REVIEW ARTICLE ANZJSurg.com
Many faces of osteosarcoma on plain radiographs Mark Clayer Musculoskeletal Tumour Unit, Department of Orthopaedics and Trauma, Royal Adelaide Hospital, Adelaide, South Australia, Australia
Key words bone cancer, osteosarcoma. Correspondence Associate Professor Mark Clayer, Musculoskeletal Tumour Unit, Department of Orthopaedics and Trauma, Royal Adelaide Hospital, 1 North Terrace, Adelaide, SA 5000, Australia. Email: [email protected] M. Clayer MD, MSc, MBBS, FRACS.
Abstract Osteosarcoma is the most common primary malignancy of bone. It is a very rare form of cancer with an annual incidence of 3:1 000 000 and so will not be seen by many surgeons. Coupled with this are the many different subtypes of this cancer that can have different appearances on imaging ranging from densely sclerotic to lytic or even cystic. They can be medullary, cortically or periosteally based. This article demonstrates the various different appearances associated with the different types of osteosarcoma which will assist surgeons in diagnosing this rare cancer.
Accepted for publication 28 July 2014. doi: 10.1111/ans.12836
Introduction
Intramedullary osteosarcomas
Osteosarcoma is the most common primary malignancy of bone.1 The annual incidence is 3:1 000 000 and accounts for approximately 20% of all primary malignant tumours of bone.2 Although it is obviously rare given the incidence, it has a predilection for children and teenagers and that poses the long-term issues of reconstruction in those with a potentially very long life ahead of them. Early diagnosis is therefore the ideal as this may lead to better reconstructive options. The definition for diagnosing an osteosarcoma is the presence of malignant osteoid. A tumour only needs a fraction of this malignant osteoid for it to be classified as an osteosarcoma. Classically, osteosarcoma is a bone-producing malignancy (so called ‘osteoblastic’) and therefore produces a sclerotic appearance on plain radiographs (Fig. 1), usually with cortical disruption and extension of bone into the soft tissues (sunburst appearance). While osteoblastic osteosarcoma is the most common, it can also have other types of matrices as the predominant feature although malignant osteoid must be present for the diagnosis of osteosarcoma. Other predominant matrices include cartilaginous (‘chondroblastic’) (Fig. 2), fibrous (‘fibroblastic’) (Fig. 3) or giant cells (‘giant cell rich’) (Fig. 4). As these forms of osteosarcoma do not have bone production as the prominent feature, sclerosis is often only a minor component of the destructive bone lesion. This can lead to confusion with the diagnosis as a number of benign conditions, that is, chronic osteomyelitis can have a similar radiographic appearance. Osteosarcomas can arise from within the bone (intramedullary) or from the cortex or periosteum of the bone (surface).
Osteoblastic (Fig. 1) This is the most common form of osteosarcoma (approximately 40% of all cases).1 It is an intramedullary, infiltrating lesion that usually arises within the metaphysis of the bone. The matrix is predominantly osteoid and so it produces a predominant sclerotic appearance on plain radiographs. The tumour broaches the cortex often lifting the periosteum to produce Codman triangles at the points the periosteum rejoins the main cortex. Areas where the periosteum has been lifted can produce a ‘sunburst’ appearance of radiating new bone spicules or ‘onion skinning’ of multiple lamellae of new bone. The soft tissue component may also be mineralized which gives it a ‘fluffy’ appearance.
ANZ J Surg 85 (2015) 22–26
Chondroblastic (Fig. 2) This is approximately 20% of all osteosarcomas.1 The chondroblastic osteosarcoma has the predominant feature of a medium- to high-grade chondroblastic focus. Calcification may be present on imaging rather than ossification, but usually the appearance is of a lytic destructive tumour. Axial osteosarcomas are more likely to be chondroblastic.3 Fibroblastic (Fig. 3) This is approximately 20% of all osteosarcomas.1 The stroma of the fibroblastic variant is composed of spindle cells that produce a herring bone pattern and osteoid is scant. The lack of osteoid produces the appearance of a lytic, destructive bone tumour. © 2014 Royal Australasian College of Surgeons
Many faces of osteosarcoma
23
Fig. 1. Osteoblastic osteosarcoma. Anteroposterior radiograph of the distal femur demonstrating a sclerotic abnormality in the supracondylar region. There is associated laminated periosteal new bone (‘onion skinning’) and a soft tissue mass medially and laterally.
Fig. 3. Fibroblastic osteosarcoma. Anteroposterior radiograph of the knee joint demonstrating patchy lytic bone loss in association with periosteal new bone in the supracondylar and condylar regions of the distal femur.
Fig. 2. Chondroblastic osteosarcoma. Anteroposterior radiograph of the knee joint demonstrating a lytic, destructive lesion involving the head, neck and proximal shaft of the fibula. Once again, there is periosteal new bone and a cortical broach but without significant sclerotic new bone.
Giant cell rich (Fig. 4) This is less than 1% of all osteosarcomas. It can be confused with giant cell tumour of bone due to the large numbers of giant cells in the stroma which appear bland and reactive, and once again osteoid may be sparse. Giant cell tumour is a benign primary tumour of bone © 2014 Royal Australasian College of Surgeons
Fig. 4. Giant cell-rich osteosarcoma. Anteroposterior radiograph of the knee joint demonstrating a lytic destructive lesion arising in the lateral condyle of the femur. Associated Codman’s triangle is more superior where the periosteum has been lifted. Obvious soft tissue mass associated with patchy ossification within. Pre-existing mal-union of the proximal tibia.
24
Fig. 5. Telangiectatic osteosarcoma. Anteroposterior radiograph of the knee joint demonstrating a lytic lesion in the proximal tibia. There is periosteal new bone formation, predominantly laterally, but no obvious cortical disruption or soft tissue extension.
Clayer
Fig. 6. Low-grade central osteosarcoma. Anteroposterior radiograph of the knee joint demonstrating a mixed pattern of sclerosis and lysis but minimal cortical disruption despite its size.
but is often destructive, and so imaging may not help in differentiating between the two. Telangiectatic (Fig. 5) This constitutes less than 4% of all osteosarcomas.1 This is often confused with an aneurysmal bone cyst as the predominant feature is cystic spaces within the bone. A significant characteristic that assists in differentiating between these two vastly different conditions is that aneurysmal bone cysts usually affect children and stabilize at skeletal maturity. In contrast, telangiectatic osteosarcomas predominantly affect those in late teens to 20s and are clearly active well beyond skeletal maturity. Low-grade central (Fig. 6) This is approximately 1% of all osteosarcomas. This is a fibroosseous lesion and so the appearance is usually of a mixed sclerotic and lytic tumour and often cortical. Paget’s osteosarcoma (Fig. 7) This is approximately 5% of all osteosarcomas.4 The key feature is the presence of Paget’s disease of bone with a bone-producing tumour associated. This form of osteosarcoma is extremely aggressive and so the tumour may be quite extensive at presentation both locally and systemically.
Surface osteosarcoma High-grade surface (Fig. 8a) This is a very rare form of osteosarcoma accounting for less than 1% of all osteosarcomas.1 This form of osteosarcoma arises from the surface and has variable amounts of mineralization within it so it appears as a soft tissue mass attached to the bone (most commonly femur or tibia) which is partially ossified.
Fig. 7. Paget’s osteosarcoma. Anteroposterior radiograph of the knee joint demonstrating a sclerotic mass replacing most of the femoral condyles with the classic X-ray appearance of Paget’s disease of bone in the remaining femur more proximal.
Parosteal (Fig. 8b) This is approximately 3% of all osteosarcomas.5 It almost exclusively arises from the posterior surface of the distal femur. It must be considered whenever a bone-forming tumour is seen in this location. © 2014 Royal Australasian College of Surgeons
Many faces of osteosarcoma
(a)
25
(b)
(c)
(d)
Fig. 8. (a) High-grade surface osteosarcoma. Anteroposterior radiograph of the proximal femur demonstrating a partially ossified mass arising from the lateral cortex of the femur. (b) Parosteal osteosarcoma. Lateral radiograph of the knee joint demonstrating a well-circumscribed mass arising from the posterior surface of the distal femur. (c) Periosteal osteosarcoma. Lateral radiograph of the proximal tibia demonstrating a subtle cortical hypertrophy adjacent to a periosteal osteosarcoma. The tumour is radiolucent and it is only the underlying bone reaction that confirms its location. (d) CT scan of the periosteal osteosarcoma shown in Figure 8c. The mass is seen juxtacortical with sunburst spiculation from the underlying cortex.
It is low grade and slow growing so a long history does not preclude this diagnosis. Periosteal (Fig. 8c,d) This is approximately 1% of all osteosarcomas. It appears as a radiolucent mass juxtacortical, rarely invading the medullary cavity. Often the adjacent cortical bone reaction to it is the only radiographic feature present.
Discussion Prolonged unilateral pain, especially around the knee in a child, the most common site for an osteosarcoma, is not a symptom that should be easily dismissed. There should be a low threshold to ordering a plain radiograph in this situation. In addition, a plain radiograph is the first and most appropriate imaging technique when investigating a mass. Although additional imaging will be required when evaluating and staging an osteosarcoma, a plain radiograph should alert the clinician to the possibility that this diagnosis is likely. The absence of sclerosis within the lesion does not preclude the diagnosis of osteosarcoma as shown in this article. Additional imaging with technetium labelled whole body bone scan, computerized tomogra© 2014 Royal Australasian College of Surgeons
phy and magnetic resonance imaging will be required but should not distract from the initial radiographic investigation. Following completion of staging with imaging, a biopsy should be performed. This needs to be a core biopsy as the presence of ossification within the matrix can complicate the successful collection of representative viable neoplastic tissue if a needle technique is used. Ideally, the biopsy is performed through the compartment that is likely to be excised and involves multiple samples of the tumour taken through the same biopsy tract. The biopsy tract needs to be identifiable, either by scar or tattooing, so that it can be excised at the time of definitive surgical excision without compromising the surgical excision. For this reason, the biopsy is best undertaken by the surgeon who is going to do the definitive surgical excision or at least under the supervision of the surgeon who will be responsible for the definitive management. The samples taken should be through the same incision but the tissue should be taken from as wide an area as possible within the tumour to avoid the risks of collecting non-viable tumour (a significant risk in all high-grade sarcomas) and to avoid sampling error as there can be significant heterogeneity within the same tumour. Not only can osteosarcomas be low, intermediate or high grade in overall nature, regardless of the location, but they can also have variable grades within the same tumour. This will impact
26
upon treatment and prognosis so it is important that the surgeon undertaking the biopsy has experience of treating osteosarcomas as much as the pathologist reviewing the specimen and the radiologist that reviews the imaging. If one facet of the features demonstrated on imaging, clinical behaviour and/or pathology is inconsistent then a repeat biopsy is indicated. For this reason, multidisciplinary teams are ideal as they reduce the risk of decision-making in a vacuum. High-grade osteosarcomas should receive neo-adjuvant chemotherapy prior to definitive surgical excision because 95% of highgrade osteosarcomas have micrometastatic disease at presentation. Obviously, the timing of chemotherapy cycles, pre-surgical imaging and operative planning are functions that also work better in a multidisciplinary team. Low-grade osteosarcomas are resistant to chemotherapy because, by definition, they have a low mitotic rate. Chemotherapy is therefore not indicated. This review demonstrates the high variation in appearance of osteosarcomas and therefore the great potential for misdiagnosis. Early diagnosis gives the best chance for curative treatment and satisfactory reconstruction.
Clayer
Acknowledgements The author would like to acknowledge the donation of Figure 6 by Mr Will Aston, Royal National Orthopaedic Hospital.
References 1. Messerschmitt P, Garcia R, Abdul-Karim F, Greenfield E, Getty P. Osteosarcoma. J. Am. Acad. Orthop. Surg. 2009; 17: 515–27. 2. Dorfman H, Czerniak B. Bone cancers. Cancer 1995; 75: 203–10. 3. Kawai A, Huvos A, Meyers P, Healey J. Osteosarcoma of the pelvis. Clin. Orthop. Relat. Res. 1998; 348: 196–207. 4. Huvos A, Butler A, Bretsky S. Osteogenic sarcoma associated with Paget’s disease of bone. Cancer 1983; 52: 1489–95. 5. Klein M, Siegal G. Osteosarcoma: anatomic and histologic variants. Am. J. Clin. Pathol. 2006; 125: 555–81.
© 2014 Royal Australasian College of Surgeons
Many faces of osteosarcoma on plain radiographs Mark Clayer Musculoskeletal Tumour Unit, Department of Orthopaedics and Trauma, Royal Adelaide Hospital, Adelaide, South Australia, Australia
Key words bone cancer, osteosarcoma. Correspondence Associate Professor Mark Clayer, Musculoskeletal Tumour Unit, Department of Orthopaedics and Trauma, Royal Adelaide Hospital, 1 North Terrace, Adelaide, SA 5000, Australia. Email: [email protected] M. Clayer MD, MSc, MBBS, FRACS.
Abstract Osteosarcoma is the most common primary malignancy of bone. It is a very rare form of cancer with an annual incidence of 3:1 000 000 and so will not be seen by many surgeons. Coupled with this are the many different subtypes of this cancer that can have different appearances on imaging ranging from densely sclerotic to lytic or even cystic. They can be medullary, cortically or periosteally based. This article demonstrates the various different appearances associated with the different types of osteosarcoma which will assist surgeons in diagnosing this rare cancer.
Accepted for publication 28 July 2014. doi: 10.1111/ans.12836
Introduction
Intramedullary osteosarcomas
Osteosarcoma is the most common primary malignancy of bone.1 The annual incidence is 3:1 000 000 and accounts for approximately 20% of all primary malignant tumours of bone.2 Although it is obviously rare given the incidence, it has a predilection for children and teenagers and that poses the long-term issues of reconstruction in those with a potentially very long life ahead of them. Early diagnosis is therefore the ideal as this may lead to better reconstructive options. The definition for diagnosing an osteosarcoma is the presence of malignant osteoid. A tumour only needs a fraction of this malignant osteoid for it to be classified as an osteosarcoma. Classically, osteosarcoma is a bone-producing malignancy (so called ‘osteoblastic’) and therefore produces a sclerotic appearance on plain radiographs (Fig. 1), usually with cortical disruption and extension of bone into the soft tissues (sunburst appearance). While osteoblastic osteosarcoma is the most common, it can also have other types of matrices as the predominant feature although malignant osteoid must be present for the diagnosis of osteosarcoma. Other predominant matrices include cartilaginous (‘chondroblastic’) (Fig. 2), fibrous (‘fibroblastic’) (Fig. 3) or giant cells (‘giant cell rich’) (Fig. 4). As these forms of osteosarcoma do not have bone production as the prominent feature, sclerosis is often only a minor component of the destructive bone lesion. This can lead to confusion with the diagnosis as a number of benign conditions, that is, chronic osteomyelitis can have a similar radiographic appearance. Osteosarcomas can arise from within the bone (intramedullary) or from the cortex or periosteum of the bone (surface).
Osteoblastic (Fig. 1) This is the most common form of osteosarcoma (approximately 40% of all cases).1 It is an intramedullary, infiltrating lesion that usually arises within the metaphysis of the bone. The matrix is predominantly osteoid and so it produces a predominant sclerotic appearance on plain radiographs. The tumour broaches the cortex often lifting the periosteum to produce Codman triangles at the points the periosteum rejoins the main cortex. Areas where the periosteum has been lifted can produce a ‘sunburst’ appearance of radiating new bone spicules or ‘onion skinning’ of multiple lamellae of new bone. The soft tissue component may also be mineralized which gives it a ‘fluffy’ appearance.
ANZ J Surg 85 (2015) 22–26
Chondroblastic (Fig. 2) This is approximately 20% of all osteosarcomas.1 The chondroblastic osteosarcoma has the predominant feature of a medium- to high-grade chondroblastic focus. Calcification may be present on imaging rather than ossification, but usually the appearance is of a lytic destructive tumour. Axial osteosarcomas are more likely to be chondroblastic.3 Fibroblastic (Fig. 3) This is approximately 20% of all osteosarcomas.1 The stroma of the fibroblastic variant is composed of spindle cells that produce a herring bone pattern and osteoid is scant. The lack of osteoid produces the appearance of a lytic, destructive bone tumour. © 2014 Royal Australasian College of Surgeons
Many faces of osteosarcoma
23
Fig. 1. Osteoblastic osteosarcoma. Anteroposterior radiograph of the distal femur demonstrating a sclerotic abnormality in the supracondylar region. There is associated laminated periosteal new bone (‘onion skinning’) and a soft tissue mass medially and laterally.
Fig. 3. Fibroblastic osteosarcoma. Anteroposterior radiograph of the knee joint demonstrating patchy lytic bone loss in association with periosteal new bone in the supracondylar and condylar regions of the distal femur.
Fig. 2. Chondroblastic osteosarcoma. Anteroposterior radiograph of the knee joint demonstrating a lytic, destructive lesion involving the head, neck and proximal shaft of the fibula. Once again, there is periosteal new bone and a cortical broach but without significant sclerotic new bone.
Giant cell rich (Fig. 4) This is less than 1% of all osteosarcomas. It can be confused with giant cell tumour of bone due to the large numbers of giant cells in the stroma which appear bland and reactive, and once again osteoid may be sparse. Giant cell tumour is a benign primary tumour of bone © 2014 Royal Australasian College of Surgeons
Fig. 4. Giant cell-rich osteosarcoma. Anteroposterior radiograph of the knee joint demonstrating a lytic destructive lesion arising in the lateral condyle of the femur. Associated Codman’s triangle is more superior where the periosteum has been lifted. Obvious soft tissue mass associated with patchy ossification within. Pre-existing mal-union of the proximal tibia.
24
Fig. 5. Telangiectatic osteosarcoma. Anteroposterior radiograph of the knee joint demonstrating a lytic lesion in the proximal tibia. There is periosteal new bone formation, predominantly laterally, but no obvious cortical disruption or soft tissue extension.
Clayer
Fig. 6. Low-grade central osteosarcoma. Anteroposterior radiograph of the knee joint demonstrating a mixed pattern of sclerosis and lysis but minimal cortical disruption despite its size.
but is often destructive, and so imaging may not help in differentiating between the two. Telangiectatic (Fig. 5) This constitutes less than 4% of all osteosarcomas.1 This is often confused with an aneurysmal bone cyst as the predominant feature is cystic spaces within the bone. A significant characteristic that assists in differentiating between these two vastly different conditions is that aneurysmal bone cysts usually affect children and stabilize at skeletal maturity. In contrast, telangiectatic osteosarcomas predominantly affect those in late teens to 20s and are clearly active well beyond skeletal maturity. Low-grade central (Fig. 6) This is approximately 1% of all osteosarcomas. This is a fibroosseous lesion and so the appearance is usually of a mixed sclerotic and lytic tumour and often cortical. Paget’s osteosarcoma (Fig. 7) This is approximately 5% of all osteosarcomas.4 The key feature is the presence of Paget’s disease of bone with a bone-producing tumour associated. This form of osteosarcoma is extremely aggressive and so the tumour may be quite extensive at presentation both locally and systemically.
Surface osteosarcoma High-grade surface (Fig. 8a) This is a very rare form of osteosarcoma accounting for less than 1% of all osteosarcomas.1 This form of osteosarcoma arises from the surface and has variable amounts of mineralization within it so it appears as a soft tissue mass attached to the bone (most commonly femur or tibia) which is partially ossified.
Fig. 7. Paget’s osteosarcoma. Anteroposterior radiograph of the knee joint demonstrating a sclerotic mass replacing most of the femoral condyles with the classic X-ray appearance of Paget’s disease of bone in the remaining femur more proximal.
Parosteal (Fig. 8b) This is approximately 3% of all osteosarcomas.5 It almost exclusively arises from the posterior surface of the distal femur. It must be considered whenever a bone-forming tumour is seen in this location. © 2014 Royal Australasian College of Surgeons
Many faces of osteosarcoma
(a)
25
(b)
(c)
(d)
Fig. 8. (a) High-grade surface osteosarcoma. Anteroposterior radiograph of the proximal femur demonstrating a partially ossified mass arising from the lateral cortex of the femur. (b) Parosteal osteosarcoma. Lateral radiograph of the knee joint demonstrating a well-circumscribed mass arising from the posterior surface of the distal femur. (c) Periosteal osteosarcoma. Lateral radiograph of the proximal tibia demonstrating a subtle cortical hypertrophy adjacent to a periosteal osteosarcoma. The tumour is radiolucent and it is only the underlying bone reaction that confirms its location. (d) CT scan of the periosteal osteosarcoma shown in Figure 8c. The mass is seen juxtacortical with sunburst spiculation from the underlying cortex.
It is low grade and slow growing so a long history does not preclude this diagnosis. Periosteal (Fig. 8c,d) This is approximately 1% of all osteosarcomas. It appears as a radiolucent mass juxtacortical, rarely invading the medullary cavity. Often the adjacent cortical bone reaction to it is the only radiographic feature present.
Discussion Prolonged unilateral pain, especially around the knee in a child, the most common site for an osteosarcoma, is not a symptom that should be easily dismissed. There should be a low threshold to ordering a plain radiograph in this situation. In addition, a plain radiograph is the first and most appropriate imaging technique when investigating a mass. Although additional imaging will be required when evaluating and staging an osteosarcoma, a plain radiograph should alert the clinician to the possibility that this diagnosis is likely. The absence of sclerosis within the lesion does not preclude the diagnosis of osteosarcoma as shown in this article. Additional imaging with technetium labelled whole body bone scan, computerized tomogra© 2014 Royal Australasian College of Surgeons
phy and magnetic resonance imaging will be required but should not distract from the initial radiographic investigation. Following completion of staging with imaging, a biopsy should be performed. This needs to be a core biopsy as the presence of ossification within the matrix can complicate the successful collection of representative viable neoplastic tissue if a needle technique is used. Ideally, the biopsy is performed through the compartment that is likely to be excised and involves multiple samples of the tumour taken through the same biopsy tract. The biopsy tract needs to be identifiable, either by scar or tattooing, so that it can be excised at the time of definitive surgical excision without compromising the surgical excision. For this reason, the biopsy is best undertaken by the surgeon who is going to do the definitive surgical excision or at least under the supervision of the surgeon who will be responsible for the definitive management. The samples taken should be through the same incision but the tissue should be taken from as wide an area as possible within the tumour to avoid the risks of collecting non-viable tumour (a significant risk in all high-grade sarcomas) and to avoid sampling error as there can be significant heterogeneity within the same tumour. Not only can osteosarcomas be low, intermediate or high grade in overall nature, regardless of the location, but they can also have variable grades within the same tumour. This will impact
26
upon treatment and prognosis so it is important that the surgeon undertaking the biopsy has experience of treating osteosarcomas as much as the pathologist reviewing the specimen and the radiologist that reviews the imaging. If one facet of the features demonstrated on imaging, clinical behaviour and/or pathology is inconsistent then a repeat biopsy is indicated. For this reason, multidisciplinary teams are ideal as they reduce the risk of decision-making in a vacuum. High-grade osteosarcomas should receive neo-adjuvant chemotherapy prior to definitive surgical excision because 95% of highgrade osteosarcomas have micrometastatic disease at presentation. Obviously, the timing of chemotherapy cycles, pre-surgical imaging and operative planning are functions that also work better in a multidisciplinary team. Low-grade osteosarcomas are resistant to chemotherapy because, by definition, they have a low mitotic rate. Chemotherapy is therefore not indicated. This review demonstrates the high variation in appearance of osteosarcomas and therefore the great potential for misdiagnosis. Early diagnosis gives the best chance for curative treatment and satisfactory reconstruction.
Clayer
Acknowledgements The author would like to acknowledge the donation of Figure 6 by Mr Will Aston, Royal National Orthopaedic Hospital.
References 1. Messerschmitt P, Garcia R, Abdul-Karim F, Greenfield E, Getty P. Osteosarcoma. J. Am. Acad. Orthop. Surg. 2009; 17: 515–27. 2. Dorfman H, Czerniak B. Bone cancers. Cancer 1995; 75: 203–10. 3. Kawai A, Huvos A, Meyers P, Healey J. Osteosarcoma of the pelvis. Clin. Orthop. Relat. Res. 1998; 348: 196–207. 4. Huvos A, Butler A, Bretsky S. Osteogenic sarcoma associated with Paget’s disease of bone. Cancer 1983; 52: 1489–95. 5. Klein M, Siegal G. Osteosarcoma: anatomic and histologic variants. Am. J. Clin. Pathol. 2006; 125: 555–81.
© 2014 Royal Australasian College of Surgeons
