Osteosarcoma: A Detailed Review

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It is a presentation covering all the important aspects of the 2nd most common tumor, osteosarcoma in extensive details.

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Osteosarcoma: A Detailed Review

  1. 1. OSTEOSARCOMA
  2. 2. INTRODUCTION • 20% OF ALL PRIMARY BONE TUMOR • SECOND-MOST COMMON PRIMARY MALIGNANCY OF BONE • INCIDENCE: 1 TO 3 PER MILLION PER YEAR • MALE: FEMALE—1.6:1(EXCEPT PAROSTEAL VARIETY) • AGE: CONVENTIONAL—2ND DECADE
  3. 3. SITE AROUD THE KNEE JT.(ARISING MAINLY FROM METAPHYSIS;INTRAMEDULLARY REGION) 52% --LOWER END OF FEMUR 20%-- UPPER END OF TIBIA 9% -- UPPER END OF HUMERUS
  4. 4. PREDISPOSING FACTORS : • RADIATION • VIRAL INFECTION: PLYOMA VIRUS/HARVEY VIRUS • CHEMICALS:BERYLLIUM 20-METHYL CHOLANTHRENE
  5. 5. CLINICAL FEATURES • PRESENTING FEATURES: - PAIN(NIGHT PAIN) -SOMETIMES ONLY TIREDNESS & LIMP -PALPABLE MASS -SKIN CONDITIONS TO BE EXAMINED CAREFULLY • H/O TRAUMA SOMETIMES DRAWS ATTENTION
  6. 6. ASSOCIATED FEATURES • EFFUSION & SWELLING OF NEARBY JOINTS • FEVER • PALLOR & CACHEXIA • REGIONAL LN • FEATURES ASSOCIATED WITH PULMONARY METASTASIS • PATHOLOGICAL #
  7. 7. OSTEOSARCOMA
  8. 8. CONTD…. DISTAL NEUROVASCULAR DEFICITS AND PRESSURE SYMPTOMS ….MAY BE ASSOCIATED WITH
  9. 9. CLASSIFICATION • PRIMARY OSTEOSARCOMA • SECONDARY OSTEOSARCOMA
  10. 10. CLASSIFICATION: WHO (PRIMARY OSTEOSARCOMA) • CENTRAL(MEDULLARY) • SURFACE(PERIPHERAL)
  11. 11. CENTRAL(MEDULLARY) • CONVENTIONAL • TELANGIECTATIC • INTRAOSSEOUS/INTAMEDULLARY (WELL-DIFFERENTIATED/LOW-GRADE) • SMALL CELL OSTEOSARCOMA
  12. 12. SURFACE(PERIPHERAL) • PAROSTEAL(LOW-GRADE) • PERIOSTEAL(LOW TO INTERMEDIATE GRADE) • HIGH-GRADE SURFACE OSTEOSARCOMA
  13. 13. SECONDARY OSTEOSARCOMA -PAGET’S DISEASE -RADIATION -BENIGN PRE-EXISTING CONDITIONS [OSTEOCHONDROMA
  14. 14. SECONDARY OSTEOSARCOMA • OLDER AGE GROUP • PROGNOSIS POOR • LONG HO DULL ACHING PAIN&RECENT LYTIC DESTRUCTION
  15. 15. PATHOLOGY: MACROSCOPY Typical osteosarcoma presents as a large illdefined lesion in the metaphyseal region of the involved bone. It typically destroys cortex and frequently extends inwards marrow cavity and outwards into the adjacent soft tissue.
  16. 16. PATHOLOGY: MACROSCOPY Tumour often elevates periosteum to produce codman’s triangle on radiograph. It also produces sunray appearance due to vessels which pass from the periosteum to the cortex & along which bone is laid down & some of the new bone may be reactionary
  17. 17. PATHOLOGY: MACROSCOPY • LARGE ILL-DEFINED LESION IN THE METAPHYSEAL REGION OF LONG BONE • LEG OF MUTTON’ APPEARANCE • STONY-HARD TO SOFT AND GRITTY IN CONSISTENCY • AREAS OF HAEMORRHAGE & NECROSIS • COLOUR: WHITE : YELLOW : BLUISH WHITE: FIBROBLASTIC OSTEOBLASTIC CARTILAGENOUS
  18. 18. CONTD… • CODMAN’S TRIANGLE ---DUE TO SUBPERIOSTEAL NEW BONE FORMATION • SUNRAY APPEARANCE ---DUE TO BONE DEPOSITION IN SUB-PERIOSTEAL SPACE ALONG THE VESSELS
  19. 19. SUNRAY APPEARENCE
  20. 20. PATHOLOGY:MICROSCOPY LICHTENSTEN’S CRITERIA TO IDENTIFY OSTEOSARCOMA : 1)SARCOMATOUS STROMA 2)SPINDLE CELLS. 3) DIRECT FORMATION OF NEOPLASTIC OSTEOID AND BONE.
  21. 21. PATHOLOGY:MICROSCOPY Hallmark of osteosarcoma is the formation of osteoid by malignant mesenchymal cells . The neoplastic mesenchymal cells in between osteoid & cartilage elements may be spindle shaped and pleomorphic with bizarre hyperchromatic nuclei and frequent mitotic figures. Giant cells may be present.
  22. 22. RADIOLOGIC INVESTIGATIONS • PLAIN RADIOGRAPH(X-RAY) • CT SCAN • MRI SCAN • BONE SCAN
  23. 23. RADIOLOGY • ARISES IN THE METAPHYSIAL REGION OF A LONG BONE • OUTGROWS FROM THE MEDULLARY CANAL TO EXTRASKELETAL REGION • DISPLAYS REPRESENTATIVE FEATURES OF A MALIGNANT LESION- PERMEATIVE GROWTH PATTERN/INDISTINCT MARGINS/CORTICAL EROSION
  24. 24. RADIOLOGY.. • PERIOSTEAL REACTION WITH FORMATION OF CODMAN’S TRIANGLE/SUNBURST APPEARANCE • WIDE VARIETY OF RADIOGRAPHIC APPEARANCE LIKE BONE CYST
  25. 25. RADIOLOGY.. • CT SCAN AND MRI SCAN ARE NOT AS INSTRUMENTAL AS PLAIN RADIOGRAPH • BONE SCAN IS USEFUL TO DETECT METASTASIS
  26. 26. RADIOLOGY..MRI SCAN • EXCELLENT FOR DESCRIBING LESIONS IN THE MARROW CAVITY • HELPFUL TO DETERMINE THE LEVEL OF RESECTION • USEFUL FOR SCREENING SKIP LESIONS • CAN DETECT MEDULLARY INVASION IN CASE OF JUXTACORTICAL TUMORS • CAN DETECT EPIPHYSEAL INVOLVEMENT AND PENETRATION OF PHYSEAL CARTILAGE
  27. 27. DIAGNOSIS • • • • • HISTORY CLINICAL EXAMINATION HAEMATOLOGY RADIOLOGICAL INVESTIGATIONS HISTOPATHOLOGIC EXAMINATION
  28. 28. MANAGEMENT: MULTIDISCIPLINARY APPROACH PRIMARY CARE PHYSICIAN ORTHOPAEDIC SURGEON RADIATION ONCOLOGIST PATHOLOGIST PHYSIOTHERAPIST REHABILITATION SPECIALIST SOCIAL WORKERS & OTHERS
  29. 29. TREATMENT OPTIONS • CHEMOTHERAPY • SURGERY • RADIOTHERAPY
  30. 30. CHEMOTHERAPY • Introduction of systemic chemotherapy has dramatically improved survival rates. • Before the routine use of chemotherapy— treatment was immediate wide or radical amputation • 80% patients died of metastasis eventually, though metastasis was not evident on presentation.
  31. 31. CHEMOTHERAPY • NEO-ADJUVANT CHEMOTHERAPY: CT ADMINISTERED BEFORE THE SURGICAL RESECTION OF PRIMARY TUMOUR • ADJUVANT CHEMOTHERAPY: CT ADMINISTERED POSTOPERATIVELY TO TREAT PRESUMED MICRO-METASTASIS
  32. 32. NEO-ADJUVANT CHEMOTHERAPY • IT SHRINKS THE TUMOUR MASS , MAKING IT EASIER FOR OPERATION • IT DECREASES THE SPREAD OF TUMOUR CELLS DURING SURGERY, • T/T AGAINST POTENTIAL MICRO-METASTASIS STARTED IMMEDIATELY, (IT ALSO GIVES IDEA ABOUT RESPONSIVENESS & EFFECTIVENESS OF THE CHEMOTHERAPEUTIC AGENT TO THE TUMOUR)
  33. 33. NEO-ADJUVANT CHEMOTHERAPY DISADVANTAGES… • IT MAY INCREASE PERI-OPERATIVE COMPLICATIONS(DELAYED WOUND HEALING, INFECTION) • NAUSEA, VOMITING AND OTHER TOXICITIES MAY CAUSE DELAY IN SURGERY.
  34. 34. MANAGEMENT… LOW GRADE OSTEOSARCOMA-- TREATED BY SURGERY ALONE. HIGH GRADE OSTEOSARCOMA-- TREATED BY NEO-ADJUVANT CHEMOTHERAPY SURGERY  ADJUVANT CHEMOTHERAPY,
  35. 35. MANAGEMENT… AFTER INDUCTION OF CHEMOTHERAPY(LASTING ABOUT 2 MONTHS) SURGICAL RESECTION IS TO BE CARRIED OUT. SURGERY IS CONTEMPLATED 3-4 WEEKS AFTER LAST DOSE OF CHEMOTHERAPEUTIC AGENT ADJUVANT CHEMOTHERAPY AGAIN STARTED 2 WEEKS AFTER OPERATION
  36. 36. COMMON AGENTS USED DOXORUBICIN – 60-75 MG/M² CARDIOTOXICITY, CISPLATIN -- 50-100 MG /M² NEPHROTOXICITY VINCRISTINE -- 1.5 MG /M²,WEEKLY PERIPHERAL NEUROPATHY METHOTREXATE – 500-1000 MG/M² IV MEGALOBLASTIC ANAEMIA, PANCYTOPENIA
  37. 37. CONTD… CYCLOPHOSPHAMIDE & IFOSFAMIDE -- 1-1.5 G/M² B S A HAEMORRHAGIC CYSTITIS DACARBAZINE –250MG/M²BSA FLU LIKE SYNDROME DACTINOMYCIN – ERYTHEMA MYELOSUPPRESION
  38. 38. CONTD… ROUTE OF ADMINISTRATION – • INTRAVENOUS – • ORAL & INTRAMUSCULAR – • INTRA ARTERIAL –
  39. 39. INTRA-ARTERIAL ADM OF CHEMOTHERAPY • HIGHER CYTOTOXIC CONC. DIRECTED AGAINST TARGET TISSUE • CISPLATIN – MOST SUCCESSFUL AGENT • INFLUENCING FACTORS — PRETREATMENT ANGIOGRAPHY, CATHETER PLACEMENT,
  40. 40. RESPONSE TO PREOPERATIVE CHEMOTHERAPY ASSESSED BY • CLINICAL • RADIOGRAPHIC • ANGIOGRAPHIC • PATHOLOGICAL PARAMETERS
  41. 41. RADIATION THERAPY • ROLE OF RADIOTHERAPY IS LIMITED IN THE TREATMENT OF OSTEO-SARCOMA --A RELATIVELY RADIO-RESISTANT TUMOR. • RADIATION THERAPY CAN PALLIATE PAIN FROM LOCAL RECURRENCE AND PREVENT NEED FOR AMPUTATION IN PATIENTS WHO ARE PRESENTED WITH DISTANT METASTASIS
  42. 42. RADIATION THERAPY INDICATIONS • POST-OPERATIVE -- WHERE SURGICAL MARGIN IS INVOLVED • PALLIATION OF PAIN FROM PRIMARY TUMOUR IN THE PRESENCE OF METASTATIC DISEASE • RADICAL TREATMENT OF INOPERABLE SITES (SKULL, VERTEBRA, ILIUM, SACRUM) • BILATERAL LUNG IRRADIATION IN PULMONARY METASTASIS
  43. 43. RADIATION THERAPY • EXTERNAL BEAM RADIATION — BY LINEAR ACCELERETER. • BRACHYTHERAPY —LIMITED ROLE • IORT – SINGLE DOSE,IN SPECIALLY PREPARED OT
  44. 44. RADIATION THERAPY • AC. SIDE EFFECTS— SKIN REACTION MILD FATIGUE ANOREXIA ALTERED SLEEP & REST CYCLE • LATE EFFECTS — LYMPHATIC & VASCULAR OBST. OSTEO-NECROSIS JOINT STIFFNESS RADIATION INDUCED SARCOMAS
  45. 45. SURGERY SURGERY IS THE MAINSTAY OF THERAPY • LIMB SACRIFICING SURGERY OR • LIMB SALVAGING SURGERY ?
  46. 46. PRINCIPLES OF SURGERY CHOICE BETWEEN LIMB SALVAGE SURGERY AND AMPUTATION MUST BE MADE ON THE BASIS OF THE EXPECTATIONS AND DESIRES OF THE INDIVIDUAL PATIENT AND THE FAMILY.
  47. 47. PRINCIPLES OF SURGERY POINTS TO BE STRESSED • SURVIVAL AFTER THE PROCEDURES • SHORT AND LONG TERM MORBIDITY • FUNCTION OF SALVAGED LIMB COMPARED TO PROSTHETICS • PSYCHOSOCIAL CONSEQUENCES
  48. 48. PRINCIPLES OF SURGERY ADVANCES IN DIAGNOSTIC IMAGING CHEMOTHERAPY (NEO-ADJUVANT CHEMOTHERAPY) SURGICAL TECHNIQUES …….HAVE MADE LIMB SALVAGE SURGERY…… A REASONABLE OPTION
  49. 49. LIMB SALVAGE SURGERY “SURGICAL PROCEDURES DESIGNED TO ACCOMPLISH REMOVAL OF MALIGNANT TUMOURS & RECONSTRUCTION OF THE LIMB WITH AN ACCEPTABLE ONCOLOGIC, FUNCTIONAL & COSMETIC RESULTS.”
  50. 50. LIMB SALVAGE SURGERY • NEW SURGICAL TECHNIQUES. • PROGNOSIS IMPROVED GREATLY.
  51. 51. LIMB SALVAGE SURGERY THREE IMPORTANT DEVELOPMENTS 1. Improvement in chemotherapy — In early 70s methotrexate and adriamycin was introduced. 2. Improvement in imaging techniques— development of CT & MRI in late 70s. 3. Advances in micro- surgical techniques
  52. 52. GUIDELINES • NO INVOLVEMENT OF MAJOR NEUROVASCULAR STRUCTURES • WIDE RESECTION OF AFFECTED BONE WITH A NORMAL MUSCLE CUFF ALL AROUND • EN-BLOCK REMOVAL OF ALL BIOPSY SITES & CONTAMINATED TISSUE
  53. 53. GUIDELINES (contd.) • RESECTION OF BONE 3-4 CM BEYOND ABNORMAL UPTAKE • RESECTION OF ADJOINING JOINT & CAPSULE. • ADEQUATE MOTOR RECONSTRUCTION • ADEQUATE SOFT TISSUE COVERAGE.
  54. 54. SURGICAL MARGINS IN ONCOLOGY
  55. 55. METHODS • BONE GRAFTING AUTOLOGUS GRAFT : VASCULARISED GRAFT ALLOGENIC GRAFT : BONE BANK • ROTATIONPLASTY • RESECTION/ARTHRODESIS • PROSTHESIS • COMPOSITE ALLOGRAFT PROSTHETIC COMPOSITES
  56. 56. CONTRAINDICATIONS • DISPLACED PATHOLOGICAL FRACTURE • INAPPROPRIATE BIOPSY SITE • INFECTION • SKELETAL IMMATURITY • MAJOR NEUROVASCULAR INVOLVEMENT • EXTENSIVE MUSCLE INVOLVEMENT
  57. 57. LIMB SALVAGE SURGERY… • LIMB SALVAGE SURGERY HAS BECOME AN ACCEPTED STANDARD OF CARE FOR PATIENTS WITH SKELETAL MALIGNANCIES INCLUDING OSTEOSARCOMA • MANY PATIENTS WHO ONCE WOULD HAVE HAD AN AMPUTATION ARE NOW HAVING THEIR LIMB SAVED
  58. 58. TREATMENT OF • PULMONARY METASTASIS • LOCAL RECURRENCE • SECONDARY DISEASE
  59. 59. PRONOSTIC FACTORS • • • • • • • EXTENT OF DISEASE AT THE TIME OF DIAGNOSIS GRADE OF THE LESION SIZE OF THE TUMOUR LOCATION OF THE TUMOUR PAGET’S SARCOMA RADIATION INDUCED SARCOMA RADIATION INDUCED NECROSIS
  60. 60. THANK YOU

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