Presentation (4) (3).pptx Malignant bone tumours presentation, classification, management

Malignant bone tumours presentation, classification, management

1. Malignant bone tumors Dr L Giri Babu {1 st year pg } Moderator ;Dr DAV Suresh [MS Ortho]

2. Osteosarcoma Defined as Primary malignant  Tumor in which  Neoplastic cells produce osteoid matrix   2 nd most common primary malignant tumor of the bone behind the multiple myeloma.  Primary osteosarcomas are more common in adolescent years and secondary osteosarcomas are more common in older age group  Male : female  3:2 

3. Osteosarcoma develop in metaphysis of long bones, especially the distal femur ,proximal tibia and proximal humerus. Germline mutation in the tumor supressor Rb gene and p53 gene are at increased risk Chromosomal abnormalities in 3,13,17,18 Chromosomes most commonly involved.  Secondary osteosarcoma commonly seen in patients with paget ‘s disease. Post radiation treatment, Fibrous dysplasia, bone infarct.

4. Classification   :  based on anatomic location and cytological grading a) Central (intramedullary) type                      b) Surface ( juxta cortical ) type 

5. Central type:   Primary osteosarcom a  Conventional high – grade osteosarcoma Low – grade intramedullary osteosarcoma Periosteal osteosarcoma Parosteal osteosarcoma Telangiectatic osteosarcoma 

6. Secondary osteosarcoma Paget disease Radiation induced Arising from others benign conditions- Fibrous dysplasia, osteochondroma

7. Surface type: - Parosteal - Periosteal - Dedifferentiated C/F : Pain Swelling- progressively increases in size Limitation of joint movements . Skin is stretched, shiny and vascular ,with prominent veins General condition- deteriorate with anaemia , loss of weight and cachexia. Pulmonary symptoms- due to secondary complications .

8. PRIMARY OSTEOSARCOMA High-grade osteosarcoma begin in an intramedullary location, may break through the cortex and form a soft tissue mass

9. PRIMARY OSTEOSARCOMA Low-grade osteosarcoma is a rare type characterized by an indolent course and benign features on radiograph. Differential Dx: osteoblastoma or fibrous dysplasia Histologically consists of slightly atypical spindle cells and irregular osseous trabeculae

10. Periosteal osteosarcoma is an intermediate grade malignancy that arises on the outer aspect of the Cortex of the bone. These osteosarcomas grows and extends in to soft tissues, ossification may appear with in Enlarged mass. Surgical resection with or without chemotherapy is standard treatment.

11. Parosteal osteosarcoma, a rare ,low grade malignancy, arises on the surface of bone and invades medullary cavity at a late stage. Presents as slow growing ( low – grade) ,hard swelling mass on the outer surface of Cortex. Differential Dx: myositis ossificans ,periosteal osteosarcoma, osteochondroma. Wide surgical excision of the tumor- bearing bone and bony reconstruction without chemotherapy It has better prognosis than others.

12. Pathophysiology: Tumor extends in two directions Towards the medulla Towards the subperiosteal area.

13.     Diagnosis :  Hematological  Plain radiography  CT   MRI  Bone scan   PET scan   Arteriography  Biopsy                     

14. Haemotological Hb% - decreased TLC - increased/ decreased ESR - Raised S.calcium – increased S.Alkaline phosphatase- increased (>400u/l)

15. Radiography: plain radiography remains the mainstay  Location & shape  Margin  Matrix mineralization  Cortical involvement  Periosteal reaction and fracture

16. Tumor arises at the metaphyseal region of the bone ,either centrally or over the Cortex. Tumor appear as regions of permeative bone destruction and irregular new bone formation. Sunray appearance: when the tumor extends beyond the Cortex, the periosteum is raised & New bone formation in lines at right angles to the Cortex .

17. Codman triangle : periosteum stripped for short distance and deposition of new bone arranged parallel to the shaft. Pathological fracture  CXR: must be taken it may show round  shadows caused by secondary deposits ( cannon ball appearance)

18. CT SCAN : To detect tumor and characterization of matrix mineralization. To assess integrity of the Cortex CT lungs to detect pulmonary metastasis Contrast CT preferred over plain CT

19. MRI : Excellent for describing lesions especially in the marrow which helps to determine level of resection  For evaluation of invasion to muscle and neurovascular structures. Bone scan : Technetium 99 radioisotope                     Extended pattern of uptake                     Not reliable for detecting skip metastasis.                     Not accurate to evaluate post neo-                            adjuvant chemo.

20. PET SCAN: Response to neo-adjuvant chemotherapy can be assessed.

21. BIOPSY: in all cases ,diagnosis should be established by a biopsy. Should be done at the growing periphery of the tumor not from the center of the lesion as it contains only necrotic cells . “Biopsy should be regarded as the final diagnostic procedure, not as a shortcut to diagnosis” Types CLOSED : FNAC Trucut - needle biopsy Jamshidi core needle biopsy. OPEN : Excisional Incisional

22. HISTOLOGY: Primary high- grade osteosarcoma

23. TREATMENT: Low-grade osteosarcoma: wide surgical resection is the treatment of choice, usually without adjuvant chemotherapy. High-grade osteosarcoma : neo- adjuvant chemotherapy, wide surgical resection/radical amputation, adjuvant chemotherapy The goal of chemotherapy is to treat the non detectable micrometastases . Neoadjuvant chemotherapy: dec size ,dec vascularity and micro metastasis. Active agent are high – dose methotrexate, ifosamide ,Adriamycin and cisplatin .

24. SURGERY Decision making- type of surgery (limb salvage or amputation) Tumor site, extent, response to chemo Patients age & expected functional result Reconstruction procedures, financial status.

25. ECIR ( extracorporial irradiation): In this surgery ,the tumor is removed by wide resection and irradiated, and the tumor bone autograft is used for reconstruction and fixed using plate. Intra operatively, the tumor margins are examined for malignant cells by intra operative frozen section which can yield results with in 20 mins . Osteosarcoma is the most radio resistant bone tumor.

26. ARTHRODESIS : Provides pain free ,stable limb with loss of motion Use of allografts or vascularized autogenous grafts to bridge the osseous gap . High risk of delayed or non –union & fracture

27. ROTATIONPLASTY: Group A1 - lesion in distal femur Group A11 - lesion in proximal tibia Group B1 - lesion in the proximal femur sparing the hip joint Group B11 – lesion in the proximal femur with involvement of hip jn Group B111 – lesion in the mid femur.

28. chondrosarcoma It is a malignant tumor of the bone with cartilaginous origin 9% of all primary malignancies of bone Primary chondrosarcoma - Between 40 and 60 years Secondary chondrosarcoma -Between 25 and 45 years

29. INCIDENCE – It is the third most common malignant tumor of bone(first two being osteosarcoma and ewings sarcoma) In long bones it arises from diaphyseometaphysial junction 5% for patients with multiple hereditary exostoses Approximately 1% for patients with solitary osteochondromas

30. Classification: Primary chondrosarcoma Secondary chondrosarcom a

31. PRIMARY CHONDROSARCOMA Central (medullary) Intra cortical Clear cell Mesenchymal Dedifferentiated

32. SECONDARY CHONDROSARCOMA (from pre existing lesions) Multiple enchondromas & Exostosis Chondroblastoma Irradiation induced Fibrous dysplasia

33. Location : Types according to the site CENTRAL PERIPHERAL (surface type)

34. COMMON SITES Pelvis Proximal femur Proximal humerus Ribs Rarely occur in the hand Incidence is higher among males

35. Clinical features: A palpable mass with increasing pain Hard in consistency with lobulated surface Continuous with the bone Slow growing Mechanical restriction of joint movements

36. Pathology : Macroscopically ,tumor is lobulated and appears as white or bluish mass of firm consistency.it often appears to have capsule, and there are areas of myxomatous degeneration and softening.

37. Irregular patchy areas of calcification are also characteristic Microscopically cartilage cells – polynucleotic and hyperchromatic Here typically formation of cartilage by the tumor cells.

38. Radiology It is arising in the medullary cavity with irregular matrix calcification .Calcification is a specific sign Gives a "punctate," "popcorn," or "comma- shaped.“ calcification

39. The size of the cartilaginous cap of an osteochondroma, is to be evaluated with Computerised Tomography (CT-Scan) or Magnetic resonance imaging (MRI). It is important in evaluating the possibility of a secondary chondrosarcoma

40. histology Conventional chondrosarcoma Composed of malignant cells with abundant cartilaginous matrix. If malignant osteoid is present → the diagnosis should be chondroblastic osteosarcoma

41. Diagnostic factors that favor the malignant transformation Hypercellularity Plump nuclei More than occasional binucleate cells Entrapment of bony trabeculae

42. Histological subtypes Clear cell chondrosarcoma Mesenchymal chondrosarcoma Dedifferentiated chondrosarcoma

43. Low-grade malignancy .Round cells with abundant clear cytoplasm Distinct cytoplasmic borders with a background of cartilaginous matrix. Multinucleated giant cells are usually apparent Clear cell chondrosarcoma

44. Clear cell Chondrosarcoma has a strong tendency to arise in an epiphysis Benign radiographic features and can be confused with chondroblastoma or giant cell tumor

45. Mesenchymal chonrocytoma High-grade tumor Small round blue cells Islands of benign-appearing cartilage. The cellular portions have a " Hemangio pericytomatous " pattern of growth with “staghorn-like" vessels.

46. Dedifferentiated chondrosarcoma High-grade sarcoma (Commonly osteosarcoma followed in frequency by fibrosarcoma and malignant fibrous histiocytoma) The radiography shows aggressive radiolucent area

47. Treatment : Toc is surgical.it does not respond to chemotherapy or radiotherapy. Low-grade chondrosarcoma Extended curettage with the use of intra operative adjuvant treatments .

48. High-grade chondrosarcoma Wide or radical resection Amputation .

49. The local recurrence rate after intraoperative tumor contamination is high. For lesions in an expendable locations, Primary wide resection without a biopsy may be indicated It is to decrease the chance of tumor contamination.

50. After wide resection  local recurrence is less than 10% Pulmonary metastases  treated with surgical resection if possible

51. Chemotherapy has no role in the treatment of conventional chondrosarcoma Radiotherapy is used only as a palliative measure for surgically inaccessible lesions Inaccessible areas include Tumour arising from  floor of pelvis  Vertebrae & spinous process

52. The prognosis depends on Size Grade Location of the lesion

53. Low-grade lesions Greater than 90% 10-year survival rate High-grade conventional chondrosarcoma 20% to 40% 10-year survival rate

54. Ewing’s sarcoma

55. Introduction Named after James Ewing who identified it in 1921 Was originally termed as diffuse endothelioma or endothelial myeloma. Currently- part of peripheral primitive neuroectodermal tumors as it shares common cytogenetic translocation of chromosome 11 & 22

56. Ewing's sarcoma is a round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long- term survival was less than 10%.

57. Ewings sarcoma family of tumors : Ewing's sarcoma Extraosseous Ewing's sarcoma Peripheral PNET Askin's tumor

58. Prevalance Second most frequent bone sarcoma after osteosarcoma in patients younger than 20 years. 2% of cancer in childhood. Caucasians are more frequently affected than asians , africans and african-americans rarely affected Common age-10 - 20 years. M>F-(M:F = 1.4:1)

59. sites Long bones diaphysis involvement is common Ribs – frequently manifests with pneumonia or pleural effusion

60. spread Generally spread through bloodstream Direct extension into adjacent bone or soft tissue. Micromets is common in all patients .

61. Approximately 50% of patients who present with metastases have pulmonary involvement. 25% - bony metastases. 20% - bone marrow involvement. Liver and lymph node metastases are rare.

62. staging No specific staging system for Ewings sarcoma The AJCC staging systems for bone or soft- tissue sarcomas may be used.

63. Pathology Poorly differentiated tumor Unknown origin. Thought to be of neural crest progenitor cell origin

64. Gross Whitish-gray soft tissue mass arises in the marrow spaces of the affected bone. Necrotic and hemorrhagic areas are frequent Periosteum elevated and is often perforated. Almost always a large soft tissue mass extending well beyond the bony boundaries. Not encapsulated and invades the surrounding muscle .

65. Gross microscopy

66. Microscopy Compact sheets of small polyhedral cells with pale cytoplasm and ill-defined boundaries. Nuclei- uniform, round or oval, and contains scattered areas of chromatin. Cytoplasm is scant Presence of glycogen in the cell

67. Occasional rosette or pseudorosette formation may be present. Must be distinguished from neuroblastoma, non-Hodgkin lymphoma and rhabdomyosarcoma .

68. Cytogenetics 80 to 90% patients with Ewing sarcoma have a translocation of chromosomes 11 and 22 or chromosomes 21 and 22.

69. Clinical features Local pain and swelling of affected area. Tender local mass is invariably present. Stiffness - common in involvement of long bone. Limp

70. Weight loss Fever Anemia Occasionally presents with pathological fractures. Other symptoms depend on the site of the lesion

71. investigations Radiographic findings : X rays : Characteristic but not pathognomonic Permeative lesion with mottled rarefaction of the medullary cavity and invasion through the overlying cortex, reflecting rapid bone destruction. Periosteal new bone formation- laminated "onion peel".

72. Moth eaten lesion Lytic or mixed lytic-sclerotic areas Codman's triangle

73. Radiographic findings resemble Osteomyelitis Osteosarcoma Histiocytosis Wilms tumor Lymphoma Metastatic neuroblastoma

74. MRI is useful to determine the extent of the lesion within the bone and adjacent soft tissue Dynamic MRI have made it possible to use to access the response to chemotherapy. CT-to search for metastatic disease in the chest

75. Bone scan - to search for other areas of bone involvement. RT-PCR -most definitive test by demonstration of chromosomal translocation t(11;22)

76. Diagnosis is usually made from histologic study of tissue sections by open or needle biopsy. And it is best to avoid making a cortical defect in a long bone, because if radiation is chosen for local control, the chances of pathologic fracture are greater. Frozen section biopsy, to ensure adequate tissue is obtained for histologic studies.

77. The Histologic differential diagnosis – Neuroblastoma Rhabdomyosarcoma Malignant lymphoma Small cell osteosarcoma Wilms tumour Desmoplastic small cell tumour

78. Laboratory tests CBC Alkaline phosphatase LDH

79. Prognosis With the advent of adjuvant chemotherapy and proper local control, the outlook has been considerably better Approximately 70% 5-year event free survival rates Large Central Lesion (esp., Pelvis) - worse outcome than those with distant tumors.

80. Prognostic factors  Unfavourable factors Distant metastasis Older than 15 years Size larger than 8cm. Central lesions( pelvis or spine). Poor response to chemotherapy

81. Favorable prognosis Distal extremity <8 cm in greatest diameter or <200 ml estimated volume. Localized Absence of radiographically identifiable soft tissue extension

82. Fever, weight loss, anemia and elevated WBC, ESR, LDH indicate more extensive disease and a poor prognosis.

83. TREATMENT: Multidisciplinary approach Includes chemotherapy, surgery, radiation therapy .

84. Depends on Where in the body the tumor started. Where the tumor has spread. The size of the tumor The result of the treatment .

85. CHEMOTHERAPY With Intensive chemotherapy reported long-term survival rate is 60-70%. Can be given before surgery(neoadjuvant) or after(adjuvant)

86. Current drugs • Doxorubicin (DXR), Cyclophsophamide (CPA), • Vincristine(VCR) • Actinomycin-D (ACT) • Ifosfamide (IFM) Etoposide(VP16)

87. VACD-IE regimen - the standard therapy for localized ewings sarcoma. 10 year event-free survival is around 50%.- first line therapy Second line therapy- Cyclophosphamide and topotecan Temozolomide and irinotecan Ifosafamide and etoposide Ifosfamide , etoposide and carboplatin Docetaxel and gemcitabine

88. Postoperatively, additional cycles of the same regimen is given. Total 48 weeks. Chemotherapy in every 2 weeks demonstrated improvement in event free survival than chemotherapy in every 3 weeks .

89. RADIATION THERAPY Effectively controls local disease, when combined with chemotherapy. Usual dose-55.8 to 6o Gy . Adequate dosages result in local control in 53 to 86%. Studies shows no difference in local control with 2cm margin compared to whole bone irradiation .

90. Definitive radiation therapy: Where resection is impossible Where only intra-lesional resection is achievable Patient refusing surgery Patient with poor surgical risk

91. Problems with radiotherapy In younger children with lower extremity primary tumors, irradiation of growth plates can lead to limb length inequality. Fracture if bone is irradiated. Late occurence of a secondary malignancy in the involved bone.

92. Surgical treatment Resection of tumor: Done after induction chemotherapy, which often decreases the size of the soft tissue mass. To avoid secondary malignancies Margins and histologic necrosis in the resected specimen are examined.

93. Surveillance Physical examination, chest x-ray: Every 2-3 months Increase interval after 24 months Annually after 5 years CBC Bone scan

94. Relapse Early- less than 2 years: Change chemotherapy Late - more than 2 years: Continue the previously used CT

95. Plasmacytoma (myeloma of bone) Plasmacytoma is the most common primary malignant tumors of the bone . Arises from the plasma cell of the reticuloendothelial tissue of the bone marrow . It can occur as solitary plasmacytoma ,multiple myeloma or generalized myelomatosis .

96. Treatment : Incurable Chemotherapy is the mainstay of treatment The main drugs used are cyclophosphamide and phenylalanine mustard Bisphosphonates (drugs that inhibit bone resorption)- reduce pathological fracture and hypercalcemia The tumor is radio sensitive and localized lesions are treated with radiation therapy for relief of pain and pressure symptoms. HSC Transplantation –prolongs life but has not been proven to be curative

97. Prognosis: Variable Median survival is 4 to 7 years, Translocation involving cyclin D1: good prognosis Deletions of 13q,17p and the t(4;14): aggressive course .

98. summary Second most common primary malignant bone tumors in children Common Age group-10-20 years (M>F) Commonly involves diaphysis of long bone Presents with local swelling and tenderness Metastasis is usually present at the time of presentation

99. Diagnosis is confirmed by histopathological studies or cytogenetic studies Treatment modalities includes Neoadjuvant therapy followed by local control of the tumor with surgery/radiotherapy and maintenance with adjuvant chemotherapy 5-year event free survival has increased from 10% to 70% with the advent of multi-chemotherapeutic agents.