History and exam
Key diagnostic factors
common
childhood and adolescence
Peak incidence in the second decade of life, with most patients (approximately 50%) being under the age of 25 years.[3]
A bone lesion in an older patient with aggressive radiological features should be considered a metastasis until shown otherwise.
worsening pain over weeks to months
male sex
Across all age groups in the US, osteosarcoma is more common in males than females for each race/ethnicity (male IR 3.6, 95% CI 3.5 to 3.80 vs. female IR 3.0, 95% CI 2.9 to 3.1), with the second peak in incidence being exclusively male.[3]
Some studies suggest that parosteal osteosarcoma (i.e., tumour arising from the metaphyseal surface of long bones) may be more common among females.[29]
Other diagnostic factors
common
race/ethnicity
The highest incidence rates in the US have been reported among black and hispanic populations (for all age cases: black population, IR, 4.1; 95% CI, 3.8 to 4.4, hispanic population, IR, 3.4; 95% CI, 3.2 to 3.6).[3]
tall stature
Globally an increased risk of osteosarcoma has been observed among the tallest populations, including those in The Netherlands, Iceland, Slovakia, and Czech Republic.[6][7] However, one study which assessed genetic risk scores (GRS) found no overall association between osteosarcoma and genetically inferred taller stature (OR=1.06, 95% CI 0.96 to 1.17, P=0.28), although the GRS for taller stature was associated with an increased risk of osteosarcoma in 154 cases with a known pathogenic cancer susceptibility gene variant (OR=1.29, 95% CI 1.03 to 1.63, P=0.03).[5]
high birthweight
Genetically inferred higher birthweight has been associated with an increased risk of osteosarcoma (OR=1.59, 95% CI 1.07 to 2.38, P=0.02). This association was strongest in cases without metastatic disease.[5]
limp
With tumours in the lower limb, patients frequently have an antalgic gait (i.e., a limping gait, due to pain on bearing weight on the affected side).
uncommon
history of trauma
The trauma, which is usually mild, is the event that draws attention to the involved body region rather than being the causative factor.[14]
limited range of motion
This may be noted in the adjacent joint and depends on the location and size of the tumour.
Risk factors
strong
childhood and adolescence
Peak incidence in the second decade of life, with most patients (approximately 50%) being under the age of 25 years.[3]
Paget's disease
Paget's disease of bone is associated with an increased risk for developing secondary osteosarcoma, commonly associated with older age groups (above 60 years).[4] A genetic predisposition may exist in these patients, which is linked to chromosome 18q23.[8] Loss of heterozygosity of chromosome 18q has been reported in patients with primary and Paget-related osteosarcoma.[9][10]
radiotherapy
Osteosarcoma is the most common post-radiation malignant neoplasm following therapy for a solid cancer in childhood.[4][11] Evidence suggests that the risk of bone sarcoma increases slowly up to a cumulative radiation organ absorbed dose of 15 Gy and then strongly increases for higher radiation doses of 30 Gy or more compared with patients not treated with radiotherapy.[12]
Rothmund-Thomson syndrome
Rare autosomal-recessive disease due to a defective gene (RECQL4) mapped on chromosome 8q24.3. Also known as poikiloderma congenitale. Clinical manifestations include skin rash, small stature, and bone dysplasias. Patients with the defective gene have an increased risk for osteosarcoma.[22]
familial retinoblastoma syndrome
Patients with this condition have an increased risk of developing osteosarcoma, possibly associated with 3p deletions.[17]
Li-Fraumeni syndrome
Familial cancer syndrome resulting from germline mutations in the p53 tumour suppressor gene. Patients have increased risk of developing numerous malignancies including breast, soft tissue, brain, adrenocortical, and bone.
race/ethnicity
The highest incidence rates in the US have been reported among black and hispanic populations (for all age cases: black population, incidence rate [IR], 4.1; 95% confidence interval [CI], 3.8 to 4.4, hispanic population, IR, 3.4; 95% CI, 3.2 to 3.6).[3]
non-familial deleterious germline variants
Emerging evidence has identified a high number of deleterious germline genetic variants in patients with osteosarcoma, particularly in the younger age group.[18][19][20][21] Approximately one fourth of patients with osteosarcoma have been reported to have a germline pathogenic variant in an established cancer-susceptibility gene, with patients aged <10 years demonstrating the highest frequency.[21]
male sex
Across all age groups in the US, osteosarcoma is more common in males than females for each race/ethnicity (male incidence rate [IR] 3.6, 95% confidence interval [CI] 3.5 to 3.80 vs. female IR 3.0, 95% CI 2.9 to 3.1), with the second peak in incidence being exclusively male.[3]
weak
tall stature
Globally an increased risk of osteosarcoma has been observed among the tallest populations, including those in The Netherlands, Iceland, Slovakia, and Czech Republic.[6][7] However, one study which assessed genetic risk scores (GRS) found no overall association between osteosarcoma and genetically inferred taller stature (Odds ratio [OR]=1.06, 95% confidence interval [CI] 0.96 to 1.17, P=0.28), although the GRS for taller stature was associated with an increased risk of osteosarcoma in 154 cases with a known pathogenic cancer susceptibility gene variant (OR=1.29, 95% CI 1.03 to 1.63, P=0.03).[5]
high birthweight
Genetically inferred higher birthweight has been associated with an increased risk of osteosarcoma (OR=1.59, 95% CI 1.07 to 2.38, P=0.02). This association was strongest in cases without metastatic disease.[5]
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