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Osteosarcoma (1)

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Highly malignant tumor of mesenchymal origin.Spindle shaped cells that produce osteoid.2nd most common primary malignant bone tumor after MM.Incidence – 1 to 3 per million per year
Treated by chemo,amputation or rotationplasty

Published in: Health & Medicine
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Osteosarcoma (1)

  1. 1. Osteo = bone/osteoid tissue Sarcoma = malignant tumour of connective tissue 02/04/12 Dr. Pruthviraj Nistane Deptt. Of Orthopaedics Govt. Medical College and Rajindra Hospital, Patiala
  2. 2. Overview <ul><li>Definition </li></ul><ul><li>Epidemiology </li></ul><ul><li>Pathogenesis </li></ul><ul><li>Skeletal distribution </li></ul><ul><li>Clinical presentation </li></ul><ul><li>Evaluation </li></ul><ul><li>Classification </li></ul><ul><li>Investigations </li></ul><ul><li>Treatment </li></ul><ul><li>Prognosis </li></ul>
  3. 3. What is osteosarcoma ? <ul><li>Highly malignant tumor of mesenchymal origin. </li></ul><ul><li>Spindle shaped cells that produce osteoid. </li></ul><ul><li>2 nd most common primary malignant bone tumor after MM. </li></ul>
  4. 4. Epidemiology <ul><li>Incidence – 1 to 3 per million per year </li></ul><ul><li>Any age </li></ul><ul><li>But 75% in 12-25yrs of age </li></ul><ul><li>Almost equal in both sexes, slightly more in males . </li></ul>
  5. 5. Epidemiology <ul><li>Associated syndromes </li></ul><ul><li>Hereditary form of retinoblastoma </li></ul><ul><li>Li-Fraumeni syndrome (p53) </li></ul><ul><li>Rothmund-Thomson syndrome (8q24) </li></ul>
  6. 6. Pathogenesis <ul><li>Unknown </li></ul><ul><li>Modal incidence correlates with rapid bone growth </li></ul><ul><li>Radiation >2000 rads </li></ul><ul><li>Chemicals – chlorantherene, AAF, Be compounds </li></ul>
  7. 7. Gross pathology <ul><li>Arise from multipotent mesenchymal cells </li></ul><ul><li>Mixture of osteoid, fibrous, cartilaginous, necrotic, </li></ul><ul><li>hemorrhagic, cystic areas </li></ul><ul><li>Destruction of cortex </li></ul>
  8. 8. Gross pathology <ul><li>Metaphyseal, Central. </li></ul><ul><li>Extension into medullary cavity and subperiosteal extension. </li></ul><ul><li>Restricted bu periosteun and epiphyseal plate, but eventually crosses it </li></ul><ul><li>Reactive periosteal </li></ul><ul><li>new bone formation </li></ul><ul><li>Metastasis – lungs </li></ul>
  9. 9. Microscopic appearance <ul><li>Stroma - Malignant connective tissue with anaplastic spindle cells </li></ul><ul><li>Matrix of osteoid/fibrous/cartilagenous tissue </li></ul>
  10. 10. Classification <ul><li>PRIMARY or SECONDARY </li></ul><ul><li>PRIMARY OSTEOSARCOMAS are </li></ul><ul><li>Conventional /classic osteosarcoma (high grade, intra medullar y) </li></ul><ul><li>Low-grade intramedullary osteosarcoma </li></ul><ul><li>Parosteal osteosarcoma </li></ul><ul><li>Periosteal osteosarcoma </li></ul><ul><li>High-grade surface osteosarcoma </li></ul><ul><li>Telangiectatic osteosarcoma, and </li></ul><ul><li>Small cell osteosarcoma. </li></ul>
  11. 11. Classification <ul><li>SECONDARY OSTEOSARCOMAS </li></ul><ul><li>Osteosarcomas occurring at the site of another disease process. </li></ul><ul><li>more common in >50 years of age </li></ul><ul><li>The most common causes are </li></ul><ul><li>Paget disease </li></ul><ul><li>Previous radiation treatment </li></ul><ul><li>Other associated conditions are </li></ul><ul><li>Fibrous dysplasia </li></ul><ul><li>Bone infarcts </li></ul><ul><li>Osteochondromas </li></ul><ul><li>Chronic osteomyelitis </li></ul><ul><li>Dedifferentiated chondrosarcomas </li></ul><ul><li>Osteogenesis imperfecta </li></ul>
  12. 12. Classic High Grade Osteosarcoma <ul><li>These aggressive, high-grade tumors begin in an intramedullary location, but may break through the cortex and form a soft-tissue mass. </li></ul><ul><li>The histologic hallmark - malignant osteoblastic spindle cells producing osteoid,presence of woven bone with malignant appearing stromal cells </li></ul><ul><li>subtypes - </li></ul><ul><li>osteoblastic, </li></ul><ul><li>chondroblastic and </li></ul><ul><li>fibroblastic </li></ul>
  13. 13. Skeletal distribution <ul><li>Distal femur </li></ul><ul><li>Proximal tibia </li></ul><ul><li>Proximal humerus </li></ul><ul><li>(sites of rapid bone growth) </li></ul><ul><li>others </li></ul><ul><li>Metaphyseal(89%)>diaphyseal(10%)>epiphyseal(1%) </li></ul>
  14. 14. Clinical Presentation <ul><li>Pain – progresssive pain </li></ul><ul><li>due to microinfarction </li></ul><ul><li>night pain in 25 % </li></ul><ul><li>Swelling - Palpable mass is noted in up to 1/3 </li></ul><ul><li>of patients at the first visit </li></ul><ul><li>Fever, malaise or other constitutional symptoms </li></ul><ul><li>are not typical of osteosarcoma </li></ul>
  15. 15. Evaluation <ul><li>Suspected diagnosis by history and physical examination </li></ul><ul><li>Supported by investigations </li></ul>
  16. 16. Plain X-ray (Most valuable) <ul><li>sclerotic </li></ul><ul><li>Lytic </li></ul>Mixed (most common)
  17. 17. Plain X-ray <ul><li>Lesions are usually permeative </li></ul><ul><li>Associated with destruction of the cancellous and cortical elements of the bone </li></ul><ul><li>Ossification within the soft tissue component, if tumour has broken through cortex </li></ul><ul><li>Intra medullary </li></ul><ul><li>Borders are ill defined </li></ul>
  18. 18. Plain X-ray <ul><li>Periosteal reaction may appear as the characteristic Codman triangle. </li></ul><ul><li>Extension of the tumor through the periosteum may result in a so-called “sunburst” or “hair on end” appearance. </li></ul>
  19. 19. Other investigations <ul><li>MRI </li></ul><ul><li>CT </li></ul><ul><li>Angiogram </li></ul><ul><li>Bone scan </li></ul><ul><li>Laboratory studies </li></ul><ul><li>Biopsy </li></ul>
  20. 20. MRI <ul><li>best to detect extent into bone and soft tissues </li></ul>
  21. 21. CT <ul><li>Not of much use </li></ul><ul><li>CT chest to detect lung metastasis </li></ul>
  22. 22. Angiogram <ul><li>Determine vascularity of the tumour </li></ul><ul><li>Detect vascular displacement </li></ul><ul><li>Relationship of vessels to the tumour </li></ul>
  23. 23. Bone scan <ul><li>A bone scan should be obtained </li></ul><ul><li>to look for skeletal metastases </li></ul><ul><li>or multi focal disease </li></ul><ul><li>Thallium scan - Monitor effects of chemotherapy </li></ul><ul><li> Detect local recurrence of tumor </li></ul>
  24. 24. laboratory studies <ul><li>Full blood count, ESR, CRP. </li></ul><ul><li>LDH (elevated level is associated with poor prognosis) </li></ul><ul><li>ALP (highly osteogenic) </li></ul><ul><li>Platelet count </li></ul><ul><li>Electrolyte levels </li></ul><ul><li>Liver function tests </li></ul><ul><li>Renal function tests </li></ul><ul><li>Urinalysis </li></ul>
  25. 25. Biopsy <ul><li>to conform the diagnosis. </li></ul><ul><li>Types </li></ul><ul><li>Fine needle aspiration </li></ul><ul><li>Core needle biopsy </li></ul><ul><li>Open incisional biopsy </li></ul>
  26. 26. Enneking staging system <ul><li>The staging system is typically depicted as follows </li></ul><ul><li>Stage I: Low grade tumors </li></ul><ul><li>I-A intra compartmental </li></ul><ul><li>I-B extra compartmental </li></ul><ul><li>Stage II: High grade tumors </li></ul><ul><li>II-A intra compartmental </li></ul><ul><li>II-B extra compartmental </li></ul><ul><li>Stage III: Any tumors with evidence of metastasis </li></ul>
  27. 27. Differential Dx <ul><li>Giant Cell Tumor </li></ul><ul><li>Chondrosarcoma </li></ul><ul><li>Fibrosarcoma </li></ul><ul><li>Aneursymal Bone Cyst </li></ul><ul><li>Ewings sarcoma </li></ul><ul><li>Osteoblastoma </li></ul><ul><li>Metastasis </li></ul><ul><li>Lymphoma </li></ul><ul><li>Osteomyelitis </li></ul><ul><li>Chondroblastoma </li></ul><ul><li>Post traumatic callus </li></ul><ul><li>Other variants </li></ul>
  28. 28. Surface osteosarcoma <ul><li>Parosteal </li></ul><ul><li>Periosteal </li></ul><ul><li>High grade surface osteosarcoma </li></ul>
  29. 29. Parosteal <ul><li>5% of osteosarcomas </li></ul><ul><li>Posterior metaphysis of </li></ul><ul><li>distal femur </li></ul><ul><li>Arises from surface,invade </li></ul><ul><li>medullary cavity in late stages </li></ul><ul><li>Tends to encircle bone </li></ul><ul><li>Low grade,Slow growing </li></ul><ul><li>Large ossified mass in centre </li></ul>
  30. 30. Periosteal <ul><li>Arises from surface of diaphysis </li></ul><ul><li>Most commonly femur and tibia </li></ul><ul><li>Characterized by bony spicule formation </li></ul><ul><li>perpendicular to shaft </li></ul><ul><li>Strands of osteoid producing spindle cells </li></ul><ul><li>radiating between lobules of cartilage </li></ul><ul><li>Sunburst </li></ul><ul><li>Low grade </li></ul>
  31. 31. High grade surface <ul><li>Very rare </li></ul><ul><li>Age group 20-30’s </li></ul><ul><li>Appearance as parosteal but histology high grade and medullary involvement more common. </li></ul>
  32. 32. Telangiectatic Osteosarcoma <ul><li>Aggressive </li></ul><ul><li>Presents with pathological fracture </li></ul><ul><li>5% of all osteosarcomas </li></ul><ul><li>arises within the diaphysis </li></ul><ul><li>Radiology </li></ul><ul><li>Often entirely osteolytic  </li></ul><ul><li>Bone and cortex destruction </li></ul><ul><li>Periosteal reaction </li></ul><ul><li>Codman's triangles </li></ul><ul><li>Pathology </li></ul><ul><li>Gross appearance is a multi-cystic similar to an aneurysmal bone cyst. </li></ul><ul><li>Microscopically it has large blood filled spaces and thin septation. Within the septa there is scanty osteoid production by the pleomorphic malignant cells </li></ul>
  33. 33. Prognostic Factors <ul><li>Extent of the disease </li></ul><ul><ul><li>Pts with pulmonary, non pulmonry (bone) or skip metastasis have poor prognosis </li></ul></ul><ul><li>Grade of the tumor </li></ul><ul><ul><li>High grade tumor have poor prognosis </li></ul></ul><ul><li>Size of the primary lesion </li></ul><ul><ul><li>Large size tumors have worse prognosis then small size tumors </li></ul></ul><ul><li>Skeletal location </li></ul><ul><ul><li>proximal tumors do worse than distal tumors. </li></ul></ul><ul><li>Secondary osteosarcoma: Poor prognosis </li></ul>
  34. 34. Treatment <ul><li>Current standard of care </li></ul><ul><li> Radiological staging </li></ul><ul><li>Biopsy to confirm diagnosis </li></ul><ul><li>Preoperative chemotherapy </li></ul><ul><li>Repeat radiological staging (access chemo response, finalize surgical treatment plan) </li></ul><ul><li> Surgical resection with wide margin </li></ul><ul><li>Reconstruction using one of many </li></ul><ul><li> techniques </li></ul><ul><li>Post op chemo based on preop response </li></ul>
  35. 35. Chemotherapy <ul><li>Chemotherapy given preoperatively - Neoadjuvant </li></ul><ul><li>Given postoperatively - Adjuvant </li></ul><ul><li>Advantages of neoadjuvant chemotherapy - </li></ul><ul><li>regression of the primary tumor, making a successful limb salvage operation easier. </li></ul><ul><li>may decrease the spread of tumor cells at the time of surgery </li></ul><ul><li>Effectively treating micrometastases at the earliest time possible. </li></ul><ul><li>It avoid tumor progression, which may occur during any delay before surgery. </li></ul><ul><li>Given for about 3-4 weeks before definitive procedure </li></ul>
  36. 36. Chemotherapy <ul><li>The drugs used most often to treat osteosarcoma are: </li></ul><ul><li>Methotrexate with leucovorin (folinic acid) </li></ul><ul><li>Doxorubicin (Adriamycin) </li></ul><ul><li>Cisplatin or carboplatin </li></ul><ul><li>Etoposide </li></ul><ul><li>Ifosfamide </li></ul><ul><li>Cyclophosphamide </li></ul><ul><li>Actinomycin D (dactinomycin) </li></ul><ul><li>Bleomycin </li></ul>
  37. 37. Surgery <ul><li>The main goal of surgery is to safely and completely remove the tumor. </li></ul><ul><li>Historically – amputation. </li></ul><ul><li>Over the past few years - limb-sparing procedures have become the standard, mainly due to advances in chemotherapy and sophisticated imaging techniques </li></ul><ul><li>Limb salvage procedures now can provide rates of local control and long-term survival equal to amputation. </li></ul>
  38. 38. Surgery choice <ul><li>Surgical procedures fall into three basic categories: </li></ul><ul><li>Amputation </li></ul><ul><li>Limb salvage </li></ul><ul><li>Rotationplasty </li></ul>
  39. 39. Decision ??? <ul><li>If the tumor can be removed safely while retaining a viable extremity, a limb sparing procedure may be appropriate. </li></ul><ul><li>If major nerves or blood vessels are involved, or if complete tumor removal results in significant loss of function, amputation may be a better choice. </li></ul><ul><li>Patient’s age, desired level of function, cosmetic preference and long-term prognosis must also be considered. </li></ul>
  40. 40. Amputation <ul><li>Amputation involves removal of the limb with a safe margin between the end of </li></ul><ul><li>the retained portion and the </li></ul><ul><li>tumor </li></ul><ul><li>It should not be viewed as a </li></ul><ul><li>failure of treatment, but rather </li></ul><ul><li>as the first step towards patient’s return to a more comfortable and productive life. </li></ul>
  41. 41. Amputation <ul><li>Indication </li></ul><ul><ul><li>1. Grossly displaced pathologic fracture </li></ul></ul><ul><ul><li>2. Encasement of neurovascular bundle </li></ul></ul><ul><ul><li>3. Tumor that enlarges during preop chemo and is adjacent to neurovascular bundle </li></ul></ul><ul><ul><li>4. Palliative measure in metastatic disease </li></ul></ul><ul><ul><li>5. If the tumor has caused massive necrosis, fungation, infection, or vascular compromise. </li></ul></ul>
  42. 42. Limb salvage surgery <ul><li>Removing the tumor with a normal cuff of tissue surrounding it while preserving vascular and nerve supply to the extremity. </li></ul>
  43. 43. <ul><li>The skeletal defect must be reconstructed by </li></ul><ul><li>Endoprosthesis (most common) – </li></ul><ul><li>replacing the removed bone with </li></ul><ul><li>a metal implant </li></ul><ul><li>Allograft (cadaveric) bone </li></ul><ul><li>Vascularized bone acquired from the patient </li></ul><ul><li>Allograft-prosthetic composite constructions </li></ul>
  44. 44. Rotationplasty <ul><li>compromise between amputation and limb salvage </li></ul><ul><li>most commonly used for osteosarcomas of the distal femur in skeletally immature patients </li></ul><ul><li>It is a procedure where the neurovascular structures and distal aspect of the limb (leg) are retained, and re-attached to the proximal portion after the tumor has been removed. </li></ul>
  45. 45. <ul><li>For functional purposes, the distal segment is turned 180 degrees so that the ankle joint functions as a knee joint, thus converting an above-knee to a below-knee amputation in order for prosthetic use to be maximized </li></ul>
  46. 46. Radiotherapy <ul><li>Radiation therapy has no major role in osteosarcoma </li></ul><ul><li>Radiation therapy may be useful in some cases where the tumor cannot be completely removed by surgery. E.g. in pelvic bones or in the bones of the face. </li></ul><ul><li>Megavoltage (upto 6000-8000 rads) </li></ul>
  47. 47. Follow up and Prognosis <ul><li>Signs of recurrence, metastasis and treatment related complications </li></ul><ul><li>Physical examination,radiographs of the primary site, serial chest imaging,bone scans and laboratory examinations </li></ul><ul><li>50 % cases with high grade osteosarcoma have some type of relapse in 5 months </li></ul><ul><li>If recurrence is detected, additional surgery (radical amputation)and chemotherapy may be warranted. </li></ul><ul><li>5 year survival rate is 5% - 23% </li></ul>
  48. 48. <ul><li>THANK YOU ! </li></ul>

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