widhe10 in Sweden it was found that
in only 30% of first consultations was a diagnosis of a
tumour made. Some incorrect non-specific diagnoses
such as tendinitis, osteitis, chondromalacia patella and
even Osgood-Schlatter disease were made. Therefore
these diagnoses should be made with care in the child and
adolescent presenting with pain around the knee. The
incidence of pathological fractures either at presentation
or during therapy varies between 5% and 10%.11
Figure 1: Conventional osteosarcoma: AP dis-
Recognising osteosarcoma on tal femur. Combination of sclerotic changes
plain radiographs corresponding to new bone formation with
The X-ray holds the key to confirm a clinical suspicion. lytic changes evident in medulla and cortex
The literature makes it clear that OS does not necessarily
present with the classic Codmans triangle and the sun-
burst appearance (that often get portrayed as the mainstay
of these diagnoses) and that these signs are non-specific.
Conventional osteosarcomas are usually found eccentri-
cally in the metaphysis of long bones with areas of radio-
dense, radiolucent or mixed patterns (Figures 1 and 2).
The key to the diagnosis is to recognise the malignant
nature of the lesion. This should be evident in recognising
cortical destruction, soft tissue infiltration and a wide
zone of transition in the medulla (Figures 3 and 4). The
sunburst appearance results from speckles of bone
developing along the newly formed vessels derived from
the periosteum, giving the appearance of sunrays.
Codmans triangle is thought to be the desperate attempt
by the periosteum to contain the tumour by laying down
reactive bone and hence lifting up the periosteum.

The key to the diagnosis is to recognise the

malignant nature of the lesion - cortical destruction,
soft tissue infiltration and a wide zone of
transition in the medulla Figure 2: Lateral view of the same tumour
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Telangiectatic osteosarcomas generally present as radiolu-

cent lesions with aggressive osteolysis and periosteal reac-
tions.12

Further staging modalities

Once there is a suspicion of a malignant lesion a complete
radiological workup is essential before a diagnosis can be
confirmed with a biopsy. The objectives of a good workup
are to delineate the local extent of the tumour, to discov-
er any skip lesions in bone and to locate any distant
metastases. This facilitates the essential tissue diagnosis
with a biopsy.

Magnetic resonance imaging

MRI is the best investigation to define the primary
tumour. It provides a good assessment of the degree of
medullary infiltration, cortex destruction, soft tissue inva-
sion, neurovascular bundle invasion and it identifies skip
lesions13 (Figure 3). Occult skip metastases of 2 mm or
more can be picked up on MRI and therefore all MRI
series should include coronal T1 sequences to scout the
whole affected bone. The T2 sequence shows peri-lesion-
al oedema well and low-mineralised areas have a high sig-
Figure 3: MRI (Gadolinium) of the same nal intensity. Gadolinium has the advantage of defining
tumour. Note the soft tissue element and the border between the tumour and cartilaginous areas
tumour infiltration into epiphysis very well12 (Figure 3).

Computed tomography
Computed tomography (CT) is of great value to evaluate
the lungs for metastases. Pulmonary metastases of 3 mm
and greater can be picked up on CT scan.14 Spiral CT is
superior to conventional CT for this purpose.

Scintigraphy (nuclear bone scan)

Bone scans with technetium-99m show an increased
uptake in primary tumour corresponding with bone for-
mation and increased vascularity in the tumour area.
Nuclear bone scanning is therefore very useful in evaluat-
ing skip metastases and metastases in other skeletal
sites.15 Positron emission tomography (PET) is also
becoming an important nuclear imaging modality.16 The
most commonly used tracer is fluorine-18 fluo-
rodeoxyglucose (F-18 FDG) which is a glucose analogue
and taken up by the cells glucose transporters.
Concentration of this marker in sarcomatous areas is an
indicator of increased metabolic activity.17-18 This 3-D
image of metabolic activity is not only useful in staging
the tumour but it also allows the evaluation of treatment
response with pre- and post-treatment image compar-
isons.

The objectives of a good workup are to delineate the

Figure 4: MRI T1 Coronal view clearly local extent of the tumour, to discover any skip
defines the borders of the tumour in the bone lesions in bone and to locate any distant metastases
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Angiography
Angiography is useful to define the tumour in relation to
adjacent neurovascular bundles and soft tissues. This
intervention has been partially replaced by MRI. However
in parosteal OS (usually on the posterior distal surface of
the femur) angiography plays a vital role defining the
femoral artery in relation to the tumour site.4

Pathology
This discussion focuses mainly on the classic medullary
OS, followed by important characteristics of the vari-
ants.

Macroscopic
The tumour is hard and compact, light yellow in colour,
localised to the medulla of the metaphysis and tends to
penetrate the soft tissue via cortex destruction.
Generally the tumour does not cross the physis; howev-
er some osteosarcomas in children do cross the physis
and extend into the epiphysis.19 The tissue comprises
varying amounts of mineralised bone, with or without
foci of cartilage or fibrous tissue. A pseudo-capsule is
often observed at the tumour edge in the soft tissue.
Figure 5: X-ray lateral view of parosteal
osteosarcoma the classic position on the Microscopic
posterior aspect of the femur The principle in diagnosing OS is to identify sarcoma-
tous, spindle-shaped cells producing a calcified tissue,
osteoid or bony tissue. Well differentiated sarcomatous
osteoblasts are the exception and bizarre undifferentiat-
ed spindle cells in masses of osteoid seem to predomi-
nate. Bone production is in a rather disorganised woven
fashion with sheets of malignant cells pushed against
malignant bone. Benign-looking giant cells may be
present. Haemorrhage and necrosis are common and
predict a poor outcome.
Conventional OS is histologically classified on the tis-
sue type that predominates, as follows:
osteoblastic
chondroblastic
fibroblastic
dedifferentiated or epitheloid. This subtype is con-
sidered when spindle cells are so poorly differenti-
ated that it is impossible to distinguish between the
sarcomatous or epitheloid origin of tumour.

Variants of osteosarcoma
Many variants have been described distinct from the
classical OS which accounts for 85% of osteosarcomas.
Osteosarcoma as such is a rather rare disease and some
of these variants are extremely rare and beyond this dis-
cussion. However, some of these variants present radio-
logically very differently from the conventional picture.
Figure 6: X-ray AP of parosteal osteosarcoma Therefore, especially in the younger population, OS
the lobulated effect is usually created by needs to be considered as part of the differential diag-
mixed osseous and cartilage tissue nosis in even radiolucent lesions.
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Osteosarcomas can also arise as a secondary phenomenon Periosteal OS is thought to arise from the inner cambi-
in a wide range of entities. The most common of these um layer of the periosteum. It is worth mentioning that
lesions arise secondary to Pagets disease. However fewer this layer contains pleuripotent cells as well as
than 1% of patients with Pagets disease develop OS.20 osteoblasts. It is a low or medium grade tumour that is
Other malignant tumours such as chondrosarcoma and predominantly chondroid tissue. It usually arises in the
fibrosarcoma as well as benign tumours can also devel- diaphysis of the tibia.22
op in Pagets disease. Osteosarcoma can also arise in High grade surface OS is a very rare juxtacortical OS
bone infarcts, bone exposed to radiation and in fibrous variant.3 It is a high grade tumour and carries the same
dysplasia. metastatic and prognostic potential as conventional OS.

Incidence and characteristics of the Staging

different primary osteosarcomas The purpose of staging is three-fold:
Refer to Table II. First, a tissue diagnosis should be established.
Second, the extent of the local tumour should be
defined in terms of medullary extension, soft tissue
Juxtacortical group and neurovascular penetration, joint involvement and
The juxtacortical tumours arise on the surface of bone.
skip lesions in the same bone.
They tend to present later4 (third to fourth decade) in
Finally, it is pivotal to identify and quantify metastat-
comparison with the adolescent presentation of the con-
ic disease.
ventional OS. These tumours arise from cells in the
Biopsies should be planned with caution and should be
periosteum.
performed by the surgeon who will perform the definitive
Parosteal OS arises from the outer fibrous layer of the
procedure. Limb salvage strategies, potential flaps and
periosteum. Histologically this is a low grade tumour and
anatomical considerations (such as the anterior-superior
has a good prognosis.3 It is classically found on the pos-
extension of the knee joint) should be considered when
terior surface of the femur with a patched-on appearance
planning the biopsy.
on X-ray leaving a line between the cortex and tumour.
There are basically two systems used for staging OS.
Dedifferentiated parosteal OS is the high grade variant
Ennekings classification (Table III)23 was published in
of parosteal OS. It can arise spontaneously from a low
1980 and contributed significantly to the research of
grade parosteal OS or it can develop secondarily from an
osteosarcomas. His system is simple to use and considers
incompletely resected lesion.4 Histologically it resembles
the histological grade of tumour, the local extent and the
conventional medullary OS.
presence of metastases.

Table II: Greenspan differential diagnosis of tumours and tumour-like lesions of

bones and joint21

Type of OS Percentage of OS Characteristics

Conventional medullary 85% Arise in the metaphysis of long bones with a predilection
for distal femur, proximal tibia and proximal humerus
Juxtacortical group 47% Arise on surface (see discussion below)
Telangiectatic 5% Very aggressive; resemble aneurysmal bone cyst or bag
of blood with fluid levels; radiolucent with aggressive
osteolysis
Giant cell rich 3% Overabundant osteoclast-like cells; benign-looking
lesion resembling giant cell tumour histologically
Low grade central <2% Slow-growing, benign-looking lesion with well-defined
sclerotic rim, usually in older people
Multifocal 1.5% Lesions develop simultaneously in different bones; exis-
tence as separate entity is in doubt
Small cell 1% Similar to Ewings sarcoma; radiolucent
Gnathic 1% Arising in mandible or maxilla; fourth to sixth decade;
good prognosis
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The other classification system is the American Joint This proved to be a vital part of management,32 espe-
Committee on Cancer (AJCC) staging system24 for muscu- cially since limb salvage surgery was also introduced.
lo-skeletal tumours (Table IV). The AJCC staging score Tumour response to neo-adjuvant therapy became an
includes tumour size which is now rated as an important important prognostic factor as it measured the regres-
prognosticator.25 sion of the tumour in response to these agents. Huvos33
histological grading system grades the response to
Medical treatment chemotherapy looking at the percentage of necrosis
(Table V). At least 30 different surgical specimens are
Before the 1970s the only treatment modality for OS was
evaluated for necrosis.
surgical. Most patients treated with an amputation for
Unfortunately there are relatively few drugs that are
local disease eventually developed metastatic disease.
effective against OS. Some novel cytotoxic drugs have
This raised the suspicion that micro-metastatic disease
shown some response against OS and will be consid-
was already present (usually in the lungs) at the time of
ered in the future and reserved for unresectable and
diagnosis. This suspicion was confirmed with studies that
chemotherapy-insensitive tumours (Table VI).
showed that within two years 8090% of patients treated
Gemcitabine is a fluorinated analogue of the nucleo-
with amputation alone developed metastatic disease.26-29
side deoxycytidine and is administered in combination
Therefore OS is a systemic disease and cannot be treated
with docetaxel. Some effects have been shown in
with surgery alone.
patients with refractory or relapsed bone metastases.34
Pemetrexed inhibits folate-dependent enzymes. It
Chemotherapy shows limited effects on OS as a single drug but has
The first drug to be proven beneficial over surgery alone some promising results in combination with other drugs
was high doses of methotrexate in the early 1970s.30 like platinum and gemcitabine.35
Subsequently doxorubicin, cisplatin and in some institu-
tions ifosfamide were added. The Multi-Institution Immunotherapy
Osteosarcoma Study (MIOS) confirmed the efficacy of A recent study by Jeys et al36 showed a survival advantage
multi-drug regimens with up to 66% of patients being in patients suffering post-operative infections, suggesting
relapse-free after two years.31 that the induced immune response aids in tumour lysis.
After the great results of these chemotherapeutic The thinking behind immunotherapy (Table VII) is that a
drugs neo-adjuvant chemotherapy was introduced hop- humoral or cell-mediated attack against the tumour could
ing to shrink the tumour prior to surgery. aid in tumour necrosis.

Table III: Ennekings classification of osteosarcoma23

Stage Grade Site Metastasis

IA Low Intracompartmental None
IB Low Extracompartmental None
IIA High Intracompartmental None
IIB High Extracompartmental None
III Any Any Regional or distant

Table IV: The New American Joint Committee on Cancer Staging System24

Stage Grade Local extent Metastases

I-A Low 8 cm None
I-B Low >8 cm None
II-A High 8 cm None
II-B High >8 cm None
III Any Any Skip metastases
IV-A Any Any Pulmonary metastases
IV-B Any Any Other metastases
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Table V: Huvos classification system

Bisphosphonates
Third generation bisphosphonates show promising
evaluating osteonecrosis of resected tumour
inhibitory effects on OS cells in vitro. It is thought that
following neo-adjuvant chemotherapy33
zoledronic acid enhances specific T-cell major histo-
compatibility complex mediated lysis that is capable of
Grade Percentage of tumour necrosis unrestricted tumour cell destruction.43 Many tumour
1 <50% of tumour is necrotic cells express tumour-specific, major histocompatibility
2 Most of the tumour is necrotic <90% complexes on their surfaces that could be the target for
these T-cells.
3 Only occasional microscopic tumour viability
noted; 9099% necrosis in each section
Radiation
4 Tumour is totally necrotic Generally external beam radiation is not very effective in
the treatment of OS.41 However exceptions to this rule are
Table VI: Effective drugs against OS unresectable pelvic tumours and minimal residual disease
post surgery. These two groups could benefit from radia-
Conventional drugsdrugs tion.44
Methotrexate
Doxorubicin (Adriamycin) Surgical treatment
Cisplatin Before the 1970s surgery was the only treatment modali-
Ifosfamide ty and most of the patients were treated with amputations.
Since the introduction of chemotherapy, limb salvage
New cytotoxic drugs
therapy has become an option.
Gemcitabine The primary goal of surgical management is to limit the
Pemetrexed local extent of the disease and to prevent metastases. The
secondary goal is to restore function.
Table VII: Immunotherapeutic agents The question is whether these goals can be achieved
successfully with limb salvage therapy instead of ampu-
MTP-PE tation. To understand the argument between limb sal-
Inhaled GM-CSF vage therapy versus amputation, the terms wide margin
Trastuzumab excision and radical excision should be explained. A
wide margin is obtained if the reactive zone (the zone
of potential infiltration) is not entered and a wide cuff
Muramyl tripeptide phosphatidylethanolamine (MTP- of normal tissue is excised with the whole tumour. The
PE) is an analogue of a dipeptide found on the cell wall of potential downfall of this excision is leaving residual
the Bacille Calmette-Guerin. This analog dipeptide stimu- tumour. A radical margin is obtained when the whole
lates a cell-mediated response with the release of multiple compartment involved (bone and/or myofascial tissue)
cytokines that could be tumouricidal.37 The Childrens is excised. If the tumour is in the distal femur it implies
Cancer Group and the Pediatric Oncology Groups individ- removing the whole femur and all involved muscle
ual evaluation of MTP-PE showed that MTP-PE as such compartments. This is therefore only possible if the leg
improved overall survival and improved event-free survival, is amputated.
after it was used in a randomised trial.38 The history evolved very slowly towards limb salvage
GM-CSF is an inhaled agent capable of activating multi- therapy. In 1980 an article by Campanacci and Laus45
ple components of the immune system.36 It has anti-tumour warned about the danger of recurrence in conservative
effect in some cancer types.40 A phase II study is presently tumour resection even in the cases of amputation. In the
being conducted evaluating its efficacy in patients with same year Campanacci et al46 confirmed that chemothera-
pulmonary metastatic relapse in OS. This drug could show py changed the biological behaviour of most tumours but
benefits in patients with metastatic lung disease or as did not prevent local recurrence rates. Therefore radical
prophylaxis in patients with high risk of developing (amputation) resections were still advocated.
metastatic disease.41 In 1986 Simon et al47 revolutionised surgical therapy
Trastuzumab is a HER-2 monoclonal antibody. The with a multicentre study including 227 patients with OS
HER-2 gene codes for a transmembrane glycoprotein serv- of the distal femur. They concluded that although radical
ing as a receptor for tyrosine kinase. HER-2 expression in dissection (amputation) lowered the rate of recurrence, it
OS is often associated with a poor histological response to did not improve survival. They proved that after more
neo-adjuvant chemotherapy.42 The role of trastuzumab still than five years limb salvage surgery was as safe as ampu-
needs to be concluded. tation in patients with high grade OS.
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In 1988 Springfield et al48 from Florida duplicated these Pathological fractures do not necessarily warrant amputa-
results and also concluded that grade IIB osteosarcoma tion and each case should be considered carefully since
(extracompartmental high grade with no metastases) limb salvage therapy has been shown to be safe.49
could be treated with a wide resection instead of amputa- The kind of amputation should be individualised for the
tion. patient. For distal femoral lesions it is unnecessary to do
In the 90s Rougraff et al49 showed that, when compared a hip disarticulation and an above-knee amputation is
to amputation, limb salvage therapy produced a better safe.51
functional outcome without decreasing the rate of long-
term survival. This finally settled the debate. These results Rotationplasty
eventually led to better surgical techniques and to the Rotationplasty remains an alternative for an amputation in
development of hardware to facilitate limb salvage sur- children with distal femoral lesions. Reconstruction in limb
gery. salvage surgery remains very difficult in the very young.
Amputation is also problematic in the very young due to the
Limb salvage surgery short lever arm for prosthesis fitting. The principle of rota-
Once the diagnosis of OS is confirmed histologically, tionplasty is to excise most of the distal femur in order to get
neo-adjuvant therapy can be started. The response of the a clear, tumour-free margin and to utilise the foot as a knee-
primary tumour is evaluated. Limb salvage (Table VIII) joint on which a prosthesis can be fitted. Rotationplasty
can be considered if the follow-up imaging modalities serves as an excellent reconstructive procedure and is gen-
show tumour shrinkage or a reduced inflammatory zone erally very well tolerated by children.52
and a wide excision is viable.
Limb salvage can only be considered if there is no pro-
gression locally or distally and if blood vessels and nerves Treatment protocol summary
are free from tumour. The adjacent joint and growth plates 1. Histological diagnosis with a biopsy.
are critically evaluated for involvement. The soft tissue 2. Staging: A complete workup to establish the pres-
cover is considered in order to allow 35 cm margins in ence of metastases and the local extent of the
bone and approximately 1 cm clean margins in soft tissue tumour.
in order to achieve a wide resection. 3. Pre-operative chemotherapy (neo-adjuvant). The
response is often quantified by repeat MRI scan
Amputation after completion of the neo-adjuvant chemothera-
Amputation still remains an important surgical modality py course.
attaining excellent local control. Every patient is always 4. Surgical ablation of tumour either with limb sal-
considered for limb salvage therapy and amputation usu- vage procedure or amputation. Unresectable
ally follows when limb salvage therapy is contraindicated. tumours will be considered for radiotherapy.
Indications for amputation: 5. Histological analysis of resected tumour for
The very young, where leg length discrepancy will be degree of necrosis.
a problem. There is a school of thought which sug- 6. If <90% necrosis, postoperative chemotherapy
gests that young children cope very well with an protocol is started. In the case of limb salvage
amputation.50 therapy, amputation should be considered.
Involvement of neuro-vascular bundle. 7. If >90% necrosis, the prognosis seems more
Tumour progression on neo-adjuvant chemotherapy. favourable and the oncologist will consider
Local recurrence or minimal tumour necrosis after chemotherapy.
neo-adjuvant chemotherapy in limb salvage therapy.
Please note that pulmonary metastases often get
treated primarily with a thoracotomy to enable early
Table VIII: Limb salvage reconstructive resection. Details of this protocol fall outside the
options extent of this discussion.

Arthrodesis
Endoprosthesis with or without arthroplasty Prognostic factors
Fibula microvascular graft Many studies with conflicting results have been published
Endoprosthesis with allograft on the prognosis. The most important prognosticator is
Expandable endoprosthesis the presence of metastasis at presentation. Survival rates
Reconstruction prosthesis like scapular shoulder for these patients vary between 1020% survival after five
reconstruction and pelvic reconstruction years.53 Patients with skip lesions or other bony metasta-
External ring fixator bone transport systems sis do even worse.
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6. Malkin D, Chilton-MacNeill S, Meister LA, et al. Tissue

The role of the orthopaedic surgeon is to specific expression of SV40 in tumors associated with the
recognise the disease early and to establish Li-Fraumeni syndrome. Oncogene 2001;20:4441.
a histological diagnosis as soon as possible 7. Carbone M, Rizzo Procopio A, et al. SV40-like sequences
in human bone tumours. Oncogene 1996;13:527.
The second prognosticator is the response of tumour to 8. Porter DE, Holder ST, Steel CM, et al. A significant pro-
neo-adjuvant chemotherapy.41,54 A good necrotic response portion of the patients with osteosarcoma may belong to
usually predicts a long-term survival in up to 90% of the Li-Fraumeni cancer families. J Bone Joint Surg [Br]
patients. 74-B:883-6.
Recent literature25 suggests that tumour size is a good 9. Cumin I, Cohen JY, David A, et al. Rothmund-Thomson
indicator of histological response to neo-adjuvant syndrome and osteosarcoma. Med PediatrOncol
chemotherapy, and therefore a good pre-workup prognos- 1996;26:414.
10. Widhe B, Widhe T. Initial symptoms and clinical fea-
ticator.
tures in osteosarcoma and Ewing sarcoma. J Bone
Joint Surg [Am] 200l;82:667-74.
Conclusion 11. Jaffe N, Spears R, Efthekari F, Robertson R, Congir A,
Osteosarcoma is a solid bone tumour usually affecting the Takaue Y, Carrasco H, Wallace S, Agala A, Raymond
adolescent and young adult. Conventional OS is usually K, et al. Pathological fractures in osteosarcoma.
found around the knee. Current treatment protocols for Impact of chemotherapy on primary tumor and sur-
high grade conventional OS without metastasis carries a vival. Cancer 1987;59:701-9.
five-year survival for up to 70% of patients. Many vari- 12. Bloem JL, Kroon HM. Osseous lesions. Radiol Clin North
ants to the conventional OS can present in atypical ways, Am 1993;31:261-78.
and although they are rare, they should be considered in 13. Hudson TM, Enneking WF, et al. Magnetic resonance
even benign-looking lesions. imaging of bone and soft tissue tumors: Early experience in
31 patients compared with computed tomography. Skeletal
In the past five years good progress has been made in the
Radiol 1983;10:137-46.
understanding of limb salvage surgery and more func-
14. Pass HI, Dwyer A, Makuch R, et al. Detection of pul-
tional and durable implants have been developed.
monary metastasis in patients with osteogenic osteosarco-
However, although many exciting new discoveries are mas: The superiority of CT scans in comparison to con-
being made on the molecular pathogenesis of OS, not ventional tomograms using dynamic analysis. J Clin Oncol
many drugs have been added to current regimens. The 1985;3:1261-5.
role of the orthopaedic surgeon is to recognise the disease 15. Chew FS, Hudson TM. Radionuclide bone scanning of
early and to establish a histological diagnosis as soon as osteosarcoma: Falsely extended uptake patterns. Am J
possible. With better knowledge of the disease, multi- Roentgenol 1982;139:49-54.
drug chemotherapeutic regimens, proper surgical skills 16. Kole AC, Nieweg OE, van Ginkel RJ, et al. Detection of
and better surgical hardware it has become possible to local recurrence of soft-tissue sarcoma with positron emis-
cure and salvage limbs, and therefore sustaining a good sion tomography using [18F]fluorodeoxyglucose. Ann
quality of life. Surg Oncol 1997;4:57-63.
17. Early JF, Mankoff DA. Tumor metabolic rates in sarcoma
The content of this article is the sole work of the author. No using FDG PET. J Nucl Med 1998;39:250-4.
benefits of any form have been derived from any commer- 18. Yamamoto T, Seino Y, Fukumoto H, et al. Over-expres-
cial party related directly or indirectly to the subject of this sion of facilitative glucose transporter genes in human
article. cancer. Biochem Biophys Res Commun 1990;170:223-
30.
References 19. Panuel M, Gentet JC, Scheiner C, et al. Physeal and epi-
1. Gibbs CP, Weber K, Scarborough T. Malignant Bone physeal extent of primary malignant bone tumour in child-
Tumours; J Bone Joint Surg 2001;83A:1728-44. hood: Correlation of preoperative MRI and the pathologi-
2. Dahlin DC, Coventry MB. Osteosarcoma, a study of 600 cal examination. Pediatr Radiol 1993;23:421-4.
cases. J Bone Joint Surg 1967;49A:101-10. 20. Dickson GR, Shirodria PV, Kanis JA, et al. Familial expan-
3. World LE, Unni KK, Beaubout JW, Sim FH, Dahlin DC. sile osteolysis: a morphological, histomorphometric and
Dedifferentiated parosteal osteosarcoma. J Bone Joint Surg serological study. Bone 1991;12:331-8.
1984;66A:53-9. 21. Greenspan A, Remagen W. Differential diagnosis of
4. Sheth DS, Yasko AW, Raymond AK, Ayala AG, Carrasco tumors and tumor-like lesions of bones and joints.
CH, Benjamin RS, Jaffe N, Murray JA. Conventional and Lippincott-Raven & Williams 1998;59-117. Philadelphia
dedifferentiated parosteal osteosarcoma: Diagnosis, treat- 22. Unni KK, Dahlin DG, Beaubout JW. Periosteal osteogenic
ment and outcome. Cancer 1996;78(10):2136-45. osteosarcoma. Cancer 1976;37:2476-85.
5. Okada K, Frassica FJ, Sim FH, Beabout JW, Bond JR, 23. Enneking WF, Spanier SS, Goodman MA. Current concept
Unni KK. Parosteal osteosarcoma. A clinicopathological review: Surgical staging of musculoskeletal sarcoma. J
study. J Bone Joint Surg [Am] 1994;76:366-78. Bone Joint Surg 1982;62A:1027-30.
SAOJ Spring 2009 8/6/09 5:18 PM Page 78

Page 78 / SA ORTHOPAEDIC JOURNAL Spring 2009 REVIEW ARTICLE

24. Greene FL, Page DL, Flemming FD: Editors. American 39. Armitage JO. Emerging applications of recombinant
Joint Committee on cancer: Cancer staging manual. 6th edi- human-granulocyte-macrophage colony-stimulating factor.
tion New York: Springer; 2002. Blood 1988;92(12):4491-508.
25. Kim MS, Lee S, Cho WH, Song WS, Koh J, Lee JA, Yoo 40. Kumar R, Yoneda J, Fidler IJ, Dong Z. GM-CSF-trans-
JY, Jeon D. Initial tumor size predicts histological response duced B16 melanoma cells are highly susceptible to lysis
and survival in localised osteosarcoma patients. J Surg by normal murine macrophages and poorly tumorigenic in
Oncol 2008;97:456-61. immune-compromised mice. J Leukoc Biol
26. Campanacci M, Cervellati G. Osteosarcoma: A review of 1999;65(1):102-8.
345 cases. Ital J Orthop Traumatol 1975;1:5-22. 41. Siegel J, Pressey JG. Current concepts on the surgical and
27. Dahlin DC. Osteosarcoma of bone and a consideration of medical management of osteosarcoma. Expert Rev
prognostic variables. Cancer Treat Rep 1978;62:189. Anticancer Ther 2008;8(8):1257-69.
28. Link MP, Goorin AM, Horowitz M, et al. Adjuvant 42. Gorlick R, Huvos AG, Heller G, et al. Expression of
chemotherapy of high grade osteosarcoma of the extremi- HER2/erB-2 correlates with survival in osteosarcoma. J
ty: Updated results of the multi-institutional osteosarcoma Clin Oncol 1988;17(9):2781-8.
study. Clin Orthop Relat Res 1991:8. 43. Muraro M, Mereuta OM, Carraro F, Madon E, Fagioli F.
29. McKenna RJ, Schwinn CP, Soong KY, et al. Sarcomata of Osteosarcoma cell line growth inhibition by zoledronate-
the osteogenic series (osteosarcoma, fibrosarcoma, chon- stimulated effector cells. Cell Immuno 2007;249(2):63-72.
drosarcoma, parosteal osteogenic sarcoma, and sarcoma 44. Ozaki T, Flege S, Kevric M, et al. Osteosarcoma of the
arising in abnormal bone): An analysis of 522 cases. J Bone pelvis: experience of the Cooperative Osteosarcoma Study
Joint Surg [Am] 1966;48:1-26. Group. J Clin Oncol 2003;21(2):334-41.
30. Jaffe N, Frei E III, Traggis D, Bishop Y. Adjuvant 45. Campanacci M, Laus M. Local recurrence after amputation
methotrexate and citrovorum-factor treatment of for osteosarcoma. J Bone Joint Surg [Br] 1980;2-B:201-7.
osteogenic sarcoma. Eng J Med 1997;291(19):994-7. 46. Campanacci M, Bacci G, Payani P, Giunti A. Multiple drug
31. Link MP, Goorin AM, Miser AW, et al. The effect of adju- chemotherapy for the primary treatment of osteosarcoma
vant chemotherapy on relapse-free survival in patients with of the extremities. J Bone Joint Surg [Br] 1980;62-B:93-
osteosarcoma of the extremity. N Engl J Med 101.
1986;314(25):1600-6. 47. Simon MA, Aschliman MA, Thomas N, Mankin HJ. Limb-
32. Winkler K, Beron G, Delling G, Heise U, kabisch H, salvage treatment versus amputation for osteosarcoma of
Purfurts C, Berger J, Ritter J, Jurgens H, Gerein V, et al. the distal end of the femur. J Bone Joint Surg [ Am]
Neoadjuvant chemotherapy of osteosarcoma: results of a 1986;68:1331-7.
randomized cooperative trial (COSS-82) with salvage 48. Springfield DS, Schmidt R, Graham-Pole J, Marcus RB Jr,
chemotherapy on histological tumor response. J Clin Oncol Spanier SS, Enneking WF. Surgical treatment of osteosar-
1988;6:329-37. coma. J Bone Surg [Am] 1980;70:1124-30.
33. Huvos AG, Rosen G, Marcove RC. Primary osteogenic sar- 49. Rougraff BT, Simon MA, Kreisl JS, Greenberg DB,
coma: pathological aspects in 20 patients after treatment Mankin HJ. Limb salvage compared with amputation for
with chemotherapy, en bloc resection, and prosthetic bone osteosarcoma of the distal end of the femur. A long term
replacement. Arch Pathol Lab Med 1977;101:14-8. oncological, functional, and quality-of-life study. J Bone
34. Anderson PM, Wiseman GA, Erlandson L. Gemcitabine Joint Surg [Am] 1994;76:649-56.
radiosensitization after high dose samarium for osteoblas- 50. Kagen LB. Use of denial in adolescents with bone cancer.
tic osteosarcoma. Clin Cancer Res 2005;11(19 Pt1):6895- Health Soc Work 1976;1:70-87.
900. 51. Scully SP, Ghert MA, Zurakowski D, Thompson RC,
35. Kindler HL. The pemetrexed/gemcitabine combination in Gebhardt MC. Pathological fractures in osteosarcoma:
pancreatic cancer. Cancer 2002;95(4 Suppl.):928-32. Prognostic importance and treatment implications. J Bone
36. Jeys LM, Grimer RJ, Carter SR, Tillman RM, Abudu A. Joint Surg [ Am] 2002;84-A:49-57.
Postoperative infection and increased survival in osteosar- 52. Cammisa FP Jr, Glasser DB, Otis JC, et al. The van Nes
coma patients: are they associated? Ann Surg Oncol tibial rotationplasty. A functionally viable reconstructive
2007;14(10):2887-95. procedure in children who have a tumor of the distal end of
37. Kleinerman ES, Snyder JS, Jaffe N. Influence of the femur. J Bone Joint Surg [Am] 1990;72:1541-7.
chemotherapy administration on monocyte activation by 53. Meyers PA, Heller G, Healey JH, Huvos A, Appelwhite A,
liposomal muramyl tripeptide phosphatidylethanolamine Sun M, La Quaglia M. Osteogenic sarcoma with clinically
in children with osteosarcoma. J Clin Oncol detectable metastasis at initial presentation. J Clin Oncol
1991;9(2):259-67. 1993;11:449-53.
38. Meyer PA, Schwartz CL, Krailo MD, et al. Osteosarcoma: 54. Davis AM, Bell RS, Goodwin PJ. Prognostic factors in
the addition of muramyl tripeptide to chemotherapy osteosarcoma: A critical review. Clin Oncol 1994;12:423-
improves overall survival report from the Childrens 31.
Oncology Group. J Cancer 2008;26(4):633-8.
SAOJ