Bone tumours by dr narmada prasad tiwari

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bone tumours .osteoid osteoma, osteosarcoma, chondroma

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Bone tumours by dr narmada prasad tiwari

  1. 1. BONE TUMOR MODERATOR-DR. S. S. THAKUR
  2. 2. • A bone tumor, is a neoplastic growth of tissue in bone. Abnormal growths found in the bone can be either benign or malignant.
  3. 3. • • • • Bones are classified according to their shapeLong bone Flat bone Short bone.
  4. 4. • • • • • • • Long bone anatomy Diaphysis: long shaft of bone Epiphysis: ends of bone Epiphyseal plate: growth plate Metaphysis: b/w epiphysis and diaphysis Articular cartilage: covers epiphysis Periosteum: bone covering (pain sensitive) Sharpey’s fibers: periosteum attaches to underlying bone • Medullary cavity: Hollow chamber in bone - red marrow produces blood cells - yellow marrow is adipose. • Endosteum: thin layer lining the medullary cavity
  5. 5. Diaphysis
  6. 6. Epiphysis
  7. 7. Metaphysis
  8. 8. • Histology of bone tissue Cells are surrounded by matrix. - 25% water - 25% protein - 50% mineral salts 4 cell types make up osseous tissue Osteoprogenitor cells Osteoblasts Osteocytes Osteoclasts
  9. 9. • Osteoprogenitor cells: - derived from mesenchyme - unspecialized stem cells - undergo mitosis and develop into osteoblasts - found on inner surface of periosteum and endosteum.
  10. 10. Osteoblasts: - bone forming cells - found on surface of bone - no ability to mitotically divide - collagen secretors Osteocytes: - mature bone cells - derived form osteoblasts - do not secrete matrix material - cellular duties include exchange of nutrients and waste with blood
  11. 11. • Osteoclasts - bone resorbing cells - bone surface - growth, maintenance and bone repair Abundant inorganic mineral salts: - Tricalcium phosphate in crystalline form called hydroxyapatite Ca3(PO4)2(OH)2 - Calcium Carbonate: CaCO3 - Magnesium Hydroxide: Mg(OH)2 - Fluoride and Sulfate
  12. 12. Osteoprogeniter cells &Osteoblast
  13. 13. Osteoclast
  14. 14. Precursors of malignancy in bone • • • • • • • • • High Risk Ollier disease (Enchondromatosis) and Maffucci syndrome Familial retinoblastoma syndrome Rothmund-Thomson syndrome (RTS) Moderate Risk Multiple osteochondromas Polyostotic Paget disease Radiation osteitis
  15. 15. • • • • • • • • Low Risk Fibrous dysplasia Bone infarct Chronic osteomyelitis Metallic and polyethylene implants Osteogenesis imperfecta Giant cell tumour Osteoblastoma and chondroblastoma
  16. 16. Classification of primary tumour involving bones Histological type Hematopoietic Chondrogenic Benign Malignant Myeloma Osteochodroma Chondroma Chondroblastoma Chondromyxoid fibroma Malignant lymphoma chondrosarcoma
  17. 17. Histological type Benign Malignant Osteogenic Osteoma Osteosarcoma Osteoid osteoma osteoblastoma Unknown origin Giant cell tumour Ewing tumour Giant cell tumour admantinoma
  18. 18. Histological type Benign Malignant Histiocytic origin Fibrous histiocytoma MFH Fibrogenic Metaphyseal fibrous Dysplastic fibroma defect Fibrosarcoma Notochordal Vascular Chordoma Hemangioma Hemangioendothelioma Hemangiopericytoma Lipogenic Lipoma Neurogenic Neurilemmoma Liposarcoma
  19. 19. Distribution of bone tumors in long bones • Epiphyseal lesions: • Chondroblastoma • Giant cell tumor • • • • Metaphyseal intramedullary lesions: Osteosarcoma Chondrosarcoma Aneurysmal bone cyst
  20. 20. • Metaphyseal lesions centered in the cortex: • Nonossifying fibroma (NOF) • Osteoid osteoma • Metaphyseal exostosis: • Osteochondroma
  21. 21. • • • • • • Diaphyseal intramedullary lesions: Ewing’s sarcoma Lymphoma Myeloma Fibrous dysplasia Enchondroma • • • Diaphyseal lesions centered in the cortex: Adamantinoma Osteoid osteoma
  22. 22. Sites of Tumors
  23. 23. Important Facts • 0.001% of all cancers • MC benign tumor--- Osteochondroma; Osteoid Osteoma • MC Skeletal malignancy– Metastasis. • MC Bone tumor in Pediatric age group & adultsOsteosarcoma • MC in < 10 y--- Ewing’s sarcoma • MC Primary bone tumor – Multiple Myeloma
  24. 24. PRESENTING SYMPTOMS • • • • • • • • Patient may present with An abnormal radiographic finding detected during evaluation of unrelated problem PAIN:- is most frequent symptom MASS:- rate of enlargement is important -Fluctuating mass can be cyst,ganglion or hemangioma -Family H/O masses near the joint may be indicator of Ollier’s disease or Maffucci Syndrome NEUROLOGICAL SYMPTOM:- found in few patients such as sacral tumors & with tumors located near the nerve causing compression of nerve,especially common in sciatic notch ,inguinal canal & popliteal fossa UNEXPLAINED SWELLING OF THE LOWER EXTREMITY:- found in pelvic tumors which are painless & without a palpable mass & cause swelling due to compression of iliac vein.
  25. 25. PHYSICAL EXAMINATION • Evaluation of patient’s general health • TUMOR MASS should be measured & its location,shape, consistency,mobility,tenderness,local temp & change with position should be noted. • SKIN & SUBCUTANEOUS TISSUE : • Small dialated superficial veins overlying the mass are produced by large tumors • Café-au-lait spots & subcutaneous neurofibromas indicate Von Recklinghausen’s disease • A venous malformation Maffucci Syndrome • REGIONAL LYMPH NODES: sign of metastatic disease • Atrophy of surrounding musculature should be recorded,also neurological deficits & adequacy of circulation.
  26. 26. HISTORY OF THE PATIENT • AGE:- most imp information,bcoz of their presentaion in sp age group. • 1st decade- usually ABC ,SBC • 2nd decade-Chondroblastoma,osteosarcoma,Ewings • 3rd decade- GCT • 4th decade- chondrosarcoma • 5th decade- Multiple myeloma • SEX:- less imp than age • RACE:- little imp, Ewings rare in african descent • H/O any exposure to radiation Tt or Carcinogens- bone seeking radionucleotide can cause sarcoma. • Various chemical carcinogens- zinc beryllium silicate, beryllium oxide. • Currently the most worrisome & controversial is Nickel which is used in many orthopedic devices.
  27. 27. LABORATORY TEST • Alkaline phosphatase – Higher . • PTH test: Lower. • Serum phosphorus: Higher • Ionized calcium and serum calcium: Higher .
  28. 28. • • • • INVESTIGATIONS X-RAY CT SCAN MRI TECHNETIUM BONE SCAN-This type of scan uses a very low radioactive material (diphosphonate) to see whether or not the cancer has spread to other bones and the damage suffered by the bone. • PET- uses radioactive glucose to locate cancer. This glucose contains a radioactive atom that is absorbed by the cancerous cells and then detected by a special camera.
  29. 29. BIOPSY • The biopsy is the most conclusive test because it confirms if the tumor is malignant or benign, the bone cancer type (primary or secondary bone cancer), and stage. • According to the tumor size and type (malignant or benign) and the biopsy's purpose (to remove the entire tumor or only a small tissue sample), there are two types of biopsies used in bone cancer diagnosis. These are: needle biopsy and incisional biopsy. • 1. Needle biopsy: During this procedure, a small hole is made in the affected bone and a tissue sample from the tumor is removed. • There are two types of needle biopsies: • Fine needle aspiration: During this procedure, the tissue sample is removed with a thin needle attached to a syringe. • Core needle aspiration: During this procedure, the surgeon removes a small cylinder of tissue sample from the tumor with a rotating knife like device. • 2. Incisional biopsy: During this procedure, the surgeon cuts into the tumor and removes a tissue sample.
  30. 30. BONE FORMING TUMOURS • Benign: Osteoma, Osteoid Osteoma, • Benign Aggressive: Osteoblastoma • Malignant: Osteogenic Sarcoma
  31. 31. Osteoma • Benign, asymptomatic, slow-growing osteogenic lesion. • Age/Sex: 40-50 yr, M:F = 2:1. • Bones involved: flat bones of the skull and face; may protrude in the paranasal sinus. • Parosteal location. • Gardner’s syndrome.
  32. 32. Ivory like bony mass
  33. 33. Figure 2: The lesion consists of dense and lamellar cortical bone with a focal area of active bone modeling. Figure 3: Photomicrograph of the more solid area of the lesion to demonstrate the cellular woven character of the bone.
  34. 34. Osteoid osteoma • Signs/Symptoms: • Pain, characteristically more intense at night, relieved by NSAID and eliminated by excision • Scoliosis • Age: • Sex: • 10-30 years • M > F (2:1) • Anatomic Distribution: • Nearly every location, most frequent in femur, tibia,( Over 50%) humerus, bones of hands and feet, vertebrae and fibula • Metaphysis / Diaphysis (cortical) of long bones • Vertebral lesions may be associated with scoliosis.
  35. 35. Small central osteolytic nidus surrounded by dense bone
  36. 36. The small, reddish central nidus is surrounded by a thick layer of sclerotic bone
  37. 37. Wedge shaped nidus which is surrounded by dense sclerotic bone.
  38. 38. New osteoid and bone formation by plump osteoblasts. The stroma is cellular and well vascularized
  39. 39. Osteoid osteoma with anastomosing trabeculae of woven bone
  40. 40. Osteoblastoma • Also called as Giant osteoid osteoma. • Osteoblastoma is similar to osteoid osteoma with more aggressive behavior. • D/D from osteoid osteoma*Pain *Absence of reactive bone * Large size • Location : – In spine or major bones of lower extremity
  41. 41. Well differentiated radiopaque/radiolucent lesion
  42. 42. Osteoblastoma.-The histologic appearance is identical to that of osteoid osteoma.
  43. 43. Recurrent osteoblastoma.-The appearance is similar to that of osteoid osteoma
  44. 44. Osteosarcoma • Most frequent primary malignant bone tumour. • Age/Sex :10-25 yrs & >40 , M:F = 3:2 • Predisposing conditions: Paget’s disease Radiation exposure Chemotherapy Benign bone lesion Foreign bodies Trauma
  45. 45. Codman’s triangle: “Sunray “ appearance
  46. 46. Tumor is located at the typical metaphyseal site. The tumor shown in A is largely restricted to bone, whereas that illustrated in B is accompanied by massive soft tissue extension.
  47. 47. ‘skip metastasis’ located in the upper half of the femur. The primary tumor was located in the lower metaphysis of the same bone
  48. 48. The malignant bone is more basophilic and has more irregular borders than the preexisting bone trabeculae.
  49. 49. Osteosarcoma showing characteristic basophilic thin trabeculae of neoplastic bone with an appearance that is reminiscent of fungal hyphae
  50. 50. Lace-like osteoid deposition is very characteristic of this neoplasm.
  51. 51. Osteoblastic osteosarcoma with finely ramifying matrix between tumor cells
  52. 52. Microscopic variants Telangiectatic : • Blood filled cystic space and thus radiologically appears as pure lytic lesion. • Pathological fractures. • Grossly the lesion simulate aneurysmal bone cyst. • Detection of malignant stroma in the septa that separate the bloody cysts.
  53. 53. Telangiectatic osteosarcoma.
  54. 54. Telangiectatic osteosarcoma. A The low-power architecture closely simulates the appearance of an aneurysmal bone cyst B Malignant osteoid is present in the septa
  55. 55. Telangiectatic osteosarcoma. Spaces containing blood are separated by septa. The cells appear malignant even at this level of magnification
  56. 56. Fibrohistiocytic
  57. 57. Small cell variant: • Uniform small size tumour cells. • Diffuse pattern of growth. • Simulate Ewing’s sarcoma and malignant lymphoma.
  58. 58. Anaplastic
  59. 59. Well differentiated intramedullary .This tumor is microscopically so bland looking as to be often underdiagnosed as a benign lesion. In contrast to fibrous dysplasia 1- this tumor shows radiographic evidence of cortical destruction. 2-Microscopically, atypia is minimal but still present. 3-The invasive growth pattern.
  60. 60. Variants defined on the basis of topographic, clinical and radiographic features: Juxtacortical (parosteal) • Slightly older age group • Juxtacortical position in the metaphysis of long bones.
  61. 61. Juxtacortical osteosarcoma of upper femur. There is only minimal involvement of the cortex Juxtacortical osteosarcoma large extracortical component
  62. 62. Juxtacortical osteosarcoma--Moderately atypical spindle tumor cells grow between irregularly shaped bone trabeculae
  63. 63. Parosteal osteosarcoma-The spindle cells demonstrate minimal atypia, and the bone appears to arise directly from the spindle cells.
  64. 64. Periosteal osteosaocoma • Grows on surface of long bones. • Upper tibial shaft or femur.
  65. 65. Periosteal osteosarcoma. The white shining appearance is due to the high content of cartilage
  66. 66. periosteal chondrosarcoma. There is a predominance of myxochondroid areas
  67. 67. Bone formation in the center of a cartilaginous lobule in periosteal osteosarcoma
  68. 68. Osteosarcoma of jaw: • Patients affected are slightly older (average age, 34 years), • And most lesions show a prominent chondroblastic component. • The most common sites of involvement are the body of the mandible and the alveolar ridge of the maxilla. Osteosarcoma in Paget’s disease. • Osteosarcoma are of the polyostotic type • Pelvis, humerus, femur tibia & skull. • Large number of osteoclasts alternating with atypical osteoblast.
  69. 69. Histochemistry, IHC & molecular genetics • Strong alkaline phosphatase activity. • Vimentin, S-100, keratin & EMA. • Osteonectin, osteocalcin, osteopontin.
  70. 70. Prognostic factors • • • • • • • • • • • • Paget’s disease Irradiation Specific bone involvement Multifocality Various types Microscopic variants Serum elevation of alkaline phosphatase Aneuploidy Post chemotherapy tumour necrosis RB gene HER2/neu expression P-glycoprotein.
  71. 71. CARTILAGE FORMING TUMOURS • Benign: Enchondroma, Periosteal Chondroma, Osteocho ndroma. • Benign Aggressive: Chondromyxoid Fibroma, Chondroblast oma. • Malignant:
  72. 72. Chondroma • Benign tumor of mature hyaline cartilage • Age – 20-50 yrs • Usually solitary,30% are multiple. • Bones involved: small bones of hand & feet. • Asymptomatic, pain & swelling. Enchondroma is the most common tumor of the bones of the hand
  73. 73. Enchondromas • Begin in spongiosa of diaphysis, from which they expand and thin cortex • Unusual in ribs and long bones Juxtacortical Chondroma • Much less common than enchondroma • Involve parosteal region of long bone or small bone of hand or foot
  74. 74. 2 syndromes characterized by multiple chondromas: • Ollier’s disease • Maffucci’s syndrome • Both disorders have 25% risk of malignant transformation to chondrosarcoma
  75. 75. Maffucci syndrome-Innumerable chondromas are seen concentrated in the distal aspect of the extremity
  76. 76. Juxta-cortical - The tumor produces a semispherical expansion of the involved bone.
  77. 77. Enchondroma-The tumor has a typical lobulated appearance
  78. 78. Osteochondroma • • • • Also known as exostosis. Most frequent benign cartilaginous tumour. Age/sex - <20yr, M:F=3:1 Bones involved: lower femur, upper tibia, upper humerus and pelvis. • Location: Metaphysis
  79. 79. • Probably not a true neoplasm. • Inactivation of both copies of the EXT gene in the growth plate chondrocytes. • Presents as slow growing mass, painful. • <1% cases show malignant transformation.
  80. 80. A- Large osteochondroma of femur with a bilobed appearance. B Cut surface of osteochondroma of ribthick cartilaginous cup
  81. 81. Projection with cortex continuous with underlying bone; may be pedunculated; cartilaginous cap with frequent calcification
  82. 82. Microscopic-Mature bone is covered by a welldifferentiated cartilaginous cap.
  83. 83. Microscopic
  84. 84. Chondroblastoma • Rare benign cartilage producing tumour. • Age/Sex : 2nd decade M:F=2:1. • Bones involved: Distal femur ,proximal humerus and tibia. • Location: Epiphysis • Pain is constant .
  85. 85. Typical sharply delineated lytic appearance of chondroblastoma of humeral head
  86. 86. Gross appearance of chondroblastoma of upper end of the humerus, associated with aneurysmal bone cyst-like changes
  87. 87. Chondroblastoma. A- Small tumor cells of round shape are accompanied by scattered osteoclasts. B-Immunoreactivity for S-100 protein in the neoplastic component.
  88. 88. Chondroblast: Prominent Indented Nucleus Eosinophilic Cytoplasm Thick Cell Membrane Uniform Appearance of Cells
  89. 89. Chondroblastoma with eosinophilic chondroid matrix, giant cells, and mononuclear cells
  90. 90. Imagine the cells present without the nuclei: The thickened cell membranes would give a chicken wire fence appearance
  91. 91. Chondromyxoid Fibroma • Benign tumour of cartilaginous origin. • Age/Sex: 20-30 yr/ M:F=2:1 • Bones involved: Long bones>flat bones >vertebrae. • Location: Metaphysis. • Localised pain with or without tenderness
  92. 92. Sharply delimited chondromyxoid fibroma of lower femoral metaphysis in a young boy.
  93. 93. A-Chondromyxoid fibroma of proximal femur extending into soft tissue B-The tumor has a lobulated appearance, in which myxochondroid islands alternate with more cellular foci.
  94. 94. Chondromyxoid fibroma- (A) An irregularly shaped hypocellular center is surrounded by a cellular spindle cell stroma. (B) The lobules contain tumor cells with small nuclei and eosinophilic cytoplasmic extensions within a myxoid background
  95. 95. Chondrosarcoma • Second most common malignant tumour of bones. • Arise de novo or from pre-existing benign cartilagenous tumour. • Divided into two major categories: *Conventional chondrosarcoma *Chondrosarcoma variants
  96. 96. Conventional chondrosarcoma • 30 – 60 yr of age. • M>F • Divided according to location: *Central *Peripheral *Juxtacortical
  97. 97. Typical chondrosarcoma of femurI-ill defined margins; fusiform thickening of shaft; perforation of cortex
  98. 98. Typical chondrosarcoma
  99. 99. Peripheral Variant: • Tumour is present on the surface of bone. • May arise de-novo or from cartilaginous cap of preexisting osteochondroma.
  100. 100. Peripheral chondrosarcoma of femur resulting in a huge exophytic mass
  101. 101. Juxtacortical(periosteal) variant: • Location: – shaft of long bone (most often femur) • Cartilaginous lobular pattern with areas of: – spotty calcification – endochondral ossification • Closely related to periosteal osteosarcoma.
  102. 102. Microscopic • Wide range of differentiation and graded into: – well differentiated – moderately differentiated – poorly differentiated
  103. 103. Well-differentiated chondrosarcoma. The tumor has a distinctly lobulated quality
  104. 104. Well differentiated- High-power appearance of grade 1 chondrosarcoma. A few doubly nucleated cells and moderate atypia .
  105. 105. Moderately differentiated - High-power appearance of grade 2 chondrosarcoma with necrosis . The nuclei are crowded and hyperchromatic
  106. 106. Poorly differentiated
  107. 107. Grading system • Grade I : lesions contain hyaline cartilage manifested by sparse cellularity. The cells typically contain dark, pyknotic nuclei. <20% of cells contain large nuclei and fine nuclear chromatin. Mitosis is absent. • Grade II: A) lesion are slightly more cellular and >20% nuclei are larger than nucleus of mature lymphocyte. Binucleate cells are easily found. Mitosis is absent. B) cellular lesions with numerous binucleated cells and nuclear atypia. Mitosis is present but not more than 1/ 10hpf. • Grade III: Mitosis atleast >=2 / 10 hpf
  108. 108. • The main differential is of low grade (Grade 1) chondrosarcoma and enchondroma. • Features consistent with chondrosarcoma are: *Pain attributable to lesion *Age greater than 50 *Cortical destruction and a soft tissue mass *Periosteal reaction and thickening *Endosteal erosion>2/3 cortical thickness on a CT scan *Size greater than 5 cm
  109. 109. Chondrosarcoma variants Dedifferentiated chondrosarcoma: • Worst prognosis. • Age/sex: sixth decade/ M:F =1:1. • Bones involved: pelvis, femur. • Poorly differentiated sarcomatous component at periphery of otherwise typical low-grade chondrosarcoma – usually central type – can be peripheral
  110. 110. Gross appearance of dedifferentiated chondrosarcoma of pelvic bone -
  111. 111. Microscopic • Dedifferentiation: – may be in initial lesion – more often in specimens from recurrent tumor: • microscopic appearance of this component may be: – – – – rhabdomyosarcoma fibrosarcoma osteosarcoma pleomorphic sarcoma with MFH-like features
  112. 112. The edge of an island of well-differentiated cartilage (upper left) is surrounded by highly pleomorphic sarcoma containing tumor giant cells
  113. 113. Chondrosarcoma is juxtaposed with high-grade malignant fibrous histiocytoma
  114. 114. Clear cell variant: • Behaves as low-grade malignancy • Can undergo dedifferentiation • Age/Sex : 30-40 yrs/M:F= 2.5:1 • Location: proximal end of femur and humerus.
  115. 115. Clear cell chondrosarcoma with faint lobulation, woven bone, and clear cells
  116. 116. Mesenchymal variant: • Usually second or third decade of life • Great variability in clinical course. • Location: – most commonly: • jaw • pelvis • femur • ribs • spine
  117. 117. Shows an island of well-differentiated cartilage in the center
  118. 118. Cellular, hemangiopericytoma-like component
  119. 119. TUMOUR LOCATION AGE/M/F SALIENT PATHOLOGIC FINDING OSTEOMA FACIAL BONE 40-50/2:1 MINERALIZED COMPACT BONE OSTEOID OSTEOMA CORTEX OF 10-30/2:1 LB OSTEOBLAS VERTEBRA TOMA E,CORTEX OF LB 10-30/2:1 OSTEOSARC METAPHYS OMA IS OF LB ACONVENTI ONAL . B-LOW GRADE CENTRAL “NIDUS” OF IMMATURE BONE SURROUNDED BY SCLEROTIC BONE. IDENTICAL TO OSTEOID OSTEOMA BUT LARGER AND OFTEN NO SCLEROSIS 10-25/3:2 A -OSTEOID FORMED DIRECTLY BY MALIGNAT CELLS -B- MILDLY ATYPICAL FIBROBLASTIC PROLIFERATION+THICK BONE TRABECULAE
  120. 120. TUMOUR LOCATION CTELANGIEC TATIC METAPHYS IS BLOOD FILLED SPACE+FIBROUS SEPTAE+HIGHLY MALIGNANT OSTEOID DPAROSTEAL CORTEX 30-60 YRS OUTSIDE PERIOSTEU M MILDLY ATYPICAL FIBROBLASTIC PROLIFERATION+THICK BONE TRABECULAE ECORTEX PERIOSTEAL INSIDE PERIOSTEU M AGE/M/F SALIENT PATHOLOGIC FINDING ABUNDAND CARTILAGE MATRIX +VARIABLE MALIGNANT OSTEOID
  121. 121. TUMOUR LOCATION AGE/M/F SALIENT PATHOLOGIC FINDING CHONDRO MA HANDS ,FEET,RIBS ,FEMUR 10-40/1:1 VARIABLY CELLULAR HYLINE CARTILAGE OSTEOCHO NDROMA METAPHYS ISOF LBS 10-30/1:1 CARTILAGE CAPPED BONY PROTRUSION CHONDROB EPIPHYSIS LASTOMA OF LBS 10-20/2:1 CHONDROID LIKE MATRIX, S-100 POSITIVE CELLS WITH GROOVED NUCLEI CHONDRO MYXOID FIBROMA 10-30/1:1 HYPOCELLULAR CHONDROMYXOID LOBULES SURROUNDED BY MORE CELLULAR SPINDLE CELL AREAS METAPHYS IS OF LBS
  122. 122. TUMOUR LOCATION AGE/M/F CHONDROSAR PELIVIS. COMA RIBS ,FEMUR ACONVENTION AL SALIENT PATHOLOGIC FINDING /3:1 METAPHYSIS 20-80 VARIABLY CELLULAR HYLINE CARTILAGE WITH PERMEATING BONE BMETAPHYSIS >30 DEDIFFERENTI ATED CONVENTIONAL CHONDROSARCOMA +HIGH GRADE SPINDLE CELL SARCOMA CMESENCHYM AL 20-50 METAPHYSIS UNDIFFERENTIATED SMALL TUMOUR CELLS WITH +HYLINE CARTILAGE E- CLEAR CELL EPIPHYSIS 20-70 CONVENTIONAL CHONDROSARCOMA +ABUNDANT LARGE CLEAR CELLS
  123. 123. THANKYOU PRESENTED BY – DR NARMADA PRASAD TIWARI

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