Download - osteosarcoma
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OSTEOSARCOMA DR. PREETHAM .N
ORTHOPAEDICS PG
GANDHI MEDICAL COLLEGE
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Highly malignant bone Tx characterised by invariable formation of neoplastic osteoid and
tumor tissue
Cell of origin :common multipotential mesenchymal cell
osteoblaticchondroblastic
fibroblastic
Neoplastic osteoid tissue and bone
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ETIOLOGY
Predisposing factors Exciting factors
Age : peak 2nd decade
BIMODAL ..after 60 yrs
Virus:RNA –harvey& moloney mouse sarcoma virus DNA: Polyoma, SV 40
Sex : m>f Radiation: > 2000 rads latent period 3 to 4 yrs
Site: metaphysis fe>ti>ph >>> jaws
Chemical : Be,20 methyl cholanthrene,Cu chelated amino fluorene
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Unicameral bone cyst Aneurysmal bone cyst Ewing’s sarcoma
Osteosarcoma Enchondroma Osteoblastoma Chondroblastoma Fibrous dysplasia
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METAPHYSIS Osteosarcoma Bone cysts Osteoblastoma Osteochondroma Enchondroma Aneurysmal bone cyst
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GROSS PATHOLOGYMetaphyseal large tumor with destruction of inner
cortex and extends into sub periosteal space
SCLEROSING TYPE & LYTIC TYPE
Consistency---- stony hard to soft and gritty
The colour of the tumor reflects its components. Bluish white- cartilaginous. White- fibrous. Yellowish white- osteoid.
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Bony necrotic areas, cystic cavities Large vascular channels & haemorrhage Medullary cavity extension >> found in xray
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Eventually periosteal penetration and soft tissue extension
Barriers to joint--- growth plate, articular cartilage
Pulmonary deposits
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MICROSCOPY Microscopic appearance is variable
Absolute criteria include(LICHTENSTEIN) Sarcomatous stroma Direct formation of tumor osteoid and bone by
malignant connective tissue
Best evidence of malignancy is seen in the advancing borders
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The central portions of the tumor are routinely the most sclerotic where formation of neoplastic bone is most pronounced.
As the anaplastic cells become enclosed in new bone, they become small and rounded, and thus may be unsuitable for diagnosis. Therefore the peripheral zones are most suitable for diagnosis.
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Prognostic significance in differentiation of primary bone sarcomas
DAHLIN subtypes of
osteosarcoma
OsteoblasticChondroblastic Fibrobalstic variants of osteosarcoma
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CLASSIFFICATION
Primary conventional osteosarcoma low-grade intramedullary osteosarcoma parosteal osteosarcoma periosteal osteosarcoma high-grade surface osteosarcoma telangiectatic osteosarcoma small cell osteosarcoma.
CENTRAL PERIPHERAL
INTRAMEDULLARYHIGH GRADE (conventional)
LOW GRADE
JUXTACORTICAL PAROSTEALPERIOSTEAL
TELANGIECTATIC
HIGH GRADE SURFACE
SMALL CELL
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Secondary
Paget’s disease
Radiation induced
HEPARIN
CYCLOSERINE
chronic osteomyelitis
bone infarcts
osteogenesis imperfecta
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CONVENTIONAL OSTEOSARCOMA
It is the most common type of osteosarcoma.
It is classified based on dominant histopathology as: Osteoblastic Fibroblastic Chondroblastic
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Radiographically, the bone involved in conventional osteosarcoma may be lytic, sclerotic or show a mixed response.
It begins in an intramedullary location but may break through the cortex and form a soft tissue mass.
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Low-grade intramedullary osteosarcoma
indolent course with relatively benign features on roentgenogram
As the name implies, it is located in an intramedullary location and only erodes through the cortex very late
Microscopically, it consists of slightly atypical spindle cells producing slightly irregular osseous trabeculae.
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Periosteal osteosarcoma intermediate-grade malignancy that arises on the
surface of the bone The most common locations are the diaphyses of the
femur and tibia It occurs in a slightly older and broader age group Histological examination of periosteal osteosarcoma
demonstrates strands of osteoid-producing spindle cells radiating between lobules of cartilage
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Anteroposterior and lateral roentgenograms of proximal femur of 67-year-old woman with periosteal
osteosarcoma
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MRI demonstrates lesion arising from surface of bone. Marrow does not appear
to be involved
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GROSS APPEARANCE
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Typical microscopic appearance of periosteal osteosarcoma. Lobules of malignant cartilage are separated by
malignant spindle cells producing osteoid.
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TELANGIECTATIC OSTEOSARCOMA
expansible, aggressive lesion simulating an anurysmal bone cyst and composed of loculated blood filled spaces, partially lined by malignant cells producing sparse osteoid formation.
These features account for its radiographic features of a purely lytic lesion which shows none of the sclerotic changes associated with conventional osteosarcoma.
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Small cell osteosarcoma It is a rare variant.
High-grade lesion that consists of small blue cells that may resemble Ewing sarcoma or lymphoma.
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Cytogenetic and immunohistochemistry studies sometimes are needed to differentiate these lesions.
This variant seems to have a worse prognosis than the conventional osteosarcoma.
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Parosteal osteosarcoma Parosteal osteosarcoma also is a rare, low-grade
malignancy It arises on the surface of the bone and invades
the medullary cavity only at a late stage It has a peculiar tendency to occur as a lobulated
ossified mass on the posterior aspect of the distal femur
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Anteroposterior and lateral roentgenograms of parosteal
osteosarcoma arising in its most common location – Lower end of femur
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High-grade surface osteosarcoma
High-grade surface osteosarcoma is the least common type of osteosarcoma
It is an aggressive tumor arising on the outer aspect of the cortex
Roentgenograms show an invasive lesion with ill-defined borders
Like conventional osteosarcoma, the microscopic appearance is that of a high-grade tumor with hypercellularity, mitotic figures, and marked nuclear pleomorphism
Unlike parosteal osteosarcoma, medullary involvement is common at the time of diagnosis.
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Secondary osteosarcomas
Secondary osteosarcomas occur at the site of another disease process.
almost half of the osteosarcomas in patients over 50 years of age.
Prognosis –poor than primary osteosarcoma
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They include Paget disease Previous radiation treatment fibrous dysplasia bone infarcts Osteochondromas chronic osteomyelitis dedifferentiated chondrosarcomas osteogenesis imperfecta
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Paget's osteosarcoma
Paget's osteosarcoma most commonly occurs in patients between the sixth and eighth decades of life.
The incidence of osteosarcoma in Paget disease is approximately 1%
Femur>humerus>pelvis>skull>tibia. Can be multicentric
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Pain,swelling at the site of old # # Failure to unite Xray: mixed blastic and lytic changes :cortical destruction :lung deposits
Osteoclastic multinucleated giant cells can be seen
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Radiation-induced osteosarcoma Radiation-induced osteosarcoma occurs in
approximately 1% of patients who have been treated with over 2500 cGy.
Occurs in unusual locations such as the skull, spine, clavicle, ribs, scapula, and pelvis.
Internal radiaion- radium External radiation- megavoltage/ orthovoltage Mc- radiation >3000 rads for benign GCT Highly osteogenic,sclerosing,profuse osteoid
and new bone formation
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CLINICAL FEATURES
PAIN Predominant symptom Appears first Initially slight and intermittent With in few weeks increases in intensity Cause of pain
Micro infarcts Minute stress fractures
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SWELLING 2ND most common complaint. Present in 90% of high grade osteosarcomas Skin over is
Stretched Shiny Dilated veins Local rise of temperature
Consistency is firm to hard. crepitus --# Joint mobility normal initially later restricted Constitutional Sx and signs of inflammtion
rare
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RADIOGRAPHIC FINDINGS
Codman’s triangle – isolated cuff of reactive sub periosteal new bone formation at the boundary of the tumor that rapidly elevates the periosteum
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RADIOGRAPHIC FINDINGS Sun burst appearance
– spicules of new bone formation seem radiating from a point. It is due to new bone formation along the blood vessels
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LONGITUDINAL LAMINATIONS:
Longitudinal periosteal laminations follow the course of intramedullary lesion.
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BIOPSY
Biopsy should be done only after clinical, laboratory, and roentgenographic examinations are complete.
Regardless of whether a needle biopsy or an open biopsy is done, the biopsy track should be considered contaminated with tumor cells.
If a tourniquet is used, the limb may be elevated before inflation but should not be exsanguinated by compression. Care should be taken to contaminate as little tissue as possible.
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BIOPSY
Transverse incisions should be avoided because they are extremely difficult or impossible to excise with the specimen.
The deep incision should go through a single muscle compartment rather than contaminating an intermuscular plane.
Major neurovascular structures should be avoided.
Soft tissue extension of a bone lesion should be sampled.
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BIOPSY
If a tourniquet has been used it should be deflated and meticulous hemostasis ensured before closure, since a hematoma would be contaminated with tumor cells
If a drain is used, it should exit in line with the incision so that the drain track also can be easily excised en bloc with the tumor
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CT SCAN
Useful for evaluation Differentiate b/w infection and tumor Exact area of cortical break Soft tissue extension, medullary spread,
proximity to NV bundle Detect skip lesions
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MRI SCAN
Better contrast discrimination Can be performed in any plane Ideal for medullary marrow assessment
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ANGIOGRAPHY
Accurate method of of detecting and measuring extent of occult soft tissue extension.
Reactive zone is seen in the early arterial phase.
. Intrinsic vascularity is seen as the tumor blush
in the late venous phase.
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Also assess any major vessel involvement by the tumor.
Arterial phase is useful in detecting sub-clinical recurrences.
It also helps in gauging the clinical response to chemotherapy.
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BONE SCAN Technetium 99 Increased uptake due to brisk
osteoblastic reaction Helpful in detecting
Skip lesions Multicentric presentations metastasis
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BIO-CHEMICAL MARKERS
Serum ALP It is increased as the tumor has neoplastic
osteoblasts Useful in prognosis and follow up Falls to near normal after surgical resection Persistence indicates, metastasis, recurrence,
residual or spreading nature
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BIO-CHEMICAL MARKERS
Osteocalcin – A Recently identified, vitamin K dependant, calcium
binding carboxy glutamic acid containing protein May be of value in diagnosis of heavily bone
producing types
Anti-human osteosarcoma monoclonal anti bodies Detected by immunochemistry These anti-bodies to sarcoma cell surface antigens
are specific to osteosarcoma.
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METASTASIS
Primary route is hematogenous and mainly occurs to lungs
Other sites include Brain Liver Lymph node
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TREATMENT
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The 5 year survival rate which was below 20% is now 60-80%.
This can be attributed to the use of Newer chemotherapeutic regimens Mega voltage radiotherapy Aggressive pulmonary resection
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STAGING
ENNEKING SYSTEM
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GENERAL CONSIDERATIONS Establishment of diagnosis by needle
biopsy or incisional biopsy. Due to fear of tumor spillage frozen section if available should be utilized.
Resection of primary tumor and reconstruction
Adjuvants Chemotherapy Radiotherapy
Rehabilitation
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AMPUTATIONS
This provides the definitive surgical treatment for osteosarcoma.
Level of amputation is the most important factor to be decided: For upper end of tibia above knee amputation For lower end of femur still controversial. Hip
disarticulation is the safer option compared to high a/k Upper end of femur – hind quarter amputation Proximal humerus – fore quarter amputation
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LIMB SPARING SURGERIES
No major neuro-vascular involvement.
Wide resection of affected bone with normal cuff in all directions.
Adequate motor reconstruction and soft tissue coverage
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PHASES OF THE PROCEDURE
Resection of the tumor Skeletal reconstruction Soft tissue and muscle transfers
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Reconstructive procedures
arthrodesis
osteoarticular allograft reconstruction, endoprosthetic reconstruction, allograft-prosthesis composite reconstruction
rotationalplasty
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Arthrodesis
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Osteoarticular allografts advantages: ability to replace ligaments, tendons, and
intraarticular structures.
complications:nonunion at the graft-host junction, fatigue fracture, articular collapse, dislocation, degenerative joint disease, and failure of ligament and tendon attachments.
a temporary measure to preserve an adjacent physis A proximal tibial osteoarticular allograft could be used
in an immature patient in an attempt to preserve the distal femoral physis until skeletal maturity. This could be converted later to an endoprosthetic reconstruction when it becomes necessary.
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Allograft-prosthesis composites
They avoid the complications of degenerative joint disease and articular collapse, while still preserving the ability to attach soft-tissue structures directly, such as the patella tendon or the hip abductors.
They are associated, however, with fatigue fracture, infection, and nonunion at the graft-host junction.
main indication for an allograft-prosthesis composite is an inadequate length of remaining host bone to secure the stem of an endoprosthesis.
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Endoprosthetic reconstruction
advantage -immediate stability that allows for quicker rehabilitation with immediate full weight bearing.
Most endoprostheses are modular, allowing for incremental
limb lengthening as an immature patient grows.
Polyethylene wear Fatigue fractures
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Considerations for Pediatric Patients future limb-length inequality must be considered. For patients who are near skeletal maturity, the reconstructed
limb can be lengthened 1 cm at the initial procedure. Also, epiphysiodesis of the contralateral limb can be done at the appropriate age to preserve limb-length equality .
expandable prostheses currently is gaining support.
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it uses energy stored in a compressed spring to allow for future expansion of the prosthesis as the child grows.
When a leg-length discrepancy develops, the child is scheduled for an expansion .
The procedure is done in the fluoroscopy suite with the patient under light sedation.
The locking mechanism on the prosthesis is identified using fluoroscopy, and an electromagnetic coil is placed over the patient's leg at that level.
The electromagnetic coil is activated for 20 seconds, which heats an element in the prosthesis, melting a small segment of polyethylene and allowing controlled expansion of the spring. The leg lengths are reevaluated under fluoroscopy, and the procedure is repeated one or two times as necessary. We have been able to gain 0.5 to 1.5 cm during each scheduled expansion session. Expansion sessions can be scheduled 4 weeks apart if needed to allow the operated leg to “catch up.” After the expansion sessions, patients usually are able to ambulate immediately without an assistive device.
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Group AI—Lesion in distal femur. The distal femur, knee joint, and proximal tibia are resected; the lower leg is rotated 180 degrees; and the tibia is joined to the remaining femur
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Group AII—Lesion in the proximal tibia. The distalmost femur, knee joint, and proximal tibia are resected. After rotation of 180 degrees, the distal tibia is joined to the distal femur
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Group BI—Lesion in the proximal femur sparing the hip joint and gluteal muscles. The upper femur and hip joint are resected, and the leg is rotated 180 degrees. The distal femur is joined to the pelvis so that the knee functions as the hip, and the ankle functions as the knee
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Group BIII—Lesion in the midfemur. The entire femur is resected. The tibia is attached to the pelvis using an endoprosthesis
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Rotationplasty
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CHEMOTHERAPY
It was previously used for end stage disease.
Now with the advent of neo-adjuvant chemotherapy it is given for all cases both pre and post operatively.
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It is based on the principle that all patients have undetectable micro-metastasis on presentation.
Multi drug ,multi cycle therapy is used.
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NEO-ADJUVANT CHEMOTHERAPY
Advantages Eliminates micro or macro metastasis Causes necrosis of primary tumor Reduces tumor size and vascularity Widens tumor free surgical margin Prevent local recurrence Prognostic indicator
Disadvantages Delayed wound healing Infection
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CHEMOTHERAPUTIC DRUGS
High dose methotrexate (HDMTX) – 8-12gms/m. sq Leucoverin 10-15mg Q6H (20hrs after HDMTX) BCD
Bleomycin – 15mg/m. sq/day Cyclophosphamide – 600mg/m. sq/day Dactinomicin – 600 mcg/m sq/day
Adriamycin – 30mg/m sq/day Cisplatin – 120mg/m sq /day
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RADIOTHERAPY
Osteosarcomas were previously regarded to be radio resistant.
Mega-voltage radiotherapy is used. Used in surgically inaccessible areas. Radiotherapy of osteosarcoma has not been
found to be successful in either reliably controlling local recurrences or preventing pulmonary metastasis.
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6000-8000 rads are given as 230/day or 1000/week.
In the pre operative period about 1000rads are given which reduces the viability of tumor cells which may disseminate in the blood stream during the procedure.
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Immuno-therapy
New method of treatment Adjuvant value Efficacy is still under study Agents include
BCG – bacilli calmette-guerine Cornybactirium parvum toxin Coleys toxin – combination of heat killed
mixture of strep. Pyogenous and serratia marcescens
Vaccine prepared from the patients own tumor cell
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Pulmonary mets
Pulmonary resection: chemotherapy reduces the size of primary tx and lung deposits, making resection easy
Large mets- lobectomy / wedge resection Contraindications: wide spread mets :poor general condition :3 or more pulmonary foci
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References
Samuel L Turek 4th edition Campbell 12th edition
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