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I.
Definition
Osteosarcoma is a primary malignant tumour of the skeleton characterised by the
direct formation of immature bone or osteoid tissue by the tumour cells.3
World Health Organization (WHO) histologic classification of bone tumours divides
osteosarcomas into central and surface tumours, and recognises a number of
II.
III.
Etiology
Etiology of osteosarcoma is unknown. A viral origin was suggested by the evidence
that bone sarcomas can be induced in selected animals by viruses or cell-free
extracts of human osteosarcomas.3
The only environmental agent known to cause osteosarcoma in human is ionising
radiation. Radiation is implicated in approximately 2% of osteosarcomas. An
increased incidence of radio-induced osteosarcoma is likely to be seen with a longer
survival after primary irradiation.3
Several families have been described with multiple members who developed
osteosarcoma, suggesting genetic predisposition to this tumour. So far, the strongest
genetic predisposition is found in patients with hereditary retinoblastoma. In patients
with retinoblastoma, osteosarcoma occurs 500 times more frequently than in the
general population.1,3
Screening large series of children with osteosarcoma revealed that approximately
3% to 4% carried a constitutional germline mutation in p53. The majority of cases
with germline p53 mutations represent patients with a family history suggestive of
Li-Fraumeni syndrome.3
IV.
Diagnostic Methods
The primary tumor must be evaluated by plain radiographs in two planes, which are
mainly helpful to describe osseous changes, plain radiographs of the involved bone
show a mixed sclerotic or lytic lesion in the affected area. The tumour erodes
through the cortex, causing elevation of periosteum and often produces a significant
soft tissue swelling. It is important to remember that periosteal elevation in an
apparent bone lesion is an indication for biopsy.3
MRI is considered the most useful tool to evaluate an osteosarcoma's intramedullary
and soft tissue extension and its relation to vessels and nerves. The region assessed
by MRI should include the whole involved bone as well as the neighboring joints, so
as to not miss skip lesions (intramedullary tumor foci without direct contact with the
primary lesion). Ideally magnetic resonance imaging (MRI), both of which should
be performed before biopsy.2
Definitive diagnosis requires histological examination of tumor material, which is
generally obtained by open biopsy. Patients with findings suggestive of
osteosarcoma should be sent to a reference center before biopsy, as inappropriate
techniques can irrevocably compromise chances for limb salvage or even cure.2
Biopsy material should be obtained by the use of either a large-core tissue biopsy or,
preferably, by an open biopsy. The use of cytologic or fine-needle aspiration should
be avoided as it frequently leads to under-diagnosis or incorrect diagnosis.3
It is important to place the biopsy tract in an area where it can be totally excised, if
the patient will be successively treated by limb salvage. When a malignant bone
tumour is suspected, it is preferable the initial biopsy to be done by the surgeon who
will do the definitive surgery.3
Systemic staging must focus on the lungs and the skeleton, in which the majority of
metastases arise, and should include chest X-rays, a CT scan of the thorax
(preferably using a spiral technique performed with 5 mm collimation and obtained
Less-defined margin not easily separated from normal bone ; areas of partially
destroyed bone adjacent to completerly lytic areas.
3. The permeative pattern
Poorly demarcated margins ; abnormal lytic bone merges imperceptibly with
surrounding normal bone.
Tumors that erode the cortex of the bone usually stimulate a periosteal response, that
is, new bone formation at the interface between the surface of the bone and the
periosteum. Slow erosion of the cortex usually stimulates a uniform periosteal
response. Additional layers of bone are added to the exterior surface of the bone to
buttress ther cortex. Eventually, the additional layers expand the bones contour.
Agressive penetration of the cortex usually elevates the periosteum and stimulates
erratic patterns of new bone formation. Examples of errratic patterns include
concentric layers of new bone ; a sunburst pattern, in which delicate rays of new
bone radiate toward the periosteum from a single focus on the underlying surface ;
and rays of new bone that grow perpendicularly, creating a brush of bristle pattern.5
VI.
VII.
Staging of any bone tumor is critical to determine future treatment and results. The
Enneking Staging System is the most commonly used arregngement. This system
based on:3,5
Stage
IA
IB
IIA
IIB
IIIA
IIIB
Grade (G)
Low (G1)
Low (G1)
High (G2)
High (G2)
Low (G1)
High (G2)
Site (T)
Intracompartmental (T1)
Extracompartmental (T2)
Intracompartmental (T1)
Extracompartmental (T2)
T1 or T2
T1 or T2
Metastasis (M)
None (M0)
None (M0)
None (M0)
None (M0)
Regional or dinstant (M1)
Regional or dinstant (M1)
Carboplatin (Paraplatin)
Cisplatin
Cyclophosphamide (Cytoxan)
Doxorubicin (Adriamycin)
Epirubicin
Etoposide
Ifosfamide (Ifex)
Prognostic
Survival has improved over the past several decades. Indeed, patients with nonmetastatic disease have a 70% chance of long-term survival. Unfortunately, patients
with metastatic disease at diagnosis and those who have recurrent disease have a
poor prognosis, with only 20% surviving at 5 years.4
Combined neoadjuvant treatment gives a cure rate of 60%70% for patients with
nonmetastatic osteosarcoma of the extremities at presentation and of about 30% for
tumours of the axial skeleton. Metastases at presentation and, in localised tumours,
anatomic site (extremity or axial), histological response to preoperative
chemotherapy (as measured histologically from the resected specimen), serum levels
of alkaline phosphatase and lactate dehydrogenase are the most powerful predictors
of survival for patients with osteosarcoma.3
Adverse prognostic factors include proximal extremity or axial tumor site, large
tumor volume, elevated serum AP or LDH, and foremost detectable primary
metastases and poor histological response to preoperative chemotherapy.2