Bone tumours

From Oncology for Medical Students

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Introduction

Embryologically, bone arises from the mesoderm. As such, primary tumours related to bone might comprise any tissue of mesodermal origin. Bone tumours are common. The largest group are benign bone tumours, followed by metastatic bone tumours, and, least commonly, primary bone malignancies.

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Benign bone tumours

Common benign bone tumours include:

  • aneurysmal bone cyst
  • simple bone cyst
  • enchondroma
  • giant cell tumour of bone.

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Aneurysmal bone cyst

Aneurysmal bone cysts (ABC) may occur in any bone. The commonest sites include the appendicular skeleton (20-25%), followed by the spine (15%) and pelvis (10%).


Aneurysmal bone cyst of ankle.png

Figure 1(a). Antero-posterior and lateral radiograph of ankle. Aneursymal bone cysts are generally located eccentrically in the metaphysis. They are radiolucent, expansile with thinning of the cortex and often have a sharp sclerotic margin.


Aneurysmal bone cyst Coronal image.jpg Aneurysmal bone cyst sagittal image.jpg


Figure 1(b). Coronal and sagittal magnetic resonance images of simple bone cyst of ankle.


Aneurysmal bone cyst axial MRI.jpg Aneurysmal bone cyst axial MRI 2.jpg


Figure 1(c). Axial magnetic resonance images of aneurysmal bone cyst of ankle MRI scan shows a well defined lesion, often lobulated with internal septations. Fluid-fluid levels are seen here as demonstrated (arrow).


Pathology

There are 2 types of ABC. The typical ABC (95%) is a blood filled lytic expansion of bone which is often separated into a multitude of compartments by thin septae of bone. A less common form, the solid ABC (5%), is characterised by an expansion of bone which is filled with a mixture of fibrous, cellular and myxoid tissue in which blood filled clefts are found.


Presentation

Because the wall of the cyst is thin, fracture may occur with minimal trauma (pathologic fracture). Prior to fracture, normal stresses on the involved bone may also cause pain. Sometimes expansion of the bone may be significant and patients may present with a lump associated with a bone or a general swelling/enlargement of one part of a bone.


Investigation

  • plain radiographs
  • nuclear bone scan
  • computed tomography
  • magnetic resonance imaging
  • biopsy


Treatment

ABC can be treated with curettage of its contents, and filling of the defect with bone graft or synthetic material (bone graft substitute or acrylic bone cement). Sometimes weakened bone also requires internal fixation.

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Simple bone cysts

Simple bone cysts occur in the young and are most commonly detected between the ages of 5-15 years. It is characterized by an expansile cavity within bone. Most commonly there is only one compartment related to the cyst (unicameral), but occasionally there may be a number of compartments (multicameral).

While simple bone cysts may occur in any bone the commonest bones are the proximal long bones (humerus, femur).


Simple bone cyst.jpg

Figure 2. Unicameral bone cysts are centrally located, well circumscribed within the metaphysis or diaphysis of long bones. They have a radiolucent appearance, often expansile with thinning of the cortex. The characteristic “fallen fragment” sign (arrow) can sometimes be seen. This represents a fracture fragment which floats within the fluid-filled cyst.


Pathology

Simple cysts are often only filled with a clear yellowish fluid. The lining of the cyst wall is by a bland pauci-cellular membrane. There are two variants of simple bone cysts namely, active and latent. Active bone cysts are usually located adjacent to the growth plate and increase in size as the child/teenager grows. Once skeletal growth slows or ceases, cysts become inactive (latent). They are usually found further away from the growth plate at this stage. Sometimes the proximity of the cyst to the growth plate interferes with normal growth and discrepancies in size or length of the bone may be noted.


Presentation

Simple cysts become symptomatic when they break or are sufficiently stressed. The potential for ongoing growth of the cyst during the period of childhood/adolescent activity may result in repeated fractures.


Investigation

  • plain radiograph
  • nuclear bone scan
  • biopsy


Treatment

Simple bone cysts may heal spontaneously after fracture. Aspiration of the fluid from the cyst and injection with corticosteroid may also lead to healing. Troublesome cysts with ongoing pain or repeated fractures may be treated with evacuation and filling with bone graft. Occasionally internal fixation may be required.

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Enchondroma

An enchondroma is a benign cartilage tumour that arises within bone. Enchondromas may arise in any bone, may be solitary or multiple, may be static or may grow. They are often noted incidentally on plain radiographs or bone scans obtained for other reasons.


Enchondroma.jpg

Figure 3. Enchondromas are commonly located in the metaphysis of long bones ie. proximal humerus, distal femur and proximal tibia. They have a mixed sclerotic and lucent appearance with calcifications (arrow) within the lesions.


Pathology

Enchondromas arise from embryological cartilage remnants that have failed to fully ossify. Under the influence of the growing skeleton, enchondromas may also increase in size until skeletal maturity. Enchondromas when detected in adulthood are often inactive, but in rare circumstances may continue to grow or even undergo malignant change. The majority of tumours remain benign and indolent.

Enchondromas are lytic lesions filled with cartilage tissue. Erosion of the inner (endosteal) surface of bone may occur from direct pressure of the cartilage tumour or by active bone destruction. If the latter occurs, then care should be taken to exclude malignant change.

Enchondromas may rarely be multiple (enchondromatosis) and is referred to as Ollier’s disease. The risk of malignant transformation is higher with Ollier’s disease than with solitary enchondromas.


Presentation

Enchondromas are usually incidentally found when bones are investigated for other reasons. Sometimes, enchondromas may undergo pathologic fracture with those located in the fingers and toes most vulnerable.


Investigation

  • plain radiographs
  • nuclear bone scan
  • computed tomography
  • biopsy


Treatment

Enchondromas which are asymptomatic with no evidence of activity may be left untreated. Those which are symptomatic may be treated with curettage, then filled with bone graft or synthetic graft material or acrylic bone cement. If there is a suspicion that the enchondroma is undergoing malignant transformation, then the approach for management is as for malignant bone tumours.

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Giant cell tumour of bone

Giant cell tumour (GCT) of bone is an expansile, destructive lesion that arises in the epiphysis of bone. It commonly occurs in the age group 20-40 years and the knee (distal femur, proximal tibia) is the most frequent site affected.


Giant cell tumour of bone antero-posterior radiograph.jpg Giant cell tumour of bone lateral radiograph.jpg

Figure 4. Antero-posterior and lateral radiograph of wrist. Giant cell tumours are lytic lesions that are located eccentrically in the metaphysis abutting the subchondral bone. They are generally well defined, often expansile and may be associated with a soft tissue component.


Pathology

GCT is characterized by the proliferation of multinucleated giant cells which are scattered throughout the tumour together with a population of mononuclear stromal cells. Sometimes, there are elements of ABC within the GCT. Action by the giant cells results in lytic destruction of the bone. The long history of the tumour allows time for bone remodeling which explains the expansile nature of the tumour. Although GCT is not malignant, it may sometimes metastasise to lung. GCT of the radius is the site most commonly associated with lung metastases.


Presentation

Pain is a feature of GCT and is characteristic of aggressive bone tumours. Typically, patients will complain of constant deep seated bone pain which is unremitting and unresponsive to analgesia, and is worse at night. It is often associated with enlargement of the epiphysis of the bone giving the impression that there is joint swelling. True swelling is caused by extraosseus soft tissue extension of tumour. Acute pain usually represents pathologic fracture.


Investigations

  • plain radiograph
  • nuclear bone scan
  • computed tomography
  • magnetic resonance imaging
  • biopsy


Treatment

Currettage and filling of the cavity with bone graft or acrylic cement is the commonest treatment option for GCT. When a joint cannot be adequately preserved then resection of the affected part of the bone and prosthetic reconstruction is a recommended option.

GCT may recur locally in the area of the surgery or systemically as a pulmonary metastasis. Regular surveillance with imaging of the affected bone and lungs is required for 5 years.

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Malignant bone tumours

The diagnosis of a malignant bone tumour is based on tumour behaviour, cell type and microscopic features of malignancy.

Because bone has a mesodermal origin, tumours may arise from any component of the mesenchyme. Malignant tumours of bone may also have components which arise from neuroectodermal tissue.


Tumour behaviour

The rapid multiplication of tumour cells leads to:

  • extension of the tumour through the medullary canal of bone
  • recruitment of osteoclasts by tumour cytokines resulting in osteolysis around the tumour
  • migration of tumour cells through the cortex of bone results in stripping up of the periosteum of bone
  • multiplication of tumour cells outside of bone (extraosseous extension) results in the formation of a mass.


Multiplication of cells within the confines of the bone together with osteolysis gives rise to the characteristic bone pain. The rapid multiplication of cells outside of bone gives rise to the firm painful mass, which is restricted by the periosteum. Stripping up of the periosteum by the invading tumour cells causes a reaction by the immature bone cells within the periosteum to make bone. This is recognised by periosteal new bone formation on radiologic imaging of the bone.


Cell type

The type of bone malignancy depends on the identification of the most differentiated cell within the abnormal population. If the tumour cells are polygonal and make bone then they are referred to as osteosarcoma. If the tumour cells are large and produce a chondroid matrix, they are referred to as a chondrosarcoma. If the cells are spindle shaped, densely packed and associated with fibrous tissue formation, they are referred to as fibrosarcomas. A particular bone tumour that arises from neuroectodermal tissue is the Ewing’s tumour. This is sometimes referred to as a small round blue cell tumour because of the typical small round blue cells identified on histology.


The most common primary malignancies of bone include:

  • osteosarcoma
  • chondrosarcoma
  • Ewing’s sarcoma.


Histologic features of malignancy

Key histologic features that support a diagnosis of malignancy include:

  • bizarre cell shapes (polymorphic)
  • high cell counts
  • mitoses
  • spontaneous tumour necrosis
  • microvascular invasion.

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Osteosarcoma

Osteosarcoma is the commonest primary malignancy of bone in the adolescent and young adult. It is a bone-forming tumour where the production of a bone matrix is the “sine qua non” of osteosarcoma. It occurs most commonly around the knee (distal femur, proximal tibia). Other areas include the proximal humerus, distal radius and pelvis. It is a fatal disease that without appropriate systemic therapy results in widespread metastases. The lung is the commonest site for spread.


Osteosarcoma antero-posterio radiograph.jpg Osteosarcoma lateral radiograph.jpg

Figure 5(a). Antero-posterio and lateral radiographs of distal femur and knee. Osteosarcomas are ill defined bone lesions with a pattern of permeative bone destruction and irregular areas of sclerotic bone formation. They are often associated with an aggressive appearing periosteal reaction (Codman’s triangle, lamellated or sunburst (arrow)) and a soft tissue mass.


Osteosarcoma MRI scan in distal femur.jpg

Figure 5(b). MRI scan of the lesion in distal femur showing a large soft tissue mass.

Osteosarcoma MRI scan medullary lesion.jpg

Figure 5(c). MRI scans shows a medullary lesion with associated periosteal reaction and large soft tissue mass.


Pathology

Osteosarcoma usually occurs in the metaphysis of long bone. Commonly it is restricted by the growth plate, which forms a barrier to tumour invasion. Extension of the tumour through metapyseal bone gives the classic diffuse swelling associated with this tumour. Osteosarcoma may also arise from pre-existing abnormalities such as osteochondromas, bone infarcts, Paget’s disease, and fibrous dysplasia. This is a rare event and accounts for a second peak in middle-aged or elderly patients. There are a number of variants of osteosarcoma including chondrogenic osteosarcoma, fibrogenic osteosarcoma, conventional osteosarcoma, small round cell osteosarcoma, telangiectatic osteosarcoma, periosteal osteosarcoma, and 2 low grade variants referred to as parosteal osteosarcoma and low-grade central osteosarcoma.

Osteosarcoma may be graded into low, intermediate and high grade, with the metastasis free survival decreasing as the grade of tumour rises.


Presentation

Patients present with increasing limb pain, which is of an insidious onset but a progressive nature. The pain is often described as a deep ache. Eventually the pain becomes unremitting and unresponsive to oral analgesics. The pain is typically worse at night.

Limb swelling is often diffuse and periarticular giving the impression of joint swelling. Enlargement of the tumour may cause restricted muscle function which may present with a loss of range of motion of an adjacent joint. Significant osteolysis may also present with pathologic fracture of the affected bone.


Investigations

  • plain radiographs
  • computed tomography
  • magnetic resonance imaging
  • nuclear bone scan
  • functional imaging
  • biopsy


Treatment

Modern multimodal treatment includes neoadjuvant chemotherapy followed by surgery then post-operative chemotherapy. Osteosarcoma is sensitive to chemotherapy and the purpose of this is to control systemic spread of disease. Chemotherapy also has an impact on the local tumour causing tumour necrosis, ossification, sometimes reduction in size and the development of a fibrous rind around the tumour, which helps to protect against local extension of disease.

The mainstay of chemotherapy is doxorubicin (Adriamycin) but additional agents have also shown efficacy, including methotrexate, ifosphamide and cisplatin.

Surgery is performed with wide margins to minmise local recurrence of disease. Reconstruction of the bone defect after resection may include biologic or prosthetic reconstructions or combinations of the two. Amputation is reserved for limb tumours that cannot be resected without ablation of the limb, or if removal of the tumour does not lead to a functional limb afterwards.


Follow-up

The local recurrence rate after appropriate multimodal therapy is less than 10%. The 5-year survival rate is approximately 75%. Regular surveillance is required to ensure that recurrent disease is detected early. This includes periodic follow up (quarterly for the first 2 years, 6 monthly for the next 2 years and yearly for the next 4 years). Chest CT and limb imaging are also performed at regular intervals.

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Chondrosarcoma

Chondrosarcoma is one of the more common sarcomas in adults. These occur in both the appendicular and the axial skeleton including flat bones like the pelvis and scapula. This tumour is characterized by the production of a chondroid matrix.

Chondrosarcoma anterio posterior radiograph.jpg

Figure 6(a). Anterio posterior radiograph of left shoulder. Chondrosarcomas are similarly located in the metaphysis of long bones but unlike enchondromas, have more aggressive radiological features. These include cortical thickening or remodeling, cortical scalloping or osteolysis and soft tissue extension.

Chondrosarcoma sagittal magnetic resonance image.jpg

Figure 6(b). Sagittal magnetic resonance image of chondrosarcoma of the proximal humerus showing intramedullary and extraosseous extension.


Pathology

The type of matrix and cellular nature allow sub-classification of chondrosarcoma into various types including conventional central chondrosarcoma, clear cell chondrosarcoma, mesenchymal chondrosarcoma and dedifferentiated chondrosarcoma. Occasionally, chondrosarcoma may arise from benign conditions such as osteochondromas or enchondromas. Patients with multiple osteochondromas or enchondromas are more vulnerable to malignant change than patients with solitary tumours.

Chondrosarcoma may be graded into low intermediate and high grade tumours with the metastasis free survival decreasing with an increase in tumour grade.


Investigation

  • plain radiographs
  • computed tomography
  • magnetic resonance imaging
  • nuclear bone scan
  • functional imaging
  • biopsy


Treatment

Chondrosarcoma are rarely responsive to chemotherapy or radiotherapy. Surgery remains the mainstay of treatment. Surgery usually involves resection with wide margins followed by reconstruction, which may be biologic, prosthetic or a combination of the two.

Adequate surgical treatment usually results in good local control of disease (<10%) and low systemic recurrences.


Follow-up

The local recurrence rate after appropriate surgery is less than 10%. The 5-year survival rate is approximately 75%. Regular surveillance is required to ensure that recurrent disease is detected early. High grade tumours are rarely responsive to chemotherapy and in this group the rate of metastasis is very high. This includes periodic follow up (quarterly for the first 2 years, 6 monthly for the next 2 years and yearly for the next 4 years). Chest CT and limb imaging is also performed at regular intervals.

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Ewing’s Tumour

Ewing’s tumour is one of the family of peripheral neuroectodermal tumours. It metastasises early and is fatal without treatment. It is sometimes referred to as a small round blue cell tumour because of its characteristic histologic appearance. Ewing’s sarcoma like osteosarcoma is a disease of adolescents and young adults. Ewing’s affects both flat and tubular bones with a preponderance for the midshaft of tubular bones.

Ewings sarcoma anterio posterior radiograph.jpg Ewings sarcoma lateral radiograph.jpg

Figure 7(a). Antero-posterior and lateral radiograph of Ewings sarcomas are often located in the diaphysis of long bones and generally have a permeative pattern of bone destruction with an associated lamellated periosteal reaction (onion-peel (arrow)) and a soft tissue mass.


Ewings sarcoma coronal MRI.jpg Ewings sarcoma axial MRI.jpg

Figure 7(b). Coronal and axial magnetic resonance images demonstrate the presence of an extensive periosteal reaction and soft tissue mass.


Pathology

A highly cellular tumour characterizes Ewing’s tumour where the tumour is packed with a large population of small round blue cell tumours. The rate of proliferation is very high and usually gives rise to a very large soft tissue extension of the tumour from bone. The tumour tends to permeate along the intramedullary canal of bone and through the cortex.

The differential diagnosis of Ewing’s tumour includes other tumours that have high populations of small round blue cell tumours including, lymphoma, neuroblastoma, small round cell osteosarcoma, rhabdomyosarcoma as well as osteomyelitis.

This is one tumour where diagnostic accuracy is critical to planning effective treatment. Immunohistology is used to detect MIC-2 staining. Chromosomal analyses are used to detect translocations of chromosome 11 and 22. Molecular pathology is used to identify the fusion gene product (EWS-FLi) that results from chromosomal translocation involving chromosome 11 and 22.


Investigation

  • plain radiographs
  • computed tomography
  • magnetic resonance imaging
  • nuclear bone scan
  • functional imaging
  • biopsy


Treatment

The key to effective Ewing’s treatment is neoadjuvant chemotherapy. Ewing’s tumour is highly sensitive to chemotherapy, which often results in marked reduction in the soft tissue component of the tumour. The responsiveness of the tumour to chemotherapy correlates with post-operative survival. Better survival is associated with post-chemotherapy necrosis of >95%. Ewing’s tumour is also radiosensitive and this modality may be employed with very large tumours; tumours that have not responded optimally to chemotherapy; tumours that may not be amenable to resection; or following resection where margins have been narrow. Surgery usually involves resection with wide margins followed by reconstruction, which may be biologic, prosthetic or a combination of the two.


Follow-up

Local tumour recurrence after appropriate surgical margins is <10%. Five-year survival following appropriate treatment is between 50-60%. Because of the high risk of recurrent systemic disease, regular rigorous surveillance is required. This includes periodic follow up (quarterly for the first 2 years, 6 monthly for the next 2 years and yearly for the next 4 years). Chest CT and limb imaging is also performed at regular intervals.

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Metastatic bone tumours

The commonest malignant tumours of bone are metastases from carcinoma. The commonest tumours that metastasise to bone are the paired midline organs including:

  • lung
  • breast
  • prostate
  • kidney
  • thyroid

Other carcinomas may also metastasise to bone but do so infrequently.

The rate of bone metastastasis is 60% but only 10% require surgical treatment. The commonest sites for bone metastasis include the femur, proximal humerus, vertebral column and pelvis. Metastasis below the knee and elbow is uncommon.


Pathology

Bone metastases may be lytic, sclerotic, or a combination of the two. While both lysis and sclerosis may weaken bone, the former is more likely to lead to pathologic fracture.

The complications of bone metastases include:

  • pain
  • pathologic fracture
  • immobility
  • hypercalcaemia
  • marrow suppression.


Presentation

Patients with bone metastases either present with bone pain of an insidious onset, or following pathologic fracture. This may be the first presentation of malignant disease or the patient may already have a history of carcinoma.


Investigations

  • plain radiographs
  • nuclear bone scan
  • computed tomography
  • biopsy


Treatment

Treatment of bone metastases depends on the presence of fracture or impending fracture. Depending on the bones involved, radiotherapy alone may be utilized (e.g. in the spine, pelvis or skull). Surgery is used to strengthen affected bone in order to protect a patient’s mobility (lower limb) and independence (upper limb). A stable and durable construct is critical for ensuring adequate application. Different surgical techniques may be employed including internal fixation with intramedullary rods or plates, and occasionally, joint replacement may also be required. Amputation may sometime be employed if metastases have either destroyed bone, making it irreparable, or there is fungation.

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