OSTEOSARCOMA DR. PREETHAM .N

ORTHOPAEDICS PG

GANDHI MEDICAL COLLEGE

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

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

Unicameral bone cyst Aneurysmal bone cyst Ewing’s sarcoma

Osteosarcoma Enchondroma Osteoblastoma Chondroblastoma Fibrous dysplasia

METAPHYSIS Osteosarcoma Bone cysts Osteoblastoma Osteochondroma Enchondroma Aneurysmal bone cyst

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.

Bony necrotic areas, cystic cavities Large vascular channels & haemorrhage Medullary cavity extension >> found in xray

Eventually periosteal penetration and soft tissue extension

Barriers to joint--- growth plate, articular cartilage

Pulmonary deposits

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

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.

Prognostic significance in differentiation of primary bone sarcomas

DAHLIN subtypes of

osteosarcoma

OsteoblasticChondroblastic Fibrobalstic variants of osteosarcoma

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

Secondary

Paget’s disease

Radiation induced

HEPARIN

CYCLOSERINE

chronic osteomyelitis

bone infarcts

osteogenesis imperfecta

CONVENTIONAL OSTEOSARCOMA

It is the most common type of osteosarcoma.

It is classified based on dominant histopathology as: Osteoblastic Fibroblastic Chondroblastic

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.

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.

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

Anteroposterior and lateral roentgenograms of proximal femur of 67-year-old woman with periosteal

osteosarcoma

MRI demonstrates lesion arising from surface of bone. Marrow does not appear

to be involved

GROSS APPEARANCE

Typical microscopic appearance of periosteal osteosarcoma. Lobules of malignant cartilage are separated by

malignant spindle cells producing osteoid.

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.

Small cell osteosarcoma It is a rare variant.

High-grade lesion that consists of small blue cells that may resemble Ewing sarcoma or lymphoma.

Cytogenetic and immunohistochemistry studies sometimes are needed to differentiate these lesions.

This variant seems to have a worse prognosis than the conventional osteosarcoma.

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

Anteroposterior and lateral roentgenograms of parosteal

osteosarcoma arising in its most common location – Lower end of femur

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.

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

They include Paget disease Previous radiation treatment fibrous dysplasia bone infarcts Osteochondromas chronic osteomyelitis dedifferentiated chondrosarcomas osteogenesis imperfecta

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

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

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

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

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

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

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

LONGITUDINAL LAMINATIONS:

Longitudinal periosteal laminations follow the course of intramedullary lesion.

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.

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.

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

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

MRI SCAN

Better contrast discrimination Can be performed in any plane Ideal for medullary marrow assessment

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.

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.

BONE SCAN Technetium 99 Increased uptake due to brisk

osteoblastic reaction Helpful in detecting

Skip lesions Multicentric presentations metastasis

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

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.

METASTASIS

Primary route is hematogenous and mainly occurs to lungs

Other sites include Brain Liver Lymph node

TREATMENT

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

STAGING

ENNEKING SYSTEM

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

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

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

PHASES OF THE PROCEDURE

Resection of the tumor Skeletal reconstruction Soft tissue and muscle transfers

Reconstructive procedures

arthrodesis

osteoarticular allograft reconstruction, endoprosthetic reconstruction, allograft-prosthesis composite reconstruction

rotationalplasty

Arthrodesis

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.

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.

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

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.

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.

  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

  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

  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

Group BIII—Lesion in the midfemur. The entire femur is resected. The tibia is attached to the pelvis using an endoprosthesis

Rotationplasty

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.

It is based on the principle that all patients have undetectable micro-metastasis on presentation.

Multi drug ,multi cycle therapy is used.

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

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

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.

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.

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

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

References

Samuel L Turek 4th edition Campbell 12th edition

THANK YOU