Malignant Primary Bone Tumours
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- Kimberly Hill
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1 Volume 05 / Issue 04 / December 2017 boa.ac.uk Page 62 JTO Subspecialty Section Malignant Primary one Tumours Paul Cool Malignant primary tumours of bone are a diverse group of tumours. Overall, the incidence is around 15 per million people a year. The most common malignant primary bone tumours are osteosarcomas (incidence 3 per million per year), chondrosarcoma and Ewing s sarcoma 1. a b The diagnosis and surgical treatment of malignant primary bone tumours is highly specialised and requires a comprehensive multidisciplinary team. Consequently, the diagnosis and treatment of these tumours is delivered by specialist units. In England, these units are in irmingham, Newcastle, Oswestry, Oxford and Stanmore. Furthermore, there is a national multidisciplinary team meeting where all cases of Ewing s sarcoma are discussed. Diagnosis Osteosarcoma (Figure 1 and 2) is most common in fast growing bones (around the knee and in the proximal humerus), whilst Ewing s sarcoma (Figure 3) usually affects the diaphysis of long bones, pelvis or scapula. oth osteosarcoma and Ewing s sarcoma are frequent in young adolescents. Chondrosarcoma (Figure 4) is uncommon in young people and usually presents with a prolonged history of low grade pain. Examination is usually nonspecific but may reveal swelling, local tenderness, joint swelling and dysfunction. Unfortunately, it is not uncommon for patients Figure 1: Sclerotic osteosarcoma of the proximal tibia (a) that has been treated with neo-adjuvant chemotherapy, excision and reconstruction with a massive endoprosthetic replacement (b). to present with a pathological fracture (Figure 4). pathological fracture potentially contaminates the surrounding tissues with tumour cells. Theoretically, this Paul Cool Patients with malignant primary bone tumours often present with a prolonged history as these tumours are rare and the diagnosis is not expected. Night pain, especially in the young adolescent, and nonmechanical pain are symptoms suggestive of a malignant bone tumour. Common risk factors are presented in Table 1 1. High Risk Moderate Risk Low Risk Ollier's disease Diaphyseal aclasia (multiple osteochondromas) Fibrous dysplasia Maffucci s syndrome Paget's disease Osteonecrosis Familial retinoblastoma Radiation osteitis Chronic osteomyelitis Table 1: Risk factors for malignant primary bone tumours.
2 Volume 05 / Issue 04 / December 2017 Page 63 boa.ac.uk a b c Figure 2: Teleangiectatic osteosarcoma of the distal femur. Figure 3: Ewing s sarcoma of the femoral diaphysis (a) and subsequent excision and reconstruction with a distal femoral endoprosthesis (b). Ewing s sarcomas often have a significant soft tissue component (c). Figure 4: Chondrosarcoma of the proximal humerus with pathological fracture. The tumour showed de-differentiation, worsening the prognosis. could jeopardise future limb salvage. However, there are reports that, provided adequate excision margins can be obtained, there is no significant difference in survival 2. lood tests are non-specific and usually of little help in the diagnosis of malignant primary tumours of bone. bout half of the patients with osteosarcoma have an elevated alkaline phosphatase; who have a worse prognosis. Similarly, an elevated LDH, ESR and CRP in Ewing s sarcoma adversely affects the prognosis. The location of the tumour within the bone can help diagnostically. Most tumours (including osteosarcoma and chondrosarcoma) are in the metaphysis. Ewing s sarcoma is usually diaphyseal. Epiphyseal tumours are unlikely to be malignant (Table 2). The age of the patient can also help diagnostically (Table 3) Osteosarcomas are malignant tumours that produce bone (Figure 1). However, in teleangiectatic osteosarcoma this is not apparent on the radiographs and a biopsy is required to appreciate osteoid formation 1. Classical radiographic features of osteosarcoma include sunray spiculae and Codman s triangle. The Codman s triangle is reactive bone formation following elevation of the periosteum from the bone by the tumour. The periosteum is well fixed to the physis; explaining the triangular shape. Similarly, in Ewing s sarcoma the diaphyseal periosteum is lifted in a fusiform manner with intermittent deposition of reactive bone (onion skinning). Chondrosarcoma has usually a longer clinical course. The cartilage matrix often shows speckled calcification (Figure 4). Dedifferentiated chondrosarcoma is a highly malignant tumour where chondrosarcoma is juxtaposed to a high-grade noncartilaginous sarcoma. Plain radiographs are the best diagnostic aid in the evaluation of bone tumours. lthough further scans can narrow the differential diagnosis, it is unlikely that they will have a major impact diagnostically. dditional scans are mainly performed for staging purposes, to determine the extent of disease. If following radiographs a malignant primary bone tumour is suspected, it is recommended to refer the patient directly to the local bone tumour treatment centre for further evaluation, staging, biopsy and treatment. Staging Patients who present with a suspected malignant primary tumour of bone require further evaluation (local and distant staging). Local staging includes plain radiographs and an MRI scan of the whole affected bone. MRI scans are particularly useful to identify the extent of disease in the soft tissues and bone marrow. one formation is better appreciated on a CT scan. In the first instance, bone sarcomas spread to the lungs, followed by dissemination to other bones. Consequently, distant staging should include >> Epiphyseal Tumours Diaphyseal Tumours ge Diaphyseal Tumours Giant cell tumour (physes closed) Chondroblastoma Intra-articular osteoid osteoma (atypical) Clear cell chondrosarcoma Eosinophilic granuloma Osteoid osteoma Fibrous dysplasia damantinoma (tibia) Ewing's sarcoma < 10 Eosinophilic granuloma Teenage Ewing s sarcoma dult Lymphoma > 60 Metastases / Myeloma Table 2: The location of the tumour in the bone can help diagnostically. Table 3: Common age for diaphyseal tumours.
3 Volume 05 / Issue 04 / December 2017 boa.ac.uk Page 64 JTO Subspecialty Section a whole-body isotope bone scan and a CT scan of the chest. Whole-body MRI scan has also been used for further evaluation in some tumours and there are reports which suggest that MRI scanning has a higher sensitivity and specificity than bone scans in identifying metastatic disease 3. However, isotope bone scanning remains the gold standard for staging of malignant primary bone tumours. The role of PET CT remains undetermined. iopsy Once all staging investigations have been performed, a biopsy is usually required. It is unlikely you will regret taken a biopsy; but you could regret not taking one! 4,5 bone biopsy should be performed under image guidance (fluoroscopy or CT) in the bone tumour treatment centre. The biopsy site should be carefully planned around an extensile approach which avoids breaching compartments and consequently jeopardising possible limb salvage. ll biopsy results should be discussed at the multidisciplinary team meeting for radiological and pathological correlation. 1 Low grade without metastases 2 High grade without metastases 3 Metastases Table 4: Enneking staging of bone tumours is a combination of stage (extent of disease) and grade (aggressiveness of the tumour). Treatment can then be planned by the oncologists and orthopaedic surgeons. Two staging systems are commonly used to guide treatment and provide prognostic information: the TNM system and Enneking staging (Table 4). Enneking staging is a combination of stage (extent of the disease) and grade (aggressiveness) of the tumour. The compartment is the affected bone and a tumour is extra compartmental if the cortex of the bone is breached on the plain radiographs 6,7. The World Health Organisation 1 recommends TNM (tumour, nodes and metastases) staging and this has been shown to be of better prognostic value (Table 5). Genetics pproximately 85% 1 of Ewing s sarcoma have a chromosomal translocation t(11;22)(q24;q12) that fuses T Primary Tumour Tx T0 T1 T2 T3 N- Regional Lymph Nodes Nx N0 N1 M Distant Metastases M0 M1 a M1 b Table 5: TNM staging of primary bone tumours. EWSR1 to FLI1 to create the EWSR1-FLI1 oncoprotein. lternate translocations have been described for the remaining 15%. The diagnosis of Ewing s sarcoma should be supported by molecular pathology to demonstrate one of the described translocations. This can be done by FISH (fluorescence in situ hybridization) or RT- PCR (reverse transcriptasepolymerase chain reaction). The molecular pathology of osteosarcoma is less well defined and subject to further research. mplification of the MDM2 (mouse double minute 2 homolog) gene is common in low grade osteosarcoma. IDH1 and 2 (isocitrate dehydrogenase) mutations are found in most chondrosarcomas, but other mutations have also been described and this is the subject of further research. The 100,000 genomes project will hopefully give further insight in the molecular pathology of these tumours. Can t be assessed No evidence of primary tumour Less than 8 cm greatest diameter More than 8 cm greatest diameter Discontinuous tumours in the primary bone Can t be assessed No regional lymph nodes Regional lymph node metastases No metastases Lung metastases Metastases at other sites Treatment Ewing s sarcoma and osteosarcoma are treated with surgery and chemotherapy. Chemotherapy is usually delivered in a neo-adjuvant setting (before and after surgery), according to defined protocols and clinical trials. Radiotherapy is another modality that can be used to treat patients with Ewing s sarcoma. Chondrosarcomas do not respond to radiotherapy or chemotherapy and treatment is surgical. It is important to excise the biopsy track during the surgical procedure as these tumours are prone to local recurrence. This further illustrates the importance of appropriate planning of the biopsy by the sarcoma unit. Local recurrence is associated with the quality of the surgical margin that has been obtained. The classification of surgical margins is summarised in Table 6. The different surgical options for bone sarcomas are summarised below: mputation Limb Salvage Excision alone (expendable bone) Excision and one Graft utograft Irradiated utograft llograft Excision Endoprosthetic Replacement Excision and rthrodesis Rotationplasty Excision and one Transport Intra-lesional Marginal Wide Radical Within the lesion Within the reactive zone, extra-capsular eyond the reactive zone in normal tissue Table 6: Surgical excision margins.
4 Volume 05 / Issue 04 / December 2017 Page 65 boa.ac.uk Endoprostheses are commonly used and have the advantage of immediate weight bearing and reliable function. The main complication is infection. lthough surface treatment of the prosthesis with silver can make it easier to deal with infection, it remains a difficult clinical problem. Hydroxyapatite coated collars in combination with cemented stems have significantly reduced the incidence of aseptic loosening and improved longevity of endoprostheses 8. iological reconstructions are more difficult and require time for the biological reconstruct to integrate with the host bone. During this period, there may be limitations on weight bearing. The main complications of biological reconstructions include non-union, infection and fracture. Prognosis efore neoadjuvant chemotherapy was available, 80% of patients with osteosarcoma treated with surgery alone died of disease. There has been a significant improvement in outcome with chemotherapy and 70% of patients who present with nonmetastatic osteosarcoma are long-term survivors. Patients who have metastatic disease at diagnosis, have a much poorer survival rate (< 20%). pproximately two-thirds of patients with non-metastatic Ewing s sarcoma are cured following successful surgical and oncological treatment. However, large pelvic tumours can be very challenging to treat. The prognosis for metastatic Ewing s sarcoma remains poor. The prognosis of chondrosarcoma depends very much on the grade and site of the disease. Dedifferentiated chondrosarcoma has a very poor prognosis and most patients die within a year. Paul Cool is a Consultant Orthopaedic and Oncological Surgeon at The Robert Jones and gnes Hunt Orthopaedic Hospital NHS Foundation Trust in Oswestry. He is the current President of the ritish Orthopaedic Oncology Society and honorary Senior Lecturer at the University of Manchester. References References can be found online at or by scanning the QR Code. Prevee-Prep for use with disposable & re-useable tourniquet cuffs Prevee-prep collar formed on the limb. This collar helps prevent the migration of prep solutions under the tourniquet cuff Prevee Prep is a tourniquet cover that: Helps to prevent the migration of prep solutions Protects tourniquet cuffs from contamination from the surgical site Comes in a full range of sizes from paediatric to XXL Designed with reference to NHS safety notice SN(SC)99/33 Medical Devices - Surgical Cuffs - Risk of urns Comes in boxes of 100 One use only Latex free Comes flat packed Fitting guide measure tapes available Fitting guide measure tapes available Power-Pod Try Oak Medical Services new range of power Power-Pod units! Oak HQ, Unit 5 lbert Street rigg, North Lincolnshire DN20 8HQ T: F: gang sockets version available Lockable castors Service and testing E: info@oakmedicalservices.co.uk W:
5 References 1. World Health Organization, International gency for Research on Cancer. WHO classification of tumours of soft tissue and bone. 4th ed. Lyon: IRC Press; p. (World Health Organization classification of tumours). 2. budu, Sferopoulos NK, Tillman RM, Carter SR, Grimer RJ. The surgical treatment and outcome of pathological fractures in localised osteosarcoma. J one Joint Surg r Sep;78(5): Stevenson JD, Watson JJ, Cool P, Cribb GL, Jenkins JPR, Leahy M, et al. Whole-body magnetic resonance imaging in myxoid liposarcoma: useful adjunct for the detection of extra-pulmonary metastatic disease. Eur J Surg Oncol EJSO [Internet] Jan [cited 2016 Mar 1]; vailable from: 4. Mankin HJ, Mankin CJ, Simon M. The hazards of the biopsy, revisited. Members of the Musculoskeletal Tumor Society. J one Joint Surg m May;78(5): Mankin HJ, Lange T, Spanier SS. THE CLSSIC: The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. The Journal of one and Joint Surgery, 1982;64: Clin Orthop Sep;450: Enneking WF, Spanier SS, Goodman M. system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Dec;(153): Enneking WF, Spanier SS, Goodman M. system for the surgical staging of musculoskeletal sarcoma Clin Orthop Oct;(415): Unwin PS, Cannon SR, Grimer RJ, Kemp H, Sneath RS, Walker PS. septic loosening in cemented custom-made prosthetic replacements for bone tumours of the lower limb. J one Joint Surg r Jan;78(1):5 13.
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